gebhart/patrepeval huggingface dataset:
The therapeutic potential of GLP‐1 receptor biased agonism (2021)

Glucagon-like peptide-1 (GLP-1) receptor agonists are effective treatments for type 2 diabetes as they stimulate insulin release and promote weight loss through appetite suppression. Their main side effect is nausea. All approved GLP-1 agonists are full agonists across multiple signalling pathways. However, selective engagement with specific intracellular effectors, or biased agonism, has been touted as a means to improve GLP-1 agonists therapeutic efficacy. In this review, I critically examine how GLP-1 receptor-mediated intracellular signalling is linked to physiological responses and discuss the implications of recent studies investigating the metabolic effects of biased GLP-1 agonists. Overall, there is little conclusive evidence that beneficial and adverse effects of GLP-1 agonists are attributable to distinct, nonoverlapping signalling pathways. Instead, G protein-biased GLP-1 agonists appear to achieve enhanced anti-hyperglycaemic efficacy by avoiding GLP-1 receptor desensitisation and downregulation, partly via reduced β-arrestin recruitment. This effect seemingly applies more to insulin release than to appetite regulation and nausea, possible reasons for which are discussed. At present, most evidence derives from cellular and animal studies, and more human data are required to determine whether this approach represents a genuine therapeutic advance. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.
Determinants of Medical Care Utilization: The Role of the Telephone in Total Medical Care (1973)

The importance of the telephone in the American medical care system is only beginning to receive appropriate attention. Fast studies indicate that a significant proportion of new diseases and a significant proportion of all medical care contacts take place by phone. A study of telephone use in a prepaid group practice system is presented. Data on telephone utilization are analyzed to determine the significance of telephone utilization of the population and to identify the patterns of telephone calls within total care seeking behavior. The purpose is to determine alternative modes of dealing with problems presented by phone or at least to assure that this important aspect of care is integrated into medical care. Telephone calls represented a significant proportion of the total medical care of the study population. About 50 per cent of all phone calls to medical core personnel were concerning symptoms of disease and approximately 40 per cent concerned laboratory results or prescriptions. Factors affecting the disposition of symptom phone calls were analyzed. It was hypothesized that the relative probability of a patient being told to come to the clinic after discussing a symptom would vary inversely with the certainty of the physician in his diagnosis and directly with the seriousness of the disease as perceived by the physician. The inferences from the data generally tended to support the hypotheses. These tendencies, however, were not strong enough to accurately predict when the physician would only discuss the symptom, give a prescription, or request a patient to visit. The concepts do not yet lend themselves to operational decision models for use by personnel trained to handle these kinds of calls, because of tremendous individual variation among physicians that confounds attempts to predict the disposition of symptom phone calls using only patient, disease, and situational variables.
Segregación socioespacial en el área metropolitana de Monterrey (AMM): forma urbana y rol de la seguridad (2015)

ResumenEn este articulo se analizan los motivos del surgimiento de distintas formas urbanas en las que la segregacion social se materializa. Al ser una de las ciudades mas grandes de Mexico, el Area Metropolitana de Monterrey (AMM) no esta exenta de este fenomeno. El hecho que refuerza la division —tanto funcional como espacial— de la ciudad es la industrializacion. Dado que el verdadero desarrollo de Monterrey se dio gracias a su proceso de industrializacion a principios del siglo pasado, la ciudad comenzo a presentar marcados casos de autosegregacion. Hasta la fecha, en Monterrey y su area metropolitana es posible observar distintos casos en que tal fenomeno se manifiesta. En el presente articulo se analiza la situacion actual de tres de dichos casos y la forma en que la seguridad ha sido un fuerte factor de influencia. AbstractThis article analyzes the reasons for the emergence of different urban forms in which the social segregation materializes itself. Being one of the biggest cities in Mexico, the Metropolitan Area of Monterrey isn’t the exception of this phenomenon. The fact that reinforces the division, functional or spatial, of the city is the industrialization. Due to the fact that the real development of Monterrey had place thanks to its process of industrialization at the beginning of the last century, important cases of auto-segregation began to appear in the city. Until this day, in Monterrey and its Metropolitan Area, it is possible to observe different cases in which this phenomenon exists. This article analyzes the present situation of three of these cases and the way in which security has been a strong factor of influence.
Trapping a Hydrazine Reduction Intermediate on the Nitrogenase Active Site (2005)

A major challenge in understanding the mechanism of nitrogenase, the enzyme responsible for the biological fixation of N(2) to two ammonias, is to trap a nitrogenous substrate at the enzyme active site in a state that is amenable to further characterization. In the present work, a strategy is described that results in the trapping of the substrate hydrazine (H(2)N-NH(2)) as an adduct bound to the active site metal cluster of nitrogenase, and this bound adduct is characterized by EPR and ENDOR spectroscopies. Earlier work has been interpreted to indicate that nitrogenous (e.g., N(2) and hydrazine) as well as alkyne (e.g., acetylene) substrates can bind at a common FeS face of the FeMo-cofactor composed of Fe atoms 2, 3, 6, and 7. Substitution of alpha-70(Val) that resides over this FeS face by the smaller amino acid alanine was also previously shown to improve the affinity and reduction rate for hydrazine. We now show that when alpha-195(His), a putative proton donor near the active site, is substituted by glutamine in combination with substitution of alpha-70(Val) by alanine, and the resulting doubly substituted MoFe protein (alpha-70(Ala)/alpha-195(Gln)) is turned over with hydrazine as substrate, the FeMo-cofactor can be freeze-trapped in a S = (1)/(2) state in high yield ( approximately 70%). The presumed hydrazine-FeMo-cofactor adduct displays a rhombic EPR signal with g = [2.09, 2.01, 1.93]. The optimal pH for the population of this state was found to be 7.4. The EPR signal showed a Curie law temperature dependence similar to the resting state EPR signal. Mims pulsed ENDOR spectroscopy at 35 GHz using (15)N-labeled hydrazine reveals that the trapped intermediate incorporates a hydrazine-derived species bound to the FeMo-cofactor; in spectra taken at g(1) this species gives a single observed (15)N signal, A(g(1)) = 1.5 MHz.
Platelet-Derived Growth Factor Induces Phosphorylation of Multiple JAK Family Kinases and STAT Proteins (1996)

Receptors for interferons and other cytokines signal through the action of associated protein tyrosine kinases of the JAK family and latent cytoplasmic transcription factors of the STAT family. Genetic and biochemical analysis of interferon signaling indicates that activation of STATs by interferons requires two distinct JAK family kinases. Loss of either of the required JAKs prevents activation of the other JAK and extinguishes STAT activation. These observations suggest that JAKs provide interferon receptors with a critical catalytic signaling function and that at least two JAKs must be incorporated into an active receptor complex. JAK and STAT proteins are also activated by ligands such as platelet-derived growth factor (PDGF), which act through receptors that possess intrinsic protein tyrosine kinase activity, raising questions about the role of JAKs in signal transduction by this class of receptors. Here, we show that all three of the ubiquitously expressed JAKs--JAK1, JAK2, and Tyk2--become phosphorylated on tyrosine in both mouse BALB/c 3T3 cells and human fibroblasts engineered to express the PDGF-beta receptor. All three proteins are also associated with the activated receptor. Through the use of cell lines each lacking an individual JAK, we find that in contrast to interferon signaling, PDGF-induced JAK phosphorylation and activation of STAT1 and STAT3 is independent of the presence of any other single JAK but does require receptor tyrosine kinase activity. These results suggests that the mechanism of JAK activation and JAK function in signaling differs between receptor tyrosine kinases and interferon receptors.
Effects of surface functional groups on protein adsorption and subsequent cell adhesion using self-assembled monolayers (2007)

We investigated initial cell adhesion on self-assembled monolayers (SAMs) of alkanethiols carrying different functional groups including methyl (CH3), hydroxyl (OH), carboxylic acid (COOH), and amine (NH2). The combination of a surface plasmon resonance (SPR) instrument and a total internal reflection fluorescence microscope (TIRFM) allowed us to examine the kinetics of protein adsorption and correlating cell adhesion. Upon exposure of the SAM surface to a serum-containing medium, serum proteins rapidly adsorbed, and cells subsequently approached the surface. Adhesion of human umbilical vein endothelial cells (HUVECs) was greatly affected by surface functional groups; HUVECs adhered well to COOH– and NH2–SAMs, whereas poorly to CH3– and OH–SAMs. The amount of adsorbed protein from the serum-containing medium varied slightly with the terminal groups of the SAMs. On COOH– and NH2–SAMs, HUVECs adhered to bovine serum albumin (BSA)-preadsorbed surfaces with a few minutes delay, suggesting that displacement of preadsorbed BSA with cell-adhesive proteins, such as fibronectin or vitronectin, supports cell adhesion to these surfaces. Since the concentration of cell-adhesive proteins is much less than that of non-adhesive proteins such as BSA, displacement of adsorbed proteins with cell-adhesive proteins plays an important role in initial cell adhesion.
An Approach for Indoor Path Computation among Obstacles that Considers User Dimension (2015)

People often transport objects within indoor environments, who need enough space for the motion. In such cases, the accessibility of indoor spaces relies on the dimensions, which includes a person and her/his operated objects. This paper proposes a new approach to avoid obstacles and compute indoor paths with respect to the user dimension. The approach excludes inaccessible spaces for a user in five steps: (1) compute the minimum distance between obstacles and find the inaccessible gaps; (2) group obstacles according to the inaccessible gaps; (3) identify groups of obstacles that influence the path between two locations; (4) compute boundaries for the selected groups; and (5) build a network in the accessible area around the obstacles in the room. Compared to the Minkowski sum method for outlining inaccessible spaces, the proposed approach generates simpler polygons for groups of obstacles that do not contain inner rings. The creation of a navigation network becomes easier based on these simple polygons. By using this approach, we can create user- and task-specific networks in advance. Alternatively, the accessible path can be generated on the fly before the user enters a room.
Reap what you sow (2008)

Post-silicon validation has recently become a major bottleneck in IC design. Several high profile IC designs have been taped-out with latent bugs, and forced the manufacturers to resort to additional design revisions. Such changes can be applied through metal fix; however, this is impractical without carefully pre-placed spare cells. In this work we perform the first comprehensive analysis of the issues related to spare-cell insertion, including the types of spare cells that should be used as well as their placement. In addition, we propose a new technique to measure the heterogeneity among signals and use it to determine spare-cell density. Finally, we integrate our findings into a novel multi-faceted approach that calculates regional demand for spare cells, identifies the most appropriate cell types, and places such cells into the layout. Our approach enables the use of metal fix at a much smaller delay cost, with a reduction of up to 37% compared to previous solutions
Synthetic Studies on Actinobolin and Bactobolin:  Synthesis of <i>N</i>-Desalanyl-<i>N</i>-[2-(trimethylsilyl)ethanesulfonyl] Derivatives from a Common Intermediate and Attempted Removal of the SES Protecting Group (1996)

Two closely related syntheses of 5,6-O-(2-propylidene)-N-desalanyl-N-2-(trimethylsilyl)ethanesulfonyl]bactobolin (9b) from (+)-12, an intermediate previously prepared from d-glucose, are reported. In each case, the key step involves a precedented stereoselective addition of LiCHCl2 in the presence of CeCl3 to a suitably protected α-amino ketone. Intermediates from both synthetic routes to 9b can be prepared by degradation of actinobolin (2) thereby establishing a potential method for the transformation of actinobolin into bactobolin. An efficient route to 5,6-O-(2-propylidene)-N-desalanyl-N-[[2-(trimethylsilyl)ethanesulfonyl]actinobolin (7b) from (+)-12 involving an unexpected cyclization of 29 was discovered. The 2-(trimethylsilyl)ethanesulfonyl (SES) protecting group in 7b was removed by reaction with Bu4NF in wet THF. The nature of the Bu4NF reagent was found to be important to the outcome of the reaction. Several improvements over our previously reported synthesis of actinobolin from d-glucose are noted. Although precedented, the removal of the SES protecting group from 9b could not be achieved thereby preventing completion of a total synthesis of bactobolin.
Distribution system short circuit analysis-A rigid approach (1992)

The authors introduce a method of short-circuit analysis applicable to more rigid study of large-scale distribution systems. This approach is oriented toward applications in distribution system operation analysis. The solution method is an iterative compensation method, which uses a single optimally ordered factorization of the bus admittance matrix (Y/sub Bus/), commonly used in power flow analysis, to simulate the fault condition. The use of this method in a short circuit analysis program enables a straightforward integration with a power flow program sharing a factorized Y/sub Bus/ solution, resulting in many advantages. Using a common factorization, both power flow and short-circuit analysis are possible in a single execution. Since the factorization is unchanged, multiple faults of varying types, including single line-to-ground, double line-to-ground, and three-phase, as well as cross-country, double three-phase, and triple double-line-to-ground faults can be simulated in one run of the program.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
A Compact Temperature Sensor Based on Micrometric Optical Fiber Coupler Tip (2012)

Get PDF Email Share Share with Facebook Share on X Post on reddit Share with LinkedIn Add to Mendeley Add to BibSonomy Share with WeChat Get Citation Copy Citation Text M. Ding, P. Wang, and G. Brambilla, "A Compact Temperature Sensor Based on Micrometric Optical Fiber Coupler Tip," in Imaging and Applied Optics Technical Papers, OSA Technical Digest (online) (Optica Publishing Group, 2012), paper STu1F.2. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Control and power electronics technology in renewable energy (2008)

As the cut-in point of research on control and power electronics technology used in renewable energy, this paper does not aim to analyze particular theories or tech-nologies in this field, but, instead, is to go back to the fountainhead of the issue to illustrate the essential concepts in this field, which are usually neglected and may become bottle-neck of the research. Research experiences have shown that con-fusion and trouble may be created if researchers do not understand these essential concepts well.
Aminopyrazoles. IV . Pyrazol‐3‐ and 5‐amines from 2,3‐dihaloalkanenitriles or 3‐chloroacrylonitriles and hydrazines (1982)

Abstract 2,3‐Dihalopropanenitriles and substituted 3‐chloropropenenitriles react with hydrazines in basic solution to form either pyrazol‐3‐amines 4 or pyrazol‐5‐amines 5 or a mixture of both isomers.
Manganese-Catalyzed Environmentally Benign Dehydrogenative Coupling of Alcohols and Amines to Form Aldimines and H<sub>2</sub>: A Catalytic and Mechanistic Study (2016)

The catalytic dehydrogenative coupling of alcohols and amines to form aldimines represents an environmentally benign methodology in organic chemistry. This has been accomplished in recent years mainly with precious-metal-based catalysts. We present the dehydrogenative coupling of alcohols and amines to form imines and H2 that is catalyzed, for the first time, by a complex of the earth-abundant Mn. Detailed mechanistic study was carried out with the aid of NMR spectroscopy, intermediate isolation, and X-ray analysis.
Making TCP Viable as a High Performance Computing Protocol (2002)

Generally, TCP is reputed to be too slow and bloated to be useful in high performance computing. However, it has very definite advantages over proprietary or special-ized protocols and could potentially be very useful in high performance computing. We researched different implemen-tations of MPI over TCP to distinguish between the limita-tions of TCP and the limitations of implementations of MPI over TCP. Next, we describe a new approach to address-ing the limitations of TCP: splintering. In contrast to OS bypass, the principle of splintering isn’t that the operating system shouldn’t be used, but that it should be used effec-tively. Finally, we describe the approach we will take in splintering processing for TCP packets. 1
Code division multiple-access techniques in optical fiber networks. I. Fundamental principles (1989)

An examination is made of fiber-optic code-division multiple-access (FO-CDMA), a technique in which low information data rates are mapped into very-high-rate address codes (signature sequences) for the purpose of achieving random, asynchronous communications free of network control, among many users. The need for a special class of signature sequences to achieve the multiple-access capability using fiber-optic signal processing techniques is discussed. A class of signature sequences called optical orthogonal codes (OOCs) that provide the auto- and cross-correlation properties required for FO-CDMA is introduced and used in an experiment to show the principles of FO-CDMA. The experiment demonstrates the auto- and cross-correlation properties of the codes. The concept of optical disk patterns, an equivalent way of representing the OOCs, is introduced. The patterns are used to derive the probability density functions associated with any two interfering OOCs. A detailed study of different interference patterns is presented, and the strongest and the weakest interference patterns are determined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Proliferation and Differentiation of MC3T3-E1 Cells on Calcium Phosphate/Chitosan Coatings (2008)

The incorporation of chitosan into electro-deposited calcium phosphate (CaP) coatings increases bone marrow stromal cell attachment. We hypothesized that such electrodeposited CaP/chitosan coatings can also enhance the proliferative ability and differentiation potential of osteoblasts. To verify this hypothesis, we cultured osteoblast-like MC3T3-E1 cells on these CaP coatings. It was found that MC3T3-E1 cells cultured on the electrodeposited CaP/chitosan coatings had cell proliferation rates higher than those on the electrodeposited CaP coatings. At the same time, both alkaline phosphatase activity and collagen expression were increased, and both bone sialoprotein and osteocalcin genes were up-regulated when MC3T3-E1 cells were cultured on the electrodeposited CaP/chitosan coatings. Additionally, within the range of selected chitosan concentrations in solution, no significant difference was found between the CaP/chitosan coatings. Our results suggest that the electrodeposited CaP/chitosan coatings are favorable to the proliferation and differentiation of MC3T3-E1 cells, which may endow them with great potential for future applications.
Combined immunohistochemical and autoradiographic analyses of antigen/antibody interactions in tumor xenograft models. (1991)

A study was conducted to establish optimal conditions which would allow for the simultaneous localization of a carcinoma antigen and its complementary radiolabeled antibody. Immunoperoxidase staining was used to identify the tumor distribution of antigen, while tissue localization of the radiolabeled antibody was identified by autoradiography. The tumor associated glycoprotein-72 (TAG-72) antigen and the high affinity murine monoclonal antibody, CC49 IgG were used as the model antigen/antibody pair. Athymic female mice bearing either CX-1 or LS-174T human colorectal adenocarcinoma xenografts were used as animal/tumor test systems. Experimental mice each received a bolus intravenous injection of the CC49 antibody which was labeled with 125I (specific activity, 0.17 to 0.26 microCi/microgram). Control mice were given a bolus injection of MOPC-21 IgG monoclonal antibody (tumor irrelevant antibody) which was also radiolabeled with 125I (specific activity, 0.24 to 0.35 microCi/microgram). At 24 hours postinjection, all tumors removed, counted for radioactivity, and fixed in formalin. The avidin/biotin immunoperoxidase complex technique was used to identify TAG-72 antigenic sites on slide-mounted tissue sections. Nonradiolabeled CC49 IgG (0.5 micrograms/ml) was used as the specific antigen binding primary antibody in the immunostaining procedures. Nonradiolabeled MOPC-21 IgG (0.5 micrograms/ml) served as the negative control. Immunohistochemically stained tissue sections were coated with photographic emulsion and processed for autoradiographic localization of 125I-CC49 or 125I-MOPC-21. After an optimal exposure time of 6 days, slides were processed and examined under a light microscope. Results of the biolocalization experiment revealed that the % of injected dose/gram of 125I-CC49 in both LS-174T and CX-1 tumors (30.4 +/- 5.2% and 20.6 +/- 5.4%, respectively) were significantly greater (p greater than 0.01) than those for 125I-MOPC-21 (4.9 +/- 0.5% and 5.1 +/- 0.7%, respectively). In both tumor lines from mice injected with 125I-CC49, dense clusters of silver grains were found over those regions which were positive for TAG-72 immunoreactivity. These dual-labeled structures were also found in contact with, or in close proximity to the microvasculature. Tumors from mice which were injected with the control radioconjugate showed a random distribution of silver grains within stromal tissue but no specific localization to TAG-72 positive regions. We conclude that intravenously administered 125I-CC49 IgG localizes specifically to antigen-containing sites in the LS-174T and CX-1 tumor models. The methods described herein should serve as useful tools for the direct study of antigen-antibody interactions in tumor biology.
Supplement: Concerning the Geographic Distribution of the Yellow Fever Mosquito (Revised Version, November 10, 1905) (1905)

L. O. Howard, Supplement: Concerning the Geographic Distribution of the Yellow Fever Mosquito (Revised Version, November 10, 1905), Public Health Reports (1896-1970), Vol. 20, No. 45 (Nov. 10, 1905), pp. 1+3-9+11