gebhart/patrepeval huggingface dataset:
Crystallization of the complex of human IFN‐γ and the extracellular domain of the IFN‐γ receptor (1995)

A complex of human interferon-gamma (IFN-gamma) with the soluble extracellular domain of the IFN-gamma receptor alpha-chain (IFN-gamma-R) has been crystallised. Crystals of the complex were grown using PEG 4000 as the precipitating agent in the presence of beta-octyl glucoside. The receptor-ligand complex crystallizes in a monoclinic space group and diffracts to about 3.0 A resolution. Isomorphous crystals have been obtained with complex containing selenomethionine and cysteine mutants of IFN-gamma, which may facilitate the ongoing X-ray structure determination.
MET exon 14 juxtamembrane splicing mutations: clinical and therapeutical perspectives for cancer therapy (2017)

The <i>MET</i> proto-oncogene plays crucial roles in cell growth and proliferation, survival and apoptosis, epithelial-mesenchymal transition (EMT) and invasion, potentially conditioning the development and progression of the carcinogenesis process. The MET-associated aberrant signaling could be triggered by a variety of mechanisms, such as mutations, gene amplification, increased gene copy number and Met/HGF protein expression. Among the various <i>MET</i> alterations, <i>MET</i> exon 14 splicing abnormalities, causing the loss of the Met juxtamembrane (JM) domain, recently emerged as a new potential oncogenic driver and have been identified and validated across different cancer and histology subtypes. Moreover, this aberration was found to be mutually exclusive with other recognized drivers, thus strongly nominating its potential oncogenic role. Recently, the clinical activity of anti-Met-targeted therapy was demonstrated particularly in patients harboring <i>MET</i> exon 14 skipping lung cancer, resulting in a renewed enthusiasm to further test MET precision therapy in prospective trials. In this review, the key preclinical and clinical data regarding <i>MET</i> exon 14 skipping splicing variants as an actionable genomic aberration in cancer are described, and the perspectives deriving from the validation of such alteration as a potential target, which may further allow driving the therapeutic approach in this molecularly selected patients' subgroup, are explored.
Vasoactive peptide release in the extracerebral circulation of humans during migraine headache (1990)

The innervation of the cranial vessels by the trigeminal nerve, the trigeminovascular system, has recently been the subject of study in view of its possible role in the mediation of some aspects of migraine. Since stimulation of the trigeminal ganglion in humans leads to facial pain and flushing and associated release of powerful neuropeptide vasodilator substances, their local release into the extracerebral circulation of humans was determined in patients who had either common or classic migraine. Venous blood was sampled from both the external jugular and cubital fossa ipsilateral to the side of headache. Plasma levels of neuropeptide Y, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide were determined using sensitive radioimmunoassays for each peptide, and values for the cubital fossa and external jugular and a control population were compared. A substantial elevation of the calcitonin gene-related peptide level in the external jugular but not the cubital fossa blood was seen in both classic and common migraine. The increase seen in classic migraine was greater than that seen with common migraine. The other peptides measured were unaltered. This finding may have importance in the pathophysiology of migraine.
Novel monocyclic and bicyclic loop mimetics of brain-derived neurotrophic factor (2006)

Brain-derived neurotrophic factor (BDNF) is a protein that promotes the survival of neurons. It is widely thought to possess clinical potential for the treatment of neurodegenerative diseases, and in recent years, has been found to play a role in the pathogenesis of some tumours. BDNF is thought to bind to its cellular receptors trkB and p75(NTR) primarily by way of solvent-exposed loops on the BDNF dimer. In this paper, we describe our recent progress towards the development of small peptides as mimetics and inhibitors of BDNF. Two classes of peptides were prepared: disulphide-constrained monomeric monocyclic peptides designed to mimic a single solvent-exposed loop; and homo- and heterodimeric bicyclic peptides designed to mimic pairs of loops. Each peptide was examined in cultures of embryonic chick dorsal root ganglion sensory neurons, both alone, and in competition with BDNF. All peptides were found to inhibit BDNF-mediated neuronal survival, while one--a dimeric peptide based on the two loop 4 regions of BDNF--behaved as a partial BDNF-like agonist. The work described in this paper supports the proposed receptor-binding role of loops 1, 2, and 4 of BDNF, and provides valuable steps towards our long-term goal of developing BDNF mimetics and inhibitors for clinical use.
<title>Safe use of ultrashort lasers</title> (1999)

We review the progress made in determining the trends in retinal damage from laser pulse from one nanosecond to one hundred femtoseconds in the visible and near-infrared wavelength regimes. These trends have suggested a maximum permissible exposure limit for laser pulses in the retinal hazard regime between one nanosecond and one hundred femtoseconds. We discuss the likely mechanisms for retinal damage and the implications to using ultrashort laser systems safely. We will summarize the challenges in appropriately addressing safety when using ultrashort laser systems in advanced applications.
Brown midrib-3 corn silage improves digestion but not performance of growing beef steers. (2000)

The brown midrib-3 (bm3) gene mutation has been incorporated into corn plants to potentially improve fiber digestibility. The objectives of this study were to determine the effect of bm3 corn silage on digestion and performance of growing beef steers and to determine whether limiting intake would further enhance fiber digestibility of bm3 corn silage. A bm3 hybrid and its isogeneic normal counterpart were harvested at three-quarters kernel milk line. Neutral detergent fiber, ADF, and ADL were 4.5, 6.9, and 1.9 units lower, respectively, and DM was 5.4 units higher for bm3 than for normal silage. In Trial 1, eight ruminally fistulated Angus crossbred steers (224 +/- 24 kg) were randomly assigned to a 2 x 2 factorial arrangement of treatments in a replicated 4 x 4 Latin square design. Steers had ad libitum feed access or were restricted to 80% of ad libitum intake of diets containing 86% normal corn silage (Control) or bm3 corn silage (BMCS). The remainder of the diets consisted of soybean meal, urea, monensin, vitamins, and minerals. Dry matter intake was greater (P < 0.01) for steers offered ad libitum access to BMCS than for those with ad libitum access to the Control diet. The BMCS treatment resulted in improved (P < 0.05) apparent total-tract digestibility of DM, OM, NDF, and ADF. Mean concentration of total VFA and molar proportions of acetate were increased (P < 0.05) by feeding BMCS. There tended to be a DMI x hybrid interaction (P = 0.16) for apparent total-tract digestibility of NDF. When diets were offered ad libitum, BMCS increased NDF digestibility by 10.5 percentage units compared with Control, but, when DMI was limited, BMCS increased NDF digestibility by 15.8 percentage units. In Trial 2, 128 steer contemporaries of those used in Trial 1 (245 +/- 13 kg) were offered ad libitum access to BMCS or Control diets as used in Trial 1. After a 112-d treatment period, concentrate in the diet was increased, and all steers were fed a common finishing diet. During the 112-d treatment period, steers receiving BMCS consumed 0.45 kg more DM/d (P < 0.05) and had similar ADG (P > 0.10), compared with those steers receiving the Control silage. This resulted in poorer (P < 0.01) feed efficiency for steers receiving BMCS. Finishing phase and overall performance of the steers was not different (P > 0.10) due to treatment. Although feeding BMCS in growth-phase diets resulted in increased daily DMI and improved digestibility of DM and fiber, it did not result in improved steer feedlot ADG compared with Control silage.
Assessment of circadian rhythms by actimetry in healthy subjects and patients with advanced colorectal cancer. (2003)

Circadian rhythms can be altered in severe illness such as cancer; the rest-activity circadian cycle has been used as a reference for the administration of chemotherapy at specific times in order to improve tolerability and efficacy. We assessed the feasibility of the method in our center in a sample of patients with metastatic colorectal cancer selected for chronomodulated chemotherapy. Activity of the circadian rhythms were measured non-invasively in 10 patients with metastatic colorectal cancer by wrist actimetry, and compared to healthy subjects. Patients and healthy subjects were requested to wear an actigraph, a wristwatch that records the number of accelerations per minute, for 3 days. Healthy subjects exhibited high activity levels during daytime, followed by low activity levels during the night. In patients, the contrast between daytime activity and nocturnal sleep was noticeably less marked, and a wide inter-patient variability was observed. All the patients wore the actigraph with a total compliance. Actimetry may provide a simple and innovative tool to study the circadian system and may be considered as an objective and accurate method to evaluate the individual health status ("conditions of life") in cancer patients, independently of all ("quality of life" questionnaires.
Electroluminescence Studies on Self-Assembled Films of PPV and CdSe Nanoparticles (1998)

Electrooptical and structural studies on self-assembled films composed of CdSe nanoparticles, poly(p-phenylene vinylene) (PPV), and different nonconjugated polyelectrolytes are reported. It is demonstrated by optical spectroscopy and X-ray reflectivity measurements that CdSe nanoparticles and PPV can successfully be incorporated into homogeneous ultrathin films by the self-assembly method. The surface roughness obtained from the X-ray measurements is 2.7 and 1.3 nm respectively for CdSe/PAH (PAH, poly(allylamine) hydrochloride) and PSS/PPV (PSS, poly(styrenesulfonic acid)) multilayer films. This allows us to stack a (PSS/PPV)*n film on top of a (CdSe/PAH)*n film to build up well-defined two-layer composite film devices. Electroluminescence studies show that pure (PSS/PPV)*n film devices exhibit green light emission but with a very short lifetime (several seconds) if operated in ambient air. During operation, the PPV emission shifts toward the blue, which indicates that the mean conjugation length of PPV is shortened due to oxidation. Oxidation of CdSe particles is also observed in (CdSe/PAH)*n devices during operation. However, the stability of CdSe particles is enhanced if they are combined alternately with PPV, and a (CdSe/PPV)*n device gives a broad, nearly white emission. The turn-on voltage of it is much smaller and better defined than that for a (CdSe/PAH)*20 device. This proves that PPV works like a charge-transportation layer rather than an emitting layer in the (CdSe/PPV)*n film device. In an ITO//PEI(CdSe/PAH)*10/(PSS/PPV)*10//Al two-layer composite film device the lifetime of PPV electroluminescence can be prolonged for at least 1 order of magnitude only after the device is first operated under backward bias (positive pole on Al electrode). This suggests that the oxygen within the film is removed by this operation due to oxidation of the particles. Afterward, this two-layer composite film device presents emission from PPV and CdSe, respectively, when the sign of the external voltage is changed.
In Vitro Gene Delivery to Hepatocytes with Galactosylated Polyethylenimine (1997)

A hepatocyte-directed vector has been developed; it includes several key features thought to favor in vivo gene delivery to the liver: electrostatically neutral particles which avoid nonspecific binding to other cells, to the extracellular matrix, and to complement proteins; asialoglycoprotein receptor-mediated endocytosis which may address the complexes to the perinuclear region; and polyethylenimine (PEI)-mediated endosome buffering and swelling as an escape mechanism to the cytoplasm. This system is based on a 5% galactose-bearing polyethylenimine (PEI-gal) polymer which is condensed with plasmid DNA to neutrality. Murine (BNL CL.2) and human (HepG2) hepatocyte-derived cell lines were transfected 10(4)-10(5)-fold more efficiently than murine fibroblasts (3T3), whether transfection was assessed globally (luciferase expression from the cell extract) or following histochemical staining (beta-galactosidase). Under these conditions, over 50% of the hepatocytes were selectively transfected in the presence of 10% serum. Transfection was suppressed by removal of the targeting galactose residues, by their replacement with glucose, or by the addition of excess asialofetuin. Thus, results from comparative and competitive experiments indicate the asialoglycoprotein receptor is involved in transfection of hepatocytes with neutral PEI-gal/DNA complexes.
Subclinical Neuropathy Among Diabetes Control and Complications Trial Participants Without Diagnosable Neuropathy at Trial Completion (2007)

Intensive and conventional treatment group subjects without diagnosable neuropathy at DCCT completion had significant differences in electrophysiologic measurements favoring the intensive treatment group. Differences in subsequent incident neuropathy between the original treatment groups may reflect, in part, their levels of subclinical neuropathy at DCCT completion, rather than persistent metabolic effects.
Thalidomide and Recurrent Aphthous Stomatitis: A Follow-Up Study (1996)

This study showed that a minority of patients responded and could stop thalidomide therapy whereas another group of patients could be maintained in remission with low doses of thalidomide which may represent a means to reduce the potentially severe side effects.
5‐Iodo‐A‐85380 binds to α‐conotoxin MII‐sensitive nicotinic acetylcholine receptors (nAChRs) as well as α4β2* subtypes (2002)

Recent work suggests that 5-iodo-A-85380, a radioiodinated analog of the 3-pyridyl ether A-85380, represents a promising imaging agent for non-invasive, in vivo studies of alphaAbeta2* nicotinic acetylcholine receptors (nAChRs; *denotes receptors containing the indicated subunits), because of its low non-specific binding, low in vivo toxicity and high selectivity for alpha4beta2* nAChRs. As an approach to elucidate nAChR subtypes expressed in striatum, we carried out competitive autoradiography in monkey and rat brain using 5-[125I]iodo-A-85380 ([125I]A-85380) and [125I]alpha-conotoxin MII, a ligand that binds with high affinity to alpha6* and alpha3* nAChRs, but not to alpha4beta2* nAChRs. Although A-85380 is reported to be selective for alpha4beta2* nAChRs, we observed that A-85380 completely inhibited [125I]alpha-conotoxin MII binding in rat striatum and that A-85380 blocked >90% of [125I] alpha-conotoxin MII sites in monkey caudate and putamen. These results suggest that A-85380 binds to non-alpha4beta2* nAChRs, including putative alpha6* nAChRs. Experiments to determine the percentage of [125I]A-85380 sites that contain alpha-conotoxin MII-sensitive (alpha6beta2*) nAChRs indicate that they represent about 10% of [125I]A-85380 sites in rodent striatum and about 30% of sites in monkey caudate and putamen. These data are important for identifying alterations in nicotinic receptor subtypes in Parkinson's disease and other basal ganglia disorders both in in vitro and in in vivo imaging studies.
Presenilin-dependent “γ-Secretase” Processing of Deleted in Colorectal Cancer (DCC) (2003)

The presenilin-gamma-secretase complex plays a critical role in mediating intramembranous proteolysis of several type I membrane proteins, including beta-amyloid precursor protein (APP) and Notch. We now show that deleted in colorectal cancer (DCC) is subject to proteolysis within the ectodomain segment both in cultured cells and in vivo and that the residual membrane-tethered DCC "stub" is subsequently processed by gamma-secretase to generate a derivative termed DCC-intracellular domain (ICD). The production of DCC-ICD is inhibited by selective gamma-secretase inhibitors, and by the expression of the dominant negative PS1 D385A variant. Moreover, the membrane-tethered DCC "stubs" accumulate to high levels in PS1-deficient embryos. We also demonstrate that expression of a DCC-Gal4 chimera is capable of activating transcription in a luciferase-based reporter assay and this activity is dependent on gamma-secretase activity. Our findings offer the proposal that DCC performs dual roles both as a cell surface receptor that modulates intracellular signaling pathways and as a transcriptional coactivator that relies on gamma-secretase-dependent production and nuclear translocation of the cytoplasmic domain.
The Murine CAR Homolog Is a Receptor for Coxsackie B Viruses and Adenoviruses (1998)

Complementary DNA clones encoding the murine homolog (mCAR) of the human coxsackievirus and adenovirus receptor (CAR) were isolated. Nonpermissive CHO cells transfected with mCAR cDNA became susceptible to infection by coxsackieviruses B3 and B4 and showed increased susceptibility to adenovirus-mediated gene transfer. These results indicate that the same receptor is responsible for virus interactions with both murine and human cells. Analysis of receptor expression in human and murine tissues should be useful in defining factors governing virus tropism in vivo.
StartleCam: a cybernetic wearable camera (2002)

StartleCam is a wearable video camera, computer, and sensing system, which enables the camera to be controlled via both conscious and preconscious events involving the wearer. Traditionally, a wearer consciously hits record on the video camera, or runs a computer script to trigger the camera according to some pre-specified frequency. The system described here offers an additional option: images are saved by the system when it detects certain events of supposed interest to the wearer. The implementation described here aims to capture events that are likely to get the user's attention and to be remembered. Attention and memory are highly correlated with what psychologists call arousal level, and the latter is often signaled by skin conductivity changes; consequently, StartleCam monitors the wearer's skin conductivity. StartleCam looks for patterns indicative of a "startle response" in the skin conductivity signal. When this response is detected, a buffer of digital images, recently captured by the wearer's digital camera, is downloaded and optionally transmitted wirelessly to a webserver. This selective storage of digital images creates a "flashbulb" memory archive for the wearable which aims to mimic the wearer. Using a startle detection filter, the StartleCam system has been demonstrated to work on several wearers in both indoor and outdoor ambulatory environments.
Palladium-Controlled β-Selective Glycosylation in the Absence of the C(2)-Ester Participatory Group (2009)

The development of a new glycosylation method for the stereoselective synthesis of beta-glycosides in the absence of the traditional C(2)-ester neighboring group effect is described. This process relies on the ability of the cationic palladium catalyst, Pd(PhCN)(2)(OTf)(2) generated in situ from Pd(PhCN)(2)Cl(2) and AgOTf, to direct beta-selectivity. The new glycosylation reaction is highly beta-selective and proceeds under mild conditions with 1-2 mol % of catalyst loading. This beta-glycosylation method has been applied to a number of glucose donors with benzyl, allyl, and p-methoxybenzyl groups incorporated at the C(2)-position as well as tribenzylated xylose and quinovose donors to prepare various disaccharides and trisaccharides with good to excellent beta-selectivity. Mechanistic studies suggest that the major operative pathway is likely to proceed via a seven-membered ring intermediate, wherein the cationic palladium complex coordinates to both the C(1)-imidate nitrogen and C(2)-oxygen of the trichloroacetimidate donor. Formation of this seven-membered ring intermediate directs the selectivity, leading to the formation of beta-glycosides.
Outbreaks Associated with Contaminated Antiseptics and Disinfectants (2007)

The Centers for Disease Control and Prevention (CDC) has estimated that health care-associated infections account for an estimated 1.7 million infections, 99,000 deaths, and $4.5 billion in excess health care costs annually (16). The key interventions used to control health care-associated infections include surveillance (27, 33), isolation of patients with communicable diseases (26) or multidrug-resistant pathogens (81), proper skin antisepsis prior to invasive procedures and hand hygiene by health care workers (12), and appropriate disinfection and sterilization of medical devices and environmental surfaces (73, 75, 79).

Multiple nosocomial outbreaks have resulted from inadequate antisepsis or disinfection. Inadequate skin antisepsis may result from a lack of intrinsic antimicrobial activity of the antiseptic, a resistant pathogen, overdilution of the antiseptic, or the use of a contaminated antiseptic. The inadequate disinfection of medical devices or environmental surfaces may result from a lack of intrinsic antimicrobial activity of the disinfectant, an incorrect choice of a disinfectant, a resistant pathogen, overdilution of the disinfectant, an inadequate duration of disinfection, a lack of contact between the disinfectant and the microbes, or the use of a contaminated disinfectant. Editorials have noted that contaminated antiseptics and disinfectants have been the occasional vehicles of hospital infections for more than 50 years (20, 72, 76). This paper concisely reviews nosocomial outbreaks associated with the use of a microbiologically contaminated germicide and focuses on the currently recommended germicides.
Snapshot of Activated G Proteins at the Membrane: The Gα q -GRK2-Gßγ Complex (2005)

G protein-coupled receptor kinase 2 (GRK2) plays a key role in the desensitization of G protein-coupled receptor signaling by phosphorylating activated heptahelical receptors and by sequestering heterotrimeric G proteins. We report the atomic structure of GRK2 in complex with Galphaq and Gbetagamma, in which the activated Galpha subunit of Gq is fully dissociated from Gbetagamma and dramatically reoriented from its position in the inactive Galphabetagamma heterotrimer. Galphaq forms an effector-like interaction with the GRK2 regulator of G protein signaling (RGS) homology domain that is distinct from and does not overlap with that used to bind RGS proteins such as RGS4.
Inverse Kinematic Solutions With Singularity Robustness for Robot Manipulator Control (1986)

The singularity problem is an inherent problem in controlling robot manipulators with articulated configuration. In this paper, we propose to determine the joint motion for the requested motion of the endeffector by evaluating the feasibility of the joint motion. The determined joint motion is called an inverse kinematic solution with singularity robustness, because it denotes feasible solution even at or in the neighborhood of singular points. The singularity robust inverse (SR-inverse) is introduced as an alternative to the pseudoinverse of the Jacobian matrix. The SR-inverse of the Jacobian matrix provides us with an approximating motion close to the desired Cartesian trajectory of the endeffector, even when the inverse kinematic solution by the inverse or the pseudoinverse of the Jacobian matrix is not feasible at or in the neighborhood of singular points. The properties of the SR-inverse are clarified by comparing it with the inverse and the pseudoinverse. The computational complexity of the SR-inverse is considered to discuss its implementability. Several simulation results are also shown to illustrate the singularity problem and the effectiveness of the inverse kinematic solution with singularity robustness.