gebhart/patrepeval huggingface dataset:
Anti-human class I MHC antibodies induce apoptosis by a pathway that is distinct from the Fas antigen-mediated pathway (1997)

5H7, an anti-human class I MHC mAb that recognizes a monomorphic determinant of the alpha3 domain, profoundly inhibits T lymphocyte activation. The present study was designed to determine the role of programmed cell death in 5H7-mediated immune suppression. Incubation of PBMC with 5H7 mAb induced a marked reduction in viable cell recovery (VCR) of T cells (<10% VCR), NK cells (<1% VCR), and B cells (<1% VCR). In addition, 5H7 inhibited proliferation and VCR of JY, DBS-521, and BevD tumor lines as well as cells transfected with HLA-B27. Morphologic changes characteristic of apoptosis were induced by 5H7, including cell membrane blebbing, cytoplasmic vacuolization, condensation of nuclear chromatin, and nuclear fragmentation. Furthermore, DNA fragmentation was demonstrated in 5H7-treated PBMC using a TdT-mediated end-labeling (TUNEL) technique. 5H7, but not anti-Fas mAb, induced apoptosis of cell lines derived from patients with Niemann-Pick disease that lack acidic sphingomyelinase activity. In addition, induction of cell death by 5H7 was not inhibited by IL-1beta-converting enzyme (ICE) inhibitors under conditions that fully suppressed Fas-mediated apoptosis. These findings suggest that signal transduction through "classical" human class I MHC molecules induces apoptosis by a Fas-independent pathway that does not require acidic sphingomyelinase, is independent of ICE protease, and may represent a unique pathway of cell death in human lymphocytes.
Establishment of Reproducible, Critical-Sized, Femoral Segmental Bone Defects in Rats (2014)

Development of new treatment methodologies for bone nonunion requires validated experimental models for their application into tissue engineering approaches. Critical-sized bone defect (CSBD) models identify the smallest size at which tissue defects fail to completely heal during the experimental period. The purpose of this study was to systematically determine a CSBD in rat femurs using external fixation. Thirty Fischer 344 rats were equally divided into six groups. Bone defects of 1, 2, 3, 4, 5, and 6 mm were created in the diaphysis of the femur, before external fixation. Defects were evaluated radiographically at weekly intervals and histologically at the predefined healing period of 8 weeks. Defects of 4 mm or more failed to achieve union in our model. Nonunions were characterized by the absence of a bridging callus and filling of the defect with fibrous and muscle tissue. Radiographically, bone ends in nonunions were rounded up to 4 weeks postsurgery. Our systematic approach for identification of a CSBD in rat femurs, revealed that externally fixed defects of 4 mm and larger, failed to heal within the 8-week time frame.
Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment (2004)

Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.
Synthesis, Pharmacologic Activity, and Structure-Activity Relationships of a Series of Propafenone-Related Modulators of Multidrug Resistance (1995)

A series of [(o-acylaryl)oxy]propanolamines have been prepared and evaluated for multidrug resistance-reverting activity in a human tumor cell model. Structure-activity relationship studies indicate that the phenylpropiophenone moiety as well as the substitution pattern at the nitrogen atom is crucial for activity of the compounds. Incorporation of the ether oxygen into a benzofuran substructure, which renders the compound an arylethanolamine, decreased biologic activity. Highest activity could be observed with the arylpiparazines 4f-h, which not only completely restored daunomycin sensitivity but also showed moderate activity in restoring etoposide toxicity.
p16/pRb pathway alterations are required for bypassing senescence in human prostate epithelial cells. (1999)

The cell cycle regulatory genes p16/CDKN2 and RB are frequently deleted in prostate cancers. In this study, we examined the role of alterations in p16 and pRb during growth, senescence, and immortalization in vitro of human prostate epithelial cells (HPECs). HPECs are established from normal prostate tissues and cultured on collagen-coated dishes. Our results show that p16 is reproducibly elevated at senescence in HPECs. HPECs are immortalized using human papilloma virus 16 E6 and/or E7 as molecular tools to inactivate p53 and/or pRb, respectively. Immortalization occurs infrequently in this system and only after a latent period during which additional genetic/epigenetic changes are thought to occur. Notably, all of the E6-immortalized HPEC lines but none of the E7 lines show inactivation of p16/CDKN2 (by deletion, methylation, or mutation) in association with immortalization. In contrast, E7 lines, in which pRb function is abrogated by E7 binding, retain the high levels of p16 observed at senescence. Thus, all lines show either a p16 or pRb inactivation. Analysis of six independent lines from metastatic prostate cancers reveals a similar loss of either p16 or pRb. Comparative genomic hybridization of HPECs shows that gains of chromosomes 5q, 8q, and 20 are nonrandomly associated with bypassing senescence (probability = 0.95). These results suggest that high levels of the cyclin-dependent kinase inhibitor p16 mediate senescence G1 arrest in HPECs and that bypassing this block by a p16/pRb pathway alteration is required for immortalization in vitro and possibly tumorigenesis in vivo. Our results further indicate that inactivation of the p16/pRb pathway alone is not sufficient to immortalize HPECs and that additional genetic alterations are required for this process.
Kinetics and mechanism of the formation of mono- and di-phthalate esters catalysed by titanium and tin alkoxides (1998)

The kinetics and mechanism of the formation of phthalate mono-esters and phthalate di-esters from phthalic anhydride and a variety of mono- and di-hydric alcohols are reported and discussed. The kinetic work is extended to a mechanistic study of the same reactions using titanium tetra-n-butoxide and tri-n-butyltin ethoxide as catalysts. The results support a mechanism involving alkoxy ligand exchange at the metal as a crucial step in the catalysis.
CpG Islands in Chromatin Organization and Gene Expression (1999)

CpG islands are stretches of DNA sequence that are enriched in the (CpG)n repeat and are present in close association with all housekeeping genes as well as some tissue-specific genes in the mammalian genome. Methylation of CpG islands strongly influences both structural organization and function of chromatin. The presence of a CpG island in a given chromosomal domain can, by itself, give rise to relatively open and active chromatin. Recently, several histone acetyltransferases, histone deacetylases, and chromatin remodeling factors have been found to be part of the transcription machinery. It is becoming increasingly clear that CpG islands and their methylation status may influence the function or recruitment of these newly discovered chromatin remodeling factors, especially the histone deacetylases. In addition, CpG islands may also play a significant role in the reorganization of chromatin during mammalian spermiogenesis.
Measurement of the elliptical birefringence of single-mode optical fibers (2001)

The polarization properties of single-mode optical fibers are theoretically modeled with use of the Jones formalism. The fiber is described as an elliptical birefringent plate. The properties predicted by this model are discussed and lead to the development of a simple experimental method to extract the parameters that describe a real fiber. A magneto-optic method that measures the beat length of the fiber is also presented and gives a more complete description of the fiber. The validity of the model is then clearly established. Finally, the wavelength dependence of the parameters characteristic of the fiber is experimentally investigated.
Gadolinium texaphyrin (Gd-Tex)-malonato-platinum conjugates: Synthesis and comparison with carboplatin in normal and Pt-resistant cell lines (2009)

The synthesis of a new PEG-solubilized gadolinium texaphyrin (Gd-Tex) conjugate containing a malonate-Pt(NH(3))(2) moiety is described. The effect of the tumor localizing Gd-Tex macrocycle on platinum activity was evaluated in cell culture. The malonate moiety, analogous to that present in carboplatin, is expected to release an aquated Pt(NH(3))(2) species under physiological conditions. The half-life in phosphate-buffered saline was found to be ca. 3 days at room temperature, and the hydrolytic product released from the conjugate was collected and confirmed as Pt-based by flameless atomic absorption spectrophotometry. Anti-proliferative activity was tested using A549 human lung cancer and A2780 human ovarian cancer cell lines. In both cell lines, the activity of the Gd-Tex conjugate was found to be similar to that of carboplatin. Efficacy against a Pt-resistant ovarian cell line greater than that displayed by carboplatin was also observed.
Low-Grade Systemic Inflammation and the Development of Type 2 Diabetes (2003)

To examine the association of low-grade systemic inflammation with diabetes, as well as its heterogeneity across subgroups, we designed a case-cohort study representing the approximately 9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants. Analytes were measured on stored plasma of 581 incident cases of diabetes and 572 noncases. Statistically significant hazard ratios of developing diabetes for those in the fourth (versus first) quartile of inflammation markers, adjusted for age, sex, ethnicity, study center, parental history of diabetes, and hypertension, ranged from 1.9 to 2.8 for sialic acid, orosomucoid, interleukin-6, and C-reactive protein. After additional adjustment for BMI, waist-to-hip ratio, and fasting glucose and insulin, only the interleukin-6 association remained statistically significant (HR = 1.6, 1.01-2.7). Exclusion of GAD antibody-positive individuals changed associations minimally. An overall inflammation score based on these four markers plus white cell count and fibrinogen predicted diabetes in whites but not African Americans (interaction P = 0.005) and in nonsmokers but not smokers (interaction P = 0.13). The fully adjusted hazard ratio comparing white nonsmokers with score extremes was 3.7 (P for linear trend = 0.008). In conclusion, a low-grade inflammation predicts incident type 2 diabetes. The association is absent in smokers and African-Americans.
Coordinate oncodevelopmental modulation of alternative splicing of fibronectin pre-messenger RNA at ED-A, ED-B, and CS1 regions in human liver tumors. (1993)

The molecular diversity of fibronectin arises from alternative RNA splicing at regions termed ED-A, ED-B, and IIICS. We investigated the splicing patterns of fibronectin pre-mRNA at both ED-B and IIICS regions in various human liver tissues with an emphasis on the expression of the alternative cell adhesive site CS1 within the IIICS region. The relative abundance of the fibronectin mRNA containing the CS1 sequence was significantly increased in both fetal and cancerous liver tissues, although it was not affected in nonmalignant tissues with chronic hepatitis and cirrhosis. Similarly, the relative abundance of the fibronectin mRNA containing the ED-B region was also increased in both fetal liver and liver tumors, showing a close parallelism with the splicing pattern at the ED-A region. Immunohistochemical examination of cancerous liver tissues with monoclonal antibodies directed to the ED-A and ED-B segments revealed that the fibronectin isoforms containing these extra peptide segments were specifically deposited in the tumor nodules. Other genes encoding kininogen, gamma chain of fibrinogen, and beta-amyloid protein precursor, all of which had been shown to be alternatively processed, did not show any significant alteration in the splicing pattern in cancerous liver tissues. These results indicate that the alternative splicing of fibronectin pre-mRNA at the ED-A, ED-B, and IIICS regions is coordinately modulated in both fetal and cancerous liver tissues toward inclusion of the extra peptide segments and that not all but only selected genes are susceptible for "fine tuning" of alternative RNA splicing in cancerous liver tissues.
Serum levels of tumor necrosis factor‐α, interleukin‐6 and interleukin‐8 are not increased in dyspeptic patients with Helicobacter pylori‐associated gastritis (2003)

We could not show elevated circulatory levels of IL-6, IL-8 and TNF-alpha in H. pylori-infected cases. We believe that H. pylori-related cytokine activation become concentrated on gastric mucosa and this pathogen-induced local inflammatory cascade does not cause changes in circulatory levels of these cytokines. Moreover, there is no correlation between the levels of serum cytokines and Sydney parameters.
Catalyst design for enhanced sustainability through fundamental surface chemistry (2016)

Decreasing energy consumption in the production of platform chemicals is necessary to improve the sustainability of the chemical industry, which is the largest consumer of delivered energy. The majority of industrial chemical transformations rely on catalysts, and therefore designing new materials that catalyse the production of important chemicals via more selective and energy-efficient processes is a promising pathway to reducing energy use by the chemical industry. Efficiently designing new catalysts benefits from an integrated approach involving fundamental experimental studies and theoretical modelling in addition to evaluation of materials under working catalytic conditions. In this review, we outline this approach in the context of a particular catalyst-nanoporous gold (npAu)-which is an unsupported, dilute AgAu alloy catalyst that is highly active for the selective oxidative transformation of alcohols. Fundamental surface science studies on Au single crystals and AgAu thin-film alloys in combination with theoretical modelling were used to identify the principles which define the reactivity of npAu and subsequently enabled prediction of new reactive pathways on this material. Specifically, weak van der Waals interactions are key to the selectivity of Au materials, including npAu. We also briefly describe other systems in which this integrated approach was applied.
실험 논문 : Pseudorabies virus ( PRV ) 를 이용한 두침 치료 기전에 대한 신경해부학적 연구 (2000)

본 실험은 pseudorabies 바이러스(PRV)의 Bartha strain을 안면신경의 측두지, 하지를 지배하는 신경(좌골신경) 및 상지를 지배하는 신경(요골, 척골, 정중신경)에 주입한 후 4일간의 생존시간이 경과한 후 척수와 뇌를 적출하여 동결절편을 제작한 후 면역조직화학적 염색기법과 X-gal 조직화학염색법을 시행하여 염색된 신경세포체를 척수와 뇌에 투사된 공통영역을 관찰하고 두침의 영역중위의 실험에서 얻어진 결과는 아래와 같다.
1. 안면신경의 측두지, 하지를 지배하는 신경(좌골신경) 및 상지를 지배하는 신경(요골, 측골, 정중신경)에서 투사된 공통된 영역은 척수에서 경수의 층판 I-IV, 흉수의 intermediolateral nucleus(IML), dorsal nucleus(D) 및 층판 X, 요수의 층판 IV, V, 천수의 층판 IV, V, IX, X등의 영역에서 관찰되었고, 뇌줄기에서는 caudoventrolateral reticular nucleus(CVL), nucleus solitary tract(Sol), rostroventrolateral nucleus(RVL), area postrema(AP), raphe nuclei(raphe pallidus, raphe obscurus, raphe magnus), inferior olivary nucleus의 등쪽부분(gigantocellular reticular nucleus, Gi), Ko¨lliker-Fuse nucleus(KF), central gray(CG), dorsal raphe nucleus(DR) and A5 영역에 표지된다. 또한 paraventricular hypothalamic nucleus(PRV)와 lateral hypothalamic reticular nucleus(LH)에서도 관찰되고 locus coeruleus(LC)와 subcoeruleus nucleus(SubCA)에서도 관찰된다. 
2. 뇌와 척수에서 공통으로 표지된 영역의 생리적 기능은 안면신경의 측두지(두침영역의 운동구를 지배하는 신경)가 사지에 분포하는 많은 근육들의 운동과 근육을 지배하는 혈관의 운동을 조절하는 기능과 관련이 있음을 제시해 준다.
3. 안면신경의 측두지는 대뇌피질의 상지와 하지의 영역에 표지 되었으며, 이는 두침영역에서 운동구가 사지의 마비와 관련된 질병를 치료할 수 있다는 이론을 형태학적으로 입증하는 증거가 될 것으로 사료된다.
이상의 실험결과는 안면신경의 측두지가 사지의 운동과 관련이 있다는 형태학적 증거이며, 이 신경이 지배하는 두침 영역의 운동구는 사지와 관련이 있을 것으로 생각된다.
Protein–protein interactions in intracellular Ca2+-release channel function (1999)

Release of Ca2+ ions from intracellular stores can occur via two classes of Ca2+-release channel (CRC) protein, the inositol 1,4, 5-trisphosphate receptors (InsP3Rs) and the ryanodine receptors (RyRs). Multiple isoforms and subtypes of each CRC class display distinct but overlapping distributions within mammalian tissues. InsP3Rs and RyRs interact with a plethora of accessory proteins which modulate the activity of their intrinsic channels. Although many aspects of CRC structure and function have been reviewed in recent years, the properties of proteins with which they interact has not been comprehensively surveyed, despite extensive current research on the roles of these modulators. The aim of this article is to review the regulation of CRC activity by accessory proteins and, wherever possible, to outline the structural details of such interactions. The CRCs are large transmembrane proteins, with the bulk of their structure located cytoplasmically. Intra- and inter-complex protein-protein interactions between these cytoplasmic domains also regulate CRC function. Some accessory proteins modulate channel activity of all CRC subtypes characterized, whereas other have class- or even isoform-specific effects. Certain accessory proteins exert both direct and indirect forms of regulation on CRCs, occasionally with opposing effects. Others are themselves modulated by changes in Ca2+ concentration, thereby participating in feedback mechanisms acting on InsP3R and RyR activity. CRCs are therefore capable of integrating numerous signalling events within a cell by virtue of such protein-protein interactions. Consequently, the functional properties of InsP3Rs and RyRs within particular cells and subcellular domains are 'customized' by the accessory proteins present.
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis (2004)

Fru-2,6-P2 (fructose 2,6-bisphosphate) is a signal molecule that controls glycolysis. Since its discovery more than 20 years ago, inroads have been made towards the understanding of the structure-function relationships in PFK-2 (6-phosphofructo-2-kinase)/FBPase-2 (fructose-2,6-bisphosphatase), the homodimeric bifunctional enzyme that catalyses the synthesis and degradation of Fru-2,6-P2. The FBPase-2 domain of the enzyme subunit bears sequence, mechanistic and structural similarity to the histidine phosphatase family of enzymes. The PFK-2 domain was originally thought to resemble bacterial PFK-1 (6-phosphofructo-1-kinase), but this proved not to be correct. Molecular modelling of the PFK-2 domain revealed that, instead, it has the same fold as adenylate kinase. This was confirmed by X-ray crystallography. A PFK-2/FBPase-2 sequence in the genome of one prokaryote, the proteobacterium Desulfovibrio desulfuricans, could be the result of horizontal gene transfer from a eukaryote distantly related to all other organisms, possibly a protist. This, together with the presence of PFK-2/FBPase-2 genes in trypanosomatids (albeit with possibly only one of the domains active), indicates that fusion of genes initially coding for separate PFK-2 and FBPase-2 domains might have occurred early in evolution. In the enzyme homodimer, the PFK-2 domains come together in a head-to-head like fashion, whereas the FBPase-2 domains can function as monomers. There are four PFK-2/FBPase-2 isoenzymes in mammals, each coded by a different gene that expresses several isoforms of each isoenzyme. In these genes, regulatory sequences have been identified which account for their long-term control by hormones and tissue-specific transcription factors. One of these, HNF-6 (hepatocyte nuclear factor-6), was discovered in this way. As to short-term control, the liver isoenzyme is phosphorylated at the N-terminus, adjacent to the PFK-2 domain, by PKA (cAMP-dependent protein kinase), leading to PFK-2 inactivation and FBPase-2 activation. In contrast, the heart isoenzyme is phosphorylated at the C-terminus by several protein kinases in different signalling pathways, resulting in PFK-2 activation.
Functional Proteomics Analysis of Signal Transduction Pathways of the Platelet-Derived Growth Factor β Receptor (1999)

We report efficient methods for using functional proteomics to study signal transduction pathways in mouse fibroblasts following stimulation with PDGF. After stimulation, complete cellular proteins were separated using two-dimensional electrophoresis and phosphorylated proteins were detected with anti-phosphotyrosine and anti-phosphoserine antibodies. About 260 and 300 phosphorylated proteins were detected with the anti-phosphotyrosine and anti-phosphoserine antibodies, respectively, at least 100 of which showed prominent changes in phosphorylation as a function of time after stimulation. Proteins showing major time-dependent changes in phosphorylation were subjected to in-gel digestion with trypsin and identified by mass spectroscopy using MALDI-TOF mass fingerprinting and ESI peptide sequencing. We have observed phosphorylated proteins known to be part of the PDGF signal transduction pathway such as ERK 1, serine/threonine protein kinase akt and protein tyrosine phosphatase syp, proteins such as proto-oncogene tyrosine kinase fgr previously known to participate in other signal transduction pathways, and some proteins such as plexin-like protein with no previously known function in signal transduction. Information about the phosphorylation site was obtained for proto-oncogene tyrosine kinase fgr and for cardiac alpha-actin. The methods used here have proven to be suitable for the identification of time-dependent changes in large numbers of proteins involved in signal transduction pathways.
XRCC3 promotes homology-directed repair of DNA damage in mammalian cells (1999)

Homology-directed repair of DNA damage has recently emerged as a major mechanism for the maintenance of genomic integrity in mammalian cells. The highly conserved strand transferase, Rad51, is expected to be critical for this process. XRCC3 possesses a limited sequence similarity to Rad51 and interacts with it. Using a novel fluorescence-based assay, we demonstrate here that error-free homology-directed repair of DNA double-strand breaks is decreased 25-fold in an XRCC3-deficient hamster cell line and can be restored to wild-type levels through XRCC3 expression. These results establish that XRCC3-mediated homologous recombination can reverse DNA damage that would otherwise be mutagenic or lethal.