gebhart/patrepeval huggingface dataset:
Eph Receptor Tyrosine Kinases in Tumor and Tumor Microenvironment (2004)

Eph receptors are a unique family of receptor tyrosine kinases (RTK) that play critical roles in embryonic patterning, neuronal targeting, and vascular development during embryogenesis. In adults, Eph RTKs and their ligands, the ephrins, are frequently overexpressed in a variety of cancers and tumor cell lines, including breast, prostate, non-small cell lung and colon cancers, melanomas, and neuroblastomas. Unlike traditional oncogenes that often function only in tumor cells, recent data show that Eph receptors mediate cell-cell interaction both in tumor cells and in tumor microenvironment, namely the tumor stroma and tumor vasculature. As such, Eph RTKs represent attractive potential targets for drug design, as targeting these molecules could attack several aspects of tumor progression simultaneously. This review will focus on recent advances in dissecting the role of Eph RTKs in tumor cells, tumor angiogenesis, and possible contribution to trafficking of inflammatory cells in cancer.
LEKTI Fragments Specifically Inhibit KLK5, KLK7, and KLK14 and Control Desquamation through a pH-dependent Interaction (2007)

LEKTI is a 15-domain serine proteinase inhibitor whose defective expression underlies the severe autosomal recessive ichthyosiform skin disease, Netherton syndrome. Here, we show that LEKTI is produced as a precursor rapidly cleaved by furin, generating a variety of single or multidomain LEKTI fragments secreted in cultured keratinocytes and in the epidermis. The identity of these biological fragments (D1, D5, D6, D8-D11, and D9-D15) was inferred from biochemical analysis, using a panel of LEKTI antibodies. The functional inhibitory capacity of each fragment was tested on a panel of serine proteases. All LEKTI fragments, except D1, showed specific and differential inhibition of human kallikreins 5, 7, and 14. The strongest inhibition was observed with D8-D11, toward KLK5. Kinetics analysis revealed that this interaction is rapid and irreversible, reflecting an extremely tight binding complex. We demonstrated that pH variations govern this interaction, leading to the release of active KLK5 from the complex at acidic pH. These results identify KLK5, a key actor of the desquamation process, as the major target of LEKTI. They disclose a new mechanism of skin homeostasis by which the epidermal pH gradient allows precisely regulated KLK5 activity and corneodesmosomal cleavage in the most superficial layers of the stratum corneum.
Platelet-derived growth factor stimulates Na+ influx in vascular smooth muscle cells (1984)

Platelet-derived growth factor (PDGF) is known to be a potent mitogenic agent for vascular smooth muscle cells. The effect of PDGF on amiloride-sensitive Na+ influx was investigated in A-10 vascular smooth muscle cells. At a dose which maximally stimulates DNA synthesis, PDGF stimulates net Na+ influx in vascular smooth muscle cells. The PDGF-stimulated Na+ influx is linear over a 5-min time course. PDGF stimulates Na+ influx in a concentration-dependent manner, with a concentration of 0.5 U/ml causing half-maximal inhibition. The effects of PDGF on Na+ influx can be mimicked by 10% fetal bovine serum or by the divalent cation ionophore A23187 (5 microM). Net Na+ influx in response to each of these agents was inhibited by amiloride and by benzamil. PDGF-stimulated net Na+ influx was blocked by the intracellular Ca2+ antagonist 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate as well as by the calmodulin antagonists trifluoperazine, chlorpromazine, and imipramine. These data suggest that PDGF may stimulate an amiloride-sensitive Na+ influx pathway via an elevation in intracellular Ca2+ and formation of a Ca-calmodulin complex. This Na+ influx pathway may be a trigger for PDGF-stimulated DNA synthesis.
Efficacy of Selected Treatments of HIV Wasting (2004)

The 3 treatments for HIV wasting assessed--rhGH, testosterone, and anabolic steroids--all demonstrated significant efficacy in increasing LBM as compared with placebo. Although meta-analysis did not indicate any statistically significant differences between these agents in the degree of efficacy in this outcome, the Food and Drug Administration-approved dose of rhGH may have advantages over the other 2 therapies in terms of improvements in functional capacity and QoL.
Circulating Tumor Cells in Breast Cancer (2013)

Circulating tumor cells (CTCs) is tumor cells that circulate in the bloodstream in patients with malignant tumors. Detecting CTCs is considered as a valuable modality as prognostic and predictive markers in patients with breast cancer. There are potential roles of CTCs for prediction of responsiveness of systemic chemotherapy by serial assay of changing patterns of CTCs number. Analysis of CTCs may provide crucial biological information for selection of optimal targeted agents. In this article, we will review and discuss potential roles and clinical applications of CTCs in patients with breast cancer.
Presence of Nuclear Bodies in Some Minicells of Escherichia coli (1969)

Electron microscopy of serial sections of Escherichia coli K-12 (P678-54) revealed that some "minicells" contain nuclear bodies.
Performances of potentially implantable rechargeable glucose sensors in vitro at body temperature. (1991)

The authors developed a glucose sensor that operates in vitro at 37 degrees C for at least three months without recharging. The use of fine carbon particles upon which to immobilize the glucose oxidase makes it possible to recharge the sensor when enzymatic activity diminishes. This may enable the sensor to perform for at least a year when implanted, and thus reduce the frequency of surgical replacement. Recharging is accomplished by inserting a hypodermic needle into the septum of an implanted reservoir. Three types of carbon were investigated: graphite powder, carbon lamp black, and low-temperature isotropic carbon powder (ULTI). Two cross-linking procedures were tested. The sensor that remained operational for the longest time used the ULTI and the cross-linking procedure that mixed the enzyme, immobilized on carbon powder, with albumin and glutaraldehyde. This sensor operated continuously at 37 degrees C for at least three months. Further, it was put through four recharge cycles with ten days of successful operation after each without change. The sensor is very stable and the results obtained with it are reproducible.
Serum concentrations of cycloserine and outcome of multidrug-resistant tuberculosis in Northern Taiwan (2014)

Lower than recommended serum CS concentrations and delayed absorption were common. It is essential to develop practical TDM to maintain proper serum drug concentrations.
The Synthesis of 17-Ester of Corticosteroids Protection of 11β-Hydroxyl by the Trimethylsilyl Group (1971)

Abstract 17–Esters of corticosteroids have received considerable attention due to their high topical anti-inflammatory activity. one of the best known is betamethasone 17-valerate which is widely used against a variety of skin diseases2. The relatively simple compound, hydrocortisone 17–butyrate (3a)3 proved to be as active topically as the more sophisticated corticosteroids such as triamcinolone acetonide, while its systemic activity is of the same order as that of hydrocortisone4.
In vivo glycation of aldehyde reductase, a major 3-deoxyglucosone reducing enzyme: identification of glycation sites (1995)

We have reported that the enzyme which reduces 3-deoxyglucosone (3-DG), a major intermediate and a potent cross-linker in the Maillard reaction, is identical with aldehyde reductase [Takahashi, M., Fujii, J., Teshima, T., Suzuki, K., Shiba, T., & Taniguchi, N. (1993) Gene 127, 249-253]. The enzyme purified from normal rat liver was found to be partially glycated as judged by binding to a boronate column and reactivity to anti-epsilon-hexitol lysine IgG. Sites of in vivo glycation of rat liver aldehyde reductase were identified by sequencing of digested peptides labeled with NaB[3H]4 and by mass spectrometry. The major glycated sites were lysines 67, 84, and 140. The glycated enzyme had low catalytic efficiency (kcat/Km) as compared to the nonglycated form. In streptozotocin-induced diabetic rats, the glycated form was significantly increased in kidneys. Because the enzyme plays a role in detoxifying 3-DG formed through the Maillard reaction in vivo, glycation of aldehyde reductase and reduction of its activity may result in the metabolic imbalance under diabetic conditions.
Light-Controlled Radical Polymerization: Mechanisms, Methods, and Applications (2016)

The use of light to mediate controlled radical polymerization has emerged as a powerful strategy for rational polymer synthesis and advanced materials fabrication. This review provides a comprehensive survey of photocontrolled, living radical polymerizations (photo-CRPs). From the perspective of mechanism, all known photo-CRPs are divided into either (1) intramolecular photochemical processes or (2) photoredox processes. Within these mechanistic regimes, a large number of methods are summarized and further classified into subcategories based on the specific reagents, catalysts, etc., involved. To provide a clear understanding of each subcategory, reaction mechanisms are discussed. In addition, applications of photo-CRP reported so far, which include surface fabrication, particle preparation, photoresponsive gel design, and continuous flow technology, are summarized. We hope this review will not only provide informative knowledge to researchers in this field but also stimulate new ideas and applications to further advance photocontrolled reactions.
TCP Westwood: congestion window control using bandwidth estimation (2002)

We study the performance of TCP Westwood (TCPW), a new TCP protocol with a sender-side modification of the window congestion control scheme. TCP Westwood controls the window using end-to-end rate estimation in a way that is totally transparent to routers and to the destination. Thus, it is compatible with any network and TCP implementation. The key innovative idea is to continuously estimate, at the TCP sender, the packet rate of the connection by monitoring the ACK reception rate. The estimated connection rate is then used to compute congestion window and slow start threshold settings after a congestion episode. Resetting the window to match available bandwidth makes TCPW more robust to sporadic losses due to wireless channel problems. These often cause conventional TCP to overreact, leading to unnecessary window reduction. Experimental studies of TCPW show significant improvements in throughput performance over Reno and SACK, particularly in mixed wired/wireless networks over high-speed links. The contributions of this paper include a model for fair and friendly sharing of the bottleneck link and a Markov Chain performance model in presence of link errors/loss. TCPW performance is compared to that of TCP Reno, and analytic results are validated against simulation results. Internet and laboratory measurements using a Linux TCPW implementation are also reported, providing further evidence of the gains achievable via TCPW.
Clinical and Theoretical Results of Intraocular Lens Power Calculation for Cataract Surgery After Photorefractive Keratectomy for Myopia (2002)

The predictability of IOL calculation for cataract surgery after PRK can be improved by using a corrected, refraction-derived K value instead of the measured, preoperative K value.
2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells (2002)

2-Methoxyestradiol (2ME2) an estrogen derivative, induces growth arrest and apoptosis in leukemic cells and is also antiangiogenic. In this study, we demonstrate that 2ME2 inhibits growth and induces apoptosis in multiple myeloma (MM) cell lines and patient cells. Significantly, 2ME2 also inhibits growth and induces apoptosis in MM cells resistant to conventional therapies including melphalan (LR-5), doxorubicin (Dox-40 and Dox-6), and dexamethasone (MM.1R). In contrast to its effects on MM cells, 2ME2 does not reduce the survival of normal peripheral blood lymphocytes. Moreover, 2ME2 enhances Dex-induced apoptosis, and its effect is not blocked by interleukin-6 (IL-6). We next examined the effect of 2ME2 on MM cells in the bone marrow (BM) milieu. 2ME2 decreases survival of BM stromal cells (BMSCs), as well as secretion of vascular endothelial growth factor (VEGF), and IL-6 triggered by the adhesion of MM cells to BMSCs. We show that apoptosis induced by 2ME2 is mediated by the release of mitochondrial cytochrome-c (cyto-c) and Smac, followed by the activation of caspases-8, -9, and -3. Finally, 2ME2 inhibits MM cell growth, prolongs survival, and decreases angiogenesis in a murine model. These studies, therefore, demonstrate that 2ME2 mediates anti-MM activity directly on MM cells and in the BM microenvironment. They provide a framework for the use of 2ME2, either alone or in combination with Dex, to overcome drug resistance and to improve outcome in MM.
T‐DNA tagging of a seed coat‐specific cryptic promoter in tobacco (1994)

T-DNA tagging with a promoterless beta-glucuronidase (GUS) gene generated a transgenic Nicotiana tabacum plant that expressed GUS activity only in developing seed coats. Cloning and deletion analysis of the GUS fusion revealed that the promoter responsible for seed coat specificity was located in the plant DNA proximal to the GUS gene. A 3.3 kb fragment corresponding to the insertion site was isolated from untransformed plants. No long open reading frames were detected in this region. Northern blots and RNase protection assays failed to detect transcripts from this region in untransformed plants. Furthermore, the insertion site was situated within the N. tomentosiformis genome of the allotetraploid species N. tabacum, in a region which is not conserved within the genus Nicotiana. It is concluded that seed coat-specific GUS expression in this transgenic plant resulted from T-DNA insertion next to a cryptic promoter. These results suggest that at least some of the fusions generated to marker genes in promoter trapping studies are not associated with conventional gene promoters. The possibility that similar insertion events play a role in gene evolution is discussed.
Influenza Virus Reservoirs and Intermediate Hosts: Dogs, Horses, and New Possibilities for Influenza Virus Exposure of Humans (2014)

Influenza A virus (IAV) infections in hosts outside the main aquatic bird reservoirs occur periodically. Although most such cross-species transmission events result in limited onward transmission in the new host, sustained influenza outbreaks have occurred in poultry and in a number of mammalian species, including humans, pigs, horses, seals, and mink. Recently, two distinct strains of IAV have emerged in domestic dogs, with each circulating widely for several years. Here, we briefly outline what is known about the role of intermediate hosts in influenza emergence, summarize our knowledge of the new canine influenza viruses (CIVs) and how they provide key new information on the process of host adaptation, and assess the risk these viruses pose to human populations.
Skeletal Regeneration by Mesenchymal Stem Cells: What Else? (2011)

1.1 The definition of MSCs Bone marrow (BM) was the first tissue described as a source of plastic-adherent, fibroblast-like cells that develops colony-forming unit fibroblastic (CFU-F) when seeded in tissue culture plates (Friedenstein et al., 1982; 1987). These cells, originally designated stromal
A mechanistic rationale for MEK inhibitor therapy in myeloma based on blockade of MAF oncogene expression (2010)

Modulating aberrant transcription of oncogenes is a relatively unexplored opportunity in cancer therapeutics. In approximately 10% of multiple myelomas, the initiating oncogenic event is translocation of musculoaponeurotic fibrosarcoma oncogene homolog (MAF), a transcriptional activator of key target genes, including cyclinD2. Our prior work showed that MAF is up-regulated in an additional 30% of multiple myeloma cases. The present study describes a common mechanism inducing MAF transcription in both instances. The second mode of MAF transcription occurred in myelomas with multiple myeloma SET domain (MMSET) translocation. MMSET knockdown decreased MAF transcription and cell viability. A small-molecule screen found an inhibitor of mitogen-activated protein kinase kinase (MEK), which activates extracellular signal-regulated kinase (ERK)-MAP kinases, reduced MAF mRNA in cells representing MMSET or MAF subgroups. ERK activates transcription of FOS, part of the AP-1 transcription factor. By chromatin immunoprecipitation, FOS bound the MAF promoter, and MEK inhibition decreased this interaction. MEK inhibition selectively induced apoptosis in MAF-expressing myelomas, and FOS inactivation was similarly toxic. Reexpression of MAF rescued cells from death induced by MMSET depletion, MEK inhibition, or FOS inactivation. The data presented herein demonstrate that the MEK-ERK pathway regulates MAF transcription, providing molecular rationale for clinical evaluation of MEK inhibitors in MAF-expressing myeloma.
Unimolecular Dissociations and Free Radical Recombination Reactions (1952)

The steric and pressure effects associated with the recombination of free radicals both depend on the nature of the activated complex, and are therefore intimately related. From a consideration of the reverse process of unimolecular dissociation, some equations are derived for these properties using an extension of earlier transition state and quasi-unimolecular theories. The present formalism differs from previous formulations of the latter in a number of ways, particularly in the expression used for the density of quantum states of the high energy molecules. Subsequent applications of the theory tentatively suggest that essentially all vibrational degrees of freedom of these molecules can contribute their energy to the vibrationally excited molecules. Consequently, vibrational anharmonicity would appear to be an important factor in intramolecular energy transfer. The present paper is an extension of a previously developed theory for the recombination of methyl radicals and iodine atoms.
Friction properties of novel PVP/PVA blend hydrogels as artificial cartilage (2009)

In this work, novel polyvinylpyrrolidone (PVP)/polyvinylalcohol (PVA) blend hydrogels were prepared by repeated freezing-thawing cycles. The factors that influenced friction properties of blend hydrogels, such as PVP content, contact load, sliding speed, and lubrication condition, were mainly studied by sliding with stainless steel ball. The results showed that friction coefficients of the PVP/PVA blend hydrogels were definitely dependent on such influence factors. The friction system consisting of blend hydrogel and stainless steel ball nearly exhibited a mixed lubrication regime especially under bovine serum lubrication, and it can be proposed as a promising method to reduce wear of the prosthesis.
Oscillatory Coupling of Hippocampal Pyramidal Cells and Interneurons in the Behaving Rat (1999)

We examined whether excitation and inhibition are balanced in hippocampal cortical networks. Extracellular field and single-unit activity were recorded by multiple tetrodes and multisite silicon probes to reveal the timing of the activity of hippocampal CA1 pyramidal cells and classes of interneurons during theta waves and sharp wave burst (SPW)-associated field ripples. The somatic and dendritic inhibition of pyramidal cells was deduced from the activity of interneurons in the pyramidal layer [int(p)] and in the alveus and st. oriens [int(a/o)], respectively. Int(p) and int(a/o) discharged an average of 60 and 20 degrees before the population discharge of pyramidal cells during the theta cycle, respectively. SPW ripples were associated with a 2.5-fold net increase of excitation. The discharge frequency of int(a/o) increased, decreased ("anti-SPW" cells), or did not change ("SPW-independent" cells) during SPW, suggesting that not all interneurons are innervated by pyramidal cells. Int(p) either fired together with (unimodal cells) or both before and after (bimodal cells) the pyramidal cell burst. During fast-ripple oscillation, the activity of interneurons in both the int(p) and int(a/o) groups lagged the maximum discharge probability of pyramidal neurons by 1-2 msec. Network state changes, as reflected by field activity, covaried with changes in the spike train dynamics of single cells and their interactions. Summed activity of parallel-recorded interneurons, but not of pyramidal cells, reliably predicted theta cycles, whereas the reverse was true for the ripple cycles of SPWs. We suggest that network-driven excitability changes provide temporal windows of opportunity for single pyramidal cells to suppress, enable, or facilitate selective synaptic inputs.
Physical mapping of adeno-associated virus serotype 4 DNA (1980)

The organization of adeno-associated virus serotype 4 (AAV 4) DNA was probed by using restriction enzymes. The cleavage sites of the following enzymes were mapped: BglII, BamI, HincII, KpnI, PstI, SalI, SstI, and XhoI. The orientation of transcription on the physical cleavage map was determined by locating the fragments which contain the 3' end of the mRNA. Strand separation gels were run for HinII fragments of AAV 4 DNA. By hybridizing AAV 4 mRNA to the resolved strands, the polarity of the DNA strands was identified. Restriction digestion of AAV 4 DNA sometimes produced terminal fragments which migrated in agarose gels as doublets. However, when AAV 4 DNA was prepared devoid of any single-stranded nicks, these terminal doublet bands were not observed upon subsequent restriction analysis. During these studies, the molecular weights of both AAV 4 and AAV 2 duplex DNA were measured and were found to be somewhat larger than previously reported (3.18 x 10(6) and 3.10 x 10(6), respectively).
Genetically engineered T cells for the treatment of cancer (2013)

T-cell immunotherapy is a promising approach to treat disseminated cancer. However, it has been limited by the ability to isolate and expand T cells restricted to tumour-associated antigens. Using ex vivo gene transfer, T cells from patients can be genetically engineered to express a novel T cell receptor or chimeric antigen receptor to specifically recognize a tumour-associated antigen and thereby selectively kill tumour cells. Indeed, genetically engineered T cells have recently been successfully used for cancer treatment in a small number of patients. Here we review the recent progress in the field, and summarize the challenges that lie ahead and the strategies being used to overcome them.
Intramolecular nucleophilic substitutions of co-ordinated aryl halides. A preparation of chromans (1980)

3-(o-Fluorophenyl)propan-1-ol can be cyclised readily to chroman either through chromium tricarbonyl complexes or (as also with substituted fluorophenylpropanols) by the action of the (η6-benzene)(η5-ethyltetramethylcyclopentadienyl)rhodium(III) cation.