gebhart/patrepeval huggingface dataset:
Discovery and Investigation ofO-Xylosylation in Engineered Proteins Containing a (GGGGS)nLinker (2013)

Protein engineering is a powerful tool for designing or modifying therapeutic proteins for enhanced efficacy, greater safety, reduced immunogenicity, and better delivery. GGGGS [(G4S)n] linkers are commonly used when engineering a protein, because of their flexibility and resistance to proteases. However, post-translational modifications (PTMs) can occur at the Ser residue in these linkers. Here, we report, for the first time, the occurrence of O-xylosylation at the serine residue in (G4S)n>2 linkers. The O-xylosylation was discovered as a result of molecular mass determination, peptide mapping analysis, and MS/MS sequencing. Our investigation showed that (i) O-xylosylation is a common PTM for (G4S)(n>2) linkers; (ii) GSG is the motif for O-xylosylation; and (iii) the total amount of xylosylation per linker increases as the number of GSG motifs in the linker increases. Our investigation has also shown that the O-xylosylation level is clone-dependent, to a certain degree, but the xylosylation level varies considerably among the proteins examined-from <2% to >25% per linker-likely depending on the accessibility to the sites by the xylosyltransferase. Our work demonstrates that potential therapeutic proteins containing (G4S)n linkers should be closely monitored for O-xylosylation in order to ensure that drugs are homogeneous and of high quality. The strategies for elimination and reduction of O-xylosylation were also examined and are discussed.
Assembly of the BclB glycoprotein into the exosporium and evidence for its role in the formation of the exosporium ‘cap’ structure in Bacillus anthracis (2012)

The outermost layer of the Bacillus anthracis spore consists of an exosporium comprised of an outer hair-like nap layer and an internal basal layer. A major component of the hair-like nap is the glycosylated collagen-like protein BclA. A second collagen-like protein, BclB, is also present in the exosporium. BclB possesses an N-terminal sequence that targets it to the exosporium and is similar in sequence to a cognate targeting region in BclA. BclB lacks, however, sequence similarity to the region of BclA thought to mediate attachment to the basal layer via covalent interactions with the basal layer protein BxpB. Here we demonstrate that BxpB is critical for correct localization of BclB during spore formation and that the N-terminal domains of the BclA and BclB proteins compete for BxpB-controlled assembly sites. We found that BclB is located principally in a region of the exosporium that excludes a short arc on one side of the exosporium (the so-called bottle-cap region). We also found that in bclB mutant spores, the distribution of exosporium proteins CotY and BxpB is altered, suggesting that BclB has roles in exosporium assembly. In bclB mutant spores, the distance between the exosporium and the coat, the interspace, is reduced.
Human domain antibodies to conserved sterically restricted regions on gp120 as exceptionally potent cross-reactive HIV-1 neutralizers (2008)

The antibody access to some conserved structures on the HIV-1 envelope glycoprotein (Env) is sterically restricted. We have hypothesized that the smallest independently folded antibody fragments (domains) could exhibit exceptionally potent and broadly cross-reactive neutralizing activity by targeting hidden conserved epitopes that are not accessible by larger antibodies. To test this hypothesis, we constructed a large (size 2.5 x 10(10)), highly diversified library of human antibody variable domains (domain antibodies) and used it for selection of binders to conserved Env structures by panning sequentially against Envs from different isolates. The highest affinity binder, m36, neutralized all tested HIV-1 isolates from clades A- D with an activity on average higher than that of C34, a peptide similar to the fusion inhibitor T20, which is in clinical use, and that of m9, which exhibits a neutralizing activity superior to known potent cross-reactive antibodies. Large-size fusion proteins of m36 exhibited diminished neutralizing activity but preincubation of virions with soluble CD4 restored it, suggesting that m36 epitope is sterically restricted and induced by CD4 (CD4i). M36 bound to gp120-CD4 complexes better than to gp120 alone and competed with CD4i antibodies. M36 is the only reported representative of a promising class of potent, broadly cross-reactive HIV-1 inhibitors based on human domain antibodies. It has potential for prevention and therapy and as an agent for exploration of the closely guarded conserved Env structures with implications for design of small molecule inhibitors and elucidation of mechanisms of virus entry and evasion of immune responses.
Metabonomics and Biomarker Discovery:  LC−MS Metabolic Profiling and Constant Neutral Loss Scanning Combined with Multivariate Data Analysis for Mercapturic Acid Analysis (2005)

In the field of metabonomics, 1H NMR and full scan mass spectrometry methods have usually been combined with principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) to detect patterns in biofluids that correspond to specific effects, usually a toxic site effect of a compound. Confounders together with great interindividual variation complicate such analysis in humans, and therefore, metabonomic data are almost restricted to animals. In our study, a constant neutral loss (CNL) scan on a linear ion trap demonstrated increased sensitivity and specificity compared to a full scan approach and was performed to detect mercapturic acids (MA), a class of effect markers. The method was applied to human volunteers administered 50 and 500 mg of acetaminophen (AAP), a model compound known to form MAs. Using a new algorithm to prepare the CNL data for chemometrics, discrimination of control and postdose samples could be performed using PCA and PLS-DA. The loadings plots clearly revealed AAP-MA as a marker, even at low-dose levels. Orthogonal signal correction (OSC) was carried out to investigate background information that is not due to exposure. Surprisingly, the OSC data provided a classification of male and female subjects showing the performance of the new approach.
Emerging approaches in the molecular design of receptor-selective peptide ligands: conformational, topographical and dynamic considerations (1990)

Design of receptor-selective peptide ligands
In Vivo Evaluation of a Biodegradable EDC/NHS‐Cross‐Linked Gelatin Peripheral Nerve Guide Conduit Material (2007)

Peripheral nerve regeneration has been evaluated using a biodegradable nerve conduit, which is made of a 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)/N-hydroxysuccinimide (NHS) cross-linked gelatin. The EDC/NHS crosslinked gelatin (ENG) conduit is brownish in appearance, and is concentric and round with a smooth outer surface and inner lumen. After subcutaneous implantation on the dorsal side of a rat, the degraded ENG conduit only evoked a mild tissue response, with the formation of a thin tissue capsule surrounding the conduit. Biodegradability of the ENG conduit and its effectiveness as a guidance channel has been examined by its use to repair a 10 mm gap in the rat sciatic nerve. As a result, the tubes degraded throughout the implantation period, but still remained circular with a thin round lumen until they were completely integrated with the enclosed nerves. Successful regeneration through the gap occurred in all the conduits over the three experimental periods of 4, 8, and 12 weeks. Histological observation showed that numerous myelinated axons had crossed through the gap region even at the shortest implantation period of 4 weeks. Peak amplitude, area under the muscle action potential curve, and nerve conductive velocity all showed an increase as a function of the recovery period, which indicates that the nerve had undergone adequate regeneration. These results indicate the superiority of the ENG materials and suggest that the novel ENG conduits provide a promising tool for neuro-regeneration.
A watermark for digital images (2002)

The growth of networked multimedia systems has magnified the need for image copyright protection. One approach used to address this problem is to add an invisible structure to an image that can be used to seal or mark it. These structures are known as digital watermarks. We describe two techniques for the invisible marking of images. We analyze the robustness of the watermarks with respect to linear and nonlinear filtering, and JPEG compression. The results show that our watermarks detect all but the most minute changes to the image.
A refreshable analog VLSI neural network chip with 400 neurons and 40 K synapses (1992)

An on-chip learning neural network LSI circuit that can refresh the analog storage synaptic weights located on a chip is described. The chip integrates 400 neurons and 40000 synapses with a 0.8- mu m double-poly double-metal CMOS technology. This device stores learned information by repeating the refresh process at 200-ms intervals.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Automatic calibration of RGBD and thermal cameras (2014)

Reasoning about a scene's thermal signature, in addition to its visual appearance and spatial configuration, would facilitate significant advances in perceptual systems. Applications involving the segmentation and tracking of persons, vehicles, and other heat-emitting objects, for example, could benefit tremendously from even coarsely accurate relative temperatures. With the increasing affordability of commercially available thermal cameras, as well as the imminent introduction of new, mobile form factors, such data will be readily and widely accessible. However, in order for thermal processing to complement existing methods in RGBD, there must be an effective procedure for calibrating RGBD and thermal cameras to create RGBDT (red, green, blue, depth, and thermal) data. In this paper, we present an automatic method for the synchronization and calibration of RGBD and thermal cameras in arbitrary environments. While traditional calibration methods fail in our multimodal setting, we leverage invariant features visible by both camera types. We first synchronize the streams with a simple optimization procedure that aligns their motion statistic time series. We then find the relative poses of the cameras by minimizing an objective that measures the alignment between edge maps from the two streams. In contrast to existing methods that use special calibration targets with key points visible to both cameras, our method requires nothing more than some edges visible to both cameras, such as those arising from humans. We evaluate our method and demonstrate that it consistently converges to the correct transform and that it results in high-quality RGBDT data.
Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice (2002)

Rheumatoid arthritis is one of the most critical diseases that impair the quality of life of patients, but its pathogenesis has not yet been fully understood. Osteopontin (OPN) is an extracellular matrix protein containing Arg-Gly-Asp (RGD) sequence, which interacts with alpha(v)beta3 integrins, promotes cell attachment, and cell migration and is expressed in both synovial cells and chondrocytes in rheumatoid arthritis; however, its functional relationship to arthritis has not been known. Therefore, we investigated the roles of OPN in the pathogenesis of inflammatory process in a rheumatoid arthritis model induced by a mixture of anti-type II collagen mAbs and lipopolysaccharide (mAbs/LPS). mAbs/LPS injection induced OPN expression in synovia as well as cartilage, and this expression was associated with joint swelling, destruction of the surface structures of the joint based on scanning electron microscopy, and loss of toluidine blue-positive proteoglycan content in the articular cartilage in wild-type mice. In contrast, OPN deficiency prevented the mice from such surface destruction, loss of proteoglycan in the articular joint cartilage, and swelling of the joints even when the mice were subjected to mAbs/LPS injection. Furthermore, mAbs/LPS injection in wild-type mice enhanced the levels of CD31-positive vessels in synovia and terminal deoxynucleotidyltransferase-mediated UTP end labeling-positive chondrocytes in the articular cartilage, whereas such angiogenesis as well as chondrocyte apoptosis was suppressed significantly in OPN-deficient mice. These results indicated that OPN plays a critical role in the destruction of joint cartilage in the rheumatoid arthritis model in mice via promotion of angiogenesis and induction of chondrocyte apoptosis.
Identification of Residues in the N-Terminal Acidic Domain of HIV-1 Vpr Essential for Virion Incorporation (1995)

Vpr is one of the auxiliary proteins encoded by the HIV-1 genome and is selectively incorporated into the virus particle. It has been shown that Vpr incorporation in the virus particle requires only the core protein Gag. In an effort to identify the domains of Vpr which are essential for incorporation into the HIV-1 virion, site-specific mutagenesis of vpr was carried out. Mutation of the highly conserved acidic residues in the N-terminal domain (amino acid positions 17-34) eliminated virion incorporation. These mutations disrupt a predicted amphipathic alpha-helical structure that is highly conserved among Vpr sequences. In contrast, alterations of the conserved cysteine (Cys76), basic domain (Arg87 and Lys95), and other residues (Gln65) did not impair the incorporation of Vpr into virus-like particles directed by HIV-1 Gag. The results presented here suggest that protein-protein interactions mediated through the putative helical domain of Vpr may participate in its incorporation into the virus particle.
A unified simulation of Schottky and ohmic contacts (2000)

The Schottky contact is an important consideration in the development of semiconductor devices. This paper shows that a practical Schottky contact model is available for a unified device simulation of Schottky and ohmic contacts. The present model includes the thermionic emission at the metal/semiconductor interface and the spatially distributed tunneling calculated at each semiconductor around the interface. Simulation results of rectifying characteristics of Schottky barrier diodes (SBD's) and resistances under high impurity concentration conditions are reasonable, compared with measurements. As examples of application to actual devices, the influence of the contact resistance on salicided MOSFETs with source/drain extension and the immunity of Schottky barrier tunnel transistors (SBTTs) from the short-channel effect (SCE) are demonstrated.
Lipid Rafts Mediate the Synaptic Localization of α-Synuclein (2004)

Alpha-synuclein contributes to the pathogenesis of Parkinson's disease (PD), but its precise role in the disorder and its normal function remain poorly understood. Consistent with a presumed role in neurotransmitter release and its prominent deposition in the dystrophic neurites of PD, alpha-synuclein localizes almost exclusively to the nerve terminal. In brain extracts, however, alpha-synuclein behaves as a soluble, monomeric protein. Using a binding assay to characterize the association of alpha-synuclein with cell membranes, we find that alpha-synuclein binds saturably and with high affinity to characteristic intracellular structures that double label for components of lipid rafts. Biochemical analysis demonstrates the interaction of alpha-synuclein with detergent-resistant membranes and reveals a shift in electrophoretic mobility of the raft-associated protein. In addition, the A30P mutation associated with PD disrupts the interaction of alpha-synuclein with lipid rafts. Furthermore, we find that both the A30P mutation and raft disruption redistribute alpha-synuclein away from synapses, indicating an important role for raft association in the normal function of alpha-synuclein and its role in the pathogenesis of PD.
Medium chain triglycerides and structured lipids (1987)

Lipids are an essential component of our body composition and necessary in our daily food intake. Conventional fats and oils are composed of glycerides of long chain fatty acids and are designated as long chain triglycerides (LCT). Body fat as well as the fats and oils in our daily intake fall into this category. In enteral and parenteral hyperalimentation, we can identify such LCT fats and oils. Soy, corn, safflower and sunflowerseed oils are typical of the LCT oils. In the search for alternative noncarbohydrate fuels, medium chain triglycerides (MCT) are unique and have established themselves in the areas of malabsorption syndrome cases and infant care and as a high energy, rapidly available fuel. Structure lipids with a MCT backbone and linoleic acid built into the triglyceride molecule have been developed to optimize the triglyceride structure that is best for patients, particularly the critically ill. Structured lipids with built-in essential fatty acid components or other polyunsaturated fatty acids promise greater flexibility in patient care and nitrogen support.
Elemental and Nutritional Analysis of Sea Buckthorn ( Hippophae rhamnoides ssp. turkestanica ) Berries of Pakistani Origin (2005)

Sea buckthorn (Hippophae rhamnoides ssp. turkestanica) is a very important medicinal plant in northern areas of Pakistan. The fruit of sea buckthorn is rich in nutrients and medicinal compounds such as vitamins, carotene, flavonoids, essential oil, carbohydrates, organic acids, amino acids, and minerals. In order to compare various populations of sea buckthorn for chemical composition, eight populations from different areas of northern Pakistan were compared using fruit characteristics. Phytochemical analysis of berries showed vitamin C (250-333 mg/100 g), seed oil (7.69-13.7%), oil in softer pulp (19.2-29.1%), phytosterol content of seed oil (3.3-5.5%), and anthocyanin (0.5-25 mg/L), while the mineral element composition analysis revealed high contents of potassium (140-360 ppm), sodium (20-80 ppm), calcium (70-98 ppm), magnesium (150-240 ppm), iron (40-150 ppm), and phosphorus (110-133 ppm). This study established sea buckthorn berries as a good source of biochemical and mineral elements. The high variation between different populations shows the potential of selecting and breeding of the raw material for various defined purposes.
Epicardial Administration of Ibutilide from Polyurethane Matrices (1994)

Polymer-drug composites known as controlled-release systems have been used effectively to prevent and treat ventricular arrhythmias in experimental studies. We wished to determine if such systems could be useful in reducing ventricular defibrillation energy requirements in an acute canine model without producing undesirable electrophysiologic effects. Ibutilide-polyurethane monolithic controlled-release matrices were formulated with ibutilide fumarate and a polyether polyurethane. In vitro drug-release characteristics of the drug matrices were determined. Two formulations were investigated: (a) 20% ibutilide by weight in polyether polyurethane, and (b) 4% ibutilide/16% dimethyl tartrate in polyurethane. Based on in vitro release studies, 20% ibutilide matrices (25 mg) would provide a 25-kg dog with a dose of 25 micrograms/kg ibutilide in a 2-h acute experimental period, and 4% ibutilide matrices were estimated to provide 3.5 micrograms/kg. We used each of these types of matrices in acute open-chest dog studies to assess electrophysiologic effects and the influence of epicardial controlled-release ibutilide, as compared with intravenous (i.v.) administration, on defibrillation energy thresholds (DFTs), using epicardial defibrillation electrodes. In monophasic defibrillation waveform studies, 20% matrices significantly decreased DFT as compared with a predrug control period [2.54 +/- 0.59 (mean +/- SEM) vs. 7.23 +/- 1.73 J, respectively, p = 0.038]. Administration of the same dose i.v. did not cause significant reduction in energy requirement. With a biphasic defibrillation waveform, 4% ibutilide matrices significantly decreased DFT as compared with control (2.53 +/- 0.34 vs. 3.42 +/- 0.46 J, respectively, p = 0.003). Administration of an equivalent i.v. dose did not cause a significant reduction in biphasic energy requirement. Both types of controlled-release systems significantly prolonged refractoriness and conduction times of ventricular extrastimuli as compared with vehicle. No proarrhythmia events were observed. Epicardial polymeric controlled-release ibutilide significantly prolonged ventricular refractoriness and conduction and thus may enhance antiarrhythmia activity. In addition, controlled-release ibutilide formulations significantly decreased DFT requirements. Thus, ibutilide-polymeric controlled-release matrix systems may be useful in conjunction with implantable defibrillators in preventing ventricular arrhythmias and reducing defibrillation energy requirements.
Gastric cancer screening and subsequent risk of gastric cancer: A large‐scale population‐based cohort study, with a 13‐year follow‐up in Japan (2005)

We prospectively investigated the association between gastric cancer screening and subsequent risk of gastric cancer in a large-scale population-based prospective cohort study, with a 13-year follow-up in Japan. Data were analyzed from a population-based cohort of 42,150 (20,326 men and 21,824 women) subjects. Approximately 36% of subjects reported that they had undergone screening photofluorography during the preceding 12 months, and were regarded as the screened group. A total of 179 gastric cancer deaths and 636 incident gastric cancers were identified during the follow-up period. We observed a 2-fold decrease in gastric cancer mortality in screened versus unscreened subjects (RR = 0.52; 95% CI = 0.36-0.74). The extent of the reduction in mortality for gastric cancer was greater than in death from all causes excluding gastric cancer (RR = 0.71; 95% CI = 0.65-0.78). A significant decrease in the incidence of advanced gastric cancer was observed in screened subjects (RR = 0.75; 95% CI = 0.58-0.96), although the overall incidence rate did not differ significantly between the screened and unscreened subjects (RR = 1.06; 95% CI = 0.90-1.25). In age-stratified analyses, a significant reduction in gastric cancer mortality was seen in screened subjects aged 40-49 years at baseline, compared with a lesser reduction in screened subjects aged 50-59 (RR = 0.30, 95% CI = 0.13-0.72; and RR = 0.60, 95% CI = 0.40-0.88, respectively). These findings suggest that gastric cancer screening may be associated with a reduced risk of mortality from gastric cancer.
Total Synthesis of TAN-1057 A/B, a New Dipeptide Antibiotic fromFlexibacter sp. PK-74 (1998)

TAN-1057 (1a, b) − a new natural dipeptide antibiotic active against methicillin resistant strains of Staphylococcus aureus − was synthesized starting from Nα, Nδ, Nω-tri-Z-L-arginine 20b via the corresponding diazoketone 21b. This upon photolysis rearranged to the ketene which was trapped by (±)-2,4,5,6-tetrahydro-5-methylamino-2-ureidopyrimidin-4-one (3) to yield the fully protected dipeptide 23 (30%). The latter was deprotected by hydrogenolysis to give the final compound as a mixture of two epimers − TAN-1057A, B − isolated previously from a strain of Flexibacter sp. PK-74. The intermediate 3 was prepared from 3-amino-2-(N-Z-N-methylamino)propionic acid methyl ester hydrochloride (16) and 2-methyl-2-thiopseudobiuret hydroiodide (18) in one step in 35% yield.