gebhart/patrepeval huggingface dataset:
Biosynthesis of Peptide Hormones Derived from Precursor Sequences (2004)

The release of hormones is subject to a complex and finely tuned regulation system. The biosynthesis plays a key role by specifically converting the prohormone precursor into its biological active product(s). A family of mammalian proteases could be identified to be responsible for the endoproteolytic processing. These subtilisin/kexin-like prohormone convertases (PC) recognize their substrates at single or pairs of basic residues with a high substrate specificity. The so far known seven members include PC1/3, PC2, furin/PACE, PACE4, PC4, PC5/6 and PC7/SPC7/LPC/PC8. PC1/3 and PC2 are the most important enzymes for the processing of prohormones, whereas furin is the only one that causes lethality in knock-out models. Tissue-specific co-localization of the prohormone and the PC as well as distinct characteristics of both, like the secondary structures, determine the possible conversion processes. Identification of such determinants implies a great potential for the development of novel drug targets. To obtain sufficient amounts for the in vitro characterization of prohormones, chemical and recombinant synthesis methods have been developed. Application of expressed protein ligation lead to the semisynthesis of the first chemically modified analogs of a full-length proneurohormone (pro-neuropeptide Y). Structural analyses mainly on peptides of the pro-oxytocin/neurophysin system and on prosomatostatin highlighted the importance of flexible turn or loop structures adjacent to the cleavage site for the specific substrate-enzyme active site interaction. Prohormones and their processing show multiple functions. Therapeutic application including PC inhibitors is very promising for the treatment of disorders like cancer.
Recent Advances in Asymmetric Organocatalytic 1,4‐Conjugate Additions (2007)

Abstract Recent progress in the field of asymmetric organocatalytic 1,4‐conjugate addition reactions, regarded as belonging among the more synthetically important carbon–carbon bond‐forming reactions, is described. The focus is on some recent advances in the following selected reactions: additions of various nucleophiles to α,β‐unsaturated cyclic and acyclic enals, enones, vinyl sulfones and nitro olefins, addition of malonates and/or ketones to acyclic enones, or of aldehydes and ketones to vinyl ketones and nitro olefins, together with some multicomponent domino reactions. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)
Recycling selectable markers in yeast. (1994)

A series of excisable marker cassettes has been constructed to facilitate recycling of selectable markers in yeast. These cassettes exploit the use of the Cre DNA recombinase to precisely excise the marker gene when desired. They are especially useful for making gene disruptions and then removing the marker gene to allow subsequent genetic manipulations with that same marker. Also described are a number of cre expression vectors that allow galactose-induced expression of the recombinase in yeast. The procedure is simple and allows rapid processing of large numbers of transformants.
Liposomes for Use in Gene Delivery (2010)

Liposomes have a wide array of uses that have been continuously expanded and improved upon since first being observed to self-assemble into vesicular structures. These arrangements can be found in many shapes and sizes depending on lipid composition. Liposomes are often used to deliver a molecular cargo such as DNA for therapeutic benefit. The lipids used to form such lipoplexes can be cationic, anionic, neutral, or a mixture thereof. Herein physical packing parameters and specific lipids used for gene delivery will be discussed, with lipids classified according to overall charge.
Identifying meaningful intra‐individual change standards for health‐related quality of life measures (2000)

Although numerous measures have been developed for the evaluation of health-related quality of life (HRQoL), strategies for identifying meaningful intra-individual change in these measures have not kept pace with instrument development. As a result, clinical trial researchers, quality assurance assessment teams and practising clinicians are without established standards to evaluate individual patient change in HRQoL measures as improved, stable or declined. This article reviews and critiques the methods that have been applied to establish intra-individual HRQoL change standards. These methods include within-person and between-persons anchor-based studies, as well as distribution-based techniques using the effect size, the standard error of measurement, the mean squared error or individual slope coefficients derived from hierarchical linear modelling. Practical approaches to improving and advancing HRQoL change evaluations that enhance the interpretation of intra-individual change are provided. Two future methodological challenges in this area of HRQoL research are examined: (1) the development of individual change standards for generic HRQoL measures; and (2) the incorporation of individual clinical assessments into the process for establishing significant intra-individual change standards.
Enhancement of Osteoblast Proliferation In Vitro by Selective Enrichment of Demineralized Freeze-dried Bone Allograft With Specific Growth Factors (2002)

Decalcified freeze-dried bone allograft (DFDBA), believed to serve as a matrix for new bone growth and to contain various bone-inducing growth factors, is currently used to regenerate periodontal defects and to restore and maintain dental alveolar ridges. Growth factors within DFDBA are extracted during the demineralization process, thus rendering the allograft incapable of spontaneous osteogenesis; however, exogenous growth factor addition to DFDBA may enhance the osteogenic capacity of native osteoblasts. This study's purpose is to evaluate murine osteoblast proliferation in the presence of various exogenous soluble growth factors as measured by fluorescence units. Osteoblasts harvested from mouse pup calvaria were cultured with 2% residual calcium-DFDBA and supplemented by one of the following growth factors or combinations of these factors: transforming growth factor-beta (TGF-beta), insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), fibroblast growth factors basic (bFGF), or vascular endothelial growth factors (VEGF). Osteoblast proliferation rates indicate that the in vitro supplementation of 2% residual calcium-DFDBA with the combination of IGF and TGF-beta, IGF and PDGF, and PDGF and TGF-beta significantly (P < or = .05) enhance murine osteoblast activity and proliferation at 7 days compared with the control containing no exogenous growth factors.
A dielectric lens-based antenna concept for high-precision industrial radar measurements at 24GHz (2012)

A lens-based antenna with a solid dielectric ellipsoid PTFE lens for industrial tank level probing radar (TLPR) is presented. Due to limitations of the application, a high antenna gain at a limited size as well as a good matching were the main design goals. The presented antenna achieves a high gain of 25.9 dBi with a beamwidth of ≈ 8.4° at an outer diameter of 74mm in simulations, which is confirmed by measurements. Despite the lens surface reflections, a good input matching of ≈ -20 dB is achieved in the full wide frequency band from 23 GHz to 28 GHz, which enables monostatic radar operation even close to the antenna. A laboratory radar setup is used to confirm the accuracy impact on distance measurements in a scenario with disturbing reflectors.
Dielectric barrier plasma dynamics for active control of separated flows (2006)

The dynamics of separation mitigation with asymmetric dielectric barrier discharges is explored by considering the gas flow past a flat plate at an angle of attack. A self-consistent model utilizing motion of electrons, ions, and neutrals is employed to couple the electric force field to the momentum of the fluid. The charge separation and concomitant electric field yield a time-averaged body force which is oriented predominantly downstream, with a smaller transverse component towards the wall. This induces a wall-jet-like feature that effectively eliminates the separation bubble. The impact of several geometric and electrical operating parameters is elucidated.
A helix-loop-helix protein related to the immunoglobulin E box-binding proteins. (1990)

A human cDNA encoding a novel protein in the helix-loop-helix family has been isolated by screening a bacteriophage expression library with a probe containing the binding site for major late transcription factor. The protein encoded by this cDNA, TFEB, probably recognizes E-box sequences in the heavy-chain immunoglobulin enhancer.
Substrate analog inhibitors of the IgA1 proteinases from Neisseria gonorrhoeae (1988)

Substrate analogues based on the amino acid sequence of the hinge region of human IgA1 around the cleavage site of the IgA1 proteinases secreted by Neisseria gonorrhoeae are competitive inhibitors of these enzymes. The octapeptide Thr-Pro-Pro-Thr-Pro-Ser-Pro-Ser, which occurs between residues 233 and 240, has an IC50 value of 0.26 mM for the type 1 proteinase and 0.50 mM for the type 2 enzyme. Acetylation of the octapeptide N-terminal amino group lowers affinity for the type 1 proteinase sixfold but does not change binding to the type 2 enzyme. Amidation of the C-terminal carboxyl group does not change binding to the type 1 proteinase but improves IC50 for the type 2 enzyme. Simultaneous blockade of both the N- and C-termini drastically lowers affinity of the octapeptide for both proteinases. Sequential replacement of the hydroxy amino acids in the blocked octapeptide with cysteine yields a series of inhibitors that generally bind to the neisserial IgA1 proteinases as well as or better than the unblocked octapeptide. The most effective inhibitor contains a cysteine residue at position 6 (P3') and has an IC50 value for the type 2 IgA1 proteinase of 50 microM. Dimerization of the cysteine-containing octapeptides significantly diminishes inhibitory properties. The substrate analogues described here are the first synthetic inhibitors of the neisserial IgA1 proteinases to be reported.
Oculohypotensive Effect of Angiotensin-Converting Enzyme Inhibitors in Acute and Chronic Models of Glaucoma (2000)

We have studied the effects of various angiotensin-converting enzyme (ACE) inhibitors on intraocular pressure (IOP) of rabbits with experimentally induced ocular hypertension and their mechanism of action. Acute ocular hypertension was induced by infusion of 5% glucose (15 ml/kg) through marginal ear vein, whereas chronic glaucoma was induced by injection of alpha-chymotrypsin into the posterior chamber of the eye. IOP was measured by tonometer. All ACE inhibitors were instilled topically in the eye in a sterile solution. The effect of ACE inhibitors also was studied on serum cholinesterase (true and pseudo) and the enzyme ACE in vitro. Enalaprilat, ramiprilat, and fosinopril produced a time-dependent decrease of IOP in both acute and chronic models of ocular hypertension in rabbits. The decrease in IOP was observed for >4 h, and the extent of decrease was comparable to that with both pilocarpine and betaxolol. Prodrugs enalapril and ramipril failed to produced any change in IOP. Losartan also produced a significant decrease in IOP in the chronic model of ocular hypertension in rabbits. All the three ACE inhibitors were found to inhibit ACE activity in aqueous humor. The enzyme cholinesterase was found to be inhibited by enalaprilat, ramiprilat, and fosinopril. However, atropine did not alter the IOP-lowering effect of enalaprilat in rabbits. Indomethacin pretreatment produced slight but significant inhibition of the IOP-lowering effect of enalaprilat in rabbits. Our data suggest that ACE inhibitors enalaprilat, ramiprilat, and fosinopril produce a significant ocular hypotensive effect in acute and chronic models of ocular hypertension in rabbits. Inhibition of ACE in aqueous humor, and in ocular tissues, resulting in reduced angiotensin II formation, could be one of the major mechanisms responsible for the IOP reduction by ACE inhibitors in rabbits.
Identification, molecular cloning, biologic properties, and tissue distribution of a novel isoform of murine low-affinity IgG receptor homologous to human Fc γ RIIB1 (1996)

A cryptic splice donor site in the first intracytoplasmic (IC) exon of the murine Fc gamma RIIB gene generates a previously unknown Fc gamma RIIB isoform. Three membrane Fc gamma RIIB polypeptides of 37, 32, and 30 kDa were immunoprecipitated by Fc gamma RIIB-specific Abs, and three Fc gamma RIIB cDNAs of 1071, 987, and 930 bp were amplified by reverse transcriptase-PCR with Fc gamma RIIB-specific oligonucleotides from the mastocytoma cells P815. The 1071-bp cDNA contains all sequences of IC exons and encodes the 37-kDa Fc gamma RIIB1 isoform. The 930-bp cDNA lacks sequences of the first IC exon and encodes the 30-kDa Fc gamma RIIB2 isoform. The 987-bp cDNA has an 84-nucleotide deletion of the first IC exon 3' sequences. When stably transfected in the lymphoma B cells IIA1.6, or in the mast cells RBL-2H3, this cDNA encoded 32-kDa Fc gamma RIIB whose biologic properties were undistinguishable from those of Fc gamma RIIB1: they inhibited B cell activation when coaggregated to B cell receptors and capped when aggregated at 37 degrees C, but failed to mediate endocytosis or phagocytosis. Sequences responsible for capping and inhibition of internalization, previously assigned to sequences encoded by the first IC exon, can thus be mapped in the 19 N-terminal residues. These residues are highly conserved in human Fc gamma RIIB1. The 87-bp first IC exon of the human gene ends by a single splice site in the downstream intron and encodes a 19-amino acid insertion. The 32-kDa Fc gamma RIIB is the murine homologue of human Fc gamma RIIB1. We propose to name it Fc gamma RIIB1'. Fc gamma RIIB1' was expressed in myeloid and lymphoid cell lines, in normal spleen cells, and in resting or LPS-activated B cells.
Human lung mast cells are enriched in the capacity to produce granulocyte-macrophage colony-stimulating factor in response to IgE-dependent stimulation (1998)

By using reverse transcription-PCR, in situ hybridization, enzyme-linked immunosorbent assay and immunocytochemistry, we have studied the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) in human lung mast cells induced by cross-linkage of high-affinity Fc epsilon receptors (Fc epsilonRI). We have also confirmed the bioactivity of GM-CSF released from lung mast cells by investigating the effect of the supernatant from lung mast cells activated with anti-IgE on the release of eosinophil cationic protein (ECP) from eosinophils. Mast cells were purified using affinity magnetic selection with monoclonal antibody (mAb) YB5.B8 (93-99% pure). Purified mast cells were precultured with IgE for 16 h before challenge with 1 microg/ml anti-IgE with or without stem cell factor (SCF). Eosinophils were purified by immunomagnetic negative selection (> 98% pure). The activation of mast cells via Fc epsilonRI enhanced the intensity of the GM-CSF signal within 2 h and the cells produced GM-CSF protein 4 h after the activation. In the absence of recombinant human (rh) SCF, anti-IgE induced a median GM-CSF response of 202 (< 15 to approximately 681) pg/10(6) mast cells/24 h, whereas in the presence of rhSCF the median IgE-dependent GM-CSF release was 356 (152 to approximately 1216) pg/10(6) mast cells/24 h. This difference was statistically significant (p = 0.0029, n = 12). In contrast, mast cells produced only a small amount of GM-CSF in the absence of anti-IgE. The mast cell supernatant induced ECP release from eosinophils and the release was significantly inhibited by blocking mAb against GM-CSF. These findings indicate that human mast cells are an important cellular source of GM-CSF and as such may contribute to chronic eosinophil-mediated inflammation.
Extracellular matrix and pulmonary hypertension: control of vascular smooth muscle cell contractility (1998)

Pulmonary hypertension is characterized by increased vascular resistance due to smooth muscle cell hyper-activity and excess deposition of extracellular matrix (ECM) in the vessel wall. We investigated the possibility that changes in cell-ECM interactions may play an active role in this process by modifying the contractile response of pulmonary vascular smooth muscle (PVSM) cells. Contractility was measured within individual cultured PVSM cells, when resting or stimulated with vasoactive agents, by quantitating changes in stiffness of the cytoskeleton (CSK) using magnetic twisting cytometry (N. Wang, J. P. Butler, and D. E. Ingber. Science 260: 1124-1127, 1993). Control studies confirmed that changes in CSK stiffness closely paralleled alterations in cell contraction and relaxation as measured in response to endothelin-1 (ET-1) and dibutyryl guanosine 3',5'-cyclic monophosphate (cGMP), respectively, in a collagen gel contraction assay. CSK stiffness and contractile tone in cultured PVSM cells increased in direct proportion as the density of fibronectin (FN) coating was raised from 10 to 500 ng/well in 96-well plates. Dibutyryl cGMP had no effect in cells on low FN, although it completely inhibited the FN-dependent increase in CSK stiffness on higher ECM densities. In contrast, ET-1 induced the greatest increase in CSK stiffness on the intermediate FN density (100 ng/well). The reduced sensitivity to ET-1 on high FN was not due to dysfunction of the contractile apparatus nor to changes in protein tyrosine phosphorylation. Taken together, these results show that ECM can modulate PVSM cell contractility and suggest that the changes in ECM observed in hypertensive vessels could play an important role in the etiology of this disease.
Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine (2013)

Infections with the Gram-negative bacterium Burkholderia pseudomallei (melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. Infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections with B. pseudomallei. At present, our understanding of what constitutes effective protective immunity against B. pseudomallei infection remains incomplete. Therefore, we conducted a study to elucidate immune correlates of vaccine-induced protective immunity against acute B. pseudomallei infection. BALB/c and C57BL/6 mice were immunized subcutaneously with a highly attenuated, Select Agent-excluded purM deletion mutant of B. pseudomallei (strain Bp82) and then subjected to intranasal challenge with virulent B. pseudomallei strain 1026b. Immunization with Bp82 generated significant protection from challenge with B. pseudomallei, and protection was associated with a significant reduction in bacterial burden in lungs, liver, and spleen of immunized mice. Humoral immunity was critically important for vaccine-induced protection, as mice lacking B cells were not protected by immunization and serum from Bp82-vaccinated mice could transfer partial protection to nonvaccinated animals. In contrast, vaccine-induced protective immunity was found to be independent of both CD4 and CD8 T cells. Tracking studies demonstrated uptake of the Bp82 vaccine strain predominately by neutrophils in vaccine-draining lymph nodes and by smaller numbers of dendritic cells (DC) and monocytes. We concluded that protection following cutaneous immunization with a live attenuated Burkholderia vaccine strain was dependent primarily on generation of effective humoral immune responses.
Composition of isolated synaptic boutons reveals the amounts of vesicle trafficking proteins (2014)

Synaptic vesicle recycling has long served as a model for the general mechanisms of cellular trafficking. We used an integrative approach, combining quantitative immunoblotting and mass spectrometry to determine protein numbers; electron microscopy to measure organelle numbers, sizes, and positions; and super-resolution fluorescence microscopy to localize the proteins. Using these data, we generated a three-dimensional model of an "average" synapse, displaying 300,000 proteins in atomic detail. The copy numbers of proteins involved in the same step of synaptic vesicle recycling correlated closely. In contrast, copy numbers varied over more than three orders of magnitude between steps, from about 150 copies for the endosomal fusion proteins to more than 20,000 for the exocytotic ones.
Infopipes for composing distributed information flows (2001)

Building applications that process information flows on existing middleware platforms is difficult, because of the variety of QoS requirements, the need for application-specific protocols, and the poor match of the commonly used abstraction of remote invocations to streaming. We propose Infopipes as a high-level abstraction for building blocks that handle information flows. The ability to query individual Infopipe elements as well as composite Infopipes for properties of supported flows enables QoS-aware configuration. Similarly to local protocol frameworks Infopipes provide a flexible infrastructure for configuring communication services from modules, but unlike protocols the abstraction uniformly includes the entire pipeline from source to sink, possibly across process and node boundaries.
Continuous analyte monitoring to aid clinical practice (1994)

Considerable progress has been made in the development of practical glucose sensors for in vivo use. In some designs, the sensor can be replaced by the patient, who "injects" a new sensor into a fresh site using a hypodermic needle. An open-loop hypoglycaemia sensor providing an alarm signal could be available soon, and it would be very useful in the management of diabetes. The sensor for this application would need to function for a minimum period of about 12 hours. Further developments in the glucose sensor area are expected to lead to a comfortable implantable sensor/pump device, which would provide closed loop control for a prolonged period. An acceptable system would be a sensor replaced every 2 to 3 days, coupled with a microprocessor-controlled pump replaced after 2 to 3 years. Further engineering input is needed to design the monitoring and control unit containing the alarm and pump systems. The world market in clinical analysis is about US $6 billion, and covers about 10% of the total expenses for health care. It is in the field of continuous microsensors that future competition for the clinical diagnostic market will take place. Funding in vivo projects is less attractive to industry than the more proven and well-established area of in vitro diagnostics. However, the benefits of in vivo monitoring to the health of the community, and the financial rewards to manufacturers are ultimately great. It is clearly of interest for industry to invest in the development and commercialisation of this high added-value technology.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>