Active-Site Monovalent Cations Revealed in a 1.55-Å-Resolution Hammerhead Ribozyme Structure

We have obtained a 1.55-Å crystal structure of a hammerhead ribozyme derived from Schistosoma mansoni under conditions that permit detailed observations of Na⁺ ion binding in the ribozyme's active site. At least two such Na⁺ ions are observed. The first Na⁺ ion binds to the N7 of G10.1 and the adjacent A9 phosphate in a manner identical with that previously observed for divalent cations. A second Na⁺ ion binds to the Hoogsteen face of G12, the general base in the hammerhead cleavage reaction, thereby potentially dissipating the negative charge of the catalytically active enolate form of the nucleotide base. A potential but more ambiguous third site bridges the A9 and scissile phosphates in a manner consistent with that of previous predictions. Hammerhead ribozymes have been observed to be active in the presence of high concentrations of monovalent cations, including Na⁺, but the mechanism by which monovalent cations substitute for divalent cations in hammerhead catalysis remains unclear. Our results enable us to suggest that Na⁺ directly and specifically substitutes for divalent cations in the hammerhead active site. The detailed geometry of the pre-catalytic active-site complex is also revealed with a new level of precision, thanks to the quality of the electron density maps obtained from what is currently the highest-resolution ribozyme structure in the Protein Data Bank.     

To share or not to share: Incentivizing data sharing in life science communities

Most scientists recognize the importance of sharing data online in an open fashion. Nonetheless, many studies have documented the concerns that accompany data sharing activities, including loss of credit or IP, misuse and the time needed to curate interoperable data. To this end, discussions around data sharing often identify incentives that could potentially ameliorate these disincentivising concerns. Nonetheless, current Open Data discussions often rely on evidence‐based studies to identify the disincentives to overcome. This results in highly specific and directed interventions. In contrast, this paper offers a different interpretation of these concerns. To do so, it makes use of the Thomas Theorem which suggests that: “If men define situations as real, they are real in their consequences”. Using empirical evidence from sub‐Saharan African (bio)chemistry laboratories, this paper illustrates how individual perceptions of research environments – whether associated with evidence or not – are highly influential in shaping data sharing practices. It concludes with the suggestion that discussion on incentivising data sharing amongst scientific communities need to take a broader set of concerns into account and offer a more creative approach to ameliorating environmental disincentives.     

基于CLDAS强迫CLM3.5模式的新疆区域土壤温度陆面过程模拟及验证

利用中国气象局国家气象信息中心研发的中国气象局陆面数据同化系统(China Meteorological Administration Land Data Assimilation System,CLDAS)大气近地面强迫资料,驱动美国国家大气研究中心公用陆面模式(Community Land Model,CLM3.5),对中国新疆地区土壤温度时空分布进行逐小时Off-line模拟(模拟时段为2009—2012年);利用国家土壤温度自动站(新疆区域105站点)数据验证CLDAS驱动场强迫下的CLM3.5模式在中国新疆地区3个土壤层(5cm、20cm和80cm)的土壤温度模拟能力。研究发现:在月变化方面,第1层(5cm)土壤温度模拟与实测值差异最大,在每年7月最大差异达5k左右;第2层(20cm)在每年7月达最大差异(3k左右),而第3层(80cm)在每年7月均模拟的很好。造成这种现象的原因可能因为新疆地区7月前后浅层土壤温度变化剧烈,温度白天最高可达300K以上,昼夜温差大,导致模式不能很好抓住浅层土壤温度的变化趋势。研究还发现,在80cm土壤深度,模式在1月、12月的模拟结果均较前两层差。在日变化方面,研究发现:较浅的两层(5cm和20cm)土壤温度模拟值在夏季和秋季均较差。与月变化模拟结果类似的是,80cm土壤层日变化在1、12月模拟较差,然而在其他时段却模拟的很好。在小时变化方面,分析发现:第1层土壤(5cm)模拟结果在每年的1—4月及9—11月的全天(即24 h),模式也会有不同的偏差:其中,在03UTC—21UTC之间主要表现为模式结果比观测结果偏高,而在日内21UTC—00UTC主要表现为模拟结果偏小。在每年的5—8月,全天模拟值都偏小,其中在09UTC达当日最大值。而距离第2层(20cm)处的土壤温度模拟值在大部分月份都偏差较小(-1K至1k之间),并在日内12UTC偏差达到当日最大值。研究发现,在土壤20cm处,模式模拟的最大值较观测值提前,而第3层(80cm)的土壤温度基本不受日内变化影响,表现较为平稳。造成这种影响的原因可能是因为新疆地区5—8月、9—11月为昼夜温差大,深层土壤温度较浅层土壤温度温差变化小,这也造成了模式对于浅层土壤模拟较深层差的主要原因。总体研究表明:CLDAS驱动场强迫下的CLM3.5模式可较为精确的模拟中国新疆地区多年平均土壤温度时空分布,并较为准确的反映中国新疆地区土壤温度的小时、日、月及年际的变化规律。模式浅温度模拟不好的原因可能与模式参数化方案及地表参数有关,后期将继续修正该问题。     

Imprint cytology of vacuum-assisted breast biopsy specimens: a rapid diagnostic tool in non-palpable solid lesions

Objective:  Imprint cytology provides a rapid preliminary diagnosis shortly after the completion of breast biopsy. This study aims to assess the validity of imprint cytology for the pre-operative diagnosis of non-palpable mammographic solid lesions excised by vacuum-assisted breast biopsy (VABB).
Methods:  Seventy-two women with non-palpable Breast Imaging Reporting and Data System 3 and 4 mammographic solid lesions without microcalcifications underwent VABB on the stereotactic Fischer's table with 11-G Mammotome vacuum probes. Imprint samples were examined (Diff-Quick stain, modified Papanicolaou stain and May-Grünwald–Giemsa). The cores were dipped into a CytoRich Red Collection fluid for a few seconds in order to obtain samples with the use of the specimen wash. After the completion of cytological procedures, the core was prepared for routine pathological study. The pathologist was blind to the preliminary cytological results. The cytological and pathological diagnoses were comparatively evaluated.
Results:  The sensitivity of the cytological imprints for cancer was 90%. The specificity of the method for cancer diagnosis was 100%. Two precursor lesions were present in the material: one case of atypical ductal hyperplasia, which was successfully detected, and one case of lobular neoplasia, which escaped detection. The cytological imprints were inadequate in four out of 72 cases (5.6%), but none of them were included within the malignant subgroup.
Conclusions:  Imprint cytology seems to be an important adjunctive tool in the management of patients with non-palpable mammographic solid lesions. Its very satisfactory sensitivity and optimal specificity could establish its use in general clinical practice.     

The flora of the Bontebok National Park in regional perspective

Six-hundred-and-fifty plant species from 280 genera and 85 families have been recorded as indigenous to the Bontebok National Park (BNP), which lies 5 km south of Swellendam, in the Western Cape. Twenty-nine of these plant species are globally threatened with extinction and another 23 are species of conservation concern. Three species (Aspalathus burchelliana, Diosma fallax, Erica filamentosa) are endemic to the park. The Asteraceae, Iridaceae and Fabaceae ranked high as speciose families, in line with the Cape Floristic Region (CFR) as a whole, while the Asphodelaceae, Crassulaceae, Poaceae and Cyperaceae were overrepresented, and the Rutaceae, Proteaceae and Ericaceae underrepresented at BNP. The largest genera were Aspalathus (19 species), Crassula (17), Pelargonium (16), Erica (15), Oxalis (12), Moraea (11), Helichrysum (10) and Hermannia (10). Geophytes were the dominant growth form (23% of species recorded), followed by dwarf shrubs (20%), herbs (16%), graminoids (15%), shrubs (13%), succulents (8%), trees (3%) and climbers (2%). Forty alien plant species were recorded (likely an underestimate of true numbers) with the Poaceae most speciose and arguably the biggest invasive threat at the park. With 20 plant species/km², the flora of BNP is richer than expected based on its location within the south-eastern CFR. Similarity with floras of other lowland and montane protected areas in the region is low (< 33% and < 20% respectively), demonstrating that a large component of BNP's flora is not conserved elsewhere. Within a landscape context, BNP forms part of a cluster of connected core sites for Renosterveld conservation. This work confirms the high importance of BNP for flora conservation nationally and even globally.     

The crystal structure of the carboxy-terminal domain of human translation initiation factor eIF5

The carboxy-terminal domain (CTD) of eukaryotic initiation factor 5 (eIF5) plays a central role in the formation of the multifactor complex (MFC), an important intermediate for the 43 S pre-initiation complex assembly. The IF5-CTD interacts directly with the translation initiation factors eIF1, eIF2-beta, and eIF3c, thus forming together with eIF2 bound Met-tRNA(i)(Met) the MFC. In this work we present the high resolution crystal structure of eIF5-CTD. This domain of the protein is exclusively composed out of alpha-helices and is homologous to the carboxy-terminal domain of eIF2B-epsilon (eIF2Bepsilon-CTD). The most striking difference in the two structures is an additional carboxy-terminal helix in eIF5. The binding sites of eIF2-beta, eIF3 and eIF1 were mapped onto the structure. eIF2-beta and eIF3 bind to non-overlapping patches of negative and positive electrostatic potential, respectively.     

Exploiting redundancy to boost performance in a RAID-10 style cluster-based file system

While aggregating the throughput of existing disks on cluster nodes is a cost-effective approach to alleviate the I/O bottleneck in cluster computing, this approach suffers from potential performance degradations due to contentions for shared resources on the same node between storage data processing and user task computation. This paper proposes to judiciously utilize the storage redundancy in the form of mirroring existed in a RAID-10 style file system to alleviate this performance degradation. More specifically, a heuristic scheduling algorithm is developed, motivated from the observations of a simple cluster configuration, to spatially schedule write operations on the nodes with less load among each mirroring pair. The duplication of modified data to the mirroring nodes is performed asynchronously in the background. The read performance is improved by two techniques: doubling the degree of parallelism and hot-spot skipping. A synthetic benchmark is used to evaluate these algorithms in a real cluster environment and the proposed algorithms are shown to be very effective in performance enhancement. Yifeng Zhu received his B.Sc. degree in Electrical Engineering in 1998 from Huazhong University of Science and Technology, Wuhan, China; the M.S. and Ph.D. degree in Computer Science from University of Nebraska – Lincoln in 2002 and 2005 respectively. He is an assistant professor in the Electrical and Computer Engineering department at University of Maine. His main research interests are cluster computing, grid computing, computer architecture and systems, and parallel I/O storage systems. Dr. Zhu is a Member of ACM, IEEE, the IEEE Computer Society, and the Francis Crowe Society. Hong Jiang received the B.Sc. degree in Computer Engineering in 1982 from Huazhong University of Science and Technology, Wuhan, China; the M.A.Sc. degree in Computer Engineering in 1987 from the University of Toronto, Toronto, Canada; and the PhD degree in Computer Science in 1991 from the Texas A&M University, College Station, Texas, USA. Since August 1991 he has been at the University of Nebraska-Lincoln, Lincoln, Nebraska, USA, where he is Professor and Vice Chair in the Department of Computer Science and Engineering. His present research interests are computer architecture, parallel/distributed computing, cluster and Grid computing, computer storage systems and parallel I/O, performance evaluation, real-time systems, middleware, and distributed systems for distance education. He has over 100 publications in major journals and international Conferences in these areas and his research has been supported by NSF, DOD and the State of Nebraska. Dr. Jiang is a Member of ACM, the IEEE Computer Society, and the ACM SIGARCH. Xiao Qin received the BS and MS degrees in computer science from Huazhong University of Science and Technology in 1992 and 1999, respectively. He received the PhD degree in computer science from the University of Nebraska-Lincoln in 2004. Currently, he is an assistant professor in the department of computer science at the New Mexico Institute of Mining and Technology. He had served as a subject area editor of IEEE Distributed System Online (2000–2001). His research interests are in parallel and distributed systems, storage systems, real-time computing, performance evaluation, and fault-tolerance. He is a member of the IEEE. Dan Feng received the Ph.D degree from Huazhong University of Science and Technology, Wuhan, China, in 1997. She is currently a professor of School of Computer, Huazhong University of Science and Technology, Wuhan, China. She is the principal scientist of the the National Grand Fundamental Research 973 Program of China “Research on the organization and key technologies of the Storage System on the next generation Internet.” Her research interests include computer architecture, storage system, parallel I/O, massive storage and performance evaluation. David Swanson received a Ph.D. in physical (computational) chemistry at the University of Nebraska-Lincoln (UNL) in 1995, after which he worked as an NSF-NATO postdoctoral fellow at the Technical University of Wroclaw, Poland, in 1996, and subsequently as a National Research Council Research Associate at the Naval Research Laboratory in Washington, DC, from 1997–1998. In 1999 he returned to UNL where he directs the Research Computing Facility and currently serves as an Assistant Research Professor in the Department of Computer Science and Engineering. The Office of Naval Research, the National Science Foundation, and the State of Nebraska have supported his research in areas such as large-scale scientific simulation and distributed systems.     

Rejoinder to Use of Principal Component Analysis and the GE -Biplot for the Graphical Exploration of Gene Expression Data

Summary This note is in response to Wouters et al. (2003, Biometrics 59, 1131–1139) who compared three methods for exploring gene expression data. Contrary to their summary that principal component analysis is not very informative, we show that it is possible to determine principal component analyses that are useful for exploratory analysis of microarray data. We also present another biplot representation, the GE‐biplot (Gene Expression biplot), that is a useful method for exploring gene expression data with the major advantage of being able to aid interpretation of both the samples and the genes relative to each other.     

国家野外试验站现状分析及网络化体系构建

为了推动筹建国家级重点野外科学观测试验站网络化管理的工作,充分发挥野外试验站所观测数据的作用.我们选取了25个野外试验站作为试点站,并于2002年8月至10月主要采用调查表、网上查询和电子邮件交流的方式进行调查,调研的主要内容涉及各野外台站的基本情况、软硬什和网络以及数据集现状,以及国外野外台站的运行状况和发展趋势.通过调查结果的分析,表明目前我国野外台站在数据监测、管理以及数据标准化与共享方面存在较多的不足之处.据此提出建立网络台站管理体系的框架,为实现我国国家级野外试验站数据标准化与信息共事的目标奠定基础.