gebhart/patrepeval huggingface dataset:
Estimates of the worldwide incidence of 25 major cancers in 1990 (1999)

The annual incidence rates (crude and age-standardized) and numbers of new cases of 25 different cancers have been estimated for the year 1990 in 23 areas of the world. The total number of new cancer cases (excluding non-melanoma skin cancer) was 8.1 million, just over half of which occur in the developing countries. The most common cancer in the world today is lung cancer, accounting for 18% of cancers of men worldwide, and 21% of cancers in men in the developed countries. Stomach cancer is second in frequency (almost 10% of all new cancers) and breast cancer, by far the most common cancer among women (21% of the total), is third. There are large differences in the relative frequency of different cancers by world area. The major cancers of developed countries (other than the 3 already named) are cancers of the colon-rectum and prostate, and in developing countries, cancers of the cervix uteri and esophagus. The implications of these patterns for cancer control, and specifically prevention, are discussed. Tobacco smoking and chewing are almost certainly the major preventable causes of cancer today.
Elacytarabine – lipid vector technology overcoming drug resistance in acute myeloid leukemia (2011)

Clinical trials in patients with hematological malignancies are reporting very encouraging efficacy results with an acceptable side effect profile. Elacytarabine has the potential to play an important role in the treatment of multiple malignancies in the future and results from an ongoing Phase III clinical trial are eagerly awaited.
Visual Properties of Transgenic Rats Harboring the Channelrhodopsin-2 Gene Regulated by the Thy-1.2 Promoter (2009)

Channelrhodopsin-2 (ChR2), one of the archea-type rhodopsins from green algae, is a potentially useful optogenetic tool for restoring vision in patients with photoreceptor degeneration, such as retinitis pigmentosa. If the ChR2 gene is transferred to retinal ganglion cells (RGCs), which send visual information to the brain, the RGCs may be repurposed to act as photoreceptors. In this study, by using a transgenic rat expressing ChR2 specifically in the RGCs under the regulation of a Thy-1.2 promoter, we tested the possibility that direct photoactivation of RGCs could restore effective vision. Although the contrast sensitivities of the optomotor responses of transgenic rats were similar to those observed in the wild-type rats, they were enhanced for visual stimuli of low-spatial frequency after the degeneration of native photoreceptors. This result suggests that the visual signals derived from the ChR2-expressing RGCs were reinterpreted by the brain to form behavior-related vision.
Stromal cell-derived factor 1alpha stimulates human glioblastoma cell growth through the activation of both extracellular signal-regulated kinases 1/2 and Akt. (2003)

In this paper, we describe the role of chemokine receptor CXCR4 activation by its natural ligand, the chemokine stromal cell-derived factor (SDF-1) (CXCL12), in glioblastoma cell growth in vitro. We show that both CXC chemokine receptor 4 (CXCR4) and SDF-1 mRNA are expressed in several human glioblastoma multiforme tumor tissues and in two human glioblastoma cell lines, U87-MG and DBTRG-05MG. These cells are able to secrete SDF-1 under basal conditions, and the rate of secretion is highly increased after lipopolysaccharide or 1% fetal bovine serum treatment. Exogenous SDF-1alpha induces proliferation in a dose-dependent manner in both cell lines. Moreover, we observed that SDF-1alpha-dependent proliferation is correlated with phosphorylation and activation of both extracellular signal-regulated kinases 1/2 and Akt and that these kinases are independently involved in glioblastoma cell proliferation. The role of CXCR4 stimulation in glioblastoma cell growth is further demonstrated by the ability of human monoclonal CXCR4 antibody (clone 12G5) to inhibit the SDF-1alpha-induced proliferation as well as the proliferation induced by SDF-1-releasing treatments (lipopolysaccharide and 1% fetal bovine serum). These data support a role for SDF-1alpha in the regulation of glioblastoma growth in vitro, likely through an autocrine/paracrine mechanism.
Role of the haeme oxygenase/carbon monoxide pathway in mechanical nociceptor hypersensitivity (2001)

The cleavage of haeme by haeme oxygenase (HO) yields carbon monoxide (CO), a biologically active molecule which exerts most of its effects via activation of soluble guanylate cyclase (sGC). In the present study, we tested the hypothesis that endogenous CO could modulate inflammatory hyperalgesia. The intensity of hyperalgesia was investigated in a model of mechanical nociceptor hypersensitivity in rats. The intra-plantar (i.pl.) administration of the HO inhibitor, ZnDPBG (Zinc deuteroporphyrin 2,4-bis glycol), potentiated in a dose-dependent manner the mechanical nociceptor hypersensitivity evoked by i.pl. administration of carrageenan. The mechanical hypersensitivity evoked by i.pl. injection of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), but not interleukin-8 (IL-8), prostaglandin E(2) (PGE(2)) or dopamine, was also enhanced by ZNDPBG: Moreover, the haeme (HO substrate) injection in the paws reduced the hypersensitivity evoked by IL-1beta, but not PGE(2). Furthermore, i.pl. administration of the gas CO reduced the hypersensitivity elicited by PGE(2). The inhibitory effect of haeme and CO upon mechanical nociceptor hypersensitivity were counteracted by a soluble guanylate cyclase (sGC) inhibitor, ODQ (1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one), suggesting that this effect of CO is mediated via cyclic GMP. Finally, the inhibitory effect of CO upon mechanical nociceptor hypersensitivity was prevented by the NO synthase blocker, L-NMMA (N(G)-monomethyl L-arginine), suggesting that the impairment of mechanical hypersensitivity elicited by CO depends on the integrity of the NO pathway. In conclusion, the results presented in this paper imply that endogenously CO produced by HO plays an anti-hyperalgesic role in inflamed paws, probably by increasing the intracellular levels of cyclic GMP in the primary afferent neurone.
The p53 Tumor-Suppressor Gene (1992)

OVER the past 15 years an examination of cancerous tissues has led to the identification of alterations in a number of genes that regulate cell growth and proliferation.1 These mutations have been identified in two distinct categories of genes, oncogenes and tumor-suppressor genes. Typically, mutations in oncogenes occur in one of the two alleles of the gene, and they act in a fashion dominant to the wild-type allele. Consequently, they are "gain of function" mutations that constitutively or permanently signal the cell to divide. Mutations in oncogenes appear to arise spontaneously in somatic tissues over the lifetime of the organism, . . .
Experimental measurement and finite-element modeling of extraordinary optoconductance inGaAs−Inmetal-semiconductor hybrid structures (2006)

We present a detailed discussion of extraordinary optoconductance (EOC). (Here optoconductance is synonymous with photoconductance.) Experimental data were acquired via macroscopic metal-semiconductor hybrid structures composed of $\mathrm{GaAs}$ and In and subjected to illumination from an Ar ion laser. A drift diffusion model using the finite element method (FEM) provided a reasonable fit to the data. EOC is explored as a function of laser position, bias current, laser power density, and temperature. The positional dependence of the voltage is accounted for by the Dember effect, with the model incorporating the excess hole distribution based on the carrier mobility, and thus the mean free path. The bias current is found to produce a linear voltage offset and does not influence the EOC. A linear relationship is found between the laser power density and the voltage in the bare and hybrid devices. This dependence is reproduced in the model by a generation rate parameter which is related to the power density. Incorporating the mobility and diffusion temperature dependence, the model directly parallels the temperature dependence of the EOC without the use of fitting parameters.
Enhanced Room-Temperature Geometric Magnetoresistance in Inhomogeneous Narrow-Gap Semiconductors (2000)

A symmetric van der Pauw disk of homogeneous nonmagnetic indium antimonide with an embedded concentric gold inhomogeneity is found to exhibit room-temperature geometric magnetoresistance as high as 100, 9100, and 750,000 percent at magnetic fields of 0.05, 0.25, and 4.0 teslas, respectively. For inhomogeneities of sufficiently large diameter relative to that of the surrounding disk, the resistance is field-independent up to an onset field above which it increases rapidly. These results can be understood in terms of the field-dependent deflection of current around the inhomogeneity.
Changes in cartilage and bone metabolism identified by serum markers in early osteoarthritis of the knee joint (1998)

Serum concentrations of two extracellular matrix molecules were determined over a 3 yr period in individuals with chronic knee pain to investigate whether sequential serum measurements of cartilage- and bone-derived molecular fragments reflect early stages of osteoarthritis (OA) of the knee joints. Thirty-eight individuals with chronic knee pain (> 3 months at inclusion) with or without radiographic evidence of knee joint OA at the 3 yr follow-up radiographic examination were studied. Serum concentrations of cartilage oligomeric matrix protein (COMP) and bone sialoprotein (BSP) increased significantly (P < 0.001) in the 23 individuals with radiographic OA at follow-up, while remaining unchanged in the 15 individuals with normal radiographs at follow-up. The baseline concentrations of the two variables did not differ between the groups. These findings suggest that pathological processes in cartilage and subchondral bone coincide in OA, and appear to be reflected by circulating levels of macromolecules released from cartilage and bone. Changes in serum levels of COMP and BSP are potential tools in studies of knee joint OA in subjects with chronic knee pain.
Cloning and characterization of canine prostate‐specific membrane antigen (2013)

The cloning, expression, biosynthesis, processing and localization of canine PSMA in mammalian cells is described. We demonstrate that canine PSMA reveals similar characteristics to human PSMA rendering this protein useful as a translational model for investigations of prostate cancer as well as a suitable antigen for targeted therapy studies in dogs.
Scaling to ultra-large-A<inf>eff</inf> using higher-order-mode fibers (2006)

Light propagation in higher-order modes of fibers yields a promising schematic for arbitrarily increasing modal areas. We demonstrate this with modes of record A <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">eff</sub> ranging from 2100 to 3100 mum <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , which experience negligible loss or mode coupling.
Identification of Murine Uterine Genes Regulated in a Ligand-Dependent Manner by the Progesterone Receptor (2005)

Progesterone (P4) acting through its cognate receptor, the progesterone receptor (PR), plays an important role in uterine physiology. The PR knockout (PRKO) mouse has demonstrated the importance of the P4-PR axis in the regulation of uterine function. To define the molecular pathways regulated by P4-PR in the mouse uterus, Affymetrix MG U74Av2 oligonucleotide arrays were used to identify alterations in gene expression after acute and chronic P4 treatments. PRKO and wild-type mice were ovariectomized and then treated with vehicle or 1 mg P4 every 12 h. Mice were killed either 4 h after the first injection (acute P4 treatment) or after the fourth injection of P4 (chronic P4 treatment). At the genomic level, the major change in gene expression after acute P4 treatment was an increase in the expression of 55 genes. Conversely, the major change in gene expression after chronic P4 treatment was an overall reduction in the expression of 102 genes. In the analysis, retinoic acid metabolic genes, cytochrome P 450 26a1 (Cyp26a1), alcohol dehydrogenase 5, and aldehyde dehydrogenase 1a1 (Aldh1a1); kallikrein genes, Klk5 and Klk6; and specific transcription factors, GATA-2 and Cited2 [cAMP-corticosterone-binding protein/p300-interacting transactivator with glutamic acid (E) and aspartic acid (D)-rich tail], were validated as regulated by the P4-PR axis. Identification and analysis of these responsive genes will help define the role of PR in regulating uterine biology.
Nitric oxide inhibition of basal and neurogenic mucus secretion in ferret tracheain vitro (1996)

1. In order to examine the role of nitric oxide (NO) on airway mucus secretion we studied the effects of the nitric oxide synthase (NOS) inhibitor L-N(G)-monomethyl-L-arginine (L-NMMA), a novel nitric oxide donor, (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (FK409), and the NO precursor L-arginine on basal mucus secretion in the ferret trachea in vitro in Ussing chambers. We also determined the effects of these agents upon secretion induced by electrical stimulation of nerves or by acetylcholine (ACh). We used 35SO4 as a mucus marker. 2. L-NMMA (0.01-1 mM) increased basal output of 35SO4-labelled macromolecules with a maximal increase above baseline of 248% at 0.1 mM L-NMMA. L-Arginine (1 mM) alone had no significant effect on basal secretion but reversed the potentiating effect of L-NMMA on basal secretion. L-NMMA-induced increases in basal mucus secretion were sustained for at least 30 min in the continuing presence of the NOS inhibitor. In contrast to the potentiating effects of L-NMMA, FK409 (100 nM) reduced basal secretion by 60% (at 1 nM and at 10 nM it was without effect). 3. Electrical stimulation (50 V, 10 Hz, 0.5 ms for 5 min) increased 35SO4 output by 174%. L-NMMA (1 and 10 mM) present during stimulation of tracheal segments resulted in significant potentiations of 214% and 116%, respectively, of the neurogenic response. The potentiated response to 10 mM L-NMMA was reversed by L-arginine (1 mM). At this dose L-arginine had no effect itself on basal secretion. In contrast to the potentiating effects of L-NMMA on neurogenic secretion, FK409 at 10 nM and 100 nM inhibited the neurogenic response by 98% and 99%. 4. At all concentrations tested, neither L-NMMA (0.01 mM-1 mM) nor FK409 (1-100 mM) had any significant effect on ACh-induced mucus secretion. 5. These observations lead us to conclude that nitric oxide, derived from constitutive NO synthase, acts as an endogenous inhibitor of both basal and neurogenic mucus secretion in ferret trachea in vitro.
Antibodies against synthetic peptides and the topology of LamB, an outer-membrane protein from Escherichia coli K12 (1989)

LamB, an outer membrane protein from Escherichia coli K12, is involved in the transport of maltose and maltodextrins across the outer membrane and constitutes a receptor for a number of bacteriophages. A recent folding model proposes that LamB spans the outer membrane through a number of transmembranous segments separated by regions exposed either to the cell exterior or to the periplasm. This model is essentially based on predictions of structure and genetic arguments relying on the hypothesis that the mutations studied did not alter the folding of the protein. In order to obtain direct evidence with the unaltered protein, we elicited polyclonal antibodies against synthetic peptides corresponding to several LamB sequences. We chose four regions. Three of them [aa 147-161 (peptide 2), aa 371-385 (peptide 3), and aa 399-413 (peptide 4)] are predicted to face the outside of the cell, and the fourth (aa 19-33 (peptide 1)] is predicted to be periplasmic. By immunoblotting against extracts of various mutants, these antibodies were shown to be specific for LamB and targeted to the selected regions. In some cases, the recognition sites for antibodies were narrowed down to parts of a region. In vivo, on intact cells, anti-peptides 2, 3, and 4 reacted with LamB in an ELISA; this confirmed that regions of peptide 2 and 3 are located, at least in part, at the cell exterior and provided the first proof for a similar, situation of the region of peptide 4. Under the same conditions, anti-peptide 1 did not react with LamB.(ABSTRACT TRUNCATED AT 250 WORDS)
PPARγ and its ligands: therapeutic implications in cardiovascular disease (2009)

The relevance of PPARgamma (peroxisome-proliferator-activated receptor gamma) as an important therapeutic target for the treatment of diabetes arises from its hypoglycaemic effects in diabetic patients and also from the critical role in the regulation of cardiovascular functions. From a clinical perspective, differences between current FDA (Food and Drug Administration)-approved PPARgamma drugs have been observed in terms of atherosclerosis and cardiac and stroke events. The adverse effects of PPARgamma-specific treatments that hamper their cardiovascular protective roles, affirm the strong need to evaluate the efficacy of the current drugs. Therefore active research is directed towards high-throughput screening and pharmacological testing of a plethora of newly identified natural or synthetic compounds. In the present review we describe the rationale behind drug design strategies targeting PPARgamma, based on current knowledge regarding the effects of such drugs in experimental animal models, as well as in clinical practice. Regarding endogenous PPARgamma ligands, several fatty acid derivatives bind PPARgamma with different affinities, although the physiological relevance of these interactions is not always evident. Recently, NO-derived unsaturated fatty acids were found to be potent agonists of PPARs, with preferential affinity for PPARgamma, compared with oxidized fatty acid derivatives. Nitroalkenes exert important bioactivities of relevance for the cardiovascular system including anti-inflammatory and antiplatelet actions, and are important mediators of vascular tone. A new generation of insulin sensitizers with PPARgamma function for the treatment of diabetes may serve to limit patients from the increased cardiovascular burden of this disease.
Switching effect and local conductivity in thin films of polydiphenylenephthalide (1995)

The switching effect induced by an electric field and pressure has been investigated in thin (∼0.5 μm) films of polydiphenylenephthalide. It has been shown that the conductivity of a polymer film is affected by highly conductive filament formation. Using a liquid crystal, we were able to visualize such filaments and to determine their parameters: size, conductivity, and surface density. The low-frequency current fluctuations in thin polymer films have also been measured. The rapid growth of current fluctuations near the switching point has been found. The results of this study are evidence for the filament model.
Discovery of Novel Dot1L Inhibitors through a Structure-Based Fragmentation Approach (2016)

Oncogenic MLL fusion proteins aberrantly recruit Dot1L, a histone methyltransferase, to ectopic loci, leading to local hypermethylation of H3K79 and misexpression of HoxA genes driving MLL-rearranged leukemias. Inhibition of the methyltransferase activity of Dot1L in this setting is predicted to reverse aberrant H3K79 methylation, leading to repression of leukemogenic genes and tumor growth inhibition. In the context of our Dot1L drug discovery program, high-throughput screening led to the identification of 2, a weak Dot1L inhibitor with an unprecedented, induced pocket binding mode. A medicinal chemistry campaign, strongly guided by structure-based consideration and ligand-based morphing, enabled the discovery of 12 and 13, potent, selective, and structurally completely novel Dot1L inhibitors.
The Clinical Relevance of the miR-197/CKS1B/STAT3-mediated PD-L1 Network in Chemoresistant Non-small-cell Lung Cancer (2015)

Programmed cell death ligand-1 (PD-L1) has recently gained considerable attention for its role in tumor immune escape. Here, we identify a miR-197/CKS1B/STAT3-mediated PD-L1 network in chemoresistant non-small-cell lung cancer (NSCLC), independent of immunoinhibitory signals. miR-197 is downregulated in platinum-resistant NSCLC specimens, resulting in the promotion of chemoresistance, tumorigenicity, and pulmonary metastasis in vitro and in vivo. Mechanistic investigations reveal that a miR-197-mediated CKS1B/STAT3 axis exerts tumor progression regulated by various oncogenic genes (Bcl-2, c-Myc, and cyclin D1), and PD-L1 is a putative biomarker of this axis. Furthermore, we demonstrate that a miR-197 mimic sensitizes PD-L1(high) drug-resistant cells to chemotherapy. These results indicate that the biological interaction between PD-L1 and chemoresistance occurs through the microRNA regulatory cascade. More importantly, expression levels of miR-197 are inversely correlated with PD-L1 expression (n = 177; P = 0.026) and are associated with worse overall survival (P = 0.015). Our discoveries suggest that the miR-197/CKS1B/STAT3-mediated network can drive tumor PD-L1 expression as a biomarker of this cascade, and miR-197 replacement therapy may be a potential treatment strategy for chemoresistant NSCLC.
Development of an effective context-free parser for continuous stochastic languages (2002)

An effective parser is developed to parse input strings according to a continuous stochastic context-free grammar. This new parser finds the most probable parse tree, so that it is the context-free analog of the Viterbi algorithm. A pruning technique is also implemented to reduce the time complexity to O(n/sup 2/).
Accurate rogue access point localization leveraging fine-grained channel information (2014)

Rogue access point (AP) has emerged as an important security problem in WLANs. However, it is a challenge task to localize the rogue AP with both high accuracy and minimal infrastructure cost. Either expensive professional infrastructure (e.g., multiple wireless sniffers) or additional hardware (e.g., directional antenna) need to be pre-deployed for rogue AP localization with high cost. Moreover, existing methods using Received Signal Strength (RSS) result in large error as RSS is suffered from the multipath and shadowing effects in complex wireless environment. In this work, we exploit the channel state information (CSI), which is readily available from commercial Wi-Fi devices, to locate the rogue AP with high accuracy. We use only a single off-the-shelf Wi-Fi device for rogue AP localization which involves minimal infrastructure requirement. Our proposed rogue AP localization framework consists of two components: direction determination and position estimation. By characterizing time domain CSI amplitude, we develop direction determination approach to estimate the direction of the rogue AP at the Wi-Fi device. We further propose two schemes to estimate position of the rogue AP: directions determined at multiple locations grounded on triangulation, or walking towards the rogue AP with direction adjustment. Results from extensive experiments in both indoor and outdoor environments show that our framework can achieve more practical and accurate rogue AP localization when comparing with existing RSS-based approach.