gebhart/patrepeval huggingface dataset:
Fibroblast growth factor receptor 4 predicts failure on tamoxifen therapy in patients with recurrent breast cancer (2008)

Tamoxifen treatment of estrogen-dependent breast cancer ultimately loses its effectiveness due to the development of resistance. From a functional screen for identifying genes responsible for tamoxifen resistance in human ZR-75-1 breast cancer cells, fibroblast growth factor (FGF) 17 was recovered. The aim of this exploratory study was to assess the predictive value of FGF17 and the receptors FGFR1-4 for the type of response to tamoxifen treatment (clinical benefit) and the duration of progression-free survival (PFS) in patients with recurrent breast cancer. mRNA levels of FGF17 and FGFR1-4 were quantified by real-time reverse transcriptase PCR in 285 estrogen receptor-positive breast carcinomas with clinical follow-up. All patients had recurrent disease and were treated with tamoxifen as first-line systemic therapy for local or distant relapse. FGF17 and FGFR1-3 mRNA levels had no significant predictive value for this group of patients. However, high FGFR4 mRNA levels analyzed as a continuous log-transformed variable predicted poor clinical benefit (odds ratio=1.22; P=0.009) and shorter PFS (hazard ratio=1.18; P<0.001). In addition, in multivariable analysis, the predictive value of FGFR4 was independent from the traditional predictive factors. Our analyses show that FGFR4 may play a role in the biological response of the tumor to tamoxifen treatment. In addition, as altered expression of FGF17 causes tamoxifen resistance in vitro, the FGF signaling pathway could be a valuable target in the treatment of breast cancer patients resistant to endocrine treatment.
Molecular analysis of the erythropoietin receptor system in patients with polycythaemia vera (1994)

Erythropoietin (EPO) is a potent regulator of the viability, proliferation and differentiation of erythroid progenitor cells. Its effect is mediated by binding to the erythropoietin receptor (EPO-R), a member of a new cytokine receptor family. Alterations of the EPO/EPO-R system have recently been shown to be involved in the pathogenesis of familial erythrocytosis and polycythaemia vera (PV). In order to define whether genetic changes in the EPO-R gene and its ligand play a role in the development of PV, the structure and expression levels of the EPO-R and EPO genes were examined in samples from bone marrow and/or peripheral blood mononuclear cells of 24 patients with PV. As expected, EPO serum levels were low and no detectable level of EPO mRNA was found by reverse polymerase chain reaction (RT-PCR) in the peripheral blood mononuclear cells of our PV patients. To search for structural alterations of the EPO-R, cDNA samples were subjected to PCR and SSCP analysis as well as sequencing. Heterogenous expression of EPO-R mRNA was observed without any structural changes, as revealed by RT-SSCP analysis using overlapping primers spanning the whole coding region of the EPO-R gene. Structural integrity of the EPO-R was further confirmed by sequencing of cloned PCR products. These data suggest that the mechanisms for the development of PV do not involve structural changes of the EPO-R gene.
A Radiation Hardened 16-Mb SRAM for Space Applications (2007)

A new high density, high performance 16-Mb static random access memory (SRAM) is being developed in a 0.15 mum CMOS RH15 technology for use in space and other strategic radiation hardened applications. The SRAM design is implemented in a 1.5 Volt, 0.15 micron and seven-layer metal CMOS technology. Using integrated process features and advanced design techniques, a small cell size of 9.3 mum <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> was utilized while achieving a SEU radiation hardness of less than IE-12 upsets/bit-day and a worst-case chip performance of less than 15 ns access time.
Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites. (1996)

Mutations in the recently identified presenilin 1 gene on chromosome 14 cause early onset familial Alzheimer disease (FAD). Herein we describe the expression and analysis of the protein coded by presenilin 1 (PS1) in NT2N neurons, a human neuronal model system. PS1 was expressed using recombinant Semliki Forest virions and detected by introduced antigenic tags or antisera to PS1-derived peptides. Immunoprecipitation revealed two major PS1 bands of approximately 43 and 50 kDa, neither of which were N-glycosylated or O-glycosylated. Immunoreactive PS1 was detected in cell bodies and dendrites of NT2N neurons but not in axons or on the cell surface. PS1 was also detected in BHK cells, where it was also intracellular and colocalized with calnexin, a marker for the rough endoplasmic reticulum. A mutant form of PS1 linked to FAD did not differ from the wild-type protein at the light microscopic level. The model system described here will enable studies of the function of PS1 in human neurons and the role of mutant PS1 in FAD.
Simple triple-label detection of seven cystic fibrosis mutations by time-resolved fluorometry (1997)

We describe a simple hybridization assay performed in microtitration wells with use of DNA probes labeled with three different lanthanide chelates for detection of seven mutations that cause cystic fibrosis. The assay is based on DNA amplification of four fragments containing the mutations (delta F508, G1717-->A, G542X, R553X, 3905 insertion T, W1282X, and N1303K) by PCR, followed by hybridization with short, allele-specific oligonucleotide probes labeled with europium, terbium, or samarium chelates. Because the technology makes it possible to hybridize three DNA probes simultaneously in one reaction, all 14 mutation-related alleles were detected in a total of five reaction wells. Blood spot specimens, obtained from children with cystic fibrosis, their parents, and their siblings, have been assayed, and for all the probes the positive signal-to-noise ratios are > 10. Solution hybridization utilizing triple-label time-resolved fluorometry combined with PCR is a suitable procedure for large-scale screening and automation.
Cross-lingual phoneme mapping for multilingual synthesis systems (2004)

Development of a multilingual text-to-speech (TTS) system usually requires a lot of time, effort and language resources. Furthermore, the implementation tends to consume large amounts of memory as the number of supported languages increases. This paper proposes a simple method for quickly increasing the language portfolio of an existing TTS system with the minimal effort and memory consumption. The crosslingual phoneme mapping modifies the phonetic transcription of a new language by presenting it with the phoneme set supported by an existing TTS system. The synthesis output of the mapped language is phonetically quite accurate but the intonation is based on the existing target language. The evaluations showed that the cross-lingual phoneme mapping could provide an adequate quality synthesis when the language portfolio must rapidly be expanded and the memory and the language resources are scarce. The method is applied best for the synthesis of short utterances including names and isolated words.
Management of sexual dysfunctions in women. (2003)

The deeper understanding of female physiology changed the perspective used to evaluate sexual difficulties. Systems like: vascular, neurological, biochemical, and endocrine are investigated as their modifications for aging or medical conditions may alter the sexual responsivity of women. New data imply that pharmacological interventions may become suitable for women. Gonadal steroids influence mood, wellbeing, and genital physiology but evidence of actions is controversial. Hormone imbalance provokes symptoms that may also derive from other conditions. Clinicians must exclude dismetabolism, depression and family crisis before diagnosing gonadal problems. The female androgen insufficiency syndrome was defined in July 2001 as altered mood, memory and wellbeing, and loss of desire. Estrogen maintains wellbeing and healthy genitals, influencing mood and sexuality. Progesterone provokes tension and nervousness, causing premenstrual syndrome. Hormone replacement is indicated in the treatment of endocrine deficiency. In research projects women receiving one preparation containing androgen reported improvement of mood, and arousal. Sildenafil cures approximately 25% of sexually dysfunctional, menopausal patients; being more effective with hormone replacement therapy (HRT) and consistently active against the block of antidepressants on orgasm. Added to psychiatric regimens, sildenafil ameliorates excitement. Sex therapy helps patients change behavior, overcome anger, communicate needs and redefine sex. We strongly believe that such crucial aspects must be addressed in therapy, even when the etiology is organic.
Literature Review-Effects of Hydrostatic Pressure on the Mechanical Behavior of Composite Materials (1995)

Hydrostatic pressure can cause significant changes in the mechanical properties of composite materials. A thorough understanding of these effects is essential for the effective design of composite structures for high-pressure applications. In this report, the literature on the effects of hydrostatic pressure on the mechanical behavior of composite materials is reviewed. This includes a general description of the effects of hydrostatic pressure on unreinforced polymers and a detailed critique of the experimental work that has been done on composite materials. The section on composites is divided into three sections: compressive, tensile, and shear testing. For each type of testing, the test materials and techniques and the physical and quantitative results are discussed.
Gene therapy of cancer (2001)

Gene therapy was initially thought of as a means to correct single gene defects in hereditary disease. In the meantime, cancer has become by far the most important indication for gene therapy in clinical trials. In the foreseeable future, the best way to achieve reasonable intratumoral concentrations of a transgene with available vectors is direct intratumoral injection with or without the aid of various techniques such as endoscopy or CT-guidance. At present, viral and non-viral methods of gene transfer are used either in vivo or ex vivo/in vitro. The most important viral vectors currently in use in clinical trials comprise retroviruses, adenoviruses, adeno-associated viruses, and herpes viruses. None of the available vectors satisfies all the criteria of an ideal gene therapeutic system, and vectors with only minimal residues of their parent viruses ("gutless vectors") as well as completely "synthetic viral vectors" will gain more and more importance in the future. Non-viral gene therapy methods include liposomes, injection of vector-free DNA ("naked DNA"), protein-DNA complexes, delivery by "gene gun," calcium-phosphate precipitation, electroporation, and intracellular microinjection of DNA. The first clinical trial of gene therapy for cancer was performed in 1991 in patients with melanoma, and since then more than 5000 patients have been treated worldwide in more than 400 clinical protocols. With the exception of a case of fatal toxicity in a young man with hereditary liver disease treated intrahepatically with high doses of adenovirus, side effects have been rare and usually mild in all these studies and expression of the transgene could be demonstrated in patients in vivo. However, despite anecdotal reports of therapeutic responses in some patients, unequivocal proof of clinical efficacy is still lacking for most of the varied approaches to gene therapy in humans. As well as our only fragmentary understanding of the molecular pathophysiology of many diseases, the principal reason for the present lack of clinical success of gene therapy is the very low transduction and expression efficiency in vivo of available vectors. Despite the complexities of gene therapy for cancer, the numerous different approaches can be subdivided into three basic concepts: (1) strengthening of the immune response against a tumour, (2) repair of cell cycle defects caused by losses of tumour suppressor genes or inappropriate activation of oncogenes, and (3) suicide gene strategies. In addition, the importance of gene marker studies and gene therapeutic protection of normal tissue are briefly covered in this review.
Human inter-α-trypsin inhibitor. Synthesis and maturation in hepatoma HepG2 cells (1989)

In hepatoma HepG2 cells, human inter-alpha-trypsin inhibitor (ITI) was synthesized as three heavy chains, H-1 (100 kDa), H-2 (110 kDa) and H-3 (113 kDa), and light hybrid chain (49.5 kDa) composed of alpha 1-microglobulin and HI-30 (ITI derivative, human inhibitor of 30 kDa). The association of at least two heavy chains, H-1 and H-3, with the HI-30 part of the light chain gave rise to a molecule similar to serum ITI. A composite protein (approximately 250 kDa) including heavy and light chains was also secreted, while alpha 1-microglobulin and ITI H-2 protein were released as separate entities. Light chain synthesis could be the limiting factor for ITI maturation.
Induction of Antitumor Immunity with Dendritic Cells Transduced with Adenovirus Vector-Encoding Endogenous Tumor-Associated Antigens (1999)

Dendritic cells (DCs) are professional Ag-presenting cells that are being considered as potential immunotherapeutic agents to promote host immune responses against tumor Ags. In this study, recombinant adenovirus (Ad) vectors encoding melanoma-associated Ags were used to transduce murine DCs, which were then tested for their ability to activate CTL and induce protective immunity against B16 melanoma tumor cells. Immunization of C57BL/6 mice with DCs transduced with Ad vector encoding the hugp100 melanoma Ag (Ad2/hugp100) elicited the development of gp100-specific CTLs capable of lysing syngeneic fibroblasts transduced with Ad2/hugp100, as well as B16 cells expressing endogenous murine gp100. The induction of gp100-specific CTLs was associated with long term protection against lethal s.c. challenge with B16 cells. It was also possible to induce effective immunity against a murine melanoma self Ag, tyrosinase-related protein-2, using DCs transduced with Ad vector encoding the Ag. The level of antitumor protection achieved was dependent on the dose of DCs and required CD4+ T cell activity. Importantly, immunization with Ad vector-transduced DCs was not impaired in mice that had been preimmunized against Ad to mimic the immune status of the general human population. Finally, DC-based immunization also afforded partial protection against established B16 tumor cells, and the inhibition of tumor growth was improved by simultaneous immunization against two melanoma-associated Ags as opposed to either one alone. Taken together, these results support the concept of cancer immunotherapy using DCs transduced with Ad vectors encoding tumor-associated Ags.
Robotic Assisted Laparoscopic Sural Nerve Grafting During Radical Prostatectomy: Initial Experience (2003)

The da Vinci remote robotic system technically facilitates sural nerve grafting during laparoscopic radical prostatectomy. Long-term potency data are essential to validate the technical success.
Cryogenic Raman spectroscopy of glycerol (2000)

In situ Raman spectra of glycerol in the spectral range 3700–300 cm−1 were obtained at 298, 223 and 77 K using a Raman microprobe. Comparative polarization Raman spectroscopy followed by band component analysis of glycerol at 298 both and 223 K were employed for band assignment. In addition to the documentary information from glycerol-related compounds, the polarization analysis (interpreted mostly from intensity changes) and the Raman wavenumber shifts registered upon cooling glycerol were the criteria used for these assignments. In the high-wavenumber region (3700–2500 cm−1) the bands at 3407, 3240, 2946, 2886 and 2763 cm−1 undergo a significant cryogenic shift to lower wavenumbers. The first two bands are assigned to antisymmetric and symmetric OH stretches, respectively, and the last three bands to CH stretching vibrations. These Raman shifts are related to intermolecular hydrogen-bond displacements upon cooling glycerol from room temperature. Below 1500 cm−1, the assignment of Raman bands is more complicated because many vibrations are coupled. Cryogenic shifts to higher wavenumbers are observed mainly for the lines attributed to the COH deformation (1342 cm−1), CCO vibration modes (1054 and 1115 cm−1) and CH2 rocks (976 and 925 cm−1). The peak at 673 cm−1 arising from a bending vibration also shifts to a higher wavenumbers on cooling. The Raman shifts are well interpreted as an effect of cooling on H-bond strengthening in glycerol. Copyright © 2000 John Wiley & Sons, Ltd.
GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma. (2015)

LBA8502 The full, final text of this abstract will be available at abstracts.asco.org at 7:30 AM (EDT) on Saturday, May 30, 2015, and in the Annual Meeting Proceedings online supplement to the June 20, 2015, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Calpain inhibitor II induces caspase-dependent apoptosis in human acute lymphoblastic leukemia and non-Hodgkin's lymphoma cells as well as some solid tumor cells. (2000)

Calpain is a calcium-dependent cysteine protease that is implicated in calcium-dependent cell death, and calpain inhibitors are generally considered as inhibitors of apoptosis. To the contrary, in the present study, we found that calpain inhibitor II (CPI-2) triggers rapid apoptosis in acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) cells. All target cell lines were killed by CPI-2, including: ALL-1, a multidrug-resistant BCR-ABL fusion transcript-positive t(9;22) pro-B ALL cell line; RS4;11, a highly radiation-resistant MLL-AF4 fusion transcript-positive t(4;11) pre-pre B ALL cell line; RAMOS, a highly radiation-resistant and p53-deficient Burkitt's lymphoma cell line; DAUDI, a Burkitt's leukemia/lymphoma cell line; NALM-6, a pre-B ALL cell line; and JURKAT and MOLT-3, two T-lineage ALL/NHL cell lines. CPI-2-induced apoptosis in LYN-deficient and BTK-deficient subclones of the DT-40 lymphoma B cell line as effectively as it did in wild-type DT-40 cells. Thus, CPI-2-induced apoptosis is not dependent on the protein tyrosine kinases LYN or BTK. Notably, caspase inhibitor I effectively inhibited CPI-2-induced apoptosis, suggesting that the inhibition of a CPI-2-susceptible protease results in caspase activation, leading to apoptosis in ALL/NHL cells. Unlike the high calpain-expressing ALL/NHL cell lines, myeloid leukemia cell lines HL-60/AML, K562/CML, and U937/AMML, or solid tumor cell lines BT-20/breast cancer, PC-3/prostate cancer, U373/glioblastoma, and HeLa/epitheloid cancer, were not susceptible to the cytotoxicity of CPI-2. Taken together, our results identify calpain as a new molecular target for the treatment of ALL and NHL. CPI-2 and its analogues represent a promising new class of antileukemia/lymphoma agents that deserves further development.
Analysis of regions of RAG-2 important for V(D)J recombination (1994)

The recombinase activating genes RAG-1 and RAG-2 operate together to activate V(D)J recombination, and thus play an essential role in the generation of immune system diversity. As a first step in understanding the function of the RAG-2 protein, we have tested a series of deletion and insertion mutations for their ability to induce V(D)J joining of a variety of model substrates. Mutants were assayed for their ability to induce deletional and inversional V(D)J joining, thereby testing their proficiency at forming both signal and coding joints, and, in some cases, for their ability to carry out recombination of both extrachromosomal and integrated recombination substrates. All these reactions were affected similarly by any one mutation. Although the RAG-2 protein shows extensive evolutionary conservation across its length, we found that the carboxy-terminal portion of RAG-2, including an acidic region, is dispensable for all forms of recombination tested. In contrast, all mutations we created in the N-terminal region severely decreased recombination. Thus, the core active region required for V(D)J recombination is confined to the first three-quarters of the RAG-2 protein.
Correction of Sickle Cell Disease in Adult Mice by Interference with Fetal Hemoglobin Silencing (2011)

Persistence of human fetal hemoglobin (HbF, α(2)γ(2)) in adults lessens the severity of sickle cell disease (SCD) and the β-thalassemias. Here, we show that the repressor BCL11A is required in vivo for silencing of γ-globin expression in adult animals, yet dispensable for red cell production. BCL11A serves as a barrier to HbF reactivation by known HbF inducing agents. In a proof-of-principle test of BCL11A as a potential therapeutic target, we demonstrate that inactivation of BCL11A in SCD transgenic mice corrects the hematologic and pathologic defects associated with SCD through high-level pancellular HbF induction. Thus, interference with HbF silencing by manipulation of a single target protein is sufficient to reverse SCD.
Antithrombotic Effect of TA-993, a Novel 1,5-Benzothiazepine Derivative, in Conscious Rats (1995)

Since reported experimental models of thrombosis are not suitable for comparison of several drugs by oral administration, we developed a convenient model for this purpose by applying direct current through an intravascular electrode. In conscious rats, which were implanted with anodal electrodes in the abdominal aorta on the day before the experiment, application of 200 microA of direct current induced the formation of a platelet-rich thrombus around the intravascular electrode. Using this model, we studied the antithrombotic effect of the novel antiplatelet agent TA-993, (-)-cis-3-acetoxy-5-(2-(dimethylamino)ethyl)-2,3-dihydro-8-methyl-2-(4- methylphenyl)-1,5-benzothiazepin-4(5H)-one maleate, and compared its effect with other antiplatelet agents. TA-993 at doses of 30 mg/kg, p.o. or more by single administration or at doses of 10 mg/kg or more by repeated administration dose-dependently suppressed the thrombus formation. Aspirin (10 mg/kg, p.o. or more), cilostazol (100 mg/kg, p.o.) and ticlopidine (30 mg/kg, p.o. or more) also suppressed the thrombus formation by single administration. These results suggest that TA-993 has a comparable antithrombotic effect with other antiplatelet agents, and thus it is a possible remedy for thrombotic and embolic diseases.
Movie Recommendation using Random Walks over the Contextual Graph (2010)

Recommender systems have become an essential tool in fighting information overload. However, the majority of recommendation algorithms focus only on using ratings information, while disregarding information about the context of the recommendation process. We present ContextWalk, a recommendation algorithm that makes it easy to include different types of contextual information. It models the browsing process of a user on a movie database website by taking random walks over the contextual graph. We present our approach in this paper and highlight a number of future extensions with additional contextual information.