gebhart/patrepeval huggingface dataset:
The diagnostic approach to immediate hypersensitivity in patients with allergic rhinitis; a comparison of nasal challenges and serum rast. (1983)

Nasal challenges performed in 182 patients with allergic rhinitis revealed 273 positive and 125 negative responses to house dust, grass pollen, cat and dog danders and aspergillus fumigatus, which all correlated with disease history and intracutaneous tests. In these randomly selected patients the specific IgE antibodies in the serum to the same allergens as those used for nasal challenges were determined quantitatively by serum RAST. Additionally, blood and nasal eosinophilia were recorded during the nasal provocation tests. In all 273 positive challenges protection tests with disodium cromoglycate (DSCG) were also performed. In 24.2% of the positive nasal challenges serum RAST was found positive and in 18.7% of them serum RAST was doubtful. In 52% of the negative nasal challenges negative serum RAST also occurred. No significant correlation was found between serum RAST and nasal challenges (X2 = 0.92; d.f. = 1; 0.20 less than p less than 0.40). No significant correlation was found between serum RAST and nasal challenges for individual allergens tested. Since the nasal provocation test is an in vivo technique, it is likely to be of value for the diagnostic confirmation of the allergic component (due to immediate hypersensitivity) in patients with allergic rhinitis than serum RAST alone. Although serum RAST cannot substitute the nasal provocation tests, it may be a useful supplementary diagnostic parameter.
Use of an automated laboratory workstation for isolation of genomic DNA suitable for PCR and allele-specific hybridization. (1993)

In this paper we describe the isolation of genomic DNA by using anion exchange chromatography performed on a Biomek 1000 Automated Laboratory Workstation. This procedure allows the automated isolation of DNA suitable for most molecular analyses employed in diagnosis of genetic pathologies and infectious diseases. The genomic DNA isolated by using the Biomek 1000 was indeed found to be suitable for polymerase chain reaction and allele-specific hybridization.
A new NEDD8-ligating system for cullin-4A (1998)

NEDD8 is a ubiquitin (Ub)-like protein. Here we report a novel ubiquitinylation-related pathway for modification by NEDD8. NEDD8 was activated by an E1 (Ub-activating enzyme)-like complex, consisting of APP-BP1 and hUba3 with high respective homologies to the amino- and carboxy-terminal regions of E1 and then linked to hUbc12 (a human homolog of yeast Ub-conjugating enzyme Ubc12p). The major target protein modified by NEDD8 was found to be Hs-cullin-4A (Cul-4A), a member of the family of human cullin/Cdc53 proteins functioning as an essential component of a multifunctional Ub-protein ligase E3 complex that has a critical role in Ub-mediated proteolysis.
Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation (2018)

Analysis of chromatin accessibility can reveal transcriptional regulatory sequences, but heterogeneity of primary tissues poses a significant challenge in mapping the precise chromatin landscape in specific cell types. Here we report single-nucleus ATAC-seq, a combinatorial barcoding-assisted single-cell assay for transposase-accessible chromatin that is optimized for use on flash-frozen primary tissue samples. We apply this technique to the mouse forebrain through eight developmental stages. Through analysis of more than 15,000 nuclei, we identify 20 distinct cell populations corresponding to major neuronal and non-neuronal cell types. We further define cell-type-specific transcriptional regulatory sequences, infer potential master transcriptional regulators and delineate developmental changes in forebrain cellular composition. Our results provide insight into the molecular and cellular dynamics that underlie forebrain development in the mouse and establish technical and analytical frameworks that are broadly applicable to other heterogeneous tissues.
Therapeutic Intervention and Targets for Sepsis (2004)

Sepsis syndrome, a systemic response to infection, can beget devastating outcomes even in previously normal individuals. Recent research in septic patients has led to the discovery that early goal-directed resuscitation guided by continuous monitoring of mixed venous hemoglobin saturation, along with moderate doses of corticosteroids, can reduce mortality. An improved understanding of the complex interaction between the inflammatory and coagulant systems in sepsis pathophysiology has resulted in novel treatments, such as recombinant human activated protein C, which improves survival in patients with severe sepsis and a high risk of death. However, despite an increased understanding of the complex pathophysiology of this syndrome and the discovery of new, effective treatments, severe sepsis still results in significant morbidity and mortality. Consequently, investigations continue into additional therapeutic agents directed against novel targets. Following a review of recent advances in sepsis treatment, we briefly discuss a few of the new, promising therapeutic strategies currently being investigated.
Computer search algorithms in protein modification and design (1998)

The computer-aided design of protein sequences requires efficient search algorithms to handle the enormous combinatorial complexity involved. A variety of different algorithms have now been applied with some success. The choice of algorithm can influence the representation of the problem in several important ways--the discreteness of the configuration, the types of energy terms that can be used and the ability to find the global minimum energy configuration. The use of dead end elimination to design the complete sequence for a small protein motif and the use of genetic and mean-field algorithms to design hydrophobic cores for proteins represent the major themes of the past year.
IN VITRO FUNCTIONAL PROPERTIES OF THE RAT BLADDER REGENERATED BY THE BLADDER ACELLULAR MATRIX GRAFT (1998)

The present study provides further evidence that augmentation cystoplasty with the BAMG leads to functional regeneration of the rat bladder detrusor smooth muscle.
Genetic and physical interactions between yeast RGR1 and SIN4 in chromatin organization and transcriptional regulation. (1995)

The SIN4 and RGR1 genes of Saccharomyces cerevisiae were identified by mutations in quite different genetic screens. We have shown that the SIN4 gene product is required for proper transcriptional regulation of many genes and that a sin4 mutation can affect either activation or repression of specific genes. We have suggested that this dual nature of SIN4 in transcriptional regulation is due to its involvement in chromatin organization. We now report that the role of RGR1 in gene regulation is similar to that of SIN4. SIN4 and RGR1 both function as negative transcriptional regulators of HO and IME1, and mutations in either gene lead to decreased expression of other genes including CTS1. Strains with sin4 or rgr1 mutations both have phenotypes similar to those caused by histone mutations, including suppression of delta insertion into promoters (Spt- phenotype), activation of promoters lacking UAS elements, and decreased superhelical density of plasmid DNA molecules. Overexpression of RGR1 suppresses the temperature sensitivity due to a sin4 mutation. Finally, we use yeast strains expressing GST fusion proteins to demonstrate that the Sin4p and Rgr1p proteins are physically associated in vivo. These results indicate that Sin4p and Rgr1p act together in vivo to organize chromatin structure and thus regulate transcription.
CHANGES IN RETINAL MORPHOLOGY AND VITAMIN A METABOLISM AS A CONSEQUENCE OF DECREASED ZINC AVAILABILITY (1982)

From the Department of Anatomy, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania, and the Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
Nuclear factor-κB as a therapeutic target in critical care medicine (2003)

Nuclear factor-kappaB is a transcriptional factor required for the gene expression of many inflammatory mediators. Nuclear factor-kappaB activation requires removal and degradation of its inhibitor kappaB, an event that occurs after phosphorylation of inhibitor kappaB by a complex of inhibitor kappaB kinases. These events allow nuclear factor-kappaB to translocate into the nucleus, where it binds to kappaB elements and initiates transcription. Inappropriate and prolonged activation of nuclear factor-kappaB has been linked to several diseases associated with inflammatory events, including septic shock, acute respiratory distress syndrome, ischemia, and reperfusion injury. Thus, the key role of nuclear factor-kappaB in regulating inflammation makes this factor a therapeutic target for reducing tissue and organ damage. Regulation and control of nuclear factor-kappaB can be achieved by gene modification strategies or by pharmacologic inhibition of the key components of the cascade that leads to nuclear factor-kappaB activation. The purpose of our review is to describe these novel therapeutic approaches and their potential efficacy.
Chemically modified nucleic acids as immunodetectable probes in hybridization experiments. (1984)

Guanine residues in nucleic acids can be modified by treatment with N-acetoxy-N-2-acetylaminofluorene and its 7-iodo derivative in an in vitro nonenzymatic reaction. The modified nucleic acids (ribo or deoxyribo, single or double stranded) are recognized by specific antibodies. They can be immunoprecipitated or used as probes in hybridization experiments and detected by immunochemical techniques.
Inhibition of vaccinia mRNA methylation by 2',5'-linked oligo(adenylic acid) triphosphate. (1981)

Extracts of interferon-treated cells synthesize unique 2',5'-linked oligo(adenylic acid) 5'-phosphates in the presence of ATP and double-stranded RNA. 2',5'-linked oligo(adenylic acid) 5'-triphosphate inhibits protein synthesis at nanomolar concentrations by activating RNase. We have observed that oligo(adenylic acid) 5'-monophosphate and 5'-triphosphate are potent inhibitors of vaccinia mRNA methylation in vitro. Both the methylation of mRNA methylation is not due to degradation of the mRNA. Inhibition of the 5'-terminal guanine at the 7 position and the 2'-O-ribose methylation of the penultimate nucleoside are inhibited. Such inhibition of the requisite modification of the 5' terminus of mRNA by 2',5'-linked oligo(adenylic acids) may be a mechanism of interferon action against both DNA and RNA viruses in which mRNAs derived from them are capped.
A good practice guide to the administration of substances and removal of blood, including routes and volumes (2001)

This article is the result of an initiative between the European Federation of Pharmaceutical Industries Associations (EFPIA) and the European Centre for the Validation of Alternative Methods (ECVAM). Its objectives are to provide the researcher in the safety evaluation laboratory with an up-to-date, easy-to-use set of data sheets to aid in the study design process whilst at the same time affording maximum welfare considerations to the experimental animals. Although this article is targeted at researchers in the European Pharmaceutical Industry, it is considered that the principles underpinning the data sets and refinement proposals are equally applicable to all those who use these techniques on animals in their research, whether in research institutes, universities or other sectors of industry. The implications of this article may lead to discussion with regulators, such as those responsible for pharmacopoeial testing. There are numerous publications dealing with the administration of test substances and the removal of blood samples, and many laboratories also have their own "in-house" guidelines that have been developed by custom and practice over many years. Within European Union Directive 86/609EEC1 we have an obligation to refine experiments to cause the minimum amount of stress. We hope that this article will provide background data useful to those responsible for protocol design and review. This guide is based on peer-reviewed publications whenever possible, but where this is not possible we have used "in-house" data and the experience of those on the working party (as well as helpful comments submitted by the industry) for a final opinion. The guide also addresses the continuing need to refine the techniques associated with the administration of substances and the withdrawal of blood, and suggests ways of doing so. Data-sharing between laboratories should be encouraged to avoid duplication of animal work, as well as sharing practical skills concerning animal welfare and scientific problems caused by "overdosing" in some way or another. The recommendations in this guide refer to the "normal" animal, and special consideration is needed, for instance, during pregnancy and lactation. Interpretation of studies may be confounded when large volumes are administered or excessive sampling employed, particularly if anaesthetics are used.
Cigarette smoke selectively enhances viral PAMP– and virus-induced pulmonary innate immune and remodeling responses in mice (2008)

Viral infections have more severe consequences in patients who have been exposed to cigarette smoke (CS) than in those not exposed to CS. For example, in chronic obstructive pulmonary disease (COPD), viruses cause more severe disease exacerbation, heightened inflammation, and accelerated loss of lung function compared with other causes of disease exacerbation. Symptomatology and mortality in influenza-infected smokers is also enhanced. To test the hypothesis that these outcomes are caused by CS-induced alterations in innate immunity, we defined the effects of CS on pathogen-associated molecular pattern-induced (PAMP-induced) pulmonary inflammation and remodeling in mice. CS was found to enhance parenchymal and airway inflammation and apoptosis induced by the viral PAMP poly(I:C). CS and poly(I:C) also induced accelerated emphysema and airway fibrosis. The effects of a combination of CS and poly(I:C) were associated with early induction of type I IFN and IL-18, later induction of IL-12/IL-23 p40 and IFN-gamma, and the activation of double-stranded RNA-dependent protein kinase (PKR) and eukaryotic initiation factor-2alpha (eIF2alpha). Further analysis using mice lacking specific proteins indicated a role for TLR3-dependent and -independent pathways as well as a pathway or pathways that are dependent on mitochondrial antiviral signaling protein (MAVS), IL-18Ralpha, IFN-gamma, and PKR. Importantly, CS enhanced the effects of influenza but not other agonists of innate immunity in a similar fashion. These studies demonstrate that CS selectively augments the airway and alveolar inflammatory and remodeling responses induced in the murine lung by viral PAMPs and viruses.
Implementation (2017)

In this chapter, we will present the technical aspects of atomistic spin dynamics, in particular how the method can be implemented in an actual computer software. This involves calculation of effective field and creation of neighbour lists for setting up the geometry of the system of interest as well as choosing a suitable integrator scheme for the SLL (or SLLG) equation. We also give examples of extraction and processing of relevant observables that are common output from simulations. Atomistic spin dynamics simulations could be a computationally heavy tool but it is also very well adapted for modern computer architectures like massive parallel computing and/or graphics processing units and we provide examples how to utilize these architectures in an efficient manner. We use our own developed software UppASD as example, but the discussion could be applied to any other atomistic spin dynamics software.
Influenza virus NS1 protein enhances the rate of translation initiation of viral mRNAs (1995)

The effect of NS1 protein on the efficiency of influenza virus mRNA translation was evaluated by determining the accumulation of nucleoprotein (NP) or M1 mRNAs in the cytoplasm of cells expressing either of these genes alone or in combination with the NS1 gene, as well as the total cell accumulation of NP or M1 protein. Coexpression of NS1, but not of NS2 protein, led to increases in the translation of these mRNAs in the range of 5- to 100-fold. This translation enhancement was specific for viral mRNAs, since the translation of neither cat nor lacZ mRNAs was affected by the coexpression of NS1 protein. The use of chimeric cat genes containing the 5'-extracistronic sequences of the influenza virus mRNAs corresponding to segment 2, 7, or 8 indicated that these sequences can in part account for the observed effect. The enhancement of viral mRNA translation mediated by NS1 protein was due to an increase in the translation initiation rate, since the sizes of NP-specific polysomes, but not those of lacZ-specific polysomes, was significantly higher in cells coexpressing NS1 protein than in those expressing only the NP gene.
Mode adaptive Unequal Error Protection for transform predictive speech and audio coders (2002)

In this paper we investigate the application of Unequal Error Protection (UEP) channel coding schemes to the Transform Predictive Coding (TPC) audio coding paradigm. The TPC paradigm has natural perceptual ordering of the bitstream that provides a good match with the UEP concept. Also introduced is the general idea of Mode Adaptive UEP schemes that adapt to the differing bit-error sensitivity profiles of signal adaptive multimode source-coders. By doing this the decoded signal quality is optimized jointly over the input signal, the channel conditions and the bit-error sensitivity profile of the source coder.
Toward 40% and higher solar cells in a new Cassegrainian PV module (2005)

We demonstrate a 40% efficient multijunction (MJ) cell capable of being used to make a 33% efficient solar concentrator PV module using the new Cassegrainian PV module design. This very high efficiency module can then produce cost competitive solar electric power.
MOSFETs with ultrashallow junction and minimum drain area formed by using solid-phase diffusion from SiGe (2001)

An advanced CMOS structure, in which a raised source/drain and contact windows formed over the field oxide, was fabricated. Ultrashallow junction formation using solid-phase diffusion from doped SiGe layers was used to fabricate MOSFETs. These MOSFETs demonstrated excellent short-channel characteristics and 70%-80%-reduced parasitic drain-junction capacitance. They have ultrashallow junctions with a depth of 25 nm and a low source/drain extension (SDE) resistance: 350 /spl Omega//sq (NMOSFETs) and 390 /spl Omega//sq (PMOSFETs). The isotropic diffused SDE structure was formed by using solid-phase diffusion, which could effectively form a shallow junction and a suitable overlap between gate and SDE. This structure results in good short-channel characteristics and high current drivability.
Providing Multiple-Channel Communication Using the Experimental Digital Switch (1982)

This report describes the functional characteristics of a circuit-switched network which is capable of providing data communication paths as well as voice channels. In the system described, the circuit switch may be shared in order to provide multiple independently switched paths through the network. Unlike a conventional circuit switch, this sharing permits only a fraction of the switching capacity to be consumed which is proportional to the allocated bandwidth of the path. Additional economy is gained by providing multiple communication paths over the single communication resource between the subscriber and the switching machine. The fraction of the communication resource which is used by the subscriber is proportional to the total bandwidth of the channels which have been allocated. This allocation is performed dynamically, in response to subscriber requests. Algorithms are presented which perform this allocation efficiently. The resulting network provides a communication vehicle which provides both data and voice services in an integrated fashion.
Signal Transduction Pathway of Human Fibroblast Growth Factor Receptor 3 (1997)

Stimulation of fibroblast growth factor receptor 3 (FGFR3) results in a variety of functional effects, including regulation of epithelial cell growth and differentiation. In order to characterize the signaling pathway through which FGFR3 regulates cell growth, L6 cells lacking any endogenous FGFR were stably transfected with the two different human isoforms, FGFR3 IIIb and FGFR3 IIIc, that result from alternative splicing of exon III of the FGFR3 gene encoding the ligand binding domain. Expression of FGFR3 IIIc in stably transfected L6 cells conferred growth responses to several members of the FGF family including FGF-1, -2, -4, and -6, while FGFR3 IIIb-expressing cells responded only to FGF-1. Activation of FGFR3 upon ligand binding resulted in activation of mitogen-activated protein kinase pathway. FGFR3 utilizes two different pools of adapter protein GRB2 to link to Ras. Activated FGFR3 predominantly interacts with GRB2.Sos in complex with a previously identified 90-kDa protein and designated protein 80K-H. In addition, 80K-H.GRB2. Sos complex was found to contain a novel 66-kDa protein. Tyrosine phophorylation of the 66-kDa protein was dependent on ligand activation of FGFR3, suggesting that the 66-kDa protein may play an important role in FGFR3-specific signaling. In addition to this unique pathway, FGFR3 also links to GRB2.Sos complex via the adapter protein Shc. Furthermore, activated FGFR3 was not able to induce dissociation of GRB2.Sos complex following Sos phosphorylation. In summary, FGFR3 signaling pathway utilizes two GRB2-containing complexes; Shc.GRB2.Sos and 80K-H.pp66.GRB2.Sos; these two complexes may alternatively link FGFG3 to mitogen-activated protein kinase. Finally, activated FGFR3 was also found to result in phosphorylation of phospholipase C-gamma but reduced phosphorylation of c-Src.
Experimental and Theoretical Evidence for Long-Lived Molecular Hydrogen AnionsH2−andD2− (2005)

The existence of (metastable) molecular hydrogen anions H2(-), D2(-), and H3(-) is demonstrated. These anion species were produced by sputtering of TiH2 and TiD2 targets with Cs+ ions and were identified by accelerator mass spectrometry. From the respective flight times through the spectrometer, lifetimes for H2(-) and D2(-) of at least 3 micros and 4 micros, respectively, can be inferred. Theoretical calculations within the nonlocal resonance model predict the existence of highly rotationally excited anions with lifetimes in the micros range. It is proposed that in sputtering molecular hydrogen species with high rotational and vibrational excitation are formed that are stable on the time scale of the experiment.