gebhart/patrepeval huggingface dataset:
An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1 (2009)

The mammalian target of rapamycin (mTOR) kinase is the catalytic subunit of two functionally distinct complexes, mTORC1 and mTORC2, that coordinately promote cell growth, proliferation, and survival. Rapamycin is a potent allosteric mTORC1 inhibitor with clinical applications as an immunosuppressant and anti-cancer agent. Here we find that Torin1, a highly potent and selective ATP-competitive mTOR inhibitor that directly inhibits both complexes, impairs cell growth and proliferation to a far greater degree than rapamycin. Surprisingly, these effects are independent of mTORC2 inhibition and are instead because of suppression of rapamycin-resistant functions of mTORC1 that are necessary for cap-dependent translation and suppression of autophagy. These effects are at least partly mediated by mTORC1-dependent and rapamycin-resistant phosphorylation of 4E-BP1. Our findings challenge the assumption that rapamycin completely inhibits mTORC1 and indicate that direct inhibitors of mTORC1 kinase activity may be more successful than rapamycin at inhibiting tumors that depend on mTORC1.
Efficacy and tolerability of a sequential, artesunate suppository plus mefloquine, treatment of severe falciparum malaria (1995)

Thirty patients with severe falciparum malaria were each given a total of 1600-mg artesunate suppository over three consecutive days followed by 1250 mg mefloquine per os, divided into two doses which were given 12 h apart. All patients were admitted for 28 days to the Bangkok Hospital for Tropical Diseases, so that the efficacy and tolerability of the treatment could be assessed. All the patients showed clinical improvement, with mean (S.D.) parasite and fever clearance times of 50.4 (13.0) and 70.7 (44.9) h, respectively. Two patients with unrousable coma (Glasgow coma score < or = 8) on admittance regained consciousness 46 and 48 h post-treatment. One other patient had acute renal failure and required dialysis. Most patients (80%) were initially hyperparasitaemic, with a mean density of 184,344 parasites/microliters blood. No deaths occurred. Efficacy was evaluated in 25 of the patients. The cure rate 28 days post-treatment was 92%. None of the patients had major adverse effects although two had tenesmus and passed stools immediately after each suppository was administered. A fresh suppository had to be inserted when this occurred. The results indicate that artesunate suppositories followed by oral mefloquine constitute a well-tolerated regimen with a high cure rate. The combination is suitable as an alternative treatment for severe malaria, particularly in children. Further, large-scale studies are required.
Fusion and Haemolysis of Erythrocytes caused by Three Togaviruses: Semliki Forest, Sindbis and Rubella (1980)

Semliki Forest, Sindbis and rubella viruses can fuse erythrocytes from several different species. Large fusion vesicles consisting of tens to hundreds of red blood cells were seen under optical conditions. For the haemagglutination and cell fusion to occur the adsorption of virus and further incubation had to be carried out at pH 5.8. Haemagglutination took place over a wide temperature range (0 to 40 degrees C) whereas fusion required temperatures between 37 and 42 degrees C. Haemolysis of red blood cells induced by togaviruses also required initial incubation at pH 5.8 to enable attachment of the virus to occur after which the pH of the buffer could be raised to neutrality without inhibiting the haemolysis. The amount of togaviruses and Sendai virus required to fuse red blood cells was about the same [I haemagglutinating unit (HAU)/ml] but different ionic conditions were required for fusion.
Biological Containers: Protein Cages as Multifunctional Nanoplatforms (2007)

Abstract Materials scientists increasingly draw inspiration from the study of how biological systems fabricate materials under mild synthetic conditions by using self‐assembled macromolecular templates. Containerlike protein architectures such as viral capsids and ferritin are examples of such biological templates. These protein cages have three distinct interfaces that can be synthetically exploited: the interior, the exterior, and the interface between subunits. The subunits that comprise the building blocks of these structures can be modified both chemically and genetically in order to impart designed functionality to different surfaces of the cage. Therefore, the cages possess a great deal of synthetic flexibility, which allows for the introduction of multifunctionality in a single cage. In addition, hierarchical assembly of the functionalized cages paves the way for development of a new class of materials with a wide range of applications from electronics to biomedicine.
miR-10b Targets Tiam1 (2010)

Understanding the mechanisms by which specific microRNAs regulate cell migration and invasion is a timely and significant problem in cancer cell biology. miR-10b is of interest in this regard because its expression is altered in breast and other cancers. Our analysis of potential miR-10b targets identified Tiam1 (T lymphoma invasion and metastasis 1), a guanidine exchange factor for Rac. We demonstrate, using an miR-10b synthetic precursor, expression vector, and antisense oligonucleotide, that miR-10b represses Tiam1 expression in breast carcinoma cells and that it interacts with the 3'-UTR of Tiam1. Consistent with the involvement of Tiam1 in cell motility, we observed that miR-10b suppresses the ability of breast carcinoma cells to migrate and invade. Importantly, we demonstrate that miR-10b also inhibits Tiam1-mediated Rac activation. These data provide a mechanism for the regulation of Tiam1-mediated Rac activation in breast cancer cells and need to be considered in the context of other reported functions for miR-10b.
Linear Synthesis of the Tumor-Associated Carbohydrate Antigens Globo-H, SSEA-3, and Gb3 (2002)

The tumor-associated carbohydrate antigens Globo-H, SSEA-3, and Gb3 were synthesized in a linear fashion using glycosyl phosphate monosaccharide building blocks. All of the building blocks were prepared from readily available common precursors. The difficult alpha-(1-->4-cis)-galactosidic linkage was installed using a galactosyl phosphate donor with high selectivity. Introduction of the beta-galactosamine unit required the screening a variety of amine protecting groups to ensure good donor reactivity and protecting group compatibility. An N-trichloroacetyl-protected galactosamine donor performed best for the installation of the beta-glycosidic linkage. Conversion of the trichloroacetyl group to the N-acetyl group was achieved under mild conditions, fully compatible with the presence of multiple glycosidic bonds. This synthetic strategy is expected to be amenable to the synthesis of the globo-series of tumor antigens on solid-support.
Sequence of the precursor to rat ornithine aminotransferase deduced from a cDNA clone. (1985)

The nucleotide sequence of ornithine aminotransferase mRNA from rat liver, including the entire coding and 3' untranslated regions, was determined from two overlapping cDNA clones. The mRNA encodes a precursor polypeptide of 439 amino acid residues with a molecular weight of 48,332. The deduced amino acid composition of the proposed mature enzyme sequence (residues 35 through 439) was in good agreement with that reported for the purified protein. The amino-terminal segment of the precursor corresponding to residues 1 through 34 has an overall positive charge, containing 6 basic residues and only a single acidic residue, and is postulated to be the mitochondrial leader sequence. The first 22 amino acid residues of the proposed leader sequences share 54% homology with the leader peptide of rat ornithine transcarbamylase precursor and more limited homology to the leader peptides of other nuclear-encoded mitochondrial matrix proteins. Homology was also observed between residues 286 through 362 ornithine aminotransferase precursor and a region containing the pyridoxyl phosphate binding domain of mitochondrial aspartate aminotransferase.
An autonomous 16 mm/sup 3/ solar-powered node for distributed wireless sensor networks (2003)

A 16 mm/sup 3/ autonomous solar-powered sensor node with bidirectional optical communication for distributed sensor networks has been demonstrated. The device digitizes integrated sensor signals and transmits/receives data over a free-space optical link. The system consists of three die - a 0.25 /spl mu/m CMOS ASIC, a 2.6 mm/sup 2/ SOI solar cell array, and a micromachined four-quadrant corner-cube retroreflector (CCR), allowing it to be used in a one-to-many network configuration. The CMOS ASIC includes a photosensor integrated 3 MHz oscillator, 69 pJ/bit optical receiver and 31 pJ/sample ADC.
Molecular Cloning and Characterization of a Novel Type of Histamine Receptor Preferentially Expressed in Leukocytes (2000)

Recently cDNA encoding the histamine H3 receptor was isolated after 15 years of considerable research. However, several studies have proposed heterogeneity of the H3 receptor. We report here the molecular cloning and characterization of a novel type of histamine receptor. A novel orphan G-protein-coupled receptor named GPRv53 was obtained through a search of the human genomic DNA data base and analyzed by rapid amplification of cDNA ends (RACE). GPRv53 possessed the features of biologic amine receptors and had the highest homology with H3 receptor among known G-protein-coupled receptors. Mammalian cells expressing GPRv53 were demonstrated to bind and respond to histamine in a concentration-dependent manner. In functional assays, not only an H3 receptor agonist, R-(alpha)-methylhistamine, but also a H3 receptor antagonist, clobenpropit, and a neuroleptic, clozapine, activated GPRv53-expressing cells. Tissue distribution analysis revealed that expression of GPRv53 is localized in the peripheral blood leukocytes, spleen, thymus, and colon, which was totally different from the H3 receptor, whose expression was restricted to the brain. The discovery of the GPRv53 receptor will open a new phase of research on the physiological role of histamine.
Negative Correlation of Distributions of Streptococcus cristatus and Porphyromonas gingivalis in Subgingival Plaque (2009)

Porphyromonas gingivalis is one of the major causative agents of adult periodontitis. One of the features of this periodontal pathogen is its ability to attach to a variety of oral bacterial surfaces and to colonize subgingival dental plaque. We have shown that Streptococcus cristatus CC5A inhibits expression of fimA, a gene encoding the major protein subunit of long fimbriae in P. gingivalis; as a result, S. cristatus interrupts formation of P. gingivalis biofilms. Here we further demonstrate that the inhibitory activity of S. cristatus affects multiple strains of P. gingivalis and that optimal inhibitory activity correlates with levels of arginine deiminase expression in S. cristatus. More strikingly, the impact of S. cristatus on P. gingivalis colonization was revealed by comparing levels of P. gingivalis and S. cristatus in subgingival dental plaque. Spearman correlation analysis indicated a negative correlation between the distributions of S. cristatus and P. gingivalis (r = -0.57; P < 0.05). These data suggest that some early colonizers of dental plaque, such as S. cristatus, may be beneficial to the host by antagonizing the colonization and accumulation of periodontal pathogens such as P. gingivalis.
Cloning and sequencing of a human pancreatic tumor mucin cDNA. (1990)

A monospecific polyclonal antiserum against deglycosylated human pancreatic tumor mucin was used to select human pancreatic mucin cDNA clones from a lambda gt11 cDNA expression library developed from a human pancreatic tumor cell line. The full-length 4.4-kilobase mucin cDNA sequence included a 72-base pair 5'-untranslated region and a 307-base pair 3'-untranslated region. The predicted amino acid sequence for this cDNA revealed a protein of 122,071 daltons containing 1,255 amino acid residues of which greater than 60% were serine, threonine, proline, alanine, and glycine. Approximately two-thirds of the protein sequence consisted of identical 20-amino acid tandem repeats which were flanked by degenerate tandem repeats and nontandem repeat sequences on both the amino-terminal and carboxyl-terminal ends. The amino acid sequence also contained five putative N-linked glycosylation sites, a putative signal sequence and transmembrane domain, and numerous serine and threonine residues (potential O-linked glycosylation sites) outside and within the tandem repeat position. The cDNA and deduced amino acid sequence of the pancreatic mucin sequence was over 99% homologous with a mucin cDNA sequence derived from breast tumor mucin, even though the native forms of these molecules are quite distinct in size and degree of glycosylation.
Elastin structure and its involvement in skin photoageing (2016)

Skin aging is a complex process that may be caused by factors that are intrinsic and extrinsic to the body. Ultraviolet (UV) radiation represents one of the main sources of skin damage over the years and characterizes a process known as photoaging. Among the changes that affect cutaneous tissue with age, the loss of elastic properties caused by changes in elastin production, increased degradation and/or processing produces a substantial impact on tissue esthetics and health. The occurrence of solar elastosis is one of the main markers of cutaneous photoaging and is characterized by disorganized and non-functional deposition of elastic fibers. The occurrence of UV radiation-induced alternative splicing of the elastin gene, which leads to inadequate synthesis of the proteins required for the correct assembly of elastic fibers, is a potential explanation for this phenomenon. Innovative studies have been fundamental for the elucidation of rarely explored photoaging mechanisms and have enabled the identification of effective therapeutic alternatives such as cosmetic products. This review addresses cutaneous photoaging and the changes that affect elastin in this process.
Mass Spectrometric Analysis of Intact Human Monoclonal Antibody Aggregates Fractionated by Size-Exclusion Chromatography (2010)

ESI-TOF MS is a useful tool complementary to HP-SEC to identify and characterize small oligomeric protein aggregates.
Chemical and Biological Applications of Digital-Microfluidic Devices (2007)

The advent of digital microfluidic lab-on-a-chip (LoC) technology offers a platform for developing diagnostic applications with the advantages of portability, reduction of the volumes of the sample and reagents, faster analysis times, increased automation, low power consumption, compatibility with mass manufacturing, and high throughput. Moreover, digital microfluidics is being applied in other areas such as airborne chemical detection, DNA sequencing by synthesis, and tissue engineering. In most diagnostic and chemical-detection applications, a key challenge is the preparation of the analyte for presentation to the on-chip detection system. Thus, in diagnostics, raw physiological samples must be introduced onto the chip and then further processed by lysing blood cells and extracting DNA. For massively parallel DNA sequencing, sample preparation can be performed off chip, but the synthesis steps must be performed in a sequential on-chip format by automated control of buffers and nucleotides to extend the read lengths of DNA fragments. In airborne particulate-sampling applications, the sample collection from an air stream must be integrated into the LoC analytical component, which requires a collection droplet to scan an exposed impacted surface after its introduction into a closed analytical section. Finally, in tissue-engineering applications, the challenge for LoC technology is to build high-resolution (less than 10 microns) 3D tissue constructs with embedded cells and growth factors by manipulating and maintaining live cells in the chip platform. This article discusses these applications and their implementation in digital-microfluidic LoC platforms.
Quantitative Imaging of Na/I Symporter Transgene Expression Using Positron Emission Tomography in the Living Animal (2004)

Transgene expression can be measured in living animals by positron emission tomography (PET) using reporter genes associated with radiolabeled substrates or ligands. We examined here whether PET images obtained with a new reporter gene system (sodium/iodide symporter (NIS) and [124I]iodide) could provide quantitative information on gene expression in mice. Mice received various doses of recombinant adenovirus in which the expression of the NIS cDNA was driven by the CMV promoter and subsequently [124I]iodide. Postmortem gamma counting of liver biopsies was correlated to the adenovirus dose and with NIS mRNA concentration. In addition, immunohistochemically NIS-positive cells increased with higher tissue activities. Finally, a linear relationship existed between the postmortem gamma counting in liver tissues and that calculated from images obtained through small animal PET scanning (r = 0.9581), although there was a bias at high and low specific values. This systematic study on 35 animals demonstrates that quantitative information on gene expression can be obtained from PET images using the NIS reporter system. This new methodology of quantitative imaging of gene expression presents the advantage of avoiding extensive radiochemistry, an important step for more disseminated use of this emerging technology. In addition, this work supports further development of the NIS system for noninvasive assessment of gene delivery in preclinical and clinical studies.
Bispecific Minibodies Targeting HER2/neu and CD16 Exhibit Improved Tumor Lysis When Placed in a Divalent Tumor Antigen Binding Format (2004)

Unconjugated monoclonal antibodies have emerged as important therapeutic agents for selected malignancies. One mechanism by which antibodies can exert cytotoxic effects is antibody-dependent cellular cytotoxicity (ADCC). In an effort to increase the efficiency of ADCC at tumor sites, we have focused on the construction of bispecific antibodies specific for the tumor antigen HER2/neu and the Fc gamma RIII-activating receptor (CD16) found on NK cells, mononuclear phagocytes, and neutrophils. Here, we describe the production of bispecific minibodies in two distinct binding formats. The parent minibody was constructed such that the IgG1 C(H)3 constant domain serves as the oligomerization domain and is attached to an anti-CD16 and an anti-HER2/ neu single-chain Fv via 19- and 29-amino acid linkers, respectively. This molecule can be expressed in mammalian cells from a dicistronic vector and has been purified using sequential affinity purification techniques. Analysis by surface plasmon resonance shows that the bispecific minibody can bind to HER2/neu and CD16, both individually and simultaneously. Furthermore, cytotoxicity studies show that the minibody can induce significant tumor cell lysis at a concentration as low as 20 nm. A trimeric, bispecific minibody (TriBi) that binds dimerically to HER2/neu and monomerically to CD16 induces equivalent cytotoxicity at lower antibody concentrations than either the parent minibody or the corresponding single-chain dimer. Both minibody constructs are stable in mouse and human serum for up to 72 h at 37 degrees C. These minibodies have the potential to target solid tumors and promote tumor lysis by natural killer cells and mononuclear phagocytes.
Experimental induction of chronic borreliosis in adult dogs exposed to Borrelia burgdorferi–infected ticks and treated with dexamethasone (2001)

Use of this technique successfully induced borreliosis in young dogs. Dogs with experimentally induced borreliosis may be useful in evaluating vaccines, chemotherapeutic agents, and the pathogenesis of borreliosis-induced arthritis.
Introduction of estrogen-responsiveness into mammalian cell lines (1986)

We introduced estrogen responsiveness as a new characteristic into rat hepatoma, mouse Ltk- and human HeLatk-cells by transfecting the human estrogen receptor (ER) cDNA. To measure the estrogen response we used Xenopus vitellogenin gene A2 constructs linked to the bacterial CAT gene. Transient cotransfections of the ER cDNA and the vitellogenin gene-CAT constructs containing the estrogen responsive element (ERE) lead to a hormone dependent induction of CAT activity whereas cotransfected vitellogenin gene constructs lacking the ERE are not inducible. Stable transfections of ER cDNA into Ltk- cells give rise to cell clones that are estrogen responsive as shown by transfection of various vitellogenin gene-CAT constructs. These results prove that the transfected ER is biologically active and is sufficient to make a cell estrogen responsive.
IBM System Blue Gene Solution: Blue Gene/P Application Development (2009)

This publication is one in a series of books written specifically for the System Blue Gene/P Solution. The Blue Gene/P system is the second generation of a massively parallel supercomputer from in the System Blue Gene Solution series. In this book, we provide an overview of the application development environment for the Blue Gene/P system. We intend to help programmers understand the requirements to develop applications on this high-performance massively parallel supercomputer.In this book, we explain instances where the Blue Gene/P system is unique in its programming environment. We also attempt to look at the differences between the System Blue Gene/L Solution and the Blue Gene/P Solution. In this book, we do not delve into great depth about the technologies that are commonly used in the supercomputing industry, such as Message Passing Interface (MPI) and Open Multi-Processing (OpenMP), nor do we try to teach parallel programming. References are provided in those instances for you to find more information if necessary.Prior to reading this book, you must have a strong background in high-performance computing (HPC) programming. The high-level programming languages that we use throughout this book are C/C++ and Fortran95. Previous experience using the Blue Gene/L system can help you better understand some concepts in this book that we do not extensively discuss. However, several publications about the Blue Gene/L system are available for you to obtain general information about the Blue Gene/L system. We recommend that you refer to IBM Redbooks on page 373 for a list of those publications.