gebhart/patrepeval huggingface dataset:
Identification of ADAM10 as a major source of HER2 ectodomain sheddase activity in HER2 overexpressing breast cancer cells (2006)

Overexpression and activating mutations of ErbB family members have been implicated in the development and progression of a variety of tumor types. Cleavage of the HER2 receptor by an as yet unidentified ectodomain sheddase has been shown to liberate the HER2 extracellular domain (ECD) leaving a fragment with constitutive kinase activity that can provide ligand-independent growth and survival signals to the cell. This process is clinically relevant since HER2 ECD serum levels in metastatic breast cancer patients are associated with a poorer prognosis. Thus, inhibition of the HER2 sheddase may provide a novel therapeutic approach for breast cancer. We describe the use of transcriptional profiling, pharmacological and in vitro approaches to identify the major source of HER2 sheddase activity. Real-time PCR was used to identify those ADAM family members which were expressed in HER2 shedding cell lines. siRNAs that selectively inhibited ADAM10 expression reduced HER2 shedding. In addition, we profiled over 1000 small molecules for in vitro inhibition of a panel of ADAM and MMP proteins; a positive correlation was observed only between ADAM10 inhibition and reduction of HER2 ECD shedding in a cell based assay. Finally, in vitro studies demonstrate that in combination with low doses of Herceptin, selective ADAM10 inhibitors decrease proliferation in HER2 overexpressing cell lines while inhibitors, that do not inhibit ADAM10, have no impact. These results are consistent with ADAM10 being a major determinant of HER2 shedding, the inhibition of which, may provide a novel therapeutic approach for treating a variety of cancers with active HER2 signaling.
Tart cherry juice increases sleep time in older adults with insomnia (830.9) (2014)

Recent studies indicate that tart cherries (Prunus cerasus) may have sleep‐enhancing effects. In a randomized crossover trial, we evaluated the effects of tart cherry juice vs. a placebo juice on various markers of sleep quality in older adults (age 68 ± 9 years). Seven participants with insomnia completed two treatment periods (tart cherry juice and placebo juice), 2 weeks each, separated by a 2 week washout period. Participants consumed 8 ounces of juice twice per day. Overnight polysomnography (PSG) was used to evaluate sleep architecture, such as the distribution of sleep stages, sleep latency and state transitions. Participants also completed questionnaires related to sleep, depression, anxiety, and fatigue. Tart cherry juice consumption increased sleep time by 85 ± 17 minutes compared to placebo as measured by PSG (P=0.02). Expression of indoleamine 2,3 dioxygenase (IDO) and PGE2 decreased after tart cherry juice consumption (P&lt;0.05) suggesting that its effects on sleep can in part be ascribed to the improvement in the expression of IDO and PGE2. This work is registered at ClinicalTrials.gov NCT01669317. Grant Funding Source : Supported by the Cherry Marketing Institute
P1‐361: Extracellular oligomeric tau inhibits memory formation in mice (2010)

In Alzheimer's disease (AD) tau protein redistributes from the axon to the somatodendritic compartment, and its levels increase in the extracellular cerebrospinal fluid (CSF). As AD progresses, tau pathology spreads through the hippocampal structure to the cortex in a contiguous, highly selective and orderly fashion. Recent studies suggest that extracellular tau may be transmitting tau pathology to neighboring neurons either indirectly through muscarinic receptors I and III or directly by entering cells and functioning as a template for intracellular tau to misfold, aggregate and cause neurodegeneration. There is also extensive literature suggesting that AD begins as a synaptic disorder that involves progressively larger areas of the brain over time. Multiple studies with mouse models indicate that soluble tau oligomers rather than neurofibrillary tangles (NFT) are causing neuron loss and memory impairment. Previously, we have shown that extracellular tau oligomers inhibited synaptic function. Here, we present dose-dependence studies to validate and better characterize this observation, and extracellular tau oligomers were evaluated for their role in associative memory formation in mice. The model of long-term potentiation (LTP) was used to evaluate dose-dependent effects of tau isoforms on synaptic function targeting the hippocampus, an area of the brain fundamentally important in memory acquisition. The contextual fear conditioning model of associative learning was used to study the effects of extracellular tau oligomers in normal mice. There was dose-dependent inhibition of LTP by extracellular tau oligomers but not monomeric tau. The IC50 was about 5 nM, and maximal inhibitory activity was observed at 50 nM. Similarly, extracellular tau oligomers, but not monomeric tau, impaired associative fear memory in mice. Validation of extracellular tau oligomers as a target for drug discovery is strongly supported by the observations that tau oligomers impair synaptic function in a dose response-dependent manner and inhibit learning and memory in mice.
Endogenous peptides bound to HLA-A3 possess a specific combination of anchor residues that permit identification of potential antigenic peptides. (1993)

A motif specific to peptides that bind to the human class I major histocompatibility complex molecule HLA-A3 was identified by sequence analysis of HPLC fractions containing endogenous peptides. Twenty-six different sequences were obtained, 19 of which were nonamers. The majority of these endogenous peptide sequences contained Leu at position (P)2, while most sequences contained Tyr or Lys at P9. In addition, Phe was shared by 16 sequences at P3. Synthetic peptides corresponding to endogenous peptide sequences were shown to bind to HLA-A3. The importance of Leu at P2 and Tyr or Lys at P9 ("anchor" residues) for peptide binding to HLA-A3 was demonstrated by the following results: (i) peptides GLFGGGGGY, GLFGGGGGK, and GLGGGGFGY, but not GLFGGGGGV, specifically bound to HLA-A3 and (ii) six nonapeptides from within the influenza A nucleoprotein, matrix, and polymerase proteins, selected for synthesis based upon their possession of P2 and P9 anchor residues, were shown to bind HLA-A3. In contrast, none of a set of eight peptides that bound to HLA-A2, or six that bound to HLA-B27, bound detectably to HLA-A3. These findings provide a rationale for the design and selection of peptides that can be recognized by HLA-A3-restricted T cells.
Improving Density Estimation by Incorporating Spatial Information (2010)

Given discrete event data, we wish to produce a probability density that can model the relative probability of events occurring in a spatial region. Common methods of density estimation, such as Kernel Density Estimation, do not incorporate geographical information. Using these methods could result in nonnegligible portions of the support of the density in unrealistic geographic locations. For example, crime density estimation models that do not take geographic information into account may predict events in unlikely places such as oceans, mountains, and so forth. We propose a set of Maximum Penalized Likelihood Estimation methods based on Total Variation and H 1 Sobolev norm regularizers in conjunction with a priori high resolution spatial data to obtain more geographically accurate density estimates. We apply this method to a residential burglary data set of the San Fernando Valley using geographic features obtained from satellite images of the region and housing density information.
Resurrecting the iron age* (2012)

Department of Anesthesiology and Critical Care Medicine, Englewood Hospital and Medical Center, Englewood, NJ; and Departments of Anesthesiology, Medicine and Surgery, Mount Sinai School of Medicine. New York, NY Department of Anesthesiology and Critical Care Medicine, Englewood Hospital and Medical Center, Englewood, NJ *See also p. 2141. The work was performed at Department of Anesthesiology and Critical Care Medicine, Englewood Hospital and Medical Center, Englewood, NJ. Dr. Shander has been a consultant for Luitpold (viforpharma), and Novartis; has received research and grant support from Novartis, Novo Nordisk, OrthoBiotech, Pfizer, and ZymoGenetics; and has been a speaker with honorarium for Novartis, OrthoBiotech, and ZymoGenetics. He is a founding member of Society for the Advancement of Blood Management where he currently serves as the President. Dr. Javidroozi has not disclosed any potential conflicts of interest.
Biodegradable amphiphilic polymer–drug conjugate micelles (2009)

The coupling of drugs to macromolecular carriers received an important impetus from Ringsdorf's notion of polymer-drug conjugates. Several water-soluble polymers, poly(ethylene glycol), poly[N-(2-hydroxypropyl) methacrylamide], poly(l-glutamic acid) and dextran, are studied intensively and have been utilized successfully in clinical research. The promising results arising from clinical trials with polymer-drug conjugates (e.g., paclitaxel, doxorubicin, camptothecins) have provided a firm foundation for other synthetic polymers, especially biodegradable polymers, used as drug delivery vehicles. This review discusses biodegradable polymeric micelles as an alternative drug-conjugate system. Particular focus is on A-B or B-A-B type biodegradable amphiphilic block copolymer such as polylactide, morpholine-2,5-dione derivatives and cyclic carbonates, which can form a core-shell micellar structure, with the hydrophobic drug-binding segment forming the hydrophobic core and the hydrophilic segment as a hydrated outer shell. Polymeric micelles can be designed to avoid uptake by cells of reticuloendothelial system and thus enhance their blood lifetime via the enhanced permeability and retention effect. Active tumor-targeting may be achieved by modifying the micelle surface with specific ligands. The potential application areas are discussed and future challenges are highlighted.
Synergistic Activation of MAP Kinase (ERK1/2) by Erythropoietin and Stem Cell Factor Is Essential for Expanded Erythropoiesis (1998)

Stem cell factor (SCF) and erythropoietin (EPO) work synergistically to support erythropoiesis, but the mechanism for this synergism is unknown. By using purified human erythroid colony-forming cells (ECFC), we have found that SCF and EPO synergistically activate MAP kinase (MAPK, ERK1/2), which correlates with the cell growth and thus may be responsible for the synergistic effects. Treatment of the cells with PD98059 and wortmannin, inhibitors of MEK and PI-3 kinase, respectively, inhibited the synergistic activation of MAPK and also the cell growth, further supporting this conclusion. Wortmannin only inhibits MAPK activation induced by EPO but not that by SCF, suggesting that SCF and EPO may activate MAPK through different pathways, which would facilitate synergy. Furthermore, EPO, but not SCF, led to activation of STAT5, whereas SCF and wortmannin had no effect on the EPO-induced STAT5 activation, suggesting that STAT5 is not involved in the synergistic action of SCF and EPO. Together, the data suggest that synergistic activation of MAPK by SCF and EPO is essential for expanded erythropoiesis.
Attaching and effacing Escherichia coli infection as a cause of diarrhea in young calves. (1990)

A form of enteric Escherichia coli infection was identified in 60 calves from 59 farming operations. The E coli responsible for these infections principally colonized the colon, inducing a distinctive lesion described as attaching and effacing. Hemorrhagic enterocolitis or blood in the feces was observed on 40% of the farms. Of affected calves, 86.6% were dairy calves (average age, 11.8 days). Forty-four calves were infected concurrently with other enteropathogens (cryptosporidia, rotavirus, coronavirus, enterotoxigenic E coli, bovine viral diarrhea virus, coccidia). Verotoxin-producing E coli was recovered from 31 calves; 8 were serotype O111:NM isolates, 3 were serotype O5:NM, and 1 was serotype O26:NM.
Understanding Latent Tuberculosis: A Moving Target (2010)

Tuberculosis (TB) remains a threat to the health of people worldwide. Infection with Mycobacterium tuberculosis can result in active TB or, more commonly, latent infection. Latently infected persons, of which there are estimated to be approximately 2 billion in the world, represent an enormous reservoir of potential reactivation TB, which can spread to other people. The immunology of TB is complex and multifaceted. Identifying the immune mechanisms that lead to control of initial infection and prevent reactivation of latent infection is crucial to combating this disease.
The Advent Project (Book) (2002)

Head-mounted miniscopes have allowed for functional fluorescence imaging in freely moving animals. However, current capabilities of state-of-the-art technology can record only up to two, spectrally distinct fluorophores. This severely limits the number of cell types identifiable in a functional imaging experiment. Here we present a pipeline that enables the distinction of nine neuronal subtypes from regions defined by behaviorally relevant cells during <i>in vivo</i> GCaMP imaging. These subtypes are identified utilizing unique fluorophores that are co-expressed with GCaMP, unmixed by spectral imaging on a confocal microscope and co-registering these spectral fingerprints with functional data obtained on miniaturized microscopes. This method facilitates detailed analyses of circuit-level encoding of behavior.
Temperature‐Triggered Collection and Release of Water from Fogs by a Sponge‐Like Cotton Fabric (2013)

A sponge-like cotton fabric autonomously collects and releases water from fogs triggered by typical day-and-night temperature variations. The reversible switching between absorbing-superhydrophilic/releasing-superhydrophobic states results from structural changes of a temperature-responsive polymer grafted on the very rough fabric-surface. This material and concept presents a breakthrough into simple and versatile solutions for collection, uni-directional flow, and purification of water captured from the atmosphere. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
PGP: Pretty Good Privacy (1994)

From the Publisher:
Use of the Internet is expanding beyond anyone's expectations. As corporations, government offices, and ordinary citizens begin to rely on the information highway to conduct business, they are realizing how important it is to protect their communications -- both to keep them a secret from prying eyes and to ensure that they are not altered during transmission. Encryption, which until recently was an esoteric field of interest only to spies, the military, and a few academics, provides a mechanism for doing this. 
PGP, which stands for Pretty Good Privacy, is a free and widely available encryption program that lets you protect files and electronic mail. Written by Phil Zimmermann and released in 1991, works on virtually every platform and has become very popular both in the U.S. and abroad. Because it uses state-of-the-art public key cryptography, can be used to authenticate messages, as well as keep them secret. With you can digitally sign a message when you send it. By checking the digital signature at the other end, the recipient can be sure that the message was not changed during transmission and that the message actually came from you. 
PGP offers a popular alternative to U.S. government initiatives like the Clipper Chip because, unlike Clipper, it does not allow the government or any other outside agency access to your secret keys. 
PGP: Pretty Good Privacy by Simson Garfinkel is both a readable technical user's guide and a fascinating behind-the-scenes look at cryptography and privacy. Part I, PGP Overview, introduces and the cryptography that underlies it. Part II, Cryptography History and Policy, describes the history of -- its personalities, legal battles, and other intrigues; it also provides background on the battles over public key cryptography patents and the U.S. government export restrictions, and other aspects of the ongoing public debates about privacy and free speech. Part III, Using PGP, describes how to use PGP: protecting files and email, creating and using keys, signing messages, certifying and distributing keys, and using key servers. Part IV, Appendices, describes how to obtain from Internet sites, how to install it on PCs, UNIX systems, and the Macintosh, and other background information. The book also contains a glossary, a bibliography, and a handy reference card that summarizes all of the commands, environment variables, and configuration variables.
BRAINSTEM CIRCUITS REGULATING GASTRIC FUNCTION (2005)

Brainstem parasympathetic circuits that modulate digestive functions of the stomach are comprised of afferent vagal fibers, neurons of the nucleus tractus solitarius (NTS), and the efferent fibers originating in the dorsal motor nucleus of the vagus (DMV). A large body of evidence has shown that neuronal communications between the NTS and the DMV are plastic and are regulated by the presence of a variety of neurotransmitters and circulating hormones as well as the presence, or absence, of afferent input to the NTS. These data suggest that descending central nervous system inputs as well as hormonal and afferent feedback resulting from the digestive process can powerfully regulate vago-vagal reflex sensitivity. This paper first reviews the essential "static" organization and function of vago-vagal gastric control neurocircuitry. We then present data on the opioidergic modulation of NTS connections with the DMV as an example of the "gating" of these reflexes, i.e., how neurotransmitters, hormones, and vagal afferent traffic can make an otherwise static autonomic reflex highly plastic.
Recent Advances in Radical C–H Activation/Radical Cross-Coupling (2017)

Research and industrial interest in radical C-H activation/radical cross-coupling chemistry has continuously grown over the past few decades. These reactions offer fascinating and unconventional approaches toward connecting molecular fragments with high atom- and step-economy that are often complementary to traditional methods. Success in this area of research was made possible through the development of photocatalysis and first-row transition metal catalysis along with the use of peroxides as radical initiators. This Review provides a brief and concise overview of the current status and latest methodologies using radicals or radical cations as key intermediates produced via radical C-H activation. This Review includes radical addition, radical cascade cyclization, radical/radical cross-coupling, coupling of radicals with M-R groups, and coupling of radical cations with nucleophiles (Nu).
CFTR Regulates Early Pathogenesis of Chronic Obstructive Lung Disease in βENaC-Overexpressing Mice (2012)

We conclude that a decrease or absence of CFTR function in airway epithelia aggravates the severity of early airway mucus obstruction and related mortality in βENaC-Tg mice. These results suggest that genetic or environmental factors that reduce CFTR activity may contribute to the onset and severity of chronic obstructive pulmonary disease and that CFTR may serve as a novel therapeutic target.
The Addition of Dilute Epinephrine Produces Equieffectiveness of Bupivacaine Enantiomers for Cutaneous Analgesia in the Rat (2000)

We investigated the effectiveness for cutaneous analgesia of bupivacaine (Bup) stereoisomers in male rats. As a model of infiltration anesthesia, inhibition of a nocifensive reflex by subcutaneous injection of 0.6 mL of different concentrations of R-, S-, and racemic-Bup was evaluated quantitatively by the fraction of times a pinprick failed to evoke a nocifensive motor response. R-Bup was more potent in the extent of block; however, S-Bup had a longer-lasting action at smaller doses. This significant difference was apparent when R-Bup and S-Bup were administered in equipotent doses of 0.06% and 0.075%, respectively. Co-injection of epinephrine (Epi) with these equipotent doses enhanced and prolonged the blocking effects of both Bup stereoisomers, although at dilutions of 1:100,000 to 1:1,000,000 Epi itself induced partial, transient analgesia. At 1:2,000,000 dilution, Epi alone had no analgesic effect; however, when co-injected with the shorter-acting R-Bup (0.06%), Epi prolonged its blocking effect to equal the duration of block evoked by equipotent S-Bup (0.075%). We conclude R-Bup is more potent for cutaneous analgesia and that the longer duration of block by S-Bup probably originates from vasoconstrictor activity. Implications Here we show that the more potent optical R-isomer of bupivacaine (Bup) can be used at a smaller dose (80%) than the S-isomer of Bup to give equal pain relief of a skin prick. Although the analgesia from R-Bup is briefer than that from equipotent S-Bup solutions, the durations become equal when a very dilute solution of the vasoconstrictor epinephrine is mixed with the R-isomer. The resulting vasoconstriction thus reduces vascular drug uptake and peak blood levels of systemic drug, reducing potential toxicity.
Temporally adaptive motion interpolation exploiting temporal masking in visual perception (1994)

In this paper we present a novel technique to dynamically adapt motion interpolation structures by temporal segmentation. The number of reference frames and the intervals between them are adjusted according to the temporal variation of the input video. Bit-rate control for this dynamic group of pictures (GOP) structure is achieved by taking advantage of temporal masking in human vision. Constant picture quality can be obtained by variable-bit-rate coding using this approach. Further improvement can be made when the intervals between reference frames are chosen by minimizing a measure of the coding difficulty of a GOP. Advantages for low bit-rate coding and implications for variable-bit-rate coding are discussed. Simulations on test video are presented for various GOP structures and temporal segmentation methods, and the results compare favorably with those for conventional fixed GOP structures.
MTPA vs MPA in the Determination of the Absolute Configuration of Chiral Alcohols by 1H NMR (1996)

Molecular mechanics, semiempirical (AM1), and aromatic shielding effect calculations and DNMR experiments show that MTPA esters are constituted by three main conformers in close populations due to restricted rotation around the Cα−CO and Cα−Ph bonds. The small predominance of one conformer and the simultaneous operation of aromatic shielding and deshielding effects on the alcohol part, due to the orientation of the Ph ring, explains the small ΔδRS values observed. A graphical description of the aromatic magnetic field distribution in the conformers of MTPA and MPA esters and its use to correlate the average chemical shifts with the absolute stereochemistry is presented. Comparison of MTPA with MPA (two conformers) as reagents for determination by NMR of absolute stereochemistry indicates that MTPA esters are intrinsically limited by the greater complexity of their conformational composition, yield very small ΔδRS values, and are consequently less reliable for configurations assignment of chiral alcohols than MPA or other arylmethoxyacetic acid reagents such as (R)- and (S)-α-methoxy-α-(9-anthryl)acetic acids.