gebhart/patrepeval huggingface dataset:
Adaptive Computation Time for Recurrent Neural Networks (2016)

This paper introduces Adaptive Computation Time (ACT), an algorithm that allows recurrent neural networks to learn how many computational steps to take between receiving an input and emitting an output. ACT requires minimal changes to the network architecture, is deterministic and differentiable, and does not add any noise to the parameter gradients. Experimental results are provided for four synthetic problems: determining the parity of binary vectors, applying binary logic operations, adding integers, and sorting real numbers. Overall, performance is dramatically improved by the use of ACT, which successfully adapts the number of computational steps to the requirements of the problem. We also present character-level language modelling results on the Hutter prize Wikipedia dataset. In this case ACT does not yield large gains in performance; however it does provide intriguing insight into the structure of the data, with more computation allocated to harder-to-predict transitions, such as spaces between words and ends of sentences. This suggests that ACT or other adaptive computation methods could provide a generic method for inferring segment boundaries in sequence data.
Infectious Bronchitis Virus Detection in Allantoic Fluid using the Polymerase Chain Reaction and a DNA Probe (1992)

A rapid extraction procedure was developed to purify infectious bronchitis virus (IBV) RNA from the allantoic fluid of inoculated embryonating eggs. Reverse transcription of viral RNA and the polymerase chain reaction (PCR) were used to amplify the viral genome from eight different strains of IBV comprising five different serotypes. A biotinylated DNA probe, prepared to a sequence within the PCR amplification product of the Beaudette strain of IBV, was used in a dot-hybridization assay; it detected the amplification products of all of the IBV strains examined. Reverse transcription and PCR amplification were judged to be specific for IBV. This was because amplification products were not detected by agarose gel electrophoresis or by dot-hybridization when template used in the PCR was extracted from allantoic fluid and the chorioallantoic membrane of uninoculated embryonating eggs or from allantoic fluid of embryonating eggs inoculated with other chicken upper respiratory viruses.
Long‐Persistent Luminescence: Wide‐Range Tuning and Enhancement of Organic Long‐Persistent Luminescence Using Emitter Dopants (Adv. Mater. 38/2018) (2018)

As described by Ryota Kabe, Chihaya Adachi, and Kazuya Jinnai in article number 1800365, greenish-blue to red and even warm white organic long-persistent luminescence (OLPL) in organic luminescent materials is achieved by energy transfer from an exciplex in the OLPL matrix to the emitter dopants. The dopants improve the brightness and emission duration respectively through efficient radiative decay and the trapping of electrons.
Gene Introduction Into Animal Tissues (1995)

Gene therapy is an approach to treat various incurable diseases by expressing foreign genes directly into the human body. A number of vector systems to introduce genetic information into tissue cells have been developed for this purpose. This review provides a critical discussion of the characteristics of various vector systems and their possible application in human gene therapy.
Dasatinib versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia (2010)

Dasatinib, administered once daily, as compared with imatinib, administered once daily, induced significantly higher and faster rates of complete cytogenetic response and major molecular response. Since achieving complete cytogenetic response within 12 months has been associated with better long-term, progression-free survival, dasatinib may improve the long-term outcomes among patients with newly diagnosed chronic-phase CML. (ClinicalTrials.gov number, NCT00481247.)
SULPHASALAZINE IS A POTENT INHIBITOR OF PROSTAGLANDIN 15‐HYDROXYDEHYDROGENASE: POSSIBLE BASIS FOR THERAPEUTIC ACTION IN ULCERATIVE COLITIS (1978)

Sulphasalazine is a potent and selective inhibitor in vitro of prostaglandin 15‐hydroxydehydrogenase in rabbit colon (ID 5() = 50 μ m ) and in several other organs of different species, but does not inhibit prostaglandin A‐13 reductase or microsomal prostaglandin synthesis from arachidonic acid. It is suggested that this action may underly the therapeutic usefulness of sulphasalazine in ulcerative colitis for the prevention of relapse.
Time-lapse cinematographic analysis of hatching of normal and frozen—thawed cow blastocysts (1980)

This paper describes time-lapse cinematography on cattle blastocysts hatching from the zona in vitro. Four normal morulae were taken on Day 6 and cultured for 5 days. During this period 3 formed normal blastocysts of which 2 hatched from the zona without undergoing any contractions. Early blastocysts were taken on Day 7, frozen and stored at low temperature. After thawing they were cultured; only 1 of the 11 behaved like the normal embryos, and the others underwent contractions and failed to hatch. These contractions could be interpreted as a sign of an alteration of the trophoblastic structure and properties.
Moisturizing effects of topical nicotinamide on atopic dry skin (2004)

Nicotinamide cream is a more effective moisturizer than white petrolatum on atopic dry skin, and may be used as a treatment adjunct in atopic dermatitis.
Characterization of group B streptococcal glyceraldehyde-3-phosphate dehydrogenase: surface localization, enzymatic activity, and proteinprotein interactions (2003)

During characterization of the surface antigens of serotype III group B streptococci (GBS), a protein with an apparent M(r) of approximately 173,500 migrating on a SDS--polyacrylamide gel was found to have an N-terminal amino acid sequence identical to that of the plasmin receptor (Plr) of group A streptococci, a surface-localized glyceraldehyde-3-phosphate dehydrogenase (GAPDH). This work begins to characterize GBS GAPDH and to assess its functional activity on the cell surface. The 1.0-kb gapC gene of GBS was amplified by PCR. plr and gapC demonstrated 87% homology. An anti-Plr monoclonal antibody reacted with GBS whole cells, suggesting GBS GAPDH is surface localized. Multiple serotypes of GBS demonstrated functional GAPDH on their surfaces. The anti-Plr monoclonal antibody recognized GBS protein bands of approximately 41 and 173.5 kDa, by Western blot. Presumably, these represent monomeric and tetrameric forms of the GAPDH molecule. GBS GAPDH was demonstrated by Western blot analysis to interact with lys- and glu-plasminogens. Fluid-phase GBS GAPDH interacted, by means of ELISA, with immobilized lys-plasminogen, glu-plasminogen, actin, and fibrinogen. Enzymatically active GAPDH, capable of binding cytoskeletal and extracellular matrix proteins, is expressed on the surface of GBS.
Antibody directed enzyme prodrug therapy (ADEPT): a review of the experimental and clinical considerations. (1999)

Over the last decade several attempts have been made to generate an active drug from an inactive precursor, by the action of an enzyme present predominantly at the tumour site. The aim was to develop a new, less cytotoxic strategy for the treatment of cancer, by exploiting properties distinguishing neoplastic and normal cells. In fact, monoclonal antibodies were used to carry enzymes at the tumour sites, in a two-step approach, known as Antibody Directed Enzyme Prodrug Therapy (ADEPT). We reviewed the experimental and clinical considerations of this strategy and we presented its problems and limitations. We concluded that ADEPT holds the potential of an effective and relatively non-toxic treatment of cancer and it is expected that the research which is in progress will make ADEPT an important element of the anticancer armament.
White matter tractography using diffusion tensor deflection (2003)

Diffusion tensor MRI provides unique directional diffusion information that can be used to estimate the patterns of white matter connectivity in the human brain. In this study, the behavior of an algorithm for white matter tractography is examined. The algorithm, called TEND, uses the entire diffusion tensor to deflect the estimated fiber trajectory. Simulations and imaging experiments on in vivo human brains were performed to investigate the behavior of the tractography algorithm. The simulations show that the deflection term is less sensitive than the major eigenvector to image noise. In the human brain imaging experiments, estimated tracts were generated in corpus callosum, corticospinal tract, internal capsule, corona radiata, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto-occipital fasciculus, and uncinate fasciculus. This approach is promising for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship between major fiber trajectories and the location and extent of brain lesions.
4-Fluorinatedl-lysine analogs as selective i-NOS inhibitors: methodology for introducing fluorine into the lysine side chain (2003)

In the literature, the introduction of fluorine into bioactive molecules has been known to enhance the biological activity relative to the parent molecule. Described in this article is the synthesis of 4R-fluoro-L-NIL (12) and 4,4-difluoro-L-NIL (23) as part of our iNOS program. Both 12 and 23 were found to be selective iNOS inhibitors as shown in Table 2 below. Secondarily, methodology to synthesize orthogonally protected 4-fluoro-L-lysine and 4,4-difluoro-L-lysine has been developed.
Differential Regulation of Membrane Type 1-Matrix Metalloproteinase Activity by ERK 1/2- and p38 MAPK-modulated Tissue Inhibitor of Metalloproteinases 2 Expression Controls Transforming Growth Factor-β1-induced Pericellular Collagenolysis (2004)

Acquisition of matrix metalloproteinase-2 (MMP-2) activity is temporally associated with increased migration and invasiveness of cancer cells. ProMMP-2 activation requires multimolecular complex assembly involving proMMP-2, membrane type 1-MMP (MT1-MMP, MMP-14), and tissue inhibitor of metalloproteinases-2 (TIMP-2). Because transforming growth factor-beta1 (TGF-beta1) promotes tumor invasion in advanced squamous cell carcinomas, the role of TGF-beta1 in the regulation of MMP activity in a cellular model of invasive oral squamous cell carcinoma was examined. Treatment of oral squamous cell carcinoma cells with TGF-beta1 promoted MMP-dependent cell scattering and collagen invasion, increased expression of MMP-2 and MT1-MMP, and enhanced MMP-2 activation. TGF-beta1 induced concomitant activation of ERK1/2 and p38 MAPK, and kinase inhibition studies revealed a negative regulatory role for ERK1/2 in modulating acquisition of MMP-2 activity. Thus, a reciprocal effect on proMMP-2 activation was observed whereupon blocking ERK1/2 phosphorylation promoted proMMP-2 activation and MT1-MMP activity, whereas inhibiting p38 MAPK activity decreased proteolytic potential. The cellular mechanism for the control of MT1-MMP catalytic activity involved concurrent reciprocal modulation of TIMP-2 expression by ERK1/2 and p38 MAPKs, such that inhibition of ERK1/2 phosphorylation decreased TIMP-2 production, and down-regulation of p38 MAPK activity enhanced TIMP-2 synthesis. Further, p38 MAPK inhibition promoted ERK1/2 phosphorylation, providing additional evidence for cross-talk between MAPK pathways. These observations demonstrate the complex reciprocal effects of ERK1/2 and p38 MAPK in the regulation of MMP activity, which could complicate the use of MAPK-specific inhibitors as therapeutic agents to down-regulate the biologic effects of TGF-beta1 on pericellular collagen degradation and tumor invasion.
Telephone Number Mapping (ENUM) Service Registration for Presence Services (2005)

This document registers a Telephone Number Mapping (ENUM) service for
presence. Specifically, this document focuses on provisioning pres
URIs in ENUM. [STANDARDS-TRACK]
Role of the PAR4 Thrombin Receptor in Stabilizing Platelet-platelet Aggregates as Revealed by a Patient with Hermansky-Pudlak Syndrome (2002)

Individuals with Hermansky-Pudlak Syndrome (HPS) lack platelet dense granules and have no ADP-autocrine response. Despite these platelet deficiencies, HPS patients exhibit a surprisingly mild bleeding phenotype. We hypothesize that activation of the PAR4 thrombin receptor compensates for the lack of an ADP-autocrine response by the P2Y12 ADP receptor in individuals with HPS. Here, we determine that PAR4 activation by thrombin occurs well after ADP release from dense granules in normal individuals. However, the signal from PAR4 stabilizes platelet-platelet aggregate formation in the absence of P2Y12 activation by ADP. Thus, the strong signal emanating from PAR4 during platelet aggregation would provide an explanation for the mild bleeding diathesis of HPS.
Mouse models in non‐alcoholic fatty liver disease and steatohepatitis research (2006)

Non-alcoholic fatty liver disease (NAFLD) represents a histological spectrum of liver disease associated with obesity, diabetes and insulin resistance that extends from isolated steatosis to steatohepatitis and cirrhosis. As well as being a potential cause of progressive liver disease in its own right, steatosis has been shown to be an important cofactor in the pathogenesis of many other liver diseases. Animal models of NAFLD may be divided into two broad categories: those caused by genetic mutation and those with an acquired phenotype produced by dietary or pharmacological manipulation. The literature contains numerous different mouse models that exhibit histological evidence of hepatic steatosis or, more variably, steatohepatitis; however, few replicate the entire human phenotype. The genetic leptin-deficient (ob/ob) or leptin-resistant (db/db) mouse and the dietary methionine/choline-deficient model are used in the majority of published research. More recently, targeted gene disruption and the use of supra-nutritional diets to induce NAFLD have gained greater prominence as researchers have attempted to bridge the phenotype gap between the available models and the human disease. Using the physiological processes that underlie the pathogenesis and progression of NAFLD as a framework, we review the literature describing currently available mouse models of NAFLD, highlight the strengths and weaknesses of established models and describe the key findings that have furthered the understanding of disease pathogenesis.
Enhancing the Activity of a β-Helical Antifreeze Protein by the Engineered Addition of Coils (2004)

The effectiveness of natural antifreeze proteins in inhibiting the growth of a seed ice crystal seems to vary with protein size. Here we have made use of the extreme regularity of the beta-helical antifreeze protein from the beetle Tenebrio molitor to explore systematically the relationship between antifreeze activity and the area of the ice-binding site. Each of the 12-amino acid, disulfide-bonded central coils of the beta-helix contains a Thr-Xaa-Thr ice-binding motif. By adding coils to, and deleting coils from, the seven-coil parent antifreeze protein, we have made a series of constructs with 6-11 coils. Misfolded forms of these antifreezes were removed by ice affinity purification to accurately compare the specific activity of each construct. There was a 10-100-fold gain in activity upon going from six to nine coils, depending on the concentration that was compared. Activity was maximal for the nine-coil construct, which gave a freezing point depression of 6.5 C degrees at 0.7 mg/mL, but actually decreased for the 10- and 11-coil constructs. This small loss in activity might result from the accumulation of a slight mismatch between the spacing of the ice-binding threonine residues and the O atoms of the ice lattice.
Antiviral Activities of Methylated Nordihydroguaiaretic Acids. 2. Targeting Herpes Simplex Virus Replication by the Mutation Insensitive Transcription Inhibitor Tetra-O-methyl-NDGA (1998)

We had previously reported that tetramethyl-O-NGDA (M4N), a synthetic derivative of the naturally occurring nordihydroguaiaretic acid (NDGA), is able to inhibit HIV Tat transactivation by blocking host Sp1 protein at the Sp1 cognate binding site on the HIV LTR promoter. The present studies were undertaken to examine whether M4N is able to inhibit the replication of herpes simplex virus (HSV), another Sp1-regulated virus. The results showed that in Vero cells, M4N inhibits at micromolar levels (IC50 = 43.5 microM) the expression of the herpes immediate early gene (alpha-ICP4), which is essential for HSV replication. An electrophoretic mobility shift assay, examining Sp1 binding to the alpha-ICP4 promoter, showed a significant inhibition of the control bands: 88% inhibition of the fast moving band (FMB) and 45% of the slow moving band (SMB), at 100 microM of drug concentration. Comparative studies between M4N and acycloguanosine (acyclovir, ACV) in cultured Vero cells revealed an interesting pattern in the drug sensitivity (IC50) and cytotoxicity (TC50) parameters. For M4N, the IC50 varied between 11.7 and 4 microM in 10 passages of HSV-1 and 4 passages of HSV-2 with no indication for a requirement of higher drug concentration. In contrast, for acyclovir, the IC50 increased from 7 microM in the first passage to 444 microM in the tenth passage of HSV-1, and >88 microM for the fourth passage of HSV-2, indicating a rapid build-up of drug resistance against acyclovir. While the selective index (SI), defined as the ratio: TC50/IC50, remained relatively constant for M4N; it dropped 60-fold for acyclovir in the endpoints of viral passages. Drug sensitivity for M4N toward the acyclovir-sensitive strain (sm44) and the acyclovir-resistant strain (ACV-10) of HSV-1 was similar, indicating no cross-resistance between M4N and acyclovir in their anti-HSV effects. These results may have an important clinical relevance since HSV has been shown to be a factor for spreading of HIV.
Carbon Material and Bioenergetic Balances of Xylitol Production from Corncobs by Debaryomyces hansenii (2003)

The effect of oxygenation on xylitol production by the yeast Debaryomyces hansenii has been investigated in this work using the liquors from corncob hydrolysis as the fermentation medium. The concentrations of consumed substrates (glucose, xylose, arabinose, acetate and oxygen) and formed products (xylitol, arabitol, ethanol, biomass and carbon dioxide) have been used, together with those previously obtained varying the hydrolysis technique, the level of adaptation of the microorganism, the sterilization procedure and the initial substrate and biomass concentrations, in carbon material balances to evaluate the percentages of xylose consumed by the yeast for the reduction to xylitol, alcohol fermentation, respiration and cell growth. The highest xylitol concentration (71 g/L) and volumetric productivity (1.5 g/L.h) were obtained semiaerobically using detoxified hydrolyzate produced by autohydrolysis-posthydrolysis, at starting levels of xylose (S(0)) and biomass (X(0)) of about 100 g/L and 12 g(DM)/L, respectively. No less than 80% xylose was addressed to xylitol production under these conditions. The experimental data collected in this work at variable oxygen levels allowed estimating a P/O ratio of 1.16 mol(ATP)/mol(O). The overall ATP requirements for biomass production and maintenance demonstrated to remarkably increase with X(0) and for S(0) >or= 130 g/L and to reach minimum values (1.9-2.1 mol(ATP)/C-mol(DM)) just under semiaerobic conditions favoring xylitol accumulation.
Abstract #4: Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating HDAC6 (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Background: Sulforaphane is an isothiocyanate compound found in broccoli, the consumption of which is associated with reduced rates of prostate cancer development. Sulforaphane, itself, prevents and induces regression of prostate and other malignancies in pre-clinical models, but the full mechanisms by which it exerts these effects remain unclear. Recent reports show that sulforaphane inhibits histone deacetylation and impairs the growth of prostate cancer cells. However, it remains quite possible that this agent may inhibit deacetylation of non-histone proteins, too. We therefore tested the hypothesis that sulforaphane treatment inhibits deacetylation of key regulatory proteins in prostate cancer cells. Specifically, we focused on the acetylation state of HSP90, a chaperone protein that stabilizes the androgen receptor (AR). We hypothesized that hyperacetylation of HSP90 using this agent would lead to AR destabilization and attenuated AR signaling. Methods: LNCaP and VCaP prostate cancer cells were used to assess the effects of treatment with sulforaphane. Co-immunoprecipitation studies were performed to assess changes in acetylation of HSP90 and its interaction with AR after sulforaphane treatment. Western blots were performed to assess the effect of increasing doses of sulforaphane on AR protein expression and the effect of proteasome inhibition on sulforaphane treatment effects. QRTPCR was performed to determine whether sulforaphane resulted in reduced AR target gene expression, and ChIP was performed to assess whether enrichment of AR was decreased at its target genes. Sulforaphane\#8217;s effects on HDAC6 enzymatic activity were assessed in an in vitro assay, and the consequences of over-expressing HDAC6, an HSP90 deacetylase, on sulforaphane treatment effects were also determined. Small interfering RNA against HDAC6 was transfected in order to compare this effect with sulforaphane treatment. Results: Sulforaphane treatment increases the acetylation of HSP90, dissociating it from AR, and consequently leads to AR protein degradation, which is reversed by proteasome inhibition, diminished AR target gene expression and reduced AR enrichment at its target genes. Sulforaphane also inhibits HDAC6 deacetylase enzymatic activity, and over-expression of HDAC6 attenuates sulforaphane-mediated AR protein depletion while small interfering RNA to HDAC6 recapitulates the sulforaphane treatment effects. Conclusions: We conclude that sulforaphane inactivation of HDAC6-mediated HSP90 deacetylation and consequent AR degradation and attenuated AR signaling may represent a principal mechanism by which this agent demonstrates activity as a chemopreventive and therapeutic agent in prostate cancer.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4.
Built-in electric-field effects in wurtzite AlGaN/GaN quantum wells (1999)

AlGaN/GaN quantum well (QW) structures are grown on c-plane sapphire substrates by molecular beam epitaxy. Control at the monolayer scale of the well thickness is achieved and sharp QW interfaces are demonstrated by the low photoluminescence linewidth. The QW transition energy as a function of the well width evidences a quantum-confined Stark effect due to the presence of a strong built-in electric field. Its origin is discussed in terms of piezoelectricity and spontaneous polarization. Its magnitude versus the Al mole fraction is determined. The role of the sample structure geometry on the electric field is exemplified by changing the thickness of the AlGaN barriers in multiple-QW structures. Straightforward electrostatic arguments well account for the overall trends of the electric-field variations.