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Background and Objectives Excess collagen synthesis in the liver plays a causal role in progression from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). Markers that identify a patient's risk for progression, characterize disease activity and provide early assessment of treatment efficacy are needed. In particular, the availability of a non‐invasive metric of the rates of liver collagen synthesis (fibrogenesis) and turnover (fibrolysis) would be extremely valuable. We evaluated novel clinical biomarkers that directly quantify hepatic fibrogenesis rate in well‐characterized patients with biopsy‐proven NAFLD. Methods Patients with suspected NAFLD and a clinical indication for liver biopsy received the stable, non‐radioactive tracer heavy water ( 2 H 2 O, 50 ml, 2–3 times daily) by mouth for 20–35 days prior to biopsy. A plasma sample was collected weekly. Collagen fractional synthesis rate (FSR) from liver biopsy tissue and FSR of lumican (a proteoglycan involved in collagen fibril assembly that exhibits increased synthesis when collagen synthesis is increased) from plasma were measured by 2 H incorporation, using tandem mass spectrometry (LC‐MS/MS). Magnetic resonance elastography (MRE) measurements of liver stiffness were obtained within 2 weeks of biopsy. Results FSR of hepatic type I collagen (Col1a1) was significantly elevated in NASH relative to NAFL (0.97% vs 0.43 %/day, p=0.03). Liver Col1a1 FSR also significantly correlated with fibrosis severity by histological score (r= 0.63), with liver stiffness by MRE (r=0.65), and with HbA1c levels (r=0.47). FSRs of fibrillar hepatic collagen subtypes (I and III) were highly correlated (r= 0.94). FSR of circulating plasma lumican correlated strongly with liver collagen FSR (r=0.69) and with liver stiffness (r=0.71). Conclusion We conclude that hepatic collagen synthesis rates increase with fibrosis severity in NAFLD patients, indicating not only markedly increased absolute rates of collagen synthesis with disease progression but also suggesting that hepatic scar is dynamic even in advanced disease and may therefore be potentially reversible. Importantly, plasma lumican FSR correlates closely with liver collagen FSR and with liver stiffness. Moreover, established clinical risk factors for disease progression (NASH diagnosis, histologic fibrosis score, diabetes) were associated with higher collagen FSR. Non‐invasive kinetic measurements of fibrogenesis, such as plasma lumican FSR, may be helpful as markers of risk for disease progression and as early read outs of treatment response in anti‐fibrotic trials in NASH. Prospective studies are required to establish the predictive power of fibrogenesis rates for disease progression or reversal. Support or Funding Information KineMed, Inc.

Este artigo analisa o crescimento exponencial do numero de detentos ocorrido nos Estados Unidos a partirde meados dos anos 70. Procura mostrar que esse crescimento nao corresponde a um aumento dacriminalidade, mas a conjugacao de tres series causais, quais sejam: o declinio do “ideal de reabilitacao”dos prisioneiros, a instrumentalizacao do medo da violencia pelos politicos e pela midia e a funcao demecanismo de controle racial assumido pelo sistema penal americano. Em suma, a hiperflacao carcerariarevela a contraface do enfraquecimento do Estado de Bem-Estar Social e a sua substituicao por um Estadopenal.PALAVRAS-CHAVE: Estado penal; Estado de bem-estar social; sistema penitenciario; punicao;criminalidade; penalogia; hiperinflacao carceraria.I. INTRODUCAOEm 1967, enquanto a Guerra do Vietna e asrevoltas raciais sacudiam os Estados Unidos, oPresidente Johnson recebia de um grupo de espe-cialistas um inventario sobre o sistema judiciarioe penitenciario americano. A “Comissao sobre aAdministracao da Lei e da Justica” revelava entaoque a populacao detida nas prisoes federais e nascasas de detencao estaduais diminuia lentamente,em torno de 1% ao ano (PRESIDENT’SCOMMISSION, 1967). Naquele ano, os estabe-lecimentos penitenciarios dos Estados Unidos con-finavam 426 000 pessoas, numero que deveriaaumentar para 523 000 em 1975, sob o efeito docrescimento demografico nacional. Nem asuperlotacao das prisoes, nem a inflacao dosefetivos carcerarios estavam na ordem do dia. Ogoverno federal se propunha, alias, a acelerar adeflacao destes ultimos atraves de um uso ampli-ado da liberdade vigiada e da generalizacao de pe-nas alternativas.Seis anos mais tarde, Richard Nixon recebiapor sua vez um relatorio sobre a evolucao do sis-tema carcerario norte-americano. A NationalAdvisory Commission on Criminal Justice Stan-dards and Goals notava, na verdade, que a popu-lacao encarcerada cessara de refluir. Mas nem porisso deixara de recomendar uma moratoria de dezanos na construcao de prisoes, assim como o fe-chamento progressivo dos estabelecimentos parajovens detentos. Isso porque estava comprovadoque “a penitenciaria, a casa de correcao e a prisaonada tem feito alem de acumular fracassosvexatorios. Sao incontestes as provas que de-monstram que essas instituicoes geram mais crimi-nalidade que a previnem” (NATIONAL ADVI-SORY COMMISSION, 1973, p. 597).Na mesma epoca, Alfred Blumstein e seuscolaboradores propunham sua teoria “homeosta-tica” do nivel de encarceramento nas sociedadesmodernas. Segundo o celebre criminalista, cadasociedade apresenta nao um nivel “normal” decriminalidade, como queria Emile Durkheim, masum nivel constante de punicao, que se traduz poruma taxa estavel de encarceramento (BLUMSTEIN

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHalide, hydride, and alkyl derivatives of (pentamethylcyclopentadienyl)bis(trimethylphosphine)rutheniumT. Don Tilley, Robert H. Grubbs, and John E. BercawCite this: Organometallics 1984, 3, 2, 274–278Publication Date (Print):February 1, 1984Publication History Published online1 May 2002Published inissue 1 February 1984https://pubs.acs.org/doi/10.1021/om00080a019https://doi.org/10.1021/om00080a019research-articleACS PublicationsRequest reuse permissionsArticle Views2982Altmetric-Citations183LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

2016 marks the 10th anniversary of the Suzhou Institute of Nano-Tech and Nano-Bionics of the Chinese Academy of Sciences (SINANO). Located in Suzhou, one of the most flourishing economic areas in China, SINANO is dedicated to the development of advanced nanoscience and technology, aims to bridge the gap between academic research and the industry of nanoscience and technology, and promotes the commercialization and utilization of intelligent properties. The research at SINANO covers a broad range of fundamental and applied research in chemistry, physics, materials science, and semiconductor devices, pursuing the development of key innovations with the aim of furthering urgent national needs and important strategic targets. Within the last decade, SINANO has grown into one of China's leading research institutions in nanoscience and technology, with a great international reputation. If we consider that the work done by the entire research enterprise is a process from zero to 100, it can be divided into three important segments. The first one, from zero to one, is the most important one. It typically includes the most original, fundamental part of research and represents the ultimate process of knowledge generation. It generates the very important fundamental intellectual properties that could have significant impact on society in the next several decades. This is also being called by many Chinese scientists as the “first mile” of the research. The 2nd segment, from 1 to 99, is a process to continue to improve and optimize the existing concept, material, and technology. In this process, scientists will need to be aware of where the weakest links are in their materials, devices, and systems, and come up with many different strategies to optimize the properties and performance of a particular material and device. This process of optimization, which sometimes seems to be incremental, is another critical step in developing a useful and commercially viable technology. The 3rd segment, from 99 to 100, represents the final step in turning a particular science breakthrough into a useful technology and product, i.e. technology transfer and commercialization. This is also a process that the general public can experience the real impact in their daily life, because of a particular scientific advancement. It is also called by many Chinese scientists the “final mile” of the research. This final step in many cases is very challenging, as not every scientific breakthrough can readily turn into a useful product. It will require close interactions between many parties: researchers, governments, and entrepreneurs. SINANO, as an institute with unique missions from the very beginning, has been carrying out research that can be categorized into all these three segments. One will see many of these good examples in this special issue of Small. From its birth in 2006, SINANO has experienced rapid development over the past 10 years. Currently, there are more than 500 formal employees plus 500 graduate students and postdocs working at SINANO. Our researchers have continued to perform innovative research at the forefront of semiconductor materials and devices, energy materials, enviromental materials, biological technologies, etc, including III-V semiconductor lasers, high-performance carbon nanofibers, high-performance polymer membranes, printable electronics, energy storage and conversion materials, nuclear acid and protein nanochips for high-sensitive disease detection, near-infrared fluorescence imaging-guided drug delivery and therapeutics, etc. The most prominent feature of the research at SINANO is that we execute the fundamental research from the view of its practical applications by taking advantage of the novel properties of materials on the nanoscale. We know that our understanding at the fundamental level, including discovery of materials with new functions, deep understanding of the structure–function relationships of materials, and the design of materials with better performances, will definitely help their industrial conversion and utilization. This special issue includes 2 reviews and 19 research articles. The topics cover nanomaterials, nanodevices, nanobiomedicine, etc. We hope that this special issue not only introduces recent research at SINANO to the scientific community, but also provides an incentive for further multi-disciplinary collaboration with other researchers from all over the world. Last but not least, we would like to express our sincere appreciation to Dr. José Oliveira and Dr. Xin Su and the Small editorial team for their efforts to publish this special issue. Peidong Yang is a Chemistry professor, and S. K. and Angela Chan Distinguished Chair Professor in Energy at the University of California, Berkeley. He is known particularly for his work on semiconductor nanowires and their photonic and energy applications. He is the director for California Research Alliance by BASF, and co-director for the Kavli Energy Nanoscience Institute. Dr. Yang received his B.A. in Chemistry from the University of Science and Technology in China in 1993 and his Ph.D. in Chemistry from Harvard University in 1997, and did his postdoctoral fellowship at the University of California, Santa Barbara in 1999. Now, he is a member of both the National Academy of Sciences and the American Academy of Arts and Sciences. Hui Yang has been the founding director of the Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences. He received his B.S. and Ph.D. degree from Peking University and Institute of Semiconductors, Chinese Academy of Sciences in 1982 and 1990, respectively. His main research interests include the growth of group III-V compound semiconductor materials and their low dimensional structures, as well as opto-electronics devices, by means of molecular beam epitaxy and metal-organic chemical vapor deposition methods. In recent, his research particularly focuses on the Gallium Nitride blue and green lasers and III-V semiconductor four-junction tandem solar cells.

The synthesis of a difluorofluorescein monocarboxaldehyde platform and its use for preparing ZP8, a new member of the Zinpyr family of neuronal Zn(2+) sensors, are described. By combining an aniline photoinduced electron transfer (PET) switch and an electron-withdrawing fluorescein scaffold, ZP8 displays reduced background fluorescence and improved dynamic range compared to previous ZP probes. The bright sensor undergoes an 11-fold increase in fluorescence intensity upon Zn(2+) complexation (Phi = 0.03-0.35) with high selectivity over cellular concentrations of Ca(2+) and Mg(2+). In addition, sensors in the ZP family have been utilized for optical imaging in biological samples using two-photon microscopy (TPM). The cell-permeable ZP3 probe is capable of identifying natural pools of labile Zn(2+) within the mossy fiber synapses of live hippocampal slices using TPM, establishing the application of this technique for monitoring endogenous Zn(2+) stores.

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