gebhart/patrepeval huggingface dataset:
Dual Native Chemical Ligation at Lysine (2009)

A thiol group introduced on the gamma-carbon of lysine mediates robust native chemical ligation at both the alpha- and epsilon-amines in two consecutive steps. Desulfurization then affords the final product, in which the lysine residue at the ligation site has an isopeptide bond on its side chain. The method is useful for the synthesis of proteins containing special post-translational modifications on lysine.
Engineering space-variant inhomogeneous media for polarization control (2004)

Novel devices for converting a linear polarization state to radial or azimuthal polarization states are realized by use of space-variant inhomogeneous media on a subwavelength scale. The two designs presented use form birefringence to locally transform the polarization state. The devices are fabricated in a GaAs substrate for operation in the far-infrared wavelength range. The experimental characterization is in good agreement with the designs, demonstrating high conversion efficiency.
Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use (2015)

Treatment of vaso-occlusive crises (VOC) or events in sickle cell disease (SCD) remains limited to symptom relief with opioids. Animal models support the effectiveness of the pan-selectin inhibitor GMI-1070 in reducing selectin-mediated cell adhesion and abrogating VOC. We studied GMI-1070 in a prospective multicenter, randomized, placebo-controlled, double-blind, phase 2 study of 76 SCD patients with VOC. Study drug (GMI-1070 or placebo) was given every 12 hours for up to 15 doses. Other treatment was per institutional standard of care. All subjects reached the composite primary end point of resolution of VOC. Although time to reach the composite primary end point was not statistically different between the groups, clinically meaningful reductions in mean and median times to VOC resolution of 41 and 63 hours (28% and 48%, P = .19 for both) were observed in the active treatment group vs the placebo group. As a secondary end point, GMI-1070 appeared safe in acute vaso-occlusion, and adverse events were not different in the two arms. Also in secondary analyses, mean cumulative IV opioid analgesic use was reduced by 83% with GMI-1070 vs placebo (P = .010). These results support a phase 3 study of GMI-1070 (now rivipansel) for SCD VOC. This trial was registered at www.clinicaltrials.gov as #NCT01119833.
Impact of the hyaluronan‐rich tumor microenvironment on cancer initiation and progression (2008)

Hyaluronan acts as a microenvironmental stimulus that can influence the malignant phenotype of cancer cells. During cancer progression, hyaluronan assembles an extracellular matrix that is favorable for both the motility and proliferation of cancer cells and the recruitment of inflammatory and bone marrow-derived progenitor cells. The varied roles of this polysaccharide are regulated via multiple mechanisms involving biosynthesis, degradation, binding with other extracellular molecules, and activation of signaling pathways. Recent animal studies have provided evidence that aberrant biosynthesis of hyaluronan accelerates tumor growth through a diverse repertoire of host-tumor interactions, such as stromal cell recruitment, angiogenesis, lymphangiogenesis, and inflammation. Hyaluronan in the tumor microenvironment thus significantly impacts cancer initiation and progression via stroma-cancer cell interactions.
Methoden der Datenanalyse (2002)

Die Datenanalyse stellt einen wesentlichen Bestandteil im Rahmen des ImmobilienmarktResearch-Prozesses dar. Nachfolgend werden im Anschluß an eine kurze Einführung in die meßtheoretischen Grundlagen sowie die statistischen Analysemethoden im wesentlichen die volkswirtschaftlichen Analysemethoden vertiefend diskutiert.
Multiplexed gene transfer to a human T‐cell line by combining Sleeping Beauty transposon system with methotrexate selection (2015)

Engineered human T-cells are a promising therapeutic modality for cancer immunotherapy. T-cells expressing chimeric antigen receptors combined with additional genes to enhance T-cell proliferation, survival, or tumor targeting may further improve efficacy but require multiple stable gene transfer events. Methods are therefore needed to increase production efficiency for multiplexed engineered cells. In this work, we demonstrate multiplexed, non-viral gene transfer to a human T-cell line with efficient selection (∼ 50%) of cells expressing up to three recombinant open reading frames. The efficient introduction of multiple genes to T-cells was achieved using the Sleeping Beauty transposon system delivered in minicircles by nucleofection. We demonstrate rapid selection for engineered cells using methotrexate (MTX) and a mutant human dihydrofolate reductase resistant to methotrexate-induced metabolic inhibition. Preferential amplification of cells expressing multiple transgenes was achieved by two successive rounds of increasing MTX concentration. This non-viral gene transfer method with MTX step selection can potentially be used in the generation of clinical-grade T-cells housing multiplexed genetic modifications.
Glucagon-like peptide 1(GLP-1) in biology and pathology (2005)

Post-translational proteolytic processing of the preproglucagon gene in the gut results in the formation of glucagon-like peptide 1 (GLP-1). Owing to its glucose-dependent insulinotropic effect, this hormone was postulated to primarily act as an incretin, i.e. to augment insulin secretion after oral glucose or meal ingestion. In addition, GLP-1 decelerates gastric emptying and suppresses glucagon secretion. Under physiological conditions, GLP-1 acts as a part of the 'ileal brake', meaning that is slows the transition of nutrients into the distal gut. Animal studies suggest a role for GLP-1 in the development and growth of the endocrine pancreas. In light of its multiple actions throughout the body, different therapeutic applications of GLP-1 are possible. Promising results have been obtained with GLP-1 in the treatment of type 2 diabetes, but its potential to reduce appetite and food intake may also allow its use for the treatment of obesity. While rapid in vivo degradation of GLP-1 has yet prevented its broad clinical use, different pharmacological approaches aiming to extend the in vivo half-life of GLP-1 or to inhibit its inactivation are currently being evaluated. Therefore, antidiabetic treatment based on GLP-1 may become available within the next years. This review will summarize the biological effects of GLP-1, characterize its role in human biology and pathology, and discuss potential clinical applications as well as current clinical studies.
Ventilator-associated pneumonia in adults in developing countries: a systematic review (2008)

Based on the existing literature, the rate of VAP in developing countries is higher than NHSN benchmark rates and is associated with a significant impact on patient outcome. Only a few studies reported successful interventions to reduce VAP. There is a clear need for additional epidemiologic studies to better understand the scope of the problem. Additionally, more work needs to be done on strategies to prevent VAP, probably with emphasis on practical, low-cost, low technology, easily implemented measures.
Bidirectional transcytosis of IgG by the rat neonatal Fc receptor expressed in a rat kidney cell line: a system to study protein transport across epithelia (2000)

The neonatal Fc receptor, FcRn, transports immunoglobulin G (IgG) across cellular barriers between mother and offspring. FcRn also protects circulating IgG from catabolism, probably during transport across the capillary endothelium. Only one cell culture model of transcytosis has been used extensively, the transport of IgA from the basolateral to the apical surface of Madin-Darby canine kidney cells by the polymeric immunoglobulin receptor (pIgR). We report that rat inner medullary collecting duct (IMCD) cells transfected with DNA encoding the (alpha) subunit of rat FcRn specifically and saturably transport Fc when grown as polarized monolayers. Using this system, we have found that transcytosis by FcRn, like transcytosis by the pIgR, depends upon an intact microtubule system. FcRn differs most strikingly from the pIgR in its ability to transport its ligand in both the apical to basolateral and basolateral to apical directions. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibited basolateral to apical transport by FcRn more than apical to basolateral transport, suggesting that there are differences in the mechanisms of transport in the two directions. Lastly, we found that transcytosis by FcRn depends upon vesicular acidification. We anticipate that the IMCD cell culture model will allow further elucidation of the mechanism of IgG transport by FcRn.
Toxoids of Streptococcal Pyrogenic Exotoxin A Are Protective in Rabbit Models of Streptococcal Toxic Shock Syndrome (2000)

Streptococcal pyrogenic exotoxins (SPEs) are superantigens that have been implicated in causing streptococcal toxic shock syndrome (STSS). Most notably, SPE serotype A is made by nearly all M-protein serotype 1 and 3 streptococci, the M types most associated with the illness (these strains contain one or more other SPEs, and those proteins are likely also to contribute to disease). We have prepared double-, triple-, and hexa-amino-acid mutants of SPE A by PCR and other mutagenesis procedures. The sites chosen for mutation were solvent-exposed residues thought to be important for T-cell receptor (TCR) or major histocompatibility complex (MHC) class II interaction. These mutants were nonsuperantigenic for human peripheral blood mononuclear cells and rabbit and mouse splenocytes and were nonlethal in two rabbit models of STSS. In addition, these mutants stimulated protective antibody responses. Interestingly, mutants that altered toxin binding to MHC class II were more immunogenic than mutants altering TCR binding. Collectively, these studies indicate that multiple-site mutants of SPE A are toxoids that may have use in protecting against the toxin's effects in STSS.
Peptide Nucleic Acid Characterization by MALDI-TOF Mass Spectrometry (1996)

Peptide nucleic acids (PNAs) are a new class of DNA mimics in which the regular nucleobases of adenine, thymine, cytosine, and guanine are connected via a peptide-like backbone. PNA molecules retain the same Watson-Crick base pairing as regular oligonucleotides, with the added benefits of greater specificity and resistance to enzymatic digestion. While the use of PNAs has grown rapidly because of their potential applications in biotechnology, little work has been done on developing analytical procedures for characterizing them. We have found matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry to be an effective tool for PNA analysis. PNA molecules survive the MALDI process intact and are easily ionized with almost no multiply-charged species. These features allow mixtures to be easily characterized. Traditional protein matrices (e.g., sinapinic acid,2,5-dihydroxybenzoic acid, alpha-cyano-4-hydroxycinnamic acid) were found to be superior to DNA matrices (e.g., trihydroxy-acetophenone, 3-hydroxypicolinic acid, picolinic acid). In addition, the new DNA matrix 6-aza-2-thiothymine worked well. The ability of MALDI-TOF-MS to ascertain PNA purity and sequence information at low picomole levels will be important as greater quality control of PNA synthesis is needed (e.g., when PNAs are used as antisense or antigene drugs).
Antibodies to the kinesin motor domain and CENP-E inhibit microtubule depolymerization-dependent motion of chromosomes in vitro. (1995)

Chromosomes can move with the ends of depolymerizing microtubules (MTs) in vitro, even in the absence of nucleotide triphosphates (Coue, M., V. A. Lombillo, and J. R. McIntosh. 1991. J. Cell Biol. 112:1165-1175.) Here, we describe an immunological investigation of the proteins important for this form of motility. Affinity-purified polyclonal antibodies to kinesin exert a severe inhibitory effect on depolymerization-dependent chromosome motion. These antibodies predominantly recognize a polypeptide of M(r) approximately 250 kD on immunoblots of CHO chromosomes and stain kinetochores as well as some vesicles that are in the chromosome preparation. Antibodies to CENP-E, a kinetochore-associated kinesin-like protein, also recognize a 250-kD electrophoretic component, but they stain only the kinetochroe region of isolated chromosomes. Polyclonal antibodies that recognize specific domains of the CENP-E polypeptide affect MT disassembly-dependent chromosome motion in different ways; antibodies to the head or tail portions slow motility threefold, while those raised against the neck region stop motion completely. Analogous antibodies that block conventional, ATP-dependent motility of cytoplasmic dynein (Vaisberg, G., M. P. Koonce, and J. R. McIntosh. 1993. J. Cell Biol. 123:849-858) have no effect on disassembly-dependent chromosome motion, even though they bind to kinetochores. These observations suggest that CENP-E helps couple chromosomes to depolymerizing MTs. A similar coupling activity may allow spindle MTs to remain kinetochore-bound while their lengths change during both prometaphase and anaphase A.
W (A or T) sequences as probes and primers suitable for genomic mapping and fingerprinting (1991)

A limitation to the use of oligonucleotide probes as tools for genetic and physical mapping has been the low hybridization positive frequency obtained by oligonucleotides of sufficient length to hybridize preferentially to cloned insert DNA (and not host E. coli genomic DNA). Both computer and experimental results now indicate that oligonucleotide probes composed of W (A or T) sequence are preferentially found in eukaryotic DNA, and can be used to provide high frequency, discriminative hybridization. Such W sequences may be useful as either probes or PCR primers in molecular diagnostic applications as well as in genetic and physical mapping.
Gr-1+CD11b+ Myeloid Cells Tip the Balance of Immune Protection to Tumor Promotion in the Premetastatic Lung (2010)

The mechanisms by which a primary tumor affects a selected distant organ before tumor cell arrival remain to be elucidated. This report shows that Gr-1+CD11b+ cells are significantly increased in lungs of mice bearing mammary adenocarcinomas before tumor cell arrival. In the premetastatic lungs, these immature myeloid cells significantly decrease IFN-gamma production and increase proinflammatory cytokines. In addition, they produce large quantities of matrix metalloproteinase 9 (MMP9) and promote vascular remodeling. Deletion of MMP9 normalizes aberrant vasculature in the premetastatic lung and diminishes lung metastasis. The production and activity of MMP9 is selectively restricted to lungs and organs with a large number of Gr-1+CD11b+ cells. Our work reveals a novel protumor mechanism for Gr-1+CD11b+ cells that changes the premetastatic lung into an inflammatory and proliferative environment, diminishes immune protection, and promotes metastasis through aberrant vasculature formation. Thus, inhibition of Gr-1+CD11b+ cells could normalize the premetastatic lung environment, improve host immunosurveillance, and inhibit tumor metastasis.
Sodium borohydride in carboxylic acid media: a phenomenal reduction system (1998)

The union of sodium borohydride and carboxylic acids has yielded an amazingly versatile and efficient set of reducing reagents. These acyloxyborohydride species reduce and N-alkylate indoles, quinolines, isoquinolines, related heterocycles, imines, enamines, oximes, enamides, and similar functional groups. They reduce amides and nitriles, aryl alcohols and ketones, aldehydes in the presence of ketones, and β-hydroxyketones to 1,3-diols stereoselectively. This reagent is also extraordinarily useful for the N-alkylation of primary and secondary amines with aldehydes and ketones in a novel reductive amination process.
Combining Active Learning and Semi-Supervised Learning by Using Selective Label Spreading (2017)

In the literature, a number of methods have been proposed for semi-supervised learning. Recently, graph-based methods of semi-supervised learning have become popular because of their capability of handling large amounts of unlabeled data. However, the existing graph based semi-supervised learning algorithms do not optimize the process of selecting better labeled data. We have developed a new selective semi-supervised learning algorithm, called selective label spreading (SLS) by integrating the active learning model into the label spreading framework. SLS optimizes the process of selecting better labeled data in order to improve classification performance. We applied SLS to the well-known hand-written digits recognition data set and demonstrated that SLS can improve the classification performance. The selective label spreading scheme requires a much smaller number of queries to achieve high accuracy compared with random query selection.
Common structural features determine the effectiveness of carvedilol, daunomycin and rolitetracycline as inhibitors of Alzheimer beta-amyloid fibril formation. (1999)

One of the major pathological features of Alzheimer's disease is the deposition of beta-amyloid peptide (Abeta). Cellular toxicity has been shown to be associated with fibrillar forms of Abeta; preventing this fibril formation is therefore viewed as a possible method of slowing disease progression in Alzheimer's disease. With the use of a series of tetracyclic and carbazole-type compounds as inhibitors of Abeta fibril formation, we here describe a number of common structural features that seem to be associated with the inhibitory properties of these agents. Compounds such as carvedilol, rolitetracycline and daunomycin, which are shown to inhibit Abeta fibril formation, also prevent the formation of species of peptide that demonstrate biological activity in a human neuroblastoma cell line. Molecular modelling data suggest that these compounds have in common the ability to adopt a specific three-dimensional pharmacophore conformation that might be essential for binding to Abeta and preventing it from forming fibrils. Understanding such drug-peptide interactions might aid the development of disease-modifying agents.
Gamma/Delta T Cells and Their Role in Protection Against Malaria (2018)

Whether and how γδT cells play a protective role in immunity against <i>Plasmodium</i> infection remain open questions. γδT cells expand in patients and mice infected with <i>Plasmodium</i> spp, and cytokine production and cytotoxic responses against blood-stage parasites are observed <i>in vitro</i>. Their expansion is associated with protective immunity induced by irradiated sporozoite immunization, and depletion of γδT cells in some mouse models of malaria excacerbates blood-stage infections. It is now clear that these cells can have many different functions, and data are emerging suggesting that in addition to having direct parasitocidal effects, they can regulate other immune cells during <i>Plasmodium</i> infections. Here we review some of the historic and more recent data on γδT cells, and in light of the new information on their potential protective roles we suggest that it is a good time to re-evaluate their activation requirements, specificity and function during malaria.
Confocal readout of three-dimensional data bits recorded by the photorefractive effect under single-photon and two-photon excitation (1999)

In three-dimensional optical bit data storage, data bits can be recorded as a result of the change in refractive index in photorefractive and photochromic materials under single-photon and two-photon excitation by a high numerical-aperture objective. In principle, these recorded data bits can be read out using reflection confocal microscopy because such a microscope exhibits an optical sectioning property for three-dimensional imaging. In this article, the conditions are described under which three-dimensional data bits recorded by the photorefractive effect under single-photon and two-photon excitation in these materials can be read in reflection confocal microscopy. The effect of the refractive-index mismatch between a volume recording medium and its immersion medium on these conditions is also considered.
[The modern approach to wound treatment]. (2001)

Growth factors play a role in cell division, migration, differentiation, protein expression, enzyme production and have a potential ability to heal wounds by stimulating angiogenesis and cellular proliferation, affecting the production and the degradation of the extracellular matrix, and by being chemotactic for inflammatory cells and fibroblasts. There are seven major families of growth factors: epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), interleukins (ILs), and colony-stimulating factor (CSF). Acute wounds contain many growth factors that play a crucial role in the initial phases of wound healing. The events of early wound healing reflect a finely balanced environment leading to uncomplicated and rapid wound healing. Chronic wounds, for many reasons, have lost this fine balance. Multiple studies have evaluated the effect that exogenously applied growth factors have on the healing of chronic wounds. In the study conducted by Knighton and colleagues, topical application of mixture of various growth factors (PDGF, TGF-beta, PDAF, PF4, PDEGF) demonstrated increased wound healing over controls. Brown and associates demonstrated a decrease in skin graft donor site healing time of 1 day using topically applied EGF. Herndon and ass. used systemic growth hormone in burned children and reduction in healing time made a significant clinical difference by allowing earlier wound coverage and decreasing the duration of hospitalization. The TGF family of growth factors is believed to be primarily responsible for excessive scar formation, especially the beta 1 and beta 2 isoforms. TGF-beta 3 isoform has recently been described and may have an inhibitory function on scar formation by being a natural antagonist to the TGF-beta 1 and TGF-beta 2 isoforms. Cytokines, especially interferon-alpha (INF-alpha), INF-alpha, and INF-alpha 2b, may also reduce scar formation. These cytokines decrease the proliferation rate of fibroblasts and reduce the rate of collagen and fibronectin synthesis by reducing the production of mRNA. Expression of nitric oxide synthase (NOS) and heat shock proteins (HSP) have an important role in wound healing, as well as trace elements (zinc, copper, manganese). Applications of some drugs (antioxidants--asiaticoside, vitamin E and ascorbic acid; calcium D-pantothenate, exogenous fibronectin; antileprosy drugs--oil of hydnocarpus; alcoholic extract of yeast) accelerate wound healing. Thymic peptide thymosin beta 4 (T beta 4R) topically applicated, increases collagen deposition and angiogenesis and stimulates keratinocyte migration. Thymosin alpha 1 (T alpha 1R), peptide isolated from the thymus, is a potent chemoattractant which accelerates angiogenesis and wound healing. On the contrary, steroid drugs, hemorrhage and denervation of wounds have negative effect on the healing process.