gebhart/patrepeval huggingface dataset:
A Real-World Approach to Insulin Therapy in Primary Care Practice (2005)

T ype 2 diabetes is a progressive disease characterized by relentless deterioration of pancreatic β-cell function.1 With the increasing incidence of type 2 diabetes, especially among younger individuals who will live longer with their disease, more patients will develop severe insulin deficiency and require insulin replacement. Because primary care providers see the vast majority of patients with type 2 diabetes, they may soon find themselves overwhelmed with insulin-requiring patients.

This article provides some practical guidelines for initiating insulin therapy in primary care practice. It is important to remember, however, that these are general guidelines and that management should be individualized for each patient.

Some primary care providers may be apprehensive about using insulin in patients with type 2 diabetes. Wallace and Matthews2 have gone so far as to suggest that patients and providers have often “colluded in implicit and unspoken contracts to continue oral agents for as long as possible.”

Concerns about hypoglycemia and patient willingness and/or ability to inject insulin are good reasons why many providers may approach insulin therapy with caution. Compounding this reluctance is the perception that insulin therapy is too complex to manage in a busy primary care practice; prescribing information provided by manufacturers has been somewhat vague regarding initial dosing and titration. Because of these factors, providers may delay in making the necessary transition from oral agents to insulin. Indeed, recent evidence suggests that the hemoglobin A1c (A1C) result that triggers glucose-lowering action is ≥ 9%.3 This is unfortunate because numerous studies have shown that excellent glycemic control can be achieved with insulin therapy in patients with type 2 diabetes.4-7 Moreover, there is an increasing body of evidence showing that early and effective intervention with insulin is more important than had been previously believed.8-10

### Early and Aggressive Intervention Matters

Insulin …
Truncated glucagon‐like peptide‐1 (proglucagon 78–107 amide), an intestinal insulin‐releasing peptide, has specific receptors on rat insulinoma cells (RIN 5AH) (1988)

We studied binding of 125I-labelled truncated-glucagon-like peptide-1 (proglucagon 78-107 amide) to a cloned rat insulin-producing cell line, RIN 5AH, in monolayer culture. Interaction of the peptide with pancreatic insulinoma cells was saturable and time dependent. Half-maximal binding was obtained when the cells were incubated in the presence of 3.3 x 10(-9) mol/l unlabelled truncated-glucagon-like peptide-1 (proglucagon 78-107 amide). Neither glucagon, full-length glucagon-like peptide-1 (proglucagon 72-107 amide) nor gastric inhibitory peptide competed for binding in concentrations up to 10(-6) mol/l.
Early Signals in Cardiac Development (2002)

The heart is the first organ to form during embryogenesis and its circulatory function is critical from early on for the viability of the mammalian embryo. Developmental abnormalities of the heart have also been widely recognized as the underlying cause of many congenital heart malformations. Hence, the developmental mechanisms that orchestrate the formation and morphogenesis of this organ have received much attention among classical and molecular embryologists. Due to the evolutionary conservation of many of these processes, major insights have been gained from the studies of a number of vertebrate and invertebrate models, including mouse, chick, amphibians, zebrafish, and Drosophila. In all of these systems, the heart precursors are generated within bilateral fields in the lateral mesoderm and then converge toward the midline to form a beating linear heart tube. The specification of heart precursors is a result of multiple tissue and cell-cell interactions that involve temporally and spatially integrated programs of inductive signaling events. In the present review, we focus on the molecular and developmental functions of signaling processes during early cardiogenesis that have been defined in both vertebrate and invertebrate models. We discuss the current knowledge on the mechanisms through which signals induce the expression of cardiogenic transcription factors and the relationships between signaling pathways and transcriptional regulators that cooperate to control cardiac induction and the formation of a linear heart tube.
Biosynthesis of human fibrinogen. Subunit interactions and potential intermediates in the assembly. (1993)

Stable transfected baby hamster kidney (BHK) cells expressing human alpha, beta, and gamma fibrinogen chains together, in various combinations of any two, or individually, were established. Several types of subunit interactions were observed in the intracellular extracts of the transfected BHK cell lines as well as in Hep G2 cells. These included: 1) formation of alpha gamma dimers linked by a disulfide bond(s), 2) formation of beta gamma dimers linked by a disulfide bond(s), 3) formation of alpha beta gamma half-molecules linked by disulfide bonds, and 4) formation of mature fibrinogen, which was also secreted into the cell culture medium. Analysis of the chain composition confirmed the stoichiometry of the alpha gamma, beta gamma, and alpha beta gamma complexes. These data are consistent with the proposal that the alpha gamma and beta gamma dimers as well as the alpha beta gamma half-molecules are intermediates in the assembly and biosynthesis of fibrinogen. In contrast, disulfide-linked alpha beta complexes were not found in transfected BHK cells or in Hep G2 cells, suggesting that the formation of disulfide bonds between these two chains most likely occurs when alpha beta gamma half-molecules are formed from alpha gamma and/or beta gamma complexes and when alpha beta gamma half-molecules dimerize to generate the mature molecule. Dimers, trimers, and larger oligomers of each individual chain linked by disulfide bonds were also identified when each chain was expressed in the absence of the other two chains. Preferential formation of alpha gamma and beta gamma complexes, rather than oligomers of individual chains, suggested that the oligomers were less likely to be intermediates in the assembly of fibrinogen. A model for fibrinogen assembly is presented based on these results.
Delivering Cas9/sgRNA ribonucleoprotein (RNP) by lentiviral capsid-based bionanoparticles for efficient ‘hit-and-run’ genome editing (2019)

Transient expression of the CRISPR/Cas9 machinery will not only reduce risks of mutagenesis from off-target activities, but also decrease possible immune response to Cas9 protein. Building on our recent developing of a system able to package up to 100 copies of Cas9 mRNA in each lentivirus-like particle (LVLP) via the specific interaction between aptamer and aptamer-binding proteins (ABP), here we develop a lentiviral capsid-based bionanoparticle system, which allows efficient packaging of Cas9/sgRNA ribonucleoprotein (RNP). We show that replacing the Tetraloop of sgRNA scaffold with a com aptamer preserves the functions of the guide RNA, and the com-modified sgRNA can package Cas9/sgRNA RNP into lentivirus-like particles via the specific interactions between ABP and aptamer, and sgRNA and Cas9 protein. These RNP bionanoparticles generated Indels on different targets in different cells with efficiencies similar to or better than our recently described Cas9 mRNA LVLPs. The new system showed fast action and reduced off-target rates, and makes it more convenient and efficient in delivering Cas9 RNPs for transient Cas9 expression and efficient genome editing.
Effectively-single-mode large core passive and active fibers with chirally-coupled-core structures (2008)

Chirally-coupled-core fibers with core sizes well exceeding those of conventional LMA provide robust single-mode output irrespective of mode excitation and fiber coiling, are spliceable, and can preserve mode-area in tight bends and reduce nonlinear effects.
Exchange bias of singly invertedFeO/Fe3O4core-shell nanocrystals (2008)

Exchange bias (EB) is investigated in singly inverted $\text{FeO}/{\text{Fe}}_{3}{\text{O}}_{4}$ core-shell nanocrystals by vibrating sample magnetometry. A horizontal and vertical shift of the field-cooled (FC) hysteresis loop with respect to the zero-field-cooled (ZFC) hysteresis loop is observed below the blocking temperature of EB $({T}_{B}^{\text{EB}}\ensuremath{\approx}{T}_{N})$. An enhancement of the superparamagnetic blocking temperature $({T}_{B}^{\text{SP}}\ensuremath{\approx}190\text{ }\text{K})$ with respect to the expected value is observed from the ZFC/FC measurement of $m(T)$. Furthermore, the value of ${T}_{B}^{\text{SP}}$ is nearly constant for applied fields ranging from 25 to 200 Oe as a result of the exchange coupling at the antiferromagnetic/ferrimagnetic interface.
Human interleukin 1 induces interleukin 1 gene expression in human vascular smooth muscle cells. (1987)

The recognition that cells of the vascular wall can secrete cytokines such as IL-1 suggests new mechanisms for initiating or sustaining inflammatory responses in blood vessels. We report that purified human monocyte-derived IL-1 or recombinant human IL-1 (rIL-1 beta and rIL-1 alpha) induce cultured human smooth muscle cells derived from veins or arteries to synthesize IL-1 beta mRNA and produce and release biologically active IL-1. rIL-1 beta also stimulated the production of PGE2 by smooth muscle cells. Exposure to rIL-1 beta (1-100 ng/ml), or rIL-1 alpha (0.01-10 ng/ml) increased IL-1 beta mRNA levels within 30 min. Actinomycin D (1 microgram/ml) prevented the induction of IL-1 beta mRNA by rIL-1. IL-1 alpha mRNA was detected in SMC treated with cycloheximide (1 microgram/ml) and rIL-1 beta, or cycloheximide alone. rIL-1 alpha and rIL-1 beta produced maximal levels of IL-1 beta mRNA after 4 h, and intracellular IL-1 biological activity after 6 h of exposure. Release of IL-1 activity in the extracellular medium began after 1 h of incubation with rIL-1 beta or rIL-1 alpha, and continued for up to 24 h. Anti-TNF antiserum that neutralized the biological activity of rTNF did not affect rIL-1-induced production of IL-1 beta mRNA or IL-1 release, suggesting that the release of TNF does not mediate these processes. Several experimental approaches indicated that the release of IL-1 by smooth muscle cells was not due to endotoxin contamination of the IL-1 preparations. Anti-IL-1 antiserum blocked the induction of smooth muscle cell IL-1 gene expression by rIL-1 beta. Polymyxin B did not prevent IL-1-induced IL-1 expression by these cells, but blocked the effect of endotoxin. Heat treatment destroyed the stimulatory capacity of rIL-1 beta, but did not affect the ability of bacterial endotoxin to induce IL-1 expression. The production of IL-1 by human vascular smooth muscle cells was not due to contamination of the cell cultures with blood monocytes, inasmuch as treatment with an antimonocyte antibody (anti-Mo2) and complement did not alter IL-1 beta mRNA content or the amount of IL-1 released from the cells in response to endotoxin, rIL-1 alpha, or rIL-1 beta.(ABSTRACT TRUNCATED AT 400 WORDS)
SUPPRESSION OF URIC ACID SYNTHESIS IN THE GOUTY HUMAN BY THE USE OF 6-DIAZO-5-OXO-L-NORLEUCINE* (1960)

A substantial number of patients with gout has been shown to produce excessive amounts of uric acid (1-4). This overproduction has been demonstrated by the excretion of greater than normal amounts of uric acid in the urine, or an excessive incorporation of isotopically labeled glycine into urinary uric acid. The present day treatment of tophaceous gout consists primarily in the administration of uricosuric agents to increase the renal excretion of the uric acid formed, with use of colchicine, ACTH gel, or phenylbutazone for management of the acute attacks. Control of the production of uric acid has been of necessity confined to limiting the purine and protein content of the diet (5). A logical approach to the treatment of those patients who overproduce uric acid would be to inhibit the excessive production by pharmacologic agents. In recent years several compounds have been reported to interfere with purine biosynthesis. Two such compounds, azaserine (o-diazoacetyl-L-serine) and 6-diazo-5-oxo-L-norleucine (DON), have been shown to suppress the forma
Transdermal Drug Delivery In Vitro Using Diffusion Cells (2012)

The assessment of percutaneous absorption of molecules is a very important step in the evaluation of any dermal or transdermal drug delivery system. In order to perform percutaneous drug absorption studies, it is essential that the methods are standardized and that the integrity of the skin is monitored and maintained to ensure that the data obtained are valid and relevant. Reproducible data on percutaneous absorption in humans are as well required to predict the systemic risk from dermal exposure to chemicals, such as hazardous substances at the workplace, agrochemicals and cosmetic ingredients. In vitro and animal models provide important tools for screening a series of drug formulations, evaluation of skin permeation enhancing properties and mechanism of action of the carrier systems and estimation of rank of skin transport for a series of drug molecules. In this review, we have summarized in vitro testing of skin absorption using static Franz-type diffusion cells.
Automated fabrication of mobility aids (AFMA): Below-knee CASD/CAM testing and evaluation program results (1992)

In 1988 the Department of Veterans Affairs Rehabilitation Research and Development Service, under the directorship of Margaret J. Giannini, M.D., began a nationally directed computer-aided design and computer-aided manufacturing (CAD/CAM) research program for the Automated Fabrication of Mobility Aids (AFMA). Under this program CAD/CAM research and development centers were established at the Prosthetics Research Study in Seattle, WA; at Northwestern University and the VA Lakeside Medical Center in Chicago, IL; and at the VA Medical Center and New York University Medical Center in New York, NY. These three centers conducted a collaborative program: (a) to introduce CAD/CAM technologies to prosthetists, physicians, therapists, and rehabilitation health care professionals in the United States; (b) to evaluate the feasibility of using CAD/CAM systems in clinical prosthetics settings; (c) to test and evaluate the University College London-Bioengineering Center's and the University of British Columbia-Medical Engineering Resource Unit's respective systems for the computer-aided design and computer-aided manufacture of prosthetic sockets (CASD/CAM) for below-knee amputees; and, (d) to obtain quantitative data for refinement of the CASD/CAM systems tested, and for the development of new, enhanced, more efficacious, and expedient systems.
Table-lookup algorithms for elementary functions and their error analysis (2002)

Table-lookup algorithms for calculating elementary functions offer superior speed and accuracy when compared with more traditional algorithms. It is shown that, with careful design, it is feasible to implement table-lookup algorithms in hardware. A uniform approach for carrying out a tight error analysis for such implementations is presented. The advantages of table-lookup algorithms over CORDIC and ordinary (without table-lookup) polynomial algorithms are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An Embedded Vision Engine (EVE) for automotive vision processing (2014)

This paper introduces Embedded Vision Engine (EVE) - a fully programmable, specialized vector processor architecture aimed at solving challenging Computer Vision applications encountered in Advanced Driver Assistance Systems (ADAS). The paper outlines the complexity of automotive vision applications, establishes why specialized architecture (like EVE) is needed and outlines the EVE architecture, its components and programming model. We present comparative benchmarks and provide an overview of many carefully crafted features of EVE for power management, inter processor communication, functional safety and software debug that helps in building a scalable, area-power efficient System-on-Chip (SoC) solutions for the cost, power and safety sensitive automotive vision space.
In VitroandIn VivoEvaluation of Human Tumor Necrosis Factor-α (hTNF α) Chemically Conjugated to Monoclonal Antibody (1998)

Human tumor necrosis-alpha (hTNF-alpha) was chemically conjugated to the murine anti-Ly-2.1 T cell antibody using heterobifunctional crosslinking agents SAMSA and SPDP. SDS-PAGE analysis of the affinity purified conjugate consisted mainly of 1:1 and 1:2 (Ly-2.1:TNF) complexes. Conjugated hTNF retained 50% of its cytotoxic activity by the L929 cytolytic assay, with an IC50 = 0.12 ng/ml. hTNF-Ly-2.1 was also cytotoxic to E3 cells (Ly-2.1+ve) with an IC50 = 1.7 microg/ml - 3 times more cytotoxic to these cells than non-conjugated hTNF in vitro. However in vivo hTNF-Ly-2.1 conjugates were more toxic to mice than hTNF. In vivo blood clearance studies in E3 tumor bearing CBF1 mice demonstrated that the half life of the conjugate was 2 hr, compared to 20 min for hTNF. In biodistribution studies, tumor accumulation of 3% was seen for hTNF-Ly-2.1 while for unconjugated hTNF no activity in tumor was detected 24hr post injection. A single dose of hTNF-Ly-2.1 increased the accumulation of 125I-anti-Ly-2.1 by 3 fold compared to controls. However, the antitumor effect of hTNF-Ly-2.1 on E3 cells in vivo was marginal with some tumor growth retardation at day 1-3. The results of these in vitro and in vivo studies on chemically conjugated h-TNF-MoAb will be helpful in the design of novel recombinant fusion proteins for targeting the biologic activity of TNF to tumours.
MMP‐2 sensitive, VEGF‐bearing bioactive hydrogels for promotion of vascular healing (2004)

We sought to develop bioactive hydrogels to facilitate arterial healing, e.g., after balloon angioplasty. Toward this end, we developed a new class of proteolytically sensitive, biologically active polyethylene glycol (PEG)-peptide hydrogels that can be formed in situ to temporarily protect the arterial injury from blood contact. Furthermore, we incorporated endothelial cell-specific biological signals with the goal of enhancing arterial reendothelialization. Here we demonstrate efficient endothelial cell anchorage and activation on PEG hydrogel matrices modified by conjugation with both the cell adhesive peptide motif RGD and an engineered variant of vascular endothelial growth factor (VEGF). By crosslinking peptide sequences for cleavage by MMP-2 into the polymer backbone, the hydrogels became sensitive to proteolytic degradation by cell-derived matrix metalloproteinases (MMPs). Analysis of molecular hallmarks associated with endothelial cell activation by VEGF-RGD hydrogel matrices revealed a 70% increase in production of the latent MMP-2 zymogen compared with PEG-peptide hydrogels lacking VEGF. By additional provision of transforming growth factor beta1 (TGF-beta1) within the PEG-peptide hydrogel, conversion of the latent MMP zymogen into its active form was demonstrated. As a result of MMP-2 activation, strongly enhanced hydrogel degradation by activated endothelial cells was observed. Our data illustrate the critical importance of growth factor activities for remodeling of synthetic biomaterials into native tissue, as it is desired in many applications of regenerative medicine. Functionalized PEG-peptide hydrogels could help restore the native vessel wall and improve the performance of angioplasty procedures.
IL-31-IL-31R Interactions Limit the Magnitude of Th2 Cytokine-Dependent Immunity and Inflammation following Intestinal Helminth Infection (2009)

IL-31 is a recently identified cytokine made predominantly by CD4(+) Th2 cells and its receptor, IL-31R, is expressed by a number of cell types including monocytes, epithelial cells, and T cells. Originally identified as a potential mediator of inflammation in the skin, we recently reported a novel function for endogenous IL-31R interactions in limiting type 2 inflammation in the lung. However, whether IL-31-IL-31R interactions regulate immunity or inflammation at other mucosal sites, such as the gut, is unknown. In this study, we report a regulatory role for IL-31-IL-31R interactions in the intestine following infection with the gastrointestinal helminth Trichuris muris, immunity to which is critically dependent on CD4(+) Th2 cells that produce IL-4 and IL-13. IL-31Ralpha was constitutively expressed in the colon and exposure to Trichuris induced the expression of IL-31 in CD4(+) T cells. In response to Trichuris infection, IL-31Ralpha(-/-) mice exhibited increased Th2 cytokine responses in the mesenteric lymph nodes and elevated serum IgE and IgG1 levels compared with wild type mice. IL-31Ralpha(-/-) mice also displayed enhanced goblet cell hyperplasia and a marked increase in secretion of goblet cell-derived resistin-like molecule beta into the intestinal lumen. Consistent with their exacerbated type 2 inflammatory responses, IL-31Ralpha(-/-) mice exhibited accelerated expulsion of Trichuris with significantly decreased worm burdens compared with their wild type counterparts early following infection. Collectively, these data provide the first evidence of a function for IL-31-IL-31R interactions in limiting the magnitude of type 2 inflammatory responses within the intestine.
Multiple Cranial Neuropathy Associated With Herpes Simplex Virus Infection and Anti-GM2 Immunoglobulin M Antibodies (2009)

Antiganglioside antibodies can appear after several acute infections and are often associated with various clinical patterns of Guillain-Barré syndrome. Thus, for example, cytomegalovirus infection has been associated with anti-GM2 antibodies and Guillain-Barré syndrome variants with severe sensory loss and cranial nerve involvement. We report on a patient who developed multiple cranial neuropathy associated with herpes simplex virus infection and anti-GM2 immunoglobulin M antibodies.
The mouse IgH 3′‐enhancer (1991)

Abstract A lymphoid‐specific transcription enhancer element has recently been identified at the far 3′ end of the rat immunoglobulin heavy chain (IgH) locus. Sequence analysis presented here reveals that this enhancer is flanked by a 350‐bp invert repeat, giving a structure reminiscent of a transposable element. We therefore screened for the equivalent enhancer in the mouse to determine whether its presence was conserved during evolution. A mouse homologue was indeed identified and is located 16 kb downstream of the C α 1 exon. It is also flanked by invert repeats and these are not repeated throughout the genome. The mouse and rat enhancers retain high sequence homology. As regard activity, the IgH 3′‐enhancer is lymphoid specific. However, this activity was detected in two plasmacytoma lines tested but not in two B cell lymphomas nor in HeLa cells suggesting that the enhancer may only play a stage‐specific role during lymphocyte differentiation. As regards function within the IgH locus, we found that inclusion of the mouse IgH 3′‐enhancer (in addition to the intron‐enhancer) on μ gene expression plasmids effected a small increase in μ mRNA levels in stable plasmacytoma transfectants.