gebhart/patrepeval huggingface dataset:
Bisantrene, an active drug in patients with advanced breast cancer. (1984)

We have previously reported that bisantrene has significant activity against a variety of tumors in the human tumor soft agar cloning assay. An update of that experience reveals that 26% of evaluable human breast cancer specimens were sensitive to bisantrene, which had activity equivalent or superior to that of doxorubicin. Because of the preclinical activity of bisantrene and its activity in the cloning assay, bisantrene was studied in a phase II clinical trial of 30 patients with advanced breast cancer refractory to standard agents. Six patients (20%) had objective complete or partial regressions, including one patient with complete regression of lymphangitic lung metastases lasting greater than 18 months, confirming the antitumor activity of this compound. Two of the six responding patients had failed doxorubicin treatment, implying a lack of complete cross-resistance. Bisantrene toxicity was acceptable in most patients, with reversible myelosuppression being the most frequent side effect. Phase III trials of this promising new agent are warranted.
Fabrication of the gating nanopore device (2009)

We synthesized gating nanopores with embedded nanogap electrodes in a solid-state nanopore using an 11-step nanofabrication process. We were able to detect Au nanoparticles passing through a 30-nm-diameter gating nanopore via an electric current between nanoelectrodes. The electric current was proportional to the duration of translocation time. The gating nanopore is expected to be a next-generated nanosystem that can be applied to single-molecule sensors.
Strategic Procurement of Assembly Systems (1993)

The International Conference on Assembly, which is held every two or three years around the world, is focused on academic research and the audience is, for the most part, the academic research community sharing their work for future application.
The epidemiology of human papillomavirus and cervical cancer. (1992)

More than one million people are affected by Kashin-Beck disease (KBD) in a limited endemic area. However, few studies focused on the clinical features of adult KBD patients. The aim of this study was to investigate the clinical features of adult KBD patients who were younger than 50 years of age during a low incidence period. A special questionnaire was designed that surveyed general data, clinical symptoms, and signs and included the Visual Analogue Scale (VAS). Anthropometrics, the joint VAS, the range of joint motion (ROM), and joint function were measured. The VAS and joint dysfunction were compared among the different joints of extremities, and the relationship among the VAS, ROM, age, course of KBD, and number of enlarged knee and elbow joints elbow was analyzed. Two hundred forty-nine adult Tibetan KBD patients, matched with 249 healthy control subjects, have been surveyed. The VAS results show that the knee is the joint associated with the most pain, followed by the elbow. The elbow shows a higher percentage of limited ROM (47.0 %). The number of enlarged joints has a significant correlation with the VAS or elbow and knee ROM compared with the age or course of disease (P < 0.05). Severe elbow and knee lesions are important clinical features of KBD in adults younger than 50 years of age during a low incidence period. The number of enlarged joints can partially predict the VAS or ROM of elbow and knee and may be used for evaluating the patient's condition and function.
Effects of vasoactive intestinal peptide or somatostatin on the expression of MADCAM-1 in the intestinal mucosa of rats with multiple organ dysfunction synarome (2009)

Objective To investigate the effects of somatostatin(SST)or vasoaetive intestinal peptide (VIP)on the expression of MAdCAM-1 in the intestinal muecosa of rats with multiple organ dysfunction syndrome (MODS)and its significance of prevention and treatment of MODS.Method Thirty six Wistar male rats were randomly divided into 6 groups(6 rats in each group),including control group,VIP group 1 and SST group1 (rats treated with VIP and SST respectively),MODS group(rats with MODS),VIP group 2 and SST group 2(NODS rats treated with VIP and SST respectively).The rat model of MODS(system inflammatory response syndrome,＞2 or-gans dysfunction)was established by occlusion of superior mesenteric arteries.0.2 ρmol·g-1 h -11 VIP or SST by intravenous injection combined with 0.25 ρmol/g VIP or SST by intraperitoneal injection were injected into rats.In each group,intestinal lymphocytes from rats labeled with 51 Cr were infused into rat veins and were quantified with γcounter in GALT.The expression of MAdCAM-1 in the intestinal mucosa was measured by western blot.Inflam-mation in the intestinal mucosa was evaluated with histological sections.Student's t test was used to assess differ-ence between the experiment group and the control group.Results In VIP group l and SST group 1,the peak values of MAdCAM-1 expression in diffusive lymphatic tissue of small intestinal were 157.67±2.52 and 154.33±3.22.and those in Peyer patches were 136.00±1.00 and 137.00±1.00.There were no significant difference when compared with control group(165.33±1.53,152.67±2.31,P＞0.05).The percentage of 51 Cr-lympho-cytes in diffusive lymphatic tissue of small intestine(1.04%±0.59%,1.01%±0.83%)showed no significant difference from control group(1.07%±0.61%,P＞0.05),and those in Peyer patches(1.83%±0.90%,1.56%±0.64%)were significantly less than control group(3.85%±2.02%,P＜0.05).In VIP group 2 and SST group 2,the peak values of MAdCAM-1 expression in diffusive lymphatic tissue of small intestinal(158.00±2.65,154.33±1.53)and Peyer patches(156.33±1.53.151.33±2.31)were significantly less than MODS group(175.33±2.52,173.00±2.65,P＜0.05).The percentage of 51 Cr-lymphocytes in diffusive lymphafic tissue of small intestine(1.58%±0.42%,1.45%±0.26%)and Peyer patches(2.14%±1.49%,0.81%±0.35%)were significantly less than MODS group(3.23%±1.69%,5.04%±1.23%,P＜0.05)and the se-vere histopathological danlage in intestine was relieved.Conclusions VIP or SST reduced intestinal lymphoeytes homing to GALT in rats with MODS through suppressing the expression of MAdCAM-1,and attenuated the inflam-matory injure in the intestinal mucosa.

Key words: 
Vasoactive intestinal polypeptide; Somatostatin; Mucosal addressin cell adhesion molecule-1; Multiole organ dysfunction syndrome
Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1 (1998)

SOCS-1, a member of the suppressor of cytokine signaling (SOCS) family, was identified in a genetic screen for inhibitors of interleukin 6 signal transduction. SOCS-1 transcription is induced by cytokines, and the protein binds and inhibits Janus kinases and reduces cytokine-stimulated tyrosine phosphorylation of signal transducers and activators of transcription 3 and the gp130 component of the interleukin 6 receptor. Thus, SOCS-1 forms part of a feedback loop that modulates signal transduction from cytokine receptors. To examine the role of SOCS-1 in vivo, we have used gene targeting to generate mice lacking this protein. SOCS-1(-/-) mice exhibited stunted growth and died before weaning with fatty degeneration of the liver and monocytic infiltration of several organs. In addition, the thymus of SOCS-1(-/-) mice was reduced markedly in size, and there was a progressive loss of maturing B lymphocytes in the bone marrow, spleen, and peripheral blood. Thus, SOCS-1 is required for in vivo regulation of multiple cell types and is indispensable for normal postnatal growth and survival.
Protein Kinase CK2 in Human Diseases (2008)

Protein kinase CK2 (formerly referred to as casein kinase II) is an evolutionary conserved, ubiquitous protein kinase. There are two paralog catalytic subunits, i.e. alpha (A1) and alpha' (A2). The alpha and alpha' subunits are linked to two beta subunits to produce a heterotetrameric structure. The catalytic alpha subunits are distantly related to the CMGC subfamily of kinases, such as the Cdk kinases. There are some peculiarities associated with protein kinase CK2, which are not found with most other protein kinases: (i) the enzyme is constitutively active, (ii) it can use ATP and GTP and (iii) it is found elevated in most tumors investigated and rapidly proliferating tissues. With the elucidation of the structure of the catalytic subunit, it was possible to explain why the enzyme is constitutively active [1] and why it can bind GTP [2]. Considerable information on the potential roles of CK2 in various disease processes including cancer has been gained in recent years, and the present review may help to further elucidate its aberrant role in many disease states. Its peculiar structural features [3-9] may be advantageous in designing tailor-made compounds with the possibility to specifically target this protein kinase [10]. Since not all the aspects of what has been published on CK2 can be covered in this review, we would like to recommend the following reviews; (i) for general information on CK2 [11-18] and (ii) with a focus on aberrant CK2 [19-22].
Targeting of the BclA and BclB proteins to the Bacillus anthracis spore surface (2008)

The exosporium is the outermost layer of the Bacillus anthracis spore. The predominant protein on the exosporium surface is BclA, a collagen-like glycoprotein. BclA is incorporated on the spore surface late in the B. anthracis sporulation pathway. A second collagen-like protein, BclB, has been shown to be surface-exposed on B. anthracis spores. We have identified sequences near the N-terminus of the BclA and BclB glycoproteins responsible for the incorporation of these proteins into the exosporium layer of the spore and used these targeting domains to incorporate reporter fluorescent proteins onto the spore surface. The BclA and BclB proteins are expressed in the mother cell cytoplasm and become spore-associated in a two-step process involving first association of the protein with the spore surface followed by attachment of the protein in a process that involves a proteolytic cleavage event. Protein domains associated with each of these events have been identified. This novel targeting system can be exploited to incorporate foreign proteins into the exosporium of inactivated, spores resulting in the surface display of recombinant immunogens for use as a potential vaccine delivery system.
Induction of Human Factor VIII Inhibitors in Rats by Immunization with Human Recombinant Factor VIII: a Small Animal Model for Humans with High Responder Inhibitor Phenotype (1996)

Hemophilia A is a clotting disorder that is due to reduced or absent coagulation factor VIII (FVIII) activity. In approximately 25% of people with severe hemophilia A, standard treatment with intravenous plasma-derived or recombinant FVIII (rFVIII) induces anti-FVIII antibodies that inhibit FVIII activity (inhibitors). We describe the development of a rat model to study the formation of inhibitors. Immunization of rats with human rFVIII in adjuvant induced an anti-human rFVIII antibody response characteristic of an anti-FVIII inhibitor response in hemophilia A patients. The rats exhibited a rapid, polyclonal secondary antibody response to human rFVIII. These antibodies were reactive against epitopes located in the heavy and light chains. All the rFVIII-immunized rats developed antibodies against the FVIII C2 domain, a region of major reactivity in hemophilia A patients with inhibitors. Furthermore, competition ELISAs demonstrated that rat and human anti-FVIII antibodies recognized identical or overlapping epitopes of the FVIII molecule. The rat anti-FVIII antibodies also functioned as human FVIII inhibitors with titers ranging from 120 to 2048 Bethesda Units (B.U.). We propose that this rat model may be useful to investigate immune responses to FVIII and may lead to better therapies for FVIII inhibitors.
Bami goreng for Mrs. Klerks and other stories on food and culture (2010)

In the Salle Saint-Jacques of the École des mines de Paris you would not want to present a paper in which culture figures as an explanatory term. Calmly but firmly the assembled members of the CSI would put you right. This notion is too big, it draws too much together, it is not sufficiently practical, material, situated – what have you. What is more, the fact that someone ‘belongs to culture X’ can never explain, say, the food she eats, as eating specific kinds of food is likely to mark what...
Expert consensus document from the European Society of Cardiology on catheter-based renal denervation (2013)

Current evidence from the available clinical trials strongly support the notion that catheter-based radiofrequency ablation of renal nerves reduces blood pressure and improves blood pressure control in patients with drug-treated resistant hypertension, with data now extending out to 36 months. Accordingly, renal denervation can be considered as a therapeutic option in patients with resistant hypertension, whose blood pressure cannot be controlled by a combination of lifestyle modification and pharmacological therapy according to current guidelines. The fact that renal denervation also reduces whole-bodysympathetic nerve activity suggests that this therapy may also be beneficial in other clinical states characterized by sympathetic nervous system activation-this may ultimately lead to new indications. © The Author 2013.
N-Glycan Processing Deficiency Promotes Spontaneous Inflammatory Demyelination and Neurodegeneration (2007)

. Susceptibility of inbred mouse strains to EAE is in part determined by major histocompatibility complex haplotype; however, other molecular mechanisms remain elusive. Galectins bind GlcNAc-branched N-glycans attached to surface glycoproteins, forming a molecular lattice that restricts lateral movement and endocytosis of glycoproteins. GlcNAc branching negatively regulates T cell activity and autoimmunity, and when absent in neurons, induces apoptosis in vivo in young adult mice. We find that EAE susceptible mouse strains PL/J, SJL, and NOD have reduced GlcNAc branching. PL/J mice display the lowest levels, partial deficiencies in N-acetylglucosaminyltransferase I, II, and V (i.e. Mgat1, -2, and -5), T cell hyperactivity and spontaneous late onset inflammatory demyelination and neurodegeneration; phenotypes markedly enhanced by Mgat5 / and Mgat5 / backgrounds in a gene dose-dependent manner. Spontaneous disease is transferable and characterized by progressive paralysis, tremor, dystonia, neuronophagia, and axonal damage in both demyelinated lesions and normal white matter, phenocopying progressive MS. Our data identify hypomorphic Golgi processing as an inherited trait that determines susceptibility to EAE, provides a unique spontaneous model of MS, and suggests GlcNAc-branching deficiency may promote T cell-mediated demyelination and neurodegeneration in MS.
Modulation of Proteoglycan and Collagen Profiles in Human Dermal Fibroblasts by High Density Micromass Culture and Treatment with Lactic Acid Suggests Change to a Chondrogenic Phenotype (2001)

Cartilage formation during embryonic development and in fracture healing in adult animals involves chondrogenic differentiation of mesenchymal precursors. Here we describe an in vitro model whereby human dermal fibroblasts, considered to be restricted to a fibroblast lineage, are apparently redirected toward a chondrogenic phenotype by high density micromass culture in the presence of lactic acid. Micromass cultures treated with 40 mM lactate exhibited increased levels of Alcian blue staining and sulfate incorporation, indicative of elevated sulfated glycosaminoglycan synthesis. Northern analysis revealed an up-regulation of chondroitin sulfate proteoglycan 1 (aggrecan) and transforming growth factor-beta 1 mRNA and a decrease in type I collagen expression. Type II collagen was detected by reverse transcription-PCR only in experimental cultures. Although the observed changes in biosynthesis and gene expression were consistent with differentiating chondrocytes, the cells displayed an elongated, fibroblast-like morphology. These findings suggest that dermal fibroblasts may be committed to differentiate along a chondrogenic pathway by in vitro culture under specific forcing conditions.
Expression of the human nephron differentiation molecules in renal cell carcinomas. (1990)

The authors tested frozen sections from 28 renal cell carcinomas (RCC)--21 clear, 1 eosinophilic, 4 basophilic, and 2 spindle-shaped cell type--with monoclonal antibodies (MAb) reacting against cytokeratin, vimentin, CD24, CALLA/CD10, villin, CD26, and HLA class I and class II molecules. These molecules are markers of specific segments of the mature kidney, and their loss or acquisition reflects the different steps of human nephrogenesis. KI67 MAb was used to evaluate cell-proliferating activity. All RCC cases expressed cytokeratin. Coexpression of vimentin was observed in 21 of 28 cases. Whether of clear or chromophilic type, all tumoral cells strongly expressed CD24 molecule, present on primitive blastema cells. All clear-type RCCs expressed CALLA/CD10 and 60% were also villin positive; some were faintly positive for CD26. CALLA, villin, and CD26 were not detected in basophilic cell type. HLA class I molecules were variably expressed in almost all cases, but HLA class II were never detected on tumoral cells. Except for the spindle-shaped population, cell-proliferating activity was low. These results favor the hypothesis that RCCs derive from cells that have 'recovered' the different options of metanephric differentiation. Clear cells show evidence of maturation toward proximal type, while basophilic cells do not. It would be of interest to evaluate the usefulness of serum measurements of villin and/or CALLA as markers in clear cell-type RCC.
DNA Repair Proteins and Telomerase Reverse Transcriptase in the Cochlear Lateral Wall of Cisplatin-Treated Rats (2009)

Cochlear lateral wall damage is a side effect of cisplatin chemotherapy. Recent studies have shown that cisplatin treatment precipitates platinated DNA adducts in the cochlear lateral wall which suggest that DNA damage may contribute to ototoxicity. Platinated adducts are high-affinity substrates for the global genomic nucleotide excision repair (GG-NeR) pathway which is facilitated by xeroderma pigmentosum (Xp) complementing proteins, such as XpC, XpD and XpA. tumor biology has shown that in addition to stimulating GG-NeR, cisplatin may deplete telomerase reverse transcriptase (teRt). in the current study Fischer344 rats were treated with cisplatin (2 mg/kg/4 days, i.p.) and their cochleae harvested for immunohistochemistry. XpC, XpD and XpA expression increased while teRt expression decreased among cisplatin treated animals compared to vehicle control. these findings suggest that in addition to forming platinated adducts, cisplatin chemotherapy may up-regulate DNA repair proteins and modify teRt expression in the cochlear lateral wall.
B Cell Selection Defects Underlie the Development of Diabetogenic APCs in Nonobese Diabetic Mice (2004)

One mechanism whereby B cells contribute to type 1 diabetes in nonobese diabetic (NOD) mice is as a subset of APCs that preferentially presents MHC class II-bound pancreatic beta cell Ags to autoreactive CD4 T cells. This results from their ability to use cell surface Ig to specifically capture beta cell Ags. Hence, we postulated a diabetogenic role for defects in the tolerance mechanisms normally blocking the maturation and/or activation of B cells expressing autoreactive Ig receptors. We compared B cell tolerance mechanisms in NOD mice with nonautoimmune strains by using the IgHEL and Ig3-83 transgenic systems, in which the majority of B cells recognize one defined Ag. NOD- and nonautoimmune-prone mice did not differ in ability to delete or receptor edit B cells recognizing membrane-bound self Ags. However, in contrast to the nonautoimmune-prone background, B cells recognizing soluble self Ags in NOD mice did not undergo partial deletion and were also not efficiently anergized. The defective induction of B cell tolerance to soluble autoantigens is most likely responsible for the generation of diabetogenic APC in NOD mice.
Addition of the Human Interferon β Scaffold Attachment Region to Retroviral Vector Backbones Increases the Level of in Vivo Transgene Expression among Progeny of Engrafted Human Hematopoietic Stem Cells (2000)

Absence of durable high-level expression of transgenes from Moloney murine leukemia (Mo-MuLV) retroviral vectors has been a hurdle in bringing effective gene therapy to the clinic. In this study we have analyzed transgene expression among the progeny of mobilized hematopoietic stem cells (HSCs), comparing Mo-MuLV and mouse stem cell virus (MSCV) vectors, with or without addition of a scaffold attachment region (SAR) from the human interferon beta gene. Retroviral (RV) vector supernatant quality was assessed by comparing NGFR transgene expression by HEL cells, and transgene delivery and expression by CD34(+) cells 72 hr after transduction, using real-time PCR and FACS analysis. This is the first description of the effect of SAR within both Mo-MuLV and MSCV vector backbones on long-term RV transgene expression among in vivo HSC progeny in HSC repopulation assays (SCID-hu bone and NOD/SCID). After transduction of mobilized CD34(+) cells with MSCV-SAR vector, transgene expression was observed among a mean of 10% of donor HSC progeny in the SCID-hu bone (range, 0.6-43%). The predominant effect of SAR was to increase the mean fluorescence intensity (MFI) of transgene expression among HSC progeny in both in vivo bone repopulation models (three- to fourfold), and after long-term stromal cultures (twofold).
Recognition of Double-Stranded Dna by Peptide Nucleic Acid (1997)

Abstract Peptide nucleic acid (PNA) is an oligonucleotide mimic in which the backbone of DNA has been replaced by a pseudopeptide. We here show that there are distinct variations as to how PNA oligomers interact with double-stranded DNA depending on choice of nucleobases. Thymine-rich homopyrimidine PNA oligomers recognise double-stranded polynucleotides by forming PNA2-DNA triplexes with the DNA purine strand. By contrast, cytosine-rich homopyrimidine PNAs add to double-stranded polynucleotides as Hoogsteen strands, forming PNA-DNA2 triplexes, while homopurine, or alternating thymine-guanine, PNA oligomers invade DNA to form PNA-DNA duplexes.
Paclitaxel (Taxol*) as Salvage Therapy for Relapsed Ovarian Cancer (1996)

Thirty-two patients with epithelial ovarian cancer received paclitaxel 175 mg/m2, by 3-hour infusion, in this prospective phase 2 study. All patients had relapsed or progressed after initial cisplatin/cyclophosphamide therapy. Thirteen patients received paclitaxel as second line therapy, 14 as third line therapy and 5 as fourth line therapy. One patient was excluded from efficacy analysis, due to a severe anaphylactic reaction to the first cycle of paclitaxel therapy. Of the 31 evaluable patients, complete remission was observed in 3 patients (9.7%) and partial remission in 11 patients (35.5%), with a total response rate of 45.2%. The median survival from diagnosis for the 31 evaluable patients was 32.5 months and the median survival following therapy with paclitaxel was 12.2 months (range 4-27 months). The 3 patients who achieved a complete response remain alive, at greater than 20 months, since commencing paclitaxel. Twelve patients (38.7%) who achieved a partial response, or had stable disease, had a median survival, after paclitaxel treatment, of greater than 18 months. This study confirms the activity of paclitaxel in relapsed ovarian cancer and demonstrates a prolonged survival benefit in greater than one third of this group of patients.