Miracle-dz/UniFAR-FTUs huggingface dataset:
Crotalid venom vascular endothelial growth factors has preferential affinity for VEGFR-1

Summary Pm-VEGF, a novel member ofVEGF family from the venom gland of Taiwan habu (Protobothrops mucrosquamatu), is a disulfidelinked homodimer with 119 amino acid residues. Recombinant fusion Pm-VEGF was expressed in Escherichia coli, purified and refolded. Surface plasmon resonance was used to determine its binding kinetics toVEGF-receptors (VEGFR). Relative to human VEGF165, the binding affinity of Pm-VEGF to the VEGFR-1 was 1.7-fold higher while affinity to the VEGFR-2 was 17-fold lower. But it did not bind theVEGFR-3 or neuropilin-1. Pm-VEGF promoted the proliferation and tissue factor production of endothelial cells, the neovascularization in the chicken chorioallantoic membrane, and increased vascular permeability. It also stimulated tissue-factor production and human monocyte chemotaxis, in accord with its specificity for VEGFR-1. Structural comparison among VEGF-proteins from various viper venoms revealed that the two subfamilies of vipers (Crotalinae and Viperinae) have evolved with distinct receptor-specificities for VEGFR-1 and VEGFR-2, respectively. Discussion on structureactivity relationships of the VEGFs further provided insight into residues important for the receptor-binding and specificities.
Stability analysis on four agent tetrahedral formations

We consider a four agent tetrahedral formation of mobile agents in 3-dimensional Euclidean space. Each agent is required to maintain prescribed inter-agent distances from its neighbors so that they collectively form a desired formation shape, a task which is now called distance-based formation control. Under a common gradient-based control law, there exists an incorrect equilibrium set in which the agents do not achieve the desired formation shape. By investigating the linearized dynamics of the system, we prove that all incorrect equilibria are unstable, which results in that desired formation shape is almost globally asymptotically stable. Numerical simulation results are also included.
A qualitative study of younger men's experience of heart attack (myocardial infarction).

OBJECTIVES The effects of heart attack, or myocardial infarction (MI), across psychosocial domains may be particularly acute in younger adults, for whom serious health events are non-normative. MI morbidity is declining in Western countries, but in England MI numbers have plateaued for the under-45 cohort, where approximately 90% of patients are male. Qualitative research on younger adults' experience of MI is limited, and no study has sampled exclusively under-45s. This study aimed to understand how a sample of men under 45 adjusted to and made sense of MI. DESIGN Qualitative research design based on semi-structured in-depth interviews. METHODS Ten men aged under 45 who had experienced MI in the past 3-6 months were purposively recruited and interviewed. Interviews were transcribed verbatim and analysed using interpretative phenomenological analysis. RESULTS Seven superordinate themes were identified. This article focuses in depth on the three most original themes: (1) 'I'm less of a man', which described experiences of losing 'maleness' (strength, independence, ability to provide) post-MI; (2) 'Shortened horizons', which covered participants' sense of foreshortened future and consequent reprioritization; and (3) 'Life loses its colour', describing the loss of pleasure from lifestyle-related changes. CONCLUSION Themes broadly overlapped with the qualitative literature on younger adult MI. However, some themes (e.g., loss of 'maleness' post-MI, and ambivalence towards MI risk factors) appeared unique to this study. Themes were also discussed in relation to risk factors for anxiety and depression and how this might inform clinical care for a younger, male population. Statement of contribution What is already known on this subject? Myocardial infarction (MI) morbidity is not declining in England for under-45s. Adjustment to MI is particularly challenging for younger adults, perhaps because it is non-normative. However, little is known about the experience of MI in younger adults. What does this study add? This is the first qualitative study to sample MI patients exclusively under 45, thereby mapping to epidemiological trends. Further support is provided for some themes identified in the existing young adult MI literature. New themes are identified here which can provide insights relevant to clinical care in this population.
Identification of seipin-linked factors that act as determinants of a lipid droplet subpopulation

Functional heterogeneity within the lipid droplet (LD) pool of a single cell has been observed, yet the underlying mechanisms remain enigmatic. Here, we report on identification of a specialized LD subpopulation characterized by a unique proteome and a defined geographical location at the nucleus–vacuole junction contact site. In search for factors determining identity of these LDs, we screened ∼6,000 yeast mutants for loss of targeting of the subpopulation marker Pdr16 and identified Ldo45 (LD organization protein of 45 kD) as a crucial targeting determinant. Ldo45 is the product of a splicing event connecting two adjacent genes (YMR147W and YMR148W/OSW5/LDO16). We show that Ldo proteins cooperate with the LD biogenesis component seipin and establish LD identity by defining positioning and surface-protein composition. Our studies suggest a mechanism to establish functional differentiation of organelles, opening the door to better understanding of metabolic decisions in cells.
Effects of b-value and number of gradient directions on diffusion MRI measures obtained with Q-ball imaging

High-angular-resolution diffusion-weighted imaging (HARDI) MRI acquisitions have become common for use with higher order models of diffusion. Despite successes in resolving complex fiber configurations and probing microstructural properties of brain tissue, there is no common consensus on the optimal b-value and number of diffusion directions to use for these HARDI methods. While this question has been addressed by analysis of the diffusion-weighted signal directly, it is unclear how this translates to the information and metrics derived from the HARDI models themselves. Using a high angular resolution data set acquired at a range of b-values, and repeated 11 times on a single subject, we study how the b-value and number of diffusion directions impacts the reproducibility and precision of metrics derived from Q-ball imaging, a popular HARDI technique. We find that Q-ball metrics associated with tissue microstructure and white matter fiber orientation are sensitive to both the number of diffusion directions and the spherical harmonic representation of the Q-ball, and often are biased when under sampled. These results can advise researchers on appropriate acquisition and processing schemes, particularly when it comes to optimizing the number of diffusion directions needed for metrics derived from Q-ball imaging.
Missed diagnosis of stroke in the emergency department: a cross-sectional analysis of a large population-based sample

Abstract Background: Some cerebrovascular events are not diagnosed promptly, potentially resulting in death or disability from missed treatments. We sought to estimate the frequency of missed stroke and examine associations with patient, emergency department (ED), and hospital characteristics. Methods: Cross-sectional analysis using linked inpatient discharge and ED visit records from the 2009 Healthcare Cost and Utilization Project State Inpatient Databases and 2008–2009 State ED Databases across nine US states. We identified adult patients admitted for stroke with a treat-and-release ED visit in the prior 30 days, considering those given a non-cerebrovascular diagnosis as probable (benign headache or dizziness diagnosis) or potential (any other diagnosis) missed strokes. Results: There were 23,809 potential and 2243 probable missed strokes representing 12.7% and 1.2% of stroke admissions, respectively. Missed hemorrhages (n=406) were linked to headache while missed ischemic strokes (n=1435) and transient ischemic attacks (n=402) were linked to headache or dizziness. Odds of a probable misdiagnosis were lower among men (OR 0.75), older individuals (18–44 years [base]; 45–64:OR 0.43; 65–74:OR 0.28; ≥75:OR 0.19), and Medicare (OR 0.66) or Medicaid (OR 0.70) recipients compared to privately insured patients. Odds were higher among Blacks (OR 1.18), Asian/Pacific Islanders (OR 1.29), and Hispanics (OR 1.30). Odds were higher in non-teaching hospitals (OR 1.45) and low-volume hospitals (OR 1.57). Conclusions: We estimate 15,000–165,000 misdiagnosed cerebrovascular events annually in US EDs, disproportionately presenting with headache or dizziness. Physicians evaluating these symptoms should be particularly attuned to the possibility of stroke in younger, female, and non-White patients.
&agr;-Smooth Muscle Actin Expressing Stroma Promotes an Aggressive Tumor Biology in Pancreatic Ductal Adenocarcinoma

Objectives: Pancreatic ductal adenocarcinoma (PDAC) is often characterized by a prominent desmoplastic stroma that is induced partially by &agr;-smooth muscle actin (SMA)-expressing activated pancreatic stellate cells (PSCs). This study aimed to investigate the significance of &agr;-SMA expression in PDAC and the correlation between &agr;-SMA mRNA levels and the patient prognosis. Methods: We obtained formalin-fixed, paraffin-embedded tissue samples from 109 patients with PDAC, who underwent pancreatectomy at our institution from 1992 to 2007. We measured &agr;-SMA mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction and investigated the association of &agr;-SMA mRNA expression with clinicopathologic parameters and survival time. We also assessed the influence of activated PSCs on malignant behaviors of pancreatic cancer cells using in vitro experiments. Results: &agr;-SMA immunoreactivity was detected exclusively in the stroma of PDAC. The group with high &agr;-SMA expression showed a significantly shorter survival, as shown by univariate analysis (P = 0.005) and multivariate analysis (P < 0.0001). &agr;-SMA-expressing activated PSCs enhanced the invasiveness, proliferation, and colony formation of pancreatic cancer cells. Conclusions: Quantitative analysis of &agr;-SMA mRNA expression using formalin-fixed, paraffin-embedded tissue samples was useful to predict the prognosis of patients with PDAC. Activated PSCs may regulate the malignant behavior of pancreatic cancer cells. Abbreviations: PDAC - pancreatic ductal adenocarcinoma, PSCs - pancreatic stellate cells, &agr;-SMA - &agr;-smooth muscle actin, FFPE - formalin-fixed paraffin-embedded, qRT-PCR - quantitative real-time reverse transcription-polymerase chain reaction, ECM - extracellular matrix, GFP - green fluorescent protein, CM - conditioned media, UICC - Union Internationale Contre le Cancer and the American Joint Committee on Cancer, COL1 - collagen type I, AC - adjuvant chemotherapy
A critical appraisal of guidelines for electronic communication between patients and clinicians: the need to modernize current recommendations

Background Patient-provider electronic communication has proliferated in recent years, yet there is a dearth of published research either leading to, or including, recommendations that improve clinical care and prevent unintended negative consequences. We critically appraise published guidelines and suggest an agenda for future work in this area. Objective To understand how existing guidelines align with current practice, evidence, and technology. Methods We performed a narrative review of provider-targeted guidelines for electronic communication between patients and providers, searching Ovid MEDLINE, Embase, and PubMed databases using relevant terms. We limited the search to articles published in English, and manually searched the citations of relevant articles. For each article, we identified and evaluated the suggested practices. Results Across 11 identified guidelines, the primary focus was on technical and administrative concerns, rather than on relational communication. Some of the security practices recommended by the guidelines are no longer needed because of shifts in technology. It is unclear the extent to which the recommendations that are still relevant are being followed. Moreover, there is no guideline-cited evidence of the effectiveness of the practices that have been proposed. Conclusion Our analysis revealed major weaknesses in current guidelines for electronic communication between patients and providers: the guidelines appear to be based on minimal evidence and offer little guidance on how best to use electronic tools to communicate effectively. Further work is needed to systematically evaluate and identify effective practices, create a framework to evaluate quality of communication, and assess the relationship between electronic communication and quality of care.
Harmonic oscillators realized using current amplifiers and grounded capacitors

New configurations of harmonic oscillators, realized using current amplifier blocks and only grounded capacitors, are introduced in this article. The proposed configurations are based on a grounded inductor simulator scheme and on a loop constructed from first‐order sections, respectively. Comparison with the already published topologies shows that the new configurations have attractive characteristics concerning their implementation in integrated form. Copyright © 2006 John Wiley & Sons, Ltd.
PACIFIC trial: new perspectives for immunotherapy in lung cancer.

Lung cancer still represents the most frequent cause of cancer-related mortality worldwide and 85% of all lung neoplastic disease are classified as non-small-cell lung cancer (NSCLC) (1); approximately one third of NSCLC are locally advanced disease at diagnosis (2). Actually, the standard-of-care for unresectable or inoperable stage IIIA and IIIB disease for patients with good performance status consists of platinum-based doublet chemotherapy (CT) concurrent with 60 Gy of radiotherapy (RT) administered daily over 6 weeks followed by possible further two cycles of consolidative CT (2). The supportive evidence for the use of concomitant chemoradiotherapy (CT/RT) is rooted in many clinical trials, with evidence of better results of concurrent CT/RT compared to either modality of administration of CT and RT, alone or sequential (3). The 5-year overall survival (OS) rate is 15–35% for stage IIIA and 5–10% for stage IIIB (4). Although survival outcomes are poor, notable is that a subset of the patients are potentially curable.
GATA3 differential expression in neuroblastoma and nephroblastoma

We have read with great interest the report by Wiles et al, published in Cancer Cytopathology, about the immunohistochemical expression of the GATA3 antibody in cytological material from neuroblastomas. They evaluated GATA3 immunohistochemical expression in neuroblastoma cytology and/or biopsy samples, and diffuse nuclear positivity was found in all 30 specimens studied. Each sample revealed either strong (n 5 26) or moderate nuclear staining (n 5 4) in more than 75% of neuroblastoma cells, regardless of the presence or lack of stromata, necrosis, or differentiation. GATA3 is a relatively recent marker useful for diagnosing tumors of various epithelial and nonepithelial origins such as mammary tumors, urothelial tumors, renal tumors, germ cell tumors, mesotheliomas, and paragangliomas. Moreover, it is usually negative in round cell sarcomas. In contrast, little is known about GATA3 expression in blastemal or other small round cell pediatric tumors. Nonaka et al reported the presence of diffuse GATA3 expression in the neuroblastoma family of tumors and a lack of expression in other small round cell tumors. The distinction between neuroblastomas and nephroblastomas may be delicate because the clinical and radiological presentation may be overlapping. Moreover, we have previously encountered important difficulties in the cytological differential diagnosis between poorly differentiated neuroblastomas without neuropils or differentiating cells from blastema-rich monophasic nephroblastomas. We initiated this study to evaluate GATA3’s immunohistochemical utility in the cytological differential diagnosis between neuroblastomas and nephroblastomas. Six cell blocks from the most recent consecutive ultrasound-guided fine-needle aspirates from neuroblastomas and 6 cell blocks from nephroblastomas were investigated. Paraffin-embedded sections were stained with the GATA3 antibody (clone L50-823; Biocare, Concord, California). Immunostaining was scored as negative, weakly positive, or strongly positive. The percentage of positive cells was also estimated. Nuclear staining was found in all 6 cases of neuroblastoma but in only 1 case of nephroblastoma. No cytoplasmic staining was observed. The intensity varied from weak (4 cases) to strong (2 cases; Figs. 1 and 2). The percentage of positive cells varied from 5% to 100%. Only 1 of the 6 cases of nephroblastoma showed weak nuclear positivity in 5% of tumor cells. The clinical data and the results of immunohistochemistry are presented in Table 1 On the basis of our results, we conclude that GATA3 may be a useful marker for differentiating neuroblastomas from nephroblastomas, especially when it is used with Phox2b and tyrosine-hydroxylase antibodies. Moreover, in some cases, GATA3 may be not specific, and positivity in a blastemal nephroblastoma may be a pitfall of a differential diagnosis with a poorly differentiated neuroblastoma. Figure 2. Weak GATA3 nuclear positivity in nephroblastoma. Figure 1. Strong GATA3 nuclear positivity in neuroblastoma.
Roles of auxin and ethylene in aerenchyma formation in sugarcane roots

ABSTRACT Although the cross-talk between auxin and ethylene has been described during plant development, the role played by auxin upon gene expression during aerenchyma formation is poorly understood. Root aerenchyma formation results from the opening of gas spaces in the cortex. It is part of a developmental program (constitutive) or due to ethylene treatment or abiotic stress (induced) such as flooding and nutrient starvation. This process relies on programmed cell death and cell wall modifications. Here we followed development of aerenchyma formation in sugarcane along 5 cm from the root apex. As a constitutive process, the aerenchyma formation was observed in the cortex from the 3rd cm onwards. This occurred despite 1-methylcyclepropene (1-MCP) treatment, an inhibitor of ethylene perception. However, this process occurred while ethylene (and auxin) levels decreased. Within the aerenchyma formation zone, the concentration of ethylene is lower in comparison to the concentration in maize. Besides, the ratio between both hormones (ethylene and auxin) was around 1:1. These pieces of evidence suggest that ethylene sensitivity and ethylene-auxin balance may play a role in the formation of aerenchyma. Furthermore, the transcriptional analysis showed that genes related to cell expansion are up-regulated due to 1-MCP treatment. Our results help explaining the regulation of the formation constitutive aerenchyma in sugarcane.
Computational phenotype prediction of ionizing-radiation-resistant bacteria with a multiple-instance learning model

Ionizing-radiation-resistant bacteria (IRRB) are important in biotechnology. The use of these bacteria for the treatment of radioactive wastes is determined by their surprising capacity of adaptation to radionuclides and a variety of toxic molecules. In silico methods are unavailable for the purpose of phenotypic prediction and genotype-phenotype relationship discovery. We analyze basal DNA repair proteins of most known proteomes sequences of IRRB and ionizing-radiation-sensitive bacteria (IRSB) in order to learn a classifier that correctly predicts unseen bacteria. In this work, we formulate the problem of predicting IRRB as a multiple-instance learning (MIL) problem and we propose a novel approach for predicting IRRB. We use a local alignment technique to measure the similarity between protein sequences to predict ionizing-radiation-resistant bacteria. The first results are satisfactory and provide a MIL-based prediction system that predicts whether a bacterium belongs to IRRB or to IRSB. The proposed system is available online.
Functional role of T-cell receptor nanoclusters in signal initiation and antigen discrimination

Significance T-cell activation requires the translation of antigen binding to the T-cell receptor (TCR) into intracellular signaling. However, how antigen recognition and signal transduction are mechanistically linked is poorly understood. Here, we used single-molecule localization microscopy to link TCR clustering to signaling. We found that the likelihood of a single receptor to initiate signaling upon ligand binding depended on receptor-to-receptor spacing, with TCRs in dense clusters having the highest signaling efficiency. This means that antigen recognition must first be translated into a spatial reorganization of receptors into dense, signaling-competent clusters before signaling can begin. Thus, the quality of an antigen in terms of signaling is given by its ability to densely cluster receptors. Antigen recognition by the T-cell receptor (TCR) is a hallmark of the adaptive immune system. When the TCR engages a peptide bound to the restricting major histocompatibility complex molecule (pMHC), it transmits a signal via the associated CD3 complex. How the extracellular antigen recognition event leads to intracellular phosphorylation remains unclear. Here, we used single-molecule localization microscopy to quantify the organization of TCR–CD3 complexes into nanoscale clusters and to distinguish between triggered and nontriggered TCR–CD3 complexes. We found that only TCR–CD3 complexes in dense clusters were phosphorylated and associated with downstream signaling proteins, demonstrating that the molecular density within clusters dictates signal initiation. Moreover, both pMHC dose and TCR–pMHC affinity determined the density of TCR–CD3 clusters, which scaled with overall phosphorylation levels. Thus, TCR–CD3 clustering translates antigen recognition by the TCR into signal initiation by the CD3 complex, and the formation of dense signaling-competent clusters is a process of antigen discrimination.
Breve revisión sobre el reconocimiento de la Lengua de Señas

Sign language involves various factors such as the position of the hand, the speed with which the sign is made and even the gestures of the face, so interpreting the meaning of a sign is a complex task. Thus, under the point of view of computing, we have been working with different proposals and researches which involve the use of different technologies and techniques that try to solve this problem. In the present work we offer a brief review about the different researches working with the problem of the classification of the signs.
A cellular non‐linear network for image fusion based on data regularization

In this paper, a synthesis method developed in the last few years is applied to derive a cellular non‐linear network (CNN) able to find an approximate solution to a variational image‐fusion problem. The functional to be minimized is based on regularization theory and takes into account two complementary principles, namely, knowledge source corroboration and belief enhancement/withdrawal, both typical of data‐fusion approaches. The obtained CNN has been tested by simulations (i.e. by numerically integrating the circuit state equations) in some case studies. The quality of the results is good, as turns out from comparisons with some standard methods. Copyright © 2006 John Wiley & Sons, Ltd.