gebhart/patrepeval huggingface dataset:
HGF/SF‐met signaling in the control of branching morphogenesis and invasion (2003)

Hepatocyte growth factor/Scatter factor (HGF/SF) is a multifunctional growth factor which can induce diverse biological events. In vitro, these include scattering, invasion, proliferation and branching morphogenesis. In vivo, HGF/SF is responsible for many processes during embryonic development and a variety of activities in adults, and many of these normal activities have been implicated in its role in tumorgenesis and metastasis. The c-Met receptor tyrosine kinase is the only known receptor for HGF/SF and mediates all HGF/SF induced biological activities. Upon HGF/SF stimulation, the c-Met receptor is tyrosine-phosphorylated which is followed by the recruitment of a group of signaling molecules and/or adaptor proteins to its cytoplasmic domain and its multiple docking sites. This action leads to the activation of several different signaling cascades that form a complete network of intra and extracellular responses. Different combinations of signaling pathways and signaling molecules and/or differences in magnitude of responses contribute to these diverse series of HGF/SF-Met induced activities and most certainly are influenced by cell type as well as different cellular environments. In this review, we focus on HGF/SF-induced branching morphogenesis and invasion, and bring together recent new findings which provide insight into how HGF/SF, via c-Met induces this response.
Whole exome sequencing and characterization of coding variation in 49,960 individuals in the UK Biobank (2019)

SUMMARY The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world. Here we describe the first tranche of large-scale exome sequence data for 49,960 study participants, revealing approximately 4 million coding variants (of which ~98.4% have frequency &lt; 1%). The data includes 231,631 predicted loss of function variants, a &gt;10-fold increase compared to imputed sequence for the same participants. Nearly all genes (&gt;97%) had ≥1 predicted loss of function carrier, and most genes (&gt;69%) had ≥10 loss of function carriers. We illustrate the power of characterizing loss of function variation in this large population through association analyses across 1,741 phenotypes. In addition to replicating a range of established associations, we discover novel loss of function variants with large effects on disease traits, including PIEZO1 on varicose veins, COL6A1 on corneal resistance, MEPE on bone density, and IQGAP2 and GMPR on blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical significance in this population, finding that 2% of the population has a medically actionable variant. Additionally, we leverage the phenotypic data to characterize the relationship between rare BRCA1 and BRCA2 pathogenic variants and cancer risk. Exomes from the first 49,960 participants are now made accessible to the scientific community and highlight the promise offered by genomic sequencing in large-scale population-based studies.
Phorbol esters and norepinephrine destabilize alpha 1B-adrenergic receptor mRNA in vascular smooth muscle cells. (1994)

The mechanism by which norepinephrine (NE) down-regulates alpha 1B-adrenergic receptor (alpha-AR) mRNA was studied in rabbit aortic smooth muscle cells. NE, phorbol esters, and bradykinin each decreased alpha-AR mRNA levels by 70-80%. The protein kinase C inhibitor (+)-1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) abolished the effects of phorbol esters and NE and decreased basal mRNA levels by 52 +/- 3%. Neither ryanodine nor EGTA inhibited down-regulation of alpha-AR mRNA by NE. Actinomycin D caused alpha-AR mRNA level to decrease with a half-life of 3.2 +/- 0.4 h and blocked the effect of H-7 to decrease basal alpha-AR mRNA level. Both NE and phorbol esters increased the rate of alpha-AR mRNA degradation. In NE-desensitized cells, phorbol esters and bradykinin each caused the expected down-regulation of alpha-AR mRNA. The protein phosphatase inhibitor okadaic acid prolonged the normally transient effect of NE for at least 24 h. We conclude that protein kinase C exerts two opposing effects on alpha-AR mRNA levels, 1) a decrease in the stability of the mRNA that requires the sustained phosphorylation of a protein kinase C substrate and 2) a permissive effect on alpha-AR gene transcription.
Amplification of Chlamydia trachomatis DNA by ligase chain reaction (1993)

Amplification of Chlamydia trachomatis DNA by polymerase chain reaction was compared with amplification by ligase chain reaction (LCR). Both amplification procedures were able to consistently amplify amounts of DNA equivalent to three C. trachomatis elementary bodies. All 15 C. trachomatis serovars were amplified to detectable levels by LCR, and no DNA from 16 organisms potentially found in clinical specimens or from Chlamydia psittaci and Chlamydia pneumoniae was amplified by LCR.
Characterizing Individual Scattering Events by Measuring the Amplitude and Phase of the Electric Field Diffusing through a Random Medium (2003)

We describe observations of the amplitude and phase of an electric field diffusing through a three-dimensional random medium, using terahertz time-domain spectroscopy. These measurements are spatially resolved with a resolution smaller than the speckle spot size and temporally resolved with a resolution better than one optical cycle. By computing correlation functions between fields measured at different positions and with different temporal delays, it is possible to obtain information about individual scattering events experienced by the diffusing field. This represents a new method for characterizing a multiply scattered wave.
Function of WW Domains as Phosphoserine- or Phosphothreonine-Binding Modules (1999)

Protein-interacting modules help determine the specificity of signal transduction events, and protein phosphorylation can modulate the assembly of such modules into specific signaling complexes. Although phosphotyrosine-binding modules have been well-characterized, phosphoserine- or phosphothreonine-binding modules have not been described. WW domains are small protein modules found in various proteins that participate in cell signaling or regulation. WW domains of the essential mitotic prolyl isomerase Pin1 and the ubiquitin ligase Nedd4 bound to phosphoproteins, including physiological substrates of enzymes, in a phosphorylation-dependent manner. The Pin1 WW domain functioned as a phosphoserine- or phosphothreonine-binding module, with properties similar to those of SRC homology 2 domains. Phosphoserine- or phosphothreonine-binding activity was required for Pin1 to interact with its substrates in vitro and to perform its essential function in vivo.
Zika virus: from pathogenesis to disease control (2016)

Zika virus is a mosquito-borne flavivirus discovered in Uganda in 1947. The virus has emerged in recent years and spread in the Pacific Area and the Americas, where it has caused large human outbreaks. The factors involved in the virus's emergence are still unknown, but probably include its introduction in naïve environments characterised by the presence of high densities of competent Aedes spp. mosquitoes and susceptible human hosts in urban areas. Unique features of Zika virus infection are sexual and transplacental transmission and associated neurological morbidities, i.e. Guillain-Barré syndrome and fetal microcephaly. Diagnosis relies on the detection of viral nucleic acids in biological samples, while detection of a specific antibody response may be inconclusive because of the broad cross-reactivity of antibodies among flaviviruses. Experimental studies have clarified some mechanisms of Zika virus pathogenesis and have identified potential targets for antiviral drugs. In animal models, the virus can infect and efficiently replicate in the placenta and in the brain, and induce fetal demise or neural damage, recapitulating human diseases. These animal models have been used to evaluate candidate vaccines and promising results have been obtained.
Ultrasonic manipulation of particles in microgravity (1998)

The manipulation of yeast cells and latex particles of diameters 1.3, 12 and in aqueous suspension in 1 and 3 MHz ultrasonic standing waves has been examined and compared in microgravity (0 g), 1 g and 1.8 g. The experiments were carried out during the 23rd ESA parabolic flight campaign. The suspended particles concentrated to form bands at half wavelength separation in the axial direction of a vertical tubular sample holder with a Bessel pressure amplitude distribution profile. At 1 g small ( latex) particles formed bands but these broke up within a few seconds. In contrast throughout 0 g bands of these particles formed and remained stable. The transition from 0 to 1.8 g during flight induced streaming which broke up the bands of latex. Bands formed with yeast cells were more stable at 1 g but, during transitions from 0 to 1.8 g, some bands broke up. Bands of the larger (12 and ) particles were stable at 0, 1 and 1.8 g and during all transitions between the fields. Thermal gradient convective flow rather than acoustic streaming was identified as the main source of flow in the sample holder at 1 g. The absence of thermal streaming at 0 g allowed manipulation of smaller particles in that situation. A frequency ramping technique appropriate for removal of particles from suspension in 1 g had a better performance in 0 g.
Genomic abnormalities in monoclonal gammopathy of undetermined significance (2002)

Translocations involving immunoglobulin (Ig) loci and chromosome 13 monosomy (Delta 13) are frequent cytogenetic findings in multiple myeloma (MM). Similar chromosomal aberrations have been identified in the monoclonal gammopathy of undetermined significance (MGUS), but their prevalence and significance remain uncertain. Bone marrow from 72 patients with MGUS (n = 62) and smoldering MM (n = 10) was evaluated for translocations between the Ig heavy chain (IgH) and chromosomes 4, 11, and 16, translocations involving Ig light chain-lambda (IgL-lambda, and Delta 13. Fluorescence in situ hybridization (FISH) analysis was done on clonal plasma cells (PCs) detected by immunofluorescence (cIg-FISH) of the cytoplasmic light chain. We also studied cells for cyclin D1 and FGFR3 up-regulation by immunohistochemistry and immunofluorescence, respectively. Twenty-seven (46%) of 59 patients had IgH translocations, and 4 (11%) of 37 had an IgL-lambda translocation. A t(11;14)(q13;q32) was found in 15 (25%) of 59 patients, a t(4;14)(p16.3;q32) in 9% of patients, and a t(14;16)(q32;q23) in 5% of patients. All patients with t(4;14)(p16.3;q32) tested (n = 3) had intense cytoplasmic fluorescence with an anti-FGFR3 antibody. PC nuclear staining of cyclin D1 was only observed in patients with t(11;14)(q13;q32); Delta 13 was detected in the clonal PCs in 50% of patients. The percentage of abnormal PCs varied with any given abnormality. No obvious clinical or biologic correlations were associated with these chromosome abnormalities. Similar translocations are found in both MGUS and MM, including t(4;14)(p16.3;q32) and t(14;16)(q32;q23). Moreover, Delta 13 is common in MGUS and unlikely to play a predominant role in the evolution of MGUS to MM.
Anaphylactic shock depends on PI3K and eNOS-derived NO (2006)

Anaphylactic shock is a sudden, life-threatening allergic reaction associated with severe hypotension. Platelet-activating factor (PAF) is implicated in the cardiovascular dysfunctions occurring in various shock syndromes, including anaphylaxis. Excessive production of the vasodilator NO causes inflammatory hypotension and shock, and it is generally accepted that transcriptionally regulated inducible iNOS is responsible for this. Nevertheless, the contribution of NO to PAF-induced shock or anaphylactic shock is still ambiguous. We studied PAF and anaphylactic shock in conscious mice. Surprisingly, hyperacute PAF shock depended entirely on NO, produced not by inducible iNOS, but by constitutive eNOS, rapidly activated via the PI3K pathway. Soluble guanylate cyclase (sGC) is generally regarded as the principal vasorelaxing mediator of NO. Nevertheless, although methylene blue partially prevented PAF shock, neither 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) nor sGCalpha1 deficiency did. Also, in 2 different models of active systemic anaphylaxis, inhibition of NOS, PI3K, or Akt or eNOS deficiency provided complete protection. In contrast to the unsubstantiated paradigm that only excessive iNOS-derived NO underlies cardiovascular collapse in shock, our data strongly support the unexpected concept that eNOS-derived NO is the principal vasodilator in anaphylactic shock and define eNOS and/or PI3K or Akt as new potential targets for treating anaphylaxis.
Multisensory Intervention for Preterm Infants Improves Sucking Organization (2015)

Further research that includes 2 or more tests, delivered the same day and/or over consecutive days, will provide researchers and clinicians a more sensitive indicator of maturational changes in feeding behaviors.
Population-based study of BRCA1 and BRCA2 mutations in 1035 unselected Finnish breast cancer patients (2000)

Population-based study of BRCA1 and BRCA2 mutations in 1035 unselectedFinnish breast cancer patients.
CBF2/DREB1C is a negative regulator of CBF1/DREB1B and CBF3/DREB1A expression and plays a central role in stress tolerance in Arabidopsis (2004)

CBF/DREB1 (C-repeat-binding factor/dehydration responsive element-binding factor 1) genes encode a small family of transcriptional activators that have been described as playing an important role in freezing tolerance and cold acclimation in Arabidopsis. To specify this role, we used a reverse genetic approach and identified a mutant, cbf2, in which the CBF2/DREB1C gene was disrupted. Here, we show that cbf2 plants have higher capacity to tolerate freezing than WT ones before and after cold acclimation and are more tolerant to dehydration and salt stress. All these phenotypes correlate with a stronger and more sustained expression of CBF/DREB1-regulated genes, which results from an increased expression of CBF1/DREB1B and CBF3/DREB1A in the mutant. In addition, we show that the expression of CBF1/DREB1B and CBF3/DREB1A in response to low temperature precedes that of CBF2/DREB1C. These results indicate that CBF2/DREB1C negatively regulates CBF1/DREB1B and CBF3/DREB1A, ensuring that their expression is transient and tightly controlled, which, in turn, guarantees the proper induction of downstream genes and the accurate development of Arabidopsis tolerance to freezing and related stresses.
Influence of long-term storage in cold hibernation on strain recovery and recovery stress of polyurethane shape memory polymer foam (2001)

In this paper, the effects of long-term storage in compressed cold hibernated elastic memory (CHEM) polyurethane foam, a kind of shape memory polymer, are investigated experimentally. The foams were pre-strained at a high temperature, which was above the glass transition temperature, to 80% and 93.4%, respectively, and then cooled back to room temperature. After various periods of cold hibernation (up to two months), they were heated up at fixed length or against different constant loads. It is found that: (1) the maximum stress that the foam could exert at fixed length depends heavily on the amount of pre-strain; (2) expansion rates of 380 and 1273% from the hibernated size against a 1 N load (pre-strained by 80 and 93.4%, respectively) are achievable. However, upon further increases in load, the expansion is reduced dramatically. It appears that the tested CHEM polyurethane foam retains its shape memory properties even after being stored in a compacted state for a long period. Complete strain recovery is attainable for a hibernation period of up to two months.
Construction of new ligand binding sites in proteins of known structure (1991)

We have devised a molecular model building computer program (DEZYMER) which builds new ligand binding sites into a protein of known three-dimensional structure. It alters only the sequence and the side-chain structure of the protein, leaving the protein backbone fold intact by definition. The program searches for a constellation of backbone positions arranged such that if appropriate side-chains were placed there, they would bind the ligand according to a pre-defined geometry of interaction specified by the experimentalist. These binding sites are introduced by the program by taking into account simple rules such as steric hindrance, atomic close-packing and hydrogen bond patterns, which are known to maintain the integrity of a protein structure to a first approximation. A test case is presented in this paper where the copper binding site found in blue-copper proteins such as plastocyanin, azurin and cupredoxin is introduced into Escherichia coli thioredoxin. The model building of one of the solutions found by the program is presented in some detail. The experimental construction and properties of this new protein are described in an accompanying paper. It is hoped that this program provides a general method for the design of ligand binding sites and enzyme active sites, which can then be tested experimentally.
Some condensations of methyl 4-acetylphenylcarbamate (2010)

Condensation of methyl 4-acetylphenylcarbamate with isatin in the presence of diethylamine afforded methyl 4-[(3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]phenylcarbamate which was converted into the corresponding chalcone on heating in glacial acetic acid in the presence of hydrochloric acid. 1,3-Dipolar cycloaddition to that chalcone of azomethine ylide generated from 2-phenacylisoquinolinium bromide by the action of triethylamine gave methyl 4-(3′-benzoyl-2-oxo-1′,2,2′,3,3′,10b′-hexahydro-1H-spiro-[indole-3,1′-pyrrolo[1,2-a]isoquinolin]-2′-ylcarbonyl)phenylcarbamate. Condensation of 2-hydroxy- and 2,4-dihydroxybenzaldehydes with methyl 4-acetylphenylcarbamate in the presence of gaseous hydrogen chloride resulted in the formation of chromenium salts with a methoxycarbonylaminophenyl fragment on the C2 atom in the heteroring.
A Mutation (Pro-30 to Leu) inCYP21 Represents a Potential Nonclassic Steroid 21-Hydroxylase Deficiency Allele (1991)

The mild nonclassic form of steroid 21-hydroxylase deficiency is one of the most common autosomal recessive disorders in humans, occurring in almost 1% of caucasians and about 3% of Ashkenazi Jews. Many patients with this disorder carry a Val-281----Leu missense mutation in the CYP21 gene. This and most other mutations causing 21-hydroxylase deficiency are normally present in the CYP21P pseudogene and have presumably been transferred to CYP21 by gene conversion. To identify other potential nonclassic alleles, we used recombinant vaccinia virus to express two mutant enzymes carrying the mutations Pro-30----Leu (normally present in CYP21P) and Ser-268----Thr (considered a normal polymorphism of CYP21). Whereas the activity of the protein carrying the Ser----Thr mutation was indeed indistinguishable from the wild type, the enzyme with the Pro----Leu substitution had 60% of wild-type activity for 17-hydroxyprogesterone and about 30% of normal activity for progesterone when assayed in intact cells. When kinetic analysis of the latter mutant enzyme was performed in cellular lysates, the first order rate constants (maximum velocity/dissociation constant) for both substrates were reduced 10- to 20-fold compared with those for the wild-type enzyme. Pro-30 is conserved in many microsomal P450 enzymes and may be important for proper orientation of the enzyme with respect to the aminoterminal transmembrane segment. The Pro----Leu mutation was present in 5 of 18 patients with nonclassic 21-hydroxylase deficiency, suggesting that this mutation indeed acts as a nonclassic deficiency allele.
Parallel Tracking and Mapping for Small AR Workspaces (2007)

This paper presents a method of estimating camera pose in an unknown scene. While this has previously been attempted by adapting SLAM algorithms developed for robotic exploration, we propose a system specifically designed to track a hand-held camera in a small AR workspace. We propose to split tracking and mapping into two separate tasks, processed in parallel threads on a dual-core computer: one thread deals with the task of robustly tracking erratic hand-held motion, while the other produces a 3D map of point features from previously observed video frames. This allows the use of computationally expensive batch optimisation techniques not usually associated with real-time operation: The result is a system that produces detailed maps with thousands of landmarks which can be tracked at frame-rate, with an accuracy and robustness rivalling that of state-of-the-art model-based systems.
Novel targets for therapeutic intervention against ischemic brain injury. (1999)

Ischemic stroke is a major health care problem worldwide, and the mechanisms that lead to ischemic brain injury are not completely defined. In the past few years, the identification of many molecules that participate in neuronal death and particularly in apoptosis, has shed light on the development of neuroprotective therapy. Glycine site antagonism of N-methyl-D-aspartate (NMDA) receptors may offer an alternative means to a blockade of glutamate neurotoxicity, which lacks most side effects associated with competitive and noncompetitive NMDA receptor antagonists. Inflammatory processes executed by some proinflammatory molecules contribute to secondary brain injury. Neutral protease calpain is capable of degrading critical cytoskeletal and regulatory proteins, mainly causing postischemic neuronal necrosis. Caspases, a family of cysteine proteases, are at the heart of the apoptotic pathway. Severe DNA damage induced by oxidative stress or apoptotic stimuli activates poly(ADP-ribose) polymerase, causing a rapid depletion of nuclear NAD pools, cellular energy, and thiols. Inhibition of these inducible molecules is expected to achieve effective neuroprotection without serious side effects because the molecules seem relatively unimportant in normal neurotransmission. In the future, the efficacy of these novel strategies should be confirmed in larger study populations, individually and in combinations, before considering clinical application.
Economics, Organization and Management. (1993)

A systematic treatment of the economics of the modern firm, this book draws on the insights of a variety of areas in modern economics and other disciplines, but presents a coherent, consistent, innovative treatment of the central problems in organizations of motivating people and coordinating their activities.
PET and MRA findings in cluster headache and MRA in experimental pain (2000)

Dilatation of cranial vessels is not specific to any particular headache syndrome but generic to cranial neurovascular activation, probably mediated by the trigeminoparasympathetic reflex. These data confirm that CH is a CNS disorder best considered as a form of neurovascular headache.