gebhart/patrepeval huggingface dataset:
Responsive Hydrogels from the Intramolecular Folding and Self-Assembly of a Designed Peptide (2002)

A general peptide design is presented that links the pH-dependent intramolecular folding of beta-hairpin peptides to their propensity to self-assemble, affording hydrogels rich in beta-sheet. Chemical responsiveness has been specifically engineered into the material by linking intramolecular folding to changes in solution pH, and mechanical responsiveness, by linking hydrogelation to self-assembly. Circular dichroic and infrared spectroscopies show that at low pH individual peptides are unstructured, affording a low-viscosity aqueous solution. Under basic conditions, intramolecular folding takes place, affording amphiphilic beta-hairpins that intermolecularly self-assemble. Rheology shows that the resulting hydrogel is rigid but is shear-thinning. However, quick mechanical strength recovery after cessation of shear is observed due to the inherent self-assembled nature of the scaffold. Characterization of the gelation process, from the molecular level up through the macroscopic properties of the material, suggests that by linking the intramolecular folding of small designed peptides to their ability to self-assemble, responsive materials can be prepared. Cryo-transmission electron and laser scanning confocal microscopies reveal a water-filled porous scaffold on both the nano- and microscale. The environmental responsiveness, morphology, and peptidic nature make this hydrogel a possible material candidate for biomedical and engineering technology.
RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells (2012)

Homologous recombination serves multiple roles in DNA repair that are essential for maintaining genomic stability. We here describe RI-1, a small molecule that inhibits the central recombination protein RAD51. RI-1 specifically reduces gene conversion in human cells while stimulating single strand annealing. RI-1 binds covalently to the surface of RAD51 protein at cysteine 319 that likely destabilizes an interface used by RAD51 monomers to oligomerize into filaments on DNA. Correspondingly, the molecule inhibits the formation of subnuclear RAD51 foci in cells following DNA damage, while leaving replication protein A focus formation unaffected. Finally, it potentiates the lethal effects of a DNA cross-linking drug in human cells. Given that this inhibitory activity is seen in multiple human tumor cell lines, RI-1 holds promise as an oncologic drug. Furthermore, RI-1 represents a unique tool to dissect the network of reaction pathways that contribute to DNA repair in cells.
A CMOS pulse-shrinking delay element for time interval measurement (2000)

A deep sub-nanosecond resolved CMOS pulse-shrinking delay element used in the time-to-digital converter (TDC) is proposed. The pulse shrinking capability of the element is controlled by the dimension ratio of the adjacent gates. This control mechanism is completely different from the bias adjustment adopted in the conventional pulse-shrinking element. Without the need of continuous calibration, the presented element possesses not only extremely fine resolution, small single-shot errors, low power consumption, but also good insensitivity to the supply voltage variation. Being fabricated with 0.35 /spl mu/m CMOS technologies, the TDC made of the new elements has been measured to have a resolution of 68 ps. The effective resolution only varies 1.5 ps for a rather large supply voltage range from 3.5 to 4.5 V. The size of the circuit is 0.35 mm/spl times/0.09 mm only, excluding the I/O pads. Under a single 3.3-V power supply, the static power dissipation, including the I/O pads, is 1 /spl mu/W. The average power consumption is measured to be merely 1.2 mW under a measurement rate of 100 ksps.
In Vitro and in Vivo Regulation of Human Tumor Antigen Expression by Human Recombinant Interferons: A Review (1994)

The ongoing development of monoclonal antibody technology may eventually lead to the selective targeting of human carcinoma lesions by MAbs conjugated with a variety of cytotoxic agents (i.e., radionuclides, drugs, etc.). The antigen phenotype of the carcinoma cell will play an important role in the efficacy of the MAbs. Clearly, the human tumor antigens that are expressed on all carcinoma cells, and with a high antigen density, should provide the optimal target for the MAbs. More often than not, however, the human tumor antigens whose expression is highly selective for human tumor cells will also exhibit a certain degree of heterogeneity. Therefore, the ability of interferon to augment the level of expression of human tumor antigens such as TAG-72 and CEA, may play an important role in an adjuvant setting for immunoscintigraphy and/or immunotherapy. More recent observations have demonstrated that interferon treatment can also enhance the amount of TAG-72 and CEA secreted by the tumor cell. The ability of interferon to enhance the shedding of both TAG-72 and CEA could be of particular importance since recent reports suggest that their presence in the sera of patients diagnosed with gastrointestinal adenocarcinoma may be complementary and that the ability to increase either marker may facilitate earlier diagnosis of recurrent disease. It is conceivable that in subsequent years effective approaches to monitoring and/or treating malignancies may include a new combination of biological/immunological therapy.
Isolation and characterization of urokinase from human plasma. (1982)

The presence of activators of the fibrinolytic system in blood plasma has been assumed for a long time but never convincingly documented by the isolation of characterized and physiologically plausible enzymes. The low catalytic efficiency of previously identified plasma plasminogen activators, which has made their physiological significance uncertain, prompted us to search for other plasma enzymes, resembling especially the potent urinary activator, urokinase. We report here the detection of a urokinase-like activity in human plasma, and the isolation of the enzyme from whole plasma protein fractions. The purified enzyme is indistinguishable from the 53,000-dalton components of human urinary urokinase in the following respects: apparent Mr on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, double immunodiffusion, amino acid analysis, two-dimensional tryptic peptide maps, catalytic efficiency with synthetic peptide substrates, and inhibitor spectrum. The results suggest (a) that the enzyme is present in plasma in a latent form whose nature remains to be defined, and (b) that the circulating concentration is at least 5 to 10 microgram/liter, and sufficient to generate substantial levels of plasmin, particularly if activation were somehow confined by localization at specific sites.
Synthesis and activity of a potent N-methyl-D-aspartic acid agonist, trans-1-aminocyclobutane-1,3-dicarboxylic acid, and related phosphonic and carboxylic acids (1990)

We report the synthesis of a series of 3-carboxy-, 3-(carboxymethyl)-, 3-(omega-phosphonoalkyl)-1-aminocyclobutane-1-carboxylic acids for evaluation as agonists or antagonists of neurotransmission at excitatory amino acid receptors, particularly N-methyl-D-aspartic acid (NMDA) receptors. The compounds were evaluated as agonists on their ability to depolarize the rat brain cortical wedge preparation or as antagonist of the actions of the selective agonists NMDA, quisqualic acid, and kainic acid. The chain-elongated glutamate derivatives with potential antagonist activity proved to be weak and frequently nonselective antagonists in this assay. The most noteworthy result was that trans isomer 7b was a very potent agonist, approximately 20 times more active than NMDA at NMDA receptors, while the cis isomer was 1/3 as potent as NMDA.
HSF-1 Interacts with Ral-binding Protein 1 in a Stress-responsive, Multiprotein Complex with HSP90 in Vivo (2003)

Heat shock factor 1 (HSF1) regulates the rapid and transient expression of heat shock genes in response to stress. The transcriptional activity of HSF1 is tightly controlled, and under physiological growth conditions, the HSF1 monomer is in a heterocomplex with the molecular chaperone HSP90. Through unknown mechanisms, transcriptionally repressed HSF1.HSP90 heterocomplexes dissociate following stress, which triggers HSF1 activation and heat shock gene transcription. Using a yeast two-hybrid screening system, we have identified Ral-binding protein 1 (RalBP1) as an additional HSF1-interacting protein. We show that RalBP1 and HSF1 interact in vivo, and transient cotransfection of HSF1 and RalBP1 into hsf1(-/-) mouse embryo fibroblasts represses HSP70 expression. Furthermore, transient cotransfection of HSF1 and the constitutively active form of RalA (RalA23V), an upstream activator of the RalBP1 signaling pathway, increases the heat-inducible expression of HSP70, whereas the dominant negative form (RalA28N) suppresses HSP70 expression. We further find that alpha-tubulin and HSP90 are also present in the RalBP1.HSF1 heterocomplexes in unstressed cells. Upon heat shock, the Ral signaling pathway is activated, and the resulting RalGTP binds RalBP1. Concurrently, HSF1 is activated, leaves the RalBP1 x HSF1 x HSP90 x alpha-tubulin heterocomplexes, and translocates into the nucleus, where it then activates transcription. In conclusion, these observations reveal that the RalGTP signal transduction pathway is critical for activation of the stress-responsive HSF1 and perhaps HSP90 molecular chaperone system.
Validation of two models to estimate the probability of malignancy in patients with solitary pulmonary nodules (2007)

Two existing prediction models are sufficiently accurate to guide decisions about the selection and interpretation of subsequent diagnostic tests in patients with SPNs, although clinicians should also consider the prevalence of malignancy in their practice setting when choosing a model.
SYMPATHETIC SKIN RESPONSE IN PATIENTS WITH MULTIPLE SCLEROSIS COMPARED WITH PATIENTS WITH SPINAL CORD TRANSECTION AND NORMAL CONTROLS (1991)

In 28 patients with definite multiple sclerosis (MS) and 21 patients with a functionally complete transection of the spinal cord sympathetic skin responses (SSR) from both the palms and soles were studied. In the patients with a complete transection at T3 or 4, SSRs were impaired in the palms as well as the soles, and most patients with a transection at T11 or T12 had normal SSRs in the soles. These findings indicate that the central pathway mediating the SSR descends to the upper thoracic cord where connections are made with the sympathetic distribution to the palms, and then to the lower thoracic cord to reach the sympathetic outflow to the soles. This is compatible with the anatomical knowledge of the sympathetic system. Of the MS patients, 75% had abnormal SSR results. The SSR for the soles was more sensitive than that for the palms. The incidence of SSR abnormality was as high as those of somatosensory evoked potential (SEP) (79%) and visual evoked potential (VEP) (75%) abnormalities. Of the patients with normal SEPs 14% had impaired SSRs and 21% had abnormal SSR with normal VEPs. When the results of these 3 tests were combined, the abnormality increased to 100%. From our study, the SSR probably reflects not only postganglionic sympathetic activity but also preganglionic function. The SSR is therefore useful in evaluating myelopathy, providing information different from that given by assessment of the somatic nervous system. Since the SSR detected a few MS lesions which were not demonstrated by other evoked potentials, it is potentially a new tool for the detection of MS lesions in addition to conventional evoked potential studies.
The fourth immunoglobulin-like domain of NCAM contains a carbohydrate recognition domain for oligomannosidic glycans implicated in association with L1 and neurite outgrowth. (1993)

We have previously shown that the neural adhesion molecules L1 and NCAM interact with each other to form a complex which binds more avidly to L1 than L1 to L1 alone (Kadmon, G., A. Kowitz, P. Altevogt, and M. Schachner. 1990a. J. Cell Biol. 110:193-208). This cis-association between L1 and NCAM is carbohydrate-dependent (Kadmon, G., A. Kowitz, P. Altevogt, and M. Schachner. 1990b. J. Cell Biol. 110:209-218). In the present study, we report that L1 and NCAM bind to each other via oligomannosidic carbohydrates expressed by L1, but not by NCAM, as shown in several experiments: (a) complex formation between L1 and NCAM is inhibited by a mAb to oligomannosidic carbohydrates and by the oligosaccharides themselves; (b) NCAM binds to oligomannosidic carbohydrates; (c) within the L1/NCAM complex, the oligomannosidic carbohydrates are hidden from accessibility to a mAb against oligomannosidic carbohydrates; (d) the recombinant protein fragment of NCAM containing the immunoglobulin-like domains and not the fragment containing the fibronectin type III homologous repeats binds to oligomannosidic glycans. Furthermore, the fourth immunoglobulin-like domain of NCAM shows sequence homology with carbohydrate recognition domains of animal C-type lectins and, surprisingly, also with plant lectins. A peptide comprising part of the C-type lectin consensus sequence in the fourth immunoglobulin-like domain of NCAM interferes with the association between L1 and NCAM. The functional importance of oligomannosidic glycans at the cell surface was shown for neurite outgrowth in vitro. When neurons from early postnatal mouse cerebellum were maintained on laminin or poly-L-lysine, neurite outgrowth was inhibited by oligomannosidic glycans, by glycopeptides, glycoproteins, or neoglycolipids containing oligomannosidic glycans, but not by nonrelated oligosaccharides or oligosaccharide derivates. Neurite outgrowth was also inhibited by the peptide comprising part of the C-type lectin consensus sequence in the fourth immunoglobulin-like domain of NCAM. The combined results suggest that carbohydrate-mediated cis-associations between adhesion molecules at the cell surface modulate their functional properties.
Do Lithium and Anticonvulsants Target the Brain Arachidonic Acid Cascade in Bipolar Disorder? (2002)

These results give rise to the hypothesis that lithium and antimanic anticonvulsants act by targeting parts of the "arachidonic acid cascade," which may be functionally hyperactive in mania. Thus, drugs that target enzymes in the cascade, such as cyclooxygenase 2 inhibitors, might be candidate treatments for mania. Also, in view of competition between arachidonic and docosahexaenoic acids in a number of functional processes, docosahexaenoic acid or its precursors would be expected to be therapeutic. Neither of these predictions is evident from other current hypotheses for the antimanic action of lithium and anticonvulsant drugs.
Fetal origins of coronary heart disease (1995)

The fetal origins hypothesis states that fetal undernutrition in middle to late gestation, which leads to disproportionate fetal growth, programmes later coronary heart disease. Animal studies have shown that undernutrition before birth programmes persisting changes in a range of metabolic, physiological, and structural parameters. Studies in humans have shown that men and women whose birth weights were at the lower end of the normal range, who were thin or short at birth, or who were small in relation to placental size have increased rates of coronary heart disease. We are beginning to understand something of the mechanisms underlying these associations. The programming of blood pressure, insulin responses to glucose, cholesterol metabolism, blood coagulation, and hormonal settings are all areas of active research.
NCBI BLAST: a better web interface (2008)

Basic Local Alignment Search Tool (BLAST) is a sequence similarity search program. The public interface of BLAST, http://www.ncbi.nlm.nih.gov/blast, at the NCBI website has recently been reengineered to improve usability and performance. Key new features include simplified search forms, improved navigation, a list of recent BLAST results, saved search strategies and a documentation directory. Here, we describe the BLAST web application's new features, explain design decisions and outline plans for future improvement.
Clinical and Radiographic Findings in Adults With Persistent Hypophosphatasemia (2014)

A serum alkaline phosphatase value below the age-adjusted lower limits of normal (hypophosphatasemia) is uncommonly encountered in clinical practice. The electronic and paper medical records of 885,165 patients treated between 2002 and 2012 at a large, rural, multispecialty health clinic were interrogated to estimate the prevalence and characterize the clinical and radiographic findings of adults whose serum alkaline phosphatase was almost always low (persistent hypophosphatasemia). We hypothesized that some of these patients might harbor previously unrecognized hypophosphatasia, a rare, inherited condition of impaired mineralization of bones and teeth. Persistent hypophosphatasemia (serum alkaline phosphatase ≤ 30 IU/L) was found in 1 of 1544 adult patients. These adult patients had more crystalline arthritis, orthopedic surgery, chondrocalcinosis, calcific periarthritis, enthesopathy, and diffuse idiopathic skeletal hyperostosis than a general adult patient population. A gender effect was observed. The clinical and radiographic findings of adult patients with persistent hypophosphatasemia resemble those of the adult form of hypophosphatasia. Clinicians should take notice of persistent hypophosphatasemia, consider the diagnosis of hypophosphatasia, and be cautious when considering potent anti-remodeling therapy in these adults. This population warrants further evaluation.
Deep Learning Approach to Semantic Segmentation in 3D Point Cloud Intra-oral Scans of Teeth (2018)

Accurate segmentation of data, derived from intra-oral scans (IOS), is a crucial step in a computer-aided design (CAD) system for many clinical tasks, such as implantology and orthodontics in modern dentistry. In order to reach the highest possible quality, a segmentation model may process a point cloud derived from an IOS in its highest available spatial resolution, especially for performing a valid analysis in finely detailed regions such as the curvatures in border lines between two teeth. In this paper, we propose an end-to-end deep learning framework for semantic segmentation of individual teeth as well as the gingiva from point clouds representing IOS. By introducing a non-uniform resampling technique, our proposed model is trained and deployed on the highest available spatial resolution where it learns the local fine details along with the global coarse structure of IOS. Furthermore, the point-wise cross-entropy loss for semantic segmentation of a point cloud is an ill-posed problem, since the relative geometrical structures between the instances (e.g. the teeth) are not formulated. By training a secondary simple network as a discriminator in an adversarial setting and penalizing unrealistic arrangements of assigned labels to the teeth on the dental arch, we improve the segmentation results considerably. Hence, a heavy post-processing stage for relational and dependency modeling (e.g. iterative energy minimization of a constructed graph) is not required anymore. Our experiments show that the proposed approach improves the performance of our baseline network and outperforms the state-of-the-art networks by achieving 0.94 IOU score.
Algorithmic methods to infer the evolutionary trajectories in cancer progression (2016)

The genomic evolution inherent to cancer relates directly to a renewed focus on the voluminous next-generation sequencing data and machine learning for the inference of explanatory models of how the (epi)genomic events are choreographed in cancer initiation and development. However, despite the increasing availability of multiple additional -omics data, this quest has been frustrated by various theoretical and technical hurdles, mostly stemming from the dramatic heterogeneity of the disease. In this paper, we build on our recent work on the "selective advantage" relation among driver mutations in cancer progression and investigate its applicability to the modeling problem at the population level. Here, we introduce PiCnIc (Pipeline for Cancer Inference), a versatile, modular, and customizable pipeline to extract ensemble-level progression models from cross-sectional sequenced cancer genomes. The pipeline has many translational implications because it combines state-of-the-art techniques for sample stratification, driver selection, identification of fitness-equivalent exclusive alterations, and progression model inference. We demonstrate PiCnIc's ability to reproduce much of the current knowledge on colorectal cancer progression as well as to suggest novel experimentally verifiable hypotheses.
Sensor-to-Digital Interface Built Entirely With Carbon Nanotube FETs (2013)

Low-power applications, such as sensing, are becoming increasingly important and demanding in terms of minimizing energy consumption, driving the search for new and innovative interface architectures and technologies. Carbon nanotube FETs (CNFETs) are excellent candidates for further energy reduction, as CNFET-based digital circuits are projected to achieve an order of magnitude improvement in energy-delay product compared with silicon-CMOS at highly scaled technology nodes. However, carbon nanotubes (CNTs) are inherently subject to imperfections and variations such as those induced by mispositioned and metallic CNTs. These substantial imperfections and variations have prevented the demonstration of complex CNFET circuits until now. This paper presents the first demonstration of a subsystem, which is a complete capacitive sensor interface circuit, implemented entirely using CNFETs that can be fabricated reproducibly in a VLSI-compatible fashion. This is made possible by: 1) a digitally oriented interface architecture and 2) the imperfection-immune design paradigm, which combines design and processing techniques to successfully overcome CNT imperfections and variations. In addition to electrical measurements, we demonstrate correct operation of our CNFET circuitry by interfacing it with a sensor used to control a handshaking robot.
Messenger RNA Turnover in Eukaryotes: Pathways and Enzymes (2004)

The control of mRNA degradation is an important component of the regulation of gene expression since the steady-state concentration of mRNA is determined both by the rates of synthesis and of decay. Two general pathways of mRNA decay have been described in eukaryotes. Both pathways share the exonucleolytic removal of the poly(A) tail (deadenylation) as the first step. In one pathway, deadenylation is followed by the hydrolysis of the cap and processive degradation of the mRNA body by a 5' exonuclease. In the second pathway, the mRNA body is degraded by a complex of 3' exonucleases before the remaining cap structure is hydrolyzed. This review discusses the proteins involved in the catalysis and control of both decay pathways.