Miracle-dz/UniFAR-FTUs huggingface dataset:
Regional cerebral blood flow correlations of somatosensory areas 3a, 3b, 1, and 2 in humans during rest: A PET and cytoarchitectural study

The concept of functional connectivity relies on the assumption that cortical areas that are directly anatomically connected will show correlations in regional blood flow (rCBF) or regional metabolism. We studied correlations of rCBF of cytoarchitectural areas 3a, 3b, 1, and 2 in the brains of 37 subjects scanned with PET during a rest condition. The cytoarchitectural areas, delineated from 10 postmortem brains with statistical methods, were transformed into the same standard anatomical format as the resting PET images. In areas 3a, 3b, and 1, somatotopically corresponding regions were intercorrelated. Area 2 was correlated with the dorsal pre‐motor area. These results were in accordance with the somatosensory connectivity in macaque monkeys. In contrast, we also found correlations between areas 3b and 1 with area 4a, and SMA, and among the left and right hand sector of areas 3a, 3b, and 1. Furthermore, there were no correlations between areas 3b, 1, and 2 with SII or other areas in the parietal operculum, nor of other areas known to be directly connected with areas 3a, 3b, 1, and 2 in macaques. This indicates that rCBF correlations between cortical areas during the rest state only partly reflect their connectivity and that this approach lacks sensitivity and is prone to reveal spurious or indirect connectivity. Hum. Brain Mapping 19:183–196, 2003. © 2003 Wiley‐Liss, Inc.
Incompatibility repressor in a RepA-like replicon of the IncFI plasmid ColV2-K94

The replication region Rep1 of the IncFI plasmid ColV2-K94 was cloned on self-replicating restriction fragments. Rep1 was structurally and functionally homologous to the RepA replicon of IncFII R plasmids. Despite this close relationship, these two replication systems were compatible with each other. The nucleotide sequence of the copA incompatibility-replication control gene of Rep1 was determined and compared with the copA sequence of RepA. Six base changes were found in a 24-base-pair span of the copA gene; these may result in the formation of a new, more stable, 49-base stem-loop structure in the potential CopA RNA repressor molecule. We postulate that these alterations weaken the interaction between RNA transcripts of the Rep1 and RepA replicons.
Adhärenz- und Invasionsverhalten von C.trachomatis-Isolaten

E434 und weitere Vergleichisolate (DICCAL8 , E1733, F1735, F1730und LGV2) wurden an unterschiedlichem Zellmaterial (adhaerenten und suspendierten McCoy und HeLaZellen, humanen primaeren Endometriumkulturen, Zellen des unteren Genitaltraktes der Maus) auf ihr quantitatives Adhaerenz und Invasionsverhalten mit unterschiedlichen Infektionsmodellen untersucht.
Learning disease relationships from clinical drug trials

Objective: Our objective is to test the limits of the assumption that better learning from data in medicine requires more granular data. We hypothesize that clinical trial metadata contains latent scientific, clinical, and regulatory expert knowledge that can be accessed to draw conclusions about the underlying biology of diseases. We seek to demonstrate that this latent information can be uncovered from the whole body of clinical trials. Materials and Methods: We extract free-text metadata from 93 654 clinical drug trials and introduce a representation that allows us to compare different trials. We then construct a network of diseases using only the trial metadata. We view each trial as the summation of expert knowledge of biological mechanisms and medical evidence linking a disease to a drug believed to modulate the pathways of that disease. Our network representation allows us to visualize disease relationships based on this underlying information. Results: Our disease network shows surprising agreement with another disease network based on genetic data and on the Medical Subject Headings (MeSH) taxonomy, yet also contains unique disease similarities. Discussion and Conclusion: The agreement of our results with other sources indicates that our premise regarding latent expert knowledge holds. The disease relationships unique to our network may be used to generate hypotheses for future biological and clinical research as well as drug repurposing and design. Our results provide an example of using experimental data on humans to generate biologically useful information and point to a set of new and promising strategies to link clinical outcomes data back to biological research.
Alagille Syndrome: A New Missense Mutation Detected by Whole-Exome Sequencing in a Case Previously Found to Be Negative by DHPLC and MLPA

Alagille syndrome (ALGS, MIM 118450) is an autosomal dominant, multisystem disorder with high variability. Two genes have been described: JAG1 and NOTCH2. The population prevalence is 1:70,000 based on the presence of neonatal liver disease. The majority of cases (∼97%) are caused by haploinsufficiency of the JAG1 gene on 20p11.2p12, either due to mutations or deletions at the locus. Less than 1% of cases are caused by mutations in NOTCH2. The most widely used methods for mutational screening include denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA). Very recently, whole-exome sequencing (WES) has become technically feasible due to the recent advances in next-generation sequencing technologies, therefore offering new opportunities for mutations/genes identification. A proband and its family, negative for the presence of mutations in JAG1 and NOTCH2 genes by neither DHPLC nor MLPA, were analyzed by WES. A missense mutation, not previously described, in JAG1 gene was identified. This result shows an improvement in the mutation detection rate due to novel sequencing technology suggesting the strong need to reanalyze all negative cases.
Historical Linguistics and Biblical Hebrew: Steps Toward an Integrated Approach

In this book the authors work toward constructing an approach to the history of ancient Hebrew that overcomes the chasm of academic specialization. The authors illustrate how cross-textual variable analysis and variation analysis advance research on Biblical Hebrew and correct theories based on extra-linguistic assumptions, intuitions, and ideologies by focusing on variation of forms/uses in the Masoretic text and variation between the Masoretic text and other textual traditions.
BMP and FGF regulatory pathways in semilunar valve precursor cells

In the developing atrioventricular (AV) valve, limb bud, and somites, cartilage cell lineage differentiation is regulated by bone morphogenetic protein (BMP), while fibroblast growth factor (FGF) controls tendon cell fate. We observed aggrecan and sox9, characteristic of cartilage cell types, and scleraxis and tenascin, characteristic of tendon cell types, in developing avian semilunar valves. Addition of BMP4 to outflow tract (OFT) precursor cells of young (E4.5) but not older (E6) chick embryos activated Smad1/5/8 and induced sox9 and aggrecan expression, while FGF4 treatment increased phosphorylated MAPK (dpERK) signaling and promoted expression of scleraxis and tenascin. These results identify BMP and FGF pathways that promote expression of cartilage‐ or tendon‐like characteristics in semilunar valve precursor cells. In contrast to AV valve precursor cells, which diversify into leaflets (cartilage‐like) or chordae tendineae (tendon‐like), semilunar valve cells exhibit both cartilage‐ and tendon‐like characteristics in the developing and mature valve cusp. Developmental Dynamics 236:971–980, 2007. © 2007 Wiley‐Liss, Inc.
The “Earth-Moon” model on software project risk management

Traditional theory on software project risk management only stands from the perspective of the general project management to analyze the risks and doesn't give full consideration to the characteristics of software projects and software engineering process. To solve this problem, this paper generalizes two types of lifecycles in the software project risk management, analyzes its relations between them, and then put forward “Earth-Moon” conceptual model on software project risk management. The key technologies involved in the new model are also analyzed and solved. In addition, the workflow and implementation arithmetic for this model are designed.
Cost-Effectiveness of Direct-Acting Antiviral Treatment in Hepatitis C–Infected Liver Transplant Candidates With Compensated Cirrhosis and Hepatocellular Carcinoma

Background Hepatitis C virus (HCV)(+) donors represent an effective strategy to increase liver donor availability to HCV-infected recipients. However, many HCV(+) transplant candidates are now receiving treatment with direct-acting anti-viral (DAA) agents that lower the risk of posttransplant HCV recurrence but could make the patient ineligible for HCV(+) livers. Methods We compared pretransplant DAA treatment versus deferred DAA treatment using a cost-effectiveness decision analysis model to estimate incremental cost-effectiveness ratios (cost per quality-adjusted life year gained) from the societal perspective across a range of HCV(+) liver availability rates. For practical considerations, the population modeled was restricted to well-compensated HCV(+) cirrhotics listed for liver transplantation with hepatocellular carcinoma MELD exception points. Results Under base case conditions, the deferred DAA treatment strategy was found to be the “dominant” strategy. That is, it provided superior health outcomes at cost savings compared to the pretransplant DAA treatment strategy. The pretransplant DAA treatment strategy trended towards cost-effectiveness as HCV(+) donor liver availability declined. However, only in 1 scenario that was highly optimized for favorable outcomes in the pretransplant DAA treatment arm (low availability of HCV(+) organs, low cost of DAA treatment, high cost of HCV recurrence) was the incremental cost-effectiveness ratio associated with HCV DAA treatment before transplant less than US $150 000/quality-adjusted life-year gained. Conclusions Deferring HCV treatment until after liver transplant and maintaining access to the expanded pool of HCV(+) donors appears to be the most cost-effective strategy for well-compensated HCV-infected cirrhotics listed for liver transplantation with hepatocellular carcinoma, even in geographic areas of relatively low HCV(+) donor availability.
Generalized steady-state modeling for hybrid AC/DC microgrids

In this paper, a generalized models are presented for different hybrid ac/dc microgrids components in the islanded mode of operation. In this scenario, power sharing schemes are based on local information to manage the system power with the absence of the main substation. Instead, the DG units operate based on droop characteristics, thereby forming a multi-slack distribution system, and accordingly stabilize the system frequency and voltage. The introduced models for the DG units and interlinking converters consider the variation of the ac frequency and dc voltage results from the multi-slack nature and different power sharing strategies between the subgrids. The solution of the nonlinear models, represent the system steady-state behavior, are contrasted with detailed time-domain simulations performed in PSCAD/EMTDC environment to evaluate the modeling accuracy.
Enlightening the photoactive site of channelrhodopsin-2 by DNP-enhanced solid-state NMR spectroscopy

Significance Channelrhodopsin-2 is a dimeric membrane protein functioning as a light-gated ion channel, which has triggered numerous optogenetic applications. We present the first NMR study, to our knowledge, by which structural details of the retinal cofactor could be resolved. This study was only possible by enhancing the detection sensitivity 60-fold through dynamic nuclear polarization (DNP), a highly promising hybrid method linking EPR with solid-state NMR spectroscopy. Our data show that ground-state channelrhodopsin-2 contains the retinal cofactor in its all-trans configuration with a slightly perturbed polyene chain. Three different photointermediates could be trapped and analyzed. Our study shows that DNP-enhanced solid-state NMR is a key method for bridging the gap between X-ray–based structure analysis and functional studies toward a highly resolved molecular picture. Channelrhodopsin-2 from Chlamydomonas reinhardtii is a light-gated ion channel. Over recent years, this ion channel has attracted considerable interest because of its unparalleled role in optogenetic applications. However, despite considerable efforts, an understanding of how molecular events during the photocycle, including the retinal trans-cis isomerization and the deprotonation/reprotonation of the Schiff base, are coupled to the channel-opening mechanism remains elusive. To elucidate this question, changes of conformation and configuration of several photocycle and conducting/nonconducting states need to be determined at atomic resolution. Here, we show that such data can be obtained by solid-state NMR enhanced by dynamic nuclear polarization applied to 15N-labeled channelrhodopsin-2 carrying 14,15-13C2 retinal reconstituted into lipid bilayers. In its dark state, a pure all-trans retinal conformation with a stretched C14-C15 bond and a significant out-of-plane twist of the H-C14-C15-H dihedral angle could be observed. Using a combination of illumination, freezing, and thermal relaxation procedures, a number of intermediate states was generated and analyzed by DNP-enhanced solid-state NMR. Three distinct intermediates could be analyzed with high structural resolution: the early P1500 K-like state, the slowly decaying late intermediate P4480, and a third intermediate populated only under continuous illumination conditions. Our data provide novel insight into the photoactive site of channelrhodopsin-2 during the photocycle. They further show that DNP-enhanced solid-state NMR fills the gap for challenging membrane proteins between functional studies and X-ray–based structure analysis, which is required for resolving molecular mechanisms.
A pilot evaluation of specialist community pharmacy services for patients with Parkinson's disease

Results Statistically significant improvements were found in the proportion of people indicating satisfaction with information on what the medicine does and on possible impact on sex life. Furthermore a significant improvement was found on the “potential problems of medication” summary score on the SIMS. During the period of the study self reported physical function improved on the PDQ-39. No changes were found on the MARS.
Aggregation and Disaggregation Techniques and Methodology in Optimization

A fundamental issue in the use of optimization models is the tradeoff between the level of detail and the ease of using and solving the model. Aggregation and disaggregation techniques have proven to be valuable tools for manipulating data and determining the appropriate policies to employ for this tradeoff. Furthermore, aggregation and disaggregation techniques offer promise for solving large-scale optimization models, supply a set of promising methodologies for studying the underlying structure of both univariate and multivariate data sets, and provide a set of tools for manipulating data for different levels of decision makers. In this paper, we develop a general framework for aggregation and disaggregation methodology, survey previous work regarding aggregation and disaggregation techniques for optimization problems, illuminate the appropriate role of aggregation and disaggregation methodology for optimization applications, and propose future research directions.
Multi-resonant vibration energy harvester using a spiral cantilever beam

The vibration energy harvesters are supposed to operate at their resonant frequencies for obtaining a optimum output, while most of the reported devices are single-resonant systems with a narrow working band. In this work, a multi-resonant vibration energy harvester is presented to make up the output limitation of the single-resonant systems. The vibration structure is designed as a spiral cantilever beam, and the proposed configuration is proved to be capable of achieving multi-resonant response and effectively increasing the working bandwidth of the harvester. Experimental results show that there will present five obvious resonant peak values, and the corresponding resonant frequencies are concentrated at around 21.6 Hz, 27.4 Hz, 34.5 Hz, 42.6 Hz, and 65.9 Hz respectively.
Cell-Cell Adhesion Mediated by Binding of Membrane-anchored Ligand LERK-2 to the EPH-related Receptor Human Embryonal Kinase 2 Promotes Tyrosine Kinase Activity*

Human embryonal kinase 2 (HEK2) is a protein-tyrosine kinase that is a member of the EPH family of receptors. Transcripts for HEK2 have a wide tissue distribution. Recently, a still growing family of ligands, which we have named LERKs, for igands of the ph-elated inases, has been isolated. In order to analyze functional effects between the LERKs and the HEK2 receptor, we expressed HEK2 cDNA in an interleukin-3-dependent progenitor cell line 32D that grows as single cells in culture. Within the group of LERKs, LERK-2 and −5 were shown to bind to HEK2. Membrane-bound and soluble forms of LERK-2 were demonstrated to signal through HEK2 as judged by receptor phosphorylation. Coincubation of HEK2 and LERK-2 expressing cells induced cell-cell adhesion and formation of cell aggregates. This interaction could be inhibited by preincubation of HEK2 expressing cells with soluble LERK-2. Coexpression of HEK2 and LERK-2 in 32D cells showed reduced kinase activity and autophosphorylation of HEK2 compared with the juxtacrine stimulation, which seems to be due to a reduced sensitivity of the receptor.
A flexible model for improving the reuse of user interface design patterns

Despite being a set of proven, well-documented, contextualized recommendations for solving frequently occurring user interface design problems, user interface design patterns are still not widely used. We believe this is due to the lack of tools to help designers find patterns and identify how they can be combined to solve user interface design problems. This paper proposes a flexible model to represent UIDPs and their relationships. The flexibility of our model, based on RDF Statements, is to provide a structure to the representation of the UIDPs in order to allow the development of tools to automate their use.
Complete mitochondrial genome of the blacktip reef shark Carcharhinus melanopterus (Carcharhiniformes: Carcharhinidae)

Abstract The complete mitochondrial genome of the blacktip reef shark Carcharhinus melanopterus is determined for the first time in this study. The gene composition and order in the mitogenome of C. melanopterus is identical to most vertebrates. The overall base composition is 31.3% A, 25.3% C, 13.3% G and 30.1% T. There are 29 bp overlaps and 21 bp short intergenic spaces in the mitogenome. Two start codons and three stop codons were found in protein-coding genes. The dihydrouridine arm of tRNA-Ser2 was replaced by a simple loop and the other tRNAs could be folded into the typical cloverleaf structure. The termination associated sequence (TAS) and the conserved sequence blocks (CSB1-3) are found in the control region.
Serial passage of MC3T3-E1 cells alters osteoblastic function and responsiveness to transforming growth factor-beta1 and bone morphogenetic protein-2.

The murine-derived clonal MC3T3-E1 cell is a well-studied osteoblast-like cell line. To understand the effects of serial passages on its cellular function, we examined changes in cell morphology, gap junctional intercellular communication (GJIC), proliferation, and osteoblastic function between early passage (<20) and late passage (>65) cells. MC3T3-E1 cells developed an elongated, spindle shape after multiple passages. Intercellular communication decreased significantly (33%) in late vs. early passage cells. Transforming growth factor-beta1 (TGF-beta1) stimulated cell proliferation in early passage cells and induced c-fos expression, while it inhibited proliferation in late passage cells. Using alkaline phosphatase (ALP) activity and osteocalcin (OC) secretion as markers for osteoblastic function and differentiation, we demonstrated that both markers were significantly reduced after multiple cell passages. Bone morphogenetic protein-2 (BMP-2) significantly enhanced ALP activity and OC secretion in early passage cells while TGF-beta1 exerted an opposite effect. Both BMP-2 and TGF-beta1 had minimal effects on late passage cells. We conclude that serial passage alters MC3T3-E1 cell morphology, and significantly diminishes GJIC, osteoblastic function, TGF-beta1-mediated cell proliferation, and responsiveness to TGF-beta1 and BMP-2. Cell passage numbers should be clearly defined in functional studies involving MC3T3-E1 cells.
Fault-tolerant design of membrane modules for organic mixture separation

Given the recent advances in membrane technology for energy efficient separation, most studies mainly focused on the development of materials while the operability issues of structured modules have been ignored. It has been well established that uncertain disturbances are inevitable and should be considered as an inherent feature in the realistic operations. It is assumed in the present work that the immediate effects of randomly-occurred faults of the system can be characterized mathematically by the uncertain parameters. An ill-designed membrane system, when operated under uncertainties, may perform poorly and result in unnecessary energy waste. Therefore, this work investigates the operational flexibility of membrane modules under the influence of random fault-induced disturbances. The recently developed volumetric flexibility index is adopted as a performance measure. The case studies presented in this paper clearly demonstrate that such an index can indeed provide insights for configuring various fault-tolerant membrane modules.
Integrative Self-Knowledge Scale: Correlations and Incremental Validity of a Cross-Cultural Measure Developed in Iran and the United States

The authors used Iranian (N = 723) and American (N = 900) samples to develop an Integrative Self-Knowledge Scale for measuring a temporally integrated understanding of processes within the self. They administered this new instrument, the Mindfulness Scale (K. W. Brown & R. M. Ryan, 2003), the Reflective and Experiential Self-Knowledge Scales (N. Ghorbani, M. N. Bing, P. J. Watson, H. R. Davison, & D. L. Lebreton, 2003), and additional sample-specific measures to 3 separate groups of university students in each society. The Integrative Self-Knowledge Scale displayed internal reliability and measurement equivalence, along with convergent, criterion, discriminant, and incremental validity. This new instrument may be useful in promoting cross-cultural research in positive psychology.