Miracle-dz/UniFAR-FTUs huggingface dataset:
A Family of 16-kDa Pancreatic Secretory Stress Proteins Form Highly Organized Fibrillar Structures upon Tryptic Activation*

A group of 16-kDa proteins, synthesized and secreted by rat pancreatic acinar cells and composed of pancreatic stone protein (PSP/reg) and isoforms of pancreatitis-associated protein (PAP), show structural homologies, including conserved amino acid sequences, cysteine residues, and highly sensitive N-terminal trypsin cleavage sites, as well as conserved functional responses in conditions of pancreatic stress. Trypsin activation of recombinant stress proteins or counterparts contained in rat pancreatic juice (PSP/reg, PAP I and PAP III) resulted in conversion of 16-kDa soluble proteins into 14-kDa soluble isoforms (pancreatic thread protein and pancreatitis-associated thread protein, respectively) that rapidly polymerize into insoluble sedimenting structures. Activated thread proteins show long lived resistance to a wide spectrum of proteases contained in pancreatic juice, including serine proteases and metalloproteinases. In contrast, PAP II, following activation with trypsin or pancreatic juice, does not form insoluble structures and is rapidly digested by pancreatic proteases. Scanning and transmission electron microscopy indicate that activated thread proteins polymerize into highly organized fibrillar structures with helical configurations. Through bundling, branching, and extension processes, these fibrillar structures form dense matrices that span large topological surfaces. These findings suggest that PSP/reg and PAP I and III isoforms consist of a family of highly regulated soluble secretory stress proteins, which, upon trypsin activation, convert into a family of insoluble helical thread proteins. Dense extracellular matrices, composed of helical thread proteins organized into higher ordered matrix structures, may serve physiological functions within luminal compartments in the exocrine pancreas.
Moral Development: Advances in Research and Theory

This book focuses on a theoretical framework (the Four-Component Model) and evaluations of the Defining Issues Test (DIT) developed by Rest and his coworkers. The authors assess their own work with the DIT and that of hundreds of other investigators. Among their conclusions are: formal education is correlated with moral judgment; there is evidence for Kohlberg's higher stages; moral education programs produce modest gains, and, there are no sex differences. The book is important for libraries wishing a complete collection on moral development. Choice
Increase of [ 18 F ] FLT Tumor Uptake In Vivo Mediated by FdUrd : Toward Improving Cell Proliferation Positron Emission Tomography

Purpose: 3′-deoxy-3′-[F]fluorothymidine ([F]FLT), a cell proliferation positron emission tomography (PET) tracer, has been shown in numerous tumors to be more specific than 2deoxy-2-[F]fluoro-D-glucose ([F]FDG) but less sensitive. We studied the capacity of a nontoxic concentration of 5-fluoro-2′-deoxyuridine (FdUrd), a thymidine synthesis inhibitor, to increase uptake of [F]FLT in tumor xenografts. Methods: The duration of the FdUrd effect in vivo on tumor cell cycling and thymidine analogue uptake was studied by varying FdUrd pretreatment timing and holding constant the timing of subsequent flow cytometry and 5-[I]iodo-2′-deoxyuridine biodistribution measurements. In [F]FLT studies, FdUrd pretreatment was generally performed 1 h before radiotracer injection. [F]FLT biodistributions were measured 1 to 3 h after radiotracer injection of mice grafted with five different human tumors and pretreated or not with FdUrd and compared with [F]FDG tumor uptake. Using microPET, the dynamic distribution of [F]FLT was followed for 1.5 h in FdUrd pretreated mice. High-field T2-weighted magnetic resonance imaging (MRI) and histology were used comparatively in assessing tumor viability and proliferation. Results: FdUrd induced an immediate increase in tumor uptake of 5-[I]iodo-2′-deoxyuridine, that vanished after 6 h, as also confirmed by flow cytometry. Biodistribution measurements showed that FdUrd pretreatment increased [F]FLT uptake in all tumors by factors of 3.2 to 7.8 compared with controls, while [F]FDG tumor uptake was about fourfold and sixfold lower in breast cancers and lymphoma. Dynamic PET in FdUrd pretreated mice showed that [F]FLT uptake in all tumors increased steadily up to 1.5 h. MRI showed a well-vascularized homogenous lymphoma with high [F]FLT uptake, while in breast cancer, a central necrosis shown by MRI was inactive in PET, consistent with the histomorphological analysis. Correspondence to: David Viertl; e-mail: David.Viertl@chuv.ch Conclusion: We showed a reliable and significant uptake increase of [F]FLT in different tumor xenografts after low-dose FdUrd pretreatment. These results show promise for a clinical application of FdUrd aimed at increasing the sensitivity of [F]FLT PET.
Fall 11-2006 Concept Frequency Distribution in Biomedical Text Summarization

Text summarization is a data reduction process. The use of text summarization enables users to reduce the amount of text that must be read while still assimilating the core info rmation. The data reduction offered by text summarization is par ticularly useful in the biomedical domain, where physicians must con tinuously find clinical trial study information to incorporat e into their patient treatment efforts. Such efforts are often h ampered by the high-volume of publications. Our contribution is tw o-fold: 1) to propose the frequency of domain concepts as a method to identify important sentences within a full-text; and 2) prop ose a novel frequency distribution model and algorithm for iden tifying important sentences based on term or concept freque ncy distribution. An evaluation of several existing sum marization systems using biomedical texts is presented in orde r to determine a performance baseline. For domain concept comparis on, a recent high-performing frequency-based algorithm using ter ms is adapted to use concepts and evaluated using both te rms and concepts. It is shown that the use of concepts perf orms closely with the use of terms for sentence selection. Our p roposed frequency distribution model and algorithm outperfo rms a stateof-the-art approach.
Obtaining Trust in Autonomous Systems: Tools for Formal Model Synthesis and Validation

An important and growing class of cyber physical systems are autonomous vehicles (AVs). While the U.S. Military has used AVs, such as unmanned air vehicles, for many years, civilian use of these vehicles, e.g., By the FBI, has been steadily increasing. Plans to equip AVs with cameras, scientific instruments, and weapons, such as tear gas and pepper spray, have led to growing mistrust of AVs and calls for greater human control and oversight. This paper describes two kinds of trust needed in systems involving AVs and how a formal model and model-based simulation can help obtain such trust. It introduces two new tools to be integrated into Formal Requirements Modeling and Analysis (FORMAL), an upgrade of NRL's Software Cost Reduction (SCR) toolset, the new tools support formal modeling and symbolic execution (via simulation) of cyber physical systems. The first tool synthesizes a formal model from scenarios. The synthesized model forms a basis for formal verification, and for model validation using simulation. The second tool, which combines the existing SCR simulator with the eBotworks 3D autonomy simulator, overcomes the SCR simulator's major limitations -- its support for only discrete computation and its inability to simulate continuous movement. To evaluate the new tools, the paper describes synthesis of a formal model of a Navy unmanned ground vehicle currently under development and simulation of its behavior.
Bach1 Deficiency and Accompanying Overexpression of Heme Oxygenase-1 Do Not Influence Aging or Tumorigenesis in Mice

Oxidative stress contributes to both aging and tumorigenesis. The transcription factor Bach1, a regulator of oxidative stress response, augments oxidative stress by repressing the expression of heme oxygenase-1 (HO-1) gene (Hmox1) and suppresses oxidative stress-induced cellular senescence by restricting the p53 transcriptional activity. Here we investigated the lifelong effects of Bach1 deficiency on mice. Bach1-deficient mice showed longevity similar to wild-type mice. Although HO-1 was upregulated in the cells of Bach1-deficient animals, the levels of ROS in Bach1-deficient HSCs were comparable to those in wild-type cells. Bach1 −/−; p53 −/− mice succumbed to spontaneous cancers as frequently as p53-deficient mice. Bach1 deficiency significantly altered transcriptome in the liver of the young mice, which surprisingly became similar to that of wild-type mice during the course of aging. The transcriptome adaptation to Bach1 deficiency may reflect how oxidative stress response is tuned upon genetic and environmental perturbations. We concluded that Bach1 deficiency and accompanying overexpression of HO-1 did not influence aging or p53 deficiency-driven tumorigenesis. Our results suggest that it is useful to target Bach1 for acute injury responses without inducing any apparent deteriorative effect.
Polymorphisms of the Steroid Sulfatase [STS] Gene are Associated With Attention Deficit Hyperactivity Disorder and Influence Brain Tissue mRNA Expression

Previous studies in animals and humans have implicated the X‐chromosome STS gene in the etiology of attentional difficulties and attention deficit hyperactivity disorder (ADHD). This family based association study has fine mapped a region of the STS gene across intron 1 and 2 previously associated with ADHD, in an extended sample of 450 ADHD probands and their parents. Significant association across this region is demonstrated individually with 7 of the 12 genotyped SNPs, as well as an allele specific haplotype of the 12 SNPs. The over transmitted risk allele of rs12861247 was also associated with reduced STS mRNA expression in normal human post‐mortem frontal cortex brain tissue compared to the non‐risk allele (P = 0.01). These results are consistent with the hypothesis arising from previous literature demonstrating that boys with deletions of the STS gene, and hence no STS protein are at a significantly increased risk of developing ADHD. Furthermore, this study has established the brain tissue transcript of STS, which except from adipose tissue, differs from that seen in all other tissues investigated. © 2010 Wiley‐Liss, Inc.
Phase I Malaria Vaccine Trial with a Long Synthetic Peptide Derived from the Merozoite Surface Protein 3 Antigen

ABSTRACT The C-terminal conserved region of Plasmodium falciparum merozoite surface protein 3 (MSP3) is the trigger antigen of a protective immune response mediated by cytophilic antibodies. In an open, randomized, two-adjuvant (Montanide ISA 720, aluminum hydroxide) phase I clinical trial we evaluated the safety and immunogenicity of increasing doses of a long synthetic peptide construct spanning the conserved region of MSP3 targeted by biologically active antibodies (MSP3-LSP). Thirty-five healthy volunteers were randomized to receive three subcutaneous injections on days 0, 30, and 120. Of the 100 injections given, 10 caused severe local reactions, 62 caused transient mild to moderate local reactions, and 28 caused no reaction. On the basis of preestablished exclusion criteria, use of the Montanide formulation led to withdrawal of five volunteers after the second injection. This led to a reduction in the subsequent vaccine doses in four of the groups. No vaccine-related serious adverse events occurred throughout the trial. After the third injection, volunteers displayed a marked specific anti-MSP3-LSP antibody response (23/30 individuals, compared with 29/34 individuals for plasma from an area where malaria is endemic), an anti-native MSP3 antibody response (19/30 individuals), a T-cell-antigen-specific proliferative response (26/30 individuals), and gamma interferon production (25/30 individuals). In conclusion, the MSP3-LSP vaccine was immunogenic with both adjuvants, although it was unacceptably reactogenic when it was combined with Montanide. The potential usefulness of the candidate vaccine is supported by the induction of a strong cytophilic response (i.e., the type of anti-MSP3 antibodies involved in antibody-dependent, monocyte-mediated protective mechanisms in areas where malaria is endemic).
Jumping to Conclusions Style along the Continuum of Delusions: Delusion-Prone Individuals Are Not Hastier in Decision Making than Healthy Individuals

Literature comparing ‘jumping to conclusions’ (JTC) between patients and healthy controls has demonstrated the importance of the reasoning bias in the development of delusions. When groups that vary along the entire delusional continuum are included, the relationship between JTC and delusionality is less clear. This study compared JTC and delusional dimensions between 28 patients with delusions, 35 delusion-prone individuals and 32 non-delusion-prone individuals. Delusion proneness was defined by an established threshold based on the Peters et al. Delusions Inventory. Two versions of the beads task (85:15 and 60:40) were used to measure JTC. As hypothesized, patients manifested hastier data gathering than the two non-clinical groups on both beads tasks. However, delusion-prone individuals did not manifest a hastier decision making style than non-delusion prone individuals. Instead, non-delusion-prone participants showed more JTC bias than delusion-prone individuals on the easier beads task. There was no evidence for a dose-response relationship between JTC and delusional dimensions, with correlations between JTC and PDI scores found in the non-delusion-prone group only. The present finding confirms the link between an extreme JTC bias and the presence of clinical delusions, and argues against a linear relationship between JTC and delusionality along the symptomatic continuum.
Development, cross-cultural adaptation, and validation of the Persian Mississippi Aphasia Screening Test in patients with post-stroke aphasia

Background: The Mississippi Aphasia Screening Test (MAST) is a brief screening test for assessing the expressive and receptive language abilities in patients with aphasia. The objective of the study was to develop and validate the Persian version of the MAST (MASTp) as a screening test for language disorders in patients with post-stroke aphasia. Methods: This study used a cross-sectional design to cross-culturally adapt the MASTp following the guidelines for the process of cross-cultural adaptation of measures. A total of 40 subjects (20 patients with post-stroke aphasia and 20 healthy subjects) were included. The MASTp was tested for floor or ceiling effects, internal consistency reliability, intra-rater reliability, discriminative validity, and factor structure. Results: There were no floor or ceiling effects for MASTp total score. The MASTp yielded values for internal consistency reliability that were not adequate (Cronbach’s alpha 0.64 and 0.66 for test and retest, respectively. The intra-rater reliability of the MASTp within a 7 day-interval was excellent for total score (ICC agreement = 0.96) and both expressive index (ICC = 0.95) and receptive index (ICC agreement = 0.98). here were statistically significant differences in MASTp total scores and both indexes between patients and healthy subjects suggesting the discriminative validity of the MASTp (P < 0.001). Factor analysis revealed a 3-factor solution, which jointly accounted for 72.06% of the total variance. Additional factor analysis suggested 6-item MASTp as a unidimensional measure. Conclusion: The MASTp is useful as a valid and reliable screening tool for evaluation of language abilities in Persian speaking patients with aphasia after stroke.
Environmental Monitoring Using Wireless Vehicular Sensor Networks

In this paper, the use of wireless vehicular sensor networks (VSN) were explored for the purpose of environmental monitoring. A prototype for the mobile sensor node that can be mounted onto vehicles, such as public buses, was introduced and from the experiments performed, it was demonstrated that the use of mobile vehicular sensors instead of static sensors allowed for higher spatial coverage at the expense of lower temporal resolution.
From age-ing to sage-ing : a profound new vision of growing older

Over two decades ago, beloved and respected rabbi Zalman Schachter-Shalomi felt an uneasiness. He was growing older, and fears about death and infirmity were haunting him. So he decided to embark on mission to get to the bottom of his fears. Through a series of events that included a vision quest in a secluded cabin and studying with Sufi masters, Buddhist teachers and Native-American shamans, Reb Zalman found a way to turn aging into the most meangful and joyous time in his life. In this inspiring and informative guide, Reb Zalman shares his wisdom and experience with readers. He shows readers how to create an aging process for themselves that is full of adventure, passion, mystery, and fulfillment, rather than anxiety. Using scientific research--both neurological and psychological-- Reb Zalman offers techniques that will expand horizons beyond the narrow view of "the present" into a grand and enduring eternity. By harnessing the power of the spirit, as well as explaining exactly how to become a sage in their own community, he gives readers a helpful and moving way to use their own experiences to nurture, heal, and perhaps even save a younger generation from the prison of how we typically regard aging. In this updated version of his popular book, Reb Zalman has added a brand new introductory chapter that provides insight into the shifts that have taken place in our culture since the first edition of this book came out in the 1990s. He speaks about the role the 78 million (now aging) Baby Boomers are currently playing in how we think about aging. Additionally he provides new inspiring ideas about the importance of an elder's role in shaping society, and explains how elders can embrace the power they have to provide value and wisdom to those around them.
Cysteinyl Peptide Capture for Shotgun Proteomics: Global Assessment of Chemoselective Fractionation

The complexity of cell and tissue proteomes presents one of the most significant technical challenges in proteomic biomarker discovery. Multidimensional liquid chromatography−tandem mass spectrometry (LC−MS/MS)-based shotgun proteomics can be coupled with selective enrichment of cysteinyl peptides (Cys-peptides) to reduce sample complexity and increase proteome coverage. Here we evaluated the impact of Cys-peptide enrichment on global proteomic inventories. We employed a new cleavable thiol-reactive biotinylating probe, N-(2-(2-(2-(2-(3-(1-hydroxy-2-oxo-2-phenylethyl)phenoxy)acetamido)ethoxy)-ethoxy)ethyl)-5-(2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide (IBB), to capture Cys-peptides after digestion. Treatment of tryptic digests with the IBB reagent followed by streptavidin capture and mild alkaline hydrolysis releases a highly purified population of Cys-peptides with a residual S-carboxymethyl tag. Isoelectric focusing (IEF) followed by LC−MS/MS of Cys-peptides significantly expanded proteome coverage in Saccharomyces cerevisiae (yeast) and in human colon carcinoma RKO cells. IBB-based fractionation enhanced detection of Cys-proteins in direct proportion to their cysteine content. The degree of enrichment typically was 2−8-fold but ranged up to almost 20-fold for a few proteins. Published copy number annotation for the yeast proteome enabled benchmarking of MS/MS spectral count data to yeast protein abundance and revealed selective enrichment of cysteine-rich, lower abundance proteins. Spectral count data further established this relationship in RKO cells. Enhanced detection of low abundance proteins was due to the chemoselectivity of Cys-peptide capture, rather than simplification of the peptide mixture through fractionation.
Conflict Resolution in Multiple Access Channels Supporting Simultaneous Successful Transmissions

We consider the Conflict Resolution Problem in the context of a multiple-access system in which several stations can transmit their messages simultaneously to the channel. We assume that there are n stations and that at most k<= n stations are active at the same time, i.e, are willing to transmit a message. If in a certain instant at most d<=k active stations transmit to the channel then their messages are successfully transmitted, whereas if more than d active stations transmit simultaneously then their messages are lost. In this latter case we say that a conflict occurs. The present paper investigates non-adaptive conflict resolution algorithms working under the assumption that active stations receive a feedback from the channel that informs them on whether their messages have been successfully transmitted. If a station becomes aware that its message has been correctly sent over the channel then it becomes immediately inactive. The measure to optimize is the number of time slots needed to solve conflicts among all active stations. The fundamental question is whether this measure decreases linearly with the number d of messages that can be simultaneously transmitted with success. We give a positive answer to this question by providing a conflict resolution algorithm that uses a 1/d ratio of the number of time slots used by the optimal conflict resolution algorithm for the case d=1. Moreover, we derive a lower bound on the number of time slots needed to solve conflicts non-adaptively which is within a log (k/d) factor from the upper bound. To this aim, we introduce a new combinatorial structure that consists in a generalization of Komlos and Greenberg codes. Constructions of these new codes are obtained via a new generalization of selectors, whereas the non-existential result is implied by a non-existential result for a new generalization of the locally thin families.
A Robust Missing Value Imputation Method MifImpute For Incomplete Molecular Descriptor Data And Comparative Analysis With Other Missing Value Imputation Methods

Missing data imputation is an important research topic in data mining. Large-scale Molecular descriptor data may contains missing values (MVs). However, some methods for downstream analyses, including some prediction tools, require a complete descriptor data matrix. We propose and evaluate an iterative imputation method MiFoImpute based on a random forest. By averaging over many unpruned regression trees, random forest intrinsically constitutes a multiple imputation scheme. Using the NRMSE and NMAE estimates of random forest, we are able to estimate the imputation error. Evaluation is performed on two molecular descriptor datasets generated from a diverse selection of pharmaceutical fields with artificially introduced missing values ranging from 10% to 30%. The experimental result demonstrates that missing values has a great impact on the effectiveness of imputation techniques and our method MiFoImpute is more robust to missing value than the other ten imputation methods used as benchmark. Additionally, MiFoImpute exhibits attractive computational efficiency and can cope with high-dimensional data.