gebhart/patrepeval huggingface dataset:
Structural Insights into the Evolution of an Antibody Combining Site (1997)

The crystal structures of a germline antibody Fab fragment and its complex with hapten have been solved at 2.1 A resolution. These structures are compared with the corresponding crystal structures of the affinity-matured antibody, 48G7, which has a 30,000 times higher affinity for hapten as a result of nine replacement somatic mutations. Significant changes in the configuration of the combining site occur upon binding of hapten to the germline antibody, whereas hapten binds to the mature antibody by a lock-and-key fit mechanism. The reorganization of the combining site that was nucleated by hapten binding is further optimized by somatic mutations that occur up to 15 from bound hapten. These results suggest that the binding potential of the primary antibody repertoire may be significantly expanded by the ability of germline antibodies to adopt more than one combining-site configuration, with both antigen binding and somatic mutation stabilizing the configuration with optimal hapten complementarity.
Re-evaluation of histological diagnoses of malignant mesothelioma by immunohistochemistry (2010)

In order to use archival tissue material with an earlier MM diagnosis for studies, histopathological re-evaluation is important. In possible sarcomatous MM cases without any positive IR for positive MM markers, radiology and clinical picture are essential parts of diagnostics. IHC based on a panel of two positive and two negative MM markers has to be adapted to the differential diagnostic needs in each single case. New diagnostic tools and techniques are desirable for cases where IHC and other established methods cannot provide a clear entity diagnosis, and in order to improve MM treatment.
Granulocyte-macrophage colony-stimulating factor enhances selective effector functions of tissue-derived macrophages (1988)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is produced by a variety of cells at sites of exposure to antigens. GM-CSF has a stimulatory effect on a number of neutrophil functions, but the effect on macrophage function is less clear. We investigated the effect of purified murine recombinant GM-CSF on murine peritoneal macrophage oxidative metabolism, Fc-dependent phagocytosis, anti-Toxoplasma activity, and expression of class II major histocompatibility antigen (Iad). GM-CSF significantly increased phorbol myristate acetate- and zymosan-elicited H2O2 release by resident and thioglycollate-elicited macrophages after 48 hours in vitro. The effect of recombinant GM-CSF was blocked by polyclonal anti-GM-CSF antibody and was not altered by lipopolysaccharide (0.01 to 1.0 microgram/mL). GM-CSF also stimulated Fc-dependent phagocytosis by peritoneal macrophages, although the stimulation of resident macrophages (1.4-fold) was less dramatic than that of thioglycollate-elicited cells (2.1-fold). GM-CSF (at doses up to 100 U/mL) had no effect on macrophage anti-Toxoplasma activity or on expression of Iad. In addition to stimulating macrophage growth, GM-CSF selectively promotes the functional capacity of tissue-derived macrophages.
Self-Assembled Ultra-Compact Energy Storage Elements Based on Hybrid Nanomembranes (2010)

Self-assembly methods combined with standard top-down approaches are demonstrated to be suitable for fabricating three-dimensional ultracompact hybrid organic/inorganic electronic devices based on rolled-up nanomembranes. Capacitors that are self-wound and manufactured in parallel are almost 2 orders of magnitude smaller than their planar counterparts and exhibit capacitances per footprint area of around 200 microF/cm(2). This value significantly exceeds that which was previously reported for metal-insulator-metal capacitors based on Al(2)O(3), and the obtained specific energy (approximately 0.55 Wh/kg) would allow their usage as ultracompact supercapacitors. By incorporating organic monolayers into the inorganic nanomembrane structure we can precisely control the electronic characteristics of the devices. The adaptation of the process for creating ultracompact batteries, coils and transformers is an attractive opportunity for reducing the size of energy storage elements, filters, and signal converters. These devices can be employed as implantable electronic circuits or new approaches for energy-harvesting applications. Furthermore, the incorporation of functional organic molecules gives rise to novel devices with almost limitless chemical and biological functionalities.
Induction of Dickkopf-1, a Negative Modulator of the Wnt Pathway, Is Associated with Neuronal Degeneration in Alzheimer's Brain (2004)

We used primary cultures of cortical neurons to examine the relationship between beta-amyloid toxicity and hyperphosphorylation of the tau protein, the biochemical substrate for neurofibrillary tangles of Alzheimer's brain. Exposure of the cultures to beta-amyloid peptide (betaAP) induced the expression of the secreted glycoprotein Dickkopf-1 (DKK1). DKK1 negatively modulates the canonical Wnt signaling pathway, thus activating the tau-phosphorylating enzyme glycogen synthase kinase-3beta. DKK1 was induced at late times after betaAP exposure, and its expression was dependent on the tumor suppressing protein p53. The antisense induced knock-down of DKK1 attenuated neuronal apoptosis but nearly abolished the increase in tau phosphorylation in betaAP-treated neurons. DKK1 was also expressed by degenerating neurons in the brain from Alzheimer's patients, where it colocalized with neurofibrillary tangles and distrophic neurites. We conclude that induction of DKK1 contributes to the pathological cascade triggered by beta-amyloid and is critically involved in the process of tau phosphorylation.
Acute Lung Injury and the Acute Respiratory Distress Syndrome (2005)

In 2005, the American Thoracic Society marks its 100th year of existence. For over a third of this span, since 1967, clinicians and investigators have struggled with a common, often lethal condition originally termed the adult respiratory distress syndrome (ARDS) (1).* While the syndrome almost certainly occurred in earlier times well before the advent of intensive care units, this date establishes its modern era. Subsequently, ARDS has more correctly come to indicate the acute respiratory distress syndrome because it occurs in children as well as in adults (2). ARDS causes severe acute respiratory failure with dynamic impairment in oxygen and carbon dioxide transfer, with the need for high levels of supplementary oxygen and a high minute ventilation (3, 4). Efforts to understand the pathophysiologic events underlying ARDS, a constellation that is now generally termed acute lung injury (ALI), have been substantial and remain a priority of the National Institutes of Health (5). The expectation has been that basic, translational, and clinical studies will result in new strategies for management of ALI/ARDS based on clear definition of the cellular and molecular events requisite in lung injury and repair. While important discoveries have been made, the goal of fundamental characterization of ALI/ARDS in a way that results in highly effective prevention and treatment remains incomplete and elusive. One major advance in supportive care, a strategy of lung protective mechanical ventilation, has substantially reduced mortality in ALI/ARDS (6, 7). This therapeutic intervention resulted from both experimental and clinical studies that evaluated the effect of different ventilation strategies on the course of ALI, and continues a theme initiated in the original description of ALI/ARDS in which positive end-expiratory pressure was introduced as a management modality (1).

In spite of the advances in supportive care of patients with ALI/ARDS, unacceptable morbidity and mortality persist and formidable challenges remain. Our objective here is to review briefly what we knew in 1967 regarding pathogenesis and what we know in 2005, and to provide a perspective on how insights have evolved over the last four decades.
Surface Analysis under Ambient Conditions Using Plasma-Assisted Desorption/Ionization Mass Spectrometry (2007)

A novel plasma-assisted desorption/ionization (PADI) method that can be coupled with atmospheric pressure sampling mass spectrometry to yield mass spectral information under ambient conditions of pressure and humidity from a range of surfaces without the requirement for sample preparation or additives is reported. PADI is carried out by generating a nonthermal plasma which interacts directly with the surface of the analyte. Desorption and ionization then occur at the surface, and ions are sampled by the mass spectrometer. The PADI technique is demonstrated and compared with desorption electrospray ionization (DESI) for the detection of active ingredients in a range of over-the-counter and prescription pharmaceutical formulations, including nonsterodial anti-inflammatory drugs (mefenamic acid, Ibugel, and ibuprofen), analgesics (paracetamol, Anadin Extra), and Beecham's "all in one" cold and flu remedy. PADI has also been successfully applied to the analysis of nicotine in tobacco and thiosulfates in garlic. PADI experiments have been performed using a prototype source interfaced with a Waters Platform LCZ single-quadrupole mass spectrometer with limited modifications and a Hiden Analytical HPR-60 molecular beam mass spectrometer (MBMS). The ability of PADI to rapidly detect active ingredients in pharmaceuticals without the need for prior sample preparation, solvents, or exposed high voltages demonstrates the potential of the technique for high-throughput screening in a pharmaceutical or forensic environment.
Fabrication of complex oral drug delivery forms by Three Dimensional Printing (tm) (2001)

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2001.
Nonaminoglycoside compounds induce readthrough of nonsense mutations (2009)

Large numbers of genetic disorders are caused by nonsense mutations for which compound-induced readthrough of premature termination codons (PTCs) might be exploited as a potential treatment strategy. We have successfully developed a sensitive and quantitative high-throughput screening (HTS) assay, protein transcription/translation (PTT)-enzyme-linked immunosorbent assay (ELISA), for identifying novel PTC-readthrough compounds using ataxia-telangiectasia (A-T) as a genetic disease model. This HTS PTT-ELISA assay is based on a coupled PTT that uses plasmid templates containing prototypic A-T mutated (ATM) mutations for HTS. The assay is luciferase independent. We screened approximately 34,000 compounds and identified 12 low-molecular-mass nonaminoglycosides with potential PTC-readthrough activity. From these, two leading compounds consistently induced functional ATM protein in ATM-deficient cells containing disease-causing nonsense mutations, as demonstrated by direct measurement of ATM protein, restored ATM kinase activity, and colony survival assays for cellular radiosensitivity. The two compounds also demonstrated readthrough activity in mdx mouse myotube cells carrying a nonsense mutation and induced significant amounts of dystrophin protein.
THE PATHOLOGY OF BERIBERI (1938)

Beriberi is a disease resulting from faulty metabolism and is directly caused by deficiency of the antineuritic vitamin B<sub>1</sub>and possibly other deficiencies in the diet. Among Orientals, this deficiency is usually produced by the too exclusive use of decorticated or polished rice; but it may equally be caused by the too exclusive use of white wheat flour and other carbohydrate staples. Clinically, beriberi is characterized by degenerative changes in the nervous system including a multiple peripheral neuritis, which may exist alone but is often combined with generalized edema and serous effusions, and by a tendency to the development of cardiac hypertrophy, which frequently results in cardiac failure and sudden death. In this definition vitamin B<sub>1</sub>, as distinguished from other fractions of the vitamin B complex, is the compound isolated and synthesized by R. R. Williams, a compound of pyrimidine and thiazole which has been designated by Williams
Multiple Feature-Classifier Combination in Automated Text Classification (2012)

Automatic text classification (ATC) is important in applications such as indexing and organizing electronic documents in databases leading to enhancement of information access and retrieval. We propose a method which employs various types of feature sets and learning algorithms to improve classification effectiveness. Unlike the conventional methods of multi-classifier combination, the proposed method considers the contributions of various types of feature sets and classifiers. It can therefore be known as multiple feature-classifier combination (MFC) method. In this paper we present empirical evaluation of MFC using two benchmarks of text collections to determine its effectiveness. Empirical evaluation show that MFC consistently outperformed all compared methods.
High capacity xylose transport in Candida intermedia PYCC 4715 (2003)

Xylose-utilising yeasts were screened to identify strains with high xylose transport capacity. Among the fastest-growing strains in xylose medium, Candida intermedia PYCC 4715 showed the highest xylose transport capacity. Maximal specific growth rate was the same in glucose and xylose media (μmax=0.5 h−1, 30°C). Xylose transport showed biphasic kinetics when cells were grown in either xylose- or glucose-limited culture. The high-affinity xylose/proton symport system (Km=0.2 mM, Vmax=7.5 mmol h−1 g−1) was more repressed by glucose than by xylose. The less specific low-affinity transport system (K=50 mM, Vmax=11 mmol h−1 g−1) appeared to operate through a facilitated-diffusion mechanism and was expressed constitutively. Inhibition experiments showed that glucose is a substrate of both xylose transport systems.
Use of the Cre/lox Recombination System to Develop a Non-lethal Knock-in Murine Model for Osteogenesis Imperfecta with an α1(I) G349C Substitution (1999)

We utilized the Cre/lox recombination system to develop the first knock-in murine model for osteogenesis imperfecta (OI). The moderately severe OI phenotype was obtained from an alpha1(I) Gly(349) --> Cys substitution in type I collagen, reproducing the mutation in a type IV OI child. We introduced four single nucleotide (nt) changes into murine col1a1 exon 23: the disease causing G-->T transversion (nt 1546), an adjacent G-->T change (nt 1551) to generate a GUC ribozyme cleavage site, and two transversions (nt 1567 C-->A and nt 1569 C-->G) to cause a Leu --> Met substitution. We also introduced a 3.2-kilobase pair transcription/translation stop cassette in intron 22, flanked by directly repeating lox recombination sites. After homologous recombination in ES cells, two male chimeras were obtained. Chimeras were mated with transgenic females expressing Cre recombinase to remove the stop cassette from a portion of the progeny's cells. To generate mice with full expression of the Gly(349) --> Cys mutation, these offspring were then mated with wild-type females. Skeletal staining and bone histology of the F2 revealed a classical OI phenotype with deformity, fragility, osteoporosis and disorganized trabecular structure. We designate these mice BrtlIV (Brittle IV). BrtlIV mice have phenotypic variability ranging from perinatal lethality to long term survival with reproductive success. The phenotypic variability is not associated with differences in expression levels of the mutant allele in total RNA derived from tissue extracts. Expression of the mutant protein is also equivalent in different phenotypes. Thus, these mice are an excellent model for delineation of the modifying factors postulated to affect human OI phenotypes. In addition, we generated knock-in mice carrying an "intronic" inclusion by mating chimeras with wild-type females. Alternative splicing involving the stop cassette results in retention of non-collagenous sequences. These mice reproduce the lethal phenotype of similar human mutations and are designated BrtlII.
Rapid Synthesis of 3-Aminoisoquinoline-5-sulfonamides Using the Buchwald-Hartwig Reaction (2009)

A rapid synthesis of previously unreported 3-aminoisoquinoline-5-sulfonamides related to known kinase inhibitors was achieved by a two-step sequential reaction of 3-chloro-5-isoquinolinesulfonyl chloride with amines. Palladium-catalysed C-N bond formation was used to introduce arylamine, alkylamine, and unsubstituted amino groups at C-3 of the isoquinoline.
Comparative genomic hybridization reveals DNA copy number gains to frequently occur in human prostate cancer (1999)

BACKGROUND Despite intensive studies over many years, there is only limited knowledge on the genetic changes underlying the development and progression of prostate cancer. No specific prostate carcinoma-related genetic event has yet been identified. METHODS In order to gain an overall view of regional chromosome gains and losses, comparative genomic hybridization (CGH) was used on a series of 16 prostate adenocarcinomas. Five benign prostate hyperplasia (BPH) samples were also evaluated. RESULTS Using CGH, chromosome alterations were observed in 81% of the prostate carcinomas analyzed. Gains of DNA copy numbers were found as the predominant imbalance, with chromosomes 3q (56%), 12q (56%), 8q (50%), Xq (50%), 4 (44%), 6q (44%), 5 (38%), 7q (38%), 9p (38%), and 13q (31%) being most frequently involved. Whereas DNA copy number gains comprised the whole chromosome or almost a whole arm of chromosomes 4, 5, 6, 9, and 13, the minimal overlapping regions on the other chromosomes were mapped to 3q25–q26, 8q21–q22, 12q13–q21, 7q31, and Xq22–q25. High-level amplifications were not found. Other chromosomes with nonrandom gains or losses of DNA sequences were discovered. The five BPH samples were found to be normal. CONCLUSIONS Amplification events at different chromosomal sites seem important in prostate cancer development. A new chromosome region with DNA copy number gains was identified on 12q, while other regions on 3q, 7q, 8q, and Xq were confirmed or narrowed down, indicating a possible role of known or putative protooncogenes in these regions for prostate cancer growth. Our low detection rate of DNA losses may to some part be explained by CGH immanent technical limitations. Prostate 39:79–86, 1999. © 1999 Wiley-Liss, Inc.
Optical Interconnects for High Performance Computing (2011)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text M. A. Taubenblatt, "Optical Interconnects for High Performance Computing," in Optical Fiber Communication Conference/National Fiber Optic Engineers Conference 2011, OSA Technical Digest (CD) (Optica Publishing Group, 2011), paper OThH3. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Human strand-specific mismatch repair occurs by a bidirectional mechanism similar to that of the bacterial reaction (1993)

Nuclear extracts prepared from a HeLa cell line have been previously shown to support strand-specific repair of heteroduplex DNAs containing a site-specific, strand-specific incision (Holmes, J.J., Clark, S., and Modrich, P. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 5837-5841; Thomas, D.C., Roberts, J.D., and Kunkel, T.A. (1991) J. Biol. Chem. 266, 3744-3751). Further analysis of the substrate specificity of the reaction has shown that in addition to G-T, A-C, G-G, and C-C, nuclear extracts also recognize and correct in a strand-specific manner A-A, A-G, T-T, and C-T mismatches, with repair in each case being inhibited by aphidicolin. The rate of repair of a circular G-T heteroduplex was found to decrease monotonically with increasing separation between the mismatch and the strand break that targets repair, as viewed along the shorter path joining the two sites in the circular substrate. This decrease is independent of the polarity of the incised strand, suggesting that the human pathway of mismatch correction may possess a bidirectional excision capability similar to that of the Escherichia coli methyl-directed system. This possibility was confirmed by analysis of excision tracts associated with the reaction. Inhibition of DNA synthesis by aphidicolin or by omission of exogenous dNTPs leads to the mismatch-provoked formation of a single-strand gap that spans the shorter path between the strand break and the mismatch, irrespective of the polarity of the incised strand. Formation of these gaps, which extend from the site of the strand break to terminate at a number of discrete sites in the region 90 to 170 nucleotides beyond the mismatch, is therefore independent of the relative orientation of the two sites. Based on similar mismatch specificities and common features of mechanism, we have concluded that the human strand-specific mismatch repair system is functionally homologous to the bacterial methyl-directed pathway.
Engineering a Dimeric Caspase-9: A Re-evaluation of the Induced Proximity Model for Caspase Activation (2005)

Caspases are responsible for the execution of programmed cell death (apoptosis) and must undergo proteolytic activation, in response to apoptotic stimuli, to function. The mechanism of initiator caspase activation has been generalized by the induced proximity model, which is thought to drive dimerization-mediated activation of caspases. The initiator caspase, caspase-9, exists predominantly as a monomer in solution. To examine the induced proximity model, we engineered a constitutively dimeric caspase-9 by relieving steric hindrance at the dimer interface. Crystal structure of the engineered caspase-9 closely resembles that of the wild-type (WT) caspase-9, including all relevant structural details and the asymmetric nature of two monomers. Compared to the WT caspase-9, this engineered dimer exhibits a higher level of catalytic activity in vitro and induces more efficient cell death when expressed. However, the catalytic activity of the dimeric caspase-9 is only a small fraction of that for the Apaf-1-activated caspase-9. Furthermore, in contrast to the WT caspase-9, the activity of the dimeric caspase-9 can no longer be significantly enhanced in an Apaf-1-dependent manner. These findings suggest that dimerization of caspase-9 may be qualitatively different from its activation by Apaf-1, and in conjunction with other evidence, posit an induced conformation model for the activation of initiator caspases.
Potentiometry of an operating organic semiconductor field-effect transistor (2001)

The potential profile across the channel of an operating sexithiophene-based field-effect transistor (FET) was investigated using an atomic force microscope with a conducting probe. A high impedance electrometer recorded the probe potential when it was placed in contact at fixed points with the channel surface. Tapping mode images taken with the same probe before and after individual point contact measurements verified that no damage was done to the device and allowed correlation of the potential profile with the device architecture. For any given source-drain bias, most of the potential drop occurred at the source and drain contacts, meaning the FET was contact limited. Moreover, the potential drop was not fixed but depended on the applied drain and gate voltages. This study demonstrates the utility of potential profiling for identifying high resistance bottlenecks to charge transport in organic-based devices.