gebhart/patrepeval huggingface dataset:
Mesoscopic hemisphere arrays for use as resist in solid state structure fabrication (1999)

The kinetics of formation of disordered arrays of hemispherically shaped islands of cesium chloride on an oxidized silicon wafer, starting from a deposited thin film of CsCl, has been investigated. The essential process step is the exposure of the CsCl thin film to water vapor. Transport of dissolved material in the adsorbed water layer occurs, driven by the size dependent solubility of CsCl. Growth rate is dominated by the kinetics of dissolution and deposition at the solid/solution boundary, rather than by interisland diffusion. The equipment and procedure are arranged so that constant humidity conditions prevail at every moment of hemisphere development. The process variables were: the effective thickness of the CsCl film, the relative humidity and the exposure time. The nature of the solid surface was found to be important and it was monitored using contact angle measurements of the water/solid interface: hydrophilic surfaces were used. The resulting arrays of hemispheres are characterized by a mean diameter, 〈d〉, a standard deviation, and a fractional surface coverage, F. Arrays from 〈d〉=450±145 Å at F=0.4 and 2050±330 Å at F=0.09, are reported.
Microwave photonics with superconducting quantum circuits (2017)

In the past 20 years, impressive progress has been made both experimentally and theoretically in superconducting quantum circuits, which provide a platform for manipulating microwave photons. This emerging field of superconducting quantum microwave circuits has been driven by many new interesting phenomena in microwave photonics and quantum information processing. For instance, the interaction between superconducting quantum circuits and single microwave photons can reach the regimes of strong, ultra-strong, and even deep-strong coupling. Many higher-order effects, unusual and less familiar in traditional cavity quantum electrodynamics with natural atoms, have been experimentally observed, e.g., giant Kerr effects, multi-photon processes, and single-atom induced bistability of microwave photons. These developments may lead to improved understanding of the counterintuitive properties of quantum mechanics, and speed up applications ranging from microwave photonics to superconducting quantum information processing. In this article, we review experimental and theoretical progress in microwave photonics with superconducting quantum circuits. We hope that this global review can provide a useful roadmap for this rapidly developing field.
The Logic of Visceral Leishmaniasis Control (1996)

Mathematical models are used to compare the effectiveness of various untested, unused, and undeveloped methods for controlling canine and human zoonotic visceral leishmaniasis (ZVL), including insecticides, vaccines, killing serologically positive and sick dogs, and drugs. For given percentage changes in control parameters, insecticides are the most effective control method. Where transmission occurs peridomestically and vectors are accessible to treatment, as in parts of tropical America, insecticides are expected to reduce the incidence of human ZVL even more effectively than they reduce the prevalence of canine leishmaniasis, a result that should encourage properly designed vector control trials. The second best strategy is to reduce susceptibility to leishmaniasis by vaccinating people or dogs, or by eliminating childhood malnutrition where it is common. Both killing vectors and reducing susceptibility (by whatever means) are more effective than killing dogs or treating them with drugs. In Europe, where vector control is less likely to be successful and canine leishmaniasis is a major veterinary problem, a dog vaccine is highly desirable. Better drugs for dogs will help case management but, with regard to bringing down the incidence in the dog population, immunization is the ultimate goal.
A small feature suppression/unsuppression system for preparing B-rep models for analysis (2005)

CAD technology plays an ever more central role in today's multidisciplinary simulation environments. While this has enabled highly complex and detailed models to be used earlier in the design process it has brought with it difficulties for simulation specialists. Most notably CAD models now contain many details which are irrelevant to simulation disciplines. CAD systems have feature trees which record feature creation but unfortunately this does not capture which features are relevant to which analysis discipline. Many features of little significance to an analysis only emerge during the construction of the model. The ability to selectively suppress and reinstate features while maintaining an audit trail of changes is required to facilitate the control of the idealisation process. Features suppressed for one analysis can be retrieved for use in another. This work uses combinatorial topology concepts to outline the necessary conditions so that CAD model simplification operations can be designed as continuous transformations. Irrelevant features can then be suppressed and subsequently reinstated, within defined limitations, independently from the order in which they were suppressed. The implementation of these concepts provides analysts with a mechanism for generating analysis models with different levels of detail, without having to repeat the simplification process from the original CAD geometry. Most importantly, the information recorded during the suppress operations forms an essential audit trail of the idealisation process and can be presented in a feature-tree like structure allowing analysts to review their modelling decisions retrospectively. The approach also facilitates the generation of local, detailed models encapsulating a feature of interest. The proposed system follows a Find and Fix paradigm, where different algorithms for feature finding and fixing can be utilised in a common cellular modelling framework.
Human pancreatic cancer cell proliferation in tissue culture is tonically inhibited by opioid growth factor. (1999)

Pancreatic adenocarcinoma is a fatal malignancy that ranks as the fourth most common cause of cancer-related mortality in the United States. The median survival after diagnosis is 3-6 months, with a 5-year survival rate of 3% or less. In spite of treatment efforts of surgery, radiation, and chemotherapy, the survival rate remains unchanged. In this study, we discovered that an endogenous opioid peptide, [Met5]-enkephalin, inhibited the growth of human pancreatic cancers in vitro; in view of this pentapeptide's action it has been termed opioid growth factor (OGF). OGF was found to be constitutively expressed, autocrine produced, and tonically capable of suppressing cell replication in an opioid receptor mediated manner. Growth inhibition was dose-related, reversible, not cytotoxic, and independent of serum. All 4 pancreatic cancer cell lines examined, representative of poor to well-differentiated neoplasias, exhibited growth regulation by OGF. Immunocytochemical studies detected both OGF and its related receptor, zeta, in the cytoplasm of log phase cells. Radioimmunoassays revealed that OGF was produced and secreted by the cells. These data suggest that a native opioid peptide, OGF, interacts with a novel opioid receptor, zeta, to arrest the growth of human pancreatic cancer.
Development and attributes of z/Architecture (2002)

The IBM z/Architecture™ instruction set architecture (ISA) is an extension of the IBM Enterprise Systems Architecture/390® (ESA/390) ISA and features 64-bit general registers, 64-bit operations, and 64-bit virtual and real addressing. In addition, z/Architecture includes new instructions to optimize the handling of modern multi-byte character encodings and to improve the performance of programs written in high-level languages. It provides compatibility for ESA/390 application programs and increases the ease of development of new application programs. This paper presents an overview of the interesting aspects of z/Architecture and some of the associated decisions and tradeoffs made in its development.
Modifications in Synthesis Strategy Improve the Yield and Efficacy of Geldanamycin−Herceptin Immunoconjugates (2002)

Geldanamycin (GA) was modified with N-tert-butyloxycarbonyl-1,3-diaminopropane to introduce a latent primary amine. After deprotection, this primary amine provided a site for introduction of a maleimide group that enabled linkage to proteins. This maleimido derivative of geldanamycin (GMB-APA-GA) was linked to the monoclonal antibody Herceptin after the antibody had been modified with Traut's reagent to introduce thiol groups. By this sequence, a new immunoconjugate (H:APA-GA) was generated that showed greater antiproliferative activity than the previously reported analogous immunoconjugate created with a 1,4-diaminobutane spacer derivative of geldanamycin to form an immunoconjugate, H:ABA-GA. Both immunoconjugates inhibited in vitro the growth of MDA-361/DYT2 cells, a cell line overexpressing the HER2 antigen, while Herceptin alone was ineffective. However, H:APA-GA showed better efficacy than H:ABA-GA (IC(50) = 0.2 vs 0.58 mg/mL and cell doubling time >12 vs 6 days, respectively). Results of the in vivo therapy experiments in a xenograft model were consistent with the in vitro findings. Treatment with Herceptin prolonged the survival of the tumor-bearing mice when compared with the control group, but H:ABA-GA and H:APA-GA were each more efficacious than unmodified Herceptin. However, unlike H:ABA-GA, the immunoconjugate H:APA-GA caused stable tumor regression (in 25% of the recipients), showing a qualitative improvement with potential clinical relevance.
Isolation of the Cyclosporin-Sensitive T Cell Transcription Factor NFATp (1993)

Nuclear factor of activated T cells (NFAT) is a transcription factor that regulates expression of the cytokine interleukin-2 (IL-2) in activated T cells. The DNA-binding specificity of NFAT is conferred by NFATp, a phosphoprotein that is a target for the immunosuppressive compounds cyclosporin A and FK506. Here, the purification of NFATp from murine T cells and the isolation of a complementary DNA clone encoding NFATp are reported. A truncated form of NFATp, expressed as a recombinant protein in bacteria, binds specifically to the NFAT site of the murine IL-2 promoter and forms a transcriptionally active complex with recombinant protein fragment react with T cell NFATp. The molecular cloning of NFATp should allow detailed analysis of a T cell transcription factor that is central to initiation of the immune response.
PrKX Is a Novel Catalytic Subunit of the cAMP-dependent Protein Kinase Regulated by the Regulatory Subunit Type I (1999)

The human X chromosome-encoded protein kinase X (PrKX) belongs to the family of cAMP-dependent protein kinases. The catalytically active recombinant enzyme expressed in COS cells phosphorylates the heptapeptide Kemptide (LRRASLG) with a specific activity of 1.5 micromol/(min.mg). Using surface plasmon resonance, high affinity interactions were demonstrated with the regulatory subunit type I (RIalpha) of cAMP-dependent protein kinase (KD = 10 nM) and the heat-stable protein kinase inhibitor (KD = 15 nM), but not with the type II regulatory subunit (RIIalpha, KD = 2.3 microM) under physiological conditions. Kemptide and autophosphorylation activities of PrKX are strongly inhibited by the RIalpha subunit and by protein kinase inhibitor in vitro, but only weakly by the RIIalpha subunit. The inhibition by the RIalpha subunit is reversed by addition of nanomolar concentrations of cAMP (Ka = 40 nM), thus demonstrating that PrKX is a novel, type I cAMP-dependent protein kinase that is activated at lower cAMP concentrations than the holoenzyme with the Calpha subunit of cAMP-dependent protein kinase. Microinjection data clearly indicate that the type I R subunit but not type II binds to PrKX in vivo, preventing the translocation of PrKX to the nucleus in the absence of cAMP. The RIIalpha subunit is an excellent substrate for PrKX and is phosphorylated in vitro in a cAMP-independent manner. We discuss how PrKX can modulate the cAMP-mediated signal transduction pathway by preferential binding to the RIalpha subunit and by phosphorylating the RIIalpha subunit in the absence of cAMP.
Gene Therapy Approaches for Inherited and Acquired Lung Diseases (1996)

Gene therapy is the treatment of any disorder or pathophysiologic state based upon the transfer of genetic information. The lung represents a major target of gene therapy for the treatment of genetic disorders such as cystic fibrosis and alpha 1-antitrypsin deficiency. Other diseases are also being targeted, including pulmonary inflammation, surfactant deficiency, pulmonary hypertension, lung cancer, and malignant mesothelioma. This review will examine some general concepts regarding gene transfer and gene therapy, provide an overview of the current vectors being developed to achieve safe and efficient gene transfer, and summarize the ongoing work to apply this new technology to the treatment of both inherited and acquired pulmonary diseases. Although tremendous progress has been made in the ability to successfully transfer genes to cells, there are several unresolved problems limiting the clinical application of this technology to human pulmonary disease. However, as vector technology evolves, gene therapy may become a reality for a number of lung diseases.
The ligase chain reaction as a primary screening tool for the detection of culture positive tuberculosis (2000)

This study is the largest clinical trial to date to report the efficacy of the ligase chain reaction as a primary screening tool to detect Mycobacterium tuberculosis infection. The authors conclude that ligase chain reaction is a useful primary screening test for tuberculosis, offering speed and discrimination in the early stages of diagnosis and complementing traditional smear and culture techniques.
A New Type of Claisen Rearrangement Involving 1,3‐Dipolar Intermediates. Preliminary communication (1978)

Abstract During the reaction of allyl ethers, allyl sulfides and allyl selenides with in situ prepared dichloroketene ( 1 ), 2 competing pathways are observed. Besides [2+2]‐cycloaddition, an unprecedented [3,3]‐sigmatropic ( Claisen ) rearrangement via a 1,3‐dipolar intermediate takes place. It leads to O‐, S‐ or Se‐esters of α,α‐dichloro‐γ, δ‐unsaturated acids containing an inverted allylic group. Starting from cyclic n ‐membered α‐vinyl‐substituted ethers, lactones with n+4 ‐membered rings are formed. A very facile synthesis of the naturally occurring macrolides (±)‐phoracantholide I ( 10 ) and (±)‐phoracantholide J ( 11 ) illustrates the synthetic utility of this new ‘ketene’ Claisen rearrangement.
Effects of trastuzumab on epidermal growth factor receptor‐dependent and ‐independent human colon cancer cells (2003)

Little information is available as to the potential role of HER-2 as a therapeutic target in colon cancers, which express much fewer HER-2 receptors than breast cancer cells. Treatment of certain human colon cancer cell lines with the HER-2 inhibitory antibody mAb 4D5 demonstrated a role for HER-2 in mediating proliferation, apoptosis and tumorigenicity. However, only the cell lines that were dependent on autocrine EGFR-mediated cell proliferation were susceptible to the antiproliferative and antitumorigenic effects of HER-2 inhibition. The relative levels of HER-2, EGFR, HER-3 and HER-4 were not predictive of responsiveness to mAb 4D5. Treatment with HER-2 antibodies caused a decrease in HER-2 protein levels in all of the colon cancer cell lines and also significantly decreased EGFR levels but only in the EGFR-dependent cell lines. Treatment with mAb 4D5 caused the rapid ubiquitination and ligand-dependent downregulation of the EGFR in an EGFR-dependent colon cancer cell line. Treatment of athymic mice engrafted with EGFR-dependent colon cancer cells with mAb 4D5 caused tumor regression and a decrease in EGFR tyrosine phosphorylation in the tumor cells. EGFR-independent colon cancer cell xenografts were resistant to mAb 4D5 therapy. Combined inhibition of HER-2 and EGFR caused large areas of necrosis in EGFR-dependent colon cancer xenografts, suggesting a benefit of combined HER-2 and EGFR inhibitor therapy. Predicting clinical responsiveness of human colon cancer cells to anti-HER-2 and anti-EGFR therapy may require demonstration of EGFR tyrosine kinase dependency of the cells.
Preparation and Characterization of Neurotoxic Tau Oligomers (2010)

Tau aggregation is a pathological hallmark of Alzheimer's disease, Parkinson's disease, and many other neurodegenerative disorders known as tauopathies. Tau aggregates take on many forms, and their formation is a multistage process with intermediate stages. Recently, tau oligomers have emerged as the pathogenic species in tauopathies and a possible mediator of amyloid-β toxicity in Alzheimer's disease. Here, we use a novel, physiologically relevant method (oligomer cross-seeding) to prepare homogeneous populations of tau oligomers and characterize these oligomers in vitro. We show that both Aβ and α-synuclein oligomers induce tau aggregation and the formation of β-sheet-rich neurotoxic tau oligomers.
Filling of glass microshells with heavy gases by radiation-simulated diffusion (2003)

The research results of an opportunity of radiation-stimulated diffusion use for laser fusion microtargets filling with heavy gases are given, which they can not be filled with by means of usual diffusion. The theoretical estimates of quantity and character of radiation damages, their distribution in the volume of an irradiated material are made. The calculations of glass microshells argon filling process in mode of vacancy and effusive mechanisms of wall permeability are carried out. The experiments on argon filling of glass microspheres are carried out by means of diffusion with irradiation of them with electrons, protons and neutrons. It is experimentally shown that the neutron irradiation of the glass microspheres placed in the chamber with argon in the reactor IBR-2 (JINR, Dubna) and their subsequent annealing has resulted in the argon penetration into microspheres.
The Pathobiology of Traumatically Induced Axonal Injury in Animals and Humans: A Review of Current Thoughts (1995)

This manuscript provides a review of those factors involved in the pathogenesis of traumatically induced axonal injury in both animals and man. The review comments on the issue of primary versus secondary, or delayed, axotomy, pointing to the fact that in cases of experimental traumatic brain injury, secondary, or delayed, axotomy predominates. This review links the process of secondary axotomy to an impairment of axoplasmic transport which is initiated, depending upon the severity of the injury, by either focal cytoskeletal. misalignment or axolemmal permeability change with concomitant cytoskeletal. collapse. Data are provided to show that these focal axonal changes are related to the focal impairment of axoplasmic transport which, in turn, triggers the progression of reactive axonal change, leading to disconnection. In the context of experimental studies, evidence is also provided to explain the damaging consequences of diffuse axonal injury. The implications of diffuse axonal injury and its attendant deafferentation are considered by noting that with mild injury such deafferentation may lead to an adaptive neuroplastic recovery, whereas in more severe injury a disordered and/or maladaptive neuroplastic re-organization occurs, consistent with the enduring morbidity associated with severe injury. In closing, the review focuses on the implications of the findings made in experimental animals for our understanding of those events ongoing in traumatically brain-injured humans. It is noted that the findings made in experimental animals have been confirmed, in large part, in humans, suggesting the relevance of animal models for continued study of human traumatically induced axonal injury.
Diabetes-Associated Sustained Activation of the Transcription Factor Nuclear Factor-κB (2001)

Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short and transient activation of NF-kappaB in vitro, we observed a long-lasting sustained activation of NF-kappaB in the absence of decreased IkappaBalpha in mononuclear cells from patients with type 1 diabetes. This was associated with increased transcription of NF-kappaBp65. A comparable increase in NF-kappaBp65 antigen and mRNA was also observed in vascular endothelial cells of diabetic rats. As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-beta peptide (Abeta) to the transmembrane receptor for AGE (RAGE) results in protein synthesis-dependent sustained activation of NF-kappaB both in vitro and in vivo. Infusion of AGE-albumin into mice bearing a beta-globin reporter transgene under control of NF-kappaB also resulted in prolonged expression of the reporter transgene. In vitro studies showed that RAGE-expressing cells induced sustained translocation of NF-kappaB (p50/p65) from the cytoplasm into the nucleus for >1 week. Sustained NF-kappaB activation by ligands of RAGE was mediated by initial degradation of IkappaB proteins followed by new synthesis of NF-kappaBp65 mRNA and protein in the presence of newly synthesized IkappaBalpha and IkappaBbeta. These data demonstrate that ligands of RAGE can induce sustained activation of NF-kappaB as a result of increased levels of de novo synthesized NF-kappaBp65 overriding endogenous negative feedback mechanisms and thus might contribute to the persistent NF-kappaB activation observed in hyperglycemia and possibly other chronic diseases.
Separate Domains of the Human Fas Ligand Dictate Self-association and Receptor Binding (1997)

The Fas receptor rapidly induces apoptosis when activated by ligand binding or by cross-linking with anti-Fas antibody. The Fas ligand (FasL), a member of the tumor necrosis factor family of ligands, is a 40-kilodalton type II transmembrane protein which is cleaved to produce soluble ligand. Although the Fas-FasL interaction plays a critical role in peripheral T cell homeostasis and cytotoxic T lymphocyte-mediated target cell killing, the requirements for human FasL receptor binding and oligomerization have not been defined. Here we report two distinct domains of the ligand which are responsible for self-association and binding to the Fas receptor. A COOH-terminal sequence of the FasL was found to be required for binding and biological activity, as verified by deletion mutagenesis, use of the NOK-1 blocking antibody and the humanized gld FasL mutation. N-Linked glycosylation of the FasL was not required for biological activity. However, the FasL expression level was dependent upon the three N-linked glycosylation sites. Moreover, the ability of the FasL to self-associate was not dependent upon transmembrane or cytoplasmic sequences, but was localized to a 47-amino acid region in its extracellular domain. These results indicate that the FasL-Fas receptor complex depends upon independent motifs located within the extracellular domain of the FasL.