gebhart/patrepeval huggingface dataset:
A novel developmental regulatory motif required for stage-specific activation of the epsilon-globin gene and nuclear factor binding in embryonic erythroid cells. (1994)

Members of the human beta-globin gene family are expressed at discrete stages of development and therefore provide an important model system for examining mechanisms of temporal gene regulation. We have previously shown that expression of the embryonic beta-like globin gene (epsilon) is mediated by a complex array of positive and negative upstream control elements. Correct developmental stage- and tissue-specific gene expression is conferred by synergistic interactions between a positive regulatory element (termed epsilon-PRE II) which is active only in embryonic erythroid cells and at least two other regulatory domains upstream of the epsilon-globin gene promoter. A nuclear factor highly enriched in cultured embryonic erythroid cells and in mouse embryonic yolk sac binds to a novel, evolutionarily conserved sequence within epsilon-PRE II. We show here that binding of this factor to the conserved element within epsilon-PRE II is critical for transcriptional activity. Point mutations that interfere with protein binding to epsilon-PRE II abolish transcriptional activation of the constitutive epsilon-globin promoter. Adult erythroid nuclei (from cultured cells or adult mouse liver) also contain a factor that binds to this region, but the complex formed migrates more rapidly during nondenaturing electrophoresis, suggesting either that distinct proteins bind to epsilon-PRE II or that a single protein is differentially modified in these cells in a way that modulates its activity. Several lines of evidence suggest that the binding factors in embryonic and adult erythroid cells are distinguished by posttranscriptional differences.
Cystoid macular edema (2008)

We review the epidemiology, pathophysiology, and etiology of cystoid macular edema (CME). Inflammatory, diabetic, post-cataract, and macular edema due to age-related macular degeneration is described. The role of chronic inflammation and hypoxia and direct macular traction is evaluated in each case according to different views from the literature. The different diagnostic methods for evaluating the edema are described. Special attention is given to fluoroangiography and the most modern methods of macula examination, such as ocular coherence tomography and multifocal electroretinography. Finally, we discuss the treatment of cystoid macular edema in relation to its etiology. In this chapter we briefly refer to the therapeutic value of laser treatment especially in diabetic maculopathy or vitrectomy in some selected cases. Our paper is focused mainly on recent therapeutic treatment with intravitreal injection of triamcinolone acetonide and anti-VEGF factors like bevacizumab (Avastin), ranibizumab (Lucentis), pegaptamid (Macugen), and others. The goal of this paper is to review the current status of this treatment for macular edema due to diabetic maculopathy, central retinal vein occlusion and post-cataract surgery. For this reason the results of recent multicenter clinical trials are quoted, as also our experience on the use of intravitreal injections of anti-VEGF factors and we discuss its value in clinical practice.
Convergent evidence that oligodendrocyte lineage transcription factor 2 ( OLIG2 ) and interacting genes influence susceptibility to schizophrenia (2006)

Abnormal oligodendrocyte function has been postulated as a primary etiological event in schizophrenia. Oligodendrocyte lineage transcription factor 2 (OLIG2) encodes a transcription factor central to oligodendrocyte development. Analysis of OLIG2 in a case-control sample (n = approximately 1,400) in the U.K. revealed several SNPs to be associated with schizophrenia (minimum P = 0.0001, gene-wide P = 0.0009). To obtain independent support for this association, we sought evidence for genetic interaction between OLIG2 and three genes of relevance to oligodendrocyte function for which we have reported evidence for association with schizophrenia: CNP, NRG1, and ERBB4. We found interaction effects on disease risk between OLIG2 and CNP (minimum P = 0.0001, corrected P = 0.008) for interaction with ERBB4 (minimum P = 0.002, corrected P = 0.04) but no evidence for interaction with NRG1. To investigate the biological plausibility of the interactions, we sought correlations between the expression of the genes. The results were similar to those of the genetic interaction analysis. OLIG2 expression significantly correlated in cerebral cortex with CNP (P < 10(-7)) and ERBB4 (P = 0.002, corrected P = 0.038) but not NRG1. In mouse striatum, Olig2 and Cnp expression also was correlated, and linkage analysis for trans-effects on gene expression suggests that each locus regulates the other's expression. Our data provide strong convergent evidence that variation in OLIG2 confers susceptibility to schizophrenia alone and as part of a network of genes implicated in oligodendrocyte function.
A likelihood ratio test for detecting patterns of disease‐marker association (1997)

A likelihood ratio test of disease-marker association is proposed, based on the observation of marker alleles transmitted from parents to affected children. The proposed association test has the advantage of identifying the population pattern of disease-marker association, differentiating between marker alleles that are positively and negatively associated with the disease. The power of the test for detecting association is evaluated and compared with three existing multi-allelic tests for some specific disease-marker association patterns. The power of the parametric tests depends crucially on the pattern of disease-marker association. An over-parameterised association model is less detrimental in terms of power than an under parameterised model.
Statistical modeling of speech signals based on generalized gamma distribution (2005)

In this letter, we propose a new statistical model, two-sided generalized gamma distribution (G/spl Gamma/D) for an efficient parametric characterization of speech spectra. G/spl Gamma/D forms a generalized class of parametric distributions, including the Gaussian, Laplacian, and Gamma probability density functions (pdfs) as special cases. We also propose a computationally inexpensive online maximum likelihood (ML) parameter estimation algorithm for G/spl Gamma/D. Likelihoods, coefficients of variation (CVs), and Kolmogorov-Smirnov (KS) tests show that G/spl Gamma/D can model the distribution of the real speech signal more accurately than the conventional Gaussian, Laplacian, Gamma, or generalized Gaussian distribution (GGD).
Protein−Ligand Mediated Aggregation of Nanoparticles:  A Study of Synthesis and Assembly Mechanism (2004)

Two difunctional, asymmetric PEG linkers were synthesized and utilized to prepare water-soluble, biotinylated CdS@SiO2 particles with various surface contents of the biotin groups. Aqueous dispersions of these particles were prepared, and upon addition of avidin, aggregation was observed using DLS, TEM, and SEM analysis. The resulting aggregates were dense but also had fractal shapes. It was shown that single-angle DLS measurements at 90° were sufficiently accurate for quickly measuring the size of the aggregates as it evolved with time. Initial aggregation rates were measured as a function of surface biotin content of the nanoparticles and initial avidin concentration. The initial rates displayed bell-shaped curve responses to variations in the avidin-to-particle ratio and biotin-to-avidin ratio, the shapes of which were attributed to the stoichiometric balance/imbalance of the avidin-to-biotin ratio in the system and to intraparticle and interparticle bridges that could sterically block avidin from reaching some biotin sites. The growth mechanism was postulated to be a step-growth process.
Antipsychotic polypharmacy among elderly patients with schizophrenia and dementia during hospitalization at a Taiwanese psychiatric hospital (2014)

FGA are still commonly used for the late-life schizophrenia at our hospital. Given their potentially hazardous side effects, FGA must be employed with caution. The use of APP involving SGA increased over the 6 years of the study period, especially among patients with dementia. However, the use of SGA in dementia began to decline after the US Food and Drug Administration's 2005 warning about SGA being associated with increased mortality in dementia patients, which contrasts with the trends examined in this study. Further controlled trials exploring the efficacy, safety, and tolerability of APP in this population are warranted to gain an additional insight into this practice.
Comparative analysis of structurally defined heparin binding sequences reveals a distinct spatial distribution of basic residues. (1993)

Heparin, among the best studied glycosaminoglycans, is well known for its involvement in a variety of physiological processes. Many proteins, whose activities are modulated via heparin binding, were identified, and the consequences of their interaction with heparin were characterized. However, in the absence of solid structural information regarding heparin-protein complexes, the mechanism by which heparin operates at the molecular level is still obscure. The structure of such a complex is hereby explored via the identification of a common motif in heparin binding sequences. To avoid ambiguity we included in our data base only sequences that have been shown experimentally to be directly involved in heparin binding. Then, a comparison of the spatial distribution of basic residues was conducted among those peptides for which three-dimensional structures were defined. Using computer graphics techniques we were able to identify a unique distribution shared by all of these segments. Two basic amino acids (most frequently arginine) are located at about 20 A apart, facing opposite directions of an alpha-helix. Other basic amino acids are dispersed between these two residues, facing one side, while nonpolar residues face the opposite side, forming an amphipathic structure. The distribution of basic amino acids in other heparin binding sequences that preserves the same spatial arrangement seems to be compatible with a beta-strand structure. The 20-A interval accommodates a glycosaminoglycan pentasaccharide, and the spatial distribution of the basic residues suggests an intertwinement of the heparin-protein complex. The dynamics of such an interaction may provide a clue regarding the ensuing change in protein activity.
Bidirectional Shunt through a Residual Atrial Septal Defect after Percutaneous Transvenous Mitral Commissurotomy (1993)

A residual atrial septal defect with bidirectional shunt was detected by transesophageal echocardiography in a 28-year-old man 3 years after percutaneous transluminal mitral commissurotomy (PTMC) with the antegrade transseptal technique. He had had severe mitral stenosis, pulmonary hypertension, and tricuspid regurgitation before the procedure. The result of PTMC was suboptimal, the pulmonary hypertension regressed only partially, and the tricuspid regurgitation remained severe. These factors contributed to the bidirectional shunt. A bidirectional shunt is known to be associated with systemic desaturation and a higher risk of paradoxical embolization and brain abscess. When PTMC is considered in patients with pulmonary hypertension and tricuspid regurgitation, a retrograde left ventricular approach with or without transseptal puncture can avoid the atrial septotomy, decrease the incidence of significant shunt, and should be a rational alternative.
Security Model with Tunnel-mode IPsec for NAT Domains (1999)

There are a variety of NAT flavors, as described in [Ref 1]. Of the domains supported by NATs, only Realm-Specific IP clients are able to pursue end-to-end IPsec secure sessions. However, all flavors of NAT are capable of offering tunnel-mode IPsec security to private domain hosts peering with nodes in external realm. This document describes a security model by which tunnel-mode IPsec security can be architected on NAT devices. A section is devoted to describing how security policies may be transparently communicated to IKE (for automated KEY exchange) during Quick Mode. Also outlined are applications that can benefit from the Security Model described.
Construction of a patient-specific atlas of the brain: Application to normal aging (2008)

We present a method for the construction of patient-specific atlases of the brain. Traditional atlases of the brain aim to characterize the variability of a population of subjects. A common approach is to average the anatomies of a population after alignment to a common coordinate system. Subjects are typically given equal weights during averaging which results in atlases that are population-specific rather than subject specific. In this paper we propose a method for the construction of patient-specific atlas for a given query subject from a large population cohort. During the atlas construction we compute the similarity between the query subject and the subjects in the population cohort. This similarity measure can be based on image similarity or other meta-information (e.g. sex, age, ethnicity, medical history, etc). We show an example of the construction of brain atlases for different ages using a cohort of 575 subjects between the ages of 18 and 80.
Thermal interference in a 0.85 µm 8 ×8 two-dimensionalvertical-cavity surface-emitting laser array (1994)

The authors present a study of the thermal interference in a two-dimensional 0.85 µm vertical-cavity surface-emitting laser array. The distance between pixels is 250 µm. The temperature of the centre pixel is found to increase by at least 15°C due to thermal interference when the other pixels are operated near the threshold current.
New technologies in fiber sensors (2007)

Since their inception in the 1960s, fiber sensors have been extensively developed for numerous applications, and they are deployed in increasing number every year. Several fiber sensors have had a major impact on important niche markets. In spite of this success, fiber sensors are having difficulty competing with established conventional sensor markets, and they still represent only a small fraction of the world's enormous market. To give them a better edge, several new technologies have been explored in recent years, with the common objective of further improving sensitivity, dynamic range, and stability, as well as reducing size and manufacturing cost.
Synthesis and β-adrenergic blocking activity of naphthyloxypropylamines (2008)

A series of 1-isopropylamino-3-(3'-substituted-2'-naphthyloxy)-2-propanols have been synthesized and their structures have been confirmed by spectral analysis. All the derivatives have shown β-adrenergic blocking effect when tested on perfused frog heart. Compound 4e exhibited 100% blockade of adrenaline response.
Adoptive Cellular Therapy for Follicular Lymphoma Using Genetically-Modified Autologous CD20-Specific T Cells. (2007)

Abstract Follicular Lymphoma (FL) is the second most common type of non-Hodgkin’s Lymphoma (NHL) in the United States, accounting for approximately 20% of NHL cases. FL is considered incurable with conventional therapies, and novel therapies are therefore urgently needed. Long-term remissions using allogeneic stem cell transplantation and donor lymphocyte infusion suggest curability using cellular therapy, but these approaches are limited by significant toxicity. We have initiated a pilot Phase I clinical trial testing the feasibility, safety, and toxicity of treating patients with relapsed FL with autologous T lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) recognizing the CD20 antigen present on B cell lymphomas. Nine patients have been registered to the protocol to date. Peripheral blood mononuclear cells were obtained from patients by apheresis, activated with anti-CD3 monoclonal antibody (OKT3) and interleukin-2 (IL-2) and transfected by electroporation with a plasmid encoding a CD20-specific scFvFc:ζ CAR as well as a neomycin-resistance selection gene. Transfectants were selected using G418 and expanded ex vivo. For the first 5 patients, cytotoxic CD8+ T cells were cloned by limiting dilution, but this process proved to be laborious and inefficient. Two patients’ clones failed to expand adequately and are off-study, and 2 additional patients received cell doses below the target level. Therefore, subsequent patients underwent oligoclonal expansion of T cells in bulk culture. T cells expressing the CAR and manifesting CD20-specific cytotoxicity were identified by flow cytometry and standard chromium release assays. Patients underwent three infusions of modified T cells at escalating doses (108, 109 and 3.3 × 109 cells/m2) over a period of 7–10 days. The 4 patients who received oligoclonal T cells also received 14 days of low-dose subcutaneous IL-2 injections (500,000 U/m2 twice daily) to prolong in vivo persistence. Seven patients underwent a total of 20 T cell infusions, and no significant toxicities attributable to the T cell infusions were observed. Cellular and immune response assays have not detected any immune responses to the genetically modified T cells in any of the treated patients, although the seventh patient has not yet been evaluated for immune responses. T cells expressing the CAR were detectable in the peripheral blood of patients by PCR for ∼14 days after infusions in the first three patients who received T cell clones, and 4–8 weeks in patients receiving oligoclonal T cells and IL-2 injections. One patient was maintained in complete remission for over a year after T cell infusions, and a second patient achieved a partial remission lasting three months. A third patient had a partial PET response. The remaining 3 patients maintained stable disease for 3–12 months. These results suggest that adoptive cellular therapy with genetically modified CD20-specific T cells is a safe and feasible approach to treating FL that warrants further investigation.
Promotion of human T lymphocyte proliferation by IL-4. (1989)

The capacity of human rIL-4 to support the proliferation of mitogen-stimulated T cells directly as well as by increasing IL-2 production or enhancing IL-2 responsiveness was investigated. IL-4 augmented proliferation of T cells stimulated with PHA, Con A, immobilized mAb to the CD3 molecular complex (OKT3), or PMA. IL-4 increased the number of mitogen-stimulated cells entering the cell cycle as well as enhancing ongoing proliferation of mitogen-activated lymphoblasts. Facilitation of initial activation by IL-4 was not inhibited by mAb to the p55 component of the IL-2R, anti-Tac, and, therefore, was not dependent on endogenous IL-2 activity. However, IL-4-mediated enhancement of ongoing T cell proliferation stimulated by PHA or OKT3 was partially but not completely blocked by anti-Tac. Analysis of the supernatants from PHA-stimulated T cell cultures indicated that IL-4 increased the production of IL-2 by mitogen-activated cells. Moreover, IL-4 increased the amount of IL-2 mRNA that accumulated in mitogen-stimulated T cells. In addition, IL-4 markedly augmented IL-2R expression by PHA-stimulated T cells. Although IL-4 promoted ongoing DNA synthesis of mitogen-stimulated T cells in an IL-2-dependent manner, it was also able to sustain their proliferation directly. Thus, IL-4 supported proliferation of PMA-activated T cells in a manner that was not inhibited by anti-Tac. Furthermore, IL-4 could augment proliferation and IL-2R expression of T cells stimulated with PHA in the presence of cyclosporin A, which blocks endogenous cytokine production or anti-Tac. Finally, IL-4 was noted to enhance proliferation of both CD4+ and CD8+ T cell subsets. The results indicate that IL-4 enhances proliferation of mitogen-activated human T cells by a number of mechanisms, including the direct promotion of cell cycle entry and subsequent DNA synthesis, enhanced production of IL-2, and increased responsiveness to IL-2 in part by up-regulation of IL-2R expression.
Highly efficient generation of heritable zebrafish gene mutations using homo- and heterodimeric TALENs (2012)

Transcription activator-like effector nucleases (TALENs) are powerful new research tools that enable targeted gene disruption in a wide variety of model organisms. Recent work has shown that TALENs can induce mutations in endogenous zebrafish genes, but to date only four genes have been altered, and larger-scale tests of the success rate, mutation efficiencies and germline transmission rates have not been described. Here, we constructed homodimeric TALENs to 10 different targets in various endogenous zebrafish genes and found that 7 nuclease pairs induced targeted indel mutations with high efficiencies ranging from 2 to 76%. We also tested obligate heterodimeric TALENs and found that these nucleases induce mutations with comparable or higher frequencies and have better toxicity profiles than their homodimeric counterparts. Importantly, mutations induced by both homodimeric and heterodimeric TALENs are passed efficiently through the germline, in some cases reaching 100% transmission. For one target gene sequence, we observed substantially reduced mutagenesis efficiency for a variant site bearing two mismatched nucleotides, raising the possibility that TALENs might be used to perform allele-specific gene disruption. Our results suggest that construction of one to two heterodimeric TALEN pairs for any given gene will, in most cases, enable researchers to rapidly generate knockout zebrafish.
Novel neuroprotective, neuritogenic and anti-amyloidogenic properties of 2,4-dinitrophenol: The gentle face of Janus (2006)

In Roman mythology, Janus was the god of gates, doors, beginnings and endings. He was usually depicted with two faces looking in opposite directions. Janus was frequently used to symbolize change and transitions, such as the progression from past to future or from one viewpoint to another. 2,4-dinitrophenol (DNP) and other nitrophenols have long been known to be toxic at high concentrations (the 'bad' face of DNP), an effect that appears essentially related to interference with cellular energy metabolism due to uncoupling of mitochondrial oxidative phosphorylation. Five years ago, however, we published the first report showing that low concentrations of DNP protect neurons against the toxicity of the amyloid-beta peptide (De Felice et al. (2001) FASEB J. 15:1297 - 1299]. Since then, other studies have provided evidence of beneficial actions of DNP (at low concentrations), including neuroprotection against different types of insult, blockade of amyloid aggregation, stimulation of neurite outgrowth and neuronal differentiation, and even extension of lifespan in certain organisms. Some of these effects appear to be due to mild mitochondrial uncoupling and prevention of cellular oxidative stress, whereas other actions are related to activation of additional intracellular signaling pathways. Thus, a novel and 'gentle' face of DNP is emerging from such studies. In this review, we discuss both toxic and beneficial actions of DNP. The evidence available so far suggests that DNP and other compounds with similar biological activities may be of significant interest to the development of novel therapeutic approaches for neurodegenerative diseases and other neurological disorders.
In Vitro Differentiation and Measurement of B Cell Progenitor Activity in Culture (2005)

As well as other blood cells, B lymphocytes originate from hematopoietic stem cells. However, it is not fully understood how their production is controlled. In the serum-free, stromal-cell-free B cell differentiation culture described here, early steps of the B lineage differentiation process are reproduced under defined conditions. This assay is useful for examining the direct effects of various soluble factors on B cell progenitors because it does not contain stromal cells or unknown factors. Additionally, this assay yields sufficient cloning to measure B cell progenitors from single cell cultures. Stromal cell coculture assays are also described that cover a wider category of precursors such as human B cell progenitors.