gebhart/patrepeval huggingface dataset:
Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy (2008)

The consensus algorithm for the medical management of type 2 diabetes was published in August 2006 with the expectation that it would be updated, based on the availability of new interventions and new evidence to establish their clinical role. The authors continue to endorse the principles used to develop the algorithm and its major features. We are sensitive to the risks of changing the algorithm cavalierly or too frequently, without compelling new information. An update to the consensus algorithm published in January 2008 specifically addressed safety issues surrounding the thiazolidinediones. In this revision, we focus on the new classes of medications that now have more clinical data and experience.
Laser treatment for further depigmentation in vitiligo (1997)

Ruby laser treatment can be an effective, fast, and safe method for removing cosmetically disturbing remnants of normal pigmentation in vitiligo patients with a positive Koebner phenomenon.
Family of the green fluorescent protein: Journey to the end of the rainbow (2002)

Members of the family of the Green Fluorescent Protein (GFP) are the only known type of natural pigments that are essentially encoded by a single gene, since both the substrate for pigment biosynthesis and the necessary catalytic moieties are provided within a single polypeptide chain. In sharp contrast to the state of knowledge just three years ago when GFP was the only known protein of its kind, a whole family of related proteins, exhibiting striking diversity of features have now been identified. This provides new possibilities for a variety of studies ranging from applied biotechnology to evolutionary ecology.
Effects of multicopy LeuO on the expression of the acid-inducible lysine decarboxylase gene in Escherichia coli (1995)

We previously reported that mutations in hns, the structural gene for the histone-like protein H-NS, cause derepressed expression of cadA, which encodes the acid-inducible lysine decarboxylase at noninducing pH (pH 8.0). This study reports the characterization of a plasmid isolated from an Escherichia coli library that suppresses the effect of an hns mutation on cadA expression. A previously sequenced open reading frame, leuO, proves to be the gene that causes the hns-complementing phenotype. The mechanism for this phenotype appears to be overexpression of leuO from a multicopy plasmid, which drastically reduces production of CadC, the essential activator for cadA induction. These results show an in vivo regulatory phenotype for leuO, consistent with its proposed protein sequence.
Nonlinear Two-Dimensional Vibrational Spectroscopy (2000)

There is currently great interest in developing the vibrational analog to two-dimensional NMR spectroscopy. One approach to implementing two-dimensional vibrational spectroscopy is to use doubly vibrationally enhanced (DOVE) four-wave mixing (FWM). Nonlinear signals occur because of correlations and mode coupling that are induced by interactions involving the driven modes. Since cross peaks do not occur between modes if interactions are absent, spectral congestion is removed and only the coupled modes remain. We describe the development of a two-dimensional doubly vibrationally enhanced four wave mixing method that extends the doubly resonant nonlinear spectroscopies to vibrational nonlinearities. We demonstrate the selective enhancements of coupled modes that are possible with the double resonances where the intensity of the enhancements reflects the strength of the interactions that are responsible for the vibrational mode coupling. We also demonstrate the capabilities for selectively enhancing specific sample components in an isotopic mixture. Since biological applications of DOVE require aqueous environments, we have examined the ability of DOVE methods to discriminate against the strong water absorption and have found that water has a small vibrational nonlinearity that allows DOVE of the solutes. Our results demonstrate the feasibility and features required to make DOVE methods practical for a wide range of scientific applications where identification of intra- and intermolecular interactions is important.
Flanking sequence effects within the pyrimidine triple-helix motif characterized by affinity cleaving (1992)

Nearest neighbor interactions affect the stabilities of triple-helical complexes. Within a pyrimidine triple-helical motif, the relative stabilities of natural base triplets T.AT, C + GC, and G.TA, as well as triplets, D3.TA and D3.CG, containing the nonnatural deoxyribonucleoside 1-(2-deoxy-beta-D-ribofuranosyl)-4-(3-benzamido)phenylimidazole (D3) were characterized by the affinity cleaving method in the context of different flanking triplets (T.AT, T.AT: T.AT, C + GC: C + GC, T.AT: G + GC, C + GC). The to be insensitive to substitutions in either the 3' or 5' directions, while the relative stabilities of triple helices containing C + GC triplets decreased as the number of adjacent C + GC triplets increased. Triple helices incorporating a G.TA interaction were most stable when this triplet was flanked by two T.AT triplets and were adversely affected when a C + GC triplet was placed in the adjacent 5' direction. Similarly, complexes containing D3.TA or D3.CG triplets were most stable when the triplet was flanked by two T.AT triplets but were destabilized when the adjacent 3' neighbor position was occupied with a C + GC triplet. This information regarding sequence composition effects in triple-helix formation establishes a set of guidelines for targeting sequences of double-helical DNA by the pyrimidine triple-helix motif.
Characterization of the Brassica napusExtraplastidial Linoleate Desaturase by Expression in Saccharomyces cerevisiae (2000)

The substrate specificity and regioselectivity of the Brassica napus extraplastidial linoleate desaturase (FAD3) was investigated in vivo in a heterologous expression system. A strain of the yeast Saccharomyces cerevisiae producing the plant enzyme was constructed and cultured in media containing a variety of fatty acids. The products of desaturation of these potential substrates were determined by gas chromatographic and mass spectrometric analysis of the yeast cultures. The results indicate that the enzyme has: (a) omega-3, as opposed to Delta-15 or double-bond-related regioselectivity, (b) the ability to desaturate substrates in the 16 to 22 carbon range, (c) a preference for substrates with omega-6 double bonds, but the ability to desaturate substrates with omega-6 hydroxyl groups or omega-9 or omega-5 double bonds, and (d) a relative insensitivity to double bonds proximal to the carboxyl end of the substrate.
Contemporary Christian Music: Public Relations Amid Scandal (2005)

Christian entertainment. While this notion is an oxymoron to many, it is no longer a foreign concept to the world of business and finance. Largely ignored in the past, this growing sector of the entertainment industry has begun to garner significant appeal with the public, and thus has attracted increased media attention–both mainstream and Christian, both positive and negative. What makes this industry entirely unique is that it is indeed both “Christian” and “entertainment,” and both elements must function with equal effectiveness for the industry to thrive. This study chronicles a decade of challenge for this industry, involving scandals and buyouts, and examines the traumas and triumphs of PR professionals faced with potentially catastrophic situations. The intent of this project is to emphasize that the industry role of public relations was so in tune with calamity that it acted routinely, responsibly, and effectively to help diffuse each circumstance presented.
Natural Killer T Cells as Targets for Therapeutic Intervention in Autoimmune Diseases (2003)

Natural killer T (NKT) cells are a subset of lymphocytes that express receptors characteristic of conventional T cells together with receptors typically found on natural killer cells. A key feature of NKT cells is the expression of a semi-invariant T cell receptor that is specific for glycolipid antigens presented by the unusual major histocompatibility complex class I-like molecule CD1d. While their precise immunological functions remain unknown, NKT cells have been implicated in the regulation of adaptive immune responses, including those directed against autoantigens. These findings raise the possibility that specific stimulation of NKT cells may be exploited for therapeutic purposes. A number of laboratories have tested this hypothesis, utilizing the sea sponge-derived agent alpha-galactosylceramide (alpha-GalCer), a specific agonist of NKT cells. Administration of alpha-GalCer to mice results in potent activation of NKT cells, rapid and robust cytokine production, and activation of a variety of cells of the innate and adaptive immune systems. Most notably, repeated administration of alpha-GalCer to mice favors the generation of conventional T lymphocytes producing T helper (Th) type 2 cytokines such as IL-4 and IL-10. These findings suggest that alpha-GalCer can modulate inflammatory conditions that are mediated by pathogenic Th1 cells. Indeed, recent studies have demonstrated that alpha-GalCer prevents the development of Type 1 diabetes in non-obese diabetic mice and central nervous system inflammation in mouse models of multiple sclerosis. Collectively, these studies provide a solid foundation for the development of NKT cell ligands as pharmacological agents for treatment of autoimmune diseases.
IL-23 is essential for T cell–mediated colitis and promotes inflammation via IL-17 and IL-6 (2006)

Uncontrolled mucosal immunity in the gastrointestinal tract of humans results in chronic inflammatory bowel disease (IBD), such as Crohn disease and ulcerative colitis. In early clinical trials as well as in animal models, IL-12 has been implicated as a major mediator of these diseases based on the ability of anti-p40 mAb treatment to reverse intestinal inflammation. The cytokine IL-23 shares the same p40 subunit with IL-12, and the anti-p40 mAbs used in human and mouse IBD studies neutralized the activities of both IL-12 and IL-23. IL-10-deficient mice spontaneously develop enterocolitis. To determine how IL-23 contributes to intestinal inflammation, we studied the disease susceptibility in the absence of either IL-23 or IL-12 in this model, as well as the ability of recombinant IL-23 to exacerbate IBD induced by T cell transfer. Our study shows that in these models, IL-23 is essential for manifestation of chronic intestinal inflammation, whereas IL-12 is not. A critical target of IL-23 is a unique subset of tissue-homing memory T cells, which are specifically activated by IL-23 to produce the proinflammatory mediators IL-17 and IL-6. This pathway may be responsible for chronic intestinal inflammation as well as other chronic autoimmune inflammatory diseases.
The heart and cardiovascular system (1986)

This book contains 72 chapters. Some of the chapter titles are: Nuclear Magnetic Resonance; Radionuclide Methods to Assess Cardiac Function, Perfusion Viability and Necrosis; NMR Imaging of the Cardiovascular System; Quantitative Angiographic Techniques; RNA Transcription in Heart Muscle; Reentry Rhythms; and Effect of Ischemia on Cardiac Electrophysiology.
A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression (2016)

Twice-weekly and thrice-weekly administration of ketamine at 0.5 mg/kg similarly maintained antidepressant efficacy over 15 days.
Vehicular congestion modeling and estimation for advanced traveler information systems (2010)

It is widely accepted that the steady increase of urban vehicular congestion requires the implementation of adequate countermeasures. Intelligent Transportation Systems (ITSs) represent one of the possible solutions, as they strive to optimize the use of the available road network resources. Within this domain, the Advanced Travel Information Systems (ATISs) specifically address the vehicular congestion problem as they provide travelers, by means of a wireless channel, with updated road information. On receiving such information, travelers use their onboard Personal Navigation Devices (PNDs) to decide the best route to their destination. Clearly, ATISs become increasingly reliable the more they accurately identify the roads that are congested. We here propose a new model for detecting congestion that supports the accurate estimation and short-term forecasting of the state of a road to be used with ATISs. Such model can be generally applied to any type of street, as it does not require any a-priori knowledge, nor an estimate of any street parameter. We present the results of several experiments, performed on different urban roads, which confirm the efficacy of our proposal.
Advances in the design and delivery of peptide subunit vaccines with a focus on Toll-like receptor agonists (2010)

Considerable success has been made with many peptide antigen formulations, and peptide-based vaccines are emerging as the next generation of prophylactic and remedial immunotherapy. However, finding an optimal platform balancing all of the requirements for an effective, specific and safe immune response remains a major challenge for many infectious and chronic diseases. This review outlines how peptide immunogenicity is influenced by the way in which peptides are presented to the immune system, underscoring the need for multifunctional delivery systems that couple antigen and adjuvant into a single construct. Particular attention is given to the ability of Toll-like receptor agonists to act as adjuvants. A survey of recent approaches to developing peptide antigen delivery systems is given, many of which incorporate Toll-like receptor agonists into the design.
A high performance 2-GHz direct-conversion front end with single-ended RF input in 0.13 um CMOS (2008)

This paper describes a 2.1-GHz CMOS front-end with a single-ended low noise amplifier (LNA) and a double balanced, current-driven passive mixer. The LNA features an on-chip transformer load to perform single-ended to differential conversion. Implemented in a 0.13 um CMOS process, it achieves 30 dB conversion gain, a low noise figure of 3.1 dB, a 40 kHz 1/f noise corner, an in-band IIP3 of −12 dBm and IIP2 better than 39 dBm, while consuming only 12 mW from a 1.5V power supply.
Use of granulocyte-macrophage colony-stimulating factor in two children treated with cord blood transplantation. (1994)

Cord blood contains stem cells in amounts similar to or slightly less than those present in a bone marrow collection to be used for bone marrow transplantation (BMT). Too few cord blood transplants (CBT) have yet been performed to define the ability to achieve engraftment and the rate of engraftment. Two cord blood transplants have been performed using granulocyte-macrophage colony stimulating factor (GM-CSF) to hasten engraftment. Two children, aged 5 and 6 years received a CBT using HLA-identical stem cells collected at the birth of a sibling. One child had X-linked lymphoproliferative disease (XLP), and the other, acute lymphoblastic leukemia in second complete remission. One had an ABO and one an Rh blood group mismatch. Conditioning therapy consisted of cyclophosphamide, melphalan, and antithymocyte globulin or busulphan and cyclophosphamide. Graft-versus-host disease prophylaxis was methotrexate and cyclosporine or cyclosporine. Both children were given GM-CSF at 5 micrograms/kg/day from day 1 until the absolute neutrophil count (ANC) reached 1.0 x 10(9)/L for 3 consecutive days. If this level was not reached by day 14, the dose of GM-CSF was doubled. Both children engrafted rapidly, with ANCs reaching 0.5 x 10(9)/L in 12 and 16 days. Engraftment was confirmed by blood group in both and sex chromosome typing in one. Both children developed mild GVHD localized to skin, which resolved with steroid therapy. The child with XLP was cured and has survived for 34 months; the second child has survived 27 months with normal marrow function but has had a relapse of leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Exploration of Pyrrolobenzodiazepine (PBD)-Dimers Containing Disulfide-Based Prodrugs as Payloads for Antibody–Drug Conjugates (2018)

A number of cytotoxic pyrrolobenzodiazepine (PBD) monomers containing various disulfide-based prodrugs were evaluated for their ability to undergo activation (disulfide cleavage) in vitro in the presence of either glutathione (GSH) or cysteine (Cys). A good correlation was observed between in vitro GSH stability and in vitro cytotoxicity toward tumor cell lines. The prodrug-containing compounds were typically more potent against cells with relatively high intracellular GSH levels (e.g., KPL-4 cells). Several antibody-drug conjugates (ADCs) were subsequently constructed from PBD dimers that incorporated selected disulfide-based prodrugs. Such HER2 conjugates exhibited potent antiproliferation activity against KPL-4 cells in vitro in an antigen-dependent manner. However, the disulfide prodrugs contained in the majority of such entities were surprisingly unstable toward whole blood from various species. One HER2-targeting conjugate that contained a thiophenol-derived disulfide prodrug was an exception to this stability trend. It exhibited potent activity in a KPL-4 in vivo efficacy model that was approximately three-fold weaker than that displayed by the corresponding parent ADC. The same prodrug-containing conjugate demonstrated a three-fold improvement in mouse tolerability properties in vivo relative to the parent ADC, which did not contain the prodrug.
Phosphatidylinositol 3-Kinase Is a Key Mediator of Central Sensitization in Painful Inflammatory Conditions (2008)

Here, we show that phosphatidylinositol 3-kinase (PI3K) is a key player in the establishment of central sensitization, the spinal cord phenomenon associated with persistent afferent inputs and contributing to chronic pain states. We demonstrated electrophysiologically that PI3K is required for the full expression of spinal neuronal wind-up. In an inflammatory pain model, intrathecal administration of LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], a potent PI3K inhibitor, dose-dependently inhibited pain-related behavior. This effect was correlated with a reduction of the phosphorylation of ERK (extracellular signal-regulated kinase) and CaMKII (calcium/calmodulin-dependent protein kinase II). In addition, we observed a significant decrease in the phosphorylation of the NMDA receptor subunit NR2B, decreased translocation to the plasma membrane of the GluR1 (glutamate receptor 1) AMPA receptor subunit in the spinal cord, and a reduction of evoked neuronal activity as measured using c-Fos immunohistochemistry. Our study suggests that PI3K is a major factor in the expression of central sensitization after noxious inflammatory stimuli.
Production of calcitonin gene related peptide, calcitonin and PTH‐related protein by a prostatic adenocarcinoma (1991)

PTH and calcitonin are the two major hormones controlling calcium metabolism. Recently two new substances related to these hormones have been isolated: calcitonin gene related peptide (CGRP) and PTH-related protein (PTHrP). CGRP is a potent vasodilator and stimulant of intestinal secretion while PTHrP is probably the agent responsible for humoral hypercalcaemia of malignancy. We report here a patient with a prostatic tumour presenting with vasodilation, diarrhoea and hypercalcaemia. Our investigations revealed that the primary prostatic and liver secondary tumour contained CGRP, calcitonin and PTHrP. Most of the immunoreactive CGRP in the tumour and plasma co-eluted with the biologically active form of CGRP. The circulating levels of CGRP correlated with the presence of the diarrhoea. PTHrP concentration in the tumours was one of the highest reported for any tumour although previous studies may have utilized less than optimal extraction procedures. The somatostatin analogue, octreotide (SMS 201-995), did not reduce the plasma CGRP or the diarrhoea, a finding similar to that seen in patients with medullary thyroid carcinoma and high plasma CGRP. The hypercalcaemia was also unaffected by octreotide administration. This is the first report of a prostatic tumour associated with over-production of calcitonin, PTHrP and CGRP. The major life-threatening effects of this unusual case of prostatic carcinoma were diarrhoea and hypercalcaemia. Both these effects could be tentatively ascribed to newly discovered substances, CGRP and PTHrP. With the greater availability of assays to measure CGRP and PTHrP in plasma, a detailed examination of the incidence of over-production of these substances in various cancers will be possible.
CD47 update: a multifaceted actor in the tumour microenvironment of potential therapeutic interest (2012)

CD47 is a ubiquitous 50 kDa five-spanning membrane receptor that belongs to the immunoglobulin superfamily. This receptor, also known as integrin-associated protein, mediates cell-to-cell communication by ligation to transmembrane signal-regulatory proteins SIRPα and SIRPγ and interacts with integrins. CD47 is also implicated in cell-extracellular matrix interactions via ligation with thrombospondins. Furthermore, CD47 is involved in many and diverse cellular processes, including apoptosis, proliferation, adhesion and migration. It also plays a key role in many immune and cardiovascular responses. Thus, this multifaceted receptor might be a central actor in the tumour microenvironment. Solid tumours are composed of not only cancer cells that actively proliferate but also other cell types including immune cells and fibroblasts that make up the tumour microenvironment. Tumour cell proliferation is strongly sustained by continuous sprouting of new vessels, which also represents a gate for metastasis. Moreover, infiltration of inflammatory cells is observed in most neoplasms. Much evidence has accumulated indicating that infiltrating leukocytes promote cancer progression. Given its ubiquitous expression on all the different cell types that compose the tumour microenvironment, targeting CD47 could represent an original therapeutic strategy in the field of oncology. We present a current overview of the biological effects associated with CD47 on cancer cells and stromal cells.
Circumvention of multidrug resistance in neoplastic cells through scavenger receptor mediated drug delivery (1995)

A conjugate of the antineoplastic drug daunomycin (DNM) with maleylated bovine serum albumin (MBSA-DNM) was taken up with high efficiency by a multidrug resistant variant, JD100, of the murine-macrophage tumour cell line, J774A.1, through the scavenger receptors resulting in cessation of DNA synthesis. In contrast, free DNM at similar concentrations did not affect the incorporation of [3H]thymidine by these cells. These results suggest that receptor-mediated intracellular delivery of antineoplastic drugs could be a viable and new approach for overcoming the problem of multidrug resistance in chemotherapy of neoplastic diseases.