gebhart/patrepeval huggingface dataset:
The default mode network and self-referential processes in depression (2009)

The recently discovered default mode network (DMN) is a group of areas in the human brain characterized, collectively, by functions of a self-referential nature. In normal individuals, activity in the DMN is reduced during nonself-referential goal-directed tasks, in keeping with the folk-psychological notion of losing one's self in one's work. Imaging and anatomical studies in major depression have found alterations in both the structure and function in some regions that belong to the DMN, thus, suggesting a basis for the disordered self-referential thought of depression. Here, we sought to examine DMN functionality as a network in patients with major depression, asking whether the ability to regulate its activity and, hence, its role in self-referential processing, was impaired. To do so, we asked patients and controls to examine negative pictures passively and also to reappraise them actively. In widely distributed elements of the DMN [ventromedial prefrontal cortex prefrontal cortex (BA 10), anterior cingulate (BA 24/32), lateral parietal cortex (BA 39), and lateral temporal cortex (BA 21)], depressed, but not control subjects, exhibited a failure to reduce activity while both looking at negative pictures and reappraising them. Furthermore, looking at negative pictures elicited a significantly greater increase in activity in other DMN regions (amygdala, parahippocampus, and hippocampus) in depressed than in control subjects. These data suggest depression is characterized by both stimulus-induced heightened activity and a failure to normally down-regulate activity broadly within the DMN. These findings provide a brain network framework within which to consider the pathophysiology of depression.
A New Pneumococcal Capsule Type, 10D, is the 100th Serotype and Has a Large cps Fragment from an Oral Streptococcus (2020)

<i>Streptococcus pneumoniae</i> (pneumococcus) is a major human pathogen producing structurally diverse capsular polysaccharides. Widespread use of highly successful pneumococcal conjugate vaccines (PCVs) targeting pneumococcal capsules has greatly reduced infections by the vaccine types but increased infections by nonvaccine serotypes. Herein, we report a new and the 100th capsule type, named serotype 10D, by determining its unique chemical structure and biosynthetic roles of all capsule synthesis locus (<i>cps</i>) genes. The name 10D reflects its serologic cross-reaction with serotype 10A and appearance of cross-opsonic antibodies in response to immunization with 10A polysaccharide in a 23-valent pneumococcal vaccine. Genetic analysis showed that 10D <i>cps</i> has three large regions syntenic to and highly homologous with <i>cps</i> loci from serotype 6C, serotype 39, and an oral streptococcus strain (<i>S. mitis</i> SK145). The 10D <i>cps</i> region syntenic to SK145 is about 6 kb and has a short gene fragment of <i>wciN</i>α at the 5' end. The presence of this nonfunctional <i>wciN</i>α fragment provides compelling evidence for a recent interspecies genetic transfer from oral streptococcus to pneumococcus. Since oral streptococci have a large repertoire of <i>cps</i> loci, widespread PCV usage could facilitate the appearance of novel serotypes through interspecies recombination.<b>IMPORTANCE</b> The polysaccharide capsule is essential for the pathogenicity of pneumococcus, which is responsible for millions of deaths worldwide each year. Currently available pneumococcal vaccines are designed to elicit antibodies to the capsule polysaccharides of the pneumococcal isolates commonly causing diseases, and the antibodies provide protection only against the pneumococcus expressing the vaccine-targeted capsules. Since pneumococci can produce different capsule polysaccharides and therefore reduce vaccine effectiveness, it is important to track the appearance of novel pneumococcal capsule types and how these new capsules are created. Herein, we describe a new and the 100th pneumococcal capsule type with unique chemical and serological properties. The capsule type was named 10D for its serologic similarity to 10A. Genetic studies provide strong evidence that pneumococcus created 10D capsule polysaccharide by capturing a large genetic fragment from an oral streptococcus. Such interspecies genetic exchanges could greatly increase diversity of pneumococcal capsules and complicate serotype shifts.
A Review on Gut Remediation of Selected Environmental Contaminants: Possible Roles of Probiotics and Gut Microbiota (2018)

Various environmental contaminants including heavy metals, pesticides and antibiotics can contaminate food and water, leading to adverse effects on human health, such as inflammation, oxidative stress and intestinal disorder. Therefore, remediation of the toxicity of foodborne contaminants in human has become a primary concern. Some probiotic bacteria, mainly <i>Lactobacilli,</i> have received a great attention due to their ability to reduce the toxicity of several contaminants. For instance, <i>Lactobacilli</i> can reduce the accumulation and toxicity of selective heavy metals and pesticides in animal tissues by inhibiting intestinal absorption of contaminants and enhancing intestinal barrier function. Probiotics have also shown to decrease the risk of antibiotic-associated diarrhea possibly via competing and producing antagonistic compounds against pathogenic bacteria. Furthermore, probiotics can improve immune function by enhancing the gut microbiota mediated anti-inflammation. Thus, these probiotic bacteria are promising candidates for protecting body against foodborne contaminants-induced toxicity. Study on the mechanism of these beneficial bacterial strains during remediation processes and particularly their interaction with host gut microbiota is an active field of research. This review summarizes the current understanding of the remediation mechanisms of some probiotics and the combined effects of probiotics and gut microbiota on remediation of foodborne contaminants in vivo.
A deleted variant of Bacillus anthracis protective antigen is non-toxic and blocks anthrax toxin action in vivo (1989)

Anthrax toxin is the only protein secreted by Bacillus anthracis that contributes to the virulence of this bacterium. An obligatory step in the action of anthrax toxin on eukaryotic cells is cleavage of the receptor-bound protective antigen (PA) protein (83 kilodaltons) to produce a 63-kilodalton, receptor-bound COOH-terminal fragment. A similar fragment can be obtained by limited treatment with trypsin. This proteolytic processing event exposes a site with high affinity for the other two anthrax toxin proteins, lethal factor and edema factor. Terminal sequencing of the purified fragment showed that the activating cleavage occurred in the sequence Arg164-Lys165-Lys166-Arg167. The gene encoding PA was mutagenized to delete residues 163-168, and the deleted PA was purified from a Bacillus subtilis host. The deleted PA was not cleaved by either trypsin or the cell-surface protease, and was non-toxic when administered with lethal factor. Purified, deleted PA protected rats when administered 90 min before injection of 20 minimum lethal doses of toxin. This mutant PA may be useful as a replacement for the PA that is the major active ingredient in the current human anthrax vaccine, because deleted PA is expected to have normal immunogenicity, but would not combine with trace amounts of LF and EF to cause toxicity.
CD32B, the human inhibitory Fc-γ receptor IIB, as a target for monoclonal antibody therapy of B-cell lymphoma (2006)

Human CD32B (FcgammaRIIB), the low-affinity inhibitory receptor for IgG, is the predominant Fc receptor (FcR) present on B cells. Immunohistochemical and expression studies have identified CD32B expression in a variety of B-cell malignancies, suggesting that CD32B is a potential immunotherapeutic target for B-cell malignancies. A high-affinity monoclonal antibody (mAb 2B6), from a novel panel of anti-human CD32B-specific mAbs, was chimerized (ch2B6) and humanized (hu2B6-3.5). Both ch2B6 and hu2B6-3.5 were capable of directing cytotoxicity by peripheral blood mononuclear cells and monocyte-derived macrophages against B-lymphoma lines in vitro. In a human B-cell lymphoma mouse xenograft model, administration of ch2B6 or hu2B6-3.5 reduced tumor growth rate and improved tumor-free survival. Both the in vitro and in vivo activities of 2B6 required an intact Fc, suggesting an FcR-mediated mechanism of action. These data support the hypothesis that CD32B is a viable target for mAb treatment of B-cell lymphoproliferative disorders.
Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential (2004)

We report here the isolation of a population of non-transformed pluripotent human cells from bone marrow after a unique expansion/selection procedure. This procedure was designed to provide conditions resembling the in vivo microenvironment that is home for the most-primitive stem cells. Marrow-adherent and -nonadherent cells were co-cultured on fibronectin, at low oxygen tension, for 14 days. Colonies of small adherent cells were isolated and further expanded on fibronectin at low density, low oxygen tension with 2% fetal bovine serum. They expressed high levels of CD29, CD63, CD81, CD122, CD164, hepatocyte growth factor receptor (cMet), bone morphogenetic protein receptor 1B (BMPR1B), and neurotrophic tyrosine kinase receptor 3 (NTRK3) and were negative for CD34, CD36, CD45, CD117 (cKit) and HLADR. The embryonic stem cell markers Oct-4 and Rex-1, and telomerase were expressed in all cultures examined. Cell-doubling time was 36 to 72 hours, and cells have been expanded in culture for more than 50 population doublings. This population of cells was consistently isolated from men and women of ages ranging from 3- to 72-years old. Colonies of cells expressed numerous markers found among embryonic stem cells as well as mesodermal-, endodermal- and ectodermal-derived lineages. They have been differentiated to bone-forming osteoblasts, cartilage-forming chondrocytes, fat-forming adipocytes and neural cells and to attachment-independent spherical clusters expressing genes associated with pancreatic islets. Based on their unique characteristics and properties, we refer to them as human marrow-isolated adult multilineage inducible cells, or MIAMI cells. MIAMI cells proliferate extensively without evidence of senescence or loss of differentiation potential and thus may represent an ideal candidate for cellular therapies of inherited or degenerative diseases.
Plant‐derived compounds and extracts with potential as aphid repellents (2008)

Abstract We devised a method for screening various substances for possible aphid repellency. Corn leaf aphids ( Rhopalosiphum maidis ) were released in an arena and allowed to select paired green tiles coated with petroleum jelly alone or petroleum jelly containing 1% of the substance being tested. Aphids adhering to tiles were counted 24 h later. If significantly fewer aphids landed on treated tiles, the substance was considered to have potential for repelling aphids. Fifty‐five substances were tested. Most showed no activity, but several including β‐citronellol, farnesol, geraniol, linalool, oils distilled from several species of Artemisia and Achillea millefolia (yarrow) oil showed some promise.
<title>Overlay and field-by-field leveling in wafer steppers using an advanced metrology system</title> (1992)

Steppers suitable for resolutions down to 0.35 micrometers are now available for the development and production of 64 mb DRAMs. At these small feature sizes, the depth of focus approaches one micron and the machine to machine overlay requirements are decreased to below 150 nm. This paper reports on the design and characterization of focus, alignment, and stage metrology in a wafer stepper which can meet the aggressive feature size demands. The characteristics of a new broad band field-by-field leveling sensor system with an enhanced process tolerance compared to conventional systems is described. Furthermore, this leveling system has been combined with a multi-axis interferometer system to support a high throughput global alignment strategy with field-by-field leveling. Wafer stepper performance results are presented including depth of focus improvements and global alignment overlay with and without field-by-field leveling. The dependency of focus on wafer structure- and resist thickness-variation is also shown. The total metrology system makes possible a two point global alignment overlay performance below 30 nm, a focus repeatability of 25 nm, and a tilt repeatability of 2 (mu) rad.
Captopril kinetics in chronic congestive heart failure (1982)

We investigated the kinetics of 25 mg Captopril by mouth in 12 patients with congestive heart failure and correlated them with the hormonal and hemodynamic changes associated with the drug. Observations were made after a single dose (25 mg orally), and after short-term therapy (25 mg t.i.d. for 3 days). Captopril kinetics were as previously reported in normal subjects, with the exception that time to maximum concentration (tmax) of free Captopril was slightly higher and the half-life (t½) was slightly shorter than in normal subjects. Total Captopril t½ was longer than normal, suggesting cumulation. Urinary excretion was slower than normal. Differences between Captopril kinetics on days 1 and 5 were that the tmax developed somewhat sooner, with a shorter t½ on day 5 and total Captopril blood levels were higher on day 5 than on day 1. Urinary excretion was greater on day 5 than on day 1. Hemodynamic improvement after a single oral dose of Captopril was significant and correlated with baseline plasma renin activity (PRA). The onset of converting-enzyme inhibition, as determined by PRA and hemodynamic improvement correlated with Captopril blood levels. Clinical Pharmacology and Therapeutics (1982) 32, 721–726; doi:10.1038/clpt.1982.228
Biological markers of cocaine addiction: implications for medications development (2003)

The search for effective medications for cocaine addiction has been elusive. The failure to find such medications so far could be due to poor understanding of the underlying biology both in the premorbid condition and following the disease state of chronic cocaine use. Population heterogeneity could be a major factor in response to medications. In an attempt to highlight the issue of biomarkers we reviewed physiological, neuroendocrine and neuroimaging studies to identify specific biological changes/markers that could be used to characterize subgroups among chronic cocaine users. Merging the biology within medications studies of cocaine abusers could prove useful for targeting specific pharmacological agents to subgroups of patients, prediction of response to medication and relapse to use.
Molecular MR imaging of melanoma angiogenesis with ανβ3‐targeted paramagnetic nanoparticles (2005)

Neovascularization is a critical component in the progression of malignant melanoma. The objective of this study was to determine whether alpha(nu)beta(3)-targeted paramagnetic nanoparticles can detect and characterize sparse alpha(nu)beta integrin expression on neovasculature induced by nascent melanoma xenografts ( approximately 30 mm(3)) at 1.5T. Athymic nude mice bearing human melanoma tumors were intravenously injected with alpha(v)beta(3)-integrin-targeted paramagnetic nanoparticles, nontargeted paramagnetic nanoparticles, or alpha(v)beta(3)-targeted-nonparamagnetic nanoparticles 2 hr before they were injected with alpha(v)beta(3)-integrin-targeted paramagnetic nanoparticles (i.e., in vivo competitive blockade) and imaged with MRI. Contrast enhancement of neovascularity in animals that received alpha(nu)beta(3)-targeted paramagnetic nanoparticles increased 173% by 120 min. Signal contrast with nontargeted paramagnetic nanoparticles was approximately 50% less than that in the targeted group (P < 0.05). Molecular MRI results were corroborated by histology. In a competitive cell adhesion assay, incubation of alpha(nu)beta(3)-expressing cells with targeted nanoparticles significantly inhibited binding to a vitronectin-coated surface, confirming the bioactivity of the targeted nanoparticles. The present study lowers the limit previously reported for detecting sparse biomarkers with molecular MRI in vivo. This technique may be employed to noninvasively detect very small regions of angiogenesis associated with nascent melanoma tumors, and to phenotype and stage early melanoma in a clinical setting.
CRC Handbook of Optical Resolutions via Diastereomeric Salt Formation (2001)

Optically active compounds are gaining ever-increasing importance in organic chemistry, both in the academic and the industrial arenas. The rational synthesis of the growing number of chiral chemicals, drugs, and natural products demands efficient methods for producing these compounds in an enantiomerically, highly pure form. Despite the available
Second-generation line probe assay for hepatitis C virus genotyping (1996)

Because of the enormous variability of hepatitis C virus (HCV), the development of reliable genotyping assays is a formidable challenge. The optimal genotyping region appears to be the 5' untranslated region (UR) because of high conservation within, but considerable variability between, genotypes. In this study, 21 probes dispersed over seven variable 5' UR areas were applied to a line probe assay (LiPA) and used to analyze 506 HCV-infected sera from different geographical regions representing a multitude of subtypes. At least 31 different reactivity patterns emerged, with 404 (80%) of 506 distributed over 11 prototype patterns, in general corresponding to subtypes 1a, 1b, 2a/2c, 2b, 3a, 5a, and 6a and several type 4 subtypes. Subtyping specificity ranged from 97% in Hong Kong to 90% in Europe but was only 11% in West Africa, while typing specificity was always 100% when samples from Vietnam were excluded. In a second evaluation, the subtype prediction by LiPA of 448 GenBank 5' UR HCV sequences was scored. Of the 58 theoretically predicted patterns, 321 sequences (72%) were covered by the 11 prototype patterns. We concluded that (i) the selected probes detected the corresponding signature motifs in the seven variable regions with 100% reliability; (ii) these motifs allowed correct type interpretation of samples collected worldwide, with the exclusion of Vietnam, Thailand, or Vietnamese patients residing in European hospitals; and (iii) subtyping specificities vary according to geographical region, with 11 prototype subtyping patterns identifying the majority of samples from Europe and the Americas. These results indicate that the LiPA is a reliable assay applicable to routine typing and subtyping of HCV specimens.
Tight junction properties of the immortalized human bronchial epithelial cell lines Calu‐3 and 16HBE14o‐ (2000)

Tight junctions (TJs) make a vital contribution to the barrier properties of the airway lining. Opening of TJs, or their frank cleavage, is suspected as a pathophysiological event in the lung, but research into the cellular and molecular mechanisms involved has been impeded by technical limitations of available experimental models. The authors have compared the properties of two epithelial cell lines derived from bronchial epithelium to explore whether these cell lines could constitute appropriate tools for the study of TJ regulation in bronchial epithelium. Investigations of TJs in 16HBE14o- cells and Calu-3 cells were made by fluorescent antibody labelling in conjunction with wide-field, confocal or 2-photon molecular excitation microscopy (2PMEM). The presence of TJ proteins was confirmed by immunoblotting and functional properties of the monolayers were studied by measurements of transepithelial electrical resistance and mannitol permeability. Cells of both lines formed confluent monolayers in which the cells expressed the TJ proteins occludin and ZO-1 in continuous circumferential patterns suggestive of functional TJs. This interpretation was supported by the development of transepithelial electrical resistances and of low paracellular permeability to solutes. Within the limits of resolution offered by 2PMEM, occludin and ZO-1 appeared to colocalize at TJs. These studies suggest that the 16HBE14o- cells and Calu-3 cell lines are potentially useful in vitro models to study how tight junction opening or cleavage changes the functional barrier properties of bronchial epithelium.
MinK Potassium Channels Are Heteromultimeric Complexes (1997)

MinK is a transmembrane protein of 130 amino acids found in the kidney, heart, and vestibular system of mammals. Its expression in Xenopus laevis oocytes induces a voltage-dependent potassium current similar to that seen in vivo. Indirect evidence has fueled speculation that function requires association of MinK and another protein endogenous to oocytes and native tissues. In this report, we show that direct covalent modification of an oocyte membrane protein alters properties of the MinK ion conduction pore; modified channels exhibit decreased potassium conduction and increased permeability to sodium and cesium. The modifying reagents, two membrane-impermeant, sulfhydryl-specific methanethiosulfonate derivatives, react only from the extracellular solution at rates that are determined by the conformational state of the channel. These findings indicate that MinK is intimately associated with an oocyte protein whose exposure to the external solution changes during channel gating and which acts with MinK to establish ion conduction pore function.
Postoperative Nachsorge nach filtrierender Glaukomchirurgie (2005)

Hintergrund: Über den Erfolg der filtrierenden Glaukomchirurgie entscheidet in der Hauptsache die postoperative Nachsorge. Die Wundheilung im Sickerkissenbereich steht hier im Vordergrund. Die präoperative Vorbehandlung der Bindehaut kann die Vernarbungsvorgänge im Bindehaut/Tenon bereits günstig beeinflussen.
TET2 as an epigenetic master regulator for normal and malignant hematopoiesis (2014)

DNA methylation is one of the critical epigenetic modifications regulating various cellular processes such as differentiation or proliferation, and its dysregulation leads to disordered stem cell function or cellular transformation. The ten-eleven translocation (TET) gene family, initially found as a chromosomal translocation partner in leukemia, turned out to be a key enzyme for DNA demethylation. TET genes hydroxylate 5-methylcytosine to 5-hydroxymethylcytosine, which is then converted to unmodified cytosine through multiple mechanisms. Somatic mutations of the TET2 gene were reported in a variety of human hematological malignancies such as leukemia, myelodysplastic syndrome, and malignant lymphoma, suggesting a critical role for TET2 in hematopoiesis. The importance of the TET-mediated cytosine demethylation pathway is also underscored by a recurrent mutation of isocitrate dehydrogenase 1 (IDH1) and IDH2 in hematological malignancies, whose mutation inhibits TET function through a novel oncometabolite, 2-hydroxyglutarate. Studies using mouse models revealed that TET2 is critical for the function of hematopoietic stem cells, and disruption of TET2 results in the expansion of multipotent as well as myeloid progenitors, leading to the accumulation of premalignant clones. In addition to cytosine demethylation, TET proteins are involved in chromatin modifications and other cellular processes through the interaction with O-linked β-N-acetylglucosamine transferase. In summary, TET2 is a critical regulator for hematopoietic stem cell homeostasis whose functional impairment leads to hematological malignancies. Future studies will uncover the whole picture of epigenetic and signaling networks wired with TET2, which will help to develop ways to intervene in cellular pathways dysregulated by TET2 mutations.