gebhart/patrepeval huggingface dataset:
Cyclic Peptides from Linear Unprotected Peptide Precursors through Thiazolidine Formation (1996)

We describe a general method for the preparation of cyclic peptides by intramolecular thiazolidine formation from linear, unprotected peptide precursors. The precursors contain a protected 1,2-aminothiol from an N-terminal cysteine and a 1,2-amino alcohol or 1,2-diol as a masked aldehyde. Thiazolidine formation was effected by oxidation of the 1,2-amino alcohol or 1,2-diol by sodium periodate to give an aldehyde, followed by deprotection of the masked 1,2-aminothiol. The cyclization could be effected at concentrations as high as 20 mM and was free from any polymerized side products. Such high efficiency of macrocyclization may be attributed to the ring-chain” tautomerism of the open chain amino-aldehyde precursor that favors a macrocyclic thiazolidine ring. Thiazolidine formation was further exploited as a capture device to position the N and C termini covalently close together and then to allow a proximity-driven O to N acyl transfer through a novel tricyclic ring contraction to yield an all amide, end-to-end cyclic lactam. These macrocyclization methods have been applied to the synthesis of cyclic peptides containing 5 to 26 amino acids.
The use of loop mirrors and chirped fibre Bragg gratings in actively-modelocked fibre lasers (1998)

The development of an all-optical communications infrastructure requires appropriate optical switching devices and supporting hardware. This thesis presents several novel fibre lasers which are useful pulse sources for high speed optical data processing and communications. They share several attributes in common: flexibility, stability and low-jitter output. They all produce short (picosecond) and are suitable as sources for soliton systems. The lasers are all-fibre systems using erbium-doped fibre for gain, and are actively-modelocked using a dual-wavelength nonlinear optical loop mirror (NOLM) as a modulator. Control over the operating wavelength and intra-cavity dispersion is obtained using a chirped in-fibre Bragg grating.Systems operating both at 76MHz and gigahertz frequencies are presented, the latter using a semiconductor laser amplifier to enhance nonlinear action in the loop mirror. A novel dual-wavelength system in which two linear cavities share a common modulator is presented with results which show that the jitter between the two wavelengths is low enough for use in switching experiments with data rates of up to 130Gbit/s.
A Panel of Neuron-Enriched Proteins as Markers for Traumatic Brain Injury in Humans (2009)

Surrogate markers have enormous potential for contributing to the diagnosis, prognosis, and therapeutic evaluation of acute brain damage, but extensive prior study of individual candidates has not yielded a biomarker in widespread clinical practice. We hypothesize that a panel of neuron-enriched proteins measurable in cerebrospinal fluid (CSF) and blood should vastly improve clinical evaluation and therapeutic management of acute brain injuries. Previously, we developed such a panel based initially on the study of protein release from degenerating cultured neurons, and subsequently on rodent models of traumatic brain injury (TBI) and ischemia, consisting of 14-3-3beta, 14-3-3zeta, three distinct phosphoforms of neurofilament H, ubiquitin hydrolase L1, neuron-specific enolase, alpha-spectrin, and three calpain- and caspase-derived fragments of alpha-spectrin. In the present study, this panel of 11 proteins was evaluated as CSF and serum biomarkers for severe TBI in humans. By quantitative Western blotting and sandwich immunoassays, the CSF protein levels were near or below the limit of detection in pre-surgical and most normal pressure hydrocephalus (NPH) controls, but following TBI nine of the 11 were routinely elevated in CSF. Whereas different markers peaked coordinately, the time to peak varied across TBI cases from 24-96 h post-injury. In serum, TBI increased all four members of the marker panel for which sandwich immunoassays are currently available: a calpain-derived NH(2)-terminal alpha-spectrin fragment and the three neurofilament H phosphoforms. Our results identify neuron-enriched proteins that may serve as a panel of CSF and blood surrogate markers for the minimally invasive detection, management, mechanistic, and therapeutic evaluation of human TBI.
Solvent-drop grinding: green polymorph control of cocrystallisationElectronic supplementary information (ESI) available: additional powder XRD patterns. See http://www.rsc.org/suppdata/cc/b4/b400978a/ (2004)

By grinding with a minimal addition of a solvent of appropriate polarity, control over the polymorphic outcome of a novel cocrystallisation involving the model pharmaceutical compound caffeine may be achieved.
Neural Network Application to Width Control in Hot Strip Mills (1995)

In order to tighten the width control in hot strip mills, a new width control model is developed by neural networks which can be used at the Roughing mill of hot ship mills. Existing models reported so far in the literature, can only take account of one or two key processing variables for in-bar width control models. In the same situation, the neural network models can consider up to twelve key processing variables. Therefore more accurate width control can be achieved by them. The basic steps for developing the neural network width model are presented in this paper. The results of this model and its relative analysis are integrated into an expert system which is expected to be implemented soon.
Cannabidiol Enhances the Inhibitory Effects of Δ9-Tetrahydrocannabinol on Human Glioblastoma Cell Proliferation and Survival (2010)

The cannabinoid 1 (CB(1)) and cannabinoid 2 (CB(2)) receptor agonist Delta(9)-tetrahydrocannabinol (THC) has been shown to be a broad-range inhibitor of cancer in culture and in vivo, and is currently being used in a clinical trial for the treatment of glioblastoma. It has been suggested that other plant-derived cannabinoids, which do not interact efficiently with CB(1) and CB(2) receptors, can modulate the actions of Delta(9)-THC. There are conflicting reports, however, as to what extent other cannabinoids can modulate Delta(9)-THC activity, and most importantly, it is not clear whether other cannabinoid compounds can either potentiate or inhibit the actions of Delta(9)-THC. We therefore tested cannabidiol, the second most abundant plant-derived cannabinoid, in combination with Delta(9)-THC. In the U251 and SF126 glioblastoma cell lines, Delta(9)-THC and cannabidiol acted synergistically to inhibit cell proliferation. The treatment of glioblastoma cells with both compounds led to significant modulations of the cell cycle and induction of reactive oxygen species and apoptosis as well as specific modulations of extracellular signal-regulated kinase and caspase activities. These specific changes were not observed with either compound individually, indicating that the signal transduction pathways affected by the combination treatment were unique. Our results suggest that the addition of cannabidiol to Delta(9)-THC may improve the overall effectiveness of Delta(9)-THC in the treatment of glioblastoma in cancer patients.
Quantitative in vivo assay of human granulocyte colony-stimulating factor using cyclophosphamide-induced neutropenic mice (1990)

Administration of human granulocyte colony-stimulating factor (hG-CSF) to mice with cyclophosphamide (CPA)-induced neutropenia for 4 consecutive days from the day after the CPA dosing (100 mg/kg) resulted in a dose-dependent increase in the peripheral blood neutrophil count 6 hours after the final hG-CSF injection. Within the hG-CSF dose range of 0.1 to 10 micrograms per mouse per day, there was a strong linear relationship (r greater than .9) between the logarithm of the dose and the peripheral blood neutrophil count in the treated mice. Using the same hG-CSF preparation, 38 experiments indicated that the regression lines are highly reproducible. Such an association never occurred with intact mice, and 100 mg/kg of CPA induced the highest response to hG- CSF. This linear relationship between the two variables allows us to determine the biologic potency of a test hG-CSF preparation relative to a reference standard using a parallel line assay, with a coefficient of precision of around .2. When assayed by this bioassay procedure, which we have termed CPA-mouse assay, natural hG-CSF and recombinant hG-CSF (produced by Chinese hamster ovary cells) were nearly equipotent in specific biologic activity. These results confirm the CPA-mouse assay as an especially useful assay method for quantifying the in vivo activity of hG-CSF.
Extracellular matrix remodeling at the early stages of liver regeneration in the rat (1997)

Previous studies have shown that activity of urokinase-type plasminogen activator (u-PA) increases very rapidly (within 1 minute) after partial hepatectomy. In view of the well-recognized roles of u-PA as one of the major initiators of the matrix proteolysis cascade and as an activator of plasminogen and hepatocyte growth factor (HGF), we studied matrix degradation in liver shortly after partial hepatectomy. The activation of plasminogen to plasmin following partial hepatectomy was examined by Western blot analysis, and a small increase in plasmin at approximately 15 minutes followed by a large elevation at approximately 3 to 6 hours after partial hepatectomy was detected. In addition, we found that fibrinogen, the major substrate for plasmin, begins to be degraded at approximately 15 to 30 minutes following partial hepatectomy. Using immunohistochemical staining, we detected that the distribution of fibrinogen in normal liver is localized to the perisinusoidal space surrounding the periportal region. A decreased distribution of fibrinogen in the periportal region was found by 15 minutes and continued through 24 hours following partial hepatectomy. In addition, the distribution of fibronectin in normal liver was localized to the perisinusoidal space surrounding the periportal and the pericentral regions. A strikingly decreased distribution of fibronectin in the periportal region was found at 5 minutes after partial hepatectomy. Furthermore, we observed that the protein levels of laminin, entactin, and fibronectin in an extracellular matrix (ECM)-enriched preparation decreased shortly after partial hepatectomy, and were restored later. No changes were observed with either vitronectin or the integrin chain alpha(v). In contrast to the protein levels of the ECM components, the messenger RNA (mRNA) levels of fibronectin, integrin chain beta1, and integrin chain alpha(v) gradually increased over 18 hours and then decreased thereafter. Taken together, these results suggest that rapid reorganization of selected ECM components are important for hepatocyte proliferation at the early stages of liver regeneration.
Frequency hopping signal separation by spatio-frequency analysis based on the MUSIC method (2002)

A procedure for frequency hopping signal separation by spatio-frequency analysis based on the MUSIC algorithm is proposed. Under the term 'frequency hopping signal separation' we understand the processes of frequency hopping emitters detection which are active in a given frequency band and observation interval as well as the estimation of their parameters. It is assumed that there is no a priory information about the number and parameters of active hoppers.
Epidemiological Study of Duodenal Erosive Disease; Its Prevalence and Nosological Position in Relation to Ulcerative Peptic Disease (1989)

The prevalence of erosive lesions was found to be 27.5% in 11838 cases examined during the last 10 years. In almost 66% of the cases, erosive lesions were localized in the duodenal bulb but mainly isolated and less often in the antro-pyloric area. In 55% of the cases, duodenal erosions coexist with ulcerative peptic disease, 20% in "active" phase and 35% in "inactive" phase. Erosive lesions, appeared autonomously in 45% of the cases. Morphologically, they can be divided in: a) periulcerative marginal erosions closely connected with activity of the ulcers; b) clustered, complete or incomplete erosions, which may or may not be associated with the ulcerative disease and often have a prolonged acyclic behaviour; c) scattered flat erosions which can at times be associated with the ulcerative peptic disease but are always related to a chronic widespread duodenitis. An epidemiological study was performed on 564 cases which were divided into 3 groups: a) cases with autonomous erosive disease; b) those with erosions associated with post-ulcerative scars; and c) those with erosions associated with active ulcers. The control group of 111 cases was characterised by duodenal active ulcers with no erosions. Statistical evaluation of the percentage differences between the 4 groups revealed that in duodenal erosive disease predisposing factors such as psychic temper, environmental and work conditions and eating habits are evident. In autonomous disease drug intake and spices and, to a less extent, alcohol and/or stress situations play a more important role. In erosions associated with an active ulcer, a dominant obsessive temper facilitated by a difficult family situation, bad eating habits and a great amount of smoking are prominent factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Association of mitochondrial copy number variation and T16189C polymorphism with colorectal cancer in North Indian population (2017)

Globally, colorectal cancer is the third most common type of cancer. Genetic instability leading to cancer development is one of the major causes for development of cancer. Alterations in mitochondrial genome, that is, mutations, single-nucleotide polymorphisms, and copy number variations are known to contribute in cancer development. The aim of our study was to investigate association of mitochondrial T16189C polymorphism and copy number variation with colorectal cancer in North Indian population. DNA isolated from peripheral blood of 126 colorectal cancer patients and 114 healthy North Indian subjects was analyzed for T16189C polymorphism and half of them for mitochondrial copy number variation. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism, and copy number variation was estimated using real-time polymerase chain reaction, numbers of mitochondrial copies and found to be significantly higher in colorectal cancer patients than healthy controls (88 (58-154), p = 0.001). In the regression analysis, increased mitochondrial copy number variation was associated with risk of colorectal cancer (odds ratio = 2.885, 95% confidence interval = 1.3-6.358). However, T16189C polymorphism was found to be significantly associated with the risk of rectal cancer (odds ratio = 5.213, p = 0.001) and non-significantly with colon cancer (odds ratio = 0.867, p = 0.791). Also, false-positive report probability analysis was done to validate the significant findings. Our results here indicate that mitochondrial copy number variation may be playing an important role in the development of colorectal cancer, and detection of mitochondrial copy number variation can be used as a biomarker for predicting the risk of colorectal cancer in North Indian subjects.
Differential functions of the two Src homology 2 domains in protein tyrosine phosphatase SH-PTP1. (1996)

SH-PTP1 (also known as PTP1C, HCP, and SHP) is a non-transmembrane protein tyrosine phosphatase (PTPase) containing two tandem Src homology 2 (SH2) domains. We show here that the two SH2 (N-SH2 and C-SH2) domains in SH-PTP1 have different functions in regulation of the PTPase domain and thereby signal transduction. While the N-terminal SH2 domain is both necessary and sufficient for autoinhibition through an intramolecular association with the PTPase domain, truncation of the C-SH2 domain [SH-PTP1 (delta CSH2) construct] has little effect on SH-PTP1 activity. A synthetic phosphotyrosine residue (pY) peptide derived from the erythropoietin receptor (EpoR pY429) binds to the N-SH2 domain and activates both wild-type SH-PTP1 and SH-PTP1 (delta CSH2) 60- to 80-fold. Another pY peptide corresponding to a phosphorylation site on the IgG Fc receptor (Fc gamma RIIB1 pY309) associates with both the C-SH2 domain (Kd = 2.8 microM and the N-SH2 domain (Kd = 15.0 microM) and also activates SH-PTP1 12-fold. By analysis of the effect of the Fc gamma RIIB1 pY309 peptide on SH-PTP1 (delta CSH2), SH-PTP1 (R30K/R33E), SH-PTP1 (R30K/R136K), and SH-PTP1 (R136K) mutants in which the function of either the N- or C-SH2 domain has been impaired, we have determined that both synthetic pY peptides stimulate SH-PTP1 by binding to its N-SH2 domain; binding of pY ligand to the C-SH2 domain has no effect on SH-PTP1 activity. We propose that the N-terminal SH2 domain serves both as a regulatory domain and as a recruiting unit, whereas the C-terminal SH2 domain acts merely as a recruiting unit.
Scintillation proximity assay in lead discovery (2008)

The SPA approach is well suited to the demands of commercial high volume automation and assay miniaturization for target-based high-throughput screening campaigns on synthetic and natural product libraries as well as for benchtop characterization and confirmation studies. In the near future, innovations in the way SPA and fluorescence-based screening strategies are multiplexed will improve our comprehensive understanding of cellular system biology and dramatically advance the lead discovery process for the treatment of complex target-related disorders.
Oral tolerance and inflammatory bowel disease (2005)

The fundamental difference in the mechanisms of oral tolerance in mice and humans requires a more focused effort to understand the human mucosal immune system before oral tolerance therapy for autoimmune and chronic inflammatory disorders reaches its full potential.
AutoDIAL: Automatic Domain Alignment Layers (2017)

Classifiers trained on given databases perform poorly when tested on data acquired in different settings. This is explained in domain adaptation through a shift among distributions of the source and target domains. Attempts to align them have traditionally resulted in works reducing the domain shift by introducing appropriate loss terms, measuring the discrepancies between source and target distributions, in the objective function. Here we take a different route, proposing to align the learned representations by embedding in any given network specific Domain Alignment Layers, designed to match the source and target feature distributions to a reference one. Opposite to previous works which define a priori in which layers adaptation should be performe d, our method is able to automatically learn the degree of feature alignment required at different levels of the deep network. Thorough experiments on different public benchmarks, in the unsupervised setting, confirm the power of our approach.
Neural Architecture Search with Bayesian Optimisation and Optimal Transport (2018)

Bayesian Optimisation (BO) refers to a class of methods for global optimisation of a function $f$ which is only accessible via point evaluations. It is typically used in settings where $f$ is expensive to evaluate. A common use case for BO in machine learning is model selection, where it is not possible to analytically model the generalisation performance of a statistical model, and we resort to noisy and expensive training and validation procedures to choose the best model. Conventional BO methods have focused on Euclidean and categorical domains, which, in the context of model selection, only permits tuning scalar hyper-parameters of machine learning algorithms. However, with the surge of interest in deep learning, there is an increasing demand to tune neural network \emph{architectures}. In this work, we develop NASBOT, a Gaussian process based BO framework for neural architecture search. To accomplish this, we develop a distance metric in the space of neural network architectures which can be computed efficiently via an optimal transport program. This distance might be of independent interest to the deep learning community as it may find applications outside of BO. We demonstrate that NASBOT outperforms other alternatives for architecture search in several cross validation based model selection tasks on multi-layer perceptrons and convolutional neural networks.
Purification and characterization of maleylacetate reductase from Alcaligenes eutrophus JMP134(pJP4) (1993)

Maleylacetate reductase (EC 1.3.1.32) plays a major role in the degradation of chloroaromatic compounds by channeling maleylacetate and some of its substituted derivatives into the 3-oxoadipate pathway. The enzyme was purified to apparent homogeneity from an extract of 2,4-dichlorophenoxyacetate (2,4-D)-grown cells of Alcaligenes eutrophus JMP134. Maleylacetate reductase appears to be a dimer of two identical subunits of 35 kDa. The pI was determined to be at pH 5.4. There was no indication of a flavin prosthetic group. The enzyme was inactivated by p-chloromercuribenzoate but not by EDTA, 1,10-phenanthroline, or dithiothreitol. Maleylacetate and 2-chloromaleylacetate were converted with similar efficiencies (with NADH as cosubstrate, Km = 31 microM for each substrate and kcat = 8,785 and 7,280/min, respectively). NADH was preferred to NADPH as the cosubstrate. Upon reduction of 2-chloramaleylacetate by the purified enzyme, chloride was liberated and the resulting maleylacetate was further reduced by a second NADH. These results and the kinetic parameters suggest that the maleylacetate reductase is sufficient to channel the 2,4-D degradation intermediate 2-chloromaleylacetate into the 3-oxoadipate pathway. In a data base search the NH2-terminal sequence of maleylacetate reductase was found to be most similar to that of TfdF, a pJP4-encoded protein of as-yet-unknown function in 2,4-D degradation.
Programmed trapping of individual bacteria using micrometre-size sieves (2011)

Monitoring the real-time behavior of spatial arrays of single living bacteria cells is only achieved with much experimental difficulty due to the small size and mobility of the cells. To address this problem, we have designed and constructed a simple microfluidic device capable of trapping single bacteria cells in spatially well-defined locations without the use of chemical surface treatments. The device exploits hydrodynamics to slow down and trap cells flowing near a narrow aperture. We have modeled this system numerically by approximating the motion of Escherichia coli cells as rigid 3-D ellipsoids. The numerical predictions for the speed and efficiency of trapping were tested by fabricating the devices and imaging GFP expressing E. coli at a high spatio-temporal resolution. We find that our numerical simulations agree well with the actual cell flow for varying trap geometries. The trapped cells are optically accessible, and combined with our ability to predict their spatial location we demonstrate the ease of this method for monitoring multiple single cells over a time course. The simplicity of the design, inexpensive materials and straightforward fabrication make it an accessible tool for any systems biology laboratory.