gebhart/patrepeval huggingface dataset:
A High-Affinity Native Human Antibody Disrupts Biofilm from Staphylococcus aureus Bacteria and Potentiates Antibiotic Efficacy in a Mouse Implant Infection Model (2016)

Many serious bacterial infections are difficult to treat due to biofilm formation, which provides physical protection and induces a sessile phenotype refractory to antibiotic treatment compared to the planktonic state. A key structural component of biofilm is extracellular DNA, which is held in place by secreted bacterial proteins from the DNABII family: integration host factor (IHF) and histone-like (HU) proteins. A native human monoclonal antibody, TRL1068, has been discovered using single B-lymphocyte screening technology. It has low-picomolar affinity against DNABII homologs from important Gram-positive and Gram-negative bacterial pathogens. The disruption of established biofilm was observedin vitroat an antibody concentration of 1.2 μg/ml over 12 h. The effect of TRL1068in vivowas evaluated in a murine tissue cage infection model in which a biofilm is formed by infection with methicillin-resistantStaphylococcus aureus(MRSA; ATCC 43300). Treatment of the established biofilm by combination therapy of TRL1068 (15 mg/kg of body weight, intraperitoneal [i.p.] administration) with daptomycin (50 mg/kg, i.p.) significantly reduced adherent bacterial count compared to that after daptomycin treatment alone, accompanied by significant reduction in planktonic bacterial numbers. The quantification of TRL1068 in sample matrices showed substantial penetration of TRL1068 from serum into the cage interior. TRL1068 is a clinical candidate for combination treatment with standard-of-care antibiotics to overcome the drug-refractory state associated with biofilm formation, with potential utility for a broad spectrum of difficult-to-treat bacterial infections.
Extraordinarily High Conductivity of Stretchable Fibers of Polyurethane and Silver Nanoflowers (2015)

Stretchable conductive composites have received considerable attention recently, and they should have high conductivity and mechanical strength. Here we report highly conductive stretchable fibers synthesized by the scalable wet spinning process using flower-shaped silver nanoparticles with nanodisc-shaped petals (Ag nanoflowers) and polyurethane. An extraordinarily high conductivity (41,245 S cm(-1)) was obtained by Ag nanoflowers, which is 2 orders of magnitude greater than that of fibers synthesized using spherical Ag nanoparticles. This was due to the enhanced surface area and vigorous coalescence of nanodisc-shaped petals during the curing process. There was a trade-off relationship between conductivity and stretchability, and the maximum rupture strain was 776%. An analytical model revealed that the enhanced adhesion between Ag nanoflowers and polyurethane provided a high Young's modulus (731.5 MPa) and ultimate strength (39.6 MPa) of the fibers. The fibers exhibited an elastic property after prestretching, and the resistance change of weft-knitted fabric was negligible up to 200% strain. The fibers with extraordinarily high conductivity, stretchability, and mechanical strength may be useful for wearable electronics applications.
What's New in 1987? (1987)

This issue begins year 9 of the Academy's Pediatric Review and Education Program and Pediatrics in Review, or, as it is officially designated, PREP 2—year 3. The topic areas for this year are neonatology, cardiology, genetics and dysmorphism, and health supervision during infancy. As in the past, the majority of articles planned for this year address educational objectives directed at these topics, and the abstracts are usually used to present material concerning the recent advances educational objectives. In a few instances, recent advances objectives serve as the basis for articles and, in rare instances, I recruit papers with no specific educational objectives. You might call this the Editor's prerogative! One of these appears in this issue, "Health Care Systems: A Pediatric Perspective," by Blim and Matlin. It addresses the important topic of new methods of organization and payment of pediatricians. Nearly 2 years ago, the Executive Board of The American Academy of Pediatrics authorized us to present occasional papers on socioeconomic issues of pertinence to pediatricians in Pediatrics in Review. This and the previously published article by Robertson on medical liability (1985;6:229) are our response to date. We will have more such articles in the future. Starting with this issue, you will find brief biographies of the authors of the review articles.
Passive intermodulation interference in communication systems (1990)

In multifrequency communications environments, such as land mobile radio sites, satellite earth stations, ships and surveillance aircraft, passive intermodulation products (PIMP) generated by nonlinear materials and metallic contacts can cause serious radio interference. This problem is well known and a wide range of coaxial cables, connectors and materials have been investigated. The paper gives an overview of passive intermodulation interference in communication systems. It describes briefly the theory of intermodulation, types of passive nonlinearities, mechanisms responsible for the generation of PIMP, guidelines for minimising PIMP generation and techniques for locating PIMP sources. Previous investigations of PIMP are summarised and the design of PIMP measurement systems is discussed. An example of PIMP measurement is also included.
[Genetically programmed cell death (apoptosis)]. (2004)

Extensively and successfully studied problems of programmed cell death are considered. Recent evidence on apoptosis genes is presented, including the bcl-2 family and other genes with similar functions. A scheme of pathways of the main apoptosis mechanism is constructed. Examples of associations of apoptosis and diseases are presented in a special section.
A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex. (1996)

Ran is a nuclear Ras-like GTPase that is required for the bidirectional transport of proteins and ribnucleoproteins across the nuclear pore complex (NPC). A key regulator of the Ran GTP/GDP cycle is the 70-kD Ran-GTPase-activating protein RanGAP1. Here, we report the identification and localization of a novel form of RanGAP1. Using peptide sequence analysis and specific mAbs, RanGAP1 was found to be modified by conjugation to a ubiquitin-like protein. Immunoblot analysis and immunolocalization by light and EM demonstrated that the 70-kD unmodified from of RanGAP1 is exclusively cytoplasmic, whereas the 90-kD modified form of RanGAP1 is associated with the cytoplasmic fibers of the NPC. The modified form of RanGAP1 also appeared to associated with the mitotic spindle apparatus during mitosis. These findings have specific implications for Ran function and broad implications for protein regulation by ubiquitin-like modifications. Moreover, the variety and function of ubiquitin-like protein modifications in the cell may be more diverse than previously realized.
Cycloaddition between propylene oxide and CO2 over metal oxide supported KI (1999)

A novel catalyst system composed of KI supported on metal oxides for cycloaddition of propylene oxide with CO2 was investigated. It was found that the activity of KI for cycloaddition was strongly enhanced by ZnO as both support and promoter, resulting in a high yield of propylene carbonate within a short reaction time. Based on the characterization of BET, XRD, TG, IR and XPS-AES, this enhancement could be attributed to both the interaction between KI and amphoteric ZnO, which gave rise to the concerted active Lewis acid–base pairs of Iδ-Mδ+ and Kδ+O-δ and the dispersion of KI on the surface of the supports. The catalytic mechanism was then proposed.
Full-Length Human Mutant Huntingtin with a Stable Polyglutamine Repeat Can Elicit Progressive and Selective Neuropathogenesis in BACHD Mice (2008)

To elucidate the pathogenic mechanisms in Huntington's disease (HD) elicited by expression of full-length human mutant huntingtin (fl-mhtt), a bacterial artificial chromosome (BAC)-mediated transgenic mouse model (BACHD) was developed expressing fl-mhtt with 97 glutamine repeats under the control of endogenous htt regulatory machinery on the BAC. BACHD mice exhibit progressive motor deficits, neuronal synaptic dysfunction, and late-onset selective neuropathology, which includes significant cortical and striatal atrophy and striatal dark neuron degeneration. Power analyses reveal the robustness of the behavioral and neuropathological phenotypes, suggesting BACHD as a suitable fl-mhtt mouse model for preclinical studies. Additional analyses of BACHD mice provide novel insights into how mhtt may elicit neuropathogenesis. First, unlike previous fl-mhtt mouse models, BACHD mice reveal that the slowly progressive and selective pathogenic process in HD mouse brains can occur without early and diffuse nuclear accumulation of aggregated mhtt (i.e., as detected by immunostaining with the EM48 antibody). Instead, a relatively steady-state level of predominantly full-length mhtt and a small amount of mhtt N-terminal fragments are sufficient to elicit the disease process. Second, the polyglutamine repeat within fl-mhtt in BACHD mice is encoded by a mixed CAA-CAG repeat, which is stable in both the germline and somatic tissues including the cortex and striatum at the onset of neuropathology. Therefore, our results suggest that somatic repeat instability does not play a necessary role in selective neuropathogenesis in BACHD mice. In summary, the BACHD model constitutes a novel and robust in vivo paradigm for the investigation of HD pathogenesis and treatment.
La paralysie supranucléaire progressive (2003)

Parmi les syndromes parkinsoniens, la paralysie supranucleaire progressive (PSP) est une maladie 20 a 30 fois plus rare que la Maladie de Parkinson (Schrag etal., 1999). Si la PSP partage avec la maladie de Parkinson plusieurs symptomes, d'autres signes aident a distinguer les deux affections. De plus, les signes histopathologiques de la PSP visibles au microscope sont tres particuliers et servent de base absolue diagnostique. Etant donne qu'il n'existe pas de marqueur biologique pour diagnostiquer la maladie, la responsabilite incombe aux cliniciens d'identifier l'ensemble minimal de signes cliniques qui assure la plus haute probabilite de ce diagnostic histopathologique. Le programme NINDS distingue deux categories, « PSP probable » et « PSP possible », chacune avec ses propres caracteristiques. La PSP « probable » n'a qu'une sensitivite de 50 p. 100, mais une specificite et une valeur predictive positive de 100 p. 100. Avec la PSP « possible », il y a plus de cas (specificite de 83 p. 100), mais on inclut des erreurs diagnostiques (specificite de 93 p. 100) et la valeur predictive positive est plus faible (83 p. 100). Pour les recherches et de nouveaux traitements, si on se concentre sur les cas de PSP probable», bien que la population disponible soit plus restreinte, le clinicien est conscient que les cas retenus ont vraiment une PSP. Les etudes therapeutiques dans la PSP sont peu nombreuses et non controlees. Aucun produit medicamenteux et aucune intervention chirurgicale n'ont montre une grande efficacite. Un nouvel axe de recherche se concentre sur la neuroprotection, et dans ce but, il faut d'abord identifier la progression naturelle des incapacites cliniques. Une etude longitudinale de 50 patients avec PSP « probable » a examine le temps moyen entre le debut des symptomes et le developpement de trois signes clefs, chacun detectable par l'echelle standardisee de Unified Parkinson's Disease Rating Scale: l'incapacite de se tenir debout sans aide, l'incapacite de parler de maniere intelligible, et l'incapacite de se nourrir sans sonde. Les courbes Kaplan-Meier montrent que la duree moyenne de la maladie avant l'apparition d'un de ces signes est de 50 mois. Si les chercheurs veulent developper des protocoles pour prevenir ou pour ralentir ces evenements, c'est dans cette periode determinante que l'effort doit se concentrer.
Modeling and measurement of tissue elastic moduli using optical coherence elastography (2008)

Mechanical forces play crucial roles in tissue growth, patterning and development. To understand the role of mechanical stimuli, biomechanical properties are of great importance, as well as our ability to measure biomechanical properties of developing and engineered tissues. To enable these measurements, a novel non-invasive, micron-scale and high-speed Optical Coherence Elastography (OCE) system has been developed utilizing a titanium:sapphire based spectral-domain Optical Coherence Tomography (OCT) system and a mechanical wave driver. This system provides axial resolution of 3 microns, transverse resolution of 13 microns, and an acquisition rate as high as 25,000 lines per second. External lowfrequency vibrations are applied to the samples in the system. Step and sinusoidal steady-state responses are obtained to first characterize the OCE system and then characterize samples. Experimental results of M-mode OCE on silicone phantoms and human breast tissues are obtained, which correspond to biomechanical models developed for this analysis. Quantified results from the OCE system correspond directly with results from an indentation method from a commercial. With micron-scale resolution and a high-speed acquisition rate, our OCE system also has the potential to rapidly measure dynamic 3-D tissue biomechanical properties.
Phase III Double-Blind Placebo-Controlled Study of Farnesyl Transferase Inhibitor R115777 in Patients With Refractory Advanced Colorectal Cancer (2004)

Single agent R115777, given at this dose and schedule, has an acceptable toxicity profile, but does not improve overall survival compared to best supportive care alone in refractory advanced CRC.
A cowpox virus gene required for multiplication in Chinese hamster ovary cells (1988)

Cowpox virus, in contrast to vaccinia virus, can multiply in Chinese hamster ovary cells. To study the genetic basis for this difference in host range, recombinants between vaccinia and cowpox viruses were isolated and their DNA restriction patterns were examined. The ability to multiply in Chinese hamster ovary cells could be correlated with the conservation of cowpox virus sequences mapping at the left end of the genome. This was further demonstrated by marker rescue of the host range phenotype with restricted cowpox virus DNA. Marker rescue with cloned restriction fragments of decreasing size enabled the fine localization of the host range function to a 2.3-kilobase-pair fragment. Nucleotide sequencing revealed that the fragment encoded a single major polypeptide of approximately 77,000 daltons. It is suggested that the role of the host range gene from cowpox virus is to prevent the early and extensive shutoff of protein synthesis that normally occurs in Chinese hamster ovary cells infected by vaccinia virus.
Genetic aspects of autosomal dominant late onset cerebellar ataxia. (1981)

The genetic features of eight families with autosomal dominant late onset cerebellar ataxia with randomly distributed associated clinical features are described. The ratio of affected to unaffected offspring of affected subjects was not significantly different from 1:1. The mutant gene was fully penetrant when cases who died before the period of risk of developing the disease were excluded. The proportion of new mutants with this disorder appears to be low. Biological fitness was not impaired. Affected females tended to have large families than affected males. The ages of onset of females and males were not significantly different, but the offspring of affected males had earlier ages of onset and death than those of affected females. A cumulative age of onset curve is presented which should aid genetic counselling of subjects at risk and their children.
Function and Morphology of the Antennal Lobe: New Developments (2000)

The antennal lobe of insects has emerged as an excellent model for olfactory processing in the CNS. In the present review we compile data from areas where substantial progress has been made during recent years: structure-function relationships within the glomerular array, integration and blend specificity, time coding and the effects of neuroactive substances and hormones on antennal lobe processing.
The Adjuvants Aluminum Hydroxide and MF59 Induce Monocyte and Granulocyte Chemoattractants and Enhance Monocyte Differentiation toward Dendritic Cells (2008)

Aluminum hydroxide (alum) and the oil-in-water emulsion MF59 are widely used, safe and effective adjuvants, yet their mechanism of action is poorly understood. We assessed the effects of alum and MF59 on human immune cells and found that both induce secretion of chemokines, such as CCL2 (MCP-1), CCL3 (MIP-1alpha), CCL4 (MIP-1beta), and CXCL8 (IL-8), all involved in cell recruitment from blood into peripheral tissue. Alum appears to act mainly on macrophages and monocytes, whereas MF59 additionally targets granulocytes. Accordingly, monocytes and granulocytes migrate toward MF59-conditioned culture supernatants. In monocytes, both adjuvants lead to increased endocytosis, enhanced surface expression of MHC class II and CD86, and down-regulation of the monocyte marker CD14, which are all phenotypic changes consistent with a differentiation toward dendritic cells (DCs). When monocyte differentiation into DCs is induced by addition of cytokines, these adjuvants enhanced the acquisition of a mature DC phenotype and lead to an earlier and higher expression of MHC class II and CD86. In addition, MF59 induces further up-regulation of the maturation marker CD83 and the lymph node-homing receptor CCR7 on differentiating monocytes. Alum induces a similar but not identical pattern that clearly differs from the response to LPS. This model suggests a common adjuvant mechanism that is distinct from that mediated by danger signals. We conclude that during vaccination, adjuvants such as MF59 may increase recruitment of immune cells into the injection site, accelerate and enhance monocyte differentiation into DCs, augment Ag uptake, and facilitate migration of DCs into tissue-draining lymph nodes to prime adaptive immune responses.
A Novel Mutation in the Switch 3 Region of Gsα in a Patient with Albright Hereditary Osteodystrophy Impairs GDP Binding and Receptor Activation (1998)

Albright hereditary osteodystrophy (AHO), a disorder characterized by skeletal abnormalities and obesity, is associated with heterozygous inactivating mutations in the gene for Gsalpha. A novel Gsalpha mutation encoding the substitution of tryptophan for a nonconserved arginine within the switch 3 region (Gsalpha R258W) was identified in an AHO patient. Although reverse transcription-polymerase chain reaction studies demonstrated that mRNA expression from wild type and mutant alleles was similar, Gsalpha expression in erythrocyte membranes from the affected patient was reduced by 50%. A Gsalpha R258W cDNA, as well as one with arginine replaced by alanine (Gsalpha R258A), was generated, and the biochemical properties of in vitro transcription/translation products were examined. When reconstituted with cyc- membranes, both mutant proteins were able to stimulate adenylyl cyclase normally in the presence of guanosine- 5'-O-(3-thiotriphosphate) (GTPgammaS) but had decreased ability in the presence of isoproterenol or AlF4- (a mixture of 10 microM AlCl3 and 10 mM NaF). The ability of each mutant to bind and be activated by GTPgammaS or AlF4- was assessed by trypsin protection assays. Both mutants were protected normally by GTPgammaS but showed reduced protection in the presence of AlF4-. The addition of excess GDP (2 mM) was able to rescue the ability of AlF4- to protect the mutants, suggesting that they might have reduced affinity for GDP. A Gsalpha R258A mutant purified from Escherichia coli had decreased affinity for GDP and an apparent rate of GDP release that was 10-fold greater than that of wild type Gsalpha. Sucrose density gradient analysis demonstrated that both Gsalpha R258W and Gsalpha R258A were thermolabile at higher temperatures and that denaturation of both mutants was prevented by the presence of 0.1 mM GTPgammaS or 2 mM GDP. The crystal structure of Gsalpha demonstrates that Arg258 interacts with a conserved residue in the helical domain (Gln170). Arg258 substitutions would be predicted to open the cleft between the GTPase and helical domains, allowing for increased GDP release in the inactive state, resulting in enhanced thermolability and reduced AlF4--induced adenylyl cyclase stimulation and trypsin protection, since activation by AlF4- requires bound GDP.
Explaining World Wide Web Traffic Self-Similarity (1995)

Recently the notion of self-similarity has been shown to apply to wide-area and local-area network traffic. In this paper we examine the mechanisms that give rise to self-similar network traffic. We present an explanation for traffic self-similarity by using a particular subset of wide area traffic: traffic due to the World Wide Web (WWW). Using an extensive set of traces of actual user executions of NCSA Mosaic, reflecting over half a million requests for WWW documents, we show evidence that WWW traffic is selfsimilar. Then we show that the self-similarity in such traffic can be explained based on the underlying distributions of WWW document sizes, the effects of caching and user preference in file transfer, the effect of user &amp;quot;think time&amp;quot;, and the superimposition of many such transfers in a local area network. To do this we rely on empirically measured distributions both from our traces and from data independently collected at over thirty WWW sites. 1 Introduction Understanding the ...
On the interaction of the finger and the kringle-2 domain of tissue-type plasminogen activator with fibrin. Inhibition of kringle-2 binding to fibrin by epsilon-amino caproic acid. (1986)

The binding of tissue-type plasminogen activator (t-PA) to fibrin is mediated both by its finger domain and by its kringle-2 domain. In this report, we investigate the relative affinities of these domains for lysine. Human recombinant t-PA deletion-mutant proteins were prepared and their ability to bind to lysine-Sepharose was investigated. Mutants containing the kringle-2 domain bound to lysine-Sepharose, whereas mutants lacking this domain but containing the finger domain, the epidermal growth factor domain or the kringle-1 domain did not bind to lysine-Sepharose. Mutant proteins containing the kringle-2 domain could be specifically eluted from lysine-Sepharose with epsilon-amino caproic acid. This lysine derivative also abolished fibrin binding by the kringle-2 domain but had no effect on the fibrin-binding property of the finger domain. Thus, a lysine-binding site is involved in the interaction of the kringle-2 domain with fibrin but not in the interaction of the finger domain with fibrin. The implications of the nature of these two distinct interactions of t-PA with fibrin on plasminogen activation by t-PA will be discussed.