gebhart/patrepeval huggingface dataset:
Ca(2+)-independent isoforms of protein kinase C differentially translocate in smooth muscle (1992)

It is generally assumed that smooth muscle contraction is dependent on changes in intracellular Ca2+ concentration ([Ca2+]i); however, we have previously reported that alpha-agonist-induced contraction of aorta smooth muscle cells can occur in the absence of changes in [Ca2+]i [Collins, E. M., M. P. Walsh, and K. G. Morgan. Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H754-H762, 1992]. The mechanism of this [Ca2+]i-independent contraction is controversial. We have now identified the Ca(2+)-independent protein kinase C (PKC) isoforms epsilon and zeta in ferret aorta and have used digital imaging microscopy to determine their subcellular distribution. At rest, epsilon-PKC is diffusely distributed in the cytosol, whereas zeta-PKC is concentrated in the perinuclear region; both isoforms are excluded from the nuclear space. Agonist stimulation causes a [Ca2+]i-independent translocation of epsilon-PKC to the surface membrane and of zeta-PKC to the intranuclear compartment. In comparison, ferret portal vein cells, which display a totally Ca(2+)-dependent agonist contraction, are lacking in epsilon-PKC but display perinuclear zeta-PKC, which translocates intranuclearly on activation. Thus the Ca(2+)-independent vascular contraction appears to be associated with plasmalemmal translocation of epsilon-PKC; in contrast, the intranuclear translocation of zeta-PKC may function in control of gene expression.
Malaria Mapping Using Transmission Models: Application to Survey Data from Mali (2005)

Geographic mapping of the distribution of malaria is complicated by the limitations of the available data. The most widely available data are from prevalence surveys, but these surveys are generally carried out at arbitrary locations and include nonstandardized and overlapping age groups. To achieve comparability between different surveys, the authors propose the use of transmission models, particularly the Garki model, to convert heterogeneous age prevalence data to a common scale of estimated entomological inoculation rates, vectorial capacity, or force of infection. They apply this approach to the analysis of survey data from Mali, collected in 1965-1998, extracted from the Mapping Malaria Risk in Africa database. They use Bayesian geostatistical models to produce smooth maps of estimates of the entomological inoculation rates obtained from the Garki model, allowing for the effect of environmental covariates. Again using the Garki model, they convert kriged entomological inoculation rates values to age-specific malaria prevalence. The approach makes more efficient use of the available data than do previous malaria mapping methods, and it produces highly plausible maps of malaria distribution.
Methods and Reproducibility of Measurement of Resistivity in the Calf Using Regional Bioimpedance Analysis (2003)

In this study, resistivity measurement by RBIA at the calf showed similar levels of fluid loading in patients post-dialysis as in normal subjects. This study also showed that change in electrode position resulted in a mean change in resistivity of <5% and repeated measurements showed a change in resistivity <3% while body weight changes were <0.2%. This technique appears to have an acceptable level of reproducibility for its application to the assessment of patient hydration.
Antisense Oligonucleotides Delivered to the Mouse CNS Ameliorate Symptoms of Severe Spinal Muscular Atrophy (2011)

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations in the SMN1 gene that result in a deficiency of SMN protein. One approach to treat SMA is to use antisense oligonucleotides (ASOs) to redirect the splicing of a paralogous gene, SMN2, to boost production of functional SMN. Injection of a 2'-O-2-methoxyethyl-modified ASO (ASO-10-27) into the cerebral lateral ventricles of mice with a severe form of SMA resulted in splice-mediated increases in SMN protein and in the number of motor neurons in the spinal cord, which led to improvements in muscle physiology, motor function and survival. Intrathecal infusion of ASO-10-27 into cynomolgus monkeys delivered putative therapeutic levels of the oligonucleotide to all regions of the spinal cord. These data demonstrate that central nervous system-directed ASO therapy is efficacious and that intrathecal infusion may represent a practical route for delivering this therapeutic in the clinic.
Interactive Learning from Policy-Dependent Human Feedback (2017)

This paper investigates the problem of interactively learning behaviors communicated by a human teacher using positive and negative feedback. Much previous work on this problem has made the assumption that people provide feedback for decisions that is dependent on the behavior they are teaching and is independent from the learner's current policy. We present empirical results that show this assumption to be false -- whether human trainers give a positive or negative feedback for a decision is influenced by the learner's current policy. Based on this insight, we introduce {\em Convergent Actor-Critic by Humans} (COACH), an algorithm for learning from policy-dependent feedback that converges to a local optimum. Finally, we demonstrate that COACH can successfully learn multiple behaviors on a physical robot.
High-Power Integrated Stimulator Output Stages With Floating Discharge Over a Wide Voltage Range for Nerve Stimulation (2009)

Two integrated nerve stimulator circuits are described. Both generate passively charge-balanced biphasic stimulating pulses of 1 to 16 mA with 10-¿s to 1-ms widths from 6- to 24-V supplies for implanted book electrodes. In both circuits, the electrodes are floating during the passive discharge anywhere within the range of the power rails, which may be up to 24 V. The first circuit is used for stimulation only. It uses a floating depletion transistor to enable continuous discharge of the electrodes, except when stimulating, without using power. The second circuit also allows neural signals to be recorded from the same tripole. It uses a modified floating complementary metal-oxide semiconductor (CMOS) discharge switch capable of operating over a range beyond the gate-to-source voltage limits of its transistors. It remains off for long periods using no power while recording. A 0.6-¿m silicon-on-insulator CMOS technology has been used. The measured performance of the circuits has been verified using multiple tripoles in saline.
Feedback control of morphogenesis in fungi by aromatic alcohols (2006)

Many fungi undergo a developmental transition from a unicellular yeast form to an invasive filamentous form in response to environmental cues. Here we describe a quorum signaling pathway that links environmental sensing to morphogenesis in Saccharomyces cerevisiae. Saccharomyces cells secrete aromatic alcohols that stimulate morphogenesis by inducing the expression of FLO11 through a Tpk2p-dependent mechanism. Mutants defective in synthesis of these alcohols show reduced filamentous growth, which is partially suppressed by the addition of these aromatic alcohols. The production of these auto signaling alcohols is regulated by nitrogen: High ammonia restricts it by repressing the expression of their biosynthetic pathway, whereas nitrogen-poor conditions activate it. Moreover, the production of these aromatic alcohols is controlled by cell density and subjected to positive feedback regulation, which requires the transcription factor Aro80p. These interactions define a quorum-sensing circuit that allows Saccharomyces to respond to both cell density and the nutritional state of the environment. These same autoregulatory molecules do not evoke the morphological switch in Candida albicans, suggesting that these molecular signals are species-specific.
IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system (2007)

ST2 is an IL-1 receptor family member with transmembrane (ST2L) and soluble (sST2) isoforms. sST2 is a mechanically induced cardiomyocyte protein, and serum sST2 levels predict outcome in patients with acute myocardial infarction or chronic heart failure. Recently, IL-33 was identified as a functional ligand of ST2L, allowing exploration of the role of ST2 in myocardium. We found that IL-33 was a biomechanically induced protein predominantly synthesized by cardiac fibroblasts. IL-33 markedly antagonized angiotensin II- and phenylephrine-induced cardiomyocyte hypertrophy. Although IL-33 activated NF-kappaB, it inhibited angiotensin II- and phenylephrine-induced phosphorylation of inhibitor of NF-kappa B alpha (I kappa B alpha) and NF-kappaB nuclear binding activity. sST2 blocked antihypertrophic effects of IL-33, indicating that sST2 functions in myocardium as a soluble decoy receptor. Following pressure overload by transverse aortic constriction (TAC), ST2(-/-) mice had more left ventricular hypertrophy, more chamber dilation, reduced fractional shortening, more fibrosis, and impaired survival compared with WT littermates. Furthermore, recombinant IL-33 treatment reduced hypertrophy and fibrosis and improved survival after TAC in WT mice, but not in ST2(-/-) littermates. Thus, IL-33/ST2 signaling is a mechanically activated, cardioprotective fibroblast-cardiomyocyte paracrine system, which we believe to be novel. IL-33 may have therapeutic potential for beneficially regulating the myocardial response to overload.
Random Switching Logic: A Countermeasure against DPA based on Transition Probability. (2004)

In this paper, we propose a new model for directly evaluating DPA leakage from logic information in CMOS circuits. This model is based on the transition probability for each gate, and is naturally applicable to various actual devices for simulating power analysis. We also report on our study of the e#ects of the previously known countermeasures on both our model and FPGA, and show the possibility of leaking information, which is caused by strict precondition for implementing a secure circuit. Furthermore, we present an e#cient countermeasure, Random Switching Logic(RSL), for relaxing the precondition, and show that RSL makes a cryptographic circuit secure through evaluation on both our model and FPGA.
Woodchuck Hepatitis Virus Enhancer I and Enhancer II Are Both Involved in N- myc2 Activation in Woodchuck Liver Tumors (1998)

Direct activation of the N-myc2 oncogene by insertion of woodchuck hepatitis virus (WHV) DNA is a major oncogenic step in woodchuck hepatocarcinogenesis. We previously reported that WHV enhancer II (We2), which controls expression of the core/pregenome RNA, can also activate the N-myc2 promoter in hepatoma cell lines. To better define the integrated WHV regulatory sequences responsible for N-myc2 promoter activation in woodchuck liver tumors, we analyzed the structure and enhancer activity of a single viral integrant found at the win locus in tumor 2260T1 and mapping approximately 175 kb 3' of N-myc2. This viral insert was made of 11 concatemerized WHV fragments, 5 of which overlapped with We2 sequences and 1 with WHV sequence homologous to that of hepatitis B virus enhancer I (We1). In transient transfection assays in hepatoma-derived cells, the We2 activator was found to be fully effective only when inserted in close proximity to the N-myc2 promoter whereas the We1 element by itself was apparently devoid of activity. In contrast, the 2260T1 viral insert exhibited a potent enhancer capacity that depended both on multimerized We2 and on We1 sequences. In a survey of different woodchuck hepatomas, both elements were commonly found within integrated viral sequences involved in long-range N-myc2 activation.
2. L'éducation générale (1988)

Durand Isabelle, Havelange Isabelle. 2. L'education generale. In: Histoire de l'education, n° 83-84, 1999. Numero double : Bibliographie d'histoire de l'education francaise : titres parus au cours de l'annee 1996 et supplements des annees anterieures, sous la direction de Isabelle Durand et Isabelle Havelange. pp. 30-78.
Probing for Integrin αvβ3Binding of RGD Peptides Using Fluorescence Polarization (2005)

Integrin alpha(v)beta(3) is an adhesion molecule involved in tumor invasion, angiogenesis, and metastasis. There is substantial interest in developing novel agents that bind to integrin alpha(v)beta(3). Here we report the synthesis and characterization of a fluorescent integrin alpha(v)beta(3) probe and its use in a nonradioactive, simple, sensitive fluorescence polarization (FP) assay to quantify binding to integrin alpha(v)beta(3). For assay validation, the FP assay was compared to a cell adhesion assay. In the two assays, probe binding to integrin alpha(v)beta(3) showed a similar dependence on probe concentration. The FP assay was successfully applied to measure the binding affinity to integrin alpha(v)beta(3) of several cyclic peptides containing the Arg-Gly-Asp (RGD) motif. The FP assay we describe here may be appropriate for high-throughput screening for integrin alpha(v)beta(3)-binding ligands used for anti-integrin therapy or noninvasive imaging of integrin expression.
Implantation: Trophectoderm projections: a potential means for locomotion, attachment and implantation of bovine, equine and human blastocysts (1996)

The behaviour of bovine, equine and human blastocysts was studied in vitro by time-lapse videomicrography and computer imaging. This study revealed that cytoplasmic extensions of the trophectoderm ['trophectoderm projections' (TEP)] were expressed by embryos of all three species, prior to or during zona escape. Bovine and human blastocysts escaped their zonae with a combination of blastocoele expansion, collapse and re-expansion coupled with the penetration of the zona pellucida by TEP. In equine embryos, after several cycles of blastocoele expansion and collapse, trophectoderm ruptured the zona with the concomitant appearance of TEP. This study provides documentation that TEP are expressed by a diverse range of mammalian species, bringing the total number of species in which this phenomenon is found to six, since TEP are also known to be expressed by guinea-pig, hamster and rhesus monkey blastocysts, representing rodents, ungulates and primates. In all species studied, the dynamic nature (extension, retraction, and angular movement) of the TEP was similar, moving in an undulating manner with rapid cycles of extension and retraction. Because TEP appear to be a general feature of mammalian blastocysts, they are implicated in one or more key events in early development, namely zona escape, attachment and/or implantation.
In vivo therapy of malignant melanoma by means of antagonists of alphav integrins. (2000)

Integrin alphavbeta3 (vitronectin receptor) has been implicated in human malignant melanoma progression and angiogenesis as a receptor that provides survival signals. However, little is known about the therapeutic potential of antagonists of alphavbeta3. In this report, we characterize the activities of 2 antagonists of alphavbeta3 integrins: a human specific monoclonal antibody (MAb), 17E6, and a cyclic RGD peptide that blocked cell adhesion and induced detachment of previously substrate-attached cells in vitro. In vivo, alphavbeta3 antagonists behaved as anti-tumor drugs in a dose- and time-dependent manner. Moreover, different therapeutic treatments proved to be effective even in the therapy of established macroscopic tumor masses, thus supporting the use of these antagonists in clinical therapy. Using a panel of 6 human melanomas and 5 carcinomas, MAb 17E6 efficiently blocked the in vivo tumor growth of melanomas expressing alphavbeta3 as xenografts but did not affect the alphavbeta3-negative (although alphav integrin-positive) tumors. This demonstrated that alphavbeta3 is a pivotal integrin for the growth of human melanomas. Furthermore, since MAb 17E6 does not recognize murine alphavbeta3, the effect is due only to the direct anti-tumor activity and not to the well-known anti-angiogenic activity of alphav-integrin antagonists. Taken together, our results confirm the essential role of alphavbeta3 integrin in the growth of human malignant melanoma in vivo and provide strong evidence of the therapeutic potential of alphav-integrin antagonists for the treatment of such tumors.
Long-term gene expression from autonomously replicating vectors in mammalian cells. (1996)

We tested the longevity of gene expression provided by autonomously replicating vectors. The vectors contain segments of human genomic DNA that provide efficient replication initiation and sequences derived from Epstein-Barr virus that provide nuclear retention. In order to monitor gene expression, the vectors also carry an expression cassette containing the chloramphenicol acetyl transferase gene. Replicating and control vectors were transfected into rapidly dividing human 293 cells, and gene expression and DNA retention were monitored. Gene expression decreased rapidly from a control vector lacking replication and retention functions, reaching near background levels by 10 days. Vectors having both replication and retention showed greatly prolonged gene expression, with vector DNA still detectable after 2 months. Autonomously replicating vectors also prolonged gene expression in rodent cells, in human lung epithelial cells, and in slowly dividing cell cultures. These results demonstrate the utility of this autonomous replication system for long-term retention and expression of introduced genes in mammalian cells. Such vectors could be useful for gene therapy, in combination with any of several methods for introduction of DNA.
RAMAN GAIN COEFFICIENT OF BARIUM NITRATE MEASURED FOR THE SPECTRAL REGION OF TI:SAPPHIRE LASER (2005)

We report the measurements of the Raman gain coefficient for a barium nitrate crystal in the spectral region of a Ti:Sapphire laser using Raman amplification. The experimentally-obtained data are well described by the known empirical formula.
Lubricin/Proteoglycan 4 Binding to CD44 Receptor: A Mechanism of the Suppression of Proinflammatory Cytokine–Induced Synoviocyte Proliferation by Lubricin (2015)

PRG4 (lubricin) is a novel putative ligand for CD44 and may control synoviocyte overgrowth in inflammatory arthropathies via a CD44-mediated mechanism.
Evaluation of potential organ culture media for eye banking using human donor corneas (2001)

Among the present test solutions, SFM appears to be the most prominent candidate for a new corneal organ culture medium and should be further tested and possibly refined to effectively substitute serum addition.
Differential phosphorylation of azidothymidine, dideoxycytidine, and dideoxyinosine in resting and activated peripheral blood mononuclear cells. (1993)

The antiviral activity of azidothymidine (AZT), dideoxycytidine (ddC), and dideoxyinosine (ddI) against HIV-1 was comparatively evaluated in PHA-stimulated PBM. The mean drug concentration which yielded 50% p24 Gag negative cultures were substantially different: 0.06, 0.2, and 6 microM for AZT, ddC, and ddI, respectively. We found that AZT was preferentially phosphorylated to its triphosphate (TP) form in PHA-PBM rather than unstimulated, resting PBM (R-PBM), producing 10- to 17-fold higher ratios of AZTTP/dTTP in PHA-PBM than in R-PBM. The phosphorylation of ddC and ddI to their TP forms was, however, much less efficient in PHA-PBM, resulting in approximately 5-fold and approximately 15-fold lower ratios of ddCTP/dCTP and ddATP/dATP, respectively, in PHA-PBM than in R-PBM. The comparative order of PHA-induced increase in cellular enzyme activities examined was: thymidine kinase > uridine kinase > deoxycytidine kinase > adenosine kinase > 5'-nucleotidase. We conclude that AZT, ddC, and ddI exert disproportionate antiviral effects depending on the activation state of the target cells, i.e., ddI and ddC exert antiviral activity more favorably in resting cells than in activated cells, while AZT preferentially protects activated cells against HIV infection. Considering that HIV-1 proviral DNA synthesis in resting lymphocytes is reportedly initiated at levels comparable with those of activated lymphocytes, the current data should have practical relevance in the design of anti-HIV chemotherapy, particularly combination chemotherapy.
Safety and immunogenicity of pneumococcal conjugate vaccine in combination with diphtheria, tetanus toxoid, pertussis and Haemophilus influenzae type b conjugate vaccine (2002)

The combination of TETRAMUNE and PnCV is safe and immunogenic.
A device for applying static loads to prosthetic limbs of transtibial amputees during spiral CT examination. (2001)

This paper describes a device that allows the imaging of prosthetic legs under load conditions using spiral computerized tomography (CT). The device consists of a chair and a vertical footplate mounted on a 17.8 x 1.9 cm oak board that is 197 cm long. The load device can be easily positioned onto the CT bed. A subject sits in the chair and applies force by pushing the foot portion of the prosthesis against the footplate. The magnitude of the force is monitored by a digital force gauge coupled to the footplate. Because the load is borne by the hips and lower back of the subject against the chair, substantial forces can be generated and steadily maintained for the 20-45 s duration of the CT study. This device has been used successfully with 19 transtibial amputees, allowing the acquisition of spiral CT studies with half and full body weight loads.
DNA-protein cross-linking and DNA interstrand cross-linking by haloethylnitrosoureas in L1210 cells. (1978)

Bifunctional alkylating agents are known to produce cross-links between DNA and protein and between paired DNA strands. The possibility of discriminating these two classes of cross-links in L1210 cells treated with haloethylnitrosoureas or nitrogen mustard was explored with the alkaline elution technique. Two classes of cross-links were demonstrated, based on sensitivity to proteinase K; the proteinase-sensitive cross-links appear to be DNA-protein cross-links, and the proteinase-resistant class may include interstrand cross-links. Proteinase-sensitive cross-links form more rapidly than do proteinase-resistant cross-links in cells treated with chloroethylnitrosoureas, perhaps because these agents can chloroethylate protein sulfhydryl or amino groups followed by rapid reaction of these chloroethylated groups with DNA. Although both types of cross-links produced by nitrogen mustard disappeared or were repaired after 24 hr, the removal of cross-links produced by chloroethylnitrosoureas either did not occur or was incomplete in 24 hr. In addition to cross-links, cells treated with haloethylnitrosoureas exhibited DNA strand breaks; a method is suggested for estimating the apparent frequencies of strand breaks and cross-links in the DNA.
Multipulse interferometric frequency-resolved optical gating (1999)

We review multipulse interferometric frequency-resolved optical gating (MI-FROG) as a technique, uniquely suited for pump-probe coherent spectroscopy using amplified visible and near-infrared short-pulse systems and/or emissive targets, for time-resolving ultrafast phase shifts and intensity changes. Application of polarization-gate MI-FROG to the study of ultrafast ionization in gases is presented.
Regression of Established Tumors Expressing P-glycoprotein by Combinations of Adriamycin, Cyclosporin Derivatives, and MRK-16 Antibodies (1997)

Combination treatment with a cyclosporin derivative and an anti-P-glycoprotein antibody can be effective in circumventing P-glycoprotein-mediated drug resistance.