gebhart/patrepeval huggingface dataset:
Cyclin D1 is a nuclear protein required for cell cycle progression in G1. (1993)

A cascade of events is triggered upon the addition of growth factor to quiescent mammalian cells, which ultimately restarts proliferation by inducing the transition from G0/G1 to S-phase. We have studied cyclin D1, a putative G1 cyclin, in normal diploid human fibroblasts. Cyclin D1 accumulated and reached a maximum level before S-phase upon the addition of serum to quiescent cells. The protein was localized to the nucleus, and it disappeared from the nucleus as cells proceeded into S-phase. Microinjection of anti-cyclin D1 antibodies or antisense plasmid prevented cells from entering S-phase, and the kinetics of inhibition showed that cyclin D1 is required at a point in the cell cycle earlier than cyclin A. These results demonstrate that cyclin D1 is a critical target of proliferative signals in G1.
Amyloid Fibril Formation in the Context of Full-length Protein (2003)

Beta2-microglobulin (beta2-m), a typical immunoglobulin domain made of seven beta-strands, is a major component of amyloid fibrils formed in dialysis-related amyloidosis. To understand the mechanism of amyloid fibril formation in the context of full-length protein, we prepared various mutants in which proline (Pro) was introduced to each of the seven beta-strands of beta2-m. The mutations affected the amyloidogenic potential of beta2-m to various degrees. In particular, the L23P, H51P, and V82P mutations significantly retarded fibril extension at pH 2.5. Among these, only L23P is included in the known "minimal" peptide sequence, which can form amyloid fibrils when isolated as a short peptide. This indicates that the residues in regions other than the minimal sequence, such as H51P and V82P, determine the amyloidogenic potential in the full-length protein. To further clarify the mutational effects, we measured their stability against guanidine hydrochloride of the native state at pH 8.0 and the amyloid fibrils at pH 2.5. The amyloidogenicity of mutants showed a significant correlation with the stability of the amyloid fibrils, and little correlation was observed with that of the native state. It has been proposed that the stability of the native state and the unfolding rate to the amyloidogenic precursor as well as the conformational preference of the denatured state determine the amyloidogenicity of the proteins. The present results reveal that, in addition, stability of the amyloid fibrils is a key factor determining the amyloidogenic potential of the proteins.
Measles Virus Suppresses Cell-mediated Immunity by Interfering with the Survival and Functions of Dendritic and T Cells (1997)

Secondary infections due to a marked immunosuppression have long been recognized as a major cause of the high morbidity and mortality rate associated with acute measles. The mechanisms underlying the inhibition of cell-mediated immunity are not clearly understood but dysfunctions of monocytes as antigen-presenting cells (APC) are implicated. In this report, we demonstrate that measles virus (MV) replicates weakly in the resting dendritic cells (DC) as in lipopolysaccharide-activated monocytes, but intensively in CD40-activated DC. The interaction of MV-infected DC with T cells not only induces syncytia formation where MV undergoes massive replication, but also leads to an impairment of DC and T cell function and cell death. CD40-activated DC decrease their capacity to produce interleukin (IL) 12, and T cells are unable to proliferate in response to MV-infected DC stimulation. A massive apoptosis of both DC and T cells is observed in the MV pulsed DC-T cell cocultures. This study suggests that DC represent a major target of MV. The enhanced MV replication during DC-T cell interaction, leading to an IL-12 production decrease and the deletion of DC and T cells, may be the essential mechanism of immunosuppression induced by MV.
In Vitro and In Vivo Evaluation of a Novel 99mTc(CO)3-Pyrazolyl Conjugate of cyclo-(Arg-Gly-Asp-d-Tyr-Lys) (2007)

Radiolabeled peptides containing the Arg-Gly-Asp amino acid sequence (single letter code = RGD) have been studied extensively to target integrin receptors upregulated on tumor cells and neovasculature. Integrins are cell surface transmembrane glycoproteins that exist as alphabeta heterodimers. The alphavbeta3 integrin is known to be overexpressed in many tumor types and is expressed at lower levels in normal tissues. Furthermore, alphavbeta3 and alphavbeta5 subtypes are expressed in neovasculature during angiogenesis. Thus, there is some impetus to image angiogenesis and tumor formation in vivo using RGD-based peptide targeting vectors. In this study, we report the design and development of a new cyclic RGD analogue cyclo-[Arg-Gly-Asp-d-Tyr-Lys(PZ)] (PZ = 3,5-Me2-pz(CH2)2N((CH2)3COOH)(CH2)2NH2) that can be radiolabeled with the [99mTc(CO)3(H2O)3]+ metal aquaion. Radiochemical evaluation of this new conjugate in vitro indicated a facile radiosynthesis of the new 99mTc-RGD conjugate with high radiolabeling yields (>or=95%) and high specific activities. In vitro internalization and blocking assays in alphavbeta3 receptor-positive, human M21 melanoma cancer cells showed the ability of this conjugate to target the integrin receptor with high specificity and selectivity. In vivo pharmacokinetic studies in normal CF-1 mice showed rapid clearance from blood with excretion primarily via/through the renal-urinary system. In vivo accumulation of radioactivity in mice bearing either alphavbeta3 receptor-positive or negative human melanoma tumors showed receptor specific uptake of tracer with accumulations of 2.50 +/- 0.29 and 0.71 +/- 0.08% ID/g in alphavbeta3 integrin positive (M21) and negative (M21L) tumors at 1 h postinjection (p.i.), respectively.
Body-Site Variation of Skin Autofluorescence (2001)

The body-site variation of skin autofluorescence was monitored in vivo in order to characterize individual contributions to the overall signal. Body sites having a range of chronic solar exposure were selected. The site-to-site spectral data sets were acquired from thirteen subjects. Incident light of 325-nm wavelength was used to excite fluorescence, observed between 360 nm and 570 nm. Principal factor analysis coupled with alternating least-squares optimization of within-subject body-site dependence revealed that two factors accounted for all of the body-site spectral variability. The factors were virtually the same for all subjects. The spectra were interpreted in terms of collagen cross-links and NADH. The body-site variation of component scores (relative concentrations) exhibited a consistent pattern between subjects. The factor assigned to collagen had highest scores at protected body sites; in contrast, NADH had highest scores at more exposed sites.
Chiral Recognition on Biopolymer-Based High-Pressure Liquid Chromatographic Chiral Stationary Phases (1991)

The chiral recognition mechanisms operating on two HPLC chiral stationary phases (CSPs) based upon immobilized biopolymers, α-chymotrypsin (ACHT-CSP) and human serum albumin (HSA-CSP) have been investigated. The results of these studies indicate that the observed stereoselectivity is a measure of the differences in binding affinities at two or more sites rather than the consequence of differential affinities at a single site. The proposed multiple site/multiple mechanism model differs from the single site/single mechanism and single site/multiple mechanisms models proposed for other HPLC-CSPs.
Comb-shaped polymers to enhance hydroxide transport in anion exchange membranes (2012)

Comb-shaped poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) polymers with quaternary ammonium (QA) groups have been synthesized organizing into well-defined micro-morphology for efficient anion (hydroxide) transport. These molecular comb structures show a dramatic enhancement in conductivity and water resistance compared with non-comb-shaped PPOs.
Evaluating the quality of hydraulic conductivity estimates from piezometer slug tests in peat (2005)

Abstract Although widely used in wetland hydrological studies, hydraulic conductivity ( K ) estimates from piezometer slug tests are often of questionable validity. Frequently, this is because insufficient attention is paid to the details of the test procedure. Further, in a potentially heterogeneous and anisotropic medium such as peat, the use of slug tests is prone to error. In this paper we address some of the methodological issues surrounding piezometer slug tests in peat. We compare slug test data with laboratory determinations of vertical and horizontal K obtained using a new method. Piezometers were installed at three depths in a floodplain fen peat in Norfolk, UK. Slug tests were initiated by both slug insertion and slug withdrawal, and repeat tests were conducted to examine the robustness of our K estimates. Most of the tests displayed departures from the log‐linear model of Hvorslev, the form of departure being consistent with compressible soil behaviour. The results suggest that insertion tests gave similar results to those initiated by withdrawal. Repeat testing showed that withdrawal data, in particular, gave highly reproducible normalized responses that were independent of the initial head. Values for K estimated using the slug tests were in the range 1 × 10 −4 to 1·6 × 10 −3 cm s −1 , which is towards the upper end of the range reported for peats generally. Laboratory tests yielded similar values of K to those obtained from the slug tests. Although the laboratory tests showed that the peat was anisotropic, the K values generated by slug testing proved relatively good estimates of both vertical and horizontal K . Copyright © 2005 John Wiley &amp; Sons, Ltd.
Basic Specification for IP Fast Reroute: Loop-Free Alternates (2008)

This document specifies an Internet standards track protocol for the Internet community, and requests discussion and suggestions for improvements.
POLYCHRONOUS WAVEFRONT COMPUTATIONS (2009)

There is great interest in methods for computing that do not involve digital machines. Many computational paradigms were inspired by brain research, such as Boolean neuronal logic [McCulloch &amp; Pitts, 1943], the perceptron [Rosenblatt, 1958], attractor neural networks [Hopfield, 1982] and cellular neural nets [Chua &amp; Yang, 1988]. All these paradigms abstract biological circuits to artificial neural networks, i.e. interconnected units (neurons) that perform computations based on the connections between the units (synapses). Here we present a novel computational framework based on polychronous wavefront dynamics. It is entirely different from an artificial neural network paradigm, rather it is based on temporal and spatial patterns of activity in pulse-propagating media and their interaction with transponders, which create pulses in response to receiving appropriate inputs, e.g. two coincident input pulses. A pulse propagates as a circular wave from its source to other transponders. Computations result from interactions between transponders, and they are encoded by the exact physical locations of transponders and by precise timings of pulses. We illustrate temporal pattern recognition, reverberating memory, temporal signal analysis and basic logical operations using polychronous wavefront computations. This work reveals novel principles for designing nanoscale computational devices.
A CRISPR–dCas Toolbox for Genetic Engineering and Synthetic Biology (2018)

Programmable control of gene expression is essential to understanding gene function, engineering cellular behaviors, and developing therapeutics. Beyond the gene editing applications enabled by the nuclease CRISPR-Cas9 and CRISPR-Cas12a, the invention of the nuclease-dead Cas molecules (dCas9 and dCas12a) offers a platform for the precise control of genome function without gene editing. Diverse dCas tools have been developed, which constitute a comprehensive toolbox that allows for interrogation of gene function and modulation of the cellular behaviors. This review summarizes current applications of the dCas tools for transcription regulation, epigenetic engineering, genome imaging, genetic screens, and chromatin immunoprecipitation. We also highlight the advantages and existing challenges of the current dCas tools in genetic engineering and synthetic biology, and provide perspectives on future directions and applications.
TheLateral Organ BoundariesGene Defines a Novel, Plant-Specific Gene Family (2002)

The LATERAL ORGAN BOUNDARIES (LOB) gene in Arabidopsis defines a new conserved protein domain. LOB is expressed in a band of cells at the adaxial base of all lateral organs formed from the shoot apical meristem and at the base of lateral roots. LOB encodes a predicted protein that does not have recognizable functional motifs, but that contains a conserved domain (the LOB domain) that is present in 42 other Arabidopsis proteins and in proteins from a variety of other plant species. Proteins showing similarity to the LOB domain were not found outside of plant databases, indicating that this unique protein may play a role in plant-specific processes. Genes encoding LOB domain proteins are expressed in a variety of temporal- and tissue-specific patterns, suggesting that they may function in diverse processes. Loss-of-function LOB mutants have no detectable phenotype under standard growth conditions, suggesting that LOB is functionally redundant or required during growth under specific environmental conditions. Ectopic expression of LOB leads to alterations in the size and shape of leaves and floral organs and causes male and female sterility. The expression of LOB at the base of lateral organs suggests a potential role for LOB in lateral organ development.
Renal ischemic-reperfusion injury in L-selectin-deficient mice (1996)

L-selectin on leukocyte surfaces mediates cell rolling on endothelium. L-selectin blockade with antibodies attenuated ischemic-reperfusion injury (IRI) in heart and skeletal muscle, but its role in renal IRI is unknown. We evaluated the role of L-selectin in renal IRI using L-selectin-deficient mice. Neutrophil migration to chemically inflamed peritoneum was reduced by 47% (P < 0.01) in L-selectin-deficient mice. Ischemia was induced by bilateral renal pedicle clamping for 30 min. Control and L-selectin groups had similar elevations of serum creatinine (1.8 +/- 0.3 vs. 1.7 +/- 0.2 mg/dl) and blood urea nitrogen (111 +/- 17 vs. 128 +/- 12 mg/dl) 24 h postischemia. Pathological assessment showed comparable degrees of tubular necrosis at 24 h. The postischemic increase in peritubular neutrophils per 10 high-power field was similar in control and L-selectin-deficient groups at 4 (28 +/- 10 vs. 22 +/- 5), 12 (245 +/- 80 vs. 236 +/- 78), and 24 h (130 +/- 12 vs. 156 +/- 18). These data argue against a significant role for L-selectin in renal IRI. Patho-physiological roles of L-selectin in vivo appear to be more complex than in vitro data would suggest.
Effects of Plasma Estrogen Sulfates in Mammary Cancer Cells* (1980)

The ability of estrogen conjugates to act as estrogen precursors in mammary tumor cells has been examined. One hour after injection of [3H]estradiol to ovariectomized C3H mice, 50–70% of the radioactivity in mammary tumor cytosol was due to estrogen conjugates (mostly sulfate) which were probably of plasma origin. Both the C3H independent mouse mammary tumors and the ovarian dependent tumors of the 9,10-dimethyl- 1,2-benzanthracene-treated rats took up and hydrolyzed [3H]- estrone sulfate in vitro. Similarly, in the MCF7 human breast cancer cell line, estrone sulfate entered the cells and was metabolized, yielding unconjugated estrone and estradiol which were finally bound to nuclear estrogen receptor. In addition, estrone-3-sulfate and estradiol-3-sulfate were found to be active on MCF7 cells in inducing secreted proteins of 46,000 and 160,000 mol wt which are induced by a 10-fold lower concentration of unconjugated estrone and estradiol. We conclude that estrogen sulfates can act in vitro as estrogen precursors in human breast cancer cells containing sulfatases and we propose to consider their possible role in vivo as estrogen precursors. The relative resistance of estrogen conjugates to charcoal adsorption lead to overestimation of estrogen receptor sites by the charcoal assay. The conjugates may also alter the evaluation of estradiol action in cell culture, since the routine charcoal treatment of serum which is efficient in adsorbing the nonconjugated steroid is shown to be inefficient in depriving the serum from estrogen sulfates. We therefore propose that the control cells cultured with steroidfree serum can be stimulated by the estrogens liberated from the estrogen sulfates of the serum if their concentration is sufficient. (Endocrinology106: 1079, 1980)
Future growth strategies: final report (2013)

This report introduces and discusses strategies by which Australian urban passenger rail operators and transport planning agencies can reduce urban rail’s existing reliance on substantial government subsidies. In particular, the report looks closely at achieving this through five separate but inter-related strategies, these being: 1) Growing patronage; 2) Road-user charging; 3) Network optimisation; 4) Spreading peak demand; and 5) Asset productivity
N‐terminal targeting of androgen receptor variant enhances response of castration resistant prostate cancer to taxane chemotherapy (2014)

Taxane-based chemotherapy is an effective treatment for castration-resistant-prostate cancer (CRPC) via stabilization of microtubules. Previous studies identified that the inhibitory effect of microtubule-targeting chemotherapy on androgen receptor (AR) activity was conferred by interfering with AR intracellular trafficking. The N-terminal domain (NTD) of AR was identified as a tubulin-interacting domain that can be effectively targeted by the novel small molecule inhibitor, EPI. Taken together this evidence provided the rationale that targeting AR nuclear translocation and activity via a combination of an antagonist of the AR NTD and taxane-based chemotherapy may enhance the therapeutic response in CRPC. The present study investigated the anti-tumor efficacy of a combination of EPI with Docetaxel chemotherapy, in cell models of CRPC, harboring the AR splice variants in addition to the full length AR. Our findings demonstrate that there was no significant effect on the androgen-mediated nuclear transport of AR variants and AR transcriptional activity by Docetaxel. The therapeutic response to Docetaxel was enhanced by inhibition of the NTD of AR (by EPI) through cycling of epithelial-mesenchymal-transition (EMT) to mesenchymal-epithelial-transition (MET) among prostate cancer epithelial cells. These results support that transient "programming" of EMT by the AR NTD inhibitor, potentially drives the sensitivity of prostate tumors with differential distribution of AR variants to microtubule-targeting chemotherapy. This study is of major significance in dissecting mechanisms to overcome taxane resistance in advanced CRPC.
Gender and the effects of an entrepreneurship training programme on entrepreneurial self-efficacy and entrepreneurial knowledge gain (2011)

The impact of entrepreneurship training on entrepreneurial self-efficacy, on entrepreneurship-related knowledge gain, and on the moderating role of gender on these relationships was studied. 122 junior high-school boys and girls participated in a one-year entrepreneurship training programme; a matched sample of 144 students did not participate. Participants’ entrepreneurial self-efficacy and entrepreneurial knowledge were assessed at the beginning and end of the programme. Boys benefited from the entrepreneurship training much more than girls. Results are further discussed in light of gender role theories.
A Three-Cascaded-Enzymes Biosensor to Determine Lactose Concentration in Raw Milk (2000)

The increasing demand for on-line measurement of milk composition directs science and industry to search for practical solutions, and biosensors may be a possibility. The specific objective of this work was to develop an electrochemical biosensor to determine lactose concentration in fresh raw milk. The sensor is based on serial reactions of three enzymes--beta-galactosidase, glucose oxidase, and horseradish peroxidase--immobilized on a glassy carbon electrode. The sequential enzymatic reactions increase the selectivity and sensitivity of the sensor. The sensor requires dilution of the raw milk and the addition of 5-aminosalicylic acid. Lactose concentrations in raw milk measured by the sensor were in good agreement with those measured by a reference laboratory using infrared technology. The results were obtained in milk samples that varied in fat and protein composition. From the results, we conclude that an electrochemical biosensor for determination of lactose concentration in fresh raw milk can be developed, and that the biosensor presented in this study maintained the qualities required for further development into an online sensor in the milking parlor.
Physicochemical Principles of Pharmacy Fourth Edition (2006)

1. Solids...7
2. Gases and Volatile Agents...35
3. Physicochemical Properties of Drug In Solution...55
4. Drug Stability...93
5. The Solubility of Drugs...139
6. Surfactans...177
7. Emulsions, Suspensions and Other Disperse Systems...229
8. Polymers and Macromolecules...273
9. Drug Absorption and Routes of Administration...329
Extracellular suppression allows mating by pheromone-deficient sterile mutants of Saccharomyces cerevisiae (1983)

MAT alpha haploids with mutations in the STE13 or KEX2 gene, and MATa haploids with mutations in the STE6 or STE14 gene, do not mate with wild-type cells of the opposite mating type. We found that such mutants were able to mate with partners that carry mutations (sst1 and sst2) that cause cells to be supersensitive to yeast mating pheromone action. Mating ability of MAT alpha ste13 and MAT alpha kex2 mutants could also be restored by adding normal MAT alpha cells to mating mixtures or by adding just the appropriate purified pheromone (alpha-factor). Therefore, the mating deficiencies caused by the ste13 and kex2 lesions, and by inference, the ste6 and ste14 mutations, appear to result only from secretion of an insufficient amount of pheromone or a nonfunctional pheromone.
A Generalized Vickrey Auction (2000)

In auction environments where bidders have pure private values, the Vickrey auction (Vickrey, 1961) provides a simple mechanism for efficiently allocating homogeneous goods. However, in environments where bidders have interdependent values, the Vickrey auction does not generally yield efficiency. This manuscript defines a “generalized Vickrey auction ” which yields efficiency when bidders have interdependent values. Each bidder reports her type to the auctioneer. Given the reports, the auctioneer determines the allocation that maximizes surplus. The payment rule is the following extension of Vickrey auction pricing: a bidder is charged for a given unit that she wins according to valuations evaluated at the minimum signal that she could have reported and still won that unit. JEL No.: D44 (Auctions)
2015 update of the drug resistance mutations in HIV-1 (2015)

The 2022 edition of the IAS-USA drug resistance mutations list updates the Figure last published in September 2019. The mutations listed are those that have been identified by specific criteria for evidence and drugs described. The Figure is designed to assist practitioners to identify key mutations associated with resistance to antiretroviral drugs, and therefore, in making clinical decisions regarding antiretroviral therapy.
Lack of inhibitory effects of Lactic acid bacteria on 1,2-dimethylhydrazine-induced colon tumors in rats (2003)

These results indicate that lactic acid bacteria lacks inhibitory effects on the progression of colon tumor in DMH-treated animals, and does not support the hypothesis that alteration of colonic flora may exert an influence on the progression of colon tumor.