gebhart/patrepeval huggingface dataset:
Large and small proteoglycans of osteoarthritic and rheumatoid articular cartilage (1995)

There is extensive degradation of both large and small PGs in diseased cartilages, but a repair process does exist, especially in OA cartilages. Chondrocytes of diseased cartilages are able to synthesize fetal-type aggrecans. Small PGs are glycosylated differently in diseased cartilages than in normal ones.
Investigation on the stabilization of the median resistance state for phase change memory cell with doublelayer chalcogenide films (2007)

The triple-level data storage capability of the phase change memory with doublelayer chalcogenide films (Sb2Te3 and Ge2Sb2Te5) was investigated. Differences in physical properties of these two chalcogenide materials contribute to the appearance of a median resistance state. However, the stable median resistance state can only be achieved by selecting appropriate programming parameters. Voltage pulses with moderate magnitude and pulse width for both set and reset operations are favorable for forming a stable median resistance stage. Interdiffusion between Sb2Te3 and Ge2Sb2Te5 layers degrades the stabilization of the median resistance state.
Solution accelerators for large-scale three-dimensional electromagnetic inverse problems (2004)

We provide a framework for preconditioning nonlinear 3D electromagnetic inverse scattering problems using nonlinear conjugate gradient (NLCG) and limited memory (LM) quasi-Newton methods. Key to our approach is the use of an approximate adjoint method that allows for an economical approximation of the Hessian that is updated at each inversion iteration. Using this approximate Hessian as a preconditoner, we show that the preconditioned NLCG iteration converges significantly faster than the non-preconditioned iteration, as well as converging to a data misfit level below that observed for the non-preconditioned method. Similar conclusions are also observed for the LM iteration; preconditioned with the approximate Hessian, the LM iteration converges faster than the non-preconditioned version. At this time, however, we see little difference between the convergence performance of the preconditioned LM scheme and the preconditioned NLCG scheme. A possible reason for this outcome is the behavior of the line search within the LM iteration. It was anticipated that, near convergence, a step size of one would be approached, but what was observed, instead, were step lengths that were nowhere near one. We provide some insights into the reasons for this behavior and suggest further research that may improve the performance of the LM methods.
Elucidation of anthracyclinone biosynthesis by stepwise cloning of genes for anthracyclines from three different Streptomyces spp. The GenBank accession number for acmA reported in this paper is AF043550. (2000)

The anthracycline skeleton is biosynthesized by aromatic (type II) polyketide synthases. Furthermore, three post-polyketide steps are needed to form the basic aglycone of anthracyclines. Auramycinone was produced in Streptomyces lividans by introducing nine structural genes from three different anthracycline-producing Streptomyces species. The genes used to construct the auramycinone biosynthesis cluster were derived from nogalamycin-, daunomycin- and aclacinomycin-producing Streptomyces strains. The biosynthetic stages were divided into polyketide and post-polyketide steps on the assumption that the first stable intermediate would be nogalonic acid, named analogously to aklanonic acid, the precursor of several anthracyclines. Single genes were cloned in the expression construct in the order determined by the proposed biosynthetic pathway. This facilitated investigation of the products formed in the heterologous host after addition of each separate gene to the construct. The results thus elucidate the biosynthesis steps, products and the genes responsible for the reactions needed to build up an anthracyclinone.
THE ANTI-INFLAMMATORY EFFECT OF DIAZOXIDE IN CORONARY ARTERY BYPASS GRAFTING (2004)

Many therapeutic strategies have been designed to suppress the inflammatory response in patients undergoing coronary artery bypass grafting (CABG). Pharmacological preconditioning with diazoxide is an alternative in effective cardioprotective strategies, but more evidence is required to show its effect on the inflammatory response. Forty patients with stable angina who were scheduled for isolated elective CABG operations were randomized into control and diazoxide (DZX) groups. In the DZX group, 1.5 mg/kg diazoxide was infused intravenously in 5 min followed by a 5-min washout before commencing the cardiopulmonary bypass. In the control group, placebo infusion was given similarly. Blood samples for cytokine measurement were collected from the radial artery and coronary sinus perioperatively, and hemodynamic data were recorded. Thirty-six patients fulfilled the data collection. Cardiac index (CI) increased in both groups over time as compared with baseline. In the DZX group, the increase of CI was greater than that in the control group (P = 0.002). Systemic and coronary sinus plasma levels of IL-6, IL-8, and IL-10 increased significantly after reperfusion in both groups as compared with baseline (P < 0.05). IL-6 and IL-8 both reached the peak value at 6 h after cardiopulmonary bypass. IL-10 reached peak level at 20 min after reperfusion in both groups. There was significantly higher IL-10 in DZX groups (P = 0.015). The ratios of IL-6 to IL-10 and IL-8 to IL-10 were significantly lower in DZX groups than in controls (P = 0.025 and P = 0.041 for each, respectively). Pharmacological preconditioning with DZX in CABG patients shifts the circulating inflammatory cytokine balance toward the anti-inflammatory direction.
Manipulation of Phytoene Levels in Tomato Fruit: Effects on Isoprenoids, Plastids, and Intermediary Metabolism (2007)

In tomato (Solanum lycopersicum), phytoene synthase-1 (PSY-1) is the key biosynthetic enzyme responsible for the synthesis of fruit carotenoids. To further our understanding of carotenoid formation in tomato fruit, we characterized the effect of constitutive expression of an additional tomato Psy-1 gene product. A quantitative data set defining levels of carotenoid/isoprenoid gene expression, enzyme activities, and metabolites was generated from fruit that showed the greatest perturbation in carotenoid content. Transcriptional upregulation, resulting in increased enzyme activities and metabolites, occurred only in the case of Psy-1, Psy-2, and lycopene cyclase B. For reactions involving 1-deoxy-d-xylulose5-phosphate synthase, geranylgeranyl diphosphate synthase, phytoene desaturase, zeta-carotene desaturase, carotene isomerase, and lycopene beta-cyclase, there were no correlations between gene expression, enzyme activities, and metabolites. Perturbations in carotenoid composition were associated with changes in plastid type and with chromoplast-like structures arising prematurely during fruit development. The levels of >120 known metabolites were determined. Comparison with the wild type illustrated that key metabolites (sucrose, glucose/fructose, and Glu) and sectors of intermediary metabolism (e.g., tricarboxylic [corrected] acid cycle intermediates and fatty acids) in the Psy-1 transgenic mature green fruit resembled changes in metabolism associated with fruit ripening. General fruit developmental and ripening properties, such as ethylene production and fruit firmness, were unaffected. Therefore, it appears that the changes to pigmentation, plastid type, and metabolism associated with Psy-1 overexpression are not connected with the ripening process.
Export of protein from the endoplasmic reticulum is regulated by a diacylglycerol/phorbol ester binding protein. (1994)

The export of vesicular stomatitis virus glycoprotein (VSV-G) from the endoplasmic reticulum (ER) involves sorting and concentration, and has been proposed to require the function of heterotrimeric G proteins. To begin to identify the basic elements of a potential signaling pathway involved in vesicle assembly, we have examined whether protein kinase C (PKC) is required for ER to Golgi transport. Calphostin C, a specific inhibitor of the highly conserved cysteine-rich C6H2 motif present in the regulatory domain of PKC was found to be a potent inhibitor of export of VSV-G and vesicle budding from the ER in vivo and in vitro (IC50 approximately 60 nM). In contrast, the diacylglycerol analog phorbol 12-myristate 13-acetate, which activates PKC, enhanced the migration of VSV-G from the ER to pre-Golgi intermediates. Neither reagent had detectable effects on the oligomerization of VSV-G prior to export nor perturbed transport of protein between compartments of the Golgi stack. In contrast to the striking effects of calphostin C, reagents that inhibit the function of the catalytic domain of PKC (including the general kinase inhibitor staurosporine, as well as the more specific inhibitors H-7, H-8, pseudosubstrate inhibitor, or chelerythrine) did not inhibit export from the ER. Export was also insensitive to down-regulation of various PKC isoforms. These results suggest that a novel protein containing the conserved C6H2 motif may serve as a potential link in a signaling pathway regulating vesicle budding from the ER.
Characterization of liquid chromatographic chiral separation on chiral crown ether stationary phases (2003)

Abstract Crown ether‐based chiral stationary phases (CSPs) have been known to be quite useful for the liquid chromatographic resolution of racemic compounds containing a primary amino group. Chiral separations on crown ether‐based CSPs are characterized by several factors. In this paper, the structural characteristics of five selected crown ether‐based CSPs, analyte characteristics and several factors characterizing chiral separations such as the mobile phase modifiers and the column temperature were reviewed. Among the various factors, the column temperature and the inorganic modifier in the mobile phase influence the chiral separations equally for the five selected crown ether‐based CSPs. In contrast, the effect of the organic and acidic modifier in the aqueous mobile phase on the chiral separations depends on the structural characteristics of CSPs.
Optimization strategies for fleet management based on wireless terminals localization in smart cities scenarios (2016)

The increasing availability and diffusion of digital wireless communication systems and localization technologies is offering new opportunities for the introduction of location-based decision support systems for the fleet and mission control management in smart cities. In this paper, the use of multi-objective evolutionary metaheuristic for dispatching fleet assets is addressed. The applications are particularly interesting for goods transportation and emergency management agencies, the proposed approach has been implemented in a full-scale decision support system prototype under experimental validation at the headquarter of the Centrale Unica Emergenza (CUE) of Trento, Italy.
Inter-relatedness of some isoenzymes of cytochrome <i>P</i>-450 from rat, rabbit and human, determined with monoclonal antibodies (1986)

Monoclonal antibodies have been raised to rat liver cytochromes P-450 b and c, and rabbit liver cytochrome P-450 form 4. A total of six antibodies have been studied. Each antibody reacted strongly both with its homologous antigen and with microsomal fractions selectively enriched with that antigen by treatment of animals with inducing compounds. However, several of the antibodies showed cross-reactivity, either within or between species. A combination of enzyme-linked immunosorbent assay, immunoadsorption, Western blotting and competitive radioimmunoassay revealed that each of the antibodies reacted with a different epitope. Proteolytic digestion of antigen followed by Western blotting of the peptide fragments enabled antibodies, otherwise identical in their reactivity, to be distinguished. It is concluded that complex structural relationships exist amongst the different isoenzymes of cytochrome P-450 and that epitope mapping will help in characterizing both animal and human cytochromes P-450.
Electrospinning and Stabilization of Fully Hydrolyzed Poly(Vinyl Alcohol) Fibers (2003)

Fully (99+ %) hydrolyzed poly(vinyl alcohol) (PVA) was electrospun from water using Triton X-100 surfactant to lower the surface tension. The diameter of the electrospun PVA fibers ranged from 100 to 700 nm. Treatment of the PVA fiber mats with methanol for 8 h stabilized the fibers against disintegration in contact with water. In addition, the mats showed increased mechanical strength due to increased crystallinity following post-spinning treatment with methanol. We suggest that methanol treatment serves to increase the degree of crystallinity, and hence the number of physical cross-links in the electrospun PVA fibers. This may occur by removal of residual water within the fibers by the alcohol, allowing PVA−water hydrogen bonding to be replaced by intermolecular polymer hydrogen bonding resulting in additional crystallization. Potential applications of electrospun PVA include filters, precursors to graphitic fibers, and biomedical materials.
A Noninvasive Method of Predicting Pulmonary-Capillary Wedge Pressure (1994)

Abstract Background. The noninvasive prediction of pulmonary-capillary wedge pressure (PCWP) is important for the recognition and treatment of a variety of cardiovascular disorders. The response of the arterial pressure to the Valsalva maneuver has been shown to correlate with the PCWP. We therefore devised a noninvasive method to measure this pressure response at the bedside and correlated these measurements with the PCWP measured directly with a pulmonary-artery catheter. Methods. Simultaneous, blinded, noninvasive measurements of the ratio of the final amplitude to the initial amplitude of the pulse wave form during the stress phase of the Valsalva maneuver (pulse-amplitude ratio) and direct measurements of the PCWP were obtained in 20 clinically stable patients and in 14 clinically unstable patients who were receiving vasoactive agents, 12 of whom also had endotracheal tubes in place. Results. Using linear regression analysis, we found that the pulse-amplitude ratio strongly correlated with the measur...
Structure‐Based Design of Selective Noncovalent CDK12 Inhibitors (2017)

Cyclin-dependent kinase (CDK) 12 knockdown via siRNA decreases the transcription of DNA-damage-response genes and sensitizes BRCA wild-type cells to poly(ADP-ribose) polymerase (PARP) inhibition. To recapitulate this effect with a small molecule, we sought a potent, selective CDK12 inhibitor. Crystal structures and modeling informed hybridization between dinaciclib and SR-3029, resulting in lead compound 5 [(S)-2-(1-(6-(((6,7-difluoro-1H-benzo[d]imidazol-2-yl)methyl)amino)-9-ethyl-9H-purin-2-yl)piperidin-2-yl)ethan-1-ol]. Further structure-guided optimization delivered a series of selective CDK12 inhibitors, including compound 7 [(S)-2-(1-(6-(((6,7-difluoro-1H-benzo[d]imidazol-2-yl)methyl)amino)-9-isopropyl-9H-purin-2-yl)piperidin-2-yl)ethan-1-ol]. Profiling of this compound across CDK9, 7, 2, and 1 at high ATP concentration, single-point kinase panel screening against 352 targets at 0.1 μm, and proteomics via kinase affinity matrix technology demonstrated the selectivity. This series of compounds inhibits phosphorylation of Ser2 on the C-terminal repeat domain of RNA polymerase II, consistent with CDK12 inhibition. These selective compounds were also acutely toxic to OV90 as well as THP1 cells.
A highly sensitive strobed comparator (1981)

A sensitive strobed comparator has been designed and extensively characterized. It is realized in a standard NMOS silicon-gate process, occupying a die area of 0.05 mm/SUP 2/ (81/mil/SUP 2/). Power consumption is 1 mW from a single 10 V supply. Resolution is 0.5 mV when a strobe signal rise from 0 V to 5 V in 20 ns. Offset voltage had a mean value of -0.5 mV with a standard deviation of 5 mV. This comparator should be useful for high-resolution analog-digital converters in NMOS technology.
Reduced reflections from multimode interference couplers (2006)

A 3 dB multimode interference (MMI) coupler optimised for low reflections is presented. The MMI was designed, fabricated and characterised. For comparison, MMIs with non-optimised layout have been included on the same sample. The measurement results show a reduction in reflectivities of more than 10 dB.
Rafts and sphingolipid biosynthesis in the kinetoplastid parasitic protozoa (2004)

Summary relatively large rafts are a feature of activated mammalian cells. These studies allow us to consider the functional role of lipid rafts in kinetoplastid parasites, which are particularly rich in lipid-anchored surface molecules. Morphological, biochemical and genetic studies indicate that lipid rafts (and sphingolipid biosythesis) are important in the differentiation of extracellular Leishmania to mammalian-infective metacyclic promastigotes, perhaps orchestrating the clearly observable reorganization of the plasma membrane during this process that leads to an activated metacyclic primed for invasion. However, the first step in the sphingolipid biosynthetic pathway (mediated by serine palmitoyltransferase), and at least regulated, de novo sphingoid base and ceramide synthesis, are not essential for the pathogenesis of intramacrophage Leishmania amastigotes.
Robust Unsupervised Multi-View Feature Learning With Dynamic Graph (2019)

Graph-based multi-view feature learning methods learn a low-dimensional embedding of the data by modeling the affinity correlations with a graph to reduce the dimension. However, the learned low-dimensional representation relies on a fixed graph that is potentially inaccurate and unreliable. Besides, the graph construction and the projection matrix leaning are separated into two independent processes. To tackle the problems, we propose a robust unsupervised multi-view feature learning method with a dynamic graph. The dynamic graph structure is constructed adaptively and the robust projection matrix is learned simultaneously. Specifically, we adaptively learn a dynamic graph which captures the intrinsic multiple view-specific relations of samples. Robust projection matrix learning suppresses the adverse noises and preserves the intrinsic graph structure. Moreover, the assigned weights are learned automatically for each view without any extra parameter. We finally develop an efficient alternative optimization algorithm to solve the objective formulation. The extensive experiments conducted on several multi-view datasets demonstrate the effectiveness of our proposed method.
Evaluation of breast lesions with contrast-enhanced ultrasound using the microvascular imaging technique: Initial observations (2008)

The objective of this study was to evaluate the usefulness of contrast-enhanced ultrasound using the microvascular imaging technique in the diagnosis of breast lesions. In 104 patients with 104 breast lesions scheduled for surgery, conventional and contrast-enhanced ultrasound using the microvascular imaging technique were performed after administration of SonoVue. The enhancement patterns of breast lesions were classified as no enhancement, peripheral enhancement, homogeneous enhancement, regional enhancement, or heterogeneous enhancement based on the morphologic features of enhancement. The diagnostic value of contrast-enhanced ultrasound using the microvascular imaging technique was analyzed with the observers blinded to the clinical data and pathology (which served as the gold standard). None of the enhancement patterns was suggestive of benignity, with a sensitivity of 18.3%, specificity of 97.7%, positive predictive value (PPV) of 91.7%, negative predictive value (NPV) of 46.2%, and accuracy of 51.5%. The peripheral enhancement pattern was suggestive of malignancy, with a sensitivity of 39.5%, specificity of 98.3%, PPV of 94.4%, NPV of 69.4%, and accuracy of 73.8%. Homogeneous, regional, and heterogeneous enhancement patterns did not show meaningful diagnostic information. Contrast-enhanced ultrasound using the microvascular imaging technique provides diagnostic information on breast lesions.
Advances in studies on antitumor activities of compoundsin Salvia miltiorrhiza (2010)

Salvia miltiorrhiza contains a variety of anti-tumor active ingredient, such as the water-soluble components (salvianolic acid A, salvianolic acid B, salvinal) and liposoluble constituents (tanshinone I, tanshinone IIA, dihydrotanshinone I, miltirone, cryptotanshinone, ailantholide, neo-tanshinlactone, and nitrogen-containing compounds). These anti-tumor active components play important roles in the different stages of tumor evolution, progression and metastasis. The discovery of new anti-tumor active ingredients must benefits the application of Salvia miltiorrhiza for clinical tumor treatment.
Agouti-Related Protein Is Posttranslationally Cleaved by Proprotein Convertase 1 to Generate Agouti-Related Protein (AGRP)83–132: Interaction between AGRP83–132 and Melanocortin Receptors Cannot Be Influenced by Syndecan-3 (2005)

Agouti-related protein (AGRP) plays a key role in energy homeostasis. The carboxyl-terminal domain of AGRP acts as an endogenous antagonist of the melanocortin-4 receptor (MC4-R). It has been suggested that the amino-terminal domain of AGRP binds to syndecan-3, thereby modulating the effects of carboxyl-terminal AGRP at the MC4-R. This model assumes that AGRP is secreted as a full-length peptide. In this study we found that AGRP is processed intracellularly after Arg(79)-Glu(80)-Pro(81)-Arg(82). The processing site suggests cleavage by proprotein convertases (PCs). RNA interference and overexpression experiments showed that PC1/3 is primarily responsible for cleavage in vitro, although both PC2 and PC5/6A can also process AGRP. Dual in situ hybridization demonstrated that PC1/3 is expressed in AGRP neurons in the rat hypothalamus. Moreover, hypothalamic extracts from PC1-null mice contained 3.3-fold more unprocessed full-length AGRP, compared with wild-type mice, based on combined HPLC and RIA analysis, demonstrating that PC1/3 plays a role in AGRP cleavage in vivo. We also found that AGRP(83-132) is more potent an antagonist than full-length AGRP, based on cAMP reporter assays, suggesting that posttranslational cleavage is required to potentiate the effect of AGRP at the MC4-R. Because AGRP is cleaved into distinct amino-terminal and carboxyl-terminal peptides, we tested whether amino-terminal peptides modulate food intake. However, intracerebroventricular injection of rat AGRP(25-47) and AGRP(50-80) had no effect on body weight, food intake, or core body temperature. Because AGRP is cleaved before secretion, syndecan-3 must influence food intake independently of the MC4-R.