gebhart/patrepeval huggingface dataset:
Antiangiogenic agents in the management of non-small cell lung cancer (2012)

Several therapies targeting angiogenesis are currently in development for non-small cell lung cancer (NSCLC). This review discusses results of recent clinical trials evaluating chemotherapy plus antiangiogenic therapy for NSCLC. Bevacizumab, an anti-VEGF antibody, is currently approved for the treatment of advanced NSCLC in combination with carboplatin and paclitaxel. Completed phase III trials evaluating bevacizumab plus chemotherapy have shown prolonged progression-free survival; however, not all trials showed significant improvement in overall survival (OS). Phase III trials of the tyrosine kinase inhibitors (TKIs) vandetanib and sorafenib and the vascular disrupting agent ASA404 also failed to improve OS compared with chemotherapy alone. Clinical trials are ongoing involving several new antiangiogenic therapies, including ramucirumab, aflibercept, cediranib, BIBF 1120, sunitinib, pazopanib, brivanib, ABT-869, axitinib, ABT-751, and NPI-2358; several of these agents have shown promising phase I/II results. Results from recently completed and ongoing phase III trials will determine if these newer antiangiogenic agents will be incorporated into clinical practice.
Improved direct bonding of Si and SiO2 surfaces by cleaning in H2SO4:H2O2:HF (1995)

A method for silicon surface preparation prior to wafer bonding is presented. By cleaning the wafers in a H2SO4:H2O2 mixture in which a small amount of HF is added, and then rinsing in H2O, the bonding behavior of the surfaces is improved, compared to other pretreatments used for bonding. The modified SPM cleaning results in a highly fluorinated chemical oxide on the Si surface. A subsequent water rinse causes substitution of F by OH groups, which increase the initial attraction of the mating surfaces. Higher contact wave velocities and bond strengths than reported for other surface pretreatments have been measured, both for bare and thermally oxidized silicon surfaces.
The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression (2006)

The expression of COMT does not appear to be altered in the cerebellum of individuals suffering from schizophrenia, bipolar disorder or depression, but does appear to be influenced by single nucleotide polymorphisms within the gene.
Interactive furniture layout using interior design guidelines (2011)

We present an interactive furniture layout system that assists users by suggesting furniture arrangements that are based on interior design guidelines. Our system incorporates the layout guidelines as terms in a density function and generates layout suggestions by rapidly sampling the density function using a hardware-accelerated Monte Carlo sampler. Our results demonstrate that the suggestion generation functionality measurably increases the quality of furniture arrangements produced by participants with no prior training in interior design.
Male Mice That Do Not Express Group VIA Phospholipase A2 Produce Spermatozoa with Impaired Motility and Have Greatly Reduced Fertility (2004)

The Group VIA Phospholipase A(2) (iPLA(2)beta) is the first recognized cytosolic Ca(2+)-independent PLA(2) and has been proposed to participate in arachidonic acid (20:4) incorporation into glycerophosphocholine lipids, cell proliferation, exocytosis, apoptosis, and other processes. To study iPLA(2)beta functions, we disrupted its gene by homologous recombination to generate mice that do not express iPLA(2)beta. Heterozygous iPLA(2)beta(+/-) breeding pairs yield a Mendelian 1:2:1 ratio of iPLA(2)beta(+/+), iPLA(2)beta(+/-), and iPLA(2)beta(-/-) pups and a 1:1 male:female gender distribution of iPLA(2)beta(-/-) pups. Several tissues of wild-type mice express iPLA(2)beta mRNA, immunoreactive protein, and activity, and testes express the highest levels. Testes or other tissues of iPLA(2)beta(-/-) mice express no iPLA(2)beta mRNA or protein, but iPLA(2)beta(-/-) testes are not deficient in 20:4-containing glycerophosphocholine lipids, indicating that iPLA(2)beta does not play an obligatory role in formation of such lipids in that tissue. Spermatozoa from iPLA(2)beta(-/-) mice have reduced motility and impaired ability to fertilize mouse oocytes in vitro and in vivo, and inhibiting iPLA(2)beta with a bromoenol lactone suicide substrate reduces motility of wild-type spermatozoa in a time- and concentration-dependent manner. Mating iPLA(2)beta(-/-) male mice with iPLA(2)beta(+/+), iPLA(2)beta(+/-), or iPLA(2)beta(-/-) female mice yields only about 7% of the number of pups produced by mating pairs with an iPLA(2)beta(+/+) or iPLA(2)beta(+/-) male, but iPLA(2)beta(-/-) female mice have nearly normal fertility. These findings indicate that iPLA(2)beta plays an important functional role in spermatozoa, suggest a target for developing male contraceptive drugs, and complement reports that disruption of the Group IVA PLA(2) (cPLA(2)alpha) gene impairs female reproductive ability.
The role of complement receptor 3 (CR3) inNeisseria gonorrhoeaeinfection of human cervical epithelia (2001)

Neisseria gonorrhoeae is an important sexually transmitted pathogen and a major cofactor in HIV-1 infection. This organism uses different mechanisms to infect male and female genital tract epithelia. Receptor-mediated endocytosis of N. gonorrhoeae is the principle mechanism of entry into male urethral epithelial cells. Infection in men leads to a pronounced inflammatory response. In contrast, N. gonorrhoeae infection in women induces ruffling of the cervical epithelia, allowing a macropinocytic mechanism of entry. Infection in women is frequently asymptomatic, suggesting suppression of the inflammatory response. N. gonorrhoeae-induced membrane ruffling and inflammation suppression are consistent with the ability of this bacterium to enter cervical epithelial cells, in vitro and in vivo, by interaction with complement receptor 3 (CR3), a receptor that does not trigger an inflammatory response. This receptor is present on cervical epithelial cells but not on male urogenital tract epithelia. N. gonorrhoeae engagement of CR3 initiates a unique mechanism of bacterial-induced membrane ruffling and internalization. These studies explain why the pathology of N. gonorrhoeae infection differs between males and females. Additionally, the observation that this receptor is present on cervical epithelia may provide insight into the pathogenesis of other sexually transmitted pathogens.
The relationship between cartilage loss on magnetic resonance imaging and radiographic progression in men and women with knee osteoarthritis (2005)

While our results provide longitudinal evidence that radiographic progression of joint space narrowing is predictive of cartilage loss assessed on MRI, radiography is not a sensitive measure, and if used alone, will miss a substantial proportion of knees with cartilage loss.
Identification and super-resolution imaging of ligand-activated receptor dimers in live cells (2013)

Molecular interactions are key to many chemical and biological processes like protein function. In many signaling processes they occur in sub-cellular areas displaying nanoscale organizations and involving molecular assemblies. The nanometric dimensions and the dynamic nature of the interactions make their investigations complex in live cells. While super-resolution fluorescence microscopies offer live-cell molecular imaging with sub-wavelength resolutions, they lack specificity for distinguishing interacting molecule populations. Here we combine super-resolution microscopy and single-molecule Förster Resonance Energy Transfer (FRET) to identify dimers of receptors induced by ligand binding and provide super-resolved images of their membrane distribution in live cells. By developing a two-color universal-Point-Accumulation-In-the-Nanoscale-Topography (uPAINT) method, dimers of epidermal growth factor receptors (EGFR) activated by EGF are studied at ultra-high densities, revealing preferential cell-edge sub-localization. This methodology which is specifically devoted to the study of molecules in interaction, may find other applications in biological systems where understanding of molecular organization is crucial.
Dynamic Imaging of Emerging Resistance during Cancer Therapy (2006)

One of the greatest challenges in developing therapeutic regimens is the inability to rapidly and objectively assess tumor response due to treatment. Moreover, tumor response to therapeutic intervention in many cases is transient, and progressive alterations within the tumor may mask the effectiveness of an initially successful therapy. The ability to detect these changes as they occur would allow timely initiation of alternative approaches, maximizing therapeutic outcome. We investigated the ability of diffusion magnetic resonance imaging (MRI) to provide a sensitive measure of tumor response throughout the course of treatment, possibly identifying changes in sensitivity to the therapy. Orthotopic 9L gliomas were subjected to two separate therapeutic regimens, with one group receiving a single 5-day cycle (1omega) of low-dose 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and a second group receiving two cycles at the same dose, bisected with 2 days of rest (2omega). Apparent diffusion coefficient maps were acquired before and throughout treatment to observe changes in water mobility, and these observations were correlated to standard measures of therapeutic response and outcome. Our results showed that diffusion MRI was indeed able to detect the emergence of a drug-resistant tumor subpopulation subsequent to an initially successful cycle of BCNU therapy, leading to minimal gains from a second cycle. These diffusion MRI findings were highly correlated with tumor growth delay, animal survival, and ex vivo growth inhibition assays showing emerging resistance in excised tumors. Overall, this study highlights the ability of diffusion MRI to provide sensitive dynamic assessment of therapy-induced response, allowing early opportunities for optimization of therapeutic protocols.
Protein Domain Histochemistry (PDH) (2012)

Specialized protein domains bind to posttranslational modifications (PTMs) of proteins, such as phosphorylation or glycosylation. When such PTM-binding protein domains are used as analytical tools, the functional states of cells and tissues can be determined with high precision. Here, we describe the use of recombinant CLEC10A (CD301), a human glycoreceptor of the C-type lectin family, for the detection of ligands in sections from formalin-fixed, paraffin-embedded normal and cancerous mammary tissues. A construct, in which part of the carbohydrate recognition domain (CRD) was deleted, was used as a negative control. In comparison to normal mammary glands, a pronounced staining of tumor tissues was observed. Because the construct with the truncated CRD did not show any tissue staining, the binding of the wild-type glycoreceptor can be attributed to its carbohydrate recognition domain. To distinguish our novel approach from immunohistochemistry, we propose the designation "protein domain histochemistry" (PDH).
Quantitative Analysis of Permeation Peptide Complexes Labeled with Technetium-99m:  Chiral and Sequence-Specific Effects on Net Cell Uptake (2003)

This study investigated sequence-specific cell uptake characteristics of Tat basic domain and related permeation peptides with an emphasis on residue chirality, length, and modified side chains. Effects on cell permeation of defined basic domain sequences within a library of 42 different peptides were evaluated using transport of radiolabeled peptides into human Jurkat leukemia cells. All other factors being equal, when the chirality of the peptide sequence was changed from l to d, uptake values increased up to 13-fold. Control experiments showed that the quantitative difference in uptake could not be attributed to increased decomposition of an l- versus a d-peptide by cellular or serum proteases. Furthermore, length, sequence, and type of chelation domain impacted peptide uptake into cells. The highest level of uptake was found with the following peptides: (23) d-Tat-Orn [Ac-rkkrr-orn-rrr-AHA-kgc-amide] and (33) d-poly-Arg(9) [Ac-rrrrrrrrr-AHA-kgc-amide]. The best of these peptide sequences could be employed as in vivo imaging and drug delivery agents to translocate substrates into cells.
Antidepressant drugs: additional clinical uses. (1989)

Three decades of psychiatric practice with tricyclic, tetracyclic, and heterocyclic antidepressants have shown that these drugs are effective not only for major depression, endogenous depression in particular, but also for a range of other disorders. Tricyclic and other antidepressants are now used to treat enuresis and attention-deficit disorders in children, bulimia and anorexia nervosa, panic disorder, posttraumatic stress disorder, obsessive-compulsive disorder, chronic pain, migraine, and peptic ulcer disease. As with some of the antidepressants, the body of literature on the relationship between clinical response in these diseases and plasma or serum levels of the drugs is not complete or well understood, but for some of these disorders, sufficient preliminary serum level data are available to take advantage of therapeutic drug monitoring as an adjunct to treatment. Therapeutic monitoring can be particularly important where studies indicate that successful therapy occurs at blood levels substantially different from those used to treat depression. This paper presents a brief overview of antidepressant treatment of these disorders, focusing on the available pharmacologic data related to serum level measurements and their relation to clinical response.
Liposome Entrapment Enhances the Hypocalcemic Action of Parenterally Administered Calcitonin* (1984)

The hypocalcemic effect of liposomal-entrapped calcitonin (CT) was evaluated in rats. Salmon CT and human CT were entrapped in liposomes composed of egg phosphatidylcholine with or without an equimolar amount of cholesterol. The liposomes were separated by Sepharose 4B chromatography into fractions consisting of large multilamellar vesicles and small unilamellar vesicles. The incorporation of CT was monitored by counting [125I]CT and by specific RIA. Liposomal entrapment enhanced the hypocalcemic potency of parenterally administered salmon CT and human CT. After iv administration, the large multilamellar vesicles were more potent than small unilamellar vesicles in their hypocalcemic effect; cholesterol inclusion in the MLV liposome preparation prolonged the hypocalcemia. However, with im administration, the cholesterol-free liposomes were more potent than their cholesterol-containing counterparts regardless of size. These studies demonstrate that liposomal entrapment can be used to enhance the hypocalcemic potency of CT. It appears that both the size and composition of the liposome preparation are important in this effect, as is the route of administration. It may be possible to produce liposome-CT preparations with advantageous pharmacological characteristics.
The Preparation of Substituted Hydroxyphenyl-pyridyl-ethanols and α-Hydroxyphenyl-α-methylpyridineethanols by the Condensation of 2-, 3-, or 4-Picolyllithium with Select Hydroxy-benzaldehydes and 4-Hydroxyacetophenone (1995)

Abstract 2-, 3-, or 4-Picolyllithium was prepared in excess lithium diiso-propylamide and condensed with several hydroxy-benzaldehydes and 4-hydroxy-acetophenone to afford substituted hydroxyphenyl-pyridyl-ethanols and α-hydroxyphenyl-α-methylpyridineethanols. In two instances. 3-picolyllithium condensed with aldehydes to presumably form the hydroxyphenyl-pyridyl-ethanol, which underwent linear dehydration to the substituted pyridyl-ethylenyl-phenol.
Enhanced mass sensing using torsional and lateral resonances in microcantilevers (2004)

We present a method to detect, with enhanced sensitivity, a target mass particle attached eccentrically to a microcantilever by measuring multiple three-dimensional modes in the microcantilever vibration spectrum. Peaks in the spectrum reveal a complex coupling between the bending, torsional, and lateral motions and detailed finite element models assist in their interpretation. The mass sensitivities of the torsional and lateral mode frequencies are an order of magnitude greater, and their Q factors significantly higher, than that of the conventionally used fundamental bending mode. These modes offer significantly enhanced mass sensing capabilities within the realm of existing microcantilever technology.
The tyrosine kinase encoded by the MET proto-oncogene is activated by autophosphorylation. (1991)

Protein tyrosine kinases are crucially involved in the control of cell proliferation. Therefore, the regulation of their activity in both normal and neoplastic cells has been under intense scrutiny. The product of the MET oncogene is a transmembrane receptorlike tyrosine kinase with a unique disulfide-linked heterodimeric structure. Here we show that the tyrosine kinase activity of the MET-encoded protein is powerfully activated by tyrosine autophosphorylation. The enhancement of activity was quantitated with a phosphorylation assay of exogenous substrates. It involved an increase in the Vmax of the enzyme-catalyzed phosphotransfer reaction. No change was observed in the Km (substrate). A causal relationship between tyrosine autophosphorylation and activation of the kinase activity was proved by (i) the kinetic agreement between autophosphorylation and kinase activation, (ii) the overlapping dose-response relationship for ATP, (iii) the specificity for ATP of the activation process, (iv) the phosphorylation of tyrosine residues only, in the Met protein, in the activation step, (v) the linear dependence of the activation from the input of enzyme assayed, and (vi) the reversal of the active state by phosphatase treatment. Autophosphorylation occurred predominantly on a single tryptic peptide, most likely via an intermolecular reaction. The structural features responsible for this positive modulation of kinase activity were all contained in the 45-kDa intracellular moiety of the Met protein.
Characterization of Secrecy Capacity for General MSR Codes under Passive Eavesdropping Model. (2015)

In this paper, we revisit the problem of characterizing the secrecy capacity of MSR codes under the passive {l1, l2}-eavesdropper model, where the eavesdropper has access to data stored on l1 nodes as well as the repair traffic for an additional l2 nodes. We analyze the secrecy capacity of MSR codes from an information theory perspective. Specifically, we investigate the basic reconstruction and regeneration properties of MSR codes and find some information theoretic features on the contents of storage nodes as well as repair traffic. Leveraging these properties with a definition of the secrecy capacity, we derive new upper bounds on the secrecy capacity for MSR codes. These explicit upper bounds on the secrecy capacity bring out an interesting fact that the secrecy capacity of MSR codes is not only related to {l1, l2}, but also closely depends on ?, the amount of data downloaded from each helper node during the repair process. Similar bounds on the secrecy capacity in the literature are either restricted to the situation that l2\leq2, or based on the assumption of linear coding. To the best of our knowledge, this is a novel characterization of the secrecy capacity of general MSR codes without the above constraints.
Moral Dilemmas in the Classroom (1980)

One approach to incorporating values and ethics in a program for the gifted is to focus on hypothetical or real moral questions which invite students to resolve particular situations.
Human papillomavirus infection in oral fluids of HIV-1-positive men:prevalence and risk factors (2014)

Human papillomavirus is one of the most common sexually transmitted diseases worldwide. The natural history of oral HPV infection is unclear, and its risk factors have not been explored. Immunocompromised individuals, as exemplified by HIV patients, are at high risk for HPV-related diseases. The mean of this study is to determine the prevalence of HPV in the oral tract of HIV-1-positive male subjects and its association with risk factors. A total of 283 oral wash samples from HIV-1-positive men were tested. The oral fluid samples were used for DNA extraction and conventional PCR amplification; HPV genotyping was performed by hybridization. HPV genotyping revealed that nine samples (3.5%) were positive for HPV DNA; the major high-risk HPV types identified were 51 and 66. Worldwide studies have shown a variable prevalence of oral HPV. The diversity of genotypes and the high prevalence of multiple infections in HIV-infected subjects can be better explained by the effects of HIV-induced immunosuppression. The most important risk factors are unprotected sexual intercourse, but other factors for this infection have been described elsewhere including smoking, age and HIV-positive serostatus. In this study, smoking was the most important risk factor for acquiring oral HPV in HIV-1-infected subjects in Brazil.
A One-Sided Signal (2008)

Changes in the distribution of a lipid within the plasma membrane affect normal cell function and virus infection.
Dasher---a data entry interface using continuous gestures and language models (2000)

Existing devices for communicating information to computers are bulky, slow to use, or unreliable. Dasher is a new interface incorporating language modelling and driven by continuous two-dimensional gestures, e.g. a mouse, touchscreen, or eye-tracker. Tests have shown that this device can be used to enter text at a rate of up to 34 words per minute, compared with typical ten-finger keyboard typing of 40-60 words per minute. Although the interface is slower than a conventional keyboard, it is small and simple, and could be used on personal data assistants and by motion-impaired computer users.
Inhibition of angiogenesis by the matrix metalloprotease inhibitor N-[2R-2-(hydroxamidocarbonymethyl)-4-methylpentanoyl)]-L-tryptophan methylamide. (1994)

The inhibitor N-[2R-2-(hydroxamidocarbonymethyl)-4-methylpentanoyl)]-L- tryptophan methylamide specifically blocks several matrix metalloproteases, enzymes which are thought to be involved in angiogenesis. An extract of Walker 256 carcinoma in Hydron pellets implanted in the corneas of Sprague-Dawley rats was used to stimulate angiogenesis from the vessels of the limbus. Angiogenesis was graded visually as the distance penetrated into the cornea and the number of vessels generated. The vessel area was also measured by image analysis using Image 1 software. Continuous i.v. administration of N-[2-(hydroxamidocarbonymethyl)-4-methylpentanoyl)]- L-tryptophan methylamide at 32 mg/kg/day (n = 17) via syringe pump reduced vessel number [25.06 +/- 5.9 (SEM) compared to 65.33 +/- 9.0] and vessel area (26.14 +/- 3.2 mm2 compared with 40.96 +/- 4.6 mm2), but not distance penetrated, compared to vehicle-treated control eyes after 6 days. These results confirm the suspected role for matrix metalloproteases in angiogenesis and suggest that inhibitors of these enzymes may be angiostatic agents.
Aniracetam has proportionately smaller effects on synapses expressing long-term potentiation: Evidence that receptor changes subserve LTP (1990)

The effects of the nootropic compound aniracetam on synaptic responses expressing long-term potentiation (LTP) were compared with those on control responses in field CA1 of hippocampal slices. The drug produced smaller percentage increases in the amplitude of potentiated, as opposed to control, inputs. Field EPSPs enhanced by the paired-pulse facilitation paradigm, however, were affected to the same degree as control responses. Since aniracetam is known to selectively augment the conductance of AMPA receptor channels, these results indicate that LTP expression is likely to involve modifications of postsynaptic receptors.