gebhart/patrepeval huggingface dataset:
Selective plasma pharmacokinetics and brain uptake in the mouse of enzyme fusion proteins derived from species-specific receptor-targeted antibodies (2012)

Enzymes may be re-engineered for brain drug targeting as an IgG-enzyme fusion protein, where the IgG is a monoclonal antibody (MAb) against an endogenous blood-brain barrier (BBB) receptor transporter, such as the insulin receptor or transferrin receptor (TfR). Iduronate 2-sulfatase (IDS) is fused to the heavy chain of a genetically engineered MAb against the human insulin receptor (HIR). Neither the HIRMAb alone, nor the HIRMAb-IDS fusion protein, is delivered across the BBB in the mouse, owing to lack of cross-reactivity of the HIRMAb with the insulin receptor in the mouse. The uptake of the HIRMAb-IDS fusion protein in peripheral organs exceeds that of the HIRMAb, which is attributed to uptake mediated via the mannose-6 phosphate receptor in non-brain organs. In contrast to the lack of BBB transport of the HIRMAb-IDS fusion protein, there is high BBB penetration in the mouse of an IDS fusion protein and a chimeric MAb against the mouse TfR. The comparison of the brain distribution of two different IgG-IDS fusion proteins, with different reactivity for an endogenous BBB receptor, illustrates the difference in brain targeting of a biopharmaceutical caused by the targeting properties of the IgG domain of the fusion protein.
Synthesis of pyrrolo[3,2-d]pyrimidines from furazano[3,4-d]pyrimidines via enolate and ene adducts (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of pyrrolo[3,2-d]pyrimidines from furazano[3,4-d]pyrimidines via enolate and ene adductsL. Eric Crane, G. Peter Beardsley, and Yoshifumi MakiCite this: J. Org. Chem. 1980, 45, 19, 3827–3831Publication Date (Print):September 1, 1980Publication History Published online1 May 2002Published inissue 1 September 1980https://pubs.acs.org/doi/10.1021/jo01307a019https://doi.org/10.1021/jo01307a019research-articleACS PublicationsRequest reuse permissionsArticle Views139Altmetric-Citations7LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Chromatin remodeling finds its place in the DNA double-strand break response (2009)

The accurate repair of chromosomal double-strand breaks (DSBs) arising from exposure to exogenous agents, such as ionizing radiation (IR) and radiomimetic drugs is crucial in maintaining genomic integrity, cellular viability and the prevention of tumorigenesis. Eukaryotic cells have evolved efficient mechanisms that sense and respond to DSBs. The DNA DSB response is facilitated by hierarchical signaling networks that orchestrate chromatin structural changes, cell-cycle checkpoints and multiple enzymatic activities to repair the broken DNA ends. Sensors and transducers signal to numerous downstream cellular effectors which function primarily by substrate posttranslational modifications including phosphorylation, acetylation, methylation and ubiquitylation. In particular, the past several years have provided important insight into the role of chromatin remodeling and histones-specific modifications to control DNA damage detection, signaling and repair. This review summarizes recently identified factors that influence this complex process and the repair of DNA DSBs in eukaryotic cells.
Active virtual guides as an apparatus for augmented reality based telemanipulation system on the Internet (2002)

In many current teleoperation architectures, remote tasks are indirectly performed by a human operator (HO) by means of a virtual environment consisting in a virtual or symbolic representation of the remote site. In order to achieve virtual tasks, the interaction of the HO and the virtual representation is monitored. Monitoring results are subsequently translated into a sequence of instructions sent to the remote robot for actual execution. This paper focuses on different strategies designed to allow a user-friendly operator interaction with the virtual representation in order to achieve complex remote tasks via the Internet. The use of active virtual guides to assist the HO in performing simple or complex tasks with enhanced performance (speed, precision and safety) is also discussed. Techniques such as virtual reality (VR), augmented reality (AR) combined with Internet-based programming facilities are investigated as part of the proposed teleoperation system named ARITI (acronym for Augmented Reality Interface for Telerobotic applications via Internet).
Toward An Architecture Of A Component-Based System Supporting Separation Of Non- Functional Concerns (2007)

The promises of component-based technology can only be fully realized when the system contains in its design a necessary level of separation of concerns. The authors propose to focus on the concerns that emerge throughout the life cycle of the system and use them as an architectural foundation for the design of a component-based framework. The proposed model comprises a set of superimposed views of the system describing its functional and non-functional concerns. This approach is illustrated by the design of a specific framework for data analysis and data acquisition and supplemented with experiences from using the systems developed with this framework at the Fermi National Accelerator Laboratory.
miR-27a as an Oncogenic microRNA of Hepatitis B Virus-related Hepatocellular Carcinoma (2013)

microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through post-transcriptional interactions with mRNA. miRNAs have recently emerged as key regulators of various cancers. Although miR- 27a has been implicated in several other cancers, its role in hepatitis B virus-related hepatocellular carcinoma (HCC) is unknown. In this study, we showed miR-27a to be frequently up-regulated in HCC tissues and HCC cell lines (HepG2 and Huh7). Overexpression of miR-27a enhanced cell proliferation, promoted migration and invasion, and activated cell cycling in HepG2 and Huh7 cells. In summary, our results suggest that up-regulation of miR-27a may play an oncogenic role in the development of HCC and might thus be a new therapeutic target in HCC patients.
An improved analytic model for the metal-insulator-semiconductor tunnel junction (1988)

Two improvements to a comprehensive analytic model that describes the steady-state current in a metal-insulator-semiconductor tunnel junction are reported. The first modification replaces the conventional two-band representation of the thin oxide band structure with a one-band model. In this approach, the electron barrier height for tunneling is always less than the hole barrier height by an amount equal to the semiconductor bandgap. The second improvement enables the energy dependence of the electron and hole tunneling probability factors to be taken into account. This is accomplished by expressing the tunneling probabilities as short-series expressions. The capability of the model to accurately predict the current-voltage characteristics of MIS tunnel junctions is demonstrated by simulating the DC performance of a tunnel emitter transistor. The results are in good agreement with experimental data.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Reasoning by cases and the formation of conditional programs (1985)

ABSTRACT (1) Reasoning by cases, a natural feature of human reasoning, has been difficult to formulate so that it can be performed naturally when needed. Several difficulties arise: (1) how to motivate the use of reasoning by cases when and only when needed, (2) how to determine an appropriate analysis of the goal into cases, and (3) how to carry out the deduction in each case and combine the results. In this paper we focus on how reasoning by cases can be naturally accomplished in the framework of derived antecedents (Smith 1982). Our main technical contributions are (1) a set of strategies that draw on the context of a deduction to provide an appropriate case analysis for a goal, and (2) inference rules for carrying out reasoning by cases and forming conditional terms for the existentially quantified variables in the initial goal. I
Abstract 2238: Self-microemulsifying drug delivery systems (SMEDDS) containing novel compounds for the chemoprevention of pancreatic cancer (2018)

Abstract Pancreatic cancer (PC) is the fourth leading cause of deaths in the United States, claiming approximately 43,000 lives every year. Existing trends suggest that it will be the second cause of death after lung cancer within the next 20 years. With mortality rates remaining high even after decades of research, scientists are now turning to develop chemopreventive strategies that may stop or delay the initiation and progression of the disease. Our study reports the chemoprevention potential of (1) a free drug combination of H1-receptor antagonist drug with Sulforaphane (SFN), a neutraceutical compound derived from broccoli and (2) lipid nanocarriers of H1-receptor antagonist drug (SP1 SMEDDS; formulation patent pending) with free SFN when administered at low doses in human pancreatic cancer cell lines (MIA PaCa-2 and Panc-1). IC50 concentrations were calculated for various treatment groups using MTS viability assay in accordance with published protocol, using 96-well microplates and incubation time of 72 h. The free drug combination revealed almost 70-fold and 20-fold enhancement in chemoprevention efficacy (based decrease in cancer cell viability) as compared to controls. Interestingly, the free drug combination (at 5µM) showed ~55 % (p&lt;0.001) inhibition in cell lines whereas no measurable response was observed with individual free drug treatments at the same concentration. This confirmed the synergistic chemoprevention potential of the free drug combination. SP1 SMEDDS were optimized for particle size, encapsulation efficiency and chemoprevention efficacy. SP1 SMEDDS (10µM) by itself exhibited 54% (p&lt;0.001) cell line inhibition whereas no measurable response was observed with free drug at that same concentration, confirming the potential of lipid nanocarriers in enhancing the chemoprevention activity. Moreover, the SP1 SMEDDS in combination with free SFN demonstrated synergistic activity with 500-fold, 140-fold and 7-fold enhancement in chemoprevention potential as compared to the free HI-receptor antagonist, SFN and the free drug combination, respectively. In conclusion, a novel lipid formulation of an H1-receptor antagonist in combination with free SFN was invented (provisional patent applied) to successfully elicit PC chemoprevention. Future studies will look into the efficacy of this novel formulation in in vivo PC models. Citation Format: Preshita Desai, Arvind Thakkar, Jeffrey Wang, Sunil Prabhu. Self-microemulsifying drug delivery systems (SMEDDS) containing novel compounds for the chemoprevention of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2238.
Cutting Edge: Typhlocolitis in NF-κB-Deficient Mice (2001)

Activation of inflammatory gene expression by the transcription factor NF-kappaB is a central pathway in many inflammatory disorders, including colitis. Increased NF-kappaB activity has been linked with development of colitis in humans and animal models, thus it was unexpected when NF-kappaB-deficient mice developed spontaneous typhlocolitis. To further characterize this finding, we induced typhlocolitis in rederived NF-kappaB-deficient mice using intragastric infection with Helicobacter hepaticus. At 6 wk postinfection (PI), severe colitis with increased type 1 cytokine expression was seen in infected mice that lacked the p50 subunit of NF-kappaB and were also heterozygous for the p65 subunit of NF-kappaB(p50(-/-)p65(+/-)). Mice lacking the p50 subunit alone (p50(-/-)) were less severely affected, and wild-type mice and p65(+/-) mice were unaffected. T cell development in NF-kappaB-deficient mice was normal. These data indicate that p50 and p65 subunits of NF-kappaB have an unexpected role in inhibiting the development of colitis.
Intensity Gradient Technique for Efficient Intra-Prediction in H.264/AVC (2008)

This study presents an intensity gradient approach for intra-prediction in H.264 encoding system, which enhances the performance and efficiency of previous fast algorithms. We propose a preprocessing stage in which eight orientation features are extracted from a macro block by the intensity gradient filters. The orientation features are utilized to select a subset of prediction modes to be involved in the rate-distortion calculation so that the encoding time can be reduced. The simulation results indicate that the intensity gradient based algorithm for intra-prediction contributes better tradeoff between rate-distorion performance and encoding complexity than the previous algorithms. Compared to H.264 reference software, the proposed algorithm introduces slight PSNR degradation and bit rate increase but saves around 76% of the total encoding time with all intra-frame coding.
Programmed death-1 (PD-1)–deficient mice are extraordinarily sensitive to tuberculosis (2010)

The programmed death-1 (PD-1) costimulatory receptor inhibits T and B cell responses and plays a crucial role in peripheral tolerance. PD-1 has recently been shown to inhibit T cell responses during chronic viral infections such as HIV. In this study, we examined the role of PD-1 in infection with Mycobacterium tuberculosis, a common co-infection with HIV. PD-1-deficient mice showed dramatically reduced survival compared with wild-type mice. The lungs of the PD-1-/- mice showed uncontrolled bacterial proliferation and focal necrotic areas with predominantly neutrophilic infiltrates, but a lower number of infiltrating T and B cells. Proinflammatory cytokines, such as TNF-alpha, IL-1, and especially IL-6 and IL-17 were significantly increased in the lung and sera of infected PD-1-/- mice, consistent with an aberrant inflammation. Microarray analysis of the lungs infected with M. tuberculosis showed dramatic differences between PD-1-/- and control mice. Using high-stringency analysis criteria (changes of twofold or greater), 367 transcripts of genes were differentially expressed between infected PD-1-/- and wild-type mice, resulting in profoundly altered inflammatory responses with implications for both innate and adaptive immunity. Overall, our studies show that the PD-1 pathway is required to control excessive inflammatory responses after M. tuberculosis infection in the lungs.
Diastereoisomeric Salt Formation and Enzyme-Catalyzed Kinetic Resolution as Complementary Methods for the Chiral Separation of <i>cis</i>-/<i>trans</i>-Enantiomers of 3-Aminocyclohexanol (2010)

This contribution demonstrates the preparative-scale synthesis of (1S,3S)-3-aminocyclohexanol by either enzymatic kinetic resolution of Cbz-protected 3-aminocyclohexanols or direct diastereoisomeric salt formation with (R)-mandelic acid. The salt formation demonstrates how a single enantiomer, (1S,3S)-3-aminocyclohexanol (R)-mandelate, can be effectively isolated from the cis/trans racemic mixture and subsequently converted to the free amine, (1S,3S)-3-aminocyclohexanol, by ion-exchange chromatography. We have also demonstrated how the other three enantiomers of 3-aminocyclohexanol can be prepared by either diastereoisomeric salt formation or enzymatic kinetic resolution.
Allogeneic hematopoietic stem cell transplantation: state of the art and new perspectives (2005)

Allogeneic hematopoietic stem cell transplantation (ASCT) is a well-established therapy for leukemias and other immunohematopoietic disorders. In more recent years, bone marrow as stem cell source has been replaced by peripheral blood stem cells, which results in faster engraftment. Cord blood grafts are increasingly used. Conditioning prior to transplant may be myeloablative or nonmyeloablative. The latter is used preferentially in patients with high age or organ impairment. Isolation in the hospital during posttransplant pancytopenia has been challenged by promising results using home care. PCR diagnosis and new antifungal and antiviral treatment have reduced morbidity and mortality. The major threat to a successful outcome after ASCT is leukemic relapse. PCR techniques to detect recipient cells in the leukemic cell lineage or minimal residual disease enable early detection of leukemic cells. Donor lymphocyte infusions have an antileukemic effect. ASCT has shown an antitumor effect in metastatic cancers from breast, kidney, colon, ovaries, prostate and pancreas. Mesenchymal stem cells may be derived from bone marrow and have the capacity to differentiate into several mesenchymal tissues, such as bone, cartilage and fat. They seem to escape the immune system and have immunomodulatory effects in vitro and in vivo. To conclude, ASCT is a potent immunotherapy.
Effect of an SiO2 layer on the superconductive properties of the high-<i>T</i> <i>c</i> Bi-Sr-Ca-Cu-O films (1990)

High-Tc Bi-Sr-Ca-Cu-O thin films were coated with electron-beam-evaporated SiO2. The room-temperature resistivity of the coated films and their superconductivity onset and zero-resistance temperatures were not affected by the dielectric film. High-frequency capacitance-voltage studies did not show any modulation of space charge in the surface layer of the superconducting film. It is observed that the high-frequency (1 MHz) capacitance of the metal-insulator-superconductor structure has an appreciable temperature dependence.
Hydraulic fracture diagnostics from Krauklis-wave resonance and tube-wave reflections (2017)

Fluid-filled fractures support guided waves known as Krauklis waves. The resonance of Krauklis waves within fractures occurs at specific frequencies; these frequencies, and the associated attenuation of the resonant modes, can be used to constrain the fracture geometry. We use numerical simulations of wave propagation along fluid-filled fractures to quantify fracture resonance. The simulations involve solution of an approximation to the compressible Navier-Stokes equation for the viscous fluid in the fracture coupled to the elastic-wave equation in the surrounding solid. Variable fracture aperture, narrow viscous boundary layers near the fracture walls, and additional attenuation from seismic radiation are accounted for in the simulations. We then determine how tube waves within a wellbore can be used to excite Krauklis waves within fractures that are hydraulically connected to the wellbore. The simulations provide the frequency-dependent hydraulic impedance of the fracture, which can then be used in a frequency-domain tube-wave code to model tube-wave reflection/transmission from fractures from a source in the wellbore or at the wellhead (e.g., water hammer from an abrupt shut-in). Tube waves at the resonance frequencies of the fracture can be selectively amplified by proper tuning of the length of a sealed section of the wellbore containing the fracture. The overall methodology presented here provides a framework for determining hydraulic fracture properties via interpretation of tube-wave data.
A Homologous Radioimmunoassay for Human Prolactin1 (1973)

We have developed a sensitive homologous radioimmunoassay for human prolactin (hPRL). Prolactin isolated from human pituitary glands was used for generating antibodies in rabbits, for iodination, and for standards. The assay is highly specific for hPRL and measures concentrations of hPRL as low as 1 ng/ml of human plasma. In this assay, the plasma concentrations of hPRL in a group of randomly selected male and female individuals averaged 13 ± 4 (SD) and 14 ± 4 ng/ml, respectively. In contrast, hPRL in the pooled plasma of pregnant women assayed 80 ng/ml; a post-partum plasma measured 215 ng/ml. Of 6 patients with acromegaly, 5 possessed hPRL levels above 34 ng/ml, the average being 40 ± 9 ng/ml. Administration of TSH releasing hormone increased plasma hPRL concentrations by 4-fold in both a male and a female subject, while LH releasing hormone depressed them slightly. The concentration of hPRL in pituitary glands removed at autopsy was 1.5 μg/mg for a male and 1.3 μg/mg for a female. These values approximate those found in other mammals.
Quinolone-Based Drugs Against Toxoplasma gondii and Plasmodium spp (2005)

Owing to the rapid emergence of multi-resistant strains of Plasmodium spp. (the causative agents of malaria) and the limitations of drugs used against Toxoplasma gondii (an important opportunistic pathogen associated with AIDS and congenital birth defects), the discovery of new therapeutical targets and the development of new drugs are needed. The presence of the prokaryotic-like organelle in apicomplexan parasites (i.e. plastids), which comprise these major human pathogens, may represent a unique target for antibiotics against these protozoa. Quinolones which are known to be highly potent against bacteria were also found to specifically disrupt these parasites. They inhibit DNA replication by interacting with two essential bacterial type II topoisomerases, DNA gyrase and topoisomerase IV. There are some clues that quinolones act on plastids with a similar mechanism of action. After a brief presentation of plasmodium and toxoplasma dedicated to their life cycle, the chemotherapies presently used in clinics to fight against these protozoa and the potential new targets and drugs, we will focus our attention on their plastid which is one of these promising new targets. Then, we will present the various drugs and generations of quinolones, the leading molecules, and their inhibitory effects against these parasites together with their pharmacological properties that have been established from in vitro and in vivo studies. We will also discuss their possible mode of action.
Correcting log ratios for signal saturation in cDNA microarrays (2004)

We present a method to correct for saturation using pixel-level data. The method is based on a censored regression model. Evaluations on several arrays indicate that the method performs well. Simulation studies suggest that the method is robust under certain model violations.
Roughening of the Si/SiO2 interface during SC1-chemical treatment studied by scanning tunneling microscopy (2000)

The Si/SiO2 interface morphology is observed with subnanometer resolution by an ultrahigh vacuum scanning tunneling microscope (STM). We analyze the roughness of the Si/SiO2 interface for a chemical oxide film formed by a wet chemical process (NH4OH/H2O2/H2O treatment). The oxide film is selectively removed by irradiating a field emission electron beam extracted from a STM tip at a temperature of 300–350 °C. We find that during the chemical process the roughness of the Si/SiO2 interface increases with the treatment time.