gebhart/patrepeval huggingface dataset:
Bioactive Compounds from the Aerial Parts of Brachystemma calycinum and Structural Revision of an Octacyclopeptide (2011)

Four new cyclic peptides, brachystemins F-I (1-4), and 11 known compounds were isolated from the aerial parts of Brachystemma calycinum. The absolute configurations of compounds 1-4 were assigned using Marfey's method. The structure of compound 5 was revised from cyclo(Pro¹-Phe²-Leu³-Ala⁴-Thr⁵-Pro⁶-Ala⁷-Gly⁸) to cyclo(Pro¹-Pro²-Ala³-Gly⁴-Leu⁵-Ala⁶-Thr⁷-Phe⁸) with QTOF/MS and X-ray diffraction analysis. The N-containing compounds were assessed for their inhibitory effects on the secretion of monocyte chemokine ligand 2 (CCL-2), interleukin 6 (IL-6), and collagen IV against high-glucose-stimulated mesangial cells. Compound 5 was evaluated for its effects on collagen I, reactive oxygen species (ROS), superoxide anion (O₂(•⁻)) production, and cell viability in mesangial cells, and on nitric oxide (NO) production in macrophage cells.
Use of Tissue Cross-reactivity Studies in the Development of Antibody-based Biopharmaceuticals (2010)

Tissue cross-reactivity (TCR) studies are screening assays recommended for antibody and antibody-like molecules that contain a complementarity-determining region (CDR), primarily to identify off-target binding and, secondarily, to identify sites of on-target binding that were not previously identified. At the present time, TCR studies involve the ex vivo immunohistochemical (IHC) staining of a panel of frozen tissues from humans and animals, are conducted prior to dosing humans, and results are filed with the initial IND/CTA to support first-in-human clinical trials. In some cases, a robust TCR assay cannot be developed, and in these cases the lack of a TCR assay should not prevent a program from moving forward. The TCR assay by itself has variable correlation with toxicity or efficacy. Therefore, any findings of interest should be further evaluated and interpreted in the context of the overall pharmacology and safety assessment data package. TCR studies are generally not recommended for surrogate molecules or for comparability assessments in the context of manufacturing/cell line changes. Overall, the design, implementation, and interpretation of TCR studies should follow a case-by-case approach.
Optically Invisible Antenna Integrated Within an OLED Touch Display Panel for IoT Applications (2017)

Future electronics and Internet of Things devices with the capability of high-speed wireless communication will increasingly rely on efficient and intelligent antennas. However, conventional wireless communication systems for small wireless electronics devices suffer from low radiation efficiencies of miniaturized antennas implemented within less-than ideal locations and real estates. Here, we introduce the original concept of utilizing the entire transparent region of high-resolution organic light-emitting diode (OLED) touch displays to render an antenna that is invisible to the human eye. A transverse magnetic resonant mode antenna is formulated based on transparent conductive polymers, which are precisely realized using mesoscale formation of electromagnetic boundary conditions. Simultaneously, these electromagnetic patterns achieve optical invisibility. We show that the transparent antenna film can be integrated inside an OLED touch display and feature efficient radiation properties at 2.4 GHz. The presented theory and measurement studies of the fabricated prototype for smartwatch application for Wi-Fi and Bluetooth connectivity inspire a broader range of integration of microwave and display technologies.
Intranasal dexmedetomidine versus intranasal midazolam as pre-anesthetic medication in pediatric age group undergoing adenotonsillectomy (2020)

Abstract Background The pre-operative period is a very stressful event for most of the individuals undergoing surgery especially the pediatric patients. So, relieving their pre-operative anxiety becomes an important concern for an anesthesiologist. Many anesthetic pre-medications are used to relieve this stress response. Of these pre-medications, midazolam and dexmedetomidine are effectively used as sedatives. The present study was planned to compare intranasal dexmedetomidine with intranasal midazolam as a pre-anesthetic medication in children. Forty-eight children aged 3–7 years, of either sex, weighing 13–22 kg, with American Society of Anesthesiologists (ASA) physical status 1 and undergoing elective adenotonsillectomy surgery were enrolled in this comparative prospective, double blinded, randomized clinical study. The children were divided into 2 groups: group D and group M, of 24 each. Forty-five minutes before induction of anesthesia, group D ( n = 24) received intranasal dexmedetomidine at a dose of 1 μg/kg and group M ( n = 24) received intranasal midazolam of 0.2 mg/kg. Results Children who were pre-medicated with dexmedetomidine had lower sedation scores, lower anxiety levels, easier child-parent separation, better mask acceptance, and lower pain scores than those who received midazolam. The incidence of emergence agitation was decreased in both groups with no significant difference. Conclusion Intranasal dexmedetomidine seems to offer some advantages compared with midazolam. Thus, it can be used effectively and safely as a pre-anesthetic medication in children undergoing any surgical procedures under general anesthesia.
Sun-to-Fuel Assessment of Routes for Fixing CO2 as Liquid Fuel (2013)

This study presents a systems approach for comparing alternative routes for converting CO2 to liquid fuel using solar energy based on a novel metric of sun-to-fuel (STF) efficiency. The metric refers to the fraction of incident solar energy that is recovered in the liquid fuel. The STF efficiency analysis identifies energy and land use efficient routes that require immediate research and development effort to speed up their progress toward long-term cost-effectiveness. The analysis’ unique insights are particularly relevant for densely populated regions, having scarce per capita land availability relative to the per capita energy demands. With atmospheric CO2 as the renewable carbon source, we present a detailed case study comparing the currently known photosynthetic routes with a theoretical route based on direct extraction of CO2 from air and its subsequent thermochemical conversion to liquid fuel. The findings indicate that the latter route could be potentially more energy and thereby land use efficient than any of the currently known photosynthetic routes, therefore, warranting its inclusion in any transportation fuels research portfolio. An interesting finding of our study is that for the interim period while CO2 extraction is still uneconomical and CO2 sourced from power plants is instead used, the relative energy efficiency of different routes remains unchanged. This suggests that the results in general are independent of the concentration of the CO2 source.
Sequence and nuclear localization of the Saccharomyces cerevisiae HAP2 protein, a transcriptional activator. (1987)

Activation of the CYC1 upstream activation site (UAS2) and other Saccharomyces cerevisiae genes encoding respiratory functions requires the products of the regulatory loci HAP2 and HAP3. We present here the DNA sequence of the yeast HAP2 gene and an initial investigation into the function of its product. The DNA sequence indicated that HAP2 encoded a 265-amino-acid protein whose carboxyl third was highly basic. Also found in the sequence was a polyglutamine tract spanning residues 120 to 133. Several experiments described herein suggest that HAP2 encodes a direct activator of transcription. First, a bifunctional HAP2-beta-galactosidase fusion gene was localized to the yeast nucleus. Second, a lexA-HAP2 fusion gene was capable of activating transcription when bound to a lexA operator site. The additional requirement for the HAP3 product in activation is discussed.
Prognosis of Oral Pre-malignant Lesions: Significance of Clinical, Histopathological, and Molecular Biological Characteristics (2003)

The concept of a two-step process of cancer development in the oral mucosa, i.e., the initial presence of a precursor subsequently developing into cancer, is well-established. Oral leukoplakia is the best-known precursor lesion. The evidence that oral leukoplakias are pre-malignant is mainly derived from follow-up studies showing that between < 1 and 18% of oral pre-malignant lesions will develop into oral cancer; it has been shown that certain clinical sub-types of leukoplakia are at a higher risk for malignant transformation than others. The presence of epithelial dysplasia may be even more important in predicting malignant development than the clinical characteristics. Three major problems, however, are attached to the importance of epithelial dysplasia in predicting malignant development: (1) The diagnosis is essentially subjective, (2) it seems that not all lesions exhibiting dysplasia will eventually become malignant and some may even regress, and (3) carcinoma can develop from lesions in which epithelial dysplasia was not diagnosed in previous biopsies. There is, therefore, a substantial need to improve the histologic assessment of epithelial dysplasia or, since epithelial dysplasia does not seem to be invariably associated with or even a necessary prerequisite for malignant development, it may be necessary to develop other methods for predicting the malignant potential of pre-malignant lesions. As a consequence of these problems, numerous attempts have been made to relate biological characteristics to the malignant potential of leukoplakias. Molecular biological markers have been suggested to be of value in the diagnosis and prognostic evaluation of leukoplakias. Markers of epithelial differentiation and, more recently, genomic markers could potentially be good candidates for improving the prognostic evaluation of precursors of oral cancer. As yet, one or a panel of molecular markers has not been determined that allows for a prognostic prediction of oral pre-cancer which is any more reliable than dysplasia recording. However, these new markers could be considered complementary to conventional prognostic evaluation.
Structure and stability of Ricinus communis haemagglutinin (1986)

The molecular properties of the haemagglutinin of Ricinus communis (RCA I or RCA 120) were evaluated by analytical ultracentrifugation, light-scattering, c.d. and fluorescence. The native molecule had a fairly expanded structure (f/f0 = 1.43) and dissociated into two subunits of equal size in 6 M-guanidinium chloride. This native structure was stable in alkali (up to pH 11) and resistant to thermal denaturation at neutrality. A pH-triggered change in the haemagglutinin conformation was observed and characterized by analytical ultracentrifugation, c.d. and fluorescence between pH 7 and 4.5, the range in which its affinity for galactosides decreased [Yamasaki, Absar & Funatsu (1985) Biochim, Biophys. Acta 828, 155-161]. These results are discussed in relation to those reported in the literature for other lectins and more especially ricin, for which a pH-dependent conformation transition has been observed in the same range of low pH.
PPARs and their metabolic modulation: new mechanisms for transcriptional regulation? (2007)

Peroxisome proliferator-activated receptors (PPARs) as ligand-activated nuclear receptors involved in the transcriptional regulation of lipid metabolism, energy balance, inflammation, and atherosclerosis are at the intersection of key pathways involved in the pathogenesis of diabetes and cardiovascular disease. Synthetic PPAR agonists like fibrates (PPAR-alpha) and thiazolidinediones (PPAR-gamma) are in therapeutic use to treat dyslipidaemia and diabetes. Despite strong encouraging in vitro, animal model, and human surrogate marker studies with these agents, recent prospective clinical cardiovascular trials have yielded mixed results, perhaps explained by concomitant drug use, study design, or a lack of efficacy of these agents on cardiovascular disease (independent of their current metabolic indications). The use of PPAR agents has also been limited by untoward effects. An alternative strategy to PPAR therapeutics is better understanding PPAR biology, the nature of natural PPAR agonists, and how these molecules are generated. Such insight might also provide valuable information about pathways that protect against the metabolic problems for which PPAR agents are currently indicated. This approach underscores the important distinction between the effects of synthetic PPAR agonists and the unequivocal biologic role of PPARs as key transcriptional regulators of metabolic and inflammatory pathways relevant to diabetes and atherosclerosis.
Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier. (1991)

Delivery of nonlipophilic drugs to the brain is hindered by the tightly apposed capillary endothelial cells that make up the blood-brain barrier. We have examined the ability of a monoclonal antibody (OX-26), which recognizes the rat transferrin receptor, to function as a carrier for the delivery of drugs across the blood-brain barrier. This antibody, which was previously shown to bind preferentially to capillary endothelial cells in the brain after intravenous administration (Jefferies, W. A., Brandon, M. R., Hunt, S. V., Williams, A. F., Gatter, K. C. & Mason, D. Y. (1984) Nature (London) 312, 162-163), labels the entire cerebrovascular bed in a dose-dependent manner. The initially uniform labeling of brain capillaries becomes extremely punctate approximately 4 hr after injection, suggesting a time-dependent sequestering of the antibody. Capillary-depletion experiments, in which the brain is separated into capillary and parenchymal fractions, show a time-dependent migration of radiolabeled antibody from the capillaries into the brain parenchyma, which is consistent with the transcytosis of compounds across the blood-brain barrier. Antibody-methotrexate conjugates were tested in vivo to assess the carrier ability of this antibody. Immunohistochemical staining for either component of an OX-26-methotrexate conjugate revealed patterns of cerebrovascular labeling identical to those observed with the unaltered antibody. Accumulation of radiolabeled methotrexate in the brain parenchyma is greatly enhanced when the drug is conjugated to OX-26.
Tannins in pasture legumes. 2. The annual and perennial Medicago species (1981)

A total of 557 accessions representing 35 species of annual and perennial medics were tested for the presence of tannins in their leaves and mature seed coats. None of the lines tested produced tannins in their leaves, while all produced tannins in their seed coats. The implications of these findings are discussed in relation to the development of bloat-resistant lucerne varieties by plant breeding.
Formation of nanopores in a SiN∕SiO2 membrane with an electron beam (2005)

An electron beam can drill nanopores in SiO2 or silicon nitride membranes and shrink a pore to a smaller diameter. Such nanopores are promising for single molecule detection. The pore formation in a 40nm thick silicon nitride∕SiO2 bilayer using an electron beam with a diameter of 8nm (full width of half height) was investigated by electron energy loss spectroscopy with silicon nitride facing toward and away from the source. The O loss shows almost linear—independent of which layer faces the source, while N loss is quite complicated. After the formation of a pore, the membrane presents a wedge shape over a 70nm radius around the nanopore.
Monoclonal antibodies to human platelet glycoprotein IIb beta that initiate distinct platelet responses (1985)

Hybridomas secreting monoclonal antibodies (MoAbs) to human platelet membrane glycoprotein IIb (GPIIb) were prepared by fusing cells of a mouse myeloma line to spleen cells from a BALB/c mouse immunized with purified GPIIb. Six of the hybridomas secreted MoAbs that recognized epitopes on the 23,000-dalton, disulfide-linked subunit of GPIIb, GPIIb beta. All six of these MoAbs agglutinated platelets in the absence of calcium. The agglutination titers of three of the MoAbs, however, were enhanced between 2 and 6 log2 dilutions when titrated in the presence of mmol/L of calcium. The enhancement in titer was the result of MoAb-induced platelet activation followed by platelet aggregation, a reaction that could also be initiated by the monovalent Fab fragments prepared from one of the MoAbs. The MoAbs did not significantly agglutinate platelets from patients with Glanzmann's thrombasthenia, confirming biochemical evidence that there is a paucity of GPIIb beta in the membranes of these cells. Our results show that MoAbs to epitopes on GPIIb beta initiate distinct platelet responses; therefore, they should be useful for studying the ways in which regions of surface glycoproteins are involved in platelet-platelet interactions. In addition, these reagents may prove of value in diagnosing and typing patients with Glanzmann's thrombasthenia.
Tracking cardiac electrical instability by computing interlead heterogeneity of T-wave morphology (2003)

Oscillations in T-wave morphology, particularly T-wave alternans (TWA), have been fundamentally linked to increased susceptibility to ventricular fibrillation (VF). We investigated whether the escalation in complexity of T-wave oscillations before VF is attributable to increased spatial heterogeneity of repolarization. Peak interlead T-wave heterogeneity (TWH) was measured by second central moment analysis of T-wave morphology in epicardial electrograms in dogs during left anterior descending coronary artery occlusion. TWH differentiated cases in which myocardial ischemia provoked VF from those without VF (563 +/- 56 vs. 139 +/- 36 microV, P < 0.01). In the former group, progressive, significant increases in TWH above preocclusion baseline (70 +/- 8 microV) began at 2.25 min after the start of occlusion and were associated successively with TWA (at 155 +/- 19 microV), T-wave multupling (at 386 +/- 100 microV), complex oscillatory T-wave forms (at 560 +/- 76 microV), discordant TWA (at 572 +/- 98 microV), and VF at 4.36 +/- 0.14 min. TWH in precordial ECGs in 12 pigs during angioplasty-balloon-induced myocardial ischemia also discriminated animals that experienced VF (from 90 +/- 14 at baseline to 382 +/- 39 microV, P < 0.05) from those without VF (from 96 +/- 17 at baseline to 199 +/- 61 microV, NS). Ischemia-induced changes in ST segment and T-wave amplitude did not predict VF. Heightened spatial heterogeneity of repolarization, as assessed by second central moment analysis of TWH, underlies TWA and increased risk for ischemia-induced VF. Monitoring spatial TWH from precordial leads could prove useful in stratifying risk for life-threatening arrhythmias.
An RNA ligase-mediated method for the efficient creation of large, synthetic RNAs (2006)

RNA ligation has been a powerful tool for incorporation of cross-linkers and nonnatural nucleotides into internal positions of RNA molecules. The most widely used method for template-directed RNA ligation uses DNA ligase and a DNA splint. While this method has been used successfully for many years, it suffers from a number of drawbacks, principally, slow and inefficient product formation and slow product release, resulting in a requirement for large quantities of enzyme. We describe an alternative technique catalyzed by T4 RNA ligase instead of DNA ligase. Using a splint design that allows the ligation junction to mimic the natural substrate of RNA ligase, we demonstrate several ligation reactions that appear to go nearly to completion. Furthermore, the reactions generally go to completion within 30 min. We present data evaluating the relative importance of various parameters in this reaction. Finally, we show the utility of this method by generating a 128-nucleotide pre-mRNA from three synthetic oligoribonucleotides. The ability to ligate synthetic or in vitro transcribed RNA with high efficiency has the potential to open up areas of RNA biology to new functional and biophysical investigation. In particular, we anticipate that site-specific incorporation of fluorescent dyes into large RNA molecules will yield a wealth of new information on RNA structure and function.
PSGR, a novel prostate-specific gene with homology to a G protein-coupled receptor, is overexpressed in prostate cancer. (2000)

PSGR, a new prostate tissue-specific gene with homology to the G protein-coupled odorant receptor gene family, has been identified. Here we report the characteristics of the predicted protein sequence of PSGR and its prostate tissue specificity and expression profile in human prostate cancer and matched normal tissues. Using multiple tissue Northern blots from over 50 different tissues, PSGR expression was restricted to human prostate tissues. Paired normal and tumor specimens from 52 primary prostate cancers, obtained by laser capture microdissection or manual microdissection, were analyzed for PSGR expression by semiquantitative and real-time PCR assays. The differential expression of PSGR between normal and tumor tissues was highly significant (P < 0.001), and 32 of 52 (62%) matched prostate specimens exhibited tumor-associated overexpression of PSGR. Of note, there was very little or no expression of PSGR in many normal specimens in comparison with the generally high expression of PSGR seen in matched tumor specimens. In situ hybridization assays showed restricted PSGR expression in the epithelial cells of the normal and tumor tissue sections. Restricted expression of PSGR in prostatic epithelial cells, overexpression of the PSGR in a significant percentage of prostate cancers, and the predicted protein sequence of PSGR with seven transmembrane domains provide a foundation for future studies evaluating the potential of PSGR as a prostate cancer gene expression marker and the utility of PSGR protein as a novel target for developing immunotherapeutic strategies for prostate cancer.
Providing Internet Access: What we learn from the INDEX Trial∗ (1999)

The Internet Demand Experiment or INDEX is a market and technology trial. Its objective is to determine how much users value different qualities of service for Interent access. Findings from the trial imply that today&amp;apos;s system of flat-rate pricing by ISPs is very inefficient. Flat-rate pricing wastes resources, requires light users to subsidize heavy users, and hinders deployment of broadband access. INDEX is a prototype of an alternative ISP model that offers differentiated-quality service on demand, with prices that reflect resource cost. In this alternative ISP consumers pay less, suppliers increase profits, and the deployment of broadband access is facilitated.
WSB1 promotes tumor metastasis by inducing pVHL degradation (2015)

The von Hippel-Lindau tumor suppressor pVHL is an E3 ligase that targets hypoxia-inducible factors (HIFs). Mutation of VHL results in HIF up-regulation and contributes to processes related to tumor progression such as invasion, metastasis, and angiogenesis. However, very little is known with regard to post-transcriptional regulation of pVHL. Here we show that WD repeat and SOCS box-containing protein 1 (WSB1) is a negative regulator of pVHL through WSB1's E3 ligase activity. Mechanistically, WSB1 promotes pVHL ubiquitination and proteasomal degradation, thereby stabilizing HIF under both normoxic and hypoxic conditions. As a consequence, WSB1 up-regulates the expression of HIF-1α's target genes and promotes cancer invasion and metastasis through its effect on pVHL. Consistent with this, WSB1 protein level negatively correlates with pVHL level and metastasis-free survival in clinical samples. This work reveals a new mechanism of pVHL's regulation by which cancer acquires invasiveness and metastatic tendency.