gebhart/patrepeval huggingface dataset:
Recent concepts in non‐alcoholic fatty liver disease (2005)

Non-alcoholic fatty liver disease (NAFLD) is present in up to one-third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors, including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however, staging the disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as cirrhosis and hepatocellular carcinoma, which occur in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.
<i>Negro Mecca: A History of the Negro in New York City, 1865-1920</i>, by Seth M. Scheiner (1967)

"Negro Mecca: A History of the Negro in New York City, 1865-1920, by Seth M. Scheiner." Canadian Journal of History, 2(2), pp. 109–110
Alpha-synuclein: from secretion to dysfunction and death (2012)

The aggregation, deposition, and dysfunction of alpha-synuclein (aSyn) are common events in neurodegenerative disorders known as synucleinopathies. These include Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. A growing body of knowledge on the biology of aSyn is emerging and enabling novel hypotheses to be tested. In particular, the hypothesis that aSyn is secreted from neurons, thus contributing to the spreading of pathology not only in the brain but also in other organs, is gaining momentum. Nevertheless, the precise mechanism(s) of secretion, as well as the consequences of extracellular aSyn species for neighboring cells are still unclear. Here, we review the current literature and integrate existing data in order to propose possible mechanisms of secretion, cell dysfunction, and death. Ultimately, the complete understanding of these processes might open novel avenues for the development of new therapeutic strategies.
Molecular assembly and evolution of multi-subunit extracellular annelid hemoglobins (1990)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.
Investigation of the Segregation of Binary Mixtures with Iron-Based Particles in a Bubbling Fluidized Bed (2019)

The characterization of the segregation phenomena in binary mixtures of solids with very different densities and/or particle sizes is highly relevant in many industrial processes. As a recent example, some advanced CO<sub>2</sub> capture systems using fluidized beds include the separation by segregation of the functional materials. In this work, we have conducted mixing-segregation experiments with particles of iron ore (a typical oxygen carrier in chemical looping combustion systems) acting as jetsam, and glass beads (representing a lower density solid present in the bed) acting as flotsam, to measure solid concentration profiles at different fluidizing gas velocities and mixture compositions of different-sized particles. The experimental concentration profiles have been interpreted using a modified version of the model proposed by Gibilaro and Rowe. A relatively simple correlation is included in the model to calculate the segregation model parameters, which depend on the physical properties of the fluidized solids. The model fits reasonably well with all experimental data, especially for mixtures with a low fraction of oxygen carriers, which are the most relevant for the design of future continuous separation of solids by segregation.
Comparative Genomics of 28 Salmonella enterica Isolates: Evidence for CRISPR-Mediated Adaptive Sublineage Evolution (2011)

Despite extensive surveillance, food-borne Salmonella enterica infections continue to be a significant burden on public health systems worldwide. As the S. enterica species comprises sublineages that differ greatly in antigenic representation, virulence, and antimicrobial resistance phenotypes, a better understanding of the species' evolution is critical for the prediction and prevention of future outbreaks. The roles that virulence and resistance phenotype acquisition, exchange, and loss play in the evolution of S. enterica sublineages, which to a certain extent are represented by serotypes, remains mostly uncharacterized. Here, we compare 17 newly sequenced and phenotypically characterized nontyphoidal S. enterica strains to 11 previously sequenced S. enterica genomes to carry out the most comprehensive comparative analysis of this species so far. These phenotypic and genotypic data comparisons in the phylogenetic species context suggest that the evolution of known S. enterica sublineages is mediated mostly by two mechanisms, (i) the loss of coding sequences with known metabolic functions, which leads to functional reduction, and (ii) the acquisition of horizontally transferred phage and plasmid DNA, which provides virulence and resistance functions and leads to increasing specialization. Matches between S. enterica clustered regularly interspaced short palindromic repeats (CRISPR), part of a defense mechanism against invading plasmid and phage DNA, and plasmid and prophage regions suggest that CRISPR-mediated immunity could control short-term phenotype changes and mediate long-term sublineage evolution. CRISPR analysis could therefore be critical in assessing the evolutionary potential of S. enterica sublineages and aid in the prediction and prevention of future S. enterica outbreaks.
Identification of the major chromaffin granule-binding protein, chromobindin A, as the cytosolic chaperonin CCT (chaperonin containing TCP-1). (1994)

Chromobindin A is a multisubunit complex ATPase that binds to chromaffin granule membranes in a calcium-dependent manner and requires ATP for release from the membrane (Martin, W. H., and Creutz, C. E. (1987) J. Biol. Chem. 262, 2803-2810). Here we report that the seven previously characterized subunits of chromobindin A cross react with antisera specific to subunits of CCT, the chaperonin containing TCP-1 (Kubota, H., Hynes, G., Carne, A., Ashworth, A., and Willison, K. (1994) Curr. Biol. 4, 89-99). The chromobindin A subunits previously called chromobindins 12, 13, 14, 15, 16, 18, and 19 cross-react specifically with subunits beta, delta, theta, alpha, zeta, xi, and gamma, respectively, of CCT. Additional similarities in subunit molecular weights, isoelectric points, and the morphologies of the two protein complexes as determined by electron microscopy support identification of chromobindin A as an adrenal medullary form of CCT. The chromobindin A/CCT complex was found to bind at least 7-fold more efficiently to affinity columns of chromaffin granule membranes than of adrenal medullary cytosol proteins, suggesting a specific interaction occurs between the complex and membrane components. The results indicate that the previously described characteristics of chromobindin A are likely to be relevant to the functions of CCT and suggest that the adrenal medullary form of CCT may play a role in the activities of secretory vesicle membranes.
Prediction of Individual Household Energy Bills Using Deep Learning (2020)

Energy bills are one of the most significant regular payments made by any household. The accurate estimation of the energy bills can help people make better decisions on their energy use. However, it is difficult for people to predict their monthly energy bills because of many influencing factors, such as weather and progressive rates. In this paper, we propose a deep learning-based prediction method of the energy bills for individual households, considering the weather. First, we proposed a gated recurrent unit-based model that can incorporate weather and date information and predict energy usage of electricity, water, and gas. Then, a weighted mean squared error is adopted for training of the proposed model for better accuracy. Finally, the predicted energy usage using the proposed model are converted to a monthly energy bill. The proposed approach is verified on the dataset consisting of energy usage data of 2,234 households and weather data of the Korea Meteorological Administration. The results show that our approach can accurately predict the energy bills of individual households with a small average error of 3,892 won.
Mitigation using a tandem construct containing a selectively unfit gene precludes establishment of <i>Brassica napus</i> transgenes in hybrids and backcrosses with weedy <i>Brassica rapa</i> (2005)

Transgenic oilseed rape (Brassica napus) plants can interbreed with nearby weedy Brassica rapa, potentially enhancing the weediness and/or invasiveness of subsequent hybrid offspring. We have previously demonstrated that transgenic mitigation effectively reduces the fitness of the transgenic dwarf and herbicide-resistant B. napus volunteers. We now report the efficacy of such a tandem construct, including a primary herbicide-resistant gene and a dwarfing mitigator gene, to preclude the risks of gene establishment in the related weed B. rapa and its backcross progeny. The transgenically mitigated and non-transgenic B. rapa x B. napus interspecific hybrids and the backcrosses (BC(1)) with B. rapa were grown alone and in competition with B. rapa weed. The reproductive fitness of hybrid offspring progressively decreased with increased B. rapa genes in the offspring, illustrating the efficacy of the concept. The fitness of F(2) interspecific non-transgenic hybrids was between 50% and 80% of the competing weedy B. rapa, whereas the fitness of the comparable T(2) interspecific transgenic hybrids was never more than 2%. The reproductive fitness of the transgenic T(2) BC(1) mixed with B. rapa was further severely suppressed to 0.9% of that of the competing weed due to dwarfism. Clearly, the mitigation technology works efficiently in a rapeseed crop-weed system under biocontainment-controlled environments, but field studies should further validate its utility for minimizing the risks of gene flow.
Effect of Food on the Pharmacokinetics of Cyclosporine in Healthy Subjects Following Oral and Intravenous Administration (1990)

The pharmacokinetics of cyclosporine were studied in healthy subjects following administration of cyclosporine both orally (10 mg kg-1) and intravenously (4 mg kg-1) without and with high fat meals. Both blood and plasma samples (separated at 37 degrees C) were analyzed for cyclosporine concentration. Blood and plasma clearances of cyclosporine were calculated to be 0.36 and 0.47 L hr-1 Kg-1, respectively, and volume of distribution at steady state was calculated to be 1.21 L Kg-1, when cyclosporine was administered without a high fat meal. Using plasma analysis, the oral bioavailability of cyclosporine was estimated to be 21 and 79%, when administered without and with a high fat meal, respectively. When cyclosporine was administered intravenously together with a high fat meal, both clearance and volume of distribution increased significantly. Blood and plasma clearances of cyclosporine were 0.44 and 0.70 L hr-1 Kg-1, respectively, when cyclosporine was administered along with a high fat meal. We conclude that food not only enhances the absorption of cyclosporine but also enhances its clearance and volume of distribution. The observed variability in clearance, bioavailability, and volume of distribution values for cyclosporine across various pharmacokinetic studies can be partially accounted by the type of food administered and the sampling matrix used for analysis.
Drug Release from Thermosetting Fatty Vehicles Filled into Hard Gelatin Capsules (1987)

An initial in vitro study has been conducted to evaluate liquid filled hard gelatin capsules as potential sustained release products. Using the model compounds salicylic acid (a weak acid) and tioconazole (a weak base), release characteristics from a series of thermosetting fatty vehicles (Gelucires) have been investigated. Rapid and sustained release profiles were obtained by using different vehicles. Drug release obeyed the pH-partition theory, and a general relationship between the release rate of salicylic acid and vehicle HLB was found. However, a similar relationship could not be identified for the release of tioconazole. Drug release occurred by diffusion or erosion and diffusion processes, dependent on the vehicle employed. Diffusion release occurred relatively slowly (particularly with tioconazole) therefore for the model systems an erodible carrier would be required to achieve release rates consistent with dosing oral sustained release products.
Activation of c-Jun N-Terminal Kinase and p38 in an Alzheimer's Disease Model Is Associated with Amyloid Deposition (2002)

The mechanisms by which neurons and synapses are lost in Alzheimer's disease (AD) are not completely understood. To characterize potential signaling events linked to AD pathogenesis, activation-specific antibodies were used to examine mitogen-activated protein kinase (MAPK) kinase pathways at various ages in mice transgenic for human amyloid precursor protein-695 with the Swedish familial AD mutations (Tg2576) and homozygous for a P264L familial AD mutation introduced by targeting of the presenilin-1 gene (PS1(P264L)). Although the c-Jun N-terminal kinase (JNK) and p38 pathways were significantly activated in the cortex at both 7 and 12 months of age, there was no significant activation of the extracellular signal-regulated kinase pathway. MAPK kinase-4, an upstream activator of JNK, was also significantly activated at 7 and 12 months, whereas c-Jun, a downstream effector of JNK-associated apoptotic signaling, was not induced. The lack of c-Jun activation is consistent with the absence of neuronal loss in both cortex and hippocampal CA1 at 12 months. The JNK activation was localized to amyloid deposits, within neurites containing phosphorylated tau. Synaptophysin was quantified biochemically as a measure of synaptic integrity and was significantly reduced in an age-dependent manner in the Tg2576/PS1(P264L) cortex but not in either PS1(P264L) or Tg2576 cortex. Stress-responsive MAP kinase pathways were activated in the brain of the Tg2576/PS1(P264L) AD model, and this activation was coincident with the age-dependent increase in amyloid deposition, tau phosphorylation, and loss of synaptophysin.
Online fluorescence anisotropy immunoassay for monitoring insulin secretion from islets of Langerhans (2016)

Insulin secretion from islets of Langerhans is a dynamic process that is essential for maintaining glucose homeostasis. The ability to measure dynamic changes in insulin levels upon glucose stimulation from single islets will allow testing of therapeutics and investigating mechanisms of defective secretion observed in metabolic diseases. Most approaches to date for measurement of rapid changes in insulin levels rely on separations, making the assays difficult to translate to non-specialist laboratories. To enable rapid measurements of secretion dynamics from a single islet in a manner that will be more suitable for transfer to non-specialized laboratories, a microfluidic online fluorescence anisotropy immunoassay was developed. A single islet was housed inside a microfluidic chamber and stimulated with varying glucose levels from a gravity-based perfusion system. The total effluent of the islet chamber containing the islet secretions was mixed with gravity-driven solutions of insulin antibody and Cy5-labeled insulin. After mixing was complete, a linearly polarized 635 nm laser was used to excite the immunoassay mixture and the emission was split into parallel and perpendicular components for determination of anisotropy. Key factors for reproducible anisotropy measurements, including temperature homogeneity and flow rate stability were optimized, which resulted in a 4 nM limit of detection for insulin with <1% RSD of anisotropy values. The capability of this system for measuring insulin secretion from single islets was shown by stimulating an islet with varying glucose levels. As the entire analysis is performed optically, this system should be readily transferable to other laboratories.
Astrocytic Regulation of Human Monocytic/Microglial Activation (2008)

Recent reports have described reduced immunological responsiveness and stimulatory capacity among monocytes/microglia that infiltrate malignant human gliomas. Herein, we demonstrate that culture of ex vivo human monocytes or primary human microglia with tumor cells isolated from glioblastoma multiforme (GBM) specimens renders them tolerogenic, capable of suppressing the function of ex vivo monocytes in the absence of tumor cells or their soluble factors. We demonstrate that the tolerance induced in monocytes/microglia by GBM tumor cells is not associated with interference with the signaling cascade associated with TLR- or CD40-induced monocyte activation. Rather, these tumor cells appear to up-regulate pathways that antagonize positive signaling pathways, including but not limited to STAT3 and STAT5. Finally, we demonstrate that the tolerogenic properties of GBM tumor cells amplify properties inherent to nontransformed astrocytes. Future studies that identify all of the molecular mechanisms by which astrocytes and malignant gliomas suppress monocyte/microglial function will have dual therapeutic benefits: suppressing these pathways may benefit patients with astrocytic tumors, while enhancing them may benefit patients with autoimmune processes within the CNS, such as multiple sclerosis.
Structure and Utilization of Tubulin Isotypes (1988)

Cells organize many of their biochemical reactions in non-membrane compartments. Recent evidence has shown that many of these compartments are liquids that form by phase separation from the cytoplasm. Here we discuss the basic physical concepts necessary ...Read More
Kinetic behaviour of calf-intestinal alkaline phosphatase with 4-methylumbelliferyl phosphate (1965)

1. The effects of varying pH, ionic strength and temperature on the parameters K(m) and V(max.) for a purified alkaline phosphatase from calf intestinal mucosa with a new fluorogenic substrate, 4-methylumbelliferyl phosphate monoester disodium salt, and an ammediol-hydrochloric acid buffer system were determined. 2. It was found that, under varying conditions, a relationship exists between K(m) and V(max.) such that V(max.)=beta/(1+alpha/K(m)), where alpha and beta are constants, temperature- and ionic strength-dependent, but pH-independent. It is shown that this relationship accounts satisfactorily for the well-known effect of varying substrate concentration on optimum pH and velocity. 3. The various results are interpreted in terms of a pH-dependent conformational equilibrium between two forms of the enzyme, E(1) and E(2). Only E(1) combines with substrate, and only E(2) reacts to give inorganic phosphate. 4. To account for the pH-variation of K(m) and V(max.) in terms of this theory, it is postulated that the conformational change is associated with a change in pK of two basic groups in the enzyme.
ANAEROBIC AND AEROBIC BACTERIOLOGY OF THE SALIVA AND GINGIVA FROM 16 CAPTIVE KOMODO DRAGONS (<i>VARANUS KOMODOENSIS</i>): NEW IMPLICATIONS FOR THE “BACTERIA AS VENOM” MODEL (2013)

It has been speculated that the oral flora of the Komodo dragon (Varanus komodoensis) exerts a lethal effect on its prey; yet, scant information about their specific oral flora bacteriology, especially anaerobes, exists. Consequently, the aerobic and anaerobic oral bacteriology of 16 captive Komodo dragons (10 adults and six neonates), aged 2-17 yr for adults and 7-10 days for neonates, from three U.S. zoos were studied. Saliva and gingival samples were collected by zoo personnel, inoculated into anaerobic transport media, and delivered by courier to a reference laboratory. Samples were cultured for aerobes and anaerobes. Strains were identified by standard methods and 16S rRNA gene sequencing when required. The oral flora consisted of 39 aerobic and 21 anaerobic species, with some variation by zoo. Adult dragons grew 128 isolates, including 37 aerobic gram-negative rods (one to eight per specimen), especially Enterobacteriaceae; 50 aerobic gram-positive bacteria (two to nine per specimen), especially Staphylococcus sciuri and Enterococcusfaecalis, present in eight of 10 and nine of 10 dragons, respectively; and 41 anaerobes (one to six per specimen), especially clostridia. All hatchlings grew aerobes but none grew anaerobes. No virulent species were isolated. As with other carnivores, captive Komodo oral flora is simply reflective of the gut and skin flora of their recent meals and environment and is unlikely to cause rapid fatal infection.
A Polymorphism in the TCF7 Gene, C883A, Is Associated With Type 1 Diabetes (2003)

Type 1 diabetes is an autoimmune disease with a Th1 phenotype in which insulin-producing beta-cells in the pancreas are destroyed. The T-cell-specific transcription factor TCF7 activates genes involved in immune regulation and is a candidate locus for genetic susceptibility to type 1 diabetes. A nonsynonymous single nucleotide polymorphism (SNP) (Pro to Thr) in the TCF7 gene, C883A, was examined in samples from 282 Caucasian multiplex type 1 diabetic families. HLA-DRB1 and -DQB1 genotypes were previously determined for these samples, allowing data stratification based on HLA-associated risk. The transmission disequilibrium test showed significant overtransmission of the A allele from fathers (64.1%, P < 0.007) and nonsignificant overtransmission (57.4%, P < 0.06) of the A allele to patients who do not carry the highest-risk HLA-DR3/DR4 genotype. Elliptical sib pair analysis showed significant associations of the A allele with type 1 diabetes in paternal transmissions (P < 0.03), transmissions to male children (P < 0.04), and in the non-DR3/DR4 group (P < 0.04). These data also suggest that TCF7 C883A may affect age of disease onset. Analysis of genotype data from surrounding SNPs suggests that this TCF7 polymorphism may itself represent a risk factor for type 1 diabetes.
A Hybrid Approach to FPGA Configuration Scrubbing (2016)

This paper describes a FPGA configuration scrubbing approach for Xilinx 7-Series FPGAs that combines the high-speed internal scrubbing available within these devices with an external scrubber. The internal scrubbing unit continuously monitors the frames of the FPGA configuration memory and corrects single-bit frame errors and is used to detect multi-bit frame errors. Multi-bit upsets are repaired by means of a secondary scrubbing mechanism that is primarily external to the FPGA fabric. This Xilinx 7-Series hybrid configuration scrubbing architecture scans 25,636,224 bits of the XC7Z020 device in several microseconds and detects upsets within 8 ms and then corrects most multi-cell upsets in under an additional 6 ms. This configuration scrubber was validated with configuration fault injection and neutron radiation testing.