gebhart/patrepeval huggingface dataset:
C‐Terminal Proteolytic Degradation of Recombinant Desulfato‐Hirudin and Its Mutants in the Yeast Saccharomyces cerevisiae (1994)

The potent thrombin inhibitor hirudin variant 1, originally isolated from the leech Hirudo medicinalis, was expressed in Saccharomyces cerevisiae under the control of a truncated glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter fragment. Fusion of the yeast acid phosphatase (PHO5) signal sequence to the hirudin gene led to quantitative secretion of recombinant desulfato-hirudin variant 1 (r-hirudin) into the extracellular medium in a growth-dependent manner. In comparison to the genuine molecule, r-hirudin lacks the sulfate group at the Tyr in position 63. Besides the full-length protein of 65 amino acids (hir65), chemical analysis revealed the presence mainly of two derivatives lacking the last amino acid Gln (hir64) or the penultimate Leu (hir63) in addition. When expressing r-hirudin in mutant strains defective in all but one of the three major known carboxypeptidases, it turned out that the vacuolar carboxypeptidase yscY as well as the alpha-factor precursor-processing carboxypeptidase, ysc alpha, participate in the C-terminal degradation of r-hirudin. Direct involvement of yscY and ysc alpha was confirmed by sequential disruption of their structural genes PRC1 and KEX1, respectively. Disruption of PRA1, coding for the yscY-processing proteinase yscA, also abolished yscY-mediated C-terminal r-hirudin degradation, but clearly reduced the overall expression yield. Since ysc alpha is described to be highly specific for basic amino acids which are not present at the C-terminus of r-hirudin, a series of r-hirudin mutants with changes in the C-terminal amino acids were constructed and analysed for ysc alpha-mediated and yscY-mediated degradation. Chromatographic analysis of the expression products confirmed the preference of ysc alpha for basic amino acids, although Tyr, Leu and Gln were also hydrolysed. It could further be concluded that ysc alpha might also be responsible for the C-terminal degradation of recombinant atrial natriuretic factor and epidermal growth factor expressed in yeast.
Gain mechanism in GaN Schottky ultraviolet detectors (2001)

Schottky barrier GaN ultraviolet detectors, both in vertical and in lateral configuration, as well as in a metal–semiconductor–metal geometry were implemented. All devices exhibit a high gain at both reverse and forward bias. The photoresponse in the forward bias is in the positive current direction. We attribute the gain to trapping of minority carriers at the semiconductor–metal interface. The excellent agreement between the calculated responsivity and the experiment indicates that the model is valid for all device structures under study, and represents a unified description of gain mechanism in GaN Schottky detectors.
Large-scale synthesis of copper nanoparticles by chemically controlled reduction for applications of inkjet-printed electronics (2008)

Copper nanoparticles are being given considerable attention as of late due to their interesting properties and potential applications in many areas of industry. One such exploitable use is as the major constituent of conductive inks and pastes used for printing various electronic components. In this study, copper nanoparticles were synthesized through a relatively large-scale (5 l), high-throughput (0.2 M) process. This facile method occurs through the chemical reduction of copper sulfate with sodium hypophosphite in ethylene glycol within the presence of a polymer surfactant (PVP), which was included to prevent aggregation and give dispersion stability to the resulting colloidal nanoparticles. Reaction yields were determined to be quantitative while particle dispersion yields were between 68 and 73%. The size of the copper nanoparticles could be controlled between 30 and 65 nm by varying the reaction time, reaction temperature, and relative ratio of copper sulfate to the surfactant. Field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) images of the particles revealed a spherical shape within the reported size regime, and x-ray analysis confirmed the formation of face-centered cubic (FCC) metallic copper. Furthermore, inkjet printing nanocopper inks prepared from the polymer-stabilized copper nanoparticles onto polyimide substrates resulted in metallic copper traces with low electrical resistivities (≥3.6 µΩ cm, or ≥2.2 times the resistivity of bulk copper) after a relatively low-temperature sintering process (200 °C for up to 60 min).
Immunostimulatory DNA: Sequence‐dependent production of potentially harmful or useful cytokines (1997)

Certain bacterial immunostimulatory (i.s.) DNA sequences containing unmethylated CpG motifs stimulate antigen-presenting cells (APC) to express a full complement of costimulatory molecules and to produce cytokines including interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. While IL-12 is key to their T helper cell (Th)1-promoting adjuvant activity, secretion of toxic levels of TNF-alpha is harmful in that it promotes toxic shock. Given the beneficial as well as harmful consequences of i.s. DNA, we investigated the possibility of identifying DNA sequences, i.e. CpG oligodeoxynucleotides (ODN) which differentially activate IL-12 versus TNF-alpha cytokine production in APC. Here, we describe an i.s. DNA sequence with these characteristics. While its potential to induce IL-12 is preserved, its ability to trigger TNF-alpha release is strongly curtailed both in vitro and in vivo. I.s. DNA could be segregated into lethal and non-lethal in a mouse toxic shock model. The non-toxic i.s. DNA was useful as an adjuvant, thus allowing cytotoxic T cell responses to the soluble protein ovalbumin and conferring a resistant Th 1 phenotype to BALB/c mice lethally infected with Leishmania major. This i.s. CpG motif may thus be prototypic for a useful immunostimulating DNA sequence that lacks harmful side effects.
Instrumentation for bedside analysis of swallowing disorders (2010)

Disordered swallowing, or dysphagia, is a common problem seen in patients undergoing treatment for cancer, stroke and neurodegenerative illnesses. This disease is associated with aspiration-induced chest infections. The methods currently used for diagnosis, however, are qualitative or based on expensive equipment. Swallowing accelerometry is a promising low-cost, quantitative and noninvasive tool for the evaluation of swallowing. This work describes the design and application of a bedside instrument able to evaluate swallowing mechanisms and to identify patients at risk of aspiration. Three-axis swallowing accelerometry was used to measure the neck vibrations associated with deglutition, providing analog signals to a virtual instrument developed in LabVIEW environment. In vivo tests in normal subjects as well as tests with disphagic patients showed that the system was able to easily and non-invasively detect changes in the swallowing acceleration pattern associated with increasing values of water volume (p < 0.02) and disphagia. We concluded that the developed system could be a useful tool for the objective bedside evaluation of patients at risk of aspiration.
Nonoperative Dilatation of Coronary-Artery Stenosis (1979)

In percutaneous transluminal coronary angioplasty, a catheter system is introduced through a systemic artery under local anesthesia to dilate a stenotic artery by controlled inflation of a distensible balloon. Over the past 18 months, we have used this technic in 50 patients. The technic was successful in 32 patients, reducing the stenosis from a mean of 84 to 34 per cent (P less than 0.001) and the coronary-pressure gradient from a mean of 58 to 19 mm Hg (P less than 0.001). Twenty-nine patients showed improvement in cardiac function during follow-up examination. Because of acute deterioration in clinical status, emergency bypass was later necessary in five patients; three showed electrocardiographic evidence of infarcts. Patients with single-vessel disease appear to be most suitable for the procedure, and a short history of pain indicates the presence of a soft (distensible) atheroma likely to respond to dilatation. We estimate that only about 10 to 15 per cent of candidates for bypass surgery have lesions suitable for this procedure. A prospective randomized trial will be necessary to evaluate its usefulness in comparison with surgical and medical management.
DNA Integrity in Plasma and Serum of Patients with Malignant and Benign Diseases (2008)

This study aimed to test the diagnostic utility of the DNA integrity index for detection of cancer. Matched serum and plasma samples of 42 patients with various forms of cancer and 17 patients with corresponding benign diseases were analyzed. DNA was isolated from 1 mL serum and plasma using the MagNA Pure LC system. Cell-free DNA was quantified by real-time PCR using the reference gene of the LightCycler t(14;18) kit. Subsequently, the DNA integrity index was calculated as the ratio in relative abundance of 347-bp versus 137-bp PCR products. We found that DNA concentrations were not different in plasma (median: 4.5 ng/mL) and serum (67.1 ng/mL) of patients with benign diseases when compared with values in plasma (5.1 ng/mL) and serum (65.4 ng/mL) of cancer patients. Similarly, the DNA integrity index in plasma (0.38), and serum of patients with benign diseases (0.29) was comparable to values in plasma (0.33) and serum (0.37) of cancer patients. Diagnostic sensitivity of DNA (AUC 0.53) and DNA integrity (AUC 0.45) was poor in plasma, and was increased only slightly by the combination of both (AUC 0.57). In serum, sensitivity of DNA (AUC 0.52) and DNA integrity (AUC 0.64) was higher and was further improved by the combination of both (AUC 0.72) reaching a sensitivity of 30% at 100% specificity. In conclusion, we could not confirm a high diagnostic utility of the DNA integrity index. However, a combination with other markers such as DNA may enhance sensitivity for cancer detection.
Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI (2004)

Recent functional imaging studies have revealed coactivation in a distributed network of cortical regions that characterizes the resting state, or default mode, of the human brain. Among the brain regions implicated in this network, several, including the posterior cingulate cortex and inferior parietal lobes, have also shown decreased metabolism early in the course of Alzheimer's disease (AD). We reasoned that default-mode network activity might therefore be abnormal in AD. To test this hypothesis, we used independent component analysis to isolate the network in a group of 13 subjects with mild AD and in a group of 13 age-matched elderly controls as they performed a simple sensory-motor processing task. Three important findings are reported. Prominent coactivation of the hippocampus, detected in all groups, suggests that the default-mode network is closely involved with episodic memory processing. The AD group showed decreased resting-state activity in the posterior cingulate and hippocampus, suggesting that disrupted connectivity between these two regions accounts for the posterior cingulate hypometabolism commonly detected in positron emission tomography studies of early AD. Finally, a goodness-of-fit analysis applied at the individual subject level suggests that activity in the default-mode network may ultimately prove a sensitive and specific biomarker for incipient AD.
Hereditary colorectal cancer in the general population: from cancer registration to molecular diagnosis (1999)

In this study of cancer genetic epidemiology, data from a tumour registry were analysed and this ultimately led to the identification and selection of families that should be tested for mutator gene mutations. With the use of a population based approach, the incidence of mutations was appreciably lower than previously reported and limited to families with full blown HNPCC. It is possible that in most families with a clinical spectrum of HNPCC (or suspected HNPCC) other DNA mismatch repair genes are involved in the pathogenesis of the disease.
Critical catalytic functional groups in the mechanism of aspartate-β-semialdehyde dehydrogenase (2004)

Aspartate-beta-semialdehyde dehydrogenase (ASADH) catalyzes the reductive dephosphorylation of beta-aspartyl phosphate to L-aspartate-beta-semialdehyde in the aspartate biosynthetic pathway. This pathway is not found in humans or other eukaryotic organisms, yet is required for the production of threonine, isoleucine, methionine and lysine in most microorganisms. The mechanism of this enzyme has been examined through the structures of two active-site mutants of ASADH from Haemophilus influenzae. Replacement of the enzyme active-site cysteine with serine (C136S) leads to a dramatic loss of catalytic activity caused by the expected decrease in nucleophilicity, but also by a change in the orientation of the serine hydroxyl group relative to the cysteine thiolate. In contrast, in the H277N active-site mutant the introduced amide is oriented in virtually the same position as that of the histidine imidazole ring. However, a shift in the position of the bound reaction intermediate to accommodate this shorter asparagine side chain, coupled with the inability of this introduced amide to serve as a proton acceptor, results in a 100-fold decrease in the catalytic efficiency of H277N relative to the native enzyme. These mutant enzymes have the same overall fold and high structural identity to native ASADH. However, small perturbations in the positioning of essential catalytic groups or reactive intermediates have dramatic effects on catalytic efficiency.
TOM, a new aromatic degradative plasmid from Burkholderia (Pseudomonas) cepacia G4 (1995)

Burkholderia (Pseudomonas) cepacia PR1(23) has been shown to constitutively express to toluene catabolic pathway distinguished by a unique toluene ortho-monooxygenase (Tom). This strain has also been shown to contain two extrachromosomal elements of < 70 and > 100 kb. A derivative strain cured of the largest plasmid, PR1(23) Cure, was unable to grow on phenol or toluene as the sole source of carbon and energy, which requires expression of the Tom pathway. Transfer of the larger plasmid from strain G4 (the parent strain inducible for Tom) enabled PR1(23) Cure to grow on toluene or phenol via inducible Tom pathway expression. Conjugal transfer of TOM23c from PR1(23) to an antibiotic-resistant derivative of PR1(23) Cure enabled the transconjugant to grow with either phenol or toluene as the sole source of carbon and energy through constitutive expression of the Tom pathway. A cloned 11.2-kb EcoRI restriction fragment of TOM23c resulted in the expression of both Tom and catechol 2,3-dioxygenase in Escherichia coli, as evidenced by its ability to oxidize trichloroethylene, toluene, m-cresol, o-cresol, phenol, and catechol. The largest resident plasmid of PR1 was identified as the source of these genes by DNA hybridization. These results indicate that the genes which encode Tom and catechol 2,3-dioxygenase are located on TOM, an approximately 108-kb degradative plasmid of B. cepacia G4.
Control of immune responses by savenger liver endothelial cells (2003)

The liver appears to be an organ favoring the induction of immune tolerance rather than immunity. Among the hepatic cell populations possibly involved in regulation of immune responses, liver sinusoidal endothelial cells (LSEC) are well suited to fulfill this role. LSEC are resident cells lining the hepatic sinusoidal wall and therefore are in intimate contact with leukocytes passing through the liver. They are equipped with numerous scavenger receptors rendering antigen-uptake in these cells extremely efficient. Antigen processing and MHC-restricted presentation of exogenous antigens for CD4 as well as CD8 T cells occurs equally with high efficiency. Importantly, CD4 and CD8 T cells that engaged in cognate interaction with LSEC have a tolerant phenotype. Thus LSEC contribute an important immune function to the liver: control of the immune response against circulating soluble antigens.
Architectural strategies for an application-specific synchronous multiprocessor environment (1988)

A multiprocessor architecture is presented that is suited for the customized and automated VLSI realization of complex low-to-medium-speed digital signal processing applications. The proposed architecture is constructed from a set of flexible and parameterizable data paths, a selection of powerful control units (for decision-making tasks), and a number of protocols for fast interprocessor communication. The flexible nature of this system allows for an efficient hardware realization utilizing the inherent parallelism of a particular application. The effectiveness of the approach is substantiated with the synthesis of several test vehicles, such as a pitch-extraction algorithm for speech, in terms of the defined architecture.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Receptor-Mediated Mechanism to Support Clinical Observation of Altered Albumin Variants (2007)

Dolcini et al.(1) recently reported in this journal a novel splice-site mutation (denoted Bartin) that causes deletion of exon 11 in the human serum albumin (HSA) gene, ALB . In spite of their uncertain relevance to pathophysiology of diseases, differences in HSA sequence have interesting correlations with functional properties and stability. Bisalbuminemia (or alloalbuminemia) is a rare inherited or acquired condition characterized by the occurrence of 2 circulating components that are observed, typically, during routine clinical electrophoresis or in genetic surveys.

Over the past decades several cases of genetic polymorphisms, described in peer-reviewed papers and listed in the analbuminemia register(2), have been characterized as representing site-specific mutations, splice-site mutations, or frame-shift mutations. The deletion reported by Dolcini et al.(1) would give rise to a C-terminally truncated HSA variant of 410 amino acids rather than the 585 amino acids …
A phase I trial of recombinant interferon-alpha and alpha-difluoromethylornithine in metastatic melanoma. (1988)

Both interferon-alpha (IFN-alpha) and alpha-difluoromethylornithine (DFMO) have shown modest activity as single-agent therapy in the treatment of malignant melanoma. Several investigators have demonstrated true synergism in vitro of the combination of DFMO and IFN-alpha against human tumor cells, including melanoma. We have investigated this combination in 17 patients with malignant melanoma in a Phase I trial. Patients were treated with 4 or 6 g/m2/day of oral DFMO in 3 divided doses for 11 days, followed by a 3-day rest period. Concomitant administration of 1.5, 3.0, 6.0 or 9.0 x 10(6) U/m2 IFN-alpha intramuscularly was given. The maximum tolerated dose was 4 g/m2/day of DFMO plus 6 x 10(6) U/m2/day of IFN-alpha. Dose-limiting toxicity occurred in 3 of 3 patients receiving 9 x 10(6) U/m2 IFN-alpha and consisted of leukopenia, fatigue, and weight loss. Other toxicities were mild and included reversible hearing loss, diarrhea, nausea, and vomiting. Three responses were seen, including one partial response (PR) of soft tissue metastases, one PR of lung and liver, and one complete response of liver metastases without clearance of carcinomatous meningitis. A Phase II trial has been initiated based on these encouraging results.
Effects of Aggregation of Nuclear-transferred Mouse Embryos Developed from Enucleated Eggs Receiving ES Cells on In Vitro and In Vivo Development. (2002)

Nuclear-transferred mouse eggs receiving embryonic stem cells develop into blastocysts at a high rate, but their potential to develop into fetuses is very low. Therefore, the present study examined the effects of aggregating of two nuclear-transferred eggs at the 8-cell stage to increase the cell number of nuclear-transferred embryos. The proportion of implantation sites on gestational day 10.5 after transfer of aggregated nuclear-transferred embryos (53%) was significantly higher than after single nuclear transfer (29%) or serial nuclear-transfer (37%). The proportion of implantation sites with fetuses did not differ significantly among the three groups (7 to 17%). These results demonstrate that the low potential of nuclear-transferred embryos with embryonic stem cells to develop into fetuses is not due to the lower cell number of nuclear-transferred embryos.
Synthesis of L-Kynurenine peptides conducted without masking the side-chain amino group (1980)

Various free L-kynurenine peptides, including an analogue of the opiate agonist leucine-enkephalin, have been synthesized by using the Na-t- butyloxycarbonyl derivative of L-kynurenine as a key precursor. By selecting appropriate mild conventional coupling procedures it was possible to carry out the synthetic operations without having to mask the side-chain amino group in any way, but intramolecular acylation with formation of a seven-membered lactam could be demonstrated under more vigorous conditions.
ChemInform Abstract: SYNTHESIS OF HOMOHARRINGTONINE AND ITS DERIVATIVE BY PARTIAL ESTERIFICATION OF CEPHALOTAXINE (1983)

Abstract Cyclopropan‐carbonsäureester (I) wird mit Methylgrignardreagenz und HBr zu (II) gespalten und dann über eine Grignardreaktion in die Säure (III) übergeführt, die mit Ameisensäure zu (IV) cyclisiert oder in die Derivate (V) umgewandelt wird.
A perceptually based adaptive sampling algorithm (1998)

A perceptually based approach for selecting image samples has been developed. An existing image processing vision model has been extended to handle color and has been simplified to run efficiently. The resulting new image quality model was inserted into an image synthesis program by first modifying the rendering algorithm so that it computed a wavelet representation. In addition to allowing image quality to be determined as the image was generated, the wavelet representation made it possible to use statistical information about the spatial frequency distribution of natural images to estimate values where samples were yet to be taken. Tests on the image synthesis algorithm showed that it correctly handled achromatic and chromatic spatial detail and that it was able predict and compensate for masking effects. The program was also shown to produce images of equivalent visual quality while using different rendering techniques.