gebhart/patrepeval huggingface dataset:
Design, construction and properties of peptide N-terminal cap templates devised to initiate α-helices. Part 2.† Caps derived from N-[(2S )-2-chloropropionyl]-(2S )-Pro-(2S )-Pro-(2S,4S )-4-thioPro-OMe (1998)

Recently, we designed 12-membered macrocyclic template caps to entrain peptides into α-helical structures, based on the covalent connection of the first and fourth residues of proline containing tetrapeptides. It was not possible to complete the synthesis of the templates from the acyclic precursors and it appeared that the generation of large molecular dipoles, caused by aligning the carbonyl groups, prevented reaction. While this work was in progress, Kemp’s group published the structure of a 12-membered macrocyclic triproline template designed to initiate an α-helix that was very similar in structure to one of our own targets. However, the compound failed to cyclise in a conformation required for α-helix initiation and one or more carboxamide dipoles were not aligned. Here we provide a detailed conformational analysis of the system and test two methods for forcing the acyclic precursor into the macrocyclic conformation required for helix initiation. The first is the destabilisation of unwanted conformations in the transition state for cyclisation, and the second is the stabilisation of the favoured transition state structure through the introduction of a hydrogen-bonding interaction. Both strategies were unsuccessful and the reasons are discussed. A successful strategy which does not require the carbonyl dipoles to align in the transition state is presented in the following paper.
Interleukin (IL)‐17 promotes macrophages to produce IL‐8, IL‐6 and tumour necrosis factor‐α in aplastic anaemia (2008)

Aplastic anaemia (AA) is thought to be an autoimmune-mediated disease with active destruction of haematopoietic cells through a T helper type 1 (Th1) cell response. Interleukin (IL)-17 is a potent proinflammatory cytokine produced by activated memory T cells. Recent studies indicate that IL-17 might be an essential effector cytokine in the T-cell mediated autoimmune process. It can drive the production of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-6 and IL-8 by a variety of cells. The present study investigated the genetic and protein expression of IL-17 in patients with AA. The effect of IL-17 on IL-6 and IL-8 production by macrophages was also studied. AA patients showed an elevated expression of IL17A mRNA in bone marrow mononuclear cells and peripheral blood mononuclear cells. Higher IL-17 in bone marrow and peripheral blood plasma was also observed in AA patients compared with normal controls. IL-17 induced the production of IL-6 and IL-8 by macrophages both from patients with AA and normal controls. IL-17 stimulation also resulted in the production of TNF-alpha. These results suggested that elevated expression of IL-17 and IL-17-induced IL-6, IL-8 and TNF-alpha may be involved in the mechanisms of AA.
High Quantum Efficiency in Organic Light-Emitting Devices with Iridium-Complex as a Triplet Emissive Center (1999)

Multilayer organic light-emitting devices with phosphorescent guest emitter, tris(2-phenylpyridine) iridium doped in a host 4,4 ′ -N,N ′ -dicarbazol-biphenyl layer were prepared. The device with the 6.5 wt% guest emitter exhibited external quantum efficiency and power luminous efficiency of 13.7% and 38.3 lm/W, respectively at the luminance of 105 cd/m 2 driven at the voltage of 4.0 V and current density of 0.215 mA/cm 2 . The half decay lifetime under continuous constant-current driving for the initial luminance of 500 cd/m 2 was 170 h.
Unpinning the GaAs Fermi level with thin heavily doped silicon overlayers (1990)

A theoretical investigation is made into the unpinning of the GaAs Fermi level (E/sub f/) at Schottky contacts by thin interfacial layers of heavily doped Si. The pinning mechanism is assumed to be a plane of interface states in the GaAs. The method used is to solve Poisson's equation numerically as a two-point boundary problem across the semiconductor. The results show that E/sub f/ can be moved from its pinned position to near the edge of the silicon valence band maximum or conduction band minimum at the Si/GaAs heterojunction with heavily doped p-Si or n-Si overlayers, respectively. This unpinning is observed with and without thick metallization on the Si. Exactly analogous results are obtained for Ge interfacial layers. The results are in good agreement with the experimental results obtained by J.R. Waldrop and R.W. Grant (1988). Although the unpinning is seen to occur for interface-state densities sufficient to pin E/sub f/ at the free GaAs surface, interface-state densities high enough to result in significant E/sub f/ pinning at metal/GaAs contacts are seen to prevent such unpinning by Si interfacial layers. It is therefore suggested that Si (or Ge) deposition gives rise to fewer interface states in the GaAs than does metal deposition.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
OpenFlow-based server load balancing gone wild (2011)

Today’s data centers host online services on multiple servers, with a front-end load balancer directing each client request to a particular replica. Dedicated load balancers are expensive and quickly become a single point of failure and congestion. The OpenFlow standard enables an alternative approach where the commodity network switches divide traffic over the server replicas, based on packet-handling rules installed by a separate controller. However, the simple approach of installing a separate rule for each client connection (or “microflow”) leads to a huge number of rules in the switches and a heavy load on the controller. We argue that the controller should exploit switch support for wildcard rules for a more scalable solution that directs large aggregates of client traffic to server replicas. We present algorithms that compute concise wildcard rules that achieve a target distribution of the traffic, and automatically adjust to changes in load-balancing policies without disrupting existing connections. We implement these algorithms on top of the NOX OpenFlow controller, evaluate their effectiveness, and propose several avenues for further research. 1
Shear response of layered silicate nanocomposites (2001)

The linear and nonlinear melt state viscoelastic properties for a series of layered silicate based intercalated polymer nanocomposites are studied to elucidate the role of highly anisotropic nanometer thick layers in altering the flow properties of such hybrids. The steady shear viscosities for the nanocomposites exhibit enhanced shear-thinning at all shear rates, with the viscosity at high shear rates being almost independent of silicate loading and comparable to that of the unfilled polymer. Further, the elasticity, as measured by the first normal stress difference, when compared at constant shear stress is surprisingly independent of the silicate loading and identical to that of the unfilled polymer. This unique combination of unfilled polymerlike viscosity and elasticity for these filled nanocomposites, is attributed to the ability of the highly-anisotropic layered silicates to be oriented in the flow direction and results in a minimal contribution by the silicate layers to both the viscosity and the elasticity of the hybrids.
Non-invasive optical spectroscopy and imaging of human brain function (1997)

Brain activity is associated with changes in optical properties of brain tissue. Optical measurements during brain activation can assess haemoglobin oxygenation, cytochrome-c-oxidase redox state, and two types of changes in light scattering reflecting either membrane potential (fast signal) or cell swelling (slow signal), respectively. In previous studies of exposed brain tissue, optical imaging of brain activity has been achieved at high temporal and microscopical spatial resolution. Now, using near-infrared light that can penetrate biological tissue reasonably well, it has become possible to assess brain activity in human subjects through the intact skull non-invasively. After early studies employing single-site near-infrared spectroscopy, first near-infrared imaging devices are being applied successfully for low-resolution functional brain imaging. Advantages of the optical methods include biochemical specificity, a temporal resolution in the millisecond range, the potential of measuring intracellular and intravascular events simultaneously and the portability of the devices enabling bedside examinations.
B-lineage colonies from normal, human bone marrow are initiated by B cells and their progenitors (1991)

Abstract We have recently described a reproducible method whereby colonies containing cells that secrete immunoglobulin (Ig) can be grown from normal, human, adult bone marrow samples. The present report characterizes the cells that initiate these colonies. It is shown that all clonogenic cells express the CD19 surface antigen, as removal of these cells before plating in the B-cell colony assay abolished the subsequent growth of plaque-forming, B-lineage colonies. Cells from both the CD10+ and CD20+ B-lineage subpopulations initiated the growth of B-cell colonies, as removal of either subset resulted in a 50% reduction in the number of resulting B-cell colonies. The removal of activated B cells (CD23+), plasma cells (PCA-1+), or myeloid cells (CD13+) did not lead to a significant depletion in B-cell colony formation. Pre-B cells that were not yet committed to Ig light chain expression were also able to differentiate and proliferate into Ig- secreting colonies under the culture conditions used. Colonies initiated by these light chain uncommitted cells were distinguished using a replicate protein immunoblotting technique, which detects the simultaneous secretion of Ig kappa and Ig lambda from single colonies. These experiments provide evidence that the CD10 antigen is expressed on B-lineage cells before Ig light chain commitment, whereas CD20 is not. In conclusion, this B-cell colony assay provides a system for studying the differentiation of bone marrow-derived B cells and their precursors into Ig-secreting cells.
High fat diet causes rebound weight gain (2012)

Obesity is at epidemic proportions but treatment options remain limited. Treatment of obesity by calorie restriction (CR) despite having initial success often fails due to rebound weight gain. One possibility is that this reflects an increased body weight (BW) set-point. Indeed, high fat diets (HFD) reduce adult neurogenesis altering hypothalamic neuroarchitecture. However, it is uncertain if these changes are associated with weight rebound or if long-term weight management is associated with reversing this. Here we show that obese mice have an increased BW set-point and lowering this set-point is associated with rescuing hypothalamic remodelling. Treating obesity by CR using HFD causes weight loss, but not rescued remodelling resulting in rebound weight gain. However, treating obesity by CR using non-HFD causes weight loss, rescued remodelling and attenuates rebound weight gain. We propose that these phenomena may explain why successful short-term weight loss improves obesity in some people but not in others.
Overexpression of the human melanoma-associated antigen ME491 partially suppresses in vivo malignant phenotypes of H-ras-transformed NIH3T3 cells in athymic nude mice (1991)

H-ras-transformed NIH3T3 cells that overexpressed a human melanoma-associated antigen ME491 (44–3H) were generated by transfection with the cloned ME491 antigen gene followed by a ‘panning’ selection, and effects of the antigen Overexpression on H-ras-mediated malignant phenotypes were studied. Although in vitro growth properties of the 44–3H overexpresser cells, both anchorage-dependent and-independent, were practically the same as those of the 44–1C control cells, 44–3H cells exhibited less malignant phenotypes in athymic nude mice (in vivo), i.e. decreased tumourigenicity after subcutaneous inoculation and prolonged survival tirne after intraperitoneal inoculation, compared with 44–1C cells. These results suggested that Overexpression of ME491 antigen partially suppressed malignant phenotypes of H-ras-transformed NIH3T3 cells in athymic nude mice through co-operating with a factor(s) or mechanism(s) that exist in vivo but not in vitro. Thus, ME491 antigen might act as a tumour suppressor under some circumstances.
Therapeutic Targeting of Hyaluronan in the Tumor Stroma (2012)

The tumor stroma, consisting of non-malignant cells and the extracellular matrix, undergoes significant quantitative and qualitative changes throughout malignant transformation and tumor progression. With increasing recognition of the role of the tumor microenvironment in disease progression, stromal components of the tumor have become attractive targets for therapeutic intervention. Stromal accumulation of the glycosaminoglycan hyaluronan occurs in many tumor types and is frequently associated with a negative disease prognosis. Hyaluronan interacts with other extracellular molecules as well as cellular receptors to form a complex interaction network influencing physicochemical properties, signal transduction, and biological behavior of cancer cells. In preclinical animal models, enzymatic removal of hyaluronan is associated with remodeling of the tumor stroma, reduction of tumor interstitial fluid pressure, expansion of tumor blood vessels and facilitated delivery of chemotherapy. This leads to inhibition of tumor growth and increased survival. Current evidence shows that abnormal accumulation of hyaluronan may be an important stromal target for cancer therapy. In this review we highlight the role of hyaluronan and hyaluronan-mediated interactions in cancer, and discuss historical and recent data on hyaluronidase-based therapies and the effect of hyaluronan removal on tumor growth.
The two alcohol dehydrogenases of Zymomonas mobilis. Purification by differential dye ligand chromatography, molecular characterisation and physiological roles (1986)

The two alcohol dehydrogenases found in Zymomonas mobilis have each been purified using dye-ligand chromatography and affinity elution with nucleotides. The isoenzyme with lower electrophoretic mobility (ZADH-1) is a zinc enzyme with properties essentially similar to preparations described elsewhere. The faster isoenzyme (ZADH-2) accounted for some 90% of the ethanol-oxidizing activity in freshly prepared extracts and corresponded to the iron-activated enzyme previously described. This enzyme was inactivated by zinc; activity could only be retained during purification by including either ferrous ions or cobaltous ions in the buffers. ZADH-2 has relatively low acetaldehyde reductase activity; consequently ZADH-1 is responsible for about half of the physiological activity (acetaldehyde reduction) in Zymomonas cells. Kinetic studies showed that ZADH-2 is activated by ethanol in both reaction directions; a hypothesis for the mechanism of activation is presented. Metal ion analyses of ZADH-2 prepared in the presence of iron or cobalt indicated one atom of the relevant metal per subunit, with no significant zinc content. N-terminal sequence analyses showed that the ZADH-1 has some homology with the Bacillus stearothermophilus enzyme, whereas ZADH-2 resembles the yeast enzyme more closely.
Electrochemical and in Situ Ellipsometric Investigation of the Permeability and Stability of Layered Polyelectrolyte Films (1999)

Utilization of layered polyelectrolyte films as sensor or ion-separation materials will depend critically on their stability and ion permeability in aqueous solution. We report electrochemical and in situ ellipsometric studies on the permeability and stability of poly(allylamine hydrochloride)/poly(styrenesulfonate) (PAH/PSS) and PAH/poly(acrylic acid) (PAA) films. The permeability of these layered polyelectrolyte films to Fe(CN)63- and Ru(NH3)63+ depends on the solution pH, the number of bilayers in the film, whether supporting electrolyte is present during film deposition, and the nature of constituent polycations and polyanions. Cyclic voltammetry and impedance spectroscopy show that film permeability is similar in pH 3.2- and pH 6.3-buffered solutions but increases dramatically in alkaline solutions. In situ ellipsometry helps to explain these results. Upon immersion in pH 3.2- and pH 6.3-buffered solutions, the thickness of PAH/PSS films increases by 40%, but swelling is constant over time. At pH 10, these films initially swell by 40% but then continue to swell for several minutes before delaminating. The onset of increased swelling corresponds with dramatic increases in film permeability. Both peak current (cyclic voltammetry) and charge-transfer resistance (ac impedance) depend nonlinearly on the number of polyelectrolyte bilayers. The structure of the first two bilayers is more porous than that of later bilayers. Adding supporting electrolyte to deposition solutions results in thicker bilayers and changes film permeability. For PAH/PSS films, the use of supporting electrolyte during film formation results in a much less permeable film (comparing films of similar thickness). In PAH/PAA films, however, the use of supporting salt results in highly permeable films (even with thicknesses as high as 44 nm). Thus proper choice of constituent polyelectrolytes and deposition conditions permits control over the permeability of layered polyelectrolyte films.
Whispering-Gallery-Mode THz-Pulse Propagation on a Single Curved Metallic Plate (2009)

We demonstrate THz-pulse propagation on a 25-cm-long semi-circular aluminum plate with low loss and negligible dispersion via whispering-gallery-modes. This represents the first demonstration of these modes on a curved metallic surface in the THz regime.
Vacuum-Assisted Closure (VAC Therapy) and the Risk of Fluid Loss in Acute Trauma (2006)

Norton, Samuel Edward MBBS(Lond), MRCS(Ed); De Souza, Beryl FRCS; Marsh, Daniel MRCS; Moir, Graeme FRCS(Plast) Author Information
Field trial of honey bee colonies bred for mechanisms of resistance againstVarroa destructor (2007)

We compared colonies selectively bred for both hygienic behavior and Suppression of Mite Reproduction (HYG/SMR) with colonies bred solely for hygienic behavior (HYG) and unselected control colonies. Colonies were evaluated for strength, brood viability, removal of freeze-killed brood, honey production, mite loads on adult bees and within worker brood, and mite reproductive success on worker brood for two years in two locations. By autumn in both years, the HYG/SMR colonies had significantly fewer mites on adult bees and in worker brood compared to the control colonies, and the HYG colonies had intermediate mite populations. Contrary to expectation, there were no differences among the lines in mite reproductive success. Further studies are required to determine if the genes and neural mechanisms that regulate the SMR trait are the same or different from those regulating hygienic behavior.
Identification and molecular cloning of a soluble human granulocyte-macrophage colony-stimulating factor receptor. (1991)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in hematopoiesis and host defense via interaction with specific cell-surface receptors in target tissues. We identified a truncated, soluble form of the low-affinity GM-CSF receptor (GMR) in chorio-carcinoma cells. Low-affinity GMR cDNAs encoding both the membrane-bound and soluble receptors were obtained by PCR using primers corresponding to the published sequence. Clones encoding the soluble receptor were identical in sequence to the membrane-bound form but contained a 97-nucleotide internal deletion. The amino acid sequence of this deleted cDNA predicts a protein that lacks the 84 C-terminal amino acids of the membrane-bound receptor, including the transmembrane and cytoplasmic domains, and contains 16 different amino acids at its C terminus. Expression of the soluble GMR cDNA in murine psi-AM cells as well as GM-CSF-dependent myeloid 32Dc13 cells produced a secreted protein that retained its capacity to bind GM-CSF in solution. RNase protection analysis indicates that this variant cDNA is derived from a naturally occurring mRNA. Soluble receptors have been identified for several other hematopoietin receptors and may be a general feature of this class. The striking similarity between the soluble form of the GMR and other hematopoietin receptors suggests that soluble binding proteins may play an important role in regulating the broad spectrum of biological responses mediated by these cytokines.
CML/RAGE signal induces calcification cascade in diabetes (2016)

Spotty calcification was predominant in the atherosclerotic plaques of amputated diabetic patients. CML/RAGE signal may induce the calcification cascade in diabetes via ROS-p38MAPK.
Dose-response study of omeprazole on meal-stimulated gastric acid secretion and gastrin release. (1983)

In a placebo-controlled, double-blind, crossover, and randomized trial, the effect of 30, 60, and 90 mg of oral omeprazole on peptone-stimulated gastric acid secretion and synchronously measured gastrin release was studied in 8 healthy subjects. Peptone-stimulated acid output was reduced dose-dependently by 42%, 80%, and 92%, respectively. In spite of a short mean plasma half-life of 52 min, the inhibitory effect lasted for greater than 4.5 h and was significantly correlated to the area under the plasma concentration time curve for omeprazole. Mean basal serum gastrin and gastrin profiles increased insignificantly without alteration of integrated gastrin output and did not show any correlation either to the omeprazole area under the plasma concentration time curve or to the inhibition of peptone-stimulated acid secretion. Side effects, significant alterations of laboratory screen, or alterations of serum concentrations of thyroid hormones were not detected. In conclusion, omeprazole is a potent and, under the conditions tested, well-tolerated inhibitor of meal-stimulated gastric acid secretion in humans.
Coding single-nucleotide polymorphisms associated with complex vs. Mendelian disease: Evolutionary evidence for differences in molecular effects (2004)

Most Mendelian diseases studied to date arise from mutations that lead to a single amino acid change in an encoded protein. An increasing number of complex diseases have also been associated with amino acid-changing single-nucleotide polymorphisms (coding SNPs, cSNPs), suggesting potential similarities between Mendelian and complex diseases at the molecular level. Here, we use two different evolutionary analyses to compare Mendelian and complex disease-associated cSNPs. In the first, we estimate the likelihood that a specific amino acid substitution in a protein will affect the protein's function, by using amino acid substitution scores derived from an alignment of related protein sequences and statistics from hidden Markov models. In the second, we use standard Ka/Ks ratios to make comparisons at the gene, rather than the individual amino acid, level. We find that Mendelian disease cSNPs have a very strong tendency to occur at highly conserved amino acid positions in proteins, suggesting that they generally have a severe impact on the function of the protein. Perhaps surprisingly, the distribution of amino acid substitution scores for complex disease cSNPs is dramatically different from the distribution for Mendelian disease cSNPs, and is indistinguishable from the distribution for "normal" human variation. Further, the distributions of Ka/Ks ratios for human and mouse orthologs indicate greater positive selection (or less negative selection) pressure on complex disease-associated genes, on average. These findings suggest that caution should be exercised when using Mendelian disease as a model for complex disease, at least with respect to molecular effects on protein function.
Features of Autoimmunity in the Abdominal Aortic Aneurysm (1996)

Our findings suggest that there are autoimmune features of AAA disease that might not only be informative in terms of AAA origin but also lead to more precise forms of pharmacologic down-regulation of disease progression.