gebhart/patrepeval huggingface dataset:
Novel clusters of highly expressed genes accompany genomic amplification in breast cancers (2007)

Breast cancer is the most common cancer in women worldwide. To identify novel amplicons involved in the mammary carcinogenesis, we constructed gene expression maps of chromosomes in 35 human breast cancer cell lines and extracted six candidate amplicons containing highly expressed gene clusters on chromosomes 8, 17, and X. We also confirmed the presence of the identified amplicons in clinical specimens by Southern blot analysis. Highly expressed genes identified in the amplicons will contribute to the characterization of breast cancer phenotypes, thereby providing novel targets for anticancer therapies.
Altered expression of G1-specific genes in human malignant myeloid cells. (1986)

We have studied the expression of cell-cycle genes specific to the G1 (2A9, 2F1, 4F1, c-myc) and S (histone H3) phases of the cell cycle in normal and malignant human myeloid cycling cells. The levels of expression were determined by measuring the amounts of specific RNA in blot hybridization assays. Levels of expression of the G1 genes were compared to the level of expression of the S-phase-specific H3 gene. This method can distinguish whether an increased expression of G1 genes is truly due to deregulation or simply reflects an increase in the fraction of proliferating cells. In a normal asynchronous system provided by the bone marrow cells of three normal donors, the expressions of the four G1-specific genes 2A9, 2F1, 4F1, and c-myc, and of the S-phase-specific gene H3 were in ratios that differed little from one individual to another. In the total RNA of eight patients in the chronic phase of chronic myelogenous leukemia, a high level of expression of G1 cell-cycle genes was paralleled by a high level of expression of the S-phase H3 gene, simply reflecting an increase in the fraction of proliferating cells. In patients with acute myelogenous leukemia (AML), the RNA levels of 2F1 and 4F1 paralleled the expression of H3-i.e., the ratios of expression 2F1/H3 and 4F1/H3 were the same as in normal bone marrow cells. However, in 9 of 10 patients with AML we found that the expression of c-myc was elevated with respect to H3 expression. The expression of 2A9 (with respect to H3) was also elevated in some of these AML patients. Two important conclusions can be drawn from these findings: increased levels of a G1-specific RNA in a tumor may not indicate overexpression of that gene but may instead simply reflect the fraction of proliferating cells; and in some patients with AML, however, the expression of certain G1 genes is truly deregulated and might contribute to the impairment of proliferative control that is associated with this phenotype.
Transdermal and Topical Drug Delivery Today (2011)

This chapter contains sections titled: Introduction Transdermal Drug Delivery Topical Drug Delivery Conclusions References
A Monte Carlo method for assessing color rendering quality with possible application to color rendering standards (2010)

Abstract The lighting industry has been increasingly challenged to reduce electrical energy consumption while providing illumination with sufficient color rendering quality. As a result, the problem of accurately assessing color rendering quality has gained increased prominence and the introduction of efficient narrow band light emitting diode (LED) sources has further intensified the debate. This study argues that there is a basic problem with the traditional method of quantifying color quality color rendering index (CRI), one that cannot be solved through minor improvements. The CRI relies on a determination of the degree of color distortion that a test source produces for a small number of test samples of specified spectral reflectance distribution, but there is no clear objective rationale for selecting these few samples. Also, any such arbitrary scoring scheme lacks an objective argument for what constitutes an acceptable score. This study proposes a new method for color rendering assessment that determines the color shift of one thousand, or more, representative reflection spectra that span the full multidimensional range of possible spectral distributions and colors. This broad sampling eliminates the intrinsic selection bias of the CRI calculation and its variants and it is compatible with a more objective standard for a color quality score, one that is statistically based on the fraction of the test spectra that experience color shifts that are less than a just noticeable difference (JND), or an agreed upon multiple of it. Since the concept of JNDs in color has been reproducibly quantified, it is hoped that this approach will be widely acceptable. © 2010 Wiley Periodicals, Inc. Col Res Appl, 2012
Data center optical networks (DCON) with OpenFlow based Software Defined Networking (SDN) (2013)

As the infrastructure of cloud computing and big data, data centers have been deployed widely. Then, how to make full use of the computing and storage resources in data centers will be the focus. Data center networks are considered important solution for the problem above, which include intra-data center and inter-data center networks. Both of them will depend on the optical networking due to its advantages, such as high bandwidth, low latency, and low energy consumption. Data center interconnected by flexi-grid optical networks is a promising scenario to allocate spectral resources for applications in a dynamic, tunable and efficient control manner. Compared with inter-data center, optical interconnect in intra-data center networks is a more pressing need and promising scenario to accommodate these applications in a dynamic, flexible and efficient manner. OpenFlow based Software Defined Networking (SDN) is considered as a good technology, which is very suitable for data center networks. This paper mainly focuses on the data center optical networks based on software defined networking (SDN), which can control the heterogeneous networks with unified resource interface. Architecture and experimental demonstration of OpenFlow-based optical interconnects in intra-data center Networks and OpenFlow-based flexi-grid optical networks for inter-data center are presented in the paper respectively. Some future works are listed finally.
ZEB1 in Pancreatic Cancer (2010)

Pancreatic cancer is one of the most malignant human neoplasias. On the molecular level, epithelial-mesenchymal transition (EMT) has been demonstrated to contribute to the malignant phenotype of pancreatic cancer cells. ZEB1 is a transcriptional repressor that has been identified as an inducer of EMT. A negative feedback loop between ZEB1 and microRNA-200c has been shown to regulate this EMT induction in various models. With respect to pancreatic cancer, primary effects of EMT comprise increased local and distant tumor cell dissemination. Another recently described feature of the EMT is the acquisition of cancer stem cell traits. For pancreatic cancer cells, antagonism between ZEB1 and stemness-inhibiting micro-RNAs has been demonstrated to contribute to this process, providing experimental support for the migrating cancer stem cell (MCSC) hypothesis. ZEB1 has also been shown to be associated with drug resistance of pancreatic cancer cells. This article reviews the biological functions of ZEB1 with a focus on pancreatic cancer.
Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study (2009)

Abstract Introduction Since current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a potent and selective protein tyrosine kinase inhibitor of c-KIT, in the monotherapy treatment of DMARD-refractory RA. Methods This was a multicentre, uncontrolled, open-label, randomised, dose-ranging, phase 2a trial. Masitinib was administered orally to 43 patients who had inadequate response to DMARDs, at initial randomised dosing levels of 3 and 6 mg/kg per day over a 12-week period. Dose adjustment was permitted based upon tolerability and response criteria. Efficacy was assessed via American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) responses, disease activity score using 28 joint counts (DAS28), index of improvement in RA (ACRn) and C-reactive protein (CRP) improvement, relative to baseline at week 12. Results Improvement was observed in all efficacy endpoints, including ACR20/50/70 scores of 54%, 26% and 8%, respectively, and a reduction in CRP level by greater than 50% for approximately half the population. This improvement was sustainable throughout an extension phase (&gt; 84 weeks) and was also independent of initial DMARD resistance (anti-tumour necrosis factor-alpha and/or methotrexate). A relatively high patient withdrawal rate (37%) required the use of last observation carried forward (LOCF) data imputation. Incidence of adverse events was high (95%), although the majority were of mild or moderate severity with a considerable decline in frequency observed after 12 weeks of treatment. Two nonfatal serious adverse events were reported. Dose-response analyses tentatively indicate that an initial dosing level of 6.0 mg/kg per day administered orally in two daily intakes is the most appropriate, based upon potency and tolerability trends. Conclusions Treatment with masitinib improved DMARD-refractory active RA. Following an initial high incidence of mostly mild to moderate side effects during the first 12 weeks of treatment, masitinib appears to be generally well tolerated. This, together with evidence of a sustainable efficacy response, suggests that masitinib is suitable for long-term treatment regimens. Since this was the first study of masitinib in a nononcologic pathology, the relatively high patient withdrawal rate observed can be partly attributed to a highly cautious response to adverse events. There is sufficient compelling evidence to warrant further placebo-controlled investigation. Trial registration ClinicalTrials.gov NCT00831922.
Elevations of Endogenous Kynurenic Acid Produce Spatial Working Memory Deficits (2006)

Kynurenic acid (KYNA) is a tryptophan metabolite that is synthesized and released by astrocytes and acts as a competitive antagonist of the glycine site of N-methyl-D-aspartate receptors at high concentrations and as a noncompetitive antagonist of the alpha7-nicotinic acetylcholine receptor at low concentrations. The discovery of increased cortical KYNA levels in schizophrenia prompted the hypothesis that elevated KYNA concentration may underlie the working memory dysfunction observed in this population that has been attributed to altered glutamatergic and/or cholinergic transmission. The present study investigated the effect of elevated endogenous KYNA on spatial working memory function in rats. Increased KYNA levels were achieved with intraperitoneal administration of kynurenine (100 mg/kg), the precursor of KYNA synthesis. Rats were treated with either kynurenine or a vehicle solution prior to testing in a radial arm maze task at various delays. Elevations of endogenous KYNA resulted in increased errors in the radial arm maze. In separate experiments, assessment of locomotor activity in an open field and latency to retrieve food reward from one of the maze arms ruled out the possibility that deficits in the maze were attributable to altered locomotor activity or motivation to consume food. These results provide evidence that increased KYNA levels produce spatial working memory deficits and are among the first to demonstrate the influence of glia-derived molecules on cognitive function. The implications for psychopathological conditions such as schizophrenia are discussed.
Phosphoprotein Analysis Using Antibodies Broadly Reactive against Phosphorylated Motifs (2002)

The substrates of most protein kinases remain unknown because of the difficulty tracing signaling pathways and identifying sites of protein phosphorylation. Here we describe a method useful in detecting subclasses of protein kinase substrates. Although the method is broadly applicable to any protein kinase for which a substrate consensus motif has been identified, we illustrate here the use of antibodies broadly reactive against phosphorylated Ser/Thr-motifs typical of AGC kinase substrates. Phosphopeptide libraries with fixed residues corresponding to consensus motifs RXRXXT*/S* (Akt motif) and S*XR (protein kinase C motif) were used as antigens to generate antibodies that recognize many different phosphoproteins containing the fixed motif. Because most AGC kinase members are phosphorylated and activated by phosphoinositide-dependent protein kinase-1 (PDK1), we used PDK1-/- ES cells to profile potential AGC kinase substrates downstream of PDK1. To identify phosphoproteins detected using the Akt substrate antibody, we characterized the antibody binding specificity to generate a specificity matrix useful in predicting antibody reactivity. Using this approach we predicted and then identified a 30-kDa phosphoprotein detected by both Akt and protein kinase C substrate antibodies as S6 ribosomal protein. Phosphospecific motif antibodies offer a new approach to protein kinase substrate identification that combines immunoreactivity data with protein data base searches based upon antibody specificity.
Inhibition of Tumor Necrosis Factor α and Ankylosing Spondylitis (2003)

to the editor: Konstantinides et al. (Oct. 10 issue) 1 evaluated the role of alteplase in patients with submassive pulmonary embolism. Their findings will be regarded by many as definitive evidence in support of the use of thrombolytic agents in such patients. However, a review of the study design, particularly the end points chosen, shows that the data do not support the authors' conclusions.
Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu (2002)

p38 mitogen-activated protein kinase (MAPK) is a member of the MAPK family which is activated by cytokines and growth factors, but its role in pathogenesis of multiple myeloma (MM) is unknown. In this study, we demonstrate that the specific p38 MAPK inhibitor VX-745 inhibits interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) secretion in bone marrow stromal cells (BMSCs), without affecting their viability. Tumor necrosis factor alpha (TNF-alpha)-induced IL-6 secretion in BMSCs is also inhibited by VX-745. Importantly, VX-745 inhibits both MM cell proliferation and IL-6 secretion in BMSCs triggered by adherence of MM cells to BMSCs, suggesting that it can inhibit paracrine MM cell growth in the BM milieu and overcome cell adhesion-related drug resistance. These studies therefore identify p38 MAPK as a novel therapeutic target to overcome drug resistance and improve patient outcome in MM.
Awareness and knowledge of oral cancer in urban pune population: a survey based questionnaire study. (2016)

A self-administered survey based questionnaire study about oral carcinoma conducted at Bharati hospital, Pune. Aims: To assess the awareness and knowledge about oral malignancy, to assess the knowledge about risk factors related to oral malignancy and to assess the awareness about signs/symptoms of oral cancer in urban Pune. A self designed questionnaire-based survey was conducted at the OPD of a tertiary care institute. Materials and Methods: A self administered questionnaire-based survey. Time period: two months Study Area: OPD of a tertiary care hospital in Pune. Total Participants: 500 persons. Statistical analysis used: The collected data were analyzed using SPSS software to assess and associate oral cancer awareness. Results: The general awareness, knowledge of signs and risk factors of oral cancer were found to be proportionate to the literacy level with the highest rate of awareness being among health-care workers and post-graduates and lowest among illiterates. It was also observed that on most of these dimensions the younger age groups (<30 years) were significantly more knowledgeable. Conclusion: The awareness of oral cancer in the population of Pune was not satisfactory, pointing to a need for further dissemination of information on this issue. This is especially important for the youngsters, as this may possibly help them keep away from indulgence in any form.
Fishing for genes controlling development (1996)

In recent years, the zebrafish has become a popular system for studying vertebrate development. Large scale mutant searches have led to the identification of >400 genes with unique functions during embryonic and larval development. A number of these genes play important roles in well studied processes, such as dorsoventral patterning of the early embryo, notochord formation and signaling, somitogenesis and neural specification. Other newly identified genes offer opportunities to investigate less well understood processes, including locomotion behavior, organogenesis, neural crest development and axonal pathfinding.
On the quantitative rat mesenteric-window angiogenesis assay (1992)

The rodent mesenteric-window angiogenesis assay permits the quantitative assessment of angiogenesis in adult, normally-vascularized mammalian tissue in the intact animal. Using appropriate optical magnifications, even very small, newly-formed vessels are recorded. The ultimate value of the model will, of course, depend on how pertinent it is to the features which govern angiogenesis in the tissues that are involved in clinically-relevant, angiogenesisrelated diseases.
The amino‐terminal domain of pyrrolysyl‐tRNA synthetase is dispensable in vitro but required for in vivo activity (2007)

Pyrrolysine (Pyl) is co-translationally inserted into a subset of proteins in the Methanosarcinaceae and in Desulfitobacterium hafniense programmed by an in-frame UAG stop codon. Suppression of this UAG codon is mediated by the Pyl amber suppressor tRNA, tRNA(Pyl), which is aminoacylated with Pyl by pyrrolysyl-tRNA synthetase (PylRS). We compared the behavior of several archaeal and bacterial PylRS enzymes towards tRNA(Pyl). Equilibrium binding analysis revealed that archaeal PylRS proteins bind tRNA(Pyl) with higher affinity (K(D)=0.1-1.0 microM) than D. hafniense PylRS (K(D)=5.3-6.9 microM). In aminoacylation the archaeal PylRS enzymes did not distinguish between archaeal and bacterial tRNA(Pyl) species, while the bacterial PylRS displays a clear preference for the homologous cognate tRNA. We also show that the amino-terminal extension present in archaeal PylRSs is dispensable for in vitro activity, but required for PylRS function in vivo.
Application of transcranial magnetic stimulation in treatment of drug‐resistant major depression—a report of two cases (1993)

Abstract We report the cases of two drug‐resistant major depressed psychotic patients, who were treated with 10 sessions of transcranial magnetic stimulations (TMS) and afterwards with 10 sessions of electroconvulsive therapy (ECT) without changing the concomitant neuroleptic and antidepressive medication. TMS did not exert a therapeutic effect in one patient and only a slight one in the other. However, there was a clear beneficial effect for ECT in the patient not responding to TMS and a slight therapeutic effect in the other. In summary, there was no clear‐cut evidence for effectiveness of TMS as a treatment for patients with psychotic, therapy resistant depression. However, since there was a slight therapeutic effect of TMS in one patient it seems worthwhile to explore its therapeutic efficacy in a larger group of depressed patients.
Duodenal and gastric delivery of levodopa in parkinsonism (1988)

To clarify the influence of gastric emptying on levodopa-related motor fluctuations in Parkinson's disease, we assessed mobility and plasma levodopa concentrations in 10 patients during five modes of levodopa administration: (1) standard intermittent oral (SIO), (2) intermittent duodenal (ID), (3) continuous duodenal infusion (CDI), (4) continuous gastric infusion (CGI), and (5) controlled-release Sinemet (CR-4). The rank order from greatest to least for both percentage of time "on" and average mobility score was CDI, CGI, ID, CR-4, and SIO. The rank order for variance of means, a measure of fluctuation, from least to greatest for mobility was CDI, CGI, CR-4, ID, SIO, and for plasma levodopa concentrations was CDI, CGI, ID, SIO, and CR-4. The results demonstrate that it is possible to produce very steady plasma concentrations of levodopa with a corresponding reduction in motor fluctuations by continuous intraduodenal administration of the drug. This mode of delivery is an ideal model for the development of optimal continuous-release preparations of levodopa. Other enteral routes have produced a more variable plasma levodopa concentration and clinical response.
Inhibition of Lapatinib-Induced Kinome Reprogramming in ERBB2-Positive Breast Cancer by Targeting BET Family Bromodomains (2015)

Therapeutics that target ERBB2, such as lapatinib, often provide initial clinical benefit, but resistance frequently develops. Adaptive responses leading to lapatinib resistance involve reprogramming of the kinome through reactivation of ERBB2/ERBB3 signaling and transcriptional upregulation and activation of multiple tyrosine kinases. The heterogeneity of induced kinases prevents their targeting by a single kinase inhibitor, underscoring the challenge of predicting effective kinase inhibitor combination therapies. We hypothesized that, to make the tumor response to single kinase inhibitors durable, the adaptive kinome response itself must be inhibited. Genetic and chemical inhibition of BET bromodomain chromatin readers suppresses transcription of many lapatinib-induced kinases involved in resistance, including ERBB3, IGF1R, DDR1, MET, and FGFRs, preventing downstream SRC/FAK signaling and AKT reactivation. Combining inhibitors of kinases and chromatin readers prevents kinome adaptation by blocking transcription, generating a durable response to lapatinib, and overcoming the dilemma of heterogeneity in the adaptive response.
Evolution of carbonic anhydrases in fungi (2009)

The ubiquitous metalloenzyme carbonic anhydrase (CA) catalyzes the interconversion of carbon dioxide and bicarbonate. This enzyme has been investigated in mammals, plants, algae, bacteria, archaea and fungi. Based on distinct structural characteristics, CAs can be assigned to five independently evolved classes (alpha, beta, gamma, delta and zeta). beta-CAs can be further subdivided into plant-type and cab-type sub-classes. The recent characterization of CAs in fungi led us to initiate a systematic search for these enzymes in filamentous ascomycetes. The genomes of basidiomycetes and hemiascomycetous yeasts contain only beta-CAs, while the filamentous ascomycetes also possess genes encoding alpha-class CAs. Here, we present a phylogenetic analysis of 97 fungal CA sequences that addresses the diversification of fungal CAs. During evolution various gene duplication and gene loss events seem to be the cause for the multiplicity of CAs in filamentous ascomycetes. Our data revealed that during the evolution of filamentous ascomycetes, a gene encoding the plant-type beta-CA was duplicated, resulting in two closely related isoforms, one with and one without an N-terminal mitochondrial target sequence (MTS). The acquisition of the MTS most likely took place after the gene duplication event and after the evolutionary separation of the fungal orders Sordariales and Eurotiales.