gebhart/patrepeval huggingface dataset:
The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cellsin vitroandin vivowith particular efficacy for small cell lung cancer (2009)

Lung cancer is the leading cause of cancer deaths in the United States. Current therapies are inadequate. Histone deacetylase inhibitors (HDACi) are a recently developed class of anticancer agents that cause increased acetylation of core histones and nonhistone proteins leading to modulation of gene expression and protein activity involved in cancer cell growth and survival pathways. We examined the efficacy of the HDACi panobinostat (LBH589) in a wide range of lung cancers and mesotheliomas. Panobinostat was cytotoxic in almost all 37 cancer cell lines tested. IC(50) and LD(50) values were in the low nmol/L range (4-470 nmol/L; median, 20 nmol/L). Small cell lung cancer (SCLC) cell lines were among the most sensitive lines, with LD(50) values consistently <25 nmol/L. In lung cancer and mesothelioma animal models, panobinostat significantly decreased tumor growth by an average of 62% when compared with vehicle control. Panobinostat was equally effective in immunocompetent and severe combined immunodeficiency mice, indicating that the inhibition of tumor growth by panobinostat was not due to direct immunologic effects. Panobinostat was, however, particularly effective in SCLC xenografts, and the addition of the chemotherapy agent etoposide augmented antitumor effects. Protein analysis of treated tumor biopsies revealed elevated amounts of cell cycle regulators such as p21 and proapoptosis factors, such as caspase 3 and 7 and cleaved poly[ADP-ribose] polymerase, coupled with decreased levels of antiapoptotic factors such as Bcl-2 and Bcl-X(L). These studies together suggest that panobinostat may be a useful adjunct in the treatment of thoracic malignancies, especially SCLC.
Design of 3D integrated inductors for RFICs (2012)

This paper discusses the design of 3D monolithic integrated inductors. The proposed 3D radio frequency (RF) integrated inductors have high inductance (L) values with an enhanced quality factors (Q). A new proposed method for 3D integrated inductors design is presented. A wide range of inductances and quality factor values can be realized. The proposed 3D inductors were designed in TSMC 0.18 μm technology and simulated using momentum.
A Phase II Trial of Perifosine in Locally Advanced, Unresectable, or Metastatic Pancreatic Adenocarcinoma (2007)

The study was suspended and subsequently terminated as a result of unacceptable adverse events during the first stage. Perifosine does not appear to be worthy of further study in this group of patients.
PROTAC-Induced Proteolytic Targeting (2012)

Small-molecule modulators of protein activity are increasingly being utilized as tools to examine the functional roles of proteins. Operating at the post-translational level, these molecules provide enhanced temporal and spatial control and mitigate the potential for compensatory responses in comparison with classical genetic approaches. Proteolysis targeting chimeric molecules, or PROTACs, are small molecules that inhibit the function of their target proteins by targeting them for degradation by the ubiquitin proteasome system. This chapter summarizes strategies for PROTAC preparation and characterization.
Renal Nerves Mediate Changes in Contralateral Renal Blood Flow after Extracorporeal Shockwave Lithotripsy (2003)

Renal blood flow falls in both kidneys following delivery of a clinical dose of shockwaves (SW) (2000 SW, 24 kV, Dornier HM3) to only one kidney. The role of renal nerves in this response was examined in a porcine model of renal denervation. Six-week-old pigs underwent unilateral renal denervation. Nerves along the renal artery of one kidney were identified, sectioned and painted with 10% phenol. Two weeks later the pigs were anesthetized and baseline renal function was determined using inulin and PAH clearances. Animals then had either sham-shockwave lithotripsy (SWL) (group 1), SWL to the innervated kidney (group 2) or SWL to the denervated kidney (group 3). Bilateral renal function was again measured 1 and 4 h after SWL. Both kidneys were then removed for analysis of norepinephrine content to validate the denervation. Renal plasma (RPF) flow was significantly reduced in shocked innervated kidneys (group 2) and shocked denervated kidneys (group 3). RPF was not reduced in the unshocked denervated kidneys of group 2. These observations suggest that renal nerves play a pivotal role in modulating the vascular response of the contralateral unshocked kidney to SWL, but only a partial role, if any, in modulating that response in the shocked kidney.
Demonstration of the transferrin receptor in human breast cancer tissue. Potential marker for identifying dividing cells (1981)

A transferrin receptor was demonstrated in tumor tissue from 10 patients with breast carcinoma and one patient with breast sarcoma. Binding studies were conducted by measuring the amont of 1251-transferrin binding to microsomal preparations of the tumor tissue. Elevated levels of specific transferrin binding were found in the tumors with a range of 11-35% of bound transferrin, whereas microsomes prepared from non-neoplastic breast tissue samples bound only 2.3% and 2.4% of the transferrin. Scatchard analysis of binding studies conducted with tissues from a breast cancer and from a breast sarcoma indicate that the receptor has a Ka = 9.0 x 10(8)M. The binding site is specific for transferrin, as studies show that non-radioactive transferrin displaced labelled transferrin, while human IgG and human albumin did not. The receptor-transferrin complex was precipitated from a detergent extract of the breast sarcoma with antiserum to human transferrin. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of the immunoprecipitate gave a polypeptide of M 90,000 daltons, which is of similar molecular weight found for the putative transferrin receptor in all of a series of human cultured cell lines previously examined.
Human spongiform encephalopathy: The national institutes of health series of 300 cases of experimentally transmitted disease (1994)

We present a synthesis of clinical, neuropathological, and biological details of the National Institutes of Health series of 300 experimentally transmitted cases of spongiform encephalopathy from among more than 1,000 cases of various neurological disorders inoculated into nonhuman primates during the past 30 years. The series comprises 278 subjects with Creutzfeldt-Jakob disease, of whom 234 had sporadic, 36 familial, and 8 iatrogenic disease; 18 patients with kuru; and 4 patients with Gerstmann-Strüssler-Scheinker syndrome. Sporadic Creutzfeldt-Jakob disease, numerically by far the most important representative, showed an average age at onset of 60 years, with the frequent early appearance of cerebellar and visual/oculomotor signs, and a broad spectrum of clinical features during the subsequent course of illness, which was usually fatal in less than 6 months. Characteristic spongiform neuropathology was present in all but 2 subjects. Microscopically visible kuru-type amyloid plaques were found in 5% of patients with Creutzfeldt-Jakob disease, 75% of those with kuru, and 100% of those with Gerstmann-Sträussler-Scheinker syndrome; brain biopsy was diagnostic in 95% of cases later confirmed at autopsy, and proteinase-resistant amyloid protein was identified in Western blots of brain extracts from 88% of tested subjects. Experimental transmission rates were highest for iatrogenic Creutzfeldt-Jakob disease (100%), kuru (95%), and sporadic Creutzfeldt-Jakob disease (90%), and considerably lower for most familial forms of disease (68%). Incubation periods as well as the durations and character of illness showed great variability, even in animals receiving the same inoculum, mirroring the spectrum of clinical profiles seen in human disease. Infectivity reached average levels of nearly 10(5) median lethal doses/gm of brain tissue, but was only irregularly present (and at much lower levels) in tissues outside the brain, and, except for cerebrospinal fluid, was never detected in bodily secretions or excretions.
Cysteinylation of maternal plasma albumin and its association with intrauterine growth restriction (2005)

We hypothesize that sustained oxidative stress present in UPI is reflected by high levels of maternal cysteinylated albumin and may be a factor in the etiology of IUGR. Results of this preliminary study suggest that measurement of maternal plasma cysteinylated albumin may be useful for monitoring pregnancies associated with UPI and for detection of IUGR.
Simultaneous production of three phenazine pigments by Pseudomonas aeruginosa Mac 436 (1969)

Pseudomonas aeruginosa Mac 436 was found to produce simultaneously three phenazine pigments identified as pyocyanine, phenazine-1-carboxylic acid, and oxychlororaphine. Production of these pigments on various media indicated a wide variation in yields depending on the composition of the media, but satisfactory yields of all three pigments were obtained. A scheme was developed for separation and assay of the pigments from the culture liquor. Details of production, isolation, assay, and identification are given.
Regulation of the glv Operon in Bacillus subtilis : YfiA (GlvR) Is a Positive Regulator of the Operon That Is Repressed through CcpA and cre (2001)

Maltose metabolism and the regulation of the glv operon of Bacillus subtilis, comprising three genes, glvA (6-phospho-alpha-glucosidase), yfiA (now designated glvR), and glvC (EIICB transport protein), were investigated. Maltose dissimilation was dependent primarily upon the glv operon, and insertional inactivation of either glvA, glvR, or glvC markedly inhibited growth on the disaccharide. A second system (MalL) contributed to a minor extent to maltose metabolism. Northern blotting revealed two transcripts corresponding to a monocistronic mRNA of glvA and a polycistronic mRNA of glvA-glvR-glvC. Primer extension analysis showed that both transcripts started at the same base (G) located 26 bp upstream of the 5' end of glvA. When glvR was placed under control of the spac promoter, expression of the glv operon was dependent upon the presence of isopropyl-beta-D-thiogalactopyranoside (IPTG). In regulatory studies, the promoter sequence of the glv operon was fused to lacZ and inserted into the amyE locus, and the resultant strain (AMGLV) was then transformed with a citrate-controlled glvR plasmid, pHYCM2VR. When cultured in Difco sporulation medium containing citrate, this transformant [AMGLV(pHYCM2VR)] expressed LacZ activity, but synthesis of LacZ was repressed by glucose. In an isogenic strain, [AMGLVCR(pHYCM2VR)], except for a mutation in the sequence of a catabolite-responsive element (cre), LacZ activity was expressed in the presence of citrate and glucose. Insertion of a citrate-controlled glvR plasmid at the amyE locus of ccpA(+) and ccpA mutant organisms yielded strains AMCMVR and AMCMVRCC, respectively. In the presence of both glucose and citrate, AMCMVR failed to express the glv operon, whereas under the same conditions high-level expression of both mRNA transcripts was found in strain AMCMVRCC. Collectively, our findings suggest that GlvR (the product of the glvR gene) is a positive regulator of the glv operon and that glucose exerts its effect via catabolite repression requiring both CcpA and cre.
Emergence of Minor Populations of Human Immunodeficiency Virus Type 1 Carrying the M184V and L90M Mutations in Subjects Undergoing Structured Treatment Interruptions (2003)

The use of structured treatment interruption (STI) in human immunodeficiency virus (HIV)-infected subjects is currently being studied as an alternative therapeutic strategy for HIV-1. The potential risk for selection of drug-resistant HIV-1 variants during STI is unknown and remains a concern. Therefore, the emergence of drug resistance in sequential plasma samples obtained from 28 subjects with chronic HIV infection was studied. They underwent 4 cycles of 2-week STI, followed by 8-week retreatment with highly active antiretroviral therapy identical to that used before STI, and they had never failed treatment before undergoing STI. At week 40, treatment was stopped for a longer period. Minor populations of drug-resistant variants were detected by quantitative real-time polymerase chain reaction, by use of allele-discriminating oligonucleotides for 2 key resistance mutations: L90M (protease) and M184V (reverse transcriptase). The approximate discriminative power was 0.1%. In 14 of 25 and in 3 of 25 subjects, the M184V and the L90M mutations, respectively, were detected as minor populations, at different times during STI. Overall, these results indicate that, in subjects undergoing multiple STIs, HIV-1 variants carrying drug-resistance mutations can emerge during periods of increased HIV-1 replication.
Isolation and Characterization of Neural Crest Stem Cells from Adult Human Hair Follicles (2010)

Neural crest (NC) is a transient embryonic tissue, whose cells are motile and multipotent until they reach their destination and differentiate according to microenvironmental cues into a variety of cell types. However, a subpopulation of these cells remains multipotent. They were found, among other locations, in a bulge of adult murine whisker follicle and were designated epidermal neural crest stem cells (EPI-NCSCs). The aim of this work is to ascertain whether the EPI-NCSCs could be isolated from human hair follicles as well. Due to their exceptional properties, they could represent potential candidates for stem cell therapy. The presented work focuses on the isolation and characterization of EPI-NCSCs from human skin. We obtained a population of cells that expressed markers of NC, NC progeny and general stem cell markers. After prolonged cultivation, the subpopulation of cells spontaneously differentiated into some of NC derivatives, i.e. neurons, smooth muscle cells and Schwann cell progenitors. Targeted differentiation with neuregulin 1 highly increased the number of Schwann cells in the culture. Human EPI-NCSCs could also grow under non-adherent conditions and form 3-dimensional spheres. Microarray analysis was performed and gene profile of human EPI-NCSCs was compared with the list of key genes of murine EPI-NCSCs and the list of genes up-regulated in newly induced NC cells. This revealed 94% and 88% similarity, respectively. All presented results strongly support the NCSC identity and multipotency of isolated human cells. These cells could thus be used in regenerative medicine, especially because of the easy accessibility of donor tissue.
Tumor cell recognition by the NK cell activating receptor NKG2D (2008)

Evidence for increased tumor incidence in NKG2D-deficient mice has set NKG2D as the first innate immune receptor implicated in immunosurveillance of tumors. In this viewpoint article, we discuss recent genetic insight into NKG2D-mediated suppression of spontaneous tumor development in the context of NKG2D signaling properties. Moreover, we identify unresolved issues and consider how an understanding of NKG2D-receptor and -ligand biology can facilitate successful therapeutic intervention of human cancer.
Design and performance of a long-span IM/DD optical transmission system using remotely pumped optical amplifiers (1990)

Novel optical transmission system configurations which use remotely pumped fibre amplifiers are proposed to increase repeater spacings. The configurations and properties of major optical components, such as the Er-doped fibre pre-amplifier and booster amplifier, developed for this system, are described. Also Raman amplification for a dispersion shifted fibre and its high power optical signal handling capacity are evaluated. Finally, fibre transmission was demonstrated at 1.8 Gb/s over 310.3 km with a 62 dB repeater gain in a direct detection repeater system.
Mechanisms of deep brain stimulation (2002)

The mechanism of action of high frequency deep brain stimulation is still unknown. However, in all circumstances and in all target nuclei so far stimulated, the effects mimic those of lesions previously made during thalamotomies, pallidotomies or even subthalamotomies, suggesting an inhibition of at least the neuronal network containing the target, if not of the target itself. On the contrary, fiber bundles are consistently activated at low or high frequencies. The hypothetical mechanisms envisioned should therefore be compatible and even produce these observed effects, to be acceptable as hypotheses. The mechanism could be either one or a combination of several causes: jamming of a feedback loop, activation of inhibitory structures included in a more complex network, blockade of membrane ion channels, deplorisation blockade, synaptic exhaustion, induction of early genes, changes in local blood flow, neuroplasticity, etc. It is probable that some are more involved in the acute effects and others in the long term changes, close to neuroplasticity. It is clear that the understanding of this strange and powerful phenomenon will profit from both clinical observation and well designed animal experiments.
Interleukin 12 administration induces T helper type 1 cells and accelerates autoimmune diabetes in NOD mice. (1995)

T cells play a major role in the development of insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. Administration of interleukin 12 (IL-12), a key cytokine which guides the development of T helper type 1 (Th1) CD4+ T cells, induces rapid onset of IDDM in NOD, but not in BALB/c mice. Histologically, IL-12 administration induces massive infiltration of lymphoid cells, mostly T cells, in the pancreatic islets of NOD mice. CD4+ pancreas-infiltrating T cells, after activation by insolubilized anti T cell receptor antibody, secrete high levels of interferon gamma and low levels of IL-4. Therefore, IL-12 administration accelerates IDDM development in genetically susceptible NOD mice, and this correlates with increased Th1 cytokine production by islet-infiltrating cells. These results hold implications for the pathogenesis, and possibly for the therapy of IDDM and of other Th1 cell-mediated autoimmune diseases.
Gβγ Subunits Mediate Src-dependent Phosphorylation of the Epidermal Growth Factor Receptor (1997)

In many cells, stimulation of mitogen-activated protein kinases by both receptor tyrosine kinases and receptors that couple to pertussis toxin-sensitive heterotrimeric G proteins proceed via convergent signaling pathways. Both signals are sensitive to inhibitors of tyrosine protein kinases and require Ras activation via phosphotyrosine-dependent recruitment of Ras guanine nucleotide exchange factors. Receptor tyrosine kinase stimulation mediates ligand-induced receptor autophosphorylation, which creates the initial binding sites for SH2 domain-containing docking proteins. However, the mechanism whereby G protein-coupled receptors mediate the phosphotyrosine-dependent assembly of a mitogenic signaling complex is poorly understood. We have studied the role of Src family nonreceptor tyrosine kinases in G protein-coupled receptor-mediated tyrosine phosphorylation in a transiently transfected COS-7 cell system. Stimulation of Gi-coupled lysophosphatidic acid and alpha2A adrenergic receptors or overexpression of Gbeta1gamma2 subunits leads to tyrosine phosphorylation of the Shc adapter protein, which then associates with tyrosine phosphoproteins of approximately 130 and 180 kDa, as well as Grb2. The 180-kDa Shc-associated tyrosine phosphoprotein band contains both epidermal growth factor (EGF) receptor and p185(neu). 3-5-fold increases in EGF receptor but not p185(neu) tyrosine phosphorylation occur following Gi-coupled receptor stimulation. Inhibition of endogenous Src family kinase activity by cellular expression of a dominant negative kinase-inactive mutant of c-Src inhibits Gbeta1gamma2 subunit-mediated and Gi-coupled receptor-mediated phosphorylation of both EGF receptor and Shc. Expression of Csk, which inactivates Src family kinases by phosphorylating the regulatory carboxyl-terminal tyrosine residue, has the same effect. The Gi-coupled receptor-mediated increase in EGF receptor phosphorylation does not reflect increased EGF receptor autophosphorylation, assayed using an autophosphorylation-specific EGF receptor monoclonal antibody. Lysophosphatidic acid stimulates binding of EGF receptor to a GST fusion protein containing the c-Src SH2 domain, and this too is blocked by Csk expression. These data suggest that Gbetagamma subunit-mediated activation of Src family nonreceptor tyrosine kinases can account for the Gi-coupled receptor-mediated tyrosine phosphorylation events that direct recruitment of the Shc and Grb2 adapter proteins to the membrane.
Ebola Virus Pathogenesis: Implications for Vaccines and Therapies (2003)

Ebola virus is an aggressive pathogen that causes a highly lethal hemorrhagic fever syndrome in humans and nonhuman primates. First recognized near the Ebola River valley during an outbreak in Zaire in 1976 (6, 20), outbreaks have occurred in Africa in the ensuing 27 years, with mortality rates ranging from 50 to 90% (26, 28). Outbreaks have been identified yearly for the past 3 years in central Africa, the most recent of which continues in the Republic of the Congo, with more than 125 fatalities to date according to the World Health Organization (http://www.who.int/csr/don/2003_05_07/en/, accessed 7 May 2003). The natural host for Ebola virus is unknown, so it has not been possible to implement programs to control or eliminate viral reservoirs of transmission to human populations. The rapid progression of Ebola virus infection has further complicated the control of this disease, affording little opportunity to develop acquired immunity. There is currently no antiviral therapy or vaccine that is effective against Ebola virus infection in humans.

Although its clinical course is well known, the specific mechanisms underlying the pathogenicity of Ebola virus have not been clearly delineated. This is due, in part, to the difficulty in obtaining samples and studying the disease in the relatively remote areas in which the outbreaks occur. In addition, a high degree of biohazard containment is required for laboratory studies and clinical analysis. Isolation of the viral cDNAs and the development of expression systems have allowed the study of Ebola virus gene products under less restrictive conditions and facilitated an understanding of the mechanisms underlying virally induced cell damage.
GATA3 Expression in Advanced Breast Cancer: Prognostic Value and Organ-Specific Relapse (2015)

These findings suggest that GATA3 may not act solely as a luminal differentiation marker, and further uncovering the molecular pathways by which GATA3 regulates the downstream targets will be crucial to our understanding of breast cancer dissemination.
Generating Sentences from a Continuous Space (2016)

The standard recurrent neural network language model (rnnlm) generates sentences one word at a time and does not work from an explicit global sentence representation. In this work, we introduce and study an rnn-based variational autoencoder generative model that incorporates distributed latent representations of entire sentences. This factorization allows it to explicitly model holistic properties of sentences such as style, topic, and high-level syntactic features. Samples from the prior over these sentence representations remarkably produce diverse and well-formed sentences through simple deterministic decoding. By examining paths through this latent space, we are able to generate coherent novel sentences that interpolate between known sentences. We present techniques for solving the difficult learning problem presented by this model, demonstrate its effectiveness in imputing missing words, explore many interesting properties of the model's latent sentence space, and present negative results on the use of the model in language modeling. but now , as they parked out front and owen stepped out of the car , he could see True: that the transition was complete . RNNLM: it , " i said . VAE: through the driver 's door . you kill him and his True: men .