gebhart/patrepeval huggingface dataset:
Mechanism of the G-protein mimetic nanobody binding to a muscarinic G-protein-coupled receptor (2018)

Protein-protein binding is key in cellular signaling processes. Molecular dynamics (MD) simulations of protein-protein binding, however, are challenging due to limited timescales. In particular, binding of the medically important G-protein-coupled receptors (GPCRs) with intracellular signaling proteins has not been simulated with MD to date. Here, we report a successful simulation of the binding of a G-protein mimetic nanobody to the M<sub>2</sub> muscarinic GPCR using the robust Gaussian accelerated MD (GaMD) method. Through long-timescale GaMD simulations over 4,500 ns, the nanobody was observed to bind the receptor intracellular G-protein-coupling site, with a minimum rmsd of 2.48 Å in the nanobody core domain compared with the X-ray structure. Binding of the nanobody allosterically closed the orthosteric ligand-binding pocket, being consistent with the recent experimental finding. In the absence of nanobody binding, the receptor orthosteric pocket sampled open and fully open conformations. The GaMD simulations revealed two low-energy intermediate states during nanobody binding to the M<sub>2</sub> receptor. The flexible receptor intracellular loops contribute remarkable electrostatic, polar, and hydrophobic residue interactions in recognition and binding of the nanobody. These simulations provided important insights into the mechanism of GPCR-nanobody binding and demonstrated the applicability of GaMD in modeling dynamic protein-protein interactions.
Relationship of Crop and Shoot Growth in Apple (1964)

A comparison of yield and shoot growth over a period of 25 years, from the 9th to the 34th year, in a trial of Lane’s Prince Albert apple on a range of rootstocks at East Mailing, has established a significant negative correlation between yield and the following year’s shoot growth for trees on M.I, M.II, M.IV, M.VII and M.IX. For trees on the very vigorous M.XVI, the correlation, though in the same direction, was lower and non-significant. A “ high ” crop (one more than 20% above the five-year running mean) led to reduction in shoot growth in the succeeding year, the average reduction varying from about 53% for trees on the dwarfing M.IX to 9% for trees on the very vigorous M.XVI. Conversely, the average increase in shoot growth following a “ low ” crop varied from about 45% on M.IX to 6% on M.XVI. No significant correlation between crop and current year’s shoot growth was found in these trees.
Generation of 90-nJ pulses with a 4-MHz repetition-rate Kerr-lens mode-locked Ti:Al_2O_3 laser operating with net positive and negative  intracavity  dispersion (2001)

We demonstrate the generation of high-energy pulses by using a low-repetition-rate Kerr-lens mode-locked laser. Repetition rates as low as 4 MHz were achieved with a long, multiple-pass cavity and a semiconductor saturable Bragg reflector. The laser generated pulses of 55-fs duration with a pulse energy of 48 nJ when it was mode locked in the net negative dispersion regime. Mode locking in the positive dispersion regime reduces instabilities and enables pulses to have durations of 80 fs and energies as high as 90 nJ. This is, to our knowledge, the highest pulse energy and the lowest repetition rate ever generated directly from a femtosecond laser resonator without cavity dumping.
Yeast strain affects 3-isopropyl-2-methoxypyrazine concentration and sensory profile in Cabernet Sauvignon wine (2008)

Background and Aims: 3-Isopropyl-2-methoxypyrazine (IPMP) is both a grape- and insect-derived trace compound found in wine that can contribute green characters. There has been renewed interest in examining how wine IPMP concentrations can be modulated due to recent concerns regarding ladybug taint – an off-flavour from IPMP extracted from Harmonia axyridis (Pallas) (multicoloured Asian lady beetle). This study sought to determine the influence of commercial Saccharomyces yeast strains on IPMP concentration in Cabernet Sauvignon wines and to describe their sensory impact. Methods and Results: Rehydrated juice from Cabernet Sauvignon concentrate was spiked with 30 ng/L IPMP and fermented in triplicate by yeast strains Lalvin BM45, Lalvin EC1118, Lalvin ICV-D21 or Lalvin ICV-D80. IPMP concentration was determined using headspace solid-phase micro-extraction coupled with gas chromatography mass spectrometry (HS-SPME-GC-MS), and was unchanged from juice levels in wine fermented by EC1118, Lalvin D21 and Lalvin D80 but increased by 11 ng/L (29%) in wine fermented by Lalvin BM45. Yeast strains differed in their sensory impact on wine made from IPMP-spiked juice for five aroma and four flavour attributes. Conclusions: HS-SPME-GC-MS allows for sensitive measurement of IPMP that, for the first time, has demonstrated the capacity for wine yeast to affect IPMP concentration. Yeast strains demonstrate varying ability to mask green or ladybug taint characters in wine. Significance of the Study: This information should be useful in guiding selection of yeast strains for juices of high IPMP concentration, including those that are multicoloured Asian lady beetle-affected, under-ripe or from varieties with high methoxypyrazine loads such as Cabernet Sauvignon.
Cd(ii)-triggered excimer–monomer conversion of a pyrene derivative: time dependent red-shift of monomer emission with cell staining application (2012)

An efficient fluorescent probe (E)-N1-((E)-2-((pyren-7-yl)methyleneamino)ethyl)-N2-((pyren-7-yl)methylene)ethane-1,2-diamine (L) has been synthesized by a facile one-step condensation reaction. L can selectively detect Cd(2+) in presence of other common metal ions in 0.1 M HEPES buffered DMSO-water (4 : 1, v/v) medium. The detection limit of Cd(2+) is 1.8 × 10(-8) M. Cd(2+) can effectively convert the excimer emission of L into its monomer emission which in turn exhibits a time-dependent red-shift.
Syntheses for 2‐amino and 2‐mercapto‐2<i>H</i>‐1,4‐benzoxazin‐3(4<i>H</i>)‐one and 2<i>H</i>‐1,4‐benzothiazin‐3(4<i>H</i>)‐one as aza and thio analogues of the natural product <i>blepharigenin</i> (1996)

Abstract 2‐Amino‐2 H ‐1,4‐benzoxazin‐3(4 H )‐one 3 , 2‐amino‐2 H ‐1,4‐benzothiazin‐3(4 H )‐one 4 , 2‐mercapto‐2 H ‐1,4‐benzoxazin‐3(4 H )‐one 7 , and 2‐mercapto‐2 H ‐1,4‐benzothiazin‐3(4 H )‐one 8 representing aza and thio analogues of the natural product's aglucone Blepharigenin (2‐hydroxy‐2 H ‐1,4‐benzoxazin‐3(4 H )‐one) from Gramineae and Acantnaceae species have been synthesized for the first time from their 2‐bromo precursors 1 and 2 . Attempts to similarly prepare the 4‐hydroxy derivatives of 7 and 8 , which would represent new thio analogues of the naturally occurring cyclic hydroxamic acid, 2,4‐dihydroxy‐2 H ‐1,4‐benzoxazin‐3(4 H )‐one, have failed.
Simulation-based models of emergency departments: (2011)

The Emergency Department (ED) of a modern hospital is a highly complex system that gives rise to numerous managerial challenges. It spans the full spectrum of operational, clinical, and financial perspectives, over varying horizons: operational—a few hours or days ahead; tactical—weeks or a few months ahead; and strategic, which involves planning on monthly and yearly scales. Simulation offers a natural framework within which to address these challenges, as realistic ED models are typically intractable analytically. We apply a general and flexible ED simulator to address several significant problems that arose in a large Israeli hospital. The article focuses mainly, but not exclusively, on workforce staffing problems over these time horizons. First, we demonstrate that our simulation model can support real-time control, which enables short-term prediction and operational planning (physician and nurse staffing) for several hours or days ahead. To this end, we present a novel simulation-based technique that implements the concept of offered-load and discover that it performs better than a common alternative. Then we evaluate ED staff scheduling that adjusts for midterm changes (tactical horizon, several weeks or months ahead). Finally, we analyze the design and staffing problems that arose from physical relocation of the ED (strategic yearly horizon). Application of the simulation-based approach led to the implementation of our design and staffing recommendations.
Skin Clamps in Cosmetic Blepharoplasty (1972)

In order to introduce a greater degree of certainty into the performance of cosmetic blepharoplasty, skin clamps have been devised to determine more exactly the shape and extent of tissue area to be excised. By placing the clamps so they pick up all excess tissue, the surgeon can view the effect of the planned excision before the surgical procedure is performed. Thus, he is enabled to steer a course between excess caution and consequent insufficient correction on the one hand, and the disaster of excess excision on the other.
Graphene Quantum Dots Derived from Carbon Fibers (2012)

Graphene quantum dots (GQDs), which are edge-bound nanometer-size graphene pieces, have fascinating optical and electronic properties. These have been synthesized either by nanolithography or from starting materials such as graphene oxide (GO) by the chemical breakdown of their extended planar structure, both of which are multistep tedious processes. Here, we report that during the acid treatment and chemical exfoliation of traditional pitch-based carbon fibers, that are both cheap and commercially available, the stacked graphitic submicrometer domains of the fibers are easily broken down, leading to the creation of GQDs with different size distribution in scalable amounts. The as-produced GQDs, in the size range of 1-4 nm, show two-dimensional morphology, most of which present zigzag edge structure, and are 1-3 atomic layers thick. The photoluminescence of the GQDs can be tailored through varying the size of the GQDs by changing process parameters. Due to the luminescence stability, nanosecond lifetime, biocompatibility, low toxicity, and high water solubility, these GQDs are demonstrated to be excellent probes for high contrast bioimaging and biosensing applications.
Microfluidic generation of microgels from synthetic and natural polymers (2009)

In this tutorial review we discuss recent advances in the application of microfluidics for the generation of microgels from synthetic and biological polymers. We summarize advantages and drawbacks of the current methods used in microfluidic synthesis and assembly of polymer microgels. Continuous microfluidic encapsulation of cells is discussed as an exemplary application of the microgels. The article is finalized with a perspective on future research in the field. The article will be of interest to chemists, cell biologists, pharmacologists, and medicinal chemists.
Aint/Tacc3 Is Highly Expressed in Proliferating Mouse Tissues During Development, Spermatogenesis, and Oogenesis (2003)

Aint was originally identified on the basis of its interaction in vitro with the aryl hydrocarbon nuclear receptor translocator (Arnt). Arnt is a common heterodimerization partner in the basic helix-loop-helix (bHLH)-PER-ARNT-SIM (PAS) protein family and is involved in diverse biological functions. These include xenobiotic metabolism, hypoxic response, and circadian rhythm. In addition, Arnt has a crucial role during development. Aint is a member of a growing family of transforming acidic coiled-coil (TACC) proteins and is the murine homologue of human TACC3. Here we report the spatiotemporal expression of Tacc3 mRNA and protein in embryonic, postnatally developing, and adult mouse tissues using in situ hybridization and immunocytochemistry. Tacc3 mRNA was highly expressed in proliferating cells of several organs during murine development. However, the only adult tissues expressing high levels were testis and ovary. Immunocytochemistry revealed that Tacc3 is a nuclear protein. Our results suggest that Tacc3 has an important role in murine development, spermatogenesis, and oogenesis.
Differential regulation of thrombospondin-1 and fibronectin by angiotensin II receptor subtypes in cultured endothelial cells (2001)

The present results suggest that the ANG II receptor subtype AT(2) mediates growth inhibition in macrovascular EC similar to what has been shown before in microvascular rat EC and that AT(2) receptors mediates remodeling of the endothelial ECM by upregulation of TSP-1 expression in both macro- and micro-vascular endothelial cells.
Advanced model transformation language constructs in the VIATRA2 framework (2006)

We present the model transformation language of the VIATRA2 framework, which provides a rule and pattern-based transformation language for manipulating graph models by combining graph transformation and abstract state machines into a single specification paradigm. This language offers advanced constructs for querying (e.g. recursive graph patterns) and manipulating models (e.g. generic and meta transformation rules) in unidirectional model transformations frequently used in formal model analysis to carry out powerful abstractions. In addition, powerful language constructs are provided for multi-level metamodeling to design modeling languages and template-based code generation.
Analysis of biodegradation performance of furfural and 5-hydroxymethylfurfural by Amorphotheca resinae ZN1 (2014)

The biological degradation performance of furfural and HMF by A. resinae ZN1 was investigated experimentally. Oxygen supply is important on the complete biodegradation of furfural and HMF by A. resinae ZN1. Furfural or HMF has the priority of substrate utilization than glucose by A. resinae ZN1. This study provided important information for detoxification enhancement and strain modification.
Structural Changes of LiMn2 O 4 Spinel Electrodes during Electrochemical Cycling (1999)

Structural changes of LiMn2O4 spinel electrodes have been investigated in 4 V Li/LixMn2O4 cells by X-ray diffraction during prolonged electrochemical cycling between 4.5 and 3.4 V at room temperature. The capacity fade that is observed during cycling is attributed, at least partly, to disproportionation reactions at the particle surface of discharged LixMn2O4 electrodes, resulting in a soluble MnO component. The disproportionation reactions are described with respect to the Li-Mn-O phase diagram. The data support recent reports that Li2Mn2O4 can be formed at the electrode surface slightly above 3 V when cells are discharged and charged at high rates.
ROSE PROCESS IMPROVES RESID FEED (1976)

A new process for residuum processing is known as ROSE (Residuum Oil Supercritical Extraction). The ROSE process involves the use of a variety of selective solvents for extractive treatment of reduced crude oils and vacuum residues. (LK)
IMMUNOACTIVE PEPTIDES, FK-156 AND FK-565. III (1983)

We investigated the effect of immunoactive peptides, FK-156 and FK-565 on host defense mechanisms against microbial invasion. It was shown that these drugs given to normal mice increased the counts of phagocytes in both peripheral blood and peritoneal cavity, and enhanced the chemotactic, phagocytic and killing activities of peritoneal macrophages and polymorphonuclear leukocytes, and stimulated the phagocytic function of the reticuloendothelial system. Enhanced host resistance to microbial infection by these immunoactive peptides might be induced by both increase in counts and enhancement of functions of phagocytes. FK-156 restored decreased counts and functions of phagocytes in mice immunosuppressed by cyclophosphamide, hydrocortisone or tumor. These findings suggest that these immunoactive peptides could be applied to prevent intractable infection in immunocompromised hosts.
Usefulness of <i>rpoB</i> Gene Sequencing for Identification of <i>Afipia</i> and <i>Bosea</i> Species, Including a Strategy for Choosing Discriminative Partial Sequences (2003)

Bacteria belonging to the genera Afipia and Bosea are amoeba-resisting bacteria that have been recently reported to colonize hospital water supplies and are suspected of being responsible for intensive care unit-acquired pneumonia. Identification of these bacteria is now based on determination of the 16S ribosomal DNA sequence. However, the 16S rRNA gene is not polymorphic enough to ensure discrimination of species defined by DNA-DNA relatedness. The complete rpoB sequences of 20 strains were first determined by both PCR and genome walking methods. The percentage of homology between different species ranged from 83 to 97% and was in all cases lower than that observed with the 16S rRNA gene; this was true even for species that differed in only one position. The taxonomy of Bosea and Afipia is discussed in light of these results. For strain identification that does not require the complete rpoB sequence (4,113 to 4,137 bp), we propose a simple computerized method that allows determination of nucleotide positions of high variability in the sequence that are bordered by conserved sequences and that could be useful for design of universal primers. A fragment of 740 to 752 bp that contained the most highly variable area (positions 408 to 420) was amplified and sequenced with these universal primers for 47 strains. The variability of this sequence allowed identification of all strains and correlated well with results of DNA-DNA relatedness. In the future, this method could be also used for the determination of variability "hot spots" in sets of housekeeping genes, not only for identification purposes but also for increasing the discriminatory power of sequence typing techniques such as multilocus sequence typing.
Inhibition of Dengue and Chikungunya Virus Infections by RIG-I-Mediated Type I Interferon-Independent Stimulation of the Innate Antiviral Response (2014)

DENV and CHIKV are two reemerging mosquito-borne viruses for which no therapeutic options currently exist. Both viruses overlap geographically in tropical regions of the world, produce similar fever-like symptoms, and are difficult to diagnose. This study investigated the inhibitory effect of a RIG-I agonist on the replication of these two viruses. RIG-I stimulation using 5'pppRNA before or after DENV or CHIKV infection generated a protective antiviral response against both pathogens in immune and nonimmune cells; interestingly, the protective response against the viruses was largely independent of the classical type I interferon response. The antiviral efficacy of 5'pppRNA highlights the therapeutic potential of RIG-I agonists against emerging viruses such as DENV and CHIKV.
A double level metallization system having 2 mu m pitch for both levels (2003)

A double-layer metal (DLM) process having 2- mu m pitch for both metal levels has been successfully developed. This DLM system has been used in a 0.7- mu m CMOS process to fabricate 1-M SRAM and 256 K SRAM devices. Some relevant design rules are 1- mu m metal line and space for both levels, and 0.9- mu m contact and via openings. To meet these requirements, the process features planarization to minimize topology at LOCOS, polysilicon, and metal levels. The technological results are presented as well as reliability and electrical results. Photographs of fully processed and functional 256 K and 1-M high-performance SRAMs are shown.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Physicians can make a difference with smokers: evidence-based clinical approaches. Presentation given during the Symposium on Smoking Cessation at the 29th World Conference of the IUATLD/UICTMR and Global Congress on Lung Health, Bangkok, Thailand, 23-26 November 1998. International Union Against Tuberculosis and Lung Disease. (1999)

Tobacco use poses one of the greatest public health challenges globally. This paper reviews the role of the physician as a key figure in promoting tobacco control and prevention. The physician is in a prime position to assist patients to stop smoking because of the high rate of contact with the general public. His/her efforts can contribute towards stemming the projected increase in smoking prevalence and resulting mortality and morbidity from cigarette-related diseases. However, the doctor is not taking full advantage of this window of opportunity to identify smokers and provide stop smoking advice. Evidence of physicians' and general practitioners' success in advising patients to stop smoking is presented. In general, clinical trials have reported abstinence rates of 5% to 10% for brief advice, and 20% to 36% for more physician involvement in providing advice and counselling. Nicotine replacement therapies (gum and patch) and other pharmacological treatments are useful adjuncts to physicians' advice to quit. Three evidence-based approaches available for the physician to use are described: 'Smokescreen for the 1990s in Australia', 'Smoking Cessation Clinical Practice Guideline' in the USA, and 'Guidelines on Smoking Cessation for General Practitioners and Other Health Professionals' in Europe. The information and resources that we have produced in industrialised countries must be translated, made culturally appropriate and distributed to physicians around the world, particularly in low income countries, so that they can fulfil their vital function of assisting patients to stop smoking.
Guidelines for advertising on health web sites: Who's guarding the Koop? (2000)

The Internet is a promising and popular tool for the global dissemination of health information to the public. According to one estimate, “health sites draw two thirds of all online users at least once.”1 Unfortunately, the power of the Internet to facilitate quick, inexpensive, and worldwide publication is also a weakness when it comes to information about health. Distinctions between trained medical professionals and quacks, tested drugs and untested compounds, and advertisements and content are difficult to make. Furthermore, the global nature of the Internet defies most current nation-specific laws regulating the practice of medicine or sales of health-related products based on unverified health claims.2

The use of the Internet has encouraged the blurring of distinctions between content areas and advertising. Criticism of the well-traveled health information web site, drkoop. com, started by the former US Surgeon General C Everett Koop,3 however, illustrates why such ambiguity is a problem for health care professionals and why the criticisms bring to mind images of foxes and henhouses.
The insulin-elicited 60-kDa phosphotyrosine protein in rat adipocytes is associated with phosphatidylinositol 3-kinase. (1993)

Insulin stimulates the tyrosine phosphorylation of a 60-kDa protein (pp60) in rat adipocytes. After insulin treatment of these cells, pp60, as well as the 160-kDa insulin receptor substrate-1 (IRS-1), were found to be associated with the enzyme phosphatidylinositol 3-kinase (PtdIns-3-kinase) in separate complexes. By contrast, pp60 was not detected in insulin-treated mouse 3T3-L1 adipocytes, which contain abundant IRS-1. PtdIns-3-kinase complex. The pp60.PtdIns 3-kinase complex was located in both the soluble and membrane fractions of the rat adipocytes. Fusion proteins containing the isolated src homology 2 domains from the 85-kDa subunit of PtdIns-3-kinase bound to pp60 in lysates of insulin-treated rat adipocytes. This finding indicates that the most likely mode of association of pp60 with PtdIns-3-kinase is through binding of phosphotyrosine residues in pp60 to these domains. By immunoaffinity chromatography on a monoclonal antibody against phosphotyrosine, pp60 was purified in high percentage yield from insulin-stimulated rat adipocytes, but the low amount of the protein obtained (about 3 ng from the adipocytes of one rat) precluded sequence analysis.