gebhart/patrepeval huggingface dataset:
Keratin 8 Phosphorylation by Protein Kinase C δ Regulates Shear Stress-mediated Disassembly of Keratin Intermediate Filaments in Alveolar Epithelial Cells (2005)

Phosphorylation of keratin intermediate filaments (IF) is known to affect their assembly state and organization; however, little is known about the mechanisms regulating keratin phosphorylation. In this study, we demonstrate that shear stress, but not stretch, causes disassembly of keratin IF in lung alveolar epithelial cells (AEC) and that this disassembly is regulated by protein kinase C delta-mediated phosphorylation of keratin 8 (K8) Ser-73. Specifically, in AEC subjected to shear stress, keratin IF are disassembled, as reflected by their increased solubility. In contrast, AEC subjected to stretch showed no changes in the state of assembly of IF. Pretreatment with the protein kinase C (PKC) inhibitor, bisindolymaleimide, prevents the increase in solubility of either K8 or its assembly partner K18 in shear-stressed AEC. Phosphoserine-specific antibodies demonstrate that K8 Ser-73 is phosphorylated in a time-dependent manner in shear-stressed AEC. Furthermore, we showed that shear stress activates PKC delta and that the PKC delta peptide antagonist, delta V1-1, significantly attenuates the shear stress-induced increase in keratin phosphorylation and solubility. These data suggested that shear stress mediates the phosphorylation of serine residues in K8, leading to the disassembly of IF in alveolar epithelial cells. Importantly, these data provided clues regarding a molecular link between mechanically induced signal transduction and alterations in cytoskeletal IF.
Hypersensitivity to DNA cross-linking agents associated with up-regulation of glucose-regulated stress protein GRP78. (1997)

We have shown previously that NAD/poly(ADP-ribose) polymerase-deficient cells that overexpress Mr 78,000 glucose-regulated stress protein (GRP78) are resistant to topoisomerase II inhibitors, such as etoposide, m-amsacrine, and doxorubicin. However, these cells have been found to be hypersensitive to DNA cross-linking agents, including melphalan, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). These observations prompted us to examine whether overexpression of GRP78 is associated with modulation of cytotoxicity of clinically useful DNA-cross-linking agents such as melphalan, BCNU, and cisplatin. We up-regulated GRP78 in V79 Chinese hamster cells by 2-5-fold using two independent approaches that include exposure to 6-aminonicotinamide, or 2-deoxyglucose. Subsequently, these GRP78-overexpressing cells were trypsinized, plated in regular medium without GRP78-inducing agents, and allowed a 5-h attachment time before being treated with melphalan, BCNU, or cisplatin for 1 h to determine clonogenic survivals. In addition, repair of DNA cross-links induced by those agents were determined by alkaline elution assay. Our results show that the GRP78-overexpressing V79 cells are hypersensitive to DNA cross-linking agents compared to the control V79 cells. Furthermore, repair of drug-induced DNA cross-links appears to be considerably slower in these cells relative to that found in control V79 cells. Thus, our results suggest that (a) up-regulation of GRP78 is associated with an impairment of DNA cross-link repair, (b) up-regulation of GRP78 is associated with potentiation of cytotoxicity induced by alkylating and platinating agents, and (c) up-regulation of GRP78 can be considered as a potentially useful tool to modulate the cytotoxicity of clinically useful alkylating and platinating agents.
운동생리학 : Plyometric training 이 하지 슬관절과 족관절의 등속성 총 일량에 미치는 영향 (2001)

플라이오메트릭 훈련방법은 1960년대 중반이후 소련 등 동구권에서 개발되어 현재까지 많은 운동에 적용되었으며, 한편 이 훈련방법에 관한 연구가 지속되고 있지만 연구결과가 항상 효과적인 것만으로 나타나지 않고 있다. 따라서 본 연구는 플라이오메트릭 훈련이 하지 슬관절의 굴곡과 신전, 족관절의 배측굴곡과 족저굴곡의 등속성 총일량에 미치는 영향의 정도를 알아보며 이 훈련법의 효과검증을 위한 목적을 위해 시도되었다. 효과검증을 위해 등속성 장비를 이용하였으며, 이때 단축성 수축과 신장성 수축을 반복해서 실시한 후 자료 분석을 시도하였다. 피험자의 선정은 운동선수의 경험이 없는 대학교 체육과 학생들을 대상으로 하였으며, 연구대상자는 9명(훈련집단=5명, 통제 집단=4명)으로 8주간의 처치 전후에 등속성 장비를 이용하여 슬관절과 족관절의 등속성 총일량을 측정하였다. 결과로 첫째, 플라이오메트릭 훈련이 좌측 하지 슬관절의 각속도 180˚/sec에서 굴곡은 훈련 전 180.40±37.69에서 훈련 8주 후 118.80±32.69로 통계적으로 유의한 차이가 나타났다(p<.05). 그러나 그 이외에는 점진적인 향상만을 가져왔다. 둘째, 플라이오메트릭 훈련이 하지 족관절의 각속도 120˚/sec에서 배측굴곡은 16.80±2.49에서 19.00±3.00으로, 족저굴곡은 50.20±5.76에서 53.60±10.11로 통계적으로 유의한 차이가 나타났다(p<05). 그러나 그 이외에서는 점진적인 향상만을 가져왔으며, 특이한 사항은 30˚/sec의 통제집단에서 통계적으로 유의한 차이가 나타났다(p<.05), 이러한 결과는 피험자에 대한 완전한 통제가 이루어지지 않은 것으로 생각된다. 결과적으로 플라이오메트릭 훈련은 하지 슬관절과 족관절의 등속성 총일량에 부분적으로 영향을 미치는 것을 알 수 있으며, 더 나아가 운동수행에도 영향을 미칠 수 있는 것을 의미한다.
BCL3 (Books for College Libraries) and the Book Jobber: The Marketing of a New Collection Development Service (1991)

When the third edition of Books for College Libraries (BCW) was released in 1988, it was available for the first time in a machine-readable format. At Midwest Library Service, the decision was made to obtain the tapes of BCL3 and investigate their possible application as a collection development tool which could be used to compare a library's holdings as reflected in their OCLC records to the idealized collection as reflected in BCL3. The hope was that this service would result in an increase of book orders for Midwest through both routine library expenditures as well as potential grants which this sort of project might engender. Several problems, some expected, some unexpected arose as this new service went into testing, but the early results suggest the viability of the project if potential clients are strictly qualified.
The cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase. (1990)

We have recently isolated an abundant cytosolic protein from human T-cells which specifically binds the immunosuppressive agent, FK-506. The FK-506-binding protein (FKBP) is a member of a novel class of proteins possessing peptidyl-prolyl cis-trans isomerase activity. These proteins are believed to play an important role in accelerating the rate at which proteins fold into their native conformations. In the present study, we demonstrate that FKBP is not a lymphoid-specific protein, but is widely distributed and phylogenically conserved. FKBP, purified from three sources (a human T-lymphocyte cell line JURKAT, bovine calf thymus, and Saccharomyces cerevisiae) exhibit identical molecular weights, immunological cross-reactivities, and a high degree of NH2-terminal amino acid sequence homology. In addition, FKBP from all sources possesses peptidyl-prolyl cis-trans isomerase activity which can be specifically inhibited by FK-506. We conclude that FKBP may serve an important biological function in all eukaryotic cells.
Adolescents' Self-Assessment of Sexual Maturation (1980)

The variability in time of onset and progression of puberty warrants the use of stage of sexual maturation rather than chronologic age in assessing biological and behavioral measures during adolescence. The necessity to undress the teenager has seriously curtailed the application of stage of sexual maturation to behavioral and developmental research. This study demonstrates that adolescents can accurately assess their own developmental stage according to Tanner's standard photographs. Self-ratings by 43 females, aged 9 to 17, and 23 males, 11 to 18, were compared to those based on physical examination by one of the investigators. Agreement with the physician rating occurred for breast stage in 37/43, for female pubic hair stage in 40/43, and for male combined pubic hair and genital stage in 21/2 (kappa coefficients: 0.81, 0.91, 0.88). The excellent agreement between physician and adolescent's assessment compared favorably with the interrater agreement of professionals. This study suggests the value of utilizing adolescent self-staging in research. In addition, this exercise provides teenagers with an objective way to understand the wide range of normal pubertal development and to follow their own sexual maturation.
Efficacy of Danazol in Hematologic Disorders (1990)

Danazol, an attenuated androgen developed for the treatment of endometriosis, has recently been found useful in the treatment of several hematologic disorders, including idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, and others. Our studies of the past 6 years have demonstrated that danazol is advantageous in the treatment of AIHA, and in specifically defined populations of ITP patients. Of 96 ITP patients treated with danazol 61% overall had excellent/good responses, but this rate varied markedly with prognostic factors, e.g. 82% in older women versus only 18% in younger women. Of 28 AIHA patients, 77% with idiopathic type and 60% with secondary type were excellent/good responders. When the drug was discontinued after 1 year or more of therapy, lasting unmaintained remissions of up to 5 years were often observed in both ITP and AIHA, a notably important benefit. The side-effects of danazol are generally much less serious than with glucocorticoids. Glucocorticoids can be tapered off and in most cases discontinued completely with danazol therapy in AIHA and chronic ITP. Approximately one third of ITP patients who failed on glucocorticoids are successfully maintained on danazol. Its mechanism of action in these disorders is currently under study in our laboratory, stimulated by new findings. Tentatively, danazol appears to modify cell membranes in a manner leading to specific immune modulations, as discussed. Further study is warranted to explore its application to other autoimmune and membrane-related disorders, and to clarify its mechanism of therapy.
COMPOSITION OF NON-STARCH POLYSACCHARIDES IN WORT AND SPENT GRAIN FROM BREWING TRIALS WITH MALT FROM A GOOD MALTING QUALITY BARLEY AND A FEED BARLEY (1993)

Worts and spent grains were obtained from pilot-scale brews using malts of two barley varieties differing in malting quality. Triumph was used as an example of a good malting quality barley and Golf as a typical feed grade barley. Arabinoxylan concentrations were similar in worts of both varieties, whereas (1–3), (1–4)-β-glucan concentrations were much higher in wort prepared from Golf malt than in wort from Triumph malt. From the worts, polysaccharide fractions were isolated by ethanol precipitation and characterised. Results indicated the presence of high molecular weight arabinoxylans and (1–3), (1–4)-β-glucans. The arabinose to xylose ratios in the precipitates were considerably higher than in total worts. Methylation analysis showed little differences between precipitated wort arabinoxylans from both varieties. In comparison to water-insoluble arabinoxylans extracted from barley and malt, the precipitated wort arabinoxylans were richer in xylopyranose residues substituted with arabinose residues at both 0–2 and 0–3. Viscosities of the hopped worts of both varieties decreased after treatment with endoxylanase 1 from Aspergillus awamori. This confirms that arabinoxylans play a role in determining wort viscosity, possibly through interactions with (1–3), (1–4)-β-glucans.
PS-OCT of occlusal and interproximal caries lesions viewed from occlusal surfaces (2006)

Previous studies have demonstrated that Polarization Sensitive Optical Coherence Tomography (PS-OCT) can be used to image early dental caries. The primary objective of this study was to compare the measured reflectivity of natural occlusal caries lesions with the relative mineral loss measured using digital microradiography. There was excellent agreement between the increase in the integrated reflectivity in the perpendicular polarization axis of the PS-OCT system and the increase in the integrated mineral loss or lesion severity for occlusal lesions. Therefore, PS-OCT is ideally suited to image natural caries lesions in the important occlusal surfaces for the assessment of the lesion severity and activity. A secondary objective was to compare the performance of a new autocorrelator-based PS-OCT system employing a novel polarization-switching probe with our polarization-maintaining fiber based PS-OCT system, both operating at 1310-nm. The new PS-OCT system produced clean images with no artifacts and achieved high penetration depth. Yet a third objective was to determine if interproximal lesions can be imaged from the occlusal surface (from above) since interproximal lesions may only be accessible in vivo from buccal or lingual surfaces or from the occlusal surface. Simulated and natural interproximal caries lesions were imaged from the occlusal surfaces as long as there was no intervening dentin.
Inhibition of the lectin-induced mitogenic response of thymocytes by glycolipids. (1979)

Exogenous gangliosides at concentrations found in serum inhibit the concanavalin A- (Con A) induced mitogenic response of mouse thymocytes. Of four gangliosides tested, the trisialoganglioside, GT1, was the most potent inhibitor. Ceramides, cerebrosides, and sialic acid were not inhibitory at any concentration tested. The inhibition by gangliosides was not due to interference with Con A binding as shown by direct binding studies with [3H]acetyl-Con A nor was it due to a nonspecific killing effect. Thymocytes exposed to a ganglioside concentration 5 times that required to inhibit mitogenesis were still capable of excluding trypan blue up to 44 hr after ganglioside addition. Furthermore, ganglioside inhibition could be reversed by washing the cells 4 hr after addition of the glycolipid. A productive interaction with Con A occurs in the presence of ganglioside as shown by a Con A-induced increase in carbohydrate metabolism. However, uridine and thymidine incorporation are inhibited by the presence of ganglioside. Complete inhibition could be achieved if the glycolipid were added as late as 24 to 28 hr after the Con A in a 48-hr mitogenic assay. The results are discussed in light of recent findings that elevated levels of gangliosides are found in in the sera of tumor-bearing animals, and it is suggested that gangliosides shed by tumor cells could be involved in the generalized immunosuppression observed in such animals.
Hexosaminidase a activity and amyotrophic lateral sclerosis (1988)

Abnormalities of GM2 ganglioside metabolism owing to hexosaminidase A (Hex A) deficiency have been associated with ALS phenotypes. The clinical features described in these ALS patients with Hex A deficiency include early onset, positive family history, and/or long disease duration. In an attempt to determine prospectively the incidence of Hex A deficiency within an ALS population, the records of The Mount Sinai Medical Center ALS Clinic were reviewed to select those patients with "atypical" ALS (total N = 52), i.e. onset before age 35, positive family history, and/or disease duration greater than 90 months. The control group (total N = 50), "typical" ALS patients, did not fulfill any of these historical criteria. Hex A activity determined in isolated peripheral blood leukocytes was normal in all typical ALS patients (mean 67.3%). Hex A deficiency was not found in any atypical ALS patients. Thus, Hex A deficiency apparently is an unusual etiology of typical or atypical ALS but is of medical and genetic importance in individual families.
Role of IFN‐γ in an experimental murine model of West Nile virus‐induced seizures (2007)

Seizures are a major complication of viral encephalitis. However, the mechanisms of seizure-associated neuronal dysfunction remain poorly understood. We report that intranasal inoculation with West Nile virus (WNV) (Sarafend) causes limbic seizures in C57BL/6 mice, but not in interferon (IFN)-gamma-deficient (IFN-gamma-/-) mice. Both strains showed similar levels of virus in the brain, as well as similar concentrations of the cytokines, tumor necrosis factor and interleukin-6, both of which can alter neuronal excitability. Experiments in chimeric IFN-gamma-/- mice reconstituted with IFN-gamma-producing leukocytes showed that IFN-gamma is not required during central nervous system infection for limbic seizure development, suggesting a role for IFN-gamma in the developing brain. This was supported responses to pentylenetetrazole, kainic acid (KA), and N-methyl-d-aspartate (NMDA). Both strains of mice exhibited similar behavior after pentylenetetrazole challenge. However, while NMDA and KA treatment resulted in characteristic seizures in C57BL/6 mice, these responses were diminished (NMDA treatment) or absent (KA treatment) in IFN-gamma-/- mice. Furthermore, NMDA-receptor blockade with MK-801 in WNV-infected C57BL/6 mice abrogated seizures and prolonged survival. Our data show that IFN-gamma plays an important role in the development of the excitatory seizure pathways in the brain and that these cascades become pathogenic in encephalitic WNV infection.
Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma (2009)

Glioblastoma (GB) is the most common malignant brain tumor in adults. It has limited treatment opportunities and is almost exclusively fatal. Owing to the central role the insulin-like growth factor-1 receptor (IGF-1R) plays in malignant cells, it has been suggested as a target for anticancer therapy including GB. The cyclolignan picropodophyllin (PPP) inhibits IGF-1R without affecting the highly homologous insulin receptor. Here, we show that PPP inhibits growth of human GB cell lines along with reduced phosphorylation of IGF-1R and AKT. In vivo, PPP-treatment causes dramatic tumor regression not only in subcutaneous xenografts but also in intracerebral xenografts, indicating passage of PPP across the blood-brain barrier.
Molecular Modeling Based Approach to Potent P2−P4 Macrocyclic Inhibitors of Hepatitis C NS3/4A Protease (2008)

Molecular modeling of inhibitor bound full length HCV NS3/4A protease structures proved to be a valuable tool in the design of a new series of potent NS3 protease inhibitors. Optimization of initial compounds provided 25a. The in vitro activity and selectivity as well as the rat pharmacokinetic profile of 25a compare favorably with the data for other NS3/4A protease inhibitors currently in clinical development for the treatment of HCV.
Improving Complex Near-IR Calibrations Using a New Wavelength Selection Algorithm (1999)

Near-infrared spectroscopy is being considered as a tool for the noninvasive determination of important cell culture media constituents, which would allow frequent, harmless sampling and computer interfacing for closed-loop control. Partial least-squares calibration models for glucose and lactate are constructed for cell culture media and aqueous media comprised of several absorbing species. Wavelength selection, having failed in previous attempts with these data, is shown to reduce the error prediction and number of required wavelengths when performed with the use of a newly developed “peak-hopping” algorithm. The selection method reduces prediction errors in every case considered here and is extendable to combined calibration models that are built for use with a particular type of sample with the aid of high-quality spectra from simpler mixtures. The new selection algorithm leads to calibrations producing accurate predictions with fewer wavelengths, in support of previous results obtained when applied to single-component Raman spectroscopy data. The findings continue to suggest that the algorithm can be used as a simple alternative to the difficult-to-configure genetic algorithm.
Detection of terminal N-linked N-acetylglucosamine residues in the Golgi apparatus using galactosyltransferase and endoglucosaminidase F/peptide N-glycosidase F: adaptation of a biochemical approach to electron microscopy. (1987)

Purified human milk beta-N-acetylglucosaminide beta 1, 4 galactosyltransferase (EC 2.4.1.38) was used to galactosylate N-acetylglucosamine (GlcNAc) residues present in ultra-thin sections of Lowicryl K4M-embedded rat and pig liver. Both endogenous galactose and galactosylated transferase products could be revealed by Ricinus communis lectin I-gold complexes (RcL I-g15). Without galactosyltransferase (GT) treatment, labeling for galactose (gal) was limited to the trans region of rat and pig hepatocyte Golgi apparatus. After exposure to GT, additional labeling was found over cis Golgi apparatus cisternae. RcL I-g15 labeling was sensitive to a purified preparation of endoglucosaminidase F/peptide N-glycosidase F (at pH 9). This indicates that endogenous gal and gal transferred by GT to terminal GlcNAc residues are present N-linked oligosaccharides. The RcL I-g15 labeling produced by GT was insensitive to extensive washing with solutions containing either EDTA and urea or SDS and 2-mercaptoethanol or 0.1 M GlcNAc. Substrate inhibition studies showed that 50 mM GlcNAc specifically inhibited the additional RcL I-g15 labeling produced by GT. The use of purified glycosyltransferases therefore appears to allow specific detection of oligosaccharide substrates and their high resolution localization in thin sections by electron microscopy.
Protein kinase Cι is required for Ras transformation and colon carcinogenesis in vivo (2004)

Protein kinase C iota (PKCiota) has been implicated in Ras signaling, however, a role for PKCiota in oncogenic Ras-mediated transformation has not been established. Here, we show that PKCiota is a critical downstream effector of oncogenic Ras in the colonic epithelium. Transgenic mice expressing constitutively active PKCiota in the colon are highly susceptible to carcinogen-induced colon carcinogenesis, whereas mice expressing kinase-deficient PKCiota (kdPKCiota) are resistant to both carcinogen- and oncogenic Ras-mediated carcinogenesis. Expression of kdPKCiota in Ras-transformed rat intestinal epithelial cells blocks oncogenic Ras-mediated activation of Rac1, cellular invasion, and anchorage-independent growth. Constitutively active Rac1 (RacV12) restores invasiveness and anchorage-independent growth in Ras-transformed rat intestinal epithelial cells expressing kdPKCiota. Our data demonstrate that PKCiota is required for oncogenic Ras- and carcinogen-mediated colon carcinogenesis in vivo and define a procarcinogenic signaling axis consisting of Ras, PKCiota, and Rac1.
Bags of Binary Words for Fast Place Recognition in Image Sequences (2012)

We propose a novel method for visual place recognition using bag of words obtained from accelerated segment test (FAST)+BRIEF features. For the first time, we build a vocabulary tree that discretizes a binary descriptor space and use the tree to speed up correspondences for geometrical verification. We present competitive results with no false positives in very different datasets, using exactly the same vocabulary and settings. The whole technique, including feature extraction, requires 22 ms/frame in a sequence with 26 300 images that is one order of magnitude faster than previous approaches.
Invasive non‐typhoidal Salmonella in Mozambican children (2009)

Clinical presentation of invasive NTS was non-specific and similar to that of other infections, with some factors being associated with NTS. Antibiotic resistance was very common to currently recommended and available antibiotics for suspected sepsis.