gebhart/patrepeval huggingface dataset:
Microfluidic cantilever detects bacteria and measures their susceptibility to antibiotics in small confined volumes (2016)

In the fight against drug-resistant bacteria, accurate and high-throughput detection is essential. Here, a bimaterial microcantilever with an embedded microfluidic channel with internal surfaces chemically or physically functionalized with receptors selectively captures the bacteria passing through the channel. Bacterial adsorption inside the cantilever results in changes in the resonance frequency (mass) and cantilever deflection (adsorption stress). The excitation of trapped bacteria using infrared radiation (IR) causes the cantilever to deflect in proportion to the infrared absorption of the bacteria, providing a nanomechanical infrared spectrum for selective identification. We demonstrate the in situ detection and discrimination of Listeria monocytogenes at a concentration of single cell per μl. Trapped Escherichia coli in the microchannel shows a distinct nanomechanical response when exposed to antibiotics. This approach, which combines enrichment with three different modes of detection, can serve as a platform for the development of a portable, high-throughput device for use in the real-time detection of bacteria and their response to antibiotics.
The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification (2015)

Mass spectrometry (MS) -based proteomics has become an indispensable tool with broad applications in systems biology and biomedical research. With recent advances in liquid chromatography (LC) and MS instrumentation, LC-MS is making increasingly significant contributions to clinical applications, especially in the area of cancer biomarker discovery and verification. To overcome challenges associated with analyses of clinical samples (for example, a wide dynamic range of protein concentrations in bodily fluids and the need to perform high throughput and accurate quantification of candidate biomarker proteins), significant efforts have been devoted to improve the overall performance of LC-MS-based clinical proteomics platforms. Reviewed here are the recent advances in LC-MS and its applications in cancer biomarker discovery and quantification, along with the potentials, limitations and future perspectives.
Cytogenetic and blood group studies of sheep/goat chimaeras (1985)

Aggregation chimaeras were composed of quarter (or 1 cell) contributions from 4-cell blastocysts of sheep or goats, or of an 8-cell blastocyst of one species enveloped in three 8-cell blastocysts of the other. Gestation was in sheep or goat recipient females. Of the 10 living animals born, 3 were identified as interspecific chimaeras by body conformation and coat type among the 7 quarter/quarter aggregations and 1 among the 3 giant aggregates. Interspecific chimaerism was identified by cytogenetic study of umbilicus and blood lymphocytes respectively of 2 of these, one from each type of aggregate. Intraspecific sex chimaerism was found in 3 other animals; 2 were of giant aggregate origin, but the 1 of quarter/quarter origin must have acquired it by placental anastomosis with a twin conceptus. Tests using species-specific monoclonal antibodies and electrophoretic separation of haemoglobins and isoenzymes demonstrated sheep and goat erythrocytes in one giant aggregate chimaera; their relative proportions and those of the blood lymphocytes changed over a period of 31 months from approximately 60% goat and 40% sheep to more than 90% sheep. The plasma transferrins and amylases did not show similar relative changes from their predominantly goat-like character and, by implication, neither did their tissues of origin.
Scalable Test Generation for Trojan Detection Using Side Channel Analysis (2018)

Hardware Trojan detection has emerged as a critical challenge to ensure security and trustworthiness of integrated circuits. A vast majority of research efforts in this area has utilized side-channel analysis for Trojan detection. Functional test generation for logic testing is a promising alternative but it may not be helpful if a Trojan cannot be fully activated or the Trojan effect cannot be propagated to the observable outputs. Side-channel analysis, on the other hand, can achieve significantly higher detection coverage for Trojans of all types/sizes, since it does not require activation/propagation of an unknown Trojan. However, they have often limited effectiveness due to poor detection sensitivity under large process variations and small Trojan footprint in side-channel signature. In this paper, we address this critical problem through a novel side-channel-aware test generation approach, based on a concept of multiple excitation of rare switching (MERS), that can significantly increase Trojan detection sensitivity. This paper makes several important contributions: 1) it presents in detail a scalable statistical test generation method, which can generate high-quality test set for creating high relative activity in arbitrary Trojan instances; 2) it analyzes the effectiveness of generated test set in terms of Trojan coverage; and 3) it describes two judicious reordering methods that can further tune the test set and greatly improve the side channel sensitivity. Simulation results demonstrate that the tests generated by MERS can significantly increase the Trojans sensitivity, thereby making Trojan detection effective using side-channel analysis.
DC-20 GHz N*M passive switches (1988)

High-order, bidirectional, DC-20-GHz switch networks are discussed. Single-chip 1*2, 1*4, and 2*2 switch MMICs have been demonstrated. Multiple chips have been used to demonstrate 4*4 and 1*16 switches. The switches all use a combination of series and shunt passive FET switching elements. The 1*4 switch is made of a single stage of switching elements, rather than the usual two stages of 1*2 switches. The 2*2 switch is comprised of two stages of 1*2 switches. The multiple-chip 4*4 switch is made of four stages of 1*2 switches (using the 2*2 switch MMICs). Two stages of 1*4 switches are used to make the 1*16 switch.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Role of RANK-Ligand Inhibition in Cancer: The Story of Denosumab (2011)

The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases-bone destruction was kept at bay a little longer. The next generation of bone metastasis treatments is well on its way in clinical development, and among them, the most advanced drug is denosumab. Denosumab is a fully human monoclonal antibody that inhibits osteoclast maturation, activation, and function by binding to receptor activator of nuclear factor kappa B ligand, with the final result being a reduced rate of bone resorption. In this review, we give an overview of relevant preclinical and clinical data regarding the use of denosumab in patients with solid tumors in general and prostate cancer in particular.
Efficient columnar storage in B-trees (2007)

Column-oriented storage formats have been proposed for query processing in relational data warehouses, specifically for fast scans over non-indexed columns. This short note proposes a data compression method that reuses traditional on-disk B-tree structures with only minor changes yet achieves storage density and scan performance comparable to specialized columnar designs. The advantage of the proposed method over alternative storage structures is that traditional algorithms can be reused, e.g., for assembling rows with multiple columns, bulk insertion and deletion, logging and recovery, consistency checking, etc.
Control of creatine metabolism by HIF is an endogenous mechanism of barrier regulation in colitis (2013)

Mucosal surfaces of the lower gastrointestinal tract are subject to frequent, pronounced fluctuations in oxygen tension, particularly during inflammation. Adaptive responses to hypoxia are orchestrated largely by the hypoxia-inducible transcription factors (HIFs). As HIF-1α and HIF-2α are coexpressed in mucosal epithelia that constitute the barrier between the lumen and the underlying immune milieu, we sought to define the discrete contribution of HIF-1 and HIF-2 transactivation pathways to intestinal epithelial cell homeostasis. The present study identifies creatine kinases (CKs), key metabolic enzymes for rapid ATP generation via the phosphocreatine-creatine kinase (PCr/CK) system, as a unique gene family that is coordinately regulated by HIF. Cytosolic CKs are expressed in a HIF-2-dependent manner in vitro and localize to apical intestinal epithelial cell adherens junctions, where they are critical for junction assembly and epithelial integrity. Supplementation with dietary creatine markedly ameliorated both disease severity and inflammatory responses in colitis models. Further, enzymes of the PCr/CK metabolic shuttle demonstrate dysregulated mucosal expression in a subset of ulcerative colitis and Crohn disease patients. These findings establish a role for HIF-regulated CK in epithelial homeostasis and reveal a fundamental link between cellular bioenergetics and mucosal barrier.
Zipf's law and the Internet (2002)

Zipf's law governs many features of the Internet. Observations of Zipf distributions, while interesting in and of themselves, have strong implications for the design and function of the Internet. The connectivity of Internet routers influences the robustness of the network while the distribution in the number of email contacts affects the spread of email viruses. Even web caching strategies are formulated to account for a Zipf distribution in the number of requests for webpages.
Molecular cloning and structural analysis of genes from Zea mays (L.) coding for members of the ras-related ypt gene family. (1992)

We have isolated, cloned, and characterized two cDNAs from Zea mays (L.), denoted yptm1 and yptm2, encoding proteins related to the ypt protein family. Amino acid similarity scores with YPT1 from yeast and ypt from mouse are in the range of 70% for yptm1 and 74% for yptm2, respectively, whereas similarities with p21 ras and other ras-related proteins are less than 40%. Most amino acid residues showing identity are clustered in the GTP/GDP binding domain. In addition, two cysteine residues close to the C-terminal ends, known to be palmitoylated and necessary for membrane binding in all eukaryotic ras-related proteins that have been characterized so far, are conserved in the maize genes as well. Northern blot hybridization analysis of poly(A)+ mRNA from etiolated maize coleoptiles revealed single mRNA species of approximately the same size as the isolated cDNAs. The gene for yptm1 is expressed at very low levels in maize coleoptiles and tissue culture cells. The gene for yptm2 is expressed at higher levels and is differentially represented in RNAs isolated from various organs of maize plants, with its highest level in leaves and flowers. The structural similarity of the genes identified suggests that they could be involved in the control of secretory processes.
A Study on the energy absorption characteristics of GFRP circular tubes fabricated by the filament winding method (2009)

In this paper, quasi-static crushing tests of composite circular tubes under axial compression load are conducted to investigate the energy absorption characteristics. Circular tubes used for this experiment are glass/epoxy (GFRP) composite tubes which are fabricated by the filament winding method. One edge of the composite tube is chamfered to reduce the initial peak load and to prevent catastrophic failure during crushing process. Energy absorption characteristics vary significantly according to the constituent materials, fabrication conditions, tube geometry and test condition. In tube geometry, according as inner diameter increase, unstable crush mode is caused by local buckling of delamination, but control of the fiber orientation should help composite tubes get stable crush mode.
Deactivating Unproductive Pathways in Multichromophoric Sensitizers (2014)

The effects of solvent and substituents on a multichromophoric complex containing a boron-dipyrromethene (Bodipy) chromophore and Pt(bpy)(bdt) (bpy = 2,2'-bipyridine, bdt =1,2-benzenedithiolate) were studied using steady-state absorption, emission, and ultrafast transient absorption spectroscopy. When the Bodipy molecule is connected to either the bpy or bdt in acetonitrile, excitation ultimately leads to the dyad undergoing triplet energy transfer (TEnT) from the redox-active Pt triplet mixed-metal-ligand-to-ligand' charge transfer ((3)MMLL'CT) state to the Bodipy (3)ππ* state in 8 and 160 ps, respectively. This is disadvantageous for solar energy applications. Here, we investigate two methods to lower the energy of the (3)MMLL'CT state, thereby making TEnT unfavorable. By switching to a low dielectric constant solvent, we are able to extend the lifetime of the (3)MMLL'CT state to over 1 ns, the time frame of our experiment. Additionally, electron-withdrawing groups, such as carboxylate and phosphonate esters, on the bpy lower the energy of the (3)MMLL'CT state such that the photoexcited dyad remains in that state and avoids TEnT to the Bodipy (3)ππ* state. It is also shown that a single methylene spacer between the bpy and phosphonate ester is sufficient to eliminate this effect, raising the energy of the (3)MMLL'CT state and inducing relaxation to the (3)ππ*.
Anellated Hemicyanine Dyes with Large Symmetrical Solvatochromism of Absorption and Fluorescence (2003)

A novel class of amphiphilic hemicyanine dyes is described where electron-pushing aniline and electron-pulling pyridinium are joined by anellated benzene rings. Enhancing the solvent polarity, the absorption band of these ANNINE dyes is shifted to the blue and the fluorescence band is shifted to the red at an invariant 00 energy. The increasing Stokes shift spans the whole visible spectrum. The divergent symmetrical solvatochromism of the positively charged chromophores is parametrized by a monopole−dipole model using a Born−Onsager−Marcus approach. From the intramolecular charge shift that is induced by electronic excitation, the linear Stark effect that is expected when the ANNINE dyes are used as voltage-sensitive probes in a biomembrane is estimated.
Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid (2007)

The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-gamma-producing CD8(+) and CD4(+) effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-gamma was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication.
Two Mononuclear Iron(II) Spin‐Crossover Complexes with a N4O2 Coordination Sphere (2013)

Abstract Two mononuclear spin‐crossover compounds Fe( L 1 ) 2 ( 1 ) and Fe( L 2 ) 2 ( 2 ) {H L 1 = 2‐hydroxy‐3‐methyl‐ N′ ‐[1‐(pyridine‐2‐yl)butylidene]benzohydrazide, H L 2 = 2‐hydroxy‐ N′ ‐[1‐(pyridine‐2‐yl)butylidene]benzohydrazide} were successfully synthesized. The magnetic measurements of the compounds revealed different thermal magnetic behavior. Compound 1 undergoes a gradual complete thermal spin crossover (SCO) with T 1/2↑/↓ = 243/240 K and a hysteresis loop of 3 K. Compound 2 shows a gradual incomplete SCO during the measurable temperature region with T 1/2 ≈ 330 K. Through the comparison of the magnetic and structural results for 1 and 2 with previously reported related compounds, the alkyl substitutions of the ligand were considered to affect the ligand‐field strength and hydrogen‐bonding interactions. In addition, photomagnetism results showed an 87 % photoconversion and 36 K of T (LIESST) (LIESST = light‐induced excited spin‐state trapping) for compound 1 . The results enrich the knowledge on how to control the spin‐crossover behavior in the new system.
Blocking of Human Sperm-Zona Interaction by Monoclonal Antibodies to a Glycoprotein Family (ZP4) of Porcine Zona Pellucida1 (1991)

To study zona pellucida antigens involved in human fertilization, five monoclonal antibodies (MAbs)--2A1, 2G3, 4A2, 4E12, and 5H4--were produced to a glycoprotein family (ZP4) isolated from heat-solubilized porcine zonae pellucidae. Each MAb reacted not only with solubilized porcine zona glycoproteins but also with the glycoproteins deglycosylated by trifluoromethanesulfonic acid treatment. They also reacted with intact zonae pellucidae of porcine and human oocytes. Three (4A2, 4E12, and 5H4) of the five MAbs showed a significant blocking effect on human sperm binding and penetration of human zonae pellucidae. The 5H4 MAb showed a strong reaction with ZP4 and ZP1 glycoprotein families of porcine zonae pellucidae, and four other MAbs reacted more strongly with ZP3 than with ZP4. The reactivity of 5H4 with porcine zona glycoproteins was destroyed by chymotrypsin digestion, but the antigen epitope was resistant to proteolysis by trypsin and endoproteinase Lys-C. A peptide fragment reactive to 5H4 was isolated by reverse-phase HPLC from endoproteinase Lys-C-treated ZP4 glycoproteins, and its molecular mass was determined to be 7 kDa by SDS-PAGE. These results suggested that the antigen epitope corresponding to 5H4 is a good candidate for development of a contraceptive vaccine.
Both IgM and IgG anti-DNA antibodies are the products of clonally selective B cell stimulation in (NZB x NZW)F1 mice. (1992)

Disease activity in systemic lupus erythematosus is closely associated with the appearance of immunoglobulin (Ig)G antibody to native DNA in both humans and mice. Like normal antibody responses, the anti-DNA autoantibody first appears as IgM and then switches to IgG. Structural studies of IgG anti-DNA suggest that these antibodies are the products of clonally selected, specifically stimulated B cells. The origins of the IgM anti-DNA have been less clear. To determine whether the earlier appearing IgM anti-DNA antibody in autoimmune mice also derives from clonally selected, specifically stimulated B cells or B cells activated by nonselective, polyclonal stimuli, we have analyzed the molecular and serological characteristics of a large number of monoclonal IgM anti-DNA antibodies from autoimmune (NZB x NZW)F1 mice. We have also analyzed IgM and IgG anti-DNA hybridomas obtained from the same individual mice to determine how the later-appearing IgG autoantibody may be related to the earlier-appearing IgM autoantibody within an individual mouse. The results demonstrate that: (a) IgM anti-DNA, like IgG, has the characteristics of a specifically stimulated antibody; (b) IgM and IgG anti-DNA antibodies have similar variable region structures and within individual mice may be produced by B cells derived from the same clonal precursors; (c) recurrent germline and somatically derived VH and VL structures may influence the specificity of anti-DNA monoclonal antibody for denatured vs. native DNA; and (d) the results provide a structural explanation for the selective development of IgG antibody to native DNA as autoimmunity to DNA progresses in (NZB x NZW)F1 mice.
Nucleophilic [18F]Fluorination and subsequent decarbonylation of methoxy‐substituted nitro‐ and halogen‐benzenes activated by one or two formyl groups (2010)

Abstract As model reactions for the introduction of 18 F into protected aromatic amino acids, the replacement of NO 2 , Cl, Br and F by [ 18 F]fluoride in 2‐isophthalaldehyde and 2‐terephthalaldehyde derivatives which model 18 F‐DOPA and 18 F‐tyrosine was investigated by comparing labelling yields and reaction rates with those of corresponding mono‐aldehyde compounds. All isophthalaldehydes showed maximum radiochemical yields (79 to 86%) at 140°C and in comparison with the corresponding mono‐aldehydes the reaction proceeded faster. At lower temperature the reaction already resulted in high yields, e.g. 2‐nitroisophthalaldehyde was labelled with a yield of 78% at 25°C after 7 min, whereas 2‐nitrobenzaldehyde only reached a yield of 1.7% under the same reaction conditions. The 18 F/NO 2 exchange in nitroterephthalaldehydes proceeded more slowly and with lower radiochemical yields when compared with corresponding isophthalaldehydes and monoaldehydes. The decarbonylation of 18 F‐labelled aromatic dialdehydic compounds with 4 eq. of Wilkinson's catalyst at 150°C in benzonitrile resulted in high yields, e.g. 2‐[ 18 F]fluoro‐5‐methoxyisophthalaldehyde and 4‐[ 18 F]fluoro‐2‐methoxy‐5‐methylisophthalaldehyde were decarbonylated efficiently with yields of 67±3% and 72±2%, respectively. Copyright © 2010 John Wiley &amp; Sons, Ltd.
Ataxin-3 Protein and RNA Toxicity in Spinocerebellar Ataxia Type 3: Current Insights and Emerging Therapeutic Strategies (2013)

Ataxin-3 is a ubiquitously expressed deubiqutinating enzyme with important functions in the proteasomal protein degradation pathway and regulation of transcription. The C-terminus of the ataxin-3 protein contains a polyglutamine (PolyQ) region that, when mutationally expanded to over 52 glutamines, causes the neurodegenerative disease spinocerebellar ataxia 3 (SCA3). In spite of extensive research, the molecular mechanisms underlying the cellular toxicity resulting from mutant ataxin-3 remain elusive and no preventive treatment is currently available. It has become clear over the last decade that the hallmark intracellular ataxin-3 aggregates are likely not the main toxic entity in SCA3. Instead, the soluble PolyQ containing fragments arising from proteolytic cleavage of ataxin-3 by caspases and calpains are now regarded to be of greater influence in pathogenesis. In addition, recent evidence suggests potential involvement of a RNA toxicity component in SCA3 and other PolyQ expansion disorders, increasing the pathogenic complexity. Herein, we review the functioning of ataxin-3 and the involvement of known protein and RNA toxicity mechanisms of mutant ataxin-3 that have been discovered, as well as future opportunities for therapeutic intervention.