gebhart/patrepeval huggingface dataset:
Specific Covalent Labeling of Recombinant Protein Molecules Inside Live Cells (1998)

Recombinant proteins containing four cysteines at the i, i + 1, i + 4, and i + 5 positions of an alpha helix were fluorescently labeled in living cells by extracellular administration of 4',5'-bis(1,3, 2-dithioarsolan-2-yl)fluorescein. This designed small ligand is membrane-permeant and nonfluorescent until it binds with high affinity and specificity to the tetracysteine domain. Such in situ labeling adds much less mass than does green fluorescent protein and offers greater versatility in attachment sites as well as potential spectroscopic and chemical properties. This system provides a recipe for slightly modifying a target protein so that it can be singled out from the many other proteins inside live cells and fluorescently stained by small nonfluorescent dye molecules added from outside the cells.
Protective effects of monoclonal antibody to VLA-4 on leukocyte adhesion and course of disease in adjuvant arthritis in rats. (1996)

Leukocyte adhesion in mesenteric venules of adjuvant arthritic rats involves VLA-4 interaction with an unknown endothelial ligand, which is completely inhibited by Mab to rat VLA-4, indicating a promising effect on clinical symptoms.
Development of a chip‐based capillary gel electrophoresis method for quantification of a half‐antibody in immunoglobulin G4 samples (2004)

A method based on microfluidic technology was developed to support quantitative analysis of recombinant monoclonal immunoglobulin G4 (IgG4) antibody samples. The assay was performed on an Agilent 2100 Bioanalyzer in combination with the Protein 200 Plus LabChip Kit and the Protein 200 Plus assay software. Capillary electrophoresis principles have been transferred to a chip format that integrates all separation, staining, virtual destaining, and detection steps. The method is referred to in this paper as chip-based capillary gel electrophoresis (GelChip-CE method). The GelChip-CE method under nonreducing conditions proved to be a quantitative test for half-antibody determination in IgG4 samples. Similar to the traditional nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) method, the GelChip-CE method includes a denaturing step prior to separation. We showed that denaturing the sample by heating resulted in an artificial increase in the amount of half-antibody detected, which could be prevented by addition of N-ethylmaleimide to the sample buffer. The GelChip-CE method allowed for analysis of IgG4 samples with more accuracy, higher precision, and a faster turnaround time than SDS-PAGE and reversed-phase high-performance liquid chromatography (RP-HPLC).
Microchannel DNA Sequencing Matrices with a Thermally Controlled “Viscosity Switch” (2000)

Polymers and hydrogels that swell or shrink in response to environmental stimuli such as changes in temperature, pH, or ionic strength are of interest as switchable materials for applications in biotechnology. In this paper, we show that thermoresponsive polymers offer some particular advantages as entangled matrices for DNA sequencing by capillary and microchip electrophoresis. Matrices based on conventional water-soluble polymers demand a compromise in their design for microchannel electrophoresis: whereas highly entangled solutions of high molar mass polymers provide optimal sequencing performance, their highly viscous solutions require application of high pressures to be loaded into electrophoresis microchannels. Here, we demonstrate the reproducible synthesis, precise characterization, and excellent DNA sequencing performance of high molar mass, thermoresponsive polymer matrices that exhibit a reversible, temperature-controlled "viscosity switch" from high-viscosity solutions at 25 degrees C to low-viscosity, microphase-separated colloidal dispersions at a chosen, elevated temperature. The viscosity switch decouples matrix loading and sieving properties, enabling acceleration of microchannel flow by 3 orders of magnitude. DNA sequencing separations yielding read lengths of 463 bases of contiguous sequence in 78 min with 97% base-calling accuracy can be achieved in these matrices. Switchable matrices will be particularly applicable to microfluidic devices with dynamic temperature control, which are likely to provide the next major leap in the efficiency of high-throughput DNA analysis.
Superoxide attenuates macrophage apoptosis by NF-kappa B and AP-1 activation that promotes cyclooxygenase-2 expression. (1999)

Macrophages are a major source of cytokines and proinflammatory radicals such as superoxide. These mediators can be both produced and utilized by macrophages in autocrine-regulatory pathways. Therefore, we studied the potential role of oxygen radical-regulatory mechanisms in reprogramming macrophage apoptosis. Preactivation of RAW 264.7 cells with a nontoxic dose of the redox cycler 2,3-dimethoxy-1,4-naphthoquinone (5 microM) for 15 h attenuated S-nitrosoglutathione (1 mM)-initiated apoptotic cell death and averted accumulation of the tumor suppressor p53, which is indicative for macrophage apoptosis. Preactivation with superoxide promoted cyclooxygenase-2 induction that was NF-kappa B and AP-1 mediated. NF-kappa B activation was confirmed by p50/p65-heterodimer formation, I kappa B-alpha degradation, and stimulation of a NF-kappa B luciferase reporter construct. Furthermore, a NF-kappa B decoy approach abrogated cyclooxygenase-2 (Cox-2) expression as well as inducible protection. The importance of AP-1 for superoxide-mediated Cox-2 expression and cell protection was substantiated by using the extracellular signal-regulated kinase-inhibitor PD98059 and the p38-inhibitor SB203580, which blocked Cox-2 expression. In corroboration, Cox-2 expression was hindered by a dominant-negative c-jun mutant (TAM67). Protection from apoptosis was verified in human macrophages with the notion that superoxide promoted Cox-2 expression, which in turn attenuated nitric oxide-evoked caspase activation. We conclude that the sublethal generation of oxygen radicals reprograms macrophages by NF-kappa B and AP-1 activation. The resulting hyporesponsiveness reveals an attenuated apoptotic program in association with Cox-2 expression.
Optical transmission of variable-pulse-width alternating-phase duobinary modulation: MATLAB Simulink simulation and comparison with carrier-suppressed return-to-zero amplitude-shift-keying experimental transmission (2008)

Transmission in a 40-Gbit/s alternating-phase (0 and ) duobinary modulation format with 67%, 50%, and 33% pulse width [modulation duobinary carrier suppression (CS) and carrier maximum pulse carving] is demonstrated. A minimum 136-ps/nm dispersion tolerance can be achieved at this transmission rate. At least 5- and 1.2-dB receiver sensitivity improvements are achieved for CS return-to-zero (RZ) 67% and 50% duobinary modulation, respectively, as compared with the experimental measurement under CS RZ differential phase-shift keying transmission over a 320-km three-span optically amplified dispersion-compensated standard single-mode fiber system. A MATLAB Simulink platform is described for simulation of the transmission performance.
High performance 40 nm nMOSFETs with HfO/sub 2/ gate dielectric and polysilicon damascene gate (2003)

We report on 40 nm nMOS transistors with HfO/sub 2/ dielectric and polySi gate integrated into a damascene structure. We fabricated HfO/sub 2/ ALD layers with EOT down to 15 /spl Aring/, exhibiting leakage current more than two decades lower than SiO/sub 2/. Small mobility degradation on 2 nm EOT nMOSFETs was observed leading to the best performances (Ion= 680 /spl mu/A//spl mu/m @ Ioff=230 nA//spl mu/m) ever obtained with HfO/sub 2/ and polySi electrodes.
The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes (2009)

Upon detection of antigen, CD4(+) T helper (Th) cells can differentiate into a number of effector types that tailor the immune response to different pathogens. Alternative Th1 and Th2 cell fates are specified by the transcription factors T-bet and GATA-3, respectively. Only a handful of target genes are known for these two factors and because of this, the mechanism through which T-bet and GATA-3 induce differentiation toward alternative cell fates is not fully understood. Here, we provide a genomic map of T-bet and GATA-3 binding in primary human T cells and identify their target genes, most of which are previously unknown. In Th1 cells, T-bet associates with genes of diverse function, including those with roles in transcriptional regulation, chemotaxis and adhesion. GATA-3 occupies genes in both Th1 and Th2 cells and, unexpectedly, shares a large proportion of targets with T-bet. Re-complementation of T-bet alters the expression of these genes in a manner that mirrors their differential expression between Th1 and Th2 lineages. These data show that the choice between Th1 and Th2 lineage commitment is the result of the opposing action of T-bet and GATA-3 at a shared set of target genes and may provide a general paradigm for the interaction of lineage-specifying transcription factors.
Amplification of human papillomavirus genomes in vitro is dependent on epithelial differentiation (1991)

Human papillomaviruses (HPVs) infect squamous epithelium and establish their genomes as episomes in proliferating basal cells. As infected cells differentiate, the viral DNA is amplified to high copy number and infectious virus is produced. Viral production has not yet been observed in vitro due to the inability of standard culture methods to duplicate most stages of epithelial differentiation. In this study, we have examined a cell line derived from a low-grade cervical lesion and found that it contained episomal copies of an HPV-31 subtype, HPV-31b, at approximately 50 copies per cell. When allowed to stratify at the air-liquid interface of in vitro raft cultures, this cell line differentiates in a manner which histologically resembles a low-grade cervical lesion in vivo. We have observed the amplification of HPV-31b genomes in distinct foci in the upper portion of the in vitro-stratified epithelium similar to that found in productive HPV infections in vivo. Although transcripts from the late region of HPV-31b were also detected specifically in stratified raft cultures, no capsid protein was found. These studies duplicate one important aspect of a productive HPV infection in vitro, the differentiation-dependent amplification of papillomavirus genomes.
Deletions of chromosome 13q, mutations in Retinoblastoma 1, and retinoblastoma protein state in human hepatocellular carcinoma. (1994)

Twenty-one tumors from 18 patients (two independent tumors were obtained from each of three patients) with hepatocellular carcinomas were examined for loss of heterozygosity (LOH) at loci on chromosome 13q, using 15 polymorphic nucleotide sequences of microsatellites as genetic markers. The results revealed LOH in a common region between the centromeric D13S127 locus (13q12.2-q14.1) and the telomeric D13S137 (13q14.3) locus, including the RB1 locus, in nine of 21 tumors. Immunohistochemical staining of paraffin-embedded tumor sections indicated loss of retinoblastoma (RB) protein expression in all tumors showing LOH except one. Absence of RB protein expression was also observed in three of 12 tumors without LOH. Single-strand conformation polymorphism analysis of polymerase chain reaction products using primers flanking all 27 exons of the RB1 gene, as well as nucleotide sequencing, revealed tumor-specific small deletions of the RB1 coding region in the remaining RB1 allele of two tumors having LOH at the RB1 locus with concomitant loss of RB protein expression. Our results indicate that the loss of a region of chromosome 13q including the RB1 locus significantly (P < 0.006) correlates with loss of RB protein in hepatocellular carcinomas. However, tumor-specific mutations of the RB1 gene were detected in only two of 13 tumors with LOH and/or lack of RB protein expression, indicating that analysis of the RB1 status at the protein level in these tumors may be more sensitive than the actual mutational analysis.
Present role and future prospects of positron emission tomography in clinical oncology (2006)

Positron emission tomography (PET) has emerged as a significant molecular imaging technique in clinical oncology and cancer research. PET with (18)F-fluorodeoxyglucose ((18)F-FDG) demonstrates elevated glucose consumption by tumor cells, and is used clinically for the accurate staging and restaging of cancer, planning of radiotherapy, and predicting response or lack of response in the early stages of treatment. Combined PET and computed tomography (PET-CT) provides both functional and morphological information of the disease to allow accurate diagnosis of cancer. PET with new radiotracers such as protein synthesis markers and proliferation markers, as well as hypoxia and receptor-binding agents, will offer patient-specific images in order to yield tailored diagnostic and prognostic information.
Application of automated environment generation to commercial software (2006)

Model checking can be an effective technique for detecting concurrency-related errors in software systems. However, due to scalability issues, to handle industrial-strength software, model checking needs to be combined with powerful reduction techniques. In this work, we applied modular model checking to detect errors in Interstage Business Process Management (I-BPM) software, a Java client-server application spanning more than 500,000 lines of code. To model check a separate module, one needs to represent its context of execution, i.e., its environment. Environment generation is a significant challenge, since the environment is to be general enough to uncover the module's errors, yet restrictive enough to allow tractable model checking.In this paper, we present an experimental study that demonstrates the effectiveness of environment generation as a reduction technique in general and the effectiveness of automated environment generation in particular. Since model checking of the original application was intractable, we compared performance of automatically generated environments to environments written previously by hand. Automatic environments were obtained using Bandera Environment Generator (BEG). We present results of modular verification for both manual and automatic environments. The results show that automatically generated environments produce systems with a smaller state space, yet, for faulty modules, uncover the errors and, for error-free modules, produce coverage similar to manual environments.
Tumor-derived exosomes in cancer progression and treatment failure (2015)

Exosomes have diameter within the range of 30-100 nm and spherical to cup-shaped nanoparticles with specific surface molecular characteristics, such as CD9 and CD63. These vesicles are present in nearly all human body fluids, including blood plasma/serum, saliva, breast milk, cerebrospinal fluid, urine, semen, and particularly enriched in tumor microenvironment. Exosomes contain multiple proteins, DNA, mRNA, miRNA, long non-coding RNA, and even genetic materials of viruses/prions. These materials are biochemically and functionally distinct and can be transferred to a recipient cell where they regulate protein expression and signaling pathways. Recently, exosomes are demonstrated to have a close relationship with tumor development and metastasis. Exosomes influence therapeutic effect in cancer patients. In this review, we describe the biogenesis, composition, and function of exosomes. The mechanism on how tumor-derived exosomes contribute to cancer progression and clinical treatment failure is also described, with special focus on their potential applications in cancer therapy.
A Longitudinal Examination of Net Promoter and Firm Revenue Growth (2007)

Managers have widely embraced and adopted the Net Promoter metric, which noted loyalty consultant Frederick Reichheld advocates as the single most reliable indicator of firm growth compared with other loyalty metrics, such as customer satisfaction and retention. Recently, however, there has been considerable debate about whether this metric is truly superior. This article (1) employs longitudinal data from 21 firms and 15,500-plus interviews from the Norwegian Customer Satisfaction Barometer to replicate the analyses used in Net Promoter research and (2) compares Reichheld and colleagues' findings with the American Customer Satisfaction Index. Using industries Reichheld cites as exemplars of Net Promoter, the research fails to replicate his assertions regarding the "clear superiority" of Net Promoter compared with other measures in those industries.
Mechanisms of pain from urinary tract infection (2014)

The pain response to urinary tract infection is largely uncharacterized, but the symptomatic response to urinary tract infection contrasts with the lack of pain response among individuals with asymptomatic bacteriuria. Quantifying pelvic pain in a murine urinary tract infection model, uropathogenic Escerichia coli induces transient pelvic pain, whereas an asymptomatic bacteriuria E. coli isolate causes no pain, thus recapitulating the spectrum of clinical responses to intravesical E. coli. These differential pain responses are not correlated with bladder colonization or inflammation, but instead are intrinsic to E. coli lipopolysaccharide and dependent on the lipopolysaccharide receptor, TLR4. Epidemiological data suggest a link between interstitial cystitis and a history of urinary tract infection, so it was evaluated whether repetitive uropathogenic E. coli instillation would result in chronic pain through central sensitization. Although repeated infection with wild type uropathogenic E. coli results in only transient episodes of acute pain, a uropathogenic E. coli mutant lacking O-antigen causes chronic, post-urinary tract infection pelvic pain. Similarly, a K-12 E. coli strain lacking O-antigen induces chronic pain that persisted long after bacterial clearance, and expressing O-antigen nullified the pain phenotype. Spinal cords isolated from mice with post-urinary tract infection chronic pain showed deficits in short-term depression consistent with central sensitization. Deleting O-antigen gene complex from a uropathogenic E. coli strain and subsequent heterologous expression of O-antigen gene clusters shows that a single bacterial isolate can exhibit pain phenotypes ranging from a null phenotype, an acute pain phenotype, to a chronic pain phenotype. Post-urinary tract infection chronic pain is also associated with voiding dysfunction and anxious/depressive behavior. These effects are also mediated by TRPV1 at the level of pain establishment and CCR2 at the level of pain maintenance. Together, these findings show that transient infection with E. coli might result in chronic visceral pain with the hallmarks of neuropathic pain. This pattern of behaviors mimics the spectrum of interstitial cystitis symptoms, thus supporting the possibility of an infectious etiology of interstitial cystitis.
Slow-wave sleep and the consolidation of long-term memory (2010)

Slow-wave sleep (SWS) has been shown to play an important role in the reinforcement of declarative memory. A dialogue between the neocortex and hippocampus is important during this consolidation and appears to be largely regulated by <1 Hz electroencephalographic (EEG) slow oscillations. Events experienced during wakefulness are encoded in the neocortex but, simultaneously they are encoded even more strongly in the hippocampus. Slow oscillations that characterize SWS originate in the neocortex and their amplitude increases with increased amounts of information encoded during prior waking. Neuronal activity is temporarily grouped by these slow oscillations into up-states of enhanced neuronal activity and down-states of neuronal silence. Grouping is not only induced in the neocortex but also in other relevant structures, such as the thalamus and the hippocampus, generating spindle activity and sharp-wave ripples, respectively. Sharp-wave ripples are known to accompany a memory replay of encoded information in the hippocampus during SWS which stimulates the transfer of this memory-related information to the neocortex. The slow oscillations synchronize this transfer with the thalamocortical spindles arriving at the neocortex at the same time as the hippocampal memory information. This synchronization is thought to be critical to the long-term storage of respective memories within neocortical networks.
Vaults. III. Vault ribonucleoprotein particles open into flower-like structures with octagonal symmetry. (1991)

The structure of rat liver vault ribonucleoprotein particles was examined using several different staining techniques in conjunction with EM and digestion with hydrolytic enzymes. Quantitative scanning transmission EM demonstrates that each vault particle has a total mass of 12.9 +/- 1 MD and contains two centers of mass, suggesting that each vault particle is a dimer. Freeze-etch reveals that each vault opens into delicate flower-like structures, in which eight rectangular petals are joined to a central ring, each by a thin hook. Vaults examined by negative stain and conventional transmission EM (CTEM) also reveal the flower-like structure. Trypsin treatment of vaults resulted exclusively in cleavage of the major vault protein (p104) and concurrently alters their structure as revealed by negative stain/CTEM, consistent with a localization of p104 to the flower petals. We propose a structural model that predicts the stoichiometry of vault proteins and RNA, defines vault dimer-monomer interactions, and describes two possible modes for unfolding of vaults into flowers. These highly dynamic structural variations are likely to play a role in vault function.
Switchable dual-band circularly polarised patchantenna with single feed (2001)

A novel patch antenna with switchable slots is proposed for dual-band circularly polarised (CP) operation. Two diode controlled slots are incorporated into the patch for dual-band operation and a pair of tuning stubs are utilised to tune the CP performance. The antenna design and experimental results are presented.
Cloning and characterization of transcripts showing virulence-related gene expression in Naegleria fowleri (1992)

The pathogenic LEE strain of Naegleria fowleri isolated from human or mouse brain loses pathogenicity when cultured axenically in a nutrient broth. To identify genes differentially expressed in highly virulent versus weakly virulent amoebae, a cDNA library was constructed by using mRNA from amoebae recovered from a mouse brain. Two cDNA clones were isolated by differential screening of the library. The transcript homologous to clone Nf314 was preferentially expressed in highly virulent cells, whereas the transcript homologous to clone Nf435 was preferentially expressed in weakly virulent cells. Other clones showed negligible differential hybridization, but actin transcript levels were slightly elevated in the highly virulent cells. The Nf314 cDNA has an open reading frame for a 53-kDa protein 94% similar and 19% identical over 194 amino acid residues to serine carboxypeptidase from yeast cells, barley, and wheat. Southern blot analysis is consistent with a single copy of the Nf314 gene in the genome. Interestingly, the increased Nf314 transcript levels were present in cells fed on mouse brain, liver, or NIH 3T3 fibroblasts but not in cells fed on bacteria or in axenic culture. Thus, the inducer of the increased gene expression correlates with use of mammalian cells as a food source without regard to level of virulence. Since amoebae fed in culture on dissociated mouse brain were weakly virulent, as measured by their abilities to kill mice, the Nf314 gene may be required but is not sufficient for increased virulence.