gebhart/patrepeval huggingface dataset:
The Metabolites of the Herbicide L-Phosphinothricin (Glufosinate) (Identification, Stability, and Mobility in Transgenic, Herbicide-Resistant, and Untransformed Plants) (1994)

The metabolism of the herbicide L-phosphinothricin (L-Pt) was analyzed in tobacco (Nicotiana tabacum), alfalfa (Medicago sativa), and carrot (Daucus carota). In transgenic, Pt-resistant plants expressing the Pt-N-acetyltransferase gene (pat), L-Pt was acetylated, resulting in two forms of N-acetyl-Pt (ac-Pt). In transgenic plants expressing only low pat-encoded acetylating activity as well as in genetically unmodified plants, three metabolic compounds 4-methylphosphinico-2-oxo-butanoic acid, 3-methylphosphinico-propanoic acid (MPP), and 4-methylphosphinico-2-hydroxy-butanoic acid (MHB) were identified. Hence, the transgene-encoded acetylation of L-Pt competes with a plant-specific degradation. The compounds MPP, MHB, and ac-Pt were found to be the final, stable products of the plant's metabolic pathways. The mobility of these stable compounds in the plant was investigated: L-Pt as well as the derived metabolites were found to be preferentially transported to the upper regions of the plant.
Salivary α‐amylase as a measure of endogenous adrenergic activity (1996)

This investigation was designed to evaluate the production rates and concentrations of salivary alpha-amylase as a measure of adrenergic activity under several conditions of stress in human subjects. Saliva and blood samples were simultaneously collected from men at four 15 min intervals both before and after regimens for exercise, a written examination, or a rest period. The regressions of salivary alpha-amylase on plasma norepinephrine (NE) concentrations were significant for both exercise (P < 0.001) and examination (P < 0.01) protocols. Aerobic exercise induced a 3-fold mean increase in alpha-amylase; both NE and epinephrine (EP) increased approximately 5-fold over control levels. Levels of alpha-amylase and NE returned to control levels within 30-45 min after exercise, but EP remained elevated by approximately 2-fold during the remaining hour of observation. During the written examination, alpha-amylase and NE, but not EP, concentrations increased in parallel. In further studies the effects of exercise and exposure to heat and cold on the relationship of salivary alpha-amylase to heart rate and body temperature were investigated. Greater intensities of exercise were associated with greater increases in alpha-amylase concentrations. During heat exposure in a sauna (66 degrees C for 40 min) amylase, heart rate and body temperature all increased progressively. However, during exposure to cold (4 degrees C for 40 min) amylase increased rapidly, though heart rate and body temperature remained unchanged. Salivary cortisol concentrations were unchanged during exposure to heat or cold. We conclude that salivary alpha-amylase concentrations are predictive of plasma catecholamine levels, particularly NE, under a variety of stressful conditions, and may be a more direct and simple end point of catecholamine activity than are changes in heart rate.
Example-based object detection in images by components (2001)

We present a general example-based framework for detecting objects in static images by components. The technique is demonstrated by developing a system that locates people in cluttered scenes. The system is structured with four distinct example-based detectors that are trained to separately find the four components of the human body: the head, legs, left arm, and right arm. After ensuring that these components are present in the proper geometric configuration, a second example-based classifier combines the results of the component detectors to classify a pattern as either a "person" or a "nonperson." We call this type of hierarchical architecture, in which learning occurs at multiple stages, an adaptive combination of classifiers (ACC). We present results that show that this system performs significantly better than a similar full-body person detector. This suggests that the improvement in performance is due to the component-based approach and the ACC data classification architecture. The algorithm is also more robust than the full-body person detection method in that it is capable of locating partially occluded views of people and people whose body parts have little contrast with the background.
Loss of Huntingtin-Mediated BDNF Gene Transcription in Huntington's Disease (2001)

Huntingtin is a 350-kilodalton protein of unknown function that is mutated in Huntington's disease (HD), a neurodegenerative disorder. The mutant protein is presumed to acquire a toxic gain of function that is detrimental to striatal neurons in the brain. However, loss of a beneficial activity of wild-type huntingtin may also cause the death of striatal neurons. Here we demonstrate that wild-type huntingtin up-regulates transcription of brain-derived neurotrophic factor (BDNF), a pro-survival factor produced by cortical neurons that is necessary for survival of striatal neurons in the brain. We show that this beneficial activity of huntingtin is lost when the protein becomes mutated, resulting in decreased production of cortical BDNF. This leads to insufficient neurotrophic support for striatal neurons, which then die. Restoring wild-type huntingtin activity and increasing BDNF production may be therapeutic approaches for treating HD.
The Chemical Vapor Deposition of Metal Boride Thin Films from Polyhedral Cluster Species (1999)

Metal boride thin film fabrication through Chemical Vapor Deposition (CVD) techniques is an area of current technological and scientific interest. These materials have attracted significant attention due to their breadth of unique physical, chemical and structural properties. CVD is clearly one of the best methods for the formation of these materials since it circumvents many of the problems associated with other technologies. We have used several boron CVD precursors, especially the boranes, to prepare many pure metal and metal boride thin film materials through an apparently general deposition reaction process. In this paper, our work on the formation of polycrystalline transition metal and lanthanide metal boride thin films from borane precursors is briefly presented. These deposited materials have been extensively characterized by techniques including scanning electron microscopy (SEM), Auger electron spectroscopy (AES), X-ray diffraction (XRD), X-ray emission spectroscopy (XES), low-energy electron diffraction (LEED), transmission electron spectroscopy (TEM) and solid state nuclear magnetic resonance spectroscopy (NMR). This CVD chemistry appears to constitute a highly efficient method for the formation of polycrystalline transition metal and lanthanide metal boride thin films. The fundamentally important chemical processes and reactions in the CVD formation of metal boride films from boranes has not, however, been previously well investigated. In our recent work which will be briefly summarized here, we have explored several of the important details of the CVD of metal borides from gas phase boranes and metal halide precursors.
Quantum Capacitance Limited Vertical Scaling of Graphene Field-Effect Transistor (2011)

A high-quality Y2O3 dielectric layer has been grown directly on graphene and used to fabricated top-gate graphene field-effect transistors (FETs), and the thickness of the dielectric layer has been reduced continuously down to 3.9 nm with an equivalent oxide thickness (EOT) of 1.5 nm and excellent insulativity. By measuring CV characteristics of two graphene FETs with different gate oxide thicknesses, the oxide capacitance and quantum capacitance are retrieved directly from the experimental CV data without introducing any additional fitting process and parameters, yielding a relative dielectric constant of κ=10 for Y2O3 on graphene and an oxide capacitance of about 2.28 μF/cm2. It is found that for a rather large gate voltage range, this oxide capacitance is comparable and sometimes even larger than the quantum capacitance of graphene. Since the total gate capacitance is determined by the smaller of the oxide and quantum capacitance, our results show that not much further improvement can be gained via further vertical scaling down of the gate oxide, suggesting that Y2O3 may be the ultimate dielectric material for graphene. It is also shown that the Y2O3 gate dielectric layer with EOT of 1.5 nm may also satisfy the ultimate lateral scaling requirement on the gate length of graphene FET and be used effectively to control a graphene FET with a gate length as small as 1 nm.
Yeasts encoding tumour antigens in cancer immunotherapy (2005)

Immunotherapy for cancer represents an attractive therapeutic target because of its specificity and lack of toxicity, but products investigated so far have been limited by neutralisation, complexity of manufacturing and requirement for patient-specific products. Recombinant yeast cells are capable of stimulating the immune system to produce highly specific and potent cellular responses against target protein antigens with little toxicity. Data from animal models suggest that Tarmogens (yeast-based immunotherapeutics) can elicit protective immunity against xenografted and chemically induced tumours. This concept is now being tested in a Phase I trial in patients with colorectal, pancreatic and non-small cell lung cancers.
Highly sensitive thermally developable positive resist systems (1988)

Acid-catalyzed thermal depolymerization of polyphthalaldehyde derivatives has been utilized in the design of highly sensitive, thermally developable, positive resist systems incorporating two stages of chemical amplification. Poly(4-chlorophthalaldehyde) mixed with triphenylsulfonium hexafluoroantimonate can be thermally developed to the substrate simply by heating the resist after exposure to &amp;lt;1 mJ/cm2 of 254-nm radiation or 1 μC/cm2 of 18-keV electron beam radiation. The images obtained by postbaking at 160 °C do not exhibit any thermal flow. Poly(4-trimethylsilylphthalaldehyde) (PSPA) sensitized with triphenylsulfonium triflate exhibits a high deep UV sensitivity of &amp;lt;2 mJ/cm2 and a high electron beam sensitivity of 1 to 2 μC/cm2 (20 keV) when the thermal development is performed at 100–130 °C. The high contrast (γ=4.3) of the PSPA resist allows thermal imaging of submicrometer features, which can then be transferred to the bottom planarizing layer by oxygen reactive ion etching (RIE). The combination of the thermal development and oxygen RIE pattern transfer provides a new mode of all dry bilayer processes.
Amyloid‐β neurotoxicity in organotypic culture is attenuated by melatonin: involvement of GSK‐3β, tau and neuroinflammation (2010)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by accumulation of extracellular deposits of amyloid-beta (Abeta) peptide in brain regions that are important for memory and cognition. The buildup of Abeta aggregates in the AD is followed by the formation of intracellular neurofibrillary tangles and activation of neuroinflammatory reactions. The present study investigated whether melatonin possesses a neuroprotective effect against Abeta-induced toxicity. For this purpose, organotypic hippocampal slices were cultured and exposed to 25 microm of Abeta(25-35) in the absence or in the presence of melatonin (25, 50, or 100 microm). In addition, the authors have investigated the involvement of GSK-3beta, tau protein, astroglial, and microglial activation, and cytokine levels in the melatonin protection against Abeta-induced neurotoxicity. Melatonin prevented the cell damage in hippocampus induced by the exposure to Abeta(25-35). In addition, melatonin significantly reduced the activation of GSK-3beta, the phosphorylation of tau protein, the glial activation and the Abeta-induced increase of TNF-alpha and IL-6 levels. On the basis of these findings, we speculate that melatonin may provide an effective therapeutic strategy for AD, by attenuating Abeta-induced phosphorylation of tau protein, and preventing GSK-3beta activation and neuroinflammation.
Bioactive Peptides in Drug Discovery and Design: Medical Aspects (1999)

Peptide research on drug discovery and design is an important field in the development of peptide mimetics, with the potential to generate important new drugs. This work inludes synthesis, function, structure-activity relationships, conformation, biology, and molecular dynamics.
Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment (2005)

Understanding the mechanisms of immune cell migration to multiple sclerosis lesions offers significant therapeutic potential. This study focused on the chemokines CXCL12 (SDF-1) and CXCL13 (BCA-1), both of which regulate B cell migration in lymphoid tissues. We report that immunohistologically CXCL12 was constitutively expressed in CNS parenchyma on blood vessel walls. In both active and chronic inactive multiple sclerosis lesions CXCL12 protein was elevated and detected on astrocytes and blood vessels. Quantitative PCR demonstrated that CXCL13 was produced in actively demyelinating multiple sclerosis lesions, but not in chronic inactive lesions or in the CNS of subjects who had no neurological disease. CXCL13 protein was localized in perivascular infiltrates and scattered infiltrating cells in lesion parenchyma. In the CSF of relapsing-remitting multiple sclerosis patients, both CXCL12 and CXCL13 were elevated. CXCL13, but not CXCL12, levels correlated strongly with intrathecal immunoglobulin production as well as the presence of B cells, plasma blasts and T cells. About 20% of CSF CD4+ cells and almost all B cells expressed the CXCL13 receptor CXCR5. In vitro, CXCL13 was produced by monocytes and at much higher levels by macrophages. CXCL13 mRNA and protein expression was induced by TNFalpha and IL-1beta but inhibited by IL-4 and IFNgamma. Together, CXCL12 and CXCL13 are elevated in active multiple sclerosis lesions and CXCL12 also in inactive lesions. The consequences of CXCL12 up-regulation could be manifold. CXCL12 localization on blood vessels indicates a possible role in leucocyte extravasation, and CXCL12 may contribute to plasma cell persistence since its receptor CXCR4 is retained during plasma cell differentiation. CXCL12 may contribute to axonal damage as it can become a neurotoxic mediator of cleavage by metalloproteases, which are present in multiple sclerosis lesions. The strong linkage of CXCL13 to immune cells and immunoglobulin levels in CSF suggests that this is one of the factors that attract and maintain B and T cells in inflamed CNS lesions. Therefore, both CXCL13 and CXCR5 may be promising therapeutic targets in multiple sclerosis.
Resistance of Human Immunodeficiency Virus Type 1 to the High-Mannose Binding Agents Cyanovirin N and Concanavalin A (2005)

Due to the biological significance of the carbohydrate component of the human immunodeficiency virus type 1 (HIV-1) glycoproteins in viral pathogenesis, the glycosylation step constitutes an attractive target for anti-HIV therapy. Cyanovirin N (CV-N), which specifically targets the high-mannose (HM) glycans on gp120, has been identified as a potent HIV-1 entry inhibitor. Concanavalin A (ConA) represents another mannose-binding lectin, although it has a lower specificity for HM glycans than that of CV-N. For the present study, we selected CV-N- and ConA-resistant HIV-1 strains in the presence of CV-N and ConA, respectively. Both resistant strains exhibited a variety of mutations eliminating N-linked glycans within gp120. Strains resistant to CV-N or ConA displayed high levels of cross-resistance towards one another. The N-glycan at position 302 was eliminated in both of the lectin-resistant strains. However, the elimination of this glycan alone by site-directed mutagenesis was not sufficient to render HIV-1 resistant to CV-N or ConA, suggesting that HIV-1 needs to mutate several N-glycans to become resistant to these lectins. Both strains also demonstrated clear cross-resistance towards the carbohydrate-dependent monoclonal antibody 2G12. In contrast, the selected strains did not show a reduced susceptibility towards the nonlectin entry inhibitors AMD3100 and enfuvirtide or towards reverse transcriptase or protease inhibitors. Recombination of the mutated gp160 genes of the strains resistant to CV-N or ConA into a wild-type background fully reproduced the (cross-)resistance profiles of the originally selected strains, pointing to the impact of the N-glycan mutations on the phenotypic resistance profiles of both selected strains.
Ribozyme termination of RNA transcripts down‐regulate seed fatty acid genes in transgenic soybean (2002)

We investigated whether termination of transcripts with a self-cleaving ribozyme can enhance nuclear retention and serve as a tool to decrease specific plant gene expression. Nuclear retention was first monitored in tobacco using the beta-glucuronidase gene terminated with either the 35S CaMV 3' untranslated sequence (UTR) or a cis-acting ribozyme. Northern blot analysis of nuclear RNA and total RNA, and in situ hybridizations showed that the ribozyme-terminated transcripts were preferentially retained in the nucleus of transgenic tobacco. Ribozyme-terminated transcripts were subsequently tested as a gene down-regulation strategy in soybean. The embryo-specific Delta-12 fatty acid desaturase FAD2-1 gene was targeted because its down-regulation elevates oleic acid content of seed storage lipids. Both ribozyme-terminated antisense and standard antisense constructs were capable of gene down-regulation, producing over 57% oleic acid compared with less than 18% in wild-type seed. Ribozyme termination cassettes were also constructed to evaluate sense transcripts for single gene down-regulation and the simultaneous down-regulation of two embryo-specific genes in soybean using a single promoter. Eight independent soybean transformants were screened that harboured standard plus sense or ribozyme terminated FAD2-1 cassette. Two of the eight ribozyme terminated transformants displayed oleic acids levels in the seed storage lipids of over 75%, while none of the standard plus sense FAD2-1 lines showed elevated oleic acid phenotypes. The dual constructs targeted FAD2-1 and the FatB gene encoding a palmitoyl-thioesterase. Five transgenic soybean lines harbouring the dual constructs had oleic acid levels, greater than 85%, and saturated fatty acids levels, less than 6%. Thus, ribozyme termination of transcripts can be utilized to specifically down-regulate endogenous gene expression in soybean.
Cycloid scanning for wide field optical coherence tomography endomicroscopy and angiography in vivo (2018)

Devices that perform wide field-of-view (FOV) precision optical scanning are important for endoscopic assessment and diagnosis of luminal organ disease such as in gastroenterology. Optical scanning for <i>in vivo</i> endoscopic imaging has traditionally relied on one or more proximal mechanical actuators, limiting scan accuracy and imaging speed. There is a need for rapid and precise two-dimensional (2D) microscanning technologies to enable the translation of benchtop scanning microscopies to <i>in vivo</i> endoscopic imaging. We demonstrate a new cycloid scanner in a tethered capsule for ultrahigh speed, side-viewing optical coherence tomography (OCT) endomicroscopy <i>in vivo</i>. The cycloid capsule incorporates two scanners: a piezoelectrically actuated resonant fiber scanner to perform a precision, small FOV, fast scan and a micromotor scanner to perform a wide FOV, slow scan. Together these scanners distally scan the beam circumferentially in a 2D cycloid pattern, generating an unwrapped 1 mm × 38 mm strip FOV. Sequential strip volumes can be acquired with proximal pullback to image centimeter-long regions. Using ultrahigh speed 1.3 μm wavelength swept-source OCT at a 1.17 MHz axial scan rate, we imaged the human rectum at 3 volumes/s. Each OCT strip volume had 166 × 2322 axial scans with 8.5 μm axial and 30 μm transverse resolution. We further demonstrate OCT angiography at 0.5 volumes/s, producing volumetric images of vasculature. In addition to OCT applications, cycloid scanning promises to enable precision 2D optical scanning for other imaging modalities, including fluorescence confocal and nonlinear microscopy.
Enrichment of CD8+ Cells From Melanoma Tumor-infiltrating Lymphocyte Cultures Reveals Tumor Reactivity for Use in Adoptive Cell Therapy (2010)

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma has shown objective response rates as high as 72%. The successful application of this therapy requires the selection of unique tumor-reactive lymphocyte cultures for each patient. This is a technically and logistically difficult undertaking, and patients who do not have tumor-reactive TIL are not considered eligible for treatment. To simplify the methods of TIL generation and extend TIL-based immunotherapy to additional patients, methods were developed to use unselected, minimally cultured ("young") TIL. Young TIL cultures contain a variable number of CD8(+), CD4(+), and CD3(-)CD56(+) natural killer cells. In this study we retrospectively investigated a role for these subsets in the clinical outcome of patients treated with TIL derived from selected microcultures. This analysis demonstrated a suggestive but nonsignificant association between the number of CD8(+) cells administered and tumor regression. We therefore investigated the feasibility of selecting CD8(+) cells from young TIL cultures for ACT therapy. The available methods for clinical scale CD8(+) enrichment proved inadequate for TIL, so an optimized CD8(+) enrichment method was developed and is reported here. We observed that CD8 (+)enrichment of some TIL cultures revealed in vitro tumor recognition that was not evident in bulk culture, and an improved in vitro recognition of tumor in other TIL cultures. In addition, the enriched CD8(+) young TIL expanded more reliably and predictably in rapid expansions than the bulk TIL. Thus, optimized CD8(+) selection combines the benefits of antigen-selected TIL and young TIL for generating lymphocyte cultures for ACT, and should be evaluated in cell transfer therapy protocols.
Enhancing performance of cooperating agents in real-time diagnostic systems (1993)

We present a data-driven protocol and a supporting architecture for communication among cooperating intelligent agents in real-time diagnostic systems. The system architecture and the exchange of information among agents are based on simplicity of agents, hierarchical organization of agents, and modular non-overlapping division of the problem domain. These features combine to enable efficient diagnosis of complex system failures in real-time environments with high data volumes and moderate failure rates. Preliminary results of the real-world application of this work to the monitoring and diagnosis of complex systems are discussed in the context of NASA's interplanetary mission operations.
Extensive Nitration of Protein Tyrosines in Human Atherosclerosis Detected by Immunohistochemistry (1994)

Oxidation of lipoproteins is important for the initiation and propagation of the atherosclerotic lesion and may involve secondary oxidants derived from nitric oxide. Nitric oxide (NO) reacts at near diffusion limited rates with superoxide (O2-.) to form the strong oxidant, peroxynitrite (ONOO-). Nitration on the ortho position of tyrosine is a major product of peroxynitrite attack on proteins. Nitrotyrosine was detected in atherosclerotic lesions of formalin-fixed human coronary arteries with polyclonal and monoclonal antibodies. Binding was pronounced in and around foamy macrophages within the atheroma deposits. Nitration was also observed in early subintimal fatty streaks. Antibody binding was completely blocked by co-incubation with 10mM nitrotyrosine, but not by equivalent concentrations of aminotyrosine or phosphotyrosine. The presence of nitrotyrosine indicates that oxidants derived from nitric oxide such as peroxynitrite are generated in human atherosclerosis and may be involved in its pathogenesis.