gebhart/patrepeval huggingface dataset:
An industrially effective environment for formal hardware verification (2005)

The Forte formal verification environment for datapath-dominated hardware is described. Forte has proven to be effective in large-scale industrial trials and combines an efficient linear-time logic model-checking algorithm, namely the symbolic trajectory evaluation (STE), with lightweight theorem proving in higher-order logic. These are tightly integrated in a general-purpose functional programming language, which both allows the system to be easily customized and at the same time serves as a specification language. The design philosophy behind Forte is presented and the elements of the verification methodology that make it effective in practice are also described.
Designing porous bioartificial membranes for clinical use with desired morphological and transport properties by phase inversion control. (2012)

Bioartificial membranes of synthetic (poly(ethylene-co-vinyl alcohol) - EVAL, Clarene (R) ) and biological (dextran) polymers with different compositions were prepared through the phase inversion process. Dimethyl sulfoxide (DMSO) solutions of EVAL and dextran were mixed under stirring in the desired proportions and coagulated in water or DMSO (solvent)/water (non-solvent) mixture. Membrane morphologies were shown to be dependent on the synthetic and biological polymer contents and on the coagulation medium composition. Component release during solid membrane formation was evaluated by a UV method and the final composition of the bioartificial membranes established, confirming the successful entrapment of the biological component in the synthetic network. The porosity degree of the bioartificial membranes was also investigated by permeability tests and the effect of morphological characteristics on transport properties was studied. Water flux across the membranes, solute permeability and sieving coefficients were also calculated. The results revealed that the transport properties of these bioartificial membranes, obtained by the phase inversion method, could be controlled by mainly changing the preparation control parameters and the EVAL-dextran ratio.
Differential Expression of MicroRNAs in Omental Adipose Tissue From Gestational Diabetes Mellitus Subjects Reveals miR-222 as a Regulator of ERα Expression in Estrogen-Induced Insulin Resistance (2014)

Omental adipose tissue plays a central role in insulin resistance in gestational diabetes mellitus (GDM), and the molecular mechanisms leading to GDM remains vague. Evidence demonstrates that maternal hormones, such as estradiol, contribute to insulin resistance in GDM. In this study we determined the differential expression patterns of microRNAs (miRNAs) in omental adipose tissues from GDM patients and pregnant women with normal glucose tolerance using AFFX miRNA expression chips. MiR-222, 1 of 17 identified differentially expressed miRNAs, was found to be significantly up-regulated in GDM by quantitative real-time PCR (P < .01), and its expression was closely related with serum estradiol level (P < .05). Furthermore, miR-222 expression was significantly increased in 3T3-L1 adipocytes with a high concentration of 17β-estradiol stimulation (P < .01), whereas the expressions of estrogen receptor (ER)-α protein and insulin-sensitive membrane transporter glucose transporter 4 (GLUT4) protein (P < .01) were markedly reduced. In addition, ERα was shown to be a direct target of miR-222 in 3T3-L1 adipocytes by using the luciferase assay. Finally, antisense oligonucleotides of miR-222 transfection was used to silence miR-222 in 3T3-L1 adipocytes. The results showed that the expressions of ERα and GLUT4, the insulin-stimulated translocation of GLUT4 from the cytoplasm to the cell membrane and glucose uptake in mature adipocytes were dramatically increased (P < .01). In conclusion, miR-222 is a potential regulator of ERα expression in estrogen-induced insulin resistance in GDM and might be a candidate biomarker and therapeutic target for GDM.
A Sodium Ion-Selective Electrode Based on a Neutral Carrier (1974)

Abstract The performance of liquid-membrane electrodes using A new, synthetic, and electrically neutral ligand in A membrane solvent incorporated in A PVC-matrix is described. In this sensor system, two different membrane solvents are compared in respect to selectivity, pH-dependence, lifetime, working range and dynamic response. Both electrodes show A linear response to sodium ion activities in the range of 10−1M to about 10−5M in unbuffered systems, with A selectivity over potassium, calcium and magnesium which permits measurements in blood serum.
The Design of Integrated Circuits to Observe Brain Activity (2008)

The ability to monitor the simultaneous electrical activity of multiple neurons in the brain enables a wide range of scientific and clinical endeavors. Recent efforts to merge miniature multielectrode neural recording arrays with integrated electronics have revealed significant circuit design challenges. Weak neural signals must be amplified and filtered using low-noise circuits placed close to the electrodes themselves, but power dissipation must strictly be limited to prevent tissue damage due to local heating. In modern recording systems with 100 or more electrodes, raw data rates of 15 Mb/s or more are easily produced. Micropower wireless telemetry circuits cannot transmit information at such high rates, so data reduction must be performed in the implanted device. In this paper, we present integrated circuits and design techniques that address the twin problems of neural signal amplification and data reduction for this severely size- and power-limited application.
Thermo-optical effects in high-power Ytterbium-doped fiber amplifiers (2011)

We investigate the effect of temperature gradients in high-power Yb-doped fiber amplifiers by a numerical beam propagation model, which takes thermal effects into account in a self-consistent way. The thermally induced change in the refractive index of the fiber leads to a thermal lensing effect, which decreases the effective mode area. Furthermore, it is demonstrated that the thermal lensing effect may lead to effective multi-mode behavior, even in single-mode designs, which could possibly lead to degradation of the output beam quality.
Delivery Systems for Gene-based Vaccines (2000)

Along with the elucidation of the role of cytotoxic T lymphocytes in the immune responses against a number of pathogens and cancer, and with the increased understanding of the cellular processing mechanisms of antigens for generation of these cells, has come an increased focus on vaccines that can generate cellular immunity along with antibodies. Promising approaches based on the delivery of genes, either as plasmid DNA or by viral vectors, have been extensively evaluated pre-clinically and in early-phase clinical trials. Although the first generation of DNA plasmid vaccines were broadly effective in animal disease models, early clinical immunogenicity pointed towards the need for increased potency. This manuscript reviews recent developments for gene-based vaccines, specifically, new approaches for formulating and delivering plasmid DNA and alphaviral replicon vectors, all of which have resulted in increased potency of gene-based vaccines.
Über die Methylierung des Sulfitions und über die Umlagerungsmechanismen der Schwefligsäure‐ in Sulfonsäure‐ Abkömmlinge (1956)

Abstract Die Sulfonsäurederivate Na‐Methansulfonat (I) und Methansulfonsäure‐methylester (II) sind stabiler als die isomeren Sulfitabkömmlinge Na‐Methylsulfit (III) und Dimethylsulfit (IV). Daher lassen sich III bzw. IV leicht in I bzw. II isomerisieren. Die Umlagerung von III in I und die von IV in II wird durch CH 3 J und die von IV in I durch Alkalijodid bewirkt. Die Reaktionsmechanismen dieser Umlagerungen werden angegeben. Im Zusammenhang damit wird gezeigt, daß die durch CH 3 J bewirkte Methylierung des SO ‐⊖. Ions am Schwefel und nicht am Sauerstoff erfolgt. In der Diskussion werden die Umlagerungs‐ und Methylierungsreaktionen theoretisch gedeutet.
Efficacy of a temperature-sensitive Sendai virus vaccine in hamsters. (1995)

A temperature-sensitive HVJ-pB strain of parainfluenza type 1 (Sendai) virus was obtained from a persistently virus-infected cell culture. Intranasal inoculation of Syrian hamsters with the HVJ-pB temperature-sensitive mutant resulted in an abortive infection but induced a specific antibody response against Sendai virus without appreciable lesions in the respiratory tract. Prior exposure to the temperature-sensitive mutant protected hamsters from subsequent challenge with virulent wild-type virus. The efficacy of protection became apparent at 5 days after vaccination and lasted for at least 720 days. For practical use of the HVJ-pB vaccine, a single intranasal administration to newborn babies aged over 15 days is recommended.
First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis (2018)

The underlying pathology of atopic dermatitis (AD) includes impaired skin barrier function, susceptibility to Staphylococcus aureus skin infection, immune dysregulation, and cutaneous dysbiosis. Our recent investigation into the potential role of Gram-negative skin bacteria in AD revealed that isolates of one particular commensal, Roseomonas mucosa, collected from healthy volunteers (HVs) improved outcomes in mouse and cell culture models of AD. In contrast, isolates of R. mucosa from patients with AD worsened outcomes in these models. These preclinical results suggested that interventions targeting the microbiome could provide therapeutic benefit for patients with AD. As a first test of this hypothesis in humans, 10 adult and 5 pediatric patients were enrolled in an open-label phase I/II safety and activity trial (the Beginning Assessment of Cutaneous Treatment Efficacy for Roseomonas in Atopic Dermatitis trial; BACTERiAD I/II). Treatment with R. mucosa was associated with significant decreases in measures of disease severity, topical steroid requirement, and S. aureus burden. There were no adverse events or treatment complications. We additionally evaluated differentiating bacterial metabolites and topical exposures that may contribute to the skin dysbiosis associated with AD and/or influence future microbiome-based treatments. These early results support continued evaluation of R. mucosa therapy with a placebo-controlled trial.
Preparation of Nano BaTiO <sub>3</sub> ‐Based Ceramics for Multilayer Ceramic Capacitor Application by Chemical Coating Method (2009)

The base‐metal‐electrode multilayer ceramic capacitors (BME MLCCs) for future application require much thinner dielectric layers (<1 μm). Therefore, the grain size and uniformity of BME MLCC powders should be effectively controlled. In this paper, the nanosized BME MLCC powders were prepared by chemical coating method. The well‐coated BaTiO 3 particles were obtained by adjusting an appropriate pH value. Transmission electron microscopy, energy‐dispersive spectroscopy, X‐ray photoelectron spectrum were utilized for the study of microstructures and element analysis. The high‐performance X7R dielectric ceramics were produced in reducing atmosphere by “two‐step” sintering method at a low temperature of 950°C. The dielectric constant at room temperature could reach ∼2400, with low dielectric loss below 1.0% and high insulation resistivity ∼10 12 Ω·cm. The ceramic grains were very homogenous with the average size below 150 nm.
A novel C2 domain binding CD33xCD3 bispecific antibody with potent T-cell redirection activity against acute myeloid leukemia (2020)

CD33 is expressed in 90% of patients with acute myeloid leukemia (AML), and its extracellular portion consists of a V domain and a C2 domain. A recent study showed that a single nucleotide polymorphism (SNP), rs12459419 (C > T), results in the reduced expression of V domain-containing CD33 and limited efficacy of V domain-binding anti-CD33 antibodies. We developed JNJ-67571244, a novel human bispecific antibody capable of binding to the C2 domain of CD33 and to CD3, to induce T-cell recruitment and CD33+ tumor cell cytotoxicity independently of their SNP genotype status. JNJ-67571244 specifically binds to CD33-expressing target cells and induces cytotoxicity of CD33+ AML cell lines in vitro along with T-cell activation and cytokine release. JNJ-67571244 also exhibited statistically significant antitumor activity in vivo in established disseminated and subcutaneous mouse models of human AML. Furthermore, this antibody depletes CD33+ blasts in AML patient blood samples with concurrent T-cell activation. JNJ-67571244 also cross-reacts with cynomolgus monkey CD33 and CD3, and dosing of JNJ-67571244 in cynomolgus monkeys resulted in T-cell activation, transient cytokine release, and sustained reduction in CD33+ leukocyte populations. JNJ-67571244 was well tolerated in cynomolgus monkeys up to 30 mg/kg. Lastly, JNJ-67571244 mediated efficient cytotoxicity of cell lines and primary samples regardless of their SNP genotype status, suggesting a potential therapeutic benefit over other V-binding antibodies. JNJ-67571244 is currently in phase 1 clinical trials in patients with relapsed/refractory AML and high-risk myelodysplastic syndrome.
Engineering a therapeutic IgG molecule to address cysteinylation, aggregation and enhance thermal stability and expression (2013)

Antibodies can undergo a variety of covalent and non-covalent degradation reactions that have adverse effects on efficacy, safety, manufacture and storage. We had identified an antibody to Angiopoietin 2 (Ang2 mAb) that neutralizes Ang2 binding to its receptor in vitro and inhibits tumor growth in vivo. Despite favorable pharmacological activity, the Ang2 mAb preparations were heterogeneous, aggregated rapidly and were poorly expressed. Here, we report the engineering of the antibody variable and constant domains to generate an antibody with reduced propensity to aggregate, enhanced homogeneity, 11°C elevated T(m), 26-fold improved level of expression and retained activity. The engineered molecule, MEDI-3617, is now compatible with the large scale material supply required for clinical trials and is currently being evaluated in Phase 1 in cancer patients. This is the first report to describe the stability engineering of a therapeutic antibody addressing non canonical cysteine residues and the design strategy reported here is generally applicable to other therapeutic antibodies and proteins.
Chemotherapeutic Efficacy of E-5-(2-Bromovinyl)-2'-Deoxyuridine for Orofacial Infection with Herpes Simplex Virus Type 1 in Mice (1982)

Systemic or topical treatment with E-5-(2-bromovinyl)2'-deoxyuridine (BVDU) showed significant efficacy against orofacial infection with herpes simplex virus type 1 (HSV-1) in hairless mice. The chemotherapeutic response to BVDU was dose-dependent and clearly evident even when the treatment was initiated during the clinical manifestation of HSV-1 infection at 72 hr after inoculation. Early initiation of therapy with BVDU at 3 or 24 hr after inoculation significantly prevented the establishment of latent HSV infection in the trigeminal ganglia of mice, but systemic treatment with BVDU did not influence already established latent HSV-1. The chemotherapeutic efficacy of BVDU was comparable to that of acyclovir in the present animal model.
Racial differences in erythrocyte cation transport. (1984)

Erythrocyte contents and ouabain-insensitive transport pathways were measured in 120 white and black normotensives and hypertensives. Mean maximal sodium-stimulated lithium-sodium countertransport rate was higher in white hypertensives than in white normotensives, and countertransport was significantly positively correlated with mean arterial pressure in whites. Values similar to those in white normotensives were found in both black normotensives and hypertensives, and countertransport was not significantly correlated with blood pressure in blacks. The rate constant for passive lithium efflux was greater in whites as compared to blacks, and the difference was not related to blood pressure level or sex. Ouabain-insensitive, furosemide-sensitive sodium and potassium effluxes were not found to be altered in hypertension. Furosemide-sensitive sodium efflux rate was lower in blacks but furosemide-sensitive potassium efflux was not similarly depressed. While white subjects demonstrated a close correlation between sodium and potassium effluxes, blacks did not. Further study of these differences in the cellular metabolism of sodium and potassium may provide clues to the pathogenesis of racial dissimilarities in total body sodium handling.
[Interspecific interactions between Cotesia plutellae and Oomyzus sokolowskii, two major parasitoids of diamondback moth, Plutella xylostella]. (2003)

The interspecific interactions between Cotesia plutellae (Kurdjumov) (Hym.: Braconidae) and Oomyzus sokolowskii (Kurdjumov) (Hym.: Eulophidae) were investigated at 28 degrees C in laboratory, by exposing the 3rd instar larvae of diamondback moth, Plutella xylostella L. (Lep.: Plutellidae) to two parasitoids concurrently, or to either species alone, and by exposing the host larvae already exposed to one species to another species. Compared with those exposures of host larvae to either one species at a time, the parasitism rates by C. plutellae were not reduced by the presence of O. sokolowskii, but the rates of parasitism by O. sokolowskii were significantly reduced by the presence of C. plutellae, when the host larvae were exposed to the two species of parasitoid concurrently. No significant differences were found between the parasitism rates done by the two species together, and those done by either one of the two species alone. When host larvae were exposed to O. sokolowskii after exposure to C. plutellae, the successful parasitism rates by C. plutellae were unaffected, while the parasitism rates by O. sokolowskii were only 8-13%. However, O. sokolowskii could parasitize the old larvae of C. plutellae developed inside host larvae. Cotesia plutellae could parasitize the host larvae parasitized previously by O. sokolowskii, and some individuals of C. plutellae in these multiparasitized hosts could develop normally and survive to adult emergence. When O. sokolowskii wasps were exposed to healthy host larvae and host larvae parasitized by C. plutellae, they preferred to parasitize the healthy ones. These results suggest that C. plutellae is the stronger competitor, but its competition capacity will be reduced by the parasitism by O. sokolowskii.
Assessing Long-Term Drug Safety: Lessons (Re) Learned from Raptiva (2010)

Efalizumab was approved for moderate to severe psoriasis in 2003 based on studies in approximately 2700 patients, of whom only 218 were exposed to the drug for more than 1 year. In 2009, after more than 46,000 patients were exposed to efalizumab, the drug was withdrawn from the market after 3 confirmed and 1 suspected case of progressive multifocal leukoencephalopathy (PML) were spontaneously reported. As PML is very rare, it is extremely unlikely that the 4 reported cases were due to chance and given that PML occurs primarily in patients who are immunosuppressed, the association is likely causal. The identification of PML as a serious, but statistically rare risk of efalizumab demonstrates the strengths and weaknesses of the current drug approval and pharmacovigilance processes for fully measuring the safety of a drug. Patients and clinicians need to be aware of the relative completeness and limitations of existing safety data of a drug when selecting a treatment.
Decolorization of textile azo dye reactive orange 16 with UV/H2O2 process (2011)

The photochemical decolorization of C.I. Reactive Orange 16 (RO16), a reactive textile azo dye by the UV/H2O2 process using a batch photoreactor with UV lamps emitting at 253.7 nm, was studied. Complete decolorization of 50.0 mg dm-3 initial dye concentration was achieved in less than 6 min under optimal conditions (25 mM initial peroxide concentration, at pH 7.0 and with UV light intensity 1950 ?W cm-2). The effect of experimental variables, such as initial pH, initial concentration of H2O2, initial dye concentration, and the intensity of UV light was studied. The highest decolorization rates were performed at peroxide concentration in range from 20 mM up to 40 mM, above which decolorization was inhibited by a scavenging effect of peroxide. The decolorization was more efficient in neutral pHs. The efficiency of the process was improved in lower initial dye concentration and at higher intensity of UV light.
Glucocorticoids and Cardiovascular Disease (2007)

Chronic excessive activation of glucocorticoid receptors induces obesity, insulin resistance, glucose intolerance, dyslipidaemia and hypertension. Subtle abnormalities of the hypothalamic-pituitary-adrenal axis and/or of tissue sensitivity to glucocorticoids are also associated with these cardiovascular risk factors in patients with the metabolic syndrome. Furthermore, glucocorticoids have direct effects on the heart and blood vessels, mediated by both glucocorticoid and mineralocorticoid receptors and modified by local metabolism of glucocorticoids by the 11beta-hydroxysteroid dehydrogenase enzymes. These effects influence vascular function, atherogenesis and vascular remodelling following intra-vascular injury or ischaemia. This article reviews the systemic and cardiovascular effects of glucocorticoids, and the evidence that glucocorticoids not only promote the incidence and progression of atherogenesis but also modify the recovery from occlusive vascular events and intravascular injury. The conclusion is that manipulation of glucocorticoid action within metabolic and cardiovascular tissues may provide novel therapeutic avenues to combat cardiovascular disease.
Skin tissue generation by laser cell printing (2012)

For the aim of ex vivo engineering of functional tissue substitutes, Laser-assisted BioPrinting (LaBP) is under investigation for the arrangement of living cells in predefined patterns. So far three-dimensional (3D) arrangements of single or two-dimensional (2D) patterning of different cell types have been presented. It has been shown that cells are not harmed by the printing procedure. We now demonstrate for the first time the 3D arrangement of vital cells by LaBP as multicellular grafts analogous to native archetype and the formation of tissue by these cells. For this purpose, fibroblasts and keratinocytes embedded in collagen were printed in 3D as a simple example for skin tissue. To study cell functions and tissue formation process in 3D, different characteristics, such as cell localisation and proliferation were investigated. We further analysed the formation of adhering and gap junctions, which are fundamental for tissue morphogenesis and cohesion. In this study, it was demonstrated that LaBP is an outstanding tool for the generation of multicellular 3D constructs mimicking tissue functions. These findings are promising for the realisation of 3D in vitro models and tissue substitutes for many applications in tissue engineering.