gebhart/patrepeval huggingface dataset:
Functional Magnetic Resonance Imaging Reveals Different Neural Substrates for the Effects of Orexin-1 and Orexin-2 Receptor Antagonists (2011)

Orexins are neuro-modulatory peptides involved in the control of diverse physiological functions through interaction with two receptors, orexin-1 (OX1R) and orexin-2 (OX2R). Recent evidence in pre-clinical models points toward a putative dichotomic role of the two receptors, with OX2R predominantly involved in the regulation of the sleep/wake cycle and arousal, and the OX1R being more specifically involved in reward processing and motivated behaviour. However, the specific neural substrates underlying these distinct processes in the rat brain remain to be elucidated. Here we used functional magnetic resonance imaging (fMRI) in the rat to map the modulatory effect of selective OXR blockade on the functional response produced by D-amphetamine, a psychostimulant and arousing drug that stimulates orexigenic activity. OXR blockade was produced by GSK1059865 and JNJ1037049, two novel OX1R and OX2R antagonists with unprecedented selectivity at the counter receptor type. Both drugs inhibited the functional response to D-amphetamine albeit with distinct neuroanatomical patterns: GSK1059865 focally modulated functional responses in striatal terminals, whereas JNJ1037049 induced a widespread pattern of attenuation characterised by a prominent cortical involvement. At the same doses tested in the fMRI study, JNJ1037049 exhibited robust hypnotic properties, while GSK1059865 failed to display significant sleep-promoting effects, but significantly reduced drug-seeking behaviour in cocaine-induced conditioned place preference. Collectively, these findings highlight an essential contribution of the OX2R in modulating cortical activity and arousal, an effect that is consistent with the robust hypnotic effect exhibited by JNJ1037049. The subcortical and striatal pattern observed with GSK1059865 represent a possible neurofunctional correlate for the modulatory role of OX1R in controlling reward-processing and goal-oriented behaviours in the rat.
Isolation, characterization and epistasis of fluoride-resistant mutants of Caenorhabditis elegans. (1994)

We have isolated 13 fluoride-resistant mutants of the nematode Caenorhabditis elegans. All the mutations are recessive and mapped to five genes. Mutants in three of the genes (class 1 genes: flr-1 X, flr-3 IV, and flr-4 X) are resistant to 400 micrograms/ml NaF. Furthermore, they grow twice as slowly as and have smaller brood size than wild-type worms even in the absence of fluoride ion. In contrast, mutants in the other two genes (class 2 genes: flr-2 V and flr-5 V) are only partially resistant to 400 micrograms/ml NaF, and they have almost normal growth rates and brood sizes in the absence of fluoride ion. Studies on the phenotypes of double mutants showed that class 2 mutations are epistatic to class 1 mutations concerning growth rate and brood size but hypostatic with respect to fluoride resistance. We propose two models that can explain the epistasis. Since fluoride ion depletes calcium ion, inhibits some protein phosphatases and activates trimeric G-proteins, studies on these mutants may lead to discovery of a new signal transduction system that controls the growth of C. elegans.
Calcitonin gene-related peptide: functional role in cerebrovascular regulation. (1986)

Distribution studies disclosed that all major cerebral arteries and cortical arterioles of the cat were invested with fine varicose nerve fibers that contained calcitonin gene-related peptide (CGRP)-like immunoreactivity; the trigeminal ganglia likewise contained CGRP immunoreactivity. Sequential immunostaining with antibodies to CGRP and to substance P (SP) revealed identical distributions of these two peptides in trigeminal ganglia and cerebrovascular nerve fibers, suggesting that CGRP and SP are colocalized in these nerves. CGRP completely disappeared from ipsilateral blood vessels after unilateral section of the trigeminal nerve. Exogenous CGRP was a potent relaxant of feline middle cerebral arteries in vitro (maximum relaxation, 10.5 +/- 1.5 mN; concentration eliciting half-maximal response, 9.6 +/- 1.3 nM). Perivascular microapplication of CGRP to individual cortical arterioles of chloralose-anesthetized cats provoked dose-dependent dilatations (maximum increase in diameter, 38 +/- 5%; concentration eliciting half-maximal response, approximately equal to 3 nM). CGRP was significantly more potent than SP as a cerebrovascular dilator, both in vitro and in situ. Chronic division of the ipsilateral trigeminal nerve in cats did not modify the magnitude of arteriolar responses to perivascular microapplication of either vasoconstrictor or vasodilator agents, but the duration of vasoconstrictor responses to norepinephrine (0.1 mM) or alkaline solutions (pH 7.6) was significantly increased. The cerebrovascular trigeminal neuronal system, in which CGRP is the most potent vasoactive constituent, may participate in a reflex or local response to excessive cerebral vasoconstriction that restores normal vascular diameter.
β-Cyclodextrin as a Scaffold for Supramolecular Chemistry, To Reverse the Regioselectivity of Nitrile Oxide Cycloadditions (1998)

β-Cyclodextrin has been used as a molecular scaffold, whereby tethering dipolarophiles to the cyclodextrin and then allowing preassociation of the modified cyclodextrins with aromatic nitrile oxides, as host−guest complexes, controls the relative orientations of the dipoles and the dipolarophiles in their cycloadditions. In this manner it has been possible to reverse the usual regioselectivity of cycloadditions of nitrile oxides, as illustrated by reactions with a terminal alkene, a terminal alkyne, and a 1,2-disubstituted alkene. For example, in aqueous solution, 4-tert-butylbenzonitrile oxide reacted with 6A-deoxy-6A-propynamido-β-cyclodextrin to give the corresponding 4- and 5-substituted isoxazoles, in a 15:1 ratio. With DMF as the solvent, to reduce the extent of host−guest complexation, the product ratio was 1:1.5. The role of complexation in these reactions is also demonstrated by contrasting these results with that of the reaction of the nitrile oxide with methyl propynoate, which afforded only the 5-substituted cycloaddition product. Molecular recognition by the cyclodextrin scaffolds was demonstrated through treatment of 4-tert-butylbenzonitrile oxide with an equimolar mixture of 6A-deoxy-6A-propynamido-β-cyclodextrin and methyl propynoate, in aqueous solution, which gave only the cycloadducts from reaction of the cyclodextrin dipolarophile.
Forward error correcting codes in synchronous fiber optic transmission systems (1997)

This paper proposes forward error correcting (FEC) code for synchronous digital hierarchy (SDH) fiber optical transmission systems. They are (18880, 18865) and (2370, 2358) shortened Hamming codes and are encoded at the multiplex-section layer; the check bits are embedded in auxiliary multiplex-section overhead (MSOH) bytes. The codes realize general circuit configurations regardless of the transmission speed or path-size, perfect compatibility with SDH format, suppressed processing delay accumulation, and decrease the chance of line-switching in the case of signal degradation. To ensure that the various requirements of each network-provider such as customized usage of SOH bytes and affordable circuit scale could be satisfied, a trial circuit board was constructed on the programmable hardware called PROTEUS, which enables flexible operation in terms of code-selection and check bit area. We actually confirm error-correcting capability through the first STM-64 FEC-coded-optical transmission experiment. The statistics of error occurrence in the optical transmission line are also studied. The result indicates that the proposed codes are effective in optical transmission systems if the BER is limited by optical noise and dispersion.
Population pharmacokinetics of the humanised monoclonal antibody, HuHMFG1 (AS1402), derived from a phase I study on breast cancer (2010)

BACKGROUND: HuHMFG1 (AS1402) is a humanised monoclonal antibody that has undergone a phase I trial in metastatic breast cancer. The aim of this study was to characterise the pharmacokinetics (PKs) of HuHMFG1 using a population PK model. METHOD: Data were derived from a phase I study of 26 patients receiving HuHMFG1 at doses ranging from 1 to 16 mg kg 1 . Data were analysed using NONMEM software and covariates were included. A limited sampling strategy (LSS) was developed using training and a validation data set. RESULTS: A linear two-compartment model was shown to be adequate to describe data. Covariate analysis indicated that weight was not related to clearance. An LSS was successfully developed on the basis of the model, in which one sample is collected immediately before the start of an infusion and the second is taken at the end of infusion. CONCLUSION: A two-compartment population PK model successfully describes HuHMFG1 behaviour. The model suggests using a fixed dose of HuHMFG1, which would simplify dosing. The model could be used to optimise dose level and dosing schedule if more data on the correlation between exposure and efficacy become available from future studies. The derived LSS could optimise further PK assessment of this antibody.
High-efficiency receptor-mediated delivery of small and large (48 kilobase gene constructs using the endosome-disruption activity of defective or chemically inactivated adenovirus particles. (1992)

One limit to successful receptor-mediated gene delivery is the exit of the endocytosed material from the endosome. We demonstrate here the delivery of marker genes to tissue culture cells using a modification of the receptor-mediated gene delivery technique that exploits the endosomolytic activity of defective adenovirus particles. In particular, greater than 90% of the transfected-cell population is found to express a beta-galactosidase gene, and, most importantly, this high level of expression can be obtained with psoralen-inactivated virus particles. Furthermore, because the delivered gene is not carried within the genome of the adenovirus particle, the size constraints are relieved, and we can, therefore, show the delivery of a 48-kilobase cosmid DNA molecule.
Monofilaments : do you use them? Do you have the correct kind? If so, are you using them correctly? : original article (2011)

Peripheral neuropathy is a risk factor for developing foot ulceration in diabetes. Early detection leading to adequate foot care can significantly reduce amputation rates. Assessment tools that are simple, objective, reproducible and comprehensive are essential. Several have been advocated ranging from the practical to the impractical and from costly to free of charge.
P-selectin mediates neutrophil adhesion to endothelial cell borders (1999)

During an acute inflammatory response, endothelial P-selectin (CD62P) can mediate the initial capture of neutrophils from the free flowing bloodstream. P-selectin is stored in secretory granules (Weibel-Palade bodies) and is rapidly expressed on the endothelial surface after stimulation with histamine or thrombin. Because neutrophil transmigration occurs preferentially at endothelial borders, we wished to determine whether P-selectin-dependent neutrophil capture (adhesion) occurs at endothelial cell borders. Under static or hydrodynamic flow (2 dyn/cm2) conditions, histamine (10(-4) M) or thrombin (0.2 U/mL) treatment induced preferential (> or = 75%) neutrophil adhesion to the cell borders of endothelial monolayers. Blocking antibody studies established that neutrophil adhesion was completely P-selectin dependent. P-selectin surface expression increased significantly after histamine treatment and P-selectin immunostaining was concentrated along endothelial borders. We conclude that preferential P-selectin expression along endothelial borders may be an important mechanism for targeting neutrophil migration at endothelial borders.
Cascaded DC-DC converter connection of photovoltaic modules (2003)

New residential scale photovoltaic (PV) arrays are commonly connected to the grid by a single DC-AC inverter connected to a series string of PV modules, or many small DC-AC inverters which connect one or two modules directly to the AC grid. This paper shows that a "converter-per-module" approach offers many advantages including individual module maximum power point tracking, which gives great flexibility in module layout, replacement, and insensitivity to shading; better protection of PV sources, and redundancy in the case of source or converter failure; easier and safer installation and maintenance; and better data gathering. Simple nonisolated per-module DC-DC converters can be series connected to create a high voltage string connected to a simplified DC-AC inverter. These advantages are available without the cost or efficiency penalties of individual DC-AC grid connected inverters. Buck, boost, buck-boost and Cuk converters are possible cascadable converters. The boost converter is best if a significant step up is required, such as with a short string of 12 PV modules. A string of buck converters requires many more modules, but can always deliver any combination of module power. The buck converter is the most efficient topology for a given cost. While flexible in voltage ranges, buck-boost and Cuk converters are always at an efficiency or alternatively cost disadvantage.
Biochemical markers in persons with preclinical familial Alzheimer disease (2008)

Our data indicate that Abeta(42) is elevated in plasma in familial Alzheimer disease (FAD) mutation carriers (MCs) and suggests that this level may decrease with disease progression prior to the development of overt dementia. We also demonstrated that the ratio of Abeta(42) to Abeta(40) was reduced in the CSF of nondemented MCs and that elevations of t-tau and p-tau(181) are sensitive indicators of presymptomatic disease. Our finding of elevated F(2)-isoprostane levels in the CSF of preclinical FAD MCs suggests that oxidative stress occurs downstream to mismetabolism of amyloid precursor protein.
Reduced yield of infectious pseudorabies virus and herpes simplex virus from cell lines producing viral glycoprotein gp50 (1988)

Pseudorabies virus (PRV) glycoprotein gp50 is the homolog of herpes simplex virus (HSV) glycoprotein D. Several cell lines that constitutively synthesize gp50 were constructed. Vero cells, HeLa cells, and pig kidney (MVPK) cells that produce gp50 all gave reduced yields of PRV and HSV progeny viruses when compared with the parent cell line or the same cell line transfected to produce a different protein. The reduction in virus yield was greatest at low multiplicities of infection. The Vero and HeLa cells that produce gp50 showed an even greater reduction in HSV yield than in PRV yield. This phenomenon may be an example in a herpesvirus of the interference observed in retroviruses or cross-protection in plant virus systems.
Bayesian Convolutional Neural Networks with Bernoulli Approximate Variational Inference (2015)

Convolutional neural networks (CNNs) work well on large datasets. But labelled data is hard to collect, and in some applications larger amounts of data are not available. The problem then is how to use CNNs with small data -- as CNNs overfit quickly. We present an efficient Bayesian CNN, offering better robustness to over-fitting on small data than traditional approaches. This is by placing a probability distribution over the CNN's kernels. We approximate our model's intractable posterior with Bernoulli variational distributions, requiring no additional model parameters. On the theoretical side, we cast dropout network training as approximate inference in Bayesian neural networks. This allows us to implement our model using existing tools in deep learning with no increase in time complexity, while highlighting a negative result in the field. We show a considerable improvement in classification accuracy compared to standard techniques and improve on published state-of-the-art results for CIFAR-10.
Integration of GaAs vertical-cavity surface emitting laser on Si by substrate removal (1994)

Substrate removal techniques are attractive for the integration of III-V compound semiconductor devices on Si for the integration of optical and electronic devices, and on thermally conducting substrates for heat sinking. Here we discuss the bonding of strained quantum well InGaAs vertical-cavity surface-emitting lasers on both Si and Cu substrates. The GaAs substrates are then removed by selective etching. Lasing was achieved with pulsed electrical pumping with Jth=2.5 kA/cm2. The performance characteristics of the Si and Cu bonded devices are compared.
Anti-TNF-alpha therapy as a clinical intervention for periprosthetic osteolysis. (2000)

Aseptic loosening of total joint arthroplastics due to periprosthetic osteolysis is a frequent cause of implant failure. The absence of clinical interventions to arrest or prevent this complication limits the use of total joint replacement especially in younger patients. Here we review recent studies implicating tumor necrosis factor (TNF)-alpha in periprosthetic osteolysis and the rationale for clinical studies of anti-TNF therapy and other interventions for periprosthetic loosening.
Results of Molecular Detection ofMycoplasma pneumoniaeamong Patients with Acute Respiratory Infection and in Their Household Contacts Reveals Children as Human Reservoirs (2001)

During a 30-month prospective study in The Netherlands, the distribution of Mycoplasma pneumoniae and respiratory viruses among 1172 patients with acute respiratory infection (ARI) who were treated in the outpatient general practitioner setting was studied. M. pneumoniae, as detected by polymerase chain reaction analysis, was present in 39 (3.3%) patients. The infection rate was similar in all age groups. Nose and throat samples collected from 79 household contacts of M. pneumoniae-positive index patients revealed M. pneumoniae in 12 (15%) cases. The frequency of M. pneumoniae among household contacts of index patients treated with appropriate antibiotics and untreated index patients was similar. Nine of the 12 M. pneumoniae-positive household contacts were <16 years old (P=.02), and 4 (44%) of them did not develop ARI. Apparently, children are a relevant reservoir for M. pneumoniae.
Synthesis of Passivating, Nylon-Like Coatings through Cross-Linking of Ultrathin Polyelectrolyte Films (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSynthesis of Passivating, Nylon-Like Coatings through Cross-Linking of Ultrathin Polyelectrolyte FilmsJeremy J. Harris, Paul M. DeRose, and Merlin L. BrueningView Author Information Department of Chemistry, Michigan State University East Lansing, Michigan 48824 Cite this: J. Am. Chem. Soc. 1999, 121, 9, 1978–1979Publication Date (Web):February 18, 1999Publication History Received21 September 1998Published online18 February 1999Published inissue 1 March 1999https://pubs.acs.org/doi/10.1021/ja9833467https://doi.org/10.1021/ja9833467rapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views2583Altmetric-Citations287LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Amides,Deposition,Electrodes,Nucleic acid structure,Polyelectrolytes Get e-Alerts
Fast and space-efficient virtual machine checkpointing (2011)

Checkpointing, i.e., recording the volatile state of a virtual machine (VM) running as a guest in a virtual machine monitor (VMM) for later restoration, includes storing the memory available to the VM. Typically, a full image of the VM's memory along with processor and device states are recorded. With guest memory sizes of up to several gigabytes, the size of the checkpoint images becomes more and more of a concern.
Detection of HIV-specific cell-mediated cytotoxicity in the peripheral blood from infected children (1993)

Cytotoxic T lymphocytes may play a significant role in containing the spread of HIV in infected individuals. Although HIV-infection is associated with immune suppression, a vigorous T lymphocyte response has been detected in infected adults. HIV can be transmitted from mother to child, either during pregnancy, when differentiation of the T lymphoid compartment is ongoing, or at birth when the neonate immune system is partially competent. The shorter asymptomatic period of pediatric infection could be related to differences in the host immune control of viral replication. HIV-specific cell-mediated cytotoxicity (CMC) from fresh and in vitro stimulated PBMC of HIV-infected children was measured. CD8+CD3+ T lymphocytes were found to be the major effector population. The vast majority of children examined had detectable HIV-specific CMC. A cross-sectional analysis of CMC responses as a function of clinical status revealed that 71% of asymptomatic children (CDC stage P1) recognized the Env protein, 14% the Gag protein, but none of them recognized the Pol protein. Cytolytic activities directed against these three proteins were detected in two thirds of paucisymptomatic children (P2A). In contrast, symptomatic children (P2B-F) did not show cytolytic activities toward the Gag and Pol proteins, and only 20% recognized the Env protein. In contrast in vitro generated secondary CTL were consistently detected at all stages of disease, even in children with low CD4+ cells counts.