gebhart/patrepeval huggingface dataset:
Role of receptor complexes in resistance or sensitivity to growth inhibition by TGFβ in intestinal epithelial cell clones (1993)

Untransformed rat intestinal epithelial cells (IEC-18) were chemically mutagenized, selected in the presence of TGF beta 1, and cloned by limiting dilution. Two clones (4-5, 4-6) were resistant to growth inhibition by both TGF beta 1 and TGF beta 2. Another clone (4-1) was more sensitive to both TGF beta isoforms (relative to parental IEC-18 cells). IC50 values for TGF beta 1 and 2 in the 4-1 cells were at least 1/9 those of the parental cells; growth rates were reduced by 49% for TGF beta 1 and by 26% for TGF beta 2 in this clone. This increased sensitivity to TGF beta was explained by the 5- to 10-fold increase, relative to parental cells, in binding of TGF beta 1 and TGF beta 2 to both the type I and II receptors. In contrast, the resistance to growth inhibition by TGF beta in the 4-5 and 4-6 cells could not be explained by a decrease in either TGF beta binding affinities or in total number of receptors expressed, by the presence of serum binding components, or by occupation of receptor binding sites with autocrine TGF-beta 1. However, in comparison to TGF beta-sensitive cells (IEC-18, 4-1), the resistant cells displayed a higher ratio of type II relative to type I receptor binding by TGF-beta 1. Thus, a critical ratio of binding to receptor subtypes correlated with growth inhibition by TGF-beta 1. Resistance to TGF-beta 2 in the same clones did not appear to be receptor related. Thus, different mechanisms for resistance to TGF-beta 1 and TGF-beta 2 were observed within a given clone.
Cerebral resuscitation after cardiac arrest: a review. (1986)

Cerebral neurons can tolerate at least 20 min of normothermic ischemic anoxia. Cerebral recovery from more than 5 min of cardiac arrest is hampered by complex secondary derangements of multiple organ systems after reperfusion. There is increasing support of our hypothesis that this "postresuscitation syndrome" includes the following: secondary cerebral perfusion failure, cerebral reoxygenation injury (cell-necrotizing cascades), and cerebral "intoxication" from derangements of extracerebral organs. To be optimal for the brain, CPR with optimal perfusion pressure must be started as promptly as possible. Significant though inconsistent mitigation of permanent brain damage after prolonged complete global brain ischemia has been achieved in animal outcome preparations with the use of the following treatments initiated at the start of reperfusion: brain-oriented extracerebral life support by protocol, intra-arterial hemodilution, hypertension, and artificial circulation, barbiturates, calcium-entry blockers, free-radical scavengers, and multifaceted treatments. We currently recommend treatment 1 for patient care and treatment 2 for clinical feasibility trials. Treatment 3, thiopental loading (starting 10 to 50 min after restoration of spontaneous circulation), was tested in a randomized clinical trial and was not shown to confer a statistically significant benefit. A calcium-entry blocker is under clinical investigation. Many other novel treatments appear promising but further animal studies are required. The complex multifactorial pathogenesis of postcardiac arrest encephalopathy requires systematic multicenter development of etiology-specific combination therapies.
The thioredoxin binding domain of bacteriophage T7 DNA polymerase confers processivity on Escherichia coli DNA polymerase I (1997)

Bacteriophage T7 DNA polymerase shares extensive sequence homology with Escherichia coli DNA polymerase I. However, in vivo, E. coli DNA polymerase I is involved primarily in the repair of DNA whereas T7 DNA polymerase is responsible for the replication of the viral genome. In accord with these roles, T7 DNA polymerase is highly processive while E. coli DNA polymerase I has low processivity. The high processivity of T7 DNA polymerase is achieved through tight binding to its processivity factor, E. coli thioredoxin. We have identified a unique 76-residue domain in T7 DNA polymerase responsible for this interaction. Insertion of this domain into the homologous site in E. coli DNA polymerase I results in a dramatic increase in the processivity of the chimeric DNA polymerase, a phenomenon that is dependent upon its binding to thioredoxin.
Palpationlike soft-material elastic modulus measurement using piezoelectric cantilevers (2006)

We have developed an all-electrical piezoelectric cantilever sensor that can self-excite and self-detect for tissue elastic modulus measurement. An all-electrical piezoelectric cantilever is consisted of a sandwich of piezoelectric layer, e.g., lead zirconate titanate (PZT), a nonpiezoelectric layer, e.g., stainless steel, and a second piezoelectric layer. The top piezoelectric layer serves as the driving layer (self-exciting) and the second piezoelectric layer as the sensing layer (self-sensing). The driving and sensing piezoelectric layers may be of different lengths. Applying a dc voltage across the driving PZT layer causes the piezoelectric cantilever to bend. The resultant bending stress in the sensing PZT layer generates a piezoelectric voltage across the sensing PZT layer that rises rapidly to a maximum before it decays with time. The maximum induced voltage was used to measure the axial displacement of the piezoelectric cantilever. With its force generation and displacement sensing capability, we show that an all-electrical piezoelectric cantilever can measure the elastic modulus of tissues both under the regular compression geometry and the flat-punch indentation geometry. In addition, the sensor can map the local elastic modulus variations of tissues much like palpation.
Hidden Topic Sentiment Model (2016)

Various topic models have been developed for sentiment analysis tasks. But the simple topic-sentiment mixture assumption prohibits them from finding fine-grained dependency between topical aspects and sentiments. In this paper, we build a Hidden Topic Sentiment Model (HTSM) to explicitly capture topic coherence and sentiment consistency in an opinionated text document to accurately extract latent aspects and corresponding sentiment polarities. In HTSM, 1) topic coherence is achieved by enforcing words in the same sentence to share the same topic assignment and modeling topic transition between successive sentences; 2) sentiment consistency is imposed by constraining topic transitions via tracking sentiment changes; and 3) both topic transition and sentiment transition are guided by a parameterized logistic function based on the linguistic signals directly observable in a document. Extensive experiments on four categories of product reviews from both Amazon and NewEgg validate the effectiveness of the proposed model.
Histological examination of β‐tricalcium phosphate graft in human femur (2002)

Prominent osteoconductive activity and the biodegradable nature of beta tricalcium phosphate (beta-TCP) for bone grafts in animal experiments has been reported. A new type of beta-TCP has been manufactured at extraordinarily high purity and has been available as potent bone grafting substitute for clinical use. The histological features of grafted beta-TCP in human bone have been analyzed. A 33-year-old female with a bone tumor of the proximal femur underwent curettage and beta-TCP graft under the diagnosis of probable benign fibrous dysplasia. Four weeks later, the proximal femur, including the grafted beta-TCP was resected because of the final diagnosis of the curettaged materials was osteosarcoma. The resected specimen revealed abundant direct new bone apposition on beta-TCP. There was no cartilaginous tissue or enchondral ossification. Bone formation was more prominent in the periphery of the grafted area than in the center. There was a considerable number of osteoclast-like giant cells surrounding the beta-TCP. This case illustrated that highly purified beta-TCP had prominent osteoconductive activity and biodegradable nature in human bone.
OptoGranules reveal the evolution of stress granules to ALS-FTD pathology (2018)

Stress granules are non-membranous assemblies of mRNA and protein that form in response to a variety of stressors. Genetic, pathologic, biophysical and cell biological studies have implicated disturbances in the dynamics of membrane-less organelles, such as stress granules, as a pathobiological component of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) 1–12 . This confluence of evidence has inspired the hypothesis that these diseases reflect an underlying disturbance in the dynamics and material properties of stress granules; however, this concept has remained largely untestable in available models of stress granule assembly, which require the confounding variable of exogenous stressors. Here we demonstrate the development and use of a light-inducible stress granule system, termed OptoGranules, which permits discrete, experimental control of the dynamics and material properties of stress granules in living cells in the absence of exogenous stressors. The nucleator in this system is Opto-G3BP1, a light-sensitive chimeric protein assembled from the intrinsically disordered region (IDR) and RNA-binding domain of G3BP1 combined with the light-sensitive oligomerization domain of Arabidopsis thaliana cryptochrome 2 (CRY2) photolyase homology region (PHR). Upon stimulation with blue light, Opto-G3BP1 initiates the rapid assembly of dynamic, cytoplasmic, liquid granules that are composed of canonical stress granule components, including G3BP1, PABP, TIA1, TIAR, eIF4G, eIF3η, ataxin 2, GLE1, TDP-43 and polyadenylated RNA. With this system, we demonstrate that persistent or repetitive assembly of stress granules is cytotoxic and is accompanied by the evolution of stress granules to neuronal cytoplasmic inclusions that recapitulate the pathology of ALS-FTD.
Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acidsD. W. Cushman, H. S. Cheung, E. F. Sabo, and M. A. OndettiCite this: Biochemistry 1977, 16, 25, 5484–5491Publication Date (Print):December 13, 1977Publication History Published online1 May 2002Published inissue 13 December 1977https://doi.org/10.1021/bi00644a014RIGHTS & PERMISSIONSArticle Views2361Altmetric-Citations721LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (990 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Caspase‐3 activation in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated mice (2001)

In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of Parkinson's disease (PD), dopaminergic (DA) neurons have been shown to die by apoptosis. Moreover, recent postmortem and in vitro results have indicated that apoptotic cell death induced by 1-methyl-4-phenylpyridinium (MPP(+)) may be mediated by caspase-3. To establish whether caspase-3 activation may indeed play a role in an in vivo model of PD, we studied caspase-3 activation in C57Bl/6 mice subchronically intoxicated with MPTP. We show that caspase-3 activation peaks early, at days 1 and 2 after the end of MPTP intoxication. In contrast, pycnotic neurons persist until day 7 postintoxication, indicating that caspase-3 activation is an early and transient phenomenon in apoptotic death of DA neurons. We further demonstrate that loss of tyrosine hydroxylase (TH) immunoreactivity in this model is indeed due to cell loss rather than to loss of TH protein expression. We conclude that mice subchronically intoxicated with MPTP represent a valid PD model to study and manipulate caspase activation in vivo.
Mechanisms Underlying the Suppression of Adjuvant‐Induced Arthritis by 6‐Mercaptopurine (1977)

Daily oral administration of 6-mercaptopurine suppressed the development of the secondary (immune) lesions of adjuvant arthritis in a dose-related manner. The degrees of arthritis suppression corresponded closely to suppressions of concurrent development of the humoral and the cellular immune response to El4 cells. A short course of therapy during the sensitization period (day - 1 to day 5 when the day of adjuvant injection is designated as day 0) appeared to be almost as effective as continued daily dosing (day - 1 to day 15). The drug did not influence the development of the primary (nonimmune) lesions of adjuvant arthritis at all dosage levels investigated. Chronic pretreatment with 10 mg/kg/day PO for 17 days had no effect on the development of carrageenin-induced acute inflammation in the rat. The suppression of adjuvant arthritis by 6-mercaptopurine, unlike suppression by cyclophosphamide, appears to result primarily from its suppressive action on the immune response.
Post-transcriptional regulation of opioid receptors in the nervous system (2004)

Three types of opioid receptors exist in the animals, each is encoded by a single gene, i.e., the mu opioid receptor gene, the delta opioid receptor gene, and the kappa opioid receptor gene. However, each opioid receptor gene produces multiple mRNA variants as a result of alternative promoter usages, splicing and/or polyadenylation. As such, a large reservoir of regulatory events has evolved for the control of the production of mRNA variants or differentially modified proteins from each opioid receptor gene. This review focuses on post-transcriptional events for the regulation of opioid receptor expression or activities, including alternative splicing, mRNA stability, translation, RNA polyadenylation, RNA transport, and covalent modification of the receptors. Variation at the mRNA level contributes, primarily, to the control of spatial and temporal expression of these receptors in different parts of neurons; whereas modification at the receptors is the key for controlling the duration and amplitude of signals generated from these receptors.
The Problem of Renal Function Monitoring in Patients Treated With the Novel Antiretroviral Drugs (2014)

Chronic kidney disease (CKD) is currently considered a major comorbidity in patients affected by HIV infection. In addition, new generation antiretroviral drugs that interact with creatinine transporters were recently introduced. Rilpivirine, dolutegravir, and cobicistat, with different mechanisms, inhibit the amount of tubular secretion of creatinine causing a slight increase in serum creatinine levels and consensual eGFRcreat reduction. This will require an unprecedented attention to renal issues, because the new drugs can also be associated to old antiretroviral drugs that may exert renal toxic effects. Owing to the interference of these drugs with creatinine secretion, an alternative way of estimating GFR would be desirable. At the moment, methods of direct GFR measurement have a high impact on the patient, are not readily available, or are not reliable in HIV patients. Consequently, use of classic formulas to estimate GFR is still recommended, considering the apparent reduction of eGFRcreat due to these drugs. Tubular function needs to be carefully monitored with simple tests such as proteinuria, phosphatemia, urinary excretion of phosphate, normoglycemic glycosuria, and excretion of uric acid. More specific and sensitive markers of tubular damage are still not readily available in all clinical labs. HIV patients treated by the novel drugs need to be monitored on a monthly basis for the first 3 months. Subsequent monitoring should be performed on a quarterly basis or guided by comorbidities.
Three Novel Functional Variants of Human U5 Small Nuclear RNA (1992)

We have identified and characterized three new variants of U5 small nuclear RNA (snRNA) from HeLa cells, called U5D, U5E, and U5F. Each variant has a 2,2,7-trimethylguanosine cap and is packaged into an Sm-precipitable small nuclear ribonucleoprotein (snRNP) particle. All retain the evolutionarily invariant 9-base loop at the top of stem 1; however, numerous base changes relative to the abundant forms of U5 snRNA are present in other regions of the RNAs, including a loop that is part of the yeast U5 minimal domain required for viability and has been shown to bind a protein in HeLa extracts. U5E and U5F each constitute 7% of the total U5 population in HeLa cells and are slightly longer than the previously characterized human U5 (A, B, and C) species. U5D, which composes 5% of HeLa cell U5 snRNAs, is present in two forms: a full-length species, U5DL, and a shorter species, U5DS, which is truncated by 15 nucleotides at its 3' end and therefore resembles the short form of U5 (snR7S) in Saccharomyces cerevisiae. We have established conditions that allow specific detection of the individual U5 variants by either Northern blotting (RNA blotting) or primer extension; likewise, U5E and U5F can be specifically and completely degraded in splicing extracts by oligonucleotide-directed RNase H cleavage. All variant U5 snRNAs are assembled into functional particles, as indicated by their immunoprecipitability with anti-(U5) RNP antibodies, their incorporation into the U4/U5/U6 tri-snRNP complex, and their presence in affinity-purified spliceosomes. The higher abundance of these U5 variants in 293 cells compared with that in HeLa cells suggests possible roles in alternative splicing.
Human Umbilical Mesenchymal Stem Cells Promote Recovery After Ischemic Stroke (2011)

Our results demonstrate the therapeutic benefits of HUMSC transplantation for ischemic stroke, likely due to the ability of the cells to produce growth-promoting factors. Thus, HUMSC transplantation may be an effective therapy in the future.
Targeting expression of a transgene to the airway surface epithelium using a ciliated cell-specific promoter (2003)

Many of the vectors being investigated for gene therapy utilize viral promoters or promoters from ubiquitously expressed genes (e.g., CMV, beta-actin). These promoters are active in many cell types and generally result in high levels of transgene expression. However, the use of these promoters for gene therapy of cystic fibrosis (CF) may produce undesirable effects by directing high levels of CFTR expression in cells that normally do not synthesize this protein. In contrast, a vector containing a ciliated cell-specific promoter and delivered to the lung would be active only in the ciliated cells that line the surface of the airways. Ciliated cells express CFTR and are in direct contact with the airway surface liquid normally regulated by CFTR. To develop a ciliated cell-specific promoter for CF gene therapy, we have characterized the promoter region of the FOXJ1 gene, a transcription factor required for ciliated cell differentiation. A fragment of the human FOXJ1 promoter region was inserted into an EGFP expression cassette and used to produce transgenic mice. Transgene-positive animals demonstrated strong EGFP expression in the ciliated cells of tracheal, bronchial, and nasal epithelium. Our results demonstrate that elements within the FOXJ1 promoter region are sufficient to target expression of transgenes to ciliated cells and may be useful for gene therapy of CF.
Micelles Based on Biodegradable Poly(l-glutamic acid)-b-Polylactide with Paramagnetic Gd Ions Chelated to the Shell Layer as a Potential Nanoscale MRI−Visible Delivery System (2007)

There is much interest in the development of a nanoscale drug delivery system with MRI visibility to optimize the delivery efficiency and therapeutic efficacy under image guidance. Here we report on the successful fabrication of nanoscale micelles based on biodegradable poly( L-glutamic acid)- b-polylactide (PG- b-PLA) block copolymer with paramagnetic Gd3+ ions chelated to their shell. PG- b-PLA was synthesized by sequential polymerization reactions: anionic polymerization of L-lactide followed by ring-opening polymerization of benzyl glutamate N-carboxylic anhydride. The metal chelator p-aminobenzyldiethylenetriaminepenta(acetic acid) (DTPA) was readily conjugated to the side chain carboxylic acids of poly( L-glutamic acid). The resulting copolymer formed spherical micelles in aqueous solution with an average diameter of 230 nm at pH 7.4. The size of PG(DTPA)- b-PLA micelles decreased with increasing pH value. DTPA-Gd chelated to the shell layer of the micelles exhibited significantly higher spin-lattice relaxivity (r1) than a small-molecular-weight MRI contrast agent, indicating that water molecules could readily access the Gd ions in the micelles. Because of the presence of multiple carboxylic acid functional groups in the shell layer, polymeric micelles based on biodegradable PG(DTPA-Gd)- b-PLA may be a suitable platform for the development of MRI-visible, targeted nanoscale drug delivery systems.
[Cytotoxic T cell]. (2002)

Cytotoxic T cell (CTL) covers several subtypes, which are CD8+, CD4 and CD4-CD8-. CTL derives from T cell repertoire in lymphoid hematopoietic stem cells. It matures in thymus and is activated in peripheral lymphoid tissues. Effector CTL kills the target cells by 2 ways. One is apoptotic effect mediated by FasL-Fas pathway and the other one is cytolytic effect mediated by granzymes. CTL has aroused great attention due to its significance in anti-tumor and anti-virus.
The use of the McKeever metallic hemiarthroplasty for unicompartmental arthritis. (1985)

We reviewed the results of sixty-one McKeever unicompartmental arthroplasties performed by the senior one of us (T. P.) for osteoarthritis of the knee. The average follow-up was five years (range, two to thirteen years). Forty-four (72 per cent) of the arthroplasties were rated as good to excellent. The average postoperative range of motion in these knees was 110 degrees. Six knees were rated as fair and eleven knees, as poor. The poor results appeared to be caused by degenerative arthritis involving ipsilateral compartments that had not been resurfaced with an implant.