gebhart/patrepeval huggingface dataset:
Optical pumping of high-density Rb with a broadband dye laser and GaAlAs diode laser arrays: Application toHe3polarization (1989)

We have studied laser optical pumping of Rb at densities up to 4\ifmmode\times\else\texttimes\fi{}${10}^{14}$ atoms/${\mathrm{cm}}^{3}$ and produced polarized $^{3}\mathrm{He}$ by spin exchange with Rb. Numerical calculations show that for a high-density Rb vapor GaAlAs diode laser arrays can provide results similar to those obtained with a broadband ${\mathrm{Kr}}^{+}$-ion--dye-laser system. We have confirmed these calculations with measurements using a 40-GHz full width at half maximum bandwidth dye laser and 100- and 500-mW GaAlAs diode laser arrays (Spectra Diode Labs Array Nos. SDL-2410C and SDL-2450C). We have optically pumped Rb of density [Rb]=4\ifmmode\times\else\texttimes\fi{}${10}^{14}$ atoms/${\mathrm{cm}}^{3}$, and we have measured up to 70% $^{3}\mathrm{He}$ polarization in a 4-${\mathrm{cm}}^{3}$ volume with 600 mW from the dye laser. With the diode laser arrays, we have pumped with 30 and 300 mW with results comparable to those obtained with the dye laser. With a 1-W diode laser array, we anticipate 70--80 % $^{3}\mathrm{He}$ polarization in a 4-${\mathrm{cm}}^{3}$ volume.
Immunohistochemical Distribution and Serum Levels of the Ca<sup>2</sup><sup>+</sup> -Binding Proteins MRP8, MRP14 and Their Heterodimeric Form MRP8/14 in Crohn’s Disease (1995)

In previous histochemical studies the distribution of the two Ca(2+)-binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 has been demonstrated in different inflammatory diseases. Monoclonal antibodies against MRP8 and MRP14 and their heterodimer MRP8/14 (27E10 epitope) were used to investigate immunohistochemically the distribution of these proteins in routinely processed small and large bowel tissues from patients with Crohn's disease (CD). Furthermore, we used a sandwich immunoassay to measure serum concentrations of MRPs in 62 patients were simultaneously assessed by the Crohn's disease activity index (CDAI) and the severity activity index of Goebell (SAI). In our immunohistochemical study, MRP8, MRP14 and heterocomplex MRP8/14 were demonstrated in the majority of granulocytes and macrophages in active CD. Additionally, a strong complex MRP8/14 immunoreactivity was present in epithelial cells adjacent to ulcerative and fissuring lesions in the bowel. Serum MRP8/14 concentrations were significantly (p < 0.0001) increased in patients with active CD (CDAI > 150, SAI > 120). No correlations were found for level of MRP14 and MRP8 alone, respectively. The follow-up of individual patients with initially active CD showed a further increase in MRP8/14 levels during acute attacks of the inflammatory process. We suggest that our assay for MRP8/14 discriminates well between active and inactive CD and may have considerable potential in the analysis of clinical disease activity in CD patients. Our morphological results confirm the finding of increased MRP8/14 serum levels in patients with active CD.
MINIREVIEW: The Steroid Receptor Superfamily: More Excitement Predicted for the Future (1990)

The overall molecular pathway for the action of steroid hormones has been known for the past 15 yr (1–9). Within the past 5 yr, the cDNAs for all major steroid hormones have been cloned and sequenced (10, 11). As might have been expected, they were related in structure and led to the definition of an even larger family of putative regulatory proteins. This superfamily of regulatory molecules was shown to include also the receptors for thyroid hormone (T3) vitamin D3 and retinoic acid. Perhaps more surprising was the inclusion of oncogenes such as v-erb A in this family. The latter is one of the two genes which comprise an oncogenic cassette in the avian myeloblastosis virus and appears to be a mutated form of a cellular gene coding for one of the multiple receptors for thyroid hormone. A summary of selected members of the steroid receptor superfamily is shown in Fig. 1.
Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A (2014)

Six recombinant factor VIII (rFVIII) products have been marketed worldwide. In 2013, the Research of Determinants of Inhibitor Development (RODIN) study group reported an unexpectedly high risk of inhibitor development with a second-generation full-length rFVIII (Product D) in previously untreated patients (PUPs) with severe hemophilia A (HA). In 1994, French public health authorities established a prospective cohort to monitor hemophilia treatment safety. A PUP subgroup was designed to investigate inhibitor risk factors. We analyzed this subcohort in view of the RODIN findings. After excluding 50 patients who participated in the RODIN study, the primary analysis focused on 303 boys with severe HA first treated with a rFVIII product. A clinically significant inhibitor was detected in 114 boys (37.6%). The inhibitor incidence was higher with Product D vs the most widely used rFVIII product (adjusted hazard ratio [aHR], 1.55; 95% confidence interval [CI], 0.97-2.49). Similar results were found for high-titer inhibitors and in 10 sensitivity analyses. No heterogeneity was observed between RODIN and our results. Combined aHRs were 1.58 (95% CI, 1.17-2.14) for all inhibitors and 1.70 (95% CI, 1.15-2.52) for high-titer inhibitors. Our results confirm the higher immunogenicity of Product D vs other rFVIII products in PUPs with severe HA.
Transapical Transcatheter Aortic Valve Implantation in Humans (2006)

This initial experience suggests that transapical aortic valve implantation without cardiopulmonary bypass is feasible in selected patients with aortic stenosis.
Physical changes that take place from birth to one (2002)

In our new babies and toddlers section, Joanna Code this month looks at the physical development of babies from birth to the age of one.
Predominant Interactions between μ-Conotoxin Arg-13 and the Skeletal Muscle Na+Channel Localized by Mutant Cycle Analysis (1998)

High-affinity mu-conotoxin block of skeletal muscle Na+ channels depends on an arginine at position 13 (Arg-13). To understand both the mechanism of toxin interaction and the general structure of its binding site in the channel mouth, we examined by thermodynamic mutant cycle analysis the interaction between the critical Arg-13 and amino acid residues known to be in the channel's outer vestibule. Arg-13 interacts specifically with domain II Glu-758 with energy of about -3.0 kcal/mol, including both electrostatic and nonelectrostatic components, and with Glu-403 with energy of about -2.0 kcal/mol. Interactions with the other charged residues in the outer vestibule were shown to be almost entirely electrostatic, because these interactions were maintained when Arg-13 was replaced by lysine. These results place the bound Arg-13 at the channel mouth adjacent to the P (pore) loops of domains I and II. Distance estimates based on interaction energies suggest that the charged vestibule residues are in relative positions similar to those of the Lipkind-Fozzard vestibule model [Lipkind, G. M., and Fozzard, H. A. (1994) Biophys. J. 66, 1-13]. Kinetic analysis suggests that Arg-13 interactions are partially formed in the ligand-channel transition state.
Distributed Training Strategies for the Structured Perceptron (2010)

Perceptron training is widely applied in the natural language processing community for learning complex structured models. Like all structured prediction learning frameworks, the structured perceptron can be costly to train as training complexity is proportional to inference, which is frequently non-linear in example sequence length. In this paper we investigate distributed training strategies for the structured perceptron as a means to reduce training times when computing clusters are available. We look at two strategies and provide convergence bounds for a particular mode of distributed structured perceptron training based on iterative parameter mixing (or averaging). We present experiments on two structured prediction problems – namedentity recognition and dependency parsing – to highlight the efficiency of this method. 1
Haemodynamics of pelvic nerve induced penile erection in the dog: possible mediation by vasoactive intestinal polypeptide. (1984)

The haemodynamics of erection were elucidated in the anaesthetized dog by analysing in quantitative terms the changes of penile arterial inflow, venous outflow and tissue volume during graded pelvic nerve stimulation. The study also provides information on possible neurotransmitter mechanisms of the erectile response. Erection evoked by pelvic nerve stimulation appeared to result from two main circulatory events: first, there was a prompt dilatation of the penile 'resistance vessels', causing a greatly increased arterial inflow which in the early phase bypassed the cavernous bodies and, hence, increased venous outflow to the same extent. Secondly, the erectile response proper began after a distinct delay (approximately equal to 20 s). This was apparently caused by sudden opening of low resistance 'shunt vessels' diverting part of the arterial inflow into the cavernous bodies, leading to rapid filling. During the filling phase arterial inflow greatly exceeded venous outflow, and returned to the venous outflow level again in the steady state of full erection. The initial dilator response seemed to ensure rapid erection by establishing a high pressure head from the arterial microvessels to the cavernous spaces. The threshold frequency for the penile vasodilator response to pelvic nerve stimulation was 1-2 Hz and was always higher for the erectile volume response, viz. 2-4 Hz. Maximal effects for both were obtained at 16 Hz, causing on the average a 25-fold increase in peak arterial inflow, a 17-fold increase in venous outflow and a 107% increase in penile volume. Muscarinic blockade by atropine caused no significant decrease in the blood flow response induced by pelvic nerve stimulation, but clearly curtailed the erectile response. This indicates that the dilatation of the penile 'resistance vessels' is mainly non-cholinergic in nature, whereas a cholinergic mechanism seems to contribute to the erectile volume response proper. Pelvic nerve stimulation caused a substantial output of vasoactive intestinal polypeptide (VIP) from the penis which was correlated in onset and duration to the vasodilator response. Intra-arterial (I.A.) infusion of VIP elicited moderate erection and a penile vasodilator response which resembled the neural response. Similar effects were evoked by I.A. infusion of substance P, but the output of this peptide from the penis during stimulation was poorly correlated to the vascular events. These in vivo observations indicate that VIP might be the neurotransmitter responsible for the non-cholinergic pelvic nerve induced penile vasodilatation.
Using an Eye-Tracking System to Improve Depth-of-Field Blur Effects and Camera Motions in Virtual Environments (2008)

International audience
Drugs in development for the treatment of schizophrenia (2009)

The overall outcome in schizophrenia is generally poor, despite the undisputed efficacy of antipsychotics in treating the acute symptoms of psychosis. There remains a subset of patients who are refractory to treatment. Also, for most patients treatment is not effective against the full spectrum of symptoms including negative and cognitive symptoms, and severe functional deficits persist. Further, while the newer drugs produce fewer motor side effects, other safety and tolerability concerns have emerged. Since the advent of antipsychotic therapy in the early 1950s, subsequent advances have been modest. While the mechanism of action of the first-generation antipsychotics appears closely linked to D2 antagonism, the second-generation antipsychotics have broader receptor-binding profiles, particularly 5-HT receptor antagonism. Attempts are now being made to develop antipsychotics with a wider spectrum of efficacy and a more favourable safety and tolerability profile by further exploring the therapeutic potential of D2 and 5-HT2 receptors, as well as investigating other putative mechanisms of action. This article adds to the current literature by providing an up-to-date review of antipsychotic drugs currently in development, focusing on the findings to date for compounds that are presently in Phase III clinical trials. While no exciting breakthroughs appear imminent, several drugs in early development have great potential.
Synthesis of Improved Lysomotropic Autophagy Inhibitors (2015)

Autophagy is a conserved cellular pathway used to recycle nutrients through lysosomal breakdown basally and under times of stress (e.g., nutrient deprivation, chemotherapeutic treatment). Oncogenes are known to induce autophagy, which may be exploited by cancers for cell survival. To identify autophagy inhibitors with potential therapeutic value for cancer, we screened a panel of antimalarial agents and found that quinacrine (QN) had 60-fold higher potency of autophagy inhibition than chloroquine (CQ), a well-known autophagy inhibitor that functions by disrupting lysosomal activity. Despite desirable autophagy inhibiting properties, QN showed considerable cytotoxicity. Therefore, we designed and synthesized a novel series of QN analogs and investigated their effects on autophagy inhibition and cell viability. Notably, we found two compounds (33 and 34), bearing a backbone of 1,2,3,4-tetrahydroacridine, had limited cytotoxicity yet strong autophagy inhibition properties. In conclusion, these improved lysomotropic autophagy inhibitors may have use as anticancer agents in combination with conventional therapies.
Requirement of Stat3 but not Stat1 activation for epidermal growth factor receptor- mediated cell growth In vitro. (1998)

Stimulation of epidermal growth factor receptor (EGFR) by ligand(s) leads to activation of signaling molecules including Stat1 and Stat3, two members of the signal transducers and activators of transcription (STAT) protein family. Activation of Stat1 and Stat3 was constitutive in transformed squamous epithelial cells, which produce elevated levels of TGF-alpha, and was enhanced by the addition of exogenous TGF-alpha. Targeting of Stat3 using antisense oligonucleotides directed against the translation initiation site, resulted in significant growth inhibition. In addition, cells stably transfected with dominant negative mutant Stat3 constructs failed to proliferate in vitro. In contrast, targeting of Stat1 using either antisense or dominant-negative strategies had no effect on cell growth. Thus, TGF-alpha/EGFR-mediated autocrine growth of transformed epithelial cells is dependent on activation of Stat3 but not Stat1.
Experiences with Recombinant Factor VIIa in Haemophiliacs (2015)

Treatment of hemophiliacs with antibodies against factor VIII and factor IX is a matter of major concern in hemophilia care. Although a number of sophisticated methods for removal of antibodies have been designed, such procedures are suitable only in life-threatening situations since they are complicated and expensive.1, 2 Much effort has been focused on finding an agent capable of activating the final common pathway of the coagulation cascade, inducing hemostasis independent of the presence of factor VIII and factor IX. Such an agent should be hemostatically active, but also safe with regard to thromboembolic complications. Currently used prothrombin complex concentrates (PCC) or activated PCC (APCC) seem only to be active in about 50% of the bleeds.3, 4 Furthermore, thromboembolic complications are being reported following the use of PCC or APCC.5, 6 Activated factor VII (FVIIa) should be an attractive candidate since it is not proteolytically active until after having formed a complex with tissue factor or other phospholipids, thereby minimizing the risk of inducing a systemic activation of the coagulation system.
Stepwise Mobilization of Focused Proteins in Capillary Isoelectric Focusing Mass Spectrometry (2000)

A stepwise mobilization strategy has been developed for the elution of complex protein mixtures, separated by capillary isoelectric focusing (CIEF) for detection using on-line electrospray ionization mass spectrometry (ESI-MS). Carrier polyampholytes are used to establish a pH gradient as well as to control the electroosmotic flow arising from the use of uncoated fused-silica capillaries. Elution of focused protein zones is achieved by controlling the mobilization pressure and voltage, leaving the remaining protein zones focused inside the capillary. Protein zones are stepwise eluted from the capillary by changing the mobilization conditions. Stepwise mobilization improves separation resolution and simplifies coupling with multistage MS (i.e., MSn) analysis since it allows more effective temporal control of protein elution from the CIEF capillary. We also describe a modified configuration for coupling CIEF with ESI-MS using a coaxial sheath flow interface that facilitate the automation of on-line CIEF-ESI-MS analyses. The stepwise mobilization strategy is demonstrated for the analysis of standard protein mixtures and soluble E. coli lysate proteins using CIEF-ESI-MS. These results indicate that inlet pressure or voltage programming to control the elution of the protein zones from the capillary (i.e., gradient mobilization) may allow for the optimization of the mobilization conditions and provide higher resolution for CIEF separation of complex mixtures with on-line MS.
In-substrate-bitline sense amplifier with array-noise-gating scheme for low-noise 4F 2 DRAM array operable at 10-fF cell capacitance (2011)

An in-substrate-bitline sense amplifier (SA) with an array-noise-gating (ANG) scheme—for stable sensing operation in a 4F2 DRAM array with cell capacitance of under 20 fF—is proposed. A circuit simulation assuming 40-nm-class 4F2 DRAM chip shows that the SA reduces noise by 58% compared to a conventional SA and achieves stable sensing operation even at cell capacitance of 10 fF.
SFmap: a web server for motif analysis and prediction of splicing factor binding sites (2010)

Alternative splicing (AS) is a post-transcriptional process considered to be responsible for the huge diversity of proteins in higher eukaryotes. AS events are regulated by different splicing factors (SFs) that bind to sequence elements on the RNA. SFmap is a web server for predicting putative SF binding sites in genomic data (http://sfmap.technion.ac.il). SFmap implements the COS(WR) algorithm, which computes similarity scores for a given regulatory motif based on information derived from its sequence environment and its evolutionary conservation. Input for SFmap is a human genomic sequence or a list of sequences in FASTA format that can either be uploaded from a file or pasted into a window. SFmap searches within a given sequence for significant hits of binding motifs that are either stored in our database or defined by the user. SFmap results are provided both as a text file and as a graphical web interface.
A Competitive Polymerase Chain Reaction Assay for Reliable Identification of Bordetella Pertussis in Nasopharyngeal Swabs (1995)

In order to optimize the identification of clinically relevant quantities of Bordetella pertussis in nasopharyngeal swabs, an automated assay introducing competitive polymerase chain reaction was established. A 183 base pair DNA fragment from a repetitive region of the Bordetella pertussis genome was amplified in a polymerase chain reaction. An internal control DNA with nine base substitutions was coamplified in the same reaction. The differentiation between the amplified B. pertussis DNA and the internal control was based on hybridisation against two different probes using Enzymun Test DNA Detection (Boehringer Mannheim). Nasopharyngeal swabs from serologically positive patients, clinically diagnosed with whooping cough, serologically negative patients after contact with B. pertussis and a negative group were compared. The advantages of competitive PCR are a reduced risk of false-positive and false-negative results and the possibility to differentiate between the different PCR positive groups.
Cardiac-Specific IGF-1 Expression Attenuates Dilated Cardiomyopathy in Tropomodulin-Overexpressing Transgenic Mice (2002)

To test the hypothesis that early interventional treatment with insulin-like growth factor-1 (IGF-1) alleviates subsequent development of dilated cardiomyopathy, cardiac-specific IGF-1 expression was introduced by selective cross-breeding into a transgenic mouse model of heart failure that displays phenotypic characteristics of severe dilation. Hemodynamic, structural, and cellular parameters of the heart were compared between nontransgenic, tropomodulin-overexpressing cardiomyopathic, and the hybrid tropomodulin/IGF-1-overexpressing mice. Beneficial effects of IGF-1 were apparent by multiple indices of cardiac structure and function, including normalization of heart mass, anatomy, hemodynamics, and apoptosis. IGF-1 expression also acted as a proliferative stimulus as evidenced by calculated increases in myocyte number as well as expression of Ki67, a nuclear marker of cellular replication. Cellular analyses revealed that IGF-1 inhibited characteristic cardiomyocyte elongation in dilated hearts and restored calcium dynamics comparable to that observed in normal cells. Collectively, these results provide novel information regarding the ability of IGF-1 to inhibit progression of cardiomyopathic disease in a defined model system and suggest that heart failure may benefit from early interventional IGF-1 treatment.
Mapping the Glycoprotein Ib-binding Site in the von Willebrand Factor A1 Domain (2000)

The von Willebrand factor (vWF) mediates platelet adhesion to exposed subendothelium at sites of vascular injury. It does this by forming a bridge between subendothelial collagen and the platelet glycoprotein Ib-IX-V complex (GPIb). The GPIb-binding site within vWF has been localized to the vWF-A1 domain. Based on the crystal structure of the vWF-A1 domain (Emsley, J., Cruz, M., Handin, R., and Liddington, R. (1998) J. Biol. Chem. 273, 10396-10401), we introduced point mutations into 16 candidate residues that might form all or part of the GPIb interaction site. We also introduced two mutations previously reported to impair vWF function yielding a total of 18 mutations. The recombinant vWF-A1 mutant proteins were then expressed in Escherichia coli, and the activity of the purified proteins was assessed by their ability to support flow-dependent platelet adhesion and their ability to inhibit ristocetin-induced platelet agglutination. Six mutations located on the front and upper anterior face of the folded vWF-A1 domain, R524S, G561S, H563T, T594S/E596A, Q604R, and S607R, showed reduced activity in all the assays, and we suggest that these residues form part of the GPIb interaction site. One mutation, G561S, with impaired activity occurs in the naturally occurring variant form of von Willebrand's disease-type 2M underscoring the physiologic relevance of the mutations described here.
The Low Density Lipoprotein Receptor Active Conformation of Apolipoprotein E (1998)

Lipid association is a prerequisite for receptor interactions of apolipoprotein E (apoE). Disc complexes of the N-terminal 22-kDa apoE3 receptor binding domain and dimyristoylphosphatidylcholine display full receptor binding activity. Studies have been performed to characterize conformational adaptations of the globular, lipid-free four-helix bundle structure that culminate in stable association of its amphipathic alpha-helices with a lipid surface. Helix-lipid interactions in bilayer disc complexes can conceivably adopt two orientations: parallel or perpendicular to the phospholipid acyl chains. Evidence based on infrared dichroism, geometrical arguments, and x-ray crystallography support the view that defined helical segments in the four-helix bundle realign upon lipid association, orienting perpendicular to the phospholipid fatty acyl chains, circumscribing the bilayer disc. Thus, it is likely that paired helical segments align in tandem, presenting a convex receptor-active surface.