gebhart/patrepeval huggingface dataset:
The PTEN tumor suppressor homolog in Caenorhabditis elegans regulates longevity and dauer formation in an insulin receptor-like signaling pathway (1999)

Inactivation of the tumor suppressor PTEN gene is found in a variety of human cancers and in cancer predisposition syndromes. Recently, PTEN protein has been shown to possess phosphatase activity on phosphatidylinositol 3,4,5-trisphosphate, a product of phosphatidylinositol 3-kinase. We have identified a homolog of PTEN in Caenorhabditis elegans and have found that it corresponds to the daf-18 gene, which had been defined by a single, phenotypically weak allele, daf-18(e1375). By analyzing an allele, daf-18(nr2037), which bears a deletion of the catalytic portion of CePTEN/DAF-18, we have shown that mutation in daf-18 can completely suppress the dauer-constitutive phenotype caused by inactivation of daf-2 or age-1, which encode an insulin receptor-like molecule and the catalytic subunit of phosphatidylinositol 3-kinase, respectively. In addition, daf-18(nr2037) dramatically shortens lifespan, both in a wild-type background and in a daf-2 mutant background that normally prolongs lifespan. The lifespan in a daf-18(nr2037) mutant can be restored to essentially that of wild type when combined with a daf-2 mutation. Our studies provide genetic evidence that, in C. elegans, the PTEN homolog DAF-18 functions as a negative regulator of the DAF-2 and AGE-1 signaling pathway, consistent with the notion that DAF-18 acts a phosphatidylinositol 3,4,5-trisphosphate phosphatase in vivo. Furthermore, our studies have uncovered a longevity-promoting activity of the PTEN homolog in C. elegans.
Stacking energies in DNA (1991)

Variations in base mono- and dipoles result in variations in stacking energies for the 10 unique neighbor pairs in DNA. Stacking energies for pair M on N, expressed as TMN, were derived by matrix decomposition of a large set of linear algebraic expressions relating the measured Tm for subtransitions emanating from large polymeric DNAs, and the fractional neighbor frequencies, fMN, for the domains responsible for the transitions, Tm = sigma fMNTMN. Tm were determined for subtransitions that dissociate in approximately all-or-none fashion in high resolution melting profiles of partially deleted and recombinant forms of pBR322 DNA. Three different analytical maneuvers were undertaken to resolve subtransitions: site-specific cleavage of domains; deletion of domains; and addition of domains. Three dozen domains of widely divergent, quasi-random neighbor frequencies were identified and assigned, resulting in a unique set of values for TMN with standard deviation, sigma = +/- 0.23 degree C. The average difference between calculated and experimental Tm for domains is only +/- 0.17 degree C, indicating that the thermodynamic properties of these domains are not in any way unusual. Assuming delta S to be constant for all pairs, the corresponding delta HMN are found to have a precision of +/- 10 calories.mol-1 and an accuracy of +/- 606 calories.mol-1. TMN used to calculate melting curves by statistical mechanical analysis of sequences of the different plasmid specimens in this study were in quantitative agreement with observed curves for most sequences. These TMN differ significantly from those determined previously and also correlate poorly with values determined by quantum chemical analysis. Stabilities of neighbor pairs, expressed as the difference in free energy between that for a given pair (MN) and that for the average of like pairs (M, N), depend on the relationship of stacked purines and pyrimidines as follows. delta delta Gpu-py(-466 cal) greater than delta delta Gpu-pu(+52 cal) greater than delta delta Gpy-pu(+335 cal) Differences between experimental Tm and Tm calculated with TMN for the isolated neighbor pairs in the B-conformation are useful in the identification of altered structures and unusual modes of dissociation of helixes. A significantly higher Tm is observed for the highly biased repeated sequence synthetic helixes dA.dT, d(AGC).d(GCT), and d(GAT).d(ATC), reflecting auxiliary sources of stability such as bifurcated hydrogen bonds and/or altered structures for these helixes.
Reproducible Imaging and Dissection of Plasmid DNA Under Liquid with the Atomic Force Microscope (1992)

Reproducible images of uncoated DNA in the atomic force microscope (AFM) have been obtained by imaging plasmid DNA on mica in n-propanol. Specially sharpened AFM tips give images with reproducible features several nanometers in size along the DNA. Plasmids can be dissected in propanol by increasing the force applied by the AFM tip at selected locations.
Apatite formation on/in hydrogel matrices using an alternate soaking process: II. Effect of swelling ratios of poly(vinyl alcohol) hydrogel matrices on apatite formation (1999)

In our previous study, we reported a novel method of apatite formation on/in a three-dimensional hydrogel matrix. Using this method, bone-like apatite could be formed on/in the hydrogel matrix under normal conditions in vitro. A poly(vinyl alcohol) (PVA) gel was used as a model matrix. The method consists of two steps: first, water is transformed in a PVA gel with a CaCl2/Tris-HCl aqueous solution (pH 7.4) and second, the gel is soaked in a Na2HPO4 aqueous solution. In the present study, we report a detailed study of the effects of the swelling ratios of PVA gels on apatite formation. Cross-sectional observations and gravimetric measurements of PVA gels with various swelling ratios were done. The amount of apatite formed on/in PVA gels increased almost linearly with an increase in the reaction cycles. The rates of apatite formation on/in PVA gels largely depended on the swelling ratios, which were approximately 0.48, 0.61, 1.28, and 1.55 mg per cycle for swelling ratios of 4.1, 10.4, 16.8, and 30.1, respectively. The apatite content in PVA-apatite composites that was obtained by this method also increased with an increase of the reaction cycles. After six reaction cycles, a PVA gel with a high swelling ratio contains approximately 70 wt% of formed apatite in the composite. On the other hand, a gel with a low swelling ratio contains about 15 wt% of formed apatite in the composite. Cross-sectional views of the PVA gels after each cycle showed that apatite crystals were formed, not only on the surface of the gel but also within it after fifteen reaction cycles. The hydrogel-apatite composites that were obtained using an alternative soaking process will be useful as not only bone substitute materials but also as soft tissue adhesive materials.
Oscillatory Protein Expression Dynamics Endows Stem Cells with Robust Differentiation Potential (2011)

The lack of understanding of stem cell differentiation and proliferation is a fundamental problem in developmental biology. Although gene regulatory networks (GRNs) for stem cell differentiation have been partially identified, the nature of differentiation dynamics and their regulation leading to robust development remain unclear. Herein, using a dynamical system modeling cell approach, we performed simulations of the developmental process using all possible GRNs with a few genes, and screened GRNs that could generate cell type diversity through cell-cell interactions. We found that model stem cells that both proliferated and differentiated always exhibited oscillatory expression dynamics, and the differentiation frequency of such stem cells was regulated, resulting in a robust number distribution. Moreover, we uncovered the common regulatory motifs for stem cell differentiation, in which a combination of regulatory motifs that generated oscillatory expression dynamics and stabilized distinct cellular states played an essential role. These findings may explain the recently observed heterogeneity and dynamic equilibrium in cellular states of stem cells, and can be used to predict regulatory networks responsible for differentiation in stem cell systems.
Template properties of mutagenic cytosine analogues in reverse transcription (2006)

We have studied the mutagenic properties of ribonucleotide analogues by reverse transcription to understand their potential as antiretroviral agents by mutagenesis of the viral genome. The templating properties of nucleotide analogues including 6-(beta-D-ribofuranosyl)-3,4-dihydro-8H-pyrimido[4,5-c](1,2)oxazin-7-one, N4-hydroxycytidine, N4-methoxycytidine, N4-methylcytidine and 4-semicarbazidocytidine, which have been reported to exhibit ambiguous base pairing properties, were examined. We have synthesized RNA templates using T3 RNA polymerase, and investigated the specificity of the incorporation of deoxyribonucleoside triphosphates opposite these cytidine analogues in RNA by HIV and AMV reverse transcriptases. Except for N4-methylcytidine, both enzymes incorporated both dAMP and dGMP opposite these analogues in RNA. This indicates that they would be highly mutagenic if present in viral RNA. To study the basis of the differences among the analogues in the incorporation ratios of dAMP to dGMP, we have carried out kinetic analysis of incorporation opposite the analogues at a defined position in RNA templates. In addition, we examined whether the triphosphates of these analogues were incorporated competitively into RNA by human RNA polymerase II. Our present data supports the view that these cytidine analogues are mutagenic when incorporated into RNA, and that they may therefore be considered as candidates for antiviral agents by causing mutations to the retroviral genome.
The X-Ray Structure of the Haloalcohol Dehalogenase HheA from Arthrobacter sp. Strain AD2: Insight into Enantioselectivity and Halide Binding in the Haloalcohol Dehalogenase Family (2006)

Haloalcohol dehalogenases are bacterial enzymes that cleave the carbon-halogen bond in short aliphatic vicinal haloalcohols, like 1-chloro-2,3-propanediol, some of which are recalcitrant environmental pollutants. They use a conserved Ser-Tyr-Arg catalytic triad to deprotonate the haloalcohol oxygen, which attacks the halogen-bearing carbon atom, producing an epoxide and a halide ion. Here, we present the X-ray structure of the haloalcohol dehalogenase HheA(AD2) from Arthrobacter sp. strain AD2 at 2.0-A resolution. Comparison with the previously reported structure of the 34% identical enantioselective haloalcohol dehalogenase HheC from Agrobacterium radiobacter AD1 shows that HheA(AD2) has a similar quaternary and tertiary structure but a much more open substrate-binding pocket. Docking experiments reveal that HheA(AD2) can bind both enantiomers of the haloalcohol substrate 1-p-nitrophenyl-2-chloroethanol in a productive way, which explains the low enantiopreference of HheA(AD2). Other differences are found in the halide-binding site, where the side chain amino group of Asn182 is in a position to stabilize the halogen atom or halide ion in HheA(AD2), in contrast to HheC, where a water molecule has taken over this role. These results broaden the insight into the structural determinants that govern reactivity and selectivity in the haloalcohol dehalogenase family.
Up-regulation of 42 kDa tubulin alpha-6 chain fragment in well-differentiated hepatocellular carcinoma tissues from patients infected with hepatitis C virus. (2011)

We performed proteomic differential display analysis of hepatitis C virus-associated 21 human hepatocellular carcinoma (HCV-HCC) tissues by using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). One of the numerous spots which was located next to three spots of glutamine synthetase showed stronger intensity in well-differentiated HCC tissues compared to non-cancerous tissues. Samples from 6 out of 21 patients showed up-regulation of this spot compared to non-cancerous tissues. After in-gel digestion, MALDITOF/MS identified the spot as tubulin alpha-6 chain. Two-dimensional immunoblot analysis confirmed that this spot was indeed tubulin alpha, and this spot was stronger in cancerous tissues than in noncancerous tissues. These results suggest that tubulin alpha-6 chain is one of the candidates for biomarkers for well-differentiated HCV-associated HCC.
The ability to re‐express polysialylated NCAM in soleus muscle after denervation is reduced in aged rats compared to young adult rats (1995)

The neural cell-adhesion molecule, NCAM, contains an unusual homopolymer of sialic acid units, polysialic acid. This carbohydrate seems to be involved in neurite outgrowth, bundling and branching, processes which are important during reinnervation. In aged rats, reinnervation of denervated muscle fibres is incomplete. In this study, age-related changes in the degree of polysialylation of NCAM re-expressed after denervation were examined using a monoclonal antibody recognizing polysialic acid and a polyclonal antibody recognizing NCAM. The results show that, after denervation, the degree of polysialylation on NCAM was clearly reduced in rat soleus muscle of aged, compared to young, adult rats. This age-related change in expression of polysialic acid probably influences the reinnervation process in aged muscle.
Remdesivir and GS-441524 Retain Antiviral Activity against Delta, Omicron, and Other Emergent SARS-CoV-2 Variants (2022)

Genetic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence and rapid spread of multiple variants throughout the pandemic, of which Omicron is currently the predominant variant circulating worldwide. SARS-CoV-2 variants of concern/variants of interest (VOC/VOI) have evidence of increased viral transmission, disease severity, or decreased effectiveness of vaccines and neutralizing antibodies. Remdesivir (RDV [VEKLURY]) is a nucleoside analog prodrug and the first FDA-approved antiviral treatment of COVID-19. Here, we present a comprehensive antiviral activity assessment of RDV and its parent nucleoside, GS-441524, against 10 current and former SARS-CoV-2 VOC/VOI clinical isolates by nucleoprotein enzyme-linked immunosorbent assay (ELISA) and plaque reduction assay. Delta and Omicron variants remained susceptible to RDV and GS-441524, with 50% effective concentration (EC<sub>50</sub>) values 0.30- to 0.62-fold of those observed against the ancestral WA1 isolate. All other tested variants exhibited EC<sub>50</sub> values ranging from 0.13- to 2.3-fold of the observed EC<sub>50</sub> values against WA1. Analysis of nearly 6 million publicly available variant isolate sequences confirmed that Nsp12, the RNA-dependent RNA polymerase (RdRp) target of RDV and GS-441524, is highly conserved across variants, with only 2 prevalent changes (P323L and G671S). Using recombinant viruses, both RDV and GS-441524 retained potency against all viruses containing frequent variant substitutions or their combination. Taken together, these results highlight the conserved nature of SARS-CoV-2 Nsp12 and provide evidence of sustained SARS-CoV-2 antiviral activity of RDV and GS-441524 across the tested variants. The observed pan-variant activity of RDV supports its continued use for the treatment of COVID-19 regardless of the SARS-CoV-2 variant.
CR1/CR2 Interactions Modulate the Functions of the Cell Surface Epidermal Growth Factor Receptor (2004)

Recent crystallographic data on the isolated extracellular domain of the epidermal growth factor receptor (EGFR) have suggested a model for its activation by ligand. We have tested this model in the context of the full-length EGFR displayed at the cell surface, by introducing mutations in two regions (CR1 and CR2) of the extracellular domain thought to be critical for regulation of receptor activation. Mutations in the CR1 and CR2 domains have opposing effects on ligand binding affinity, receptor dimerization, tyrosine kinase activation, and signaling competence. Tyr(246) is a critical residue in the CR1 loop, which is implicated in the positioning and stabilization of the receptor dimer interface after ligand binding; mutations of Tyr(246) impair or abolish receptor function. Mutations in CR2, which weaken the interaction that restricts the receptor to the tethered (inactive) state, enhance responsiveness to EGF by increasing affinity for the ligand. However, weakening of the CR1/CR2 interaction does not result in spontaneous activation of the receptors' kinase. We have used an antibody (mAb 806), which recognizes a transition state of the EGF receptor between the negatively constrained, tethered state and the fully active back-to-back dimer conformation, to follow conformational changes in the wild-type and mutant EGF receptors after ligand binding. Our results suggest that EGFR on the cell surface can be untethered, but this form is inactive; thus, untethering of the receptor is not sufficient for activation, and ligand binding is essential for the correct positioning of the two receptor subunits to achieve kinase activation.
Staden: Searching for Motifs in Protein Sequences (1994)

The program PIP contains several ways of defining and searching for motifs (,). Searches for exact matches and percentage matches, the use of score matrices, and the creation and use of weight matrices are described here. All of the searches produce both listed and graphical output.
State of the Art in Stereoscopic and Autostereoscopic Displays (2011)

Underlying principles of stereoscopic direct-view displays, binocular head-mounted displays, and autostereoscopic direct-view displays are explained and some early work as well as the state of the art in those technologies are reviewed. Stereoscopic displays require eyewear and can be categorized based on the multiplexing scheme as: 1) color multiplexed (old technology but there are some recent developments; low-quality due to color reproduction and crosstalk issues; simple and does not require additional electronics hardware); 2) polarization multiplexed (requires polarized light output and polarization-based passive eyewear; high-resolution and high-quality displays available); and 3) time multiplexed (requires faster display hardware and active glasses synchronized with the display; high-resolution commercial products available). Binocular head-mounted displays can readily provide 3-D, virtual images, immersive experience, and more possibilities for interactive displays. However, the bulk of the optics, matching of the left and right ocular images and obtaining a large field of view make the designs quite challenging. Some of the recent developments using unconventional optical relays allow for thin form factors and open up new possibilities. Autostereoscopic displays are very attractive as they do not require any eyewear. There are many possibilities in this category including: two-view (the simplest implementations are with a parallax barrier or a lenticular screen), multiview, head tracked (requires active optics to redirect the rays to a moving viewer), and super multiview (potentially can solve the accommodation–convergence mismatch problem). Earlier 3-D booms did not last long mainly due to the unavailability of enabling technologies and the content. Current developments in the hardware technologies provide a renewed interest in 3-D displays both from the consumers and the display manufacturers, which is evidenced by the recent commercial products and new research results in this field.
Software‐defined network‐based prioritization to avoid video freezes in HTTP adaptive streaming (2016)

Summary HTTP adaptive streaming (HAS) is becoming the de facto standard for video streaming services over the Internet. In HAS, each video is segmented and stored in different qualities. Rate adaptation heuristics, deployed at the client, allow the most appropriate quality level to be dynamically requested, based on the current network conditions. It has been shown that state‐of‐the‐art heuristics perform suboptimal when sudden bandwidth drops occur, therefore leading to freezes in the video playout, the main factor influencing users' quality of experience (QoE). This issue is aggravated in case of live events, where the client‐side buffer has to be kept as small as possible in order to reduce the playout delay between the user and the live signal. In this article, we propose a framework capable of increasing the QoE of HAS clients by reducing video freezes. The framework is based on OpenFlow, a widely adopted protocol to implement the software‐defined networking principle. An OpenFlow controller is in charge of introducing prioritized delivery of HAS segments, based on the network conditions and the HAS clients' status. Particularly, the HAS clients' status is obtained without any explicit clients‐to‐controller communication, and thus, no extra signaling is introduced into the network. Moreover, this OpenFlow controller is transparent to the quality decision process of the clients, as it assists the delivery of the segments, but it does not determine the actual quality to be requested. In order to provide a comprehensive analysis of the proposed approach, we investigate the performance of the proposed OpenFlow‐based framework in the presence of realistic Internet cross‐traffic. Particularly, we model two types of applications, namely, HTTP web browsing and progressive download video streaming, which currently represent the majority of Internet traffic together with HAS. By evaluating this novel approach through emulation in several multi‐client scenarios, we show how the proposed approach can reduce freeze time for the HAS clients due to network congestion up to 10 times compared with state‐of‐the‐art heuristics, without impacting the performance of the cross‐traffic applications. Copyright © 2016 John Wiley &amp; Sons, Ltd.
Lifetime determination of low sample concentrations: a new cuvette for highly accurate and sensitive fluorescence measurements. (1992)

A new cuvette was developed for spectrofluorometric measurements which increases the efficiency of recorded fluorescence emission by at least two-fold, decreasing, at the same time, the noise component of the record. It is suited for both steady-state and dynamic fluorescence measurements. Comparative data for both the classical and the novel cuvettes are presented here.
Overexpression of HER-2 as a resistance mechanism to hormonal therapy for breast cancer. (2001)

Hormonal therapy leads to improved survival in oestrogen receptor (ER) positive early breast cancer and long-term responses in advanced disease. However, resistance to such therapy is a serious clinical problem. This article considers the data for and against there being a significant role for the oncogene HER-2 in such resistance. Transfection of HER-2 into MCF-7 cells leads to resistance to tamoxifen but data differ in relation to the oestrogen dependence of such cells. A number of retrospective studies have been conducted of HER-2 status in adjuvant trials of tamoxifen. Most of these also suggest a negative role but individually the studies do not have the statistical power to be conclusive. Recent studies in the neoadjuvant context have shown a significant antiproliferative effect of endocrine therapy in HER-2 positive/ER positive tumours but this is much less than in HER-2 negative/ER positive tumours. It is concluded that incomplete hormonal resistance results from co-expression of HER-2 and ER and that this may differ between different hormonal agents.
2,4-Bis(Arylamino)-6-Methyl Pyrimidines as Antimicrobial Agents (1981)

Department of Chemistry, Bose Institute, Calcutta-700 009 <em>Manuscript received 8 September 1980, accepted 10 March 1981</em> Nine 2,4-<em>bis</em>(arylamino) pyrimidines having - CH<sub>3</sub> substitution either in C-5 or C-6 in the pyrimidine ring have been synthesized. All these compounds have been tested against some gram-positive and gram-negative bacteria and a pathogenic strain of yeast, <em>Candida</em> <em>albicans</em> for their antimicrobial activity. 2,4-<em>bis</em>(<em>p</em>-chloro-anilino)- and 2,4-<em>bis</em>(<em>p</em>-bromo-anilino) pyrimidine derivatives have been found to possess significant activity.
Estimation of the ED50 and Its Error by Means of Logarithmic-Probit Graph Paper. (1944)

SummaryA log-probit graph paper is described by which a simple graphic estimation of the ED50 and its standard error may be quickly made.