gebhart/patrepeval huggingface dataset:
Role of Toxin Functional Domains in Anthrax Pathogenesis (2000)

We investigated the role of the functional domains of anthrax toxins during infection. Three proteins produced by Bacillus anthracis, the protective antigen (PA), the lethal factor (LF), and the edema factor (EF), combine in pairs to produce the lethal (PA+LF) and edema (PA+EF) toxins. A genetic strategy was developed to introduce by allelic exchange specific point mutations or in-frame deletions into B. anthracis toxin genes, thereby impairing either LF metalloprotease or EF adenylate cyclase activity or PA functional domains. In vivo effects of toxin mutations were analyzed in an experimental infection of mice. A tight correlation was observed between the properties of anthrax toxins delivered in vivo and their in vitro activities. The synergic effects of the lethal and edema toxins resulted purely from their enzymatic activities, suggesting that in vivo these toxins may act together. The PA-dependent antibody response to LF induced by immunization with live B. anthracis was used to follow the in vivo interaction of LF and PA. We found that the binding of LF to PA in vivo was necessary and sufficient for a strong antibody response against LF, whereas neither LF activity nor binding of lethal toxin complex to the cell surface was required. Mutant PA proteins were cleaved in mice sera. Thus, our data provide evidence that, during anthrax infection, PA may interact with LF before binding to the cell receptor. Immunoprotection studies indicated that the strain producing detoxified LF and EF, isogenic to the current live vaccine Sterne strain, is a safe candidate for use as a vaccine against anthrax.
Phase 2: a dose-escalation study of OncoGel (ReGel/paclitaxel), a controlled-release formulation of paclitaxel, as adjunctive local therapy to external-beam radiation in patients with inoperable esophageal cancer (2009)

OncoGel, a novel injectable formulation of paclitaxel in a biocompatible biodegradable gel (ReGel), provides controlled release of paclitaxel at the injection site, resulting in high intralesional paclitaxel concentrations and continuous radiosensitization without attendant systemic toxicities. This dose-escalation study evaluated the toxicity, pharmacokinetics, and preliminary antitumor activity of OncoGel injected intralesionally in patients with inoperable esophageal cancer who were candidates for palliative external-beam radiotherapy (RT). Eleven patients with inoperable advanced esophageal cancer received a single administration of OncoGel into the primary tumor using conventional endoscopic techniques. Three cohorts received approximately one-third of the tumor volume with increasing paclitaxel concentrations to achieve 0.48, 1.0, and 2.0 mg paclitaxel/cm tumor volume. Subsequent to injection, RT was initiated (50.4 Gy in 1.8 Gy fractions). Pharmacokinetic sampling was performed. All patients completed the study. No dose-limiting toxicities were reported. Dysphagia improved and tumor size decreased in most patients. Biopsies were negative for carcinoma in 4 of 11 patients. Peak paclitaxel plasma concentrations were low (0.53-2.73 ng/ml) and directly related to the absolute amount of paclitaxel administered. Paclitaxel was detectable in plasma for 24 h in all patients and for 3 weeks in six patients. OncoGel given as an adjunct to RT was well tolerated in patients with inoperable esophageal cancer and provided prolonged paclitaxel release with minimal systemic exposure. OncoGel plus RT seemed to reduce tumor burden as evidenced by dysphagia improvement, tumor size reduction, and negative esophageal biopsies. The addition of OncoGel to combined modality therapy merits continued clinical development.
Bioactive Nanoengineered Hydrogels for Bone Tissue Engineering: A Growth-Factor-Free Approach (2015)

Despite bone's impressive ability to heal after traumatic injuries and fractures, a significant need still exists for developing strategies to promote healing of nonunion defects. To address this issue, we developed collagen-based hydrogels containing two-dimensional nanosilicates. Nanosilicates are ultrathin nanomaterials with a high degree of anisotropy and functionality that results in enhanced surface interactions with biological entities compared to their respective three-dimensional counterparts. The addition of nanosilicates resulted in a 4-fold increase in compressive modulus along with an increase in pore size compared to collagen-based hydrogels. In vitro evaluation indicated that the nanocomposite hydrogels are capable of promoting osteogenesis in the absence of any osteoinductive factors. A 3-fold increase in alkaline phosphatase activity and a 4-fold increase in the formation of a mineralized matrix were observed with the addition of the nanosilicates to the collagen-based hydrogels. Overall, these results demonstrate the multiple functions of nanosilicates conducive to the regeneration of bone in nonunion defects, including increased network stiffness and porosity, injectability, and enhanced mineralized matrix formation in a growth-factor-free microenvironment.
Sequence-specific interactions of UvrABC endonuclease with psoralen interstrand cross-links. (1994)

The nature of the Uvr protein-DNA complexes formed on psoralen-DNA interstrand cross-links was analyzed by DNase I footprinting and correlated with the incision efficiency of the UvrABC endonuclease on the cross-links of different DNA sequences. Our results indicate that the repair specificity is dependent on the DNA sequence and the psoralen orientation in the cross-link. On the strand that will be cut, a 30-nucleotide long UvrAB footprint with a DNase I hypersensitive site at the 11th nucleotide 5' to the lesion was observed and subsequently rearranged to a 22-nucleotide long UvrB-lesion footprint. On the strand that will not be cut, the UvrAB-lesion footprint had no 5' DNase I hypersensitive site and did not form the UvrB-lesion footprint. Although UvrABC incision requires the formation of UvrB-lesion complex on the strand which will be cut, the affinities of these complexes do not correlate with the incision efficiencies, suggesting that the overall reaction can be driven forward by a favorable next step such as UvrC incision. A study of the time-dependent interconversion of UvrAB-lesion complex to UvrB-lesion complex on a cross-link revealed a secondary recognition of the UvrB-lesion complex by UvrA2(B) proteins in vitro.
Circulating CD20 is detectable in the plasma of patients with chronic lymphocytic leukemia and is of prognostic significance (2003)

CD20 is a 33- to 36-kDa transmembrane phosphoprotein involved in the activation, proliferation, and differentiation of B lymphocytes. The predicted amino acid sequence of the CD20 suggests 4 transmembrane-spanning regions with both N- and C-termini located in the cytoplasm. We demonstrate herein that significant levels of circulating CD20 (cCD20) can be detected in the plasma of patients with chronic lymphocytic leukemia (CLL) and that cCD20 interferes with the binding of rituximab, a humanized anti-CD20 monoclonal antibody, to CLL cells. An enzyme-linked immunosorbent assay (ELISA) was developed to measure circulating cCD20 levels in the plasma. We measured cCD20 levels in the plasma of 180 patients with CLL and correlated these levels with clinical characteristics and outcome. Circulating CD20 levels correlated positively with beta(2)-microglobulin level (p =.006) and percentage of CD38(+) cells (p =.03) and negatively with platelet count (p =.004) and hemoglobin level (p =.02). Patients with advanced Rai (III/IV) or Binet (C) stage disease had significantly higher levels of cCD20 than did patients with earlier-stage disease (P =.01 and P =.006, respectively). There was no correlation between cCD20 level and age, lymphocyte count, or white blood cell count. Using a recursive classification method, we found that patients with a cCD20 level more than 1875 nM/L had significantly shorter survival than those with cCD20 1875 nM/L or below (P =.01). The prognostic value of cCD20 was independent of Rai staging or hemoglobin level. Prospective evaluation is indicated to establish whether rituximab dosing should be adjusted according to cCD20 levels.
Erasing Core Boundaries for Robust and Configurable Performance (2010)

Single-thread performance, reliability and power efficiency are critical design challenges of future multicore systems. Although point solutions have been proposed to address these issues, a more fundamental change to the fabric of multicore systems is necessary to seamlessly combat these challenges. Towards this end, this paper proposes CoreGenesis, a dynamically adaptive multiprocessor fabric that blurs out individual core boundaries, and encourages resource sharing across cores for performance, fault tolerance and customized processing. Further, as a manifestation of this vision, the paper provides details of a unified performance-reliability solution that can assemble variable-width processors from a network of (potentially broken) pipeline stage-level resources. This design relies on interconnection flexibility, microarchitectural innovations, and compiler directed instruction steering, to merge pipeline resources for high single-thread performance. The same flexibility enables it to route around broken components, achieving sub-core level defect isolation. Together, the resulting fabric consists of a pool of pipeline stage-level resources that can be fluidly allocated for accelerating single-thread performance, throughput computing, or tolerating failures.
Optical time domain reflectometry on optical amplifier systems (1989)

The use of optical time-domain reflectometry (OTDR) on long-span fiber transmission systems containing in-line optical amplifiers is discussed. Having identified the specific requirements for OTDR equipment, measurements were carried out on systems of up to 300 km in length, containing three semiconductor laser amplifiers. The results demonstrate that OTDR can be used not only for fault location on fiber links several hundred kilometers in length but also as an alternative to standard system supervisory techniques, thus providing the potential for minimizing the hardware in the optical amplifier stages of future long-span fiber optic transmission systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Identification of a gene that positively regulates expression of listeriolysin, the major virulence factor of listeria monocytogenes. (1990)

We have isolated, by molecular cloning and genetic complementation of a listeriolysin-negative mutant, a gene required for the expression of this virulence factor in Listeria monocytogenes. The mutant strain SLCC53, which was nonhemolytic and avirulent, harbored a deletion of 450 base pairs located approximately 1500 base pairs upstream of the listeriolysin gene. No transcripts corresponding to the listeriolysin gene were detected in the mutant. DNA sequencing of this region from the hemolytic strain EGD revealed that the region deleted in the mutant would abrogate expression of a 27-kDa polypeptide. Introduction of a recombinant plasmid expressing this 27-kDa polypeptide restored hemolytic activity to the mutant and increased the hemolytic activity of the wild-type L. monocytogenes strain EGD. We have designated the gene encoding the 27-kDa polypeptide prfA, for positive regulatory factor of listeriolysin (lisA) expression. The prfA gene regulates transcription of the lisA gene positively.
Effects of Recombinant Leptin Therapy in a Child with Congenital Leptin Deficiency (1999)

Severely obese (ob/ob) mice are deficient in the adipocyte-derived hormone leptin, which acts on the hypothalamus to control appetite and energy expenditure.1 The administration of leptin to these mice corrects their obesity by reducing their food intake and increasing their energy expenditure.2–4 These mice also have hyperinsulinemia, corticosterone excess, and infertility, which also are reversed by treatment with leptin.5 In humans, serum leptin concentrations, in general, correlate positively with indexes of obesity.6,7 We previously described two cousins with severe, early-onset obesity and undetectable serum leptin concentrations who were homozygous for a frame-shift mutation in the leptin . . .
Interleukin-12: An Update on its Immunological Activities, Signaling and Regulation of Gene Expression (2005)

Interleukin-12 (IL-12) is a heterodimeric cytokine composed of the p35 and p40 subunits. It is produced by antigen-presenting cells and plays a critical role in host defense against intracellular microbial infection and control of malignancy via its ability to stimulate both innate and adaptive immune effector cells. The potency of IL-12 renders itself to stringent regulation of the timing, locality and magnitude of its production during an immune response. Subversion of the delicate control and balance frequently leads to immunologic disorders. In this article, we provide an update, since our last review of the subject four years ago, on recent advances in: (1) uncovering of novel activities of IL-12 and related molecules in various immunological settings and models; and (2) dissection of the physiological pathways involved in the modulation of IL-12 production by pathogens and immune regulators. The increased understanding of IL-12 immunobiology and expression will likely benefit the development of therapeutic modalities to correct immune dysfunctions.
Singlet Fission (2010)

The literature on singlet fission dealing with organic chromophores, from the time of the initial discovery of the phenomenon to the present day has been reviewed (235 refs).
Polymer-coated surface enhanced Raman scattering (SERS) gold nanoparticles for multiplexed labeling of chronic lymphocytic leukemia cells (2012)

The ease and flexibility of functionalization and inherent light scattering properties of plasmonic nanoparticles make them suitable contrast agents for measurement of cell surface markers. Immunophenotyping of lymphoproliferative disorders is traditionally undertaken using fluorescence detection methods which have a number of limitations. Herein, surface-enhanced Raman scattering (SERS) gold nanoparticles conjugated to monoclonal antibodies are used for the selective targeting of CD molecules on the surface of chronic lymphocytic leukemia (CLL) cells. Raman-active reporters were physisorbed on to the surface of 60 nm spherical Au nanoparticles, the particles were coated with 5kDa polyethylene glycol (PEG) including functionalities for conjugation to monoclonal IgG1 antibodies. A novel method for quantifying the number of antibodies bound to SERS probes on an individual basis as opposed to obtaining averages from solution was demonstrated using metal dots in transmission electron microscopy (TEM). The specificity of the interaction between SERS probes and surface CD molecules of CLL cells was assessed using Raman spectroscopy and dark field microscopy. An in-depth study of SERS probe targeting to B lymphocyte marker CD20 was undertaken, and proof-of-concept targeting using different SERS nanoparticle dyes specific for cell surface CD19, CD45 and CD5 demonstrated using SERS spectroscopy.
Natural History of Warts (1963)

The natural history of warts was recorded by examining 1,000 institutionalized mentally defective children for 2 years. Treatment of warts was withheld. We found: (1) The overall incidence increased from 18% to 25% in 2 years. (2) The dynamic aspect of warts was reflected by the fact that two-thirds of the original lesions in 168 cases involuted within 2 years. (3) Involution occurred almost twice as often in boys as girls. (4) Age and mental development of the patient and the incidence of warts in the immediate environment did not influence the rate of disappearance. (5) New warts occurred 3 times as frequently in infected children as in uninfected ones. The role of the reservoir of warts in the community and in the individual is stressed as important prerequisites to infection. Therapy based on these findings should always be conservative and not mutilating. It should be directed at reducing the reservoir in the infected person and his immediate environment.
Induction of the Estrogen Specific Mitogenic Response of MCF-7 Cells by Selected Analogues of Estradiol-17β:  A 3D QSAR Study (1997)

Analogues of estradiol-17 beta (E2) have been evaluated for estrogen receptor (ER) binding affinity and mitogenic potential in the human breast cancer cell line MCF-7. These 42 compounds represent subtle modifications of the natural estrogen structure through the placement of hydroxyl, amino, nitro, or iodo groups around the ring system in addition to, or as replacement of, the 3- and 17 beta-hydroxyls of E2. The mitogenic activity of the analogues was found to be related to ER binding only to a limited extent. In order to elucidate structural features that are uniquely responsible for receptor binding affinity or mitogen potential of estrogens, the three-dimensional quantitative structure-activity (QSAR) method Comparative Molecular Field Analysis (CoMFA) was employed. Separate CoMFA models for receptor binding and cell growth stimulation were optimized through the use of various alignment rules and region step size. Whereas the CoMFA contour plots did outline the shared structural requirements for the two measured biological properties, specific topological features in this set of estrogens were delineated that distinguish mitogenic potential from ER binding ability. In particular, steric interference zones which affected growth extend in a band from above the A-ring to position 4 and below, whereas the ER binding steric interference zones are limited to isolated polyhedra in the 1, 2 and 4 positions and the alpha face of the B-ring. In addition, electronegative features located around the A-, B-, or C-rings contribute to receptor affinity. However, growth is dependent only on electronegative and electropositive properties near the 3-position. In a final QSAR model for the mitogenic response, the value of ER binding was included along with structural features as a descriptor in CoMFA. The resulting 3D-QSAR has the most predictive potential of the models in this study and can be considered a prototype model for the general evaluation of a steroidal estrogen's growth stimulating ability in MCF-7 cells. For example, the location of D-ring contours illustrate the model's preference for 17 beta-hydroxy steroids over the less mitogenic 17 alpha- and 16 alpha-hydroxy compounds. In addition, the enhanced mitogenic effect of steric bulk in the 11 alpha-position is also evident. The QSAR studies in this report illustrate the fact that while ER binding may be a required factor of the estrogen dependent growth response in MCF-7 cells, particular structural characteristics, in addition to those responsible for tight receptor binding, must be present to induce an optimal mitogenic response. Therefore, this report demonstrates that the CoMFA QSAR method can be utilized to characterize structural features of test compounds that account for different types of estrogenic responses.
Transparent conducting oxides for electro‐optical plasmonic modulators (2014)

Abstract: The ongoing quest for ultra‐compact optical devices has reached a bottleneck due to the diffraction limit in conventional photonics. New approaches that provide subwavelength optical elements, and therefore lead to miniaturization of the entire photonic circuit, are urgently required. Plasmonics, which combines nanoscale light confinement and optical‐speed processing of signals, has the potential to enable the next generation of hybrid information‐processing devices, which are superior to the current photonic dielectric components in terms of speed and compactness. New plasmonic materials (other than metals), or optical materials with metal‐like behavior, have recently attracted a lot of attention due to the promise they hold to enable low‐loss, tunable, CMOScompatible devices for photonic technologies. In this review, we provide a systematic overview of various compact optical modulator designs that utilize a class of the most promising new materials as the active layer or core— namely, transparent conducting oxides. Such modulators can be made low‐loss, compact, and exhibit high tunability while offering low cost and compatibility with existing semiconductor technologies. A detailed analysis of different configurations and their working characteristics, such as their extinction ratio, compactness, bandwidth, and losses, is performed identifying the most promising designs.
HELIQUEST: a web server to screen sequences with specific α-helical properties (2008)

http://heliquest.ipmc.cnrs.fr.
Identification of a lineage of multipotent hematopoietic progenitors (1997)

All multipotent hematopoietic progenitors in C57BL-Thy-1.1 bone marrow are divided among three subpopulations of Thy-1.1(lo) Sca-1+ Lin(-/lo) c-kit+ cells: long-term reconstituting Mac-1- CD4- c-kit+ cells and transiently reconstituting Mac-1(lo) CD4- or Mac-1(lo) CD4(lo) cells. This study shows that the same populations, with similar functional activities, exist in mice whose hematopoietic systems were reconstituted by hematopoietic stem cells after lethal irradiation. We demonstrate that these populations form a lineage of multipotent progenitors from long-term self-renewing stem cells to the most mature multipotent progenitor population. In reconstituted mice, Mac-1- CD4- c-kit+ cells gave rise to Mac-1(lo) CD4- cells, which gave rise to Mac-1(lo) CD4(lo) cells. Mac-1- CD4- c-kit+ cells had long-term self-renewal potential, with each cell being capable of giving rise to more than 10(4) functionally similar Mac-1- CD4- c-kit+ cells. At least half of Mac-1(lo) CD4- cells had transient self-renewal potential, detected in the spleen 7 days after reconstitution. Mac-1(lo) CD4(lo) cells did not have detectable self-renewal potential. The identification of a lineage of multipotent progenitors provides an important tool for identifying genes that regulate self-renewal and lineage commitment.
Applications of the FIB lift-out technique for TEM specimen preparation (1998)

A site-specific technique for cross-section transmission electron microscopy specimen preparation of difficult materials is presented. A focused ion beam was used to slice an electron transparent membrane from a specific area of interest within a bulk sample. Micromanipulation lift-out procedures were then used to transport the electron-transparent specimen to a carbon-coated copper grid for subsequent TEM analysis. The FIB (focused ion beam) lift-out technique is a fast method for the preparation of site-specific TEM specimens. The versatility of this technique is demonstrated by presenting cross-sectioned TEM specimens from several types of materials systems, including a multi-layered integrated circuit on a Si substrate, a galvanized steel, a polycrystalline SiC ceramic fiber, and a ZnSe optical ceramic. These specimens have both complex surface geometry and interfaces with complex chemistry. FIB milling was performed sequentially through different layers of cross-sectioned materials so that preferential sputtering was not a factor in preparing TEM specimens. The FIB lift-out method for TEM analysis is a useful technique for the study of complex materials systems for TEM analysis.