gebhart/patrepeval huggingface dataset:
Pulmonary Arterial Hypertension (2019)

The high prevalence of pulmonary arterial hypertension (PAH) in patients with obstructive sleep apnea (OSA) and the putative pathophysiologic connections have been extensively documented. Conversely, patients with established PAH are at risk for sleep-related ventilatory instability, including OSA, central sleep apnea, and nocturnal desaturations. This chapter reviews the prevalence and pathophysiologic interactions of these conditions, the interplay with associated disorders, and the effects of continuous positive airway pressure therapy on pulmonary hemodynamics. In patients with OSA, chronic effects of repetitive hypoxia as well as comorbidities, including chronic obstructive pulmonary disease and left-sided heart dysfunction, play a role in promoting pulmonary hypertension. Sleep disordered breathing, representing a spectrum of sleep-related breathing disorders inclusive of OSA, is highly prevalent among patients with established pulmonary hypertension. Obstructive events, central sleep apnea, and nocturnal hypoxia are within the spectrum of sleep-related breathing disorders in pulmonary hypertension. The mechanisms for these associations remain speculative.
Online recognition of freely handwritten Japanese characters using directional feature densities (2003)

The authors propose an online handwritten Japanese character recognition method permitting both stroke number and stroke order variations. The method is based on the pattern matching technique. Matching is done by the multiple similarity method using directional feature densities, which are independent of both stroke number and stroke order. This method has achieved a good recognition rate, 91%, for 2965 freely written Japanese kanji characters.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Ultrastable Substrates for Surface-Enhanced Raman Spectroscopy:  Al2O3 Overlayers Fabricated by Atomic Layer Deposition Yield Improved Anthrax Biomarker Detection (2006)

A new method to stabilize and functionalize surfaces for surface-enhanced Raman spectroscopy (SERS) is demonstrated. Atomic layer deposition (ALD) is used to deposit a sub-1-nm alumina layer on silver film-over-nanosphere (AgFON) substrates. The resulting overlayer maintains and stabilizes the SERS activity of the underlying silver while presenting the surface chemistry of the alumina overlayer, a commonly used polar adsorbent in chromatographic separations. The relative affinity of analytes for alumina-modified AgFON substrates can be determined by their polarity. On the basis of SERS measurements, dipicolinic acid displays the strongest binding to the ALD alumina-modified AgFON among a set of pyridine derivatives with varying polarity. This strong affinity for carboxylate groups makes the SERS substrate an ideal candidate for bacillus spores detection using the dipicolinate biomarker. The SERS signal from extracted dipicolinate was measured over the spore concentration range 10(-14)-10(-12) M to determine the saturation binding capacity of the alumina-modified AgFON surface. The adsorption constant was determined to be Kspore = 9.0 x 10(13) M(-1). A 10-s data collection time is capable of achieving a limit of detection of approximately 1.4 x 10(3) spores. The shelf life of prefabricated substrates is at least 9 months prior to use. In comparison to the bare AgFON substrates, the ALD-modified AgFON substrates demonstrate twice the sensitivity with 6 times shorter data acquisition time and 7 times longer temporal stability. ALD expands the palette of available chemical methods to functionalize SERS substrates, which will enable improved and diverse chemical control over the nature of analyte-surface binding for biomedical, homeland security, and environmental applications.
Maf and Nrl can bind to AP-1 sites and form heterodimers with Fos and Jun. (1994)

The c-maf proto-oncogene and the neural retina specific gene nrl encode members of a new bZIP protein subfamily. We have examined the dimerization and DNA binding properties of this new protein family using polypeptides encompassing the leucine zipper and basic regions. Purified polypeptides bound specifically to the AP-1 and CRE sites as well as to variants of the AP-1 site. Maf and Nrl were also able to form heterodimers with Fos and Jun in vitro. All pairwise combinations of Maf, Nrl, Fos and Jun could be co-immunoprecipitated by antisera directed against either subunit. Heterodimers among these proteins bound to the AP-1 site, although with different affinities. Mutations in the leucine zipper dimerization interface or in the basic DNA contact region inhibited heterodimer formation and binding to the AP-1 site. These results indicate that Maf and Nrl together with Fos and Jun family proteins form a bZIP protein superfamily whose members can form an array of heterodimers that have overlapping DNA binding specificities.
OBLIQUE MULTI-CAMERA SYSTEMS – ORIENTATION AND DENSE MATCHING ISSUES (2014)

Abstract. The use of oblique imagery has become a standard for many civil and mapping applications, thanks to the development of airborne digital multi-camera systems, as proposed by many companies (Blomoblique, IGI, Leica, Midas, Pictometry, Vexcel/Microsoft, VisionMap, etc.). The indisputable virtue of oblique photography lies in its simplicity of interpretation and understanding for inexperienced users allowing their use of oblique images in very different applications, such as building detection and reconstruction, building structural damage classification, road land updating and administration services, etc. The paper reports an overview of the actual oblique commercial systems and presents a workflow for the automated orientation and dense matching of large image blocks. Perspectives, potentialities, pitfalls and suggestions for achieving satisfactory results are given. Tests performed on two datasets acquired with two multi-camera systems over urban areas are also reported.
Synthesis and evaluation of inhibitors of E. coli PgaB, a polysaccharide de-N-acetylase involved in biofilm formation (2012)

Many medically important biofilm forming bacteria produce similar polysaccharide intercellular adhesins (PIA) consisting of partially de-N-acetylated β-(1 → 6)-N-acetylglucosamine polymers (dPNAG). In Escherichia coli, de-N-acetylation of the β-(1 → 6)-N-acetylglucosamine polymer (PNAG) is catalysed by the carbohydrate esterase family 4 deacetylase PgaB. The de-N-acetylation of PNAG is essential for productive PNAG-dependent biofilm formation. Here, we describe the development of a fluorogenic assay to monitor PgaB activity in vitro and the synthesis of a series of PgaB inhibitors. The synthesized inhibitors consist of a metal chelating functional group on a glucosamine scaffold to target the active site metal ion of PgaB. Optimal inhibition was observed with N-thioglycolyl amide (K(i) = 480 μM) and N-methyl-N-glycolyl amide (K(i) = 320 μM) glucosamine derivatives. A chemoenzymatic synthesis of an N-thioglycolyl amide PNAG pentasaccharide led to an inhibitor with an improved K(i) of 280 μM.
Epitope‐specificity of recombinant antibodies reveals promiscuous peptide‐binding properties (2012)

Protein-peptide interactions are a common occurrence and essential for numerous cellular processes, and frequently explored in broad applications within biology, medicine, and proteomics. Therefore, understanding the molecular mechanism(s) of protein-peptide recognition, specificity, and binding interactions will be essential. In this study, we report the first detailed analysis of antibody-peptide interaction characteristics, by combining large-scale experimental peptide binding data with the structural analysis of eight human recombinant antibodies and numerous peptides, targeting tryptic mammalian and eukaryote proteomes. The results consistently revealed that promiscuous peptide-binding interactions, that is, both specific and degenerate binding, were exhibited by all antibodies, and the discovery was corroborated by orthogonal data, indicating that this might be a general phenomenon for low-affinity antibody-peptide interactions. The molecular mechanism for the degenerate peptide-binding specificity appeared to be executed through the use of 2-3 semi-conserved anchor residues in the C-terminal part of the peptides, in analogue to the mechanism utilized by the major histocompatibility complex-peptide complexes. In the long-term, this knowledge will be instrumental for advancing our fundamental understanding of protein-peptide interactions, as well as for designing, generating, and applying peptide specific antibodies, or peptide-binding proteins in general, in various biotechnical and medical applications.
Ligand-Dependent Regulation of Plasmid-Based Transgene Expression in Vivo (1999)

As gene therapy advances, the ability to regulate transgene expression will become paramount for safety and efficacy. In this study, we investigate the ability of the mifepristone-dependent GeneSwitch system to regulate the expression of trangenes delivered to mice by nonviral methods. Two plasmids, one encoding the chimeric GeneSwitch protein, the other an inducible transgene for secreted human placental alkaline phosphatase (SEAP), were delivered to the hind-limb muscles of adult mice. Modulation of the level of secretion of the transgene product into serum was achieved by intraperitoneal administration of low doses of the drug mifepristone (MFP). The EC50 for induction of transgene expression by MFP was 0.03 +/- 0.005 mg/kg. The maximal level of transgene expression after induction was equal to or higher than that displayed by a plasmid driven by the CMV enhancer/promoter. The average magnitude of induction was 14- to 19-fold. Multiple rounds of drug-dependent regulation of transgene expression in vivo were demonstrated. In BALB/c mice, the ability to regulate transgene expression persisted for approximately 3 weeks, until the appearance of neutralizing antibodies to the secreted transgene product. In immune-deficient mice, the ability to repetitively regulate transgene expression persisted for at least 5 weeks. Although the dynamic range of regulation needs improvement, the plasmid-based GeneSwitch system has features that are attractive for gene therapy applications.
Monoamine oxidase inhibitors: potential for drug abuse. (1976)

Both the amphetamines and MAO inhibitors share common clinical and pharmacological properties, namely, (i) to clinically induce euphoriant-stimulating type and psychotomimetic effects in certain individuals, and (ii) to increase, albeit by different mechanisms, the amount of functionally available neurotransmitter (catecholamines and indoleamines) at the receptor site. The present data now indicate that, like the amphetamines, the use of MAO inhibitors can be clinically associated with dependence-tolerance. Perhaps these clinical findings will converge with other clinical-biochemical data in helping to define the specific amine(s) responsible for not only the clinical effects of these drugs but also the etiopathogenesis of major psychiatric illnesses such as the affective disorders and schizophrenia.
A fully distributed routing control scheme in an ATM switch (1990)

The authors discuss a fully distributed routing control scheme, called the flooding technique to be applied to an ATM (asynchronous transfer mode) switch architecture for setting up CBO (continuous bit stream oriented) calls. The aim of the flooding technique is to find, in a completely distributed fashion, an available path (between the source and destination line units) through the switching fabric in order to route the cells belonging to a CBO call. The main advantages of this technique in obtaining a centralized solution are improvements in system performance and fault tolerance and a greater flexibility in case the system grows. The switch architecture and its mode of operation are also described. In particular, the different strategies for handling CBO and nonisochronous classes of traffic are presented and some properties on the topology of switching fabric are given.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Role of Phenylalanine at Position 6 in Glucagon's Mechanism of Biological Action:  Multiple Replacement Analogues of Glucagon (1997)

Extensive evidence gathered from structure-activity relationship analysis has identified and confirmed specific positions in the glucagon sequence that are important either for binding to its receptor or for signal transduction. Fifteen glucagon analogues have been designed and synthesized by incorporating structural changes in the N-terminal region of glucagon, in particular histidine-1, phenylalanine-6, and aspartic acid-9. This investigation was conducted to study the role of phenylalanine at position 6 on the glucagon mechanism of action. These glucagon analogues have been made by either deleting or substituting hydrophobic groups, hydrophilic groups, aromatic amino acids, or a D-phenylalanine residue at this position. The structures of the new analogues are as follows: [des-His1, des-Phe6, Glu9]glucagon-NH2 (1); [des-His1,Ala6,Glu9]glucagon-NH2 (2); [des-His1,Tyr6,Glu9]glucagon-NH2 (3); [des-His1,Trp6,Glu9]-glucagon-NH2 (4); [des-His1,D-Phe6,Glu9]glucagon-NH2 (5); [des-His1,Nle6,Glu9]glucagon-NH2 (6); [des-His1,Asp6,Glu9]glucagon-NH2 (7); [des-His1,des-Gly4,Glu9]glucagon-NH2 (8); [desPhe6,-Glu9]glucagon-NH2 (9); [des-Phe6]glucagon-NH2 (10); [des-His1, des-Phe6]glucagon-NH2 (11); [des-His1, des-Phe6,Glu9]glucagon (12); [des-Phe6,Glu9]glucagon (13); [des-Phe6]glucagon (14); and [des-His1, des-Phe6]glucagon (15). The receptor binding potencies IC50 values are 48 (1), 126 (2), 40 (3), 19 (4), 100 (5), 48 (6), 2000 (7), 52 (8), 113 (9), 512 (10), 128 (11), 1000 (12), 2000 (13), 500 (14), and 200 nM (15). All analogues were found to be antagonists unable to activate the adenylate cyclase system even at concentrations as high as 10(-5) M except for analogues 6 and 8, which were found to be weak partial agonists/partial antagonists with maximum stimulation between 6-12%. In competitive inhibition experiments, all the analogues caused a right shift of the glucagon-stimulated adenylate cyclase dose-response curve. The pA2 values were 8.20 (1), 6.40 (2), 6.20 (3), 6.25 (4), 6.30 (5), 6.30 (7), 6.05 (8), 6.20 (9), 6.30 (10), 6.25 (11), 6.10 (12), 6.20 (13), 6.20 (14), and 6.35 (15).
In vivo and in vitro activity of an immunoglobulin Fc fragment (Fcab) with engineered Her‐2/neu binding sites (2014)

Antigen-binding Fc fragments (Fcabs) are a new unique class of immunotherapeutics. They are small (50 kD) fully functional antibody alternatives that bind antigen and elicit effector functions such as antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity. Since Fcabs carry the natural FcRn binding site of antibodies, they have very favorable pharmacokinetics. We showed recently that Fcab H10-03-6 is a high-affinity binder of Her-2/neu (ErbB2/neu) mediating killing of Her-2/neu-overexpressing tumor cells in the presence of immune effector cells, strongly suggesting that the mechanism of killing is due to ADCC. The present study further confirms ADCC as the mechanism by which H10-03-6 mediates tumor cell killing, since H10-03-6 was shown to interact simultaneously with Her-2/neu and the Fc receptor CD16a. The epitope recognized by H10-03-6 overlaps with that of the clinically used monoclonal antibody trastuzumab. However, unlike trastuzumab, Fcab H10-03-6 did not inhibit proliferation of human tumor cells in vitro even under conditions favoring Her-2/neu crosslinking. Treatment of mice harboring human BT-474 cell xenograft tumors with Fcab H10-03-6 led to statistically significant retardation of tumor growth. For the first time, in vivo properties of an Fcab are presented, supporting the view that Fcabs could become highly efficacious immunotherapeutics for human use.
Metabolic Pathways for Cytotoxic End Product Formation from Glutamate- and Aspartate-Containing Peptides by Porphyromonas gingivalis (2000)

Metabolic pathways involved in the formation of cytotoxic end products by Porphyromonas gingivalis were studied. The washed cells of P. gingivalis ATCC 33277 utilized peptides but not single amino acids. Since glutamate and aspartate moieties in the peptides were consumed most intensively, a dipeptide of glutamate or aspartate was then tested as a metabolic substrate of P. gingivalis. P. gingivalis cells metabolized glutamylglutamate to butyrate, propionate, acetate, and ammonia, and they metabolized aspartylaspartate to butyrate, succinate, acetate, and ammonia. Based on the detection of metabolic enzymes in the cell extracts and stoichiometric calculations (carbon recovery and oxidation/reduction ratio) during dipeptide degradation, the following metabolic pathways were proposed. Incorporated glutamylglutamate and aspartylaspartate are hydrolyzed to glutamate and aspartate, respectively, by dipeptidase. Glutamate is deaminated and oxidized to succinyl-coenzyme A (CoA) by glutamate dehydrogenase and 2-oxoglutarate oxidoreductase. Aspartate is deaminated into fumarate by aspartate ammonia-lyase and then reduced to succinyl-CoA by fumarate reductase and acyl-CoA:acetate CoA-transferase or oxidized to acetyl-CoA by a sequential reaction of fumarase, malate dehydrogenase, oxaloacetate decarboxylase, and pyruvate oxidoreductase. The succinyl-CoA is reduced to butyryl-CoA by a series of enzymes, including succinate-semialdehyde dehydrogenase, 4-hydroxybutyrate dehydrogenase, and butyryl-CoA oxidoreductase. A part of succinyl-CoA could be converted to propionyl-CoA through the reactions initiated by methylmalonyl-CoA mutase. The butyryl- and propionyl-CoAs thus formed could then be converted into acetyl-CoA by acyl-CoA:acetate CoA-transferase with the formation of corresponding cytotoxic end products, butyrate and propionate. The formed acetyl-CoA could then be metabolized further to acetate.
Half-Baked Cookies (2016)

Modern websites use multiple authentication cookies to allow visitors to the site different levels of access. The complexity of modern web applications can make it difficult for a web application programmer to ensure that the use of authentication cookies does not introduce vulnerabilities. Even when a programmer has access to all of the source code, this analysis can be challenging; the problem becomes even more vexing when web programmers cobble together off-the-shelf libraries to implement authentication. We have assembled a checklist for modern web programmers to verify that the cookie based authentication mechanism is securely implemented. Then, we developed a tool, Newton, to help a web application programmer to identify authentication cookies for specific parts of the website and to verify that they are securely implemented according to the checklist. We used Newton to analyze 149 sites, including the Alexa top-200 and many other popular sites across a range of categories including search, shopping, and finance. We found that 113 of them---including high-profile sites such as Yahoo, Amazon, and Fidelity---were vulnerable to hijacking attacks. Many websites have already acknowledged and fixed the vulnerabilities that we found using Newton and reported to them.
Interaction of CD2 with its ligand, LFA-3, in human T cell proliferation. (1988)

Recently, it has been demonstrated that lymphocyte function-associated Ag (LFA-3) is a natural ligand for CD2 and that this receptor-ligand interaction functions in cell-cell adhesion. In this report, we demonstrate that LFA-3 plays a role in T cell activation. L cells were transfected with human genomic DNA and sorted for expression of LFA-3. We demonstrate that LFA-3+ L cells, together with anti-CD3 mAb or with suboptimal doses of PHA, stimulate proliferation of human peripheral blood T cells. Furthermore, thymocyte proliferation was induced by LFA-3+ L cells and suboptimal doses of PHA. Proliferation was inhibited by mAb directed against either CD2 or LFA-3. Stimulation of thymocytes by the combination of PHA and LFA-3+ L cells resulted in the increased expression of the IL-2R, as well as of the surface Ag 4F2, transferrin receptor, and HLA-DR. These data support the conclusion that LFA-3 plays a role in CD2-dependent T cell activation. LFA-3 is widely distributed and is expressed on all APC and target cells. Thus, the ability of the CD2/LFA-3 interaction to costimulate with an anti-CD3 mAb suggests that the CD2/LFA-3 interaction may be involved not only in an Ag-independent alternate pathway of T cell activation but also in Ag-specific T cell activation.
Molecular wires and devices: Advances and issues (2005)

Substantial advances have been made in (a) our experimental and theoretical understanding of simple tunnel junctions based on molecules, (b) the role of contacts tunneling and (c) experimental studies of redox-state gated transport. In addition, a new thermally-activated transport process has been discovered in a non-redox active system. Substantial challenges remain. The engineering of molecular contacts to technologically important electronic materials will stretch the ingenuity of synthetic chemists. The theory community must rise to the challenge of describing redox-mediated transport using first-principles, parameter free approaches. These advances will enable a new generation of devices that span the silicon (electronic) and carbon (bio-organic) worlds.
Novel method for identifying sequence-specific DNA-binding proteins. (1985)

We developed a general method for the enrichment and identification of sequence-specific DNA-binding proteins. A well-characterized protein-DNA interaction is used to isolate from crude cellular extracts or fractions thereof proteins which bind to specific DNA sequences; the method is based solely on this binding property of the proteins. The DNA sequence of interest, cloned adjacent to the lac operator DNA segment is incubated with a lac repressor-beta-galactosidase fusion protein which retains full operator and inducer binding properties. The DNA fragment bound to the lac repressor-beta-galactosidase fusion protein is precipitated by the addition of affinity-purified anti-beta-galactosidase immobilized on beads. This forms an affinity matrix for any proteins which might interact specifically with the DNA sequence cloned adjacent to the lac operator. When incubated with cellular extracts in the presence of excess competitor DNA, any protein(s) which specifically binds to the cloned DNA sequence of interest can be cleanly precipitated. When isopropyl-beta-D-thiogalactopyranoside is added, the lac repressor releases the bound DNA, and thus the protein-DNA complex consisting of the specific restriction fragment and any specific binding protein(s) is released, permitting the identification of the protein by standard biochemical techniques. We demonstrate the utility of this method with the lambda repressor, another well-characterized DNA-binding protein, as a model. In addition, with crude preparations of the yeast mitochondrial RNA polymerase, we identified a 70,000-molecular-weight peptide which binds specifically to the promoter region of the yeast mitochondrial 14S rRNA gene.
Surgical treatment of the epilepsies (1993)

Prologue: toward a surgical cure for epilepsy - the work of Wilder Penfield and his school at the Montreal Neurologic Institute, William Feindel. Part 1 Identification of surgical candidates. Part 2 Non-invasive pre-operative evaluation. Part 3 Invasive pre-operative evaluation. Part 4 Surgical treatment. Part 5 Post-operative follow-up. Epilogue: general impressions of the past-present and future, Herbert H. Jasper. Appendices: historical perspectives, Jerome Engel Jr pre-surgical evaluation protocols guidelines for multi-centre research, B. Vickrey et al basic research in the setting of an epilepsy surgery centre, P. Schwartzkroin.