gebhart/patrepeval huggingface dataset:
A systems neuroscience approach to autism: Biological, cognitive, and clinical perspectives (2003)

Autism is a behaviorally defined disorder characterized by a broad constellation of symptoms. Numerous studies directed to the biological substrate demonstrate clear effects of neurodevelopmental differences that will likely point to the etiology, course, and long-term outcomes of the disorder. Consistently replicated research on the neural underpinnings of autism is reviewed. In general, results suggest several main conclusions: First, autism is a heterogeneous disorder and is likely to have multiple possible etiologies; second, structural brain studies have indicated a variety of diffuse anatomical differences, reflective of an early developmental change in the growth or pruning of neural tissue, rather than localized lesions; similarly, neurochemical studies suggest early, neuromodulatory discrepancies rather than gross or localized abnormalities; and finally, there are a number of limitations on studies of brain activity that to date preclude definitive answers to questions of how the brain functions differently in autism. The large number of active research programs investigating the cognitive neuroscience of autism spectrum disorders, in combination with the exciting development of new methodologies and tools in this area, indicates the drama and excitement of work in this area.
A fibrinogen receptor from group B Streptococcus interacts with fibrinogen by repetitive units with novel ligand binding sites (2002)

Group B Streptococcus (GBS) is a frequent cause of bacterial sepsis and meningitis in neonates. During the course of infection, GBS colonizes and invades a number of host compartments, thereby interacting with different host proteins. In the present report, we describe the isolation of the fbsA gene, which encodes a fibrinogen receptor from GBS. The deduced FbsA protein is characterized by repetitive units, each 16 amino acids in length. Sequencing of the fbsA gene from five different GBS strains revealed significant variation in the number of repeat-encoding units. The deletion of the fbsA gene in the genome of GBS 6313 completely abolished fibrinogen binding, suggesting that FbsA is the major fibrinogen receptor in this strain. Growth of the fbsA deletion mutant in human blood was significantly impaired, indicating that FbsA protects GBS from opsonophagocytosis. In Western blot experiments with truncated FbsA -proteins, the repeat region of FbsA was identified as mediating fibrinogen binding. Using synthetic peptides, even a single repeat unit of FbsA was demonstrated to bind to fibrinogen. Spot membrane analysis and competitive binding experiments with peptides carrying single amino acid substitutions allowed the prediction of a fibrinogen-binding motif with the consensus sequence G-N/S/T-V-L-A/E/M/Q-R-R-X-K/R/W-A/D/E/N/Q-A/F/I/L/V/Y-X-X-K/R-X-X.
Hepatobiliary delivery of polyaminopolycarboxylate chelates: synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate (1991)

A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance.
Potential Mechanisms for IgG4 Inhibition of Immediate Hypersensitivity Reactions (2016)

IgG4 is the least abundant IgG subclass in human serum, representing less than 5% of all IgG. Increases in IgG4 occur following chronic exposure to antigen and are generally associated with states of immune tolerance. In line with this, IgG4 is regarded as an anti-inflammatory antibody with a limited ability to elicit effective immune responses. Furthermore, IgG4 attenuates allergic responses by inhibiting the activity of IgE. The mechanism by which IgG4 inhibits IgE-mediated hypersensitivity has been investigated using a variety of model systems leading to two proposed mechanisms. First by sequestering antigen, IgG4 can function as a blocking antibody, preventing cross-linking of receptor bound IgE. Second IgG4 has been proposed to co-stimulate the inhibitory IgG receptor FcγRIIb, which can negatively regulate FcεRI signaling and in turn inhibit effector cell activation. Recent advances in our understanding of the structural features of human IgG4 have shed light on the unique functional and immunologic properties of IgG4. The aim of this review is to evaluate our current understanding of IgG4 biology and reassess the mechanisms by which IgG4 functions to inhibit IgE-mediated allergic responses.
Observation of optical precursors at pulse propagation in GaAs (1991)

We have observed optical precursors by studying propagation of ultrashort optical pulses with a steeply rising and an exponentially decaying trailing edge through a 0.2-\ensuremath{\mu}m-thick GaAs crystal near the exciton resonance. The appearance of a fast pulse front---the precursor---independent of the detuning with respect to the resonance, was accompanied by a delayed main pulse. The delay of the main pulse varies with detuning in according with theoretical predictions.
Blockade of Vascular Endothelial Growth Factor Receptor I (VEGF-RI), but not VEGF-RII, Suppresses Joint Destruction in the K/BxN Model of Rheumatoid Arthritis (2003)

It was recently shown that vascular endothelial growth factor (VEGF), a growth factor for endothelial cells, plays a pivotal role in rheumatoid arthritis. VEGF binds to specific receptors, known as VEGF-RI and VEGF-RII. We assessed the physical and histological effects of selective blockade of VEGF and its receptors in transgenic K/BxN mice, a model of rheumatoid arthritis very close to the human disease. Mice were treated with anti-mouse VEGF Ab, anti-mouse VEGF-RI and -RII Abs, and an inhibitor of VEGF-RI tyrosine kinase. Disease activity was monitored using clinical indexes and by histological examination. We found that synovial cells from arthritic joints express VEGF, VEGF-RI, and VEGF-RII. Treatment with anti-VEGF-RI strongly attenuated the disease throughout the study period, while anti-VEGF only transiently delayed disease onset. Treatment with anti-VEGF-RII had no effect. Anti-VEGF-RI reduced the intensity of clinical manifestations and, based on qualitative and semiquantitative histological analyses, prevented joint damage. Treatment with a VEGF-RI tyrosine kinase inhibitor almost abolished the disease. These results show that VEGF is a key factor in pannus development, acting through the VEGF-RI pathway. The observation that in vivo administration of specific inhibitors targeting the VEGF-RI pathway suppressed arthritis and prevented bone destruction opens up new possibilities for the treatment of rheumatoid arthritis.
cAMP response element-binding protein is activated by Ca2+/calmodulin- as well as cAMP-dependent protein kinase. (1991)

In a variety of nerve cells of the brain, action potentials activate gene expression by means of Ca2+ influx. To determine how Ca2+ influx alters gene expression, we have examined the pattern of phosphorylation of a protein that binds to the cAMP response element (CRE). We have found that purified bovine brain CRE-binding protein is a substrate for the Ca2+/calmodulin-dependent kinase II (Cam kinase) as it is for the cAMP-dependent protein kinase (kinase A). Tryptic peptide maps show that the same peptide is phosphorylated in vitro both by kinase A and by Cam kinase. Moreover, in vitro transcription assays using a CRE-containing c-fos promoter indicate that phosphorylation of CRE-binding protein by Cam kinase increases gene transcription. Thus, action potentials in nerve cells and the consequent influx of Ca2+ can activate CRE-binding proteins by means of Cam kinase. This kinase therefore provides a direct second-messenger pathway by which impulse activity at the membrane can influence gene transcription. This has been shown independently by Sheng et al. (Sheng, M., Thomson, M. A. & Greenberg, M. E. (1991) Science, in press), who found that depolarization and Ca2+ influx mediate induction of c-fos in PC12 rat pheochromocytoma cells through phosphorylation of CRE-binding protein. These several findings indicate that CRE-binding protein(s) is a convergence point for synaptic activity acting through kinase A and impulse activity acting through Cam kinase. Together the two kinases could activate transcription in a synergistic manner, which could allow CRE-binding protein to couple short-term to long-term associative forms of synaptic plasticity.
Follow-up colonoscopy in patients with colorectal adenomatous polyps (1987)

Forty-four asymptomatic patients with adenomatous colorectal polyps were followed by repeated colonoscopies and subsequent removal of new polyps. The median follow-up time was 34 months (range, 4 to 131 months). Twenty-six patients (59 percent) developed new adenomatous polyps. Therecurrence rate was 69 percent in patients with multiple polyps compared with 54 percent in patients with a single polyp. The location of new polyps was in the same colonic segment in 81 percent of the patients, but not at the same site in the colon where a previous polyp had been removed. The histopathology and size of new polyps compared with the initial polyps showed a significant improvement in histopathology toward more benign polyps (P<0.02) and smaller polyps (P<0.001). In patients who initially had single adenomatous polyps, new polyp(s) were diagnosed after a mean time of 23 months compared initially. Patients with atypia in initial polyp(s) developed new polyp(s) after a mean time of 11 months compared with 23 months in patients without atypia. The mean time from a colon with no polyps to the diagnosis of a new adenomatous polyp less than 5 mm in size was 11.5 months, which was a statistically significant shorter time than the 19.4 months observed for the development of polyps 5 mm or larger.
Design of tumor-homing and pH-responsive polypeptide–doxorubicin nanoparticles with enhanced anticancer efficacy and reduced side effects (2015)

Tumor-homing and pH-responsive polypeptide-drug nanoparticles for targeted cancer therapy are precisely designed by site-specific drug conjugation to a bioactive and well-defined elastin-like polypeptide through an acid-labile linker. In a murine cancer model, these nanoparticles show significantly better anti-tumor efficacy and less systemic toxicity than not only free drugs, but also polypeptide-drug nanoparticles without the tumor-homing function.
Cytolysis of B-16 Melanoma Tumor Cells Mediated by the Myeloperoxidase and Lactoperoxidase Systems (1996)

Halide-dependent cytolysis of B-16 melanoma cells mediated by myeloperoxidase and lactoperoxidase systems was observed by turbidimetry. A significant decrease in turbidity, which is indicative of cytolysis, was found when a system consisting of myeloperoxidase, a source of hydrogen peroxide (glucose+glucose oxidase), and chloride or bromide were added to a B-16 melanoma cell suspension in the pH 4.7-6.0 region. The myeloperoxidase could be replaced by lactoperoxidase in the system containing bromide, but not that containing chloride. B-16 melanoma cells exposed to myeloperoxidase or lactoperoxidase systems at pH 5.5 or 7.0 were implanted by subcutaneous inoculation into C57BL/6CrSlc mice. After 14 days, a significant suppression of the growth of black tumors was detected in the groups of mice inoculated with melanoma cells exposed to the systems containing myeloperoxidase, glucose, glucose oxidase and chloride or bromide, or the system containing lactoperoxidase, glucose, glucose oxidase and bromide, at pH 5.5, but no significant suppression was observed at pH 7.0. From these findings, we concluded that the exposure of B-16 melanoma cells to a system consisting of myeloperoxidase, hydrogen peroxide (generated by the glucose+glucose oxidase system) and chloride or bromide, or of lactoperoxidase, the hydrogen peroxide and bromide, at moderately acidic pH, causes cytolysis is accompanied by cell death.
Escherichia coli FadR Positively Regulates Transcription of the fabB Fatty Acid Biosynthetic Gene (2001)

In Escherichia coli expression of the genes of fatty acid degradation (fad) is negatively regulated at the transcriptional level by FadR protein. In contrast the unsaturated fatty acid biosynthetic gene, fabA, is positively regulated by FadR. We report that fabB, a second unsaturated fatty acid biosynthetic gene, is also positively regulated by FadR. Genomic array studies that compared global transcriptional differences between wild-type and fadR-null mutant strains, as well as in cultures of each strain grown in the presence of exogenous oleic acid, indicated that expression of fabB was regulated in a manner very similar to that of fabA expression. A series of genetic and biochemical tests confirmed these observations. Strains containing both fabB and fadR mutant alleles were constructed and shown to exhibit synthetic lethal phenotypes, similar to those observed in fabA fadR mutants. A fadR strain was hypersensitive to cerulenin, an antibiotic that at low concentrations specifically targets the FabB protein. A transcriptional fusion of chloramphenicol acetyltransferase (CAT) to the fabB promoter produces lower levels of CAT protein in a strain lacking functional FadR. The ability of a putative FadR binding site within the fabB promoter to form a complex with purified FadR protein was determined by a gel mobility shift assay. These experiments demonstrate that expression of fabB is positively regulated by FadR.
Roles of O‐linked oligosaccharides in immune responses (2001)

Many functional glycoproteins are expressed on the lymphocyte cell surface. Some of them carry O-linked oligosaccharides (O-glycans), which are conjugated through serine or threonine residues. During various biological processes, including T-cell activation, a tetrasaccharide on the T-cell surface is dramatically converted to a branched hexasaccharide, called core2 O-glycan. The same structural change in O-glycans is also found on the lymphocytes from patients with immunodeficiency conditions such as Wiskott-Aldrich syndrome and AIDS. Several studies revealing the roles of core2 O-glycans in immune responses show that this is a biologically significant change. In particular, core2 O-glycans expressed on the cell surface reduce cell–cell interactions, thereby regulating immune responses. Furthermore, core2 O-glycan is a key backbone structure in forming selectin ligands. Thus, O-linked oligosaccharides, in particular those containing core2 branches, play vital roles in immune responses and may play dual roles in certain situations. This review will summarize the results obtained from various studies investigating the roles of O-glycans in immunological processes. BioEssays 23:46–53, 2001. © 2001 John Wiley & Sons, Inc.
Trityl tetrakis[3,5-bis(trifluoromethyl)phenyl]borate: a new hydride abstraction reagent (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTrityl tetrakis[3,5-bis(trifluoromethyl)phenyl]borate: a new hydride abstraction reagentSteven R. Bahr and Philip BoudjoukCite this: J. Org. Chem. 1992, 57, 20, 5545–5547Publication Date (Print):September 1, 1992Publication History Published online1 May 2002Published inissue 1 September 1992https://pubs.acs.org/doi/10.1021/jo00046a048https://doi.org/10.1021/jo00046a048research-articleACS PublicationsRequest reuse permissionsArticle Views3030Altmetric-Citations146LEARN 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-Alertsclose Get e-Alerts
Lasers and materials in selective laser sintering (2003)

Selective laser sintering (SLS) is one of the most rapidly growing rapid prototyping techniques (RPT). This is mainly due to its suitability to process almost any material: polymers, metals, ceramics (including foundry sand) and many types of composites. The material should be supplied as powder that may occasionally contain a sacrificial polymer binder that has to be removed (debinded) afterwards. The interaction between the laser beam and the powder material used in SLS is one of the dominant phenomena that defines the feasibility and quality of any SLS process. This paper surveys the current state of SLS in terms of materials and lasers. It describes investigations carried out experimentally and by numerical simulation in order to get insight into laser-material interaction and to control this interaction properly.
Noninvasive Imaging of Immune Checkpoint Ligand PD-L1 in Tumors and Metastases for Guiding Immunotherapy (2017)

Immunotherapy holds great promise in cancer treatment. The challenges in advancing immunotherapies lie in patient stratification and monitoring therapy. Noninvasive detection of immune checkpoint ligand PD-L1 can serve as an important biomarker for guidance and monitoring of immunotherapy. Here in, we provide an overview of our efforts to develop clinically translatable PD-L1-specific imaging agents for quantitative and real-time assessment of PD-L1 expression in tumor microenvironment.
Improved bacterial recombineering by parallelized protein discovery (2020)

Abstract Exploiting bacteriophage-derived homologous recombination processes has enabled precise, multiplex editing of microbial genomes and the construction of billions of customized genetic variants in a single day. The techniques that enable this, Multiplex Automated Genome Engineering (MAGE) and directed evolution with random genomic mutations (DIvERGE), are however currently limited to a handful of microorganisms for which single-stranded DNA-annealing proteins (SSAPs) that promote efficient recombineering have been identified. Thus, to enable genome-scale engineering in new hosts, highly efficient SSAPs must first be found. Here we introduce a high-throughput method for SSAP discovery that we call Serial Enrichment for Efficient Recombineering (SEER). By performing SEER in E. coli to screen hundreds of putative SSAPs, we identify highly active variants PapRecT and CspRecT. CspRecT increases the efficiency of single-locus editing to as high as 50% and improves multiplex editing by 5 to 10-fold in E. coli , while PapRecT enables efficient recombineering in Pseudomonas aeruginosa , a concerning human pathogen. CspRecT and PapRecT are also active in other, clinically and biotechnologically relevant enterobacteria. We envision that the deployment of SEER in new species will pave the way toward pooled interrogation of genotype-to-phenotype relationships in previously intractable bacteria.
Toward self-organized mobile ad hoc networks: the terminodes project (2001)

This article provides a technical overview of mobile ad hoc networks and describes their long-term potential. It covers current research, and describes major technical challenges, including networking, real-time services, and software. It shows that by their very nature, mobile ad hoc networks can bring a paradigm shift in the way networks are organized and operated, and can even lead to a fundamental change in the relationships between information technology and societal organization. As an illustration of these concepts, the article also contains an overall description of our long-term research project, called terminodes.
Spring brings breezes, wheezes, and pollen oxidases (2005)

While the release of pollen into the air is essential for the reproduction of plants, the accidental yet inevitable uptake of pollen into human airways can cause symptoms of seasonal allergies and asthma. The symptomatic response to pollen is caused by granulocytes that produce inflammation, which is due in part to oxidative stress through the action of NADPH oxidases. The recruitment of these inflammatory granulocytes was previously thought to depend entirely on the activation of an adaptive immune response. In this issue of the JCI, Boldogh et al. demonstrate that pollens contain endogenous NADPH oxidase activity, which functions to generate local "danger signals" in nearby airway epithelium. These signals in turn trigger the early recruitment of granulocytes, even in the absence of the adaptive immune response. These findings suggest that inhibition of the pollen oxidase may provide a way to antagonize allergic inflammation at a very early step.