Miracle-dz/UniFAR-FTUs huggingface dataset:
Double-stranded RNA under force and torque: Similarities to and striking differences from double-stranded DNA

Significance RNA, like DNA, can form double helices held together by the pairing of complementary bases, and such helices are ubiquitous in functional RNAs. Here we apply external forces and torques to individual double-stranded RNA molecules to determine the mechanical properties and conformational transitions of these fundamental biological building blocks. For small forces and torques, RNA helices behave like elastic rods, and we have determined their bending, stretching, and twisting stiffness. Surprisingly, we find that RNA shortens when it is overwound, whereas DNA lengthens. Finally, we twist RNA until it buckles and forms a loop, and find the timescale of this transition to be much slower for RNA compared with DNA, suggesting unexpected differences in their flexibilities on short length scales. RNA plays myriad roles in the transmission and regulation of genetic information that are fundamentally constrained by its mechanical properties, including the elasticity and conformational transitions of the double-stranded (dsRNA) form. Although double-stranded DNA (dsDNA) mechanics have been dissected with exquisite precision, much less is known about dsRNA. Here we present a comprehensive characterization of dsRNA under external forces and torques using magnetic tweezers. We find that dsRNA has a force–torque phase diagram similar to that of dsDNA, including plectoneme formation, melting of the double helix induced by torque, a highly overwound state termed “P-RNA,” and a highly underwound, left-handed state denoted “L-RNA. ” Beyond these similarities, our experiments reveal two unexpected behaviors of dsRNA: Unlike dsDNA, dsRNA shortens upon overwinding, and its characteristic transition rate at the plectonemic buckling transition is two orders of magnitude slower than for dsDNA. Our results challenge current models of nucleic acid mechanics, provide a baseline for modeling RNAs in biological contexts, and pave the way for new classes of magnetic tweezers experiments to dissect the role of twist and torque for RNA–protein interactions at the single-molecule level.
Fetal growth cessation in late pregnancy: its impact on predicted size parameters used to classify small for gestational age neonates

Abstract Objective: To evaluate the impact of late 3rd trimester fetal growth cessation on anatomical birth characteristic predictions used in classifying SGA neonates. Methods: A prospective longitudinal study was performed in 119 pregnancies with normal neonatal growth outcomes. Seven biometric parameters were measured at 3–4 weeks intervals using 3D ultrasonography. Rossavik size models were determined to predict birth characteristics at different ages. Percent Differences (% Diff) were calculated from predicted and measured birth characteristics. Growth Cessation Ages (GCA) were identified when no systematic change in % Diff values occurred after specified prediction ages. Systematic and random prediction errors were compared using different assumptions about the GCA. Predicted and measured size parameters were used to determine six new Growth Potential Realization Index (GPRI) reference ranges. Five were used to sub-classify 34 SGA neonates (weight < 10th percentile) based on the number of abnormal GPRI values. Results: Growth cessation ages were 38 weeks for HC, AC, mid-thigh circumference, estimated weight and mid-arm circumference. Crown-heel length GCA was 38.5 weeks. At GCA, birth characteristics had prediction errors that varied from 0.08 ± 3.4% to 15.7 ± 9.1% and zero % Diff slopes after 38 weeks. Assuming growth to delivery gave increased systematic and random prediction errors as well as positive % Diff slopes after 38 weeks, MA. Seventeen of the SGA neonates had 0 or 1 abnormal GPRI values [Subgroup 1] and 17 others had 2 or more abnormal values [Subgroup 2]. In Subgroup 1, 4/85 (4.7%) of GPRI's were abnormal while in Subgroup 2, 43/85 (50.6%) were abnormal. Use of only one type of GPRI for SGA subclassification resulted in substantial false negative and some false positive rates when compared to subclassification based on all five GPRI values. Conclusions: Growth cessation occurred at approximately 38 weeks for all six birth characteristics studied. SGA neonates can be separated into normal and growth restricted subgroups based on the frequency of abnormal GPRI values (GPRI Profile Classification).
Characterization of Genetically Modified T-Cell Receptors that Recognize the CEA:691-699 Peptide in the Context of HLA-A2.1 on Human Colorectal Cancer Cells

Purpose: Carcinoembryonic antigen (CEA) is a tumor-associated protein expressed on a variety of adenocarcinomas. To develop an immunotherapy for patients with cancers that overexpress CEA, we isolated and genetically modified a T-cell receptors (TCRs) that specifically bound a CEA peptide on human cancer cells. Experimental Design: HLA-A2.1 transgenic mice were immunized with CEA:691-699. A CEA-reactive TCR was isolated from splenocytes of these mice and was genetically introduced into human peripheral blood lymphocytes via RNA electroporation or retroviral transduction. Amino acid substitutions were introduced throughout the complementarity determining regions (CDR1, CDR2, and CDR3) of both TCR α and β chains to improve recognition of CEA. Results: Murine lymphocytes bearing the CEA-reactive TCR specifically recognized peptide-loaded T2 cells and HLA-A2.1+ CEA+ human colon cancer cells. Both CD8+ and CD4+ human lymphocytes expressing the murine TCR specifically recognized peptide-loaded T2 cells. However, only gene-modified CD8+ lymphocytes specifically recognized HLA-A2.1+ CEA+ colon cancer cell lines, and tumor cell recognition was weak and variable. We identified two substitutions in the CDR3 of the α chain that significantly influenced tumor cell recognition by human peripheral blood lymphocytes. One substitution, T for S at position 112 (S112T), enhanced tumor cell recognition by CD8+ lymphocytes, and a second dually substituted receptor (S112T L110F) enhanced tumor cell recognition by CD4+ T cells. Conclusions: The modified CEA-reactive TCRs are good candidates for future gene therapy clinical trials and show the power of selected amino acid substitutions in the antigen-binding regions of the TCR to enhance desired reactivities.
A Role for Snf2-Related Nucleosome-Spacing Enzymes in Genome-Wide Nucleosome Organization

Three chromatin remodeling enzymes in yeast drive higher-order chromatin compaction. The positioning of nucleosomes within the coding regions of eukaryotic genes is aligned with respect to transcriptional start sites. This organization is likely to influence many genetic processes, requiring access to the underlying DNA. Here, we show that the combined action of Isw1 and Chd1 nucleosome-spacing enzymes is required to maintain this organization. In the absence of these enzymes, regular positioning of the majority of nucleosomes is lost. Exceptions include the region upstream of the promoter, the +1 nucleosome, and a subset of locations distributed throughout coding regions where other factors are likely to be involved. These observations indicate that adenosine triphosphate–dependent remodeling enzymes are responsible for directing the positioning of the majority of nucleosomes within the Saccharomyces cerevisiae genome.
La atención y los límites de la experiencia consciente 1 Attention and the limits of conscious experience

The phenomenological conception of common sense inspired by James (1890) claims that attending is essentially a conscious mental phenomenon. The modal philosophical implications of this thesis regarding the nature of attention are clear. It is not possible to attend something without being conscious of that thing. On the basis of classical studies on visual pathologies such as blindsight and recent experiments with non-pathological subjects, this paper argues that the Jamesian philosophical conclusion regarding the metaphysics of attention is false. Evidence suggests that in fact it is possible to attend to objects without consciously experiencing them.
Germline variation in NCF4, an innate immunity gene, is associated with an increased risk of colorectal cancer

Chronic inflammation has been implicated in the etiology of colorectal adenoma and cancer; however, few key inflammatory genes mediating this relationship have been identified. In this study, we investigated the association of germline variation in innate immunity genes in relation to the risk of colorectal neoplasia. Our study was based on the analysis of samples collected from the prostate, lung, colorectal and ovarian (PLCO) Cancer Screening Trial. We investigated the association between 196 tag single nucleotide polymorphisms (SNPs) in 20 key innate immunity genes with risk of advanced colorectal adenoma and cancer in 719 adenoma cases, 481 cancer cases and 719 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). After Bonferroni correction, the AG/GG genotype of rs5995355, which is upstream of NCF4, was associated with an increased risk of colorectal cancer (OR = 2.43, 95% CI = 1.73–3.39; p < 0.0001). NCF4 is part of the NAPDH complex, a key factor in biochemical pathways and the innate immune response. While not definitive, our analyses suggest that the variant allele does not affect expression of NCF4, but rather modulates activity of the NADPH complex. Additional studies on the functional consequences of rs5995355 in NCF4 may help to clarify the mechanistic link between inflammation and colorectal cancer.
Personalizing cognitive-behavioral treatment for pediatric obsessive-compulsive disorder

ABSTRACT Introduction: Pediatric obsessive-compulsive disorder (OCD) is a heterogeneous psychiatric condition that affects approximately 1–2% of youth. Exposure and response prevention (ERP), a behavioral intervention, is considered the first-line treatment for pediatric OCD. Although efficacious, a myriad of factors may complicate care for youth with OCD, suggesting the potential benefits of personalizing care for these youth. Areas covered: Factors such as comorbid psychopathology, familial factors (e.g., symptom accommodation, parental psychopathology), insight, developmental stage, and types of OCD symptom dimensions can each negatively affect treatment progress. Each of these factors are covered in length, with suggested clinical modifications provided in detail. Expert commentary: Youth with OCD will optimally benefit from mental health professionals that are appropriately trained in using the core components of ERP (i.e., exposure therapy). Adequate training and psychoeducation about factors that may complicate care are necessary to ensure that these youth receive targeted, personalized care that is efficacious.
The Dialogic Mindset in Organization Development

Abstract Extending the argument made in Bushe and Marshak (2009) of the emergence of a new species of Organization Development (OD) that we label Dialogic, to differentiate it from the foundational Diagnostic form, we argue that how any OD method is used in practice will be depend on the mindset of the practitioner. Six variants of Dialogic OD practice are reviewed and compared to aid in identification of a Weberian ideal-type Dialogic Mindset, consisting of eight premises that distinguish it from the foundational Diagnostic Mindset. Three core change processes that underlie all successful Dialogic OD processes are proposed, and suggestions for future research offered.
Automatic Labelling and Selection of Training Samples for High-Resolution Remote Sensing Image Classification over Urban Areas

Supervised classification is the commonly used method for extracting ground information from images. However, for supervised classification, the selection and labelling of training samples is an expensive and time-consuming task. Recently, automatic information indexes have achieved satisfactory results for indicating different land-cover classes, which makes it possible to develop an automatic method for labelling the training samples instead of manual interpretation. In this paper, we propose a method for the automatic selection and labelling of training samples for high-resolution image classification. In this way, the initial candidate training samples can be provided by the information indexes and open-source geographical information system (GIS) data, referring to the representative land-cover classes: buildings, roads, soil, water, shadow, and vegetation. Several operations are then applied to refine the initial samples, including removing overlaps, removing borders, and semantic constraints. The proposed sampling method is evaluated on a series of high-resolution remote sensing images over urban areas, and is compared to classification with manually labeled training samples. It is found that the proposed method is able to provide and label a large number of reliable samples, and can achieve satisfactory results for different classifiers. In addition, our experiments show that active learning can further enhance the classification performance, as active learning is used to choose the most informative samples from the automatically labeled samples.
Batf3 and Id2 Have a Synergistic Effect on Irf8-Directed Classical CD8α+ Dendritic Cell Development

Dendritic cells (DCs) are heterogeneous cell populations represented by different subtypes, each varying in terms of gene expression patterns and specific functions. Recent studies identified transcription factors essential for the development of different DC subtypes, yet molecular mechanisms for the developmental program and functions remain poorly understood. In this study, we developed and characterized a mouse DC progenitor-like cell line, designated DC9, from Irf8−/− bone marrow cells as a model for DC development and function. Expression of Irf8 in DC9 cells led to plasmacytoid DCs and CD8α+ DC–like cells, with a concomitant increase in plasmacytoid DC– and CD8α+ DC–specific gene transcripts and induction of type I IFNs and IL12p40 following TLR ligand stimulation. Irf8 expression in DC9 cells led to an increase in Id2 and Batf3 transcript levels, transcription factors shown to be important for the development of CD8α+ DCs. We show that, without Irf8, expression of Id2 and Batf3 was not sufficient for directing classical CD8α+ DC development. When coexpressed with Irf8, Batf3 and Id2 had a synergistic effect on classical CD8α+ DC development. We demonstrate that Irf8 is upstream of Batf3 and Id2 in the classical CD8α+ DC developmental program and define the hierarchical relationship of transcription factors important for classical CD8α+ DC development.
MassSieve: Panning MS/MS peptide data for proteins

We present MassSieve, a Java‐based platform for visualization and parsimony analysis of single and comparative LC‐MS/MS database search engine results. The success of mass spectrometric peptide sequence assignment algorithms has led to the need for a tool to merge and evaluate the increasing data set sizes that result from LC‐MS/MS‐based shotgun proteomic experiments. MassSieve supports reports from multiple search engines with differing search characteristics, which can increase peptide sequence coverage and/or identify conflicting or ambiguous spectral assignments.
Hodgkin Lymphoma Among US Solid Organ Transplant Recipients

Background. To assess the risk and identify risk factors of Hodgkin lymphoma (HL) in solid organ transplant recipients. Prior research has been limited by the rarity of HL and the requirement for extended follow-up after transplantation. Methods. Using data from the Scientific Registry of Transplant Recipients (SRTR), we conducted a retrospective cohort study of US solid organ transplant recipients (1997–2007). We estimated hazard ratios (HRs) for HL risk factors using proportional hazards regression. Standardized incidence ratios (SIRs) compared HL risk in the transplant cohort with the general population. Results. The cohort included 283,190 transplant recipients (average follow-up: 3.7 years after transplantation). Based on 73 cases, HL risk factors included male gender (HR: 2.1, 95% CI: 1.2–3.7), young age (4.0, 2.3–6.8), and Epstein-Barr virus (EBV) seronegativity at the time of transplantation (3.1, 1.2–8.1). Among tumors with EBV status information, 79% were EBV positive, including all tumors in recipients who were initially seronegative. Overall, HL risk was higher than in the general population (SIR: 2.2) and increased monotonically over time after transplantation (SIR: 4.1 at 8–10 years posttransplant). Excess HL risk was especially high after heart and/or lung transplantation (SIR: 3.2). Conclusion. HL is a late complication of solid organ transplantation. The high HL risk in recipients who were young or EBV seronegative at the time of transplant and the fact that most HL tumors were EBV positive highlight the role of primary EBV infection and poor immune control of this virus. The occurrence of HL may rise with improved long-term survival in transplant recipients.
Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease.

CONTEXT Blood-based analytes may be indicators of pathological processes in Alzheimer disease (AD). OBJECTIVE To identify plasma proteins associated with AD pathology using a combined proteomic and neuroimaging approach. DESIGN Discovery-phase proteomics to identify plasma proteins associated with correlates of AD pathology. Confirmation and validation using immunodetection in a replication set and an animal model. SETTING A multicenter European study (AddNeuroMed) and the Baltimore Longitudinal Study of Aging. PARTICIPANTS Patients with AD, subjects with mild cognitive impairment, and healthy controls with standardized clinical assessments and structural neuroimaging. MAIN OUTCOME MEASURES Association of plasma proteins with brain atrophy, disease severity, and rate of clinical progression. Extension studies in humans and transgenic mice tested the association between plasma proteins and brain amyloid. RESULTS Clusterin/apolipoprotein J was associated with atrophy of the entorhinal cortex, baseline disease severity, and rapid clinical progression in AD. Increased plasma concentration of clusterin was predictive of greater fibrillar amyloid-beta burden in the medial temporal lobe. Subjects with AD had increased clusterin messenger RNA in blood, but there was no effect of single-nucleotide polymorphisms in the gene encoding clusterin with gene or protein expression. APP/PS1 transgenic mice showed increased plasma clusterin, age-dependent increase in brain clusterin, as well as amyloid and clusterin colocalization in plaques. CONCLUSIONS These results demonstrate an important role of clusterin in the pathogenesis of AD and suggest that alterations in amyloid chaperone proteins may be a biologically relevant peripheral signature of AD.
A systems programming language for wireless networked embedded systems

Wireless networked sensors raise a great number of programming challenges in applications. In this paper, we present AntC, a systems programming language, which focuses on the super-micro embedded system that supports wireless networked sensors. It provides four broad characteristics: it is a component-oriented application design; it integrates an embedded OS with two-level dispatcher; it improves the fault tolerance in run-time; furthermore, the improvement on multiplatform adaptability allows AntC program to be easily transplanted to other platforms with different embedded processors.
Ventilatory acclimatization to moderate hypoxemia in man. The role of spinal fluid (H+).

This study has assessed the regulation of arterial blood and cerebrospinal fluid (CSF) pH and thereby their contribution to the control of breathing in normal man during various stages of ventilatory acclimatization to 3,100 m altitude. CSF acid-base status was determined: (a) from measurements of lumbar spinal fluid during steady-state conditions of chronic normoxia (250 m altitude) and at + 8 h and + 3-4 wk of hypobaric hypoxia; and (b) from changes in cerebral venous P(CO2) at + 1 h hypoxic exposure. After 3-4 wk at 3,100 m, CSF [H(+)] remained significantly alkaline to values obtained in either chronic normoxia or with 1 h hypoxic exposure and was compensated to the same extent ( approximately 66%) as was arterial blood [H(+)]. Ventilatory acclimatization to 3,100 m bore no positive relationship to accompanying changes in arterial P(O2) and pH and CSF pH: (a) CSF pH either increased or remained constant at 8 h and at 3-4 wk hypoxic exposure, respectively, coincident with significant, progressive reductions in Pa(CO2); (b) arterial P(O2) and pH increased progressively with time of exposure; and (c) in the steady-state of acclimatization to 3,100 m the combination of chemical stimuli present, i.e. Pa(O2) = 60 mm Hg, pHa and pH(CSF) = + 0.03-0.04 > control, was insufficient to produce the observed hyperventilation (Pa(CO2) = 32 mm Hg). It was postulated that ventilatory acclimatization to 3,100 m altitude was mediated by factors other than CSF [H(+)] and that the combination of chronic hypoxemia and hypocapnia of moderate degrees provided no mechanisms for the specific regulation of CSF [H(CO3) (-)] and hence for homeostasis of CSF [H(+)].
Antecedents and consequences of consumer-customized product identification: An identity theory perspective

Kwon, So Yeon, Ph.D. Purdue University, December 2015. Antecedents and Consequences of Consumer-Customized Product Identification: An Identity Theory Perspective. Major Professor: Christopher J. Kowal. Customization is considered one of the key sources of value creation in a highly competitive and segmented market. Recent research has demonstrated that the key to successful customization experiences lies in the degree to which consumers feel connected to a product that is customized. This study investigated consumers’ psychological connection to customized products by exploring the variable, “consumercustomized product identification (C-C identification). ” Building upon identity theory and research on “extended self,” this study investigated (1) two key antecedents that influence C-C identification, (2) attitudinal and behavioral consequences of C-C identification, and (3) the moderating role of product involvement in C-C identification development. In order to examine the proposed hypotheses, a scenario-based survey was administered with three product categories (i.e., personalized media, fashion & textiles, and food). A similar pattern of results was found across the three product categories. This study demonstrated that consumers developed identification with customized products when the value of the customization experiences was congruent with consumers’ sense of self (i.e., identity congruence) and when the customized products signaled consumers’ unique identity to others (i.e., identity distinctiveness). Consumers’ identification with customized products enhanced favorable attitude toward customized products and