gebhart/patrepeval huggingface dataset:
Cellular Mechanisms of Altered Contractility in the Hypertrophied Heart (1999)

To investigate the cellular mechanisms for altered Ca2+ homeostasis and contractility in cardiac hypertrophy, we measured whole-cell L-type Ca2+ currents (ICa,L), whole-cell Ca2+ transients ([Ca2+]i), and Ca2+ sparks in ventricular cells from 6-month-old spontaneously hypertensive rats (SHRs) and from age- and sex-matched Wistar-Kyoto and Sprague-Dawley control rats. By echocardiography, SHR hearts had cardiac hypertrophy and enhanced contractility (increased fractional shortening) and no signs of heart failure. SHR cells had a voltage-dependent increase in peak [Ca2+]i amplitude (at 0 mV, 1330+/-62 nmol/L [SHRs] versus 836+/-48 nmol/L [controls], P<0.05) that was not associated with changes in ICa,L density or kinetics, resting [Ca2+]i, or Ca2+ content of the sarcoplasmic reticulum (SR). SHR cells had increased time of relaxation. Ca2+ sparks from SHR cells had larger average amplitudes (173+/-192 nmol/L [SHRs] versus 109+/-64 nmol/L [control]; P<0.05), which was due to redistribution of Ca2+ sparks to a larger amplitude population. This change in Ca2+ spark amplitude distribution was not associated with any change in the density of ryanodine receptors, calsequestrin, junctin, triadin 1, Ca2+-ATPase, or phospholamban. Therefore, SHRs with cardiac hypertrophy have increased contractility, [Ca2+]i amplitude, time to relaxation, and average Ca2+ spark amplitude ("big sparks"). Importantly, big sparks occurred without alteration in the trigger for SR Ca2+ release (ICa,L), SR Ca2+ content, or the expression of several SR Ca2+-cycling proteins. Thus, cardiac hypertrophy in SHRs is linked with an alteration in the coupling of Ca2+ entry through L-type Ca2+ channels and the release of Ca2+ from the SR, leading to big sparks and enhanced contractility. Alterations in the microdomain between L-type Ca2+ channels and SR Ca2+ release channels may underlie the changes in Ca2+ homeostasis observed in cardiac hypertrophy. Modulation of SR Ca2+ release may provide a new therapeutic strategy for cardiac hypertrophy and for its progression to heart failure and sudden death.
A MEANDERED LOOP ANTENNA FOR LTE/WWAN OPERATIONS IN A SMART PHONE (2010)

Abstract—This paper presents a multiband meandered loop antenna for smart phone applications. The proposed antenna which features a meandered folded-loop generates two resonance modes in the LTE/GSM bands. The current distributions of the excited resonance modes are analyzed to investigate the mode characteristic. By using a capacitively coupled feed on the backplane, the impedance bandwidth is broadened to cover LTE/WWAN bands. The simulation performed in this research used a high frequency structure simulator (HFSS) to optimally design the antenna, and a practical structure was constructed for the test. Details of the various antenna parameters are presented and discussed in this paper.
Generation and Carbonyl Addition of Dibromofluoromethyllithium (1995)

When CFBr3 was treated with n-BuLi at -130 °C, thermally labile LiCFBr2 was generated which reacted smoothly with a coexisting electrophile RR’CO to give an adduct RR’C(OH)CFBr2 in good yield.
Synthesis of Novel d-2‘-Deoxy-2‘- C-difluoromethylene-4‘-thiocytidine as a Potential Antitumor Agent (2002)

[reaction: see text] 2'-Deoxy-2'-C-difluoromethylene-4'-thiocytidine (4) as a potential antitumor agent was synthesized starting from L-xylose via 2-deoxy-2-C-difluoromethylene-4-thiosugar as a key intermediate. An elimination product, 8, was always formed as the major product during removal of the protecting groups under acidic or basic conditions. However, utilizing neutral reaction conditions to remove the protecting groups afforded the desired product 4 exclusively.
Evolution of the K65R, K103N and M184V/I reverse transcriptase mutations in HIV-1-infected patients experiencing virological failure between 2005 and 2010 (2013)

The global prevalence of resistance-associated mutations to tenofovir, lamivudine/emtricitabine and efavirenz decreased over time between 2005 and 2010. Despite a stable rate of efavirenz and protease inhibitor use, this phenomenon can be explained by an increased use of single-tablet regimens, which simplify drug intake and maximize adherence.
Design, Synthesis, and SAR of 2‐Dialkylamino‐4‐arylpyrimidines as Potent and Selective Corticotropin‐Releasing Factor1 (CRF1) Receptor Antagonists. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Overexpression of Insulin-Like Growth Factor-1 Attenuates the Myocyte Renin-Angiotensin System in Transgenic Mice (1999)

Constitutive overexpression of insulin-like growth factor-1 (IGF-1) in myocytes protects them from apoptosis and interferes with myocyte hypertrophy in the normal and pathological heart. Conversely, angiotensin II (Ang II) triggers cell death and promotes myocyte hypertrophy. Moreover, activation of p53 upregulates the cellular renin-angiotensin system (RAS). Therefore, IGF-1 overexpression in FVB.Igf+/- mice may downregulate the local RAS through the attenuation of p53 and p53-inducible genes. On this basis, p53 DNA binding activity to angiotensinogen (Aogen), bax, and the AT1 receptor was determined in left ventricular myocytes from FVB.Igf-/- and FVB.Igf+/- mice. The quantity of Bax, Bcl-2, Aogen, and AT1 receptor in these cells was evaluated. The presence of Mdm2-p53 complexes was also established. Finally, Ang II levels in myocytes were measured. Upregulation of IGF-1 in myocytes was associated with a protein-to-protein interaction between Mdm2 and p53, which attenuated p53 transcriptional activity for bax, Aogen, and AT1 receptor. Similarly, the amount of Bax, Aogen, and AT1 receptor proteins in these cells decreased. In contrast, the expression of Bcl-2 remained constant. The downregulation of Aogen in myocytes from FVB.Igf+/- mice was characterized by a reduction in Ang II. In conclusion, IGF-1 negatively influences the myocyte RAS through the upregulation of Mdm2 and its binding to p53. This may represent the molecular mechanism responsible for the effects of IGF-1 on cell viability and myocyte hypertrophy in the nonpathological and pathological heart in vivo.
A reconfigurable architecture for network intrusion detection using principal component analysis (2006)

In this work, we develop an architecture for principal component analysis (PCA) to be used as an outlier detection method for high-speed network intrusion detection systems (NIDS). PCA is a common statistical method used in multivariate optimization problems in order to reduce the dimensionality of data while retaining a large fraction of the data characteristic. First, using KDD Cup 1999 data sets composed of all normal connections, PCA is used to project the training set onto eigenspace vectors representing the mean of the data. These eigenspace vectors are then used to predict malicious connections in a workload containing normal and attack behavior. Our simulations show that the proposed architecture correctly classifies attacks with detection rates exceeding 99% and false alarms rates below 2%. For next generation NIDS, anomaly detection methods must satisfy the demands of Gigabit Ethernet. FPGAs are an attractive medium to handle both high throughput and adaptability to the dynamic nature of intrusion detection. Using hardware parallelism and extensive pipelining, our architecture is implemented on FPGAs to achieve Gigabit link speeds. Particularly, our simulation results show that for a realistic workload our architecture clocks at 92.82 MHz on a Virtex-II Pro FPGA and achieves a 23.76 Gbps throughout.
Local and Systemic Toxicity of Intraoral Submucosal Injections of Phentolamine Mesylate (OraVerse) (2009)

OraVerse, an injectable formulation of phentolamine mesylate (PM), was recently approved by the U.S. Food and Drug Administration (FDA) for reversal of anesthesia of the lip and tongue and associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor. Because PM had not been approved previously for submucosal administration, 2 Good Laboratory Practices (GLP) studies in dogs designed to investigate systemic toxicity and the local effects of single and repeated dosing of OraVerse on the inferior alveolar nerve and branches of the superior alveolar nerve and adjacent soft tissues after local administration were conducted. Systemic toxicity was measured by preinjection and postinjection clinical examinations, clinical chemistry, and gross and microscopic examinations of major organs after necropsy. No evidence of systemic toxicity was detected. Local nerve and adjacent tissue damage was assessed by conventional histopathology. Nerve degeneration was evident in 1 animal. Mild perineural inflammation adjacent to the inferior alveolar nerve and inflammatory exudates were observed in submucosal tissues in several animals. No changes were observed in the nerves at injection sites of dogs from any dose group that were considered directly related to the test articles. These data reveal that single and repeated intraoral administrations of OraVerse are well tolerated in beagle dogs.
Carboxypeptidase yscS: gene structure and function of the vacuolar enzyme (1991)

The gene encoding carboxypeptidase yscS in Saccharomyces cerevisiae, CPS1, was cloned by complementation of the cps1-3 mutation. The cloned CPS1 gene, which again enabled a leucine auxotrophic cps1-3 mutant to grow on the modified dipeptide Cbz-Gly-Leu (Cbz, benzyloxycarbonyl) as sole leucine source, was sequenced and found to consist of an open reading frame of 1728 bp encoding a protein of 576 amino acids. The putative protein contains a hydrophobic stretch of 20 amino acids and a putative signal sequence cleavage site. Five putative N-glycosylation sites are also in the protein sequence. This data is consistent with the previous finding of carboxypeptidase yscS being a vacuolar peptidase. Chromosomal disruption of the CPS1 gene completely abolishes carboxypeptidase yscS activity. This protein is yet another member of the peptidases in S. cerevisiae involved in nitrogen metabolism.
DYNAMIC CHANGES IN THE ULTRASTRUCTURE OF THE ACINAR CELL OF THE RAT PAROTID GLAND DURING THE SECRETORY CYCLE (1969)

Synchronization of the secretory cycle in vivo was obtained by injecting isoprenaline as an inducer of secretion. A quantitative correlation between enzyme release, its subsequent reaccumulation, and the sequence of ultrastructural changes was found. At the ultrastructural level secretion was paralleled by depletion of zymogen granules through fusion of the granule membrane with the lumen membrane and discharge of the content. Each zymogen granule membrane, once connected with the lumen, acted as a lumen membrane. Fusion was thus sequential and resulted in a dramatic enlargement of the lumen space. During the entire process the passage between the lumen and the intercellular space remained blocked by the tight junctions, as shown by their impenetrability to ferritin. Reduction of the lumen size following enzyme discharge seemed to be achieved by withdrawal of lumen membrane in the form of small smooth vesicles which appeared mostly in the apical part of the cell. At the same time, the cell retracted towards the lumen, the whole process being completed within 2 hr from onset of secretion. Disappearance of the smooth vesicle followed, concomitant with formation of many condensing vacuoles and appearance of mature zymogen granules. The fate of the zymogen granule membrane, including its fusion with the lumen membrane, resorption in the form of small smooth vesicles, and its eventual reutilization mediated by the Golgi system, is discussed.
Epidermal electronics: Skin sweat patch (2012)

An ultrathin, stretchable, and conformal sensor system for skin-mounted sweat measurement is characterized and demonstrated in this paper. As an epidermal device, the sweat sensor is mechanically designed for comfortable wear on the skin by employing interdigitated electrodes connected via stretchable serpentine-shaped conductors. Experimental results show that the sensor is sensitive to measuring frequency, sweat level and stretching deformation. It was found that 20kHz signals provide the most sensitive performance: electrical impedance changes 50% while sweat level increases from 20 to 80. In addition, sensor elongation from 15 up to 50% affected the measurement sensitivity of both electrical impedance and capacitance.
Tumor necrosis factor alpha-induced angiogenesis depends on in situ platelet-activating factor biosynthesis. (1994)

Tumor necrosis factor (TNF) alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Therefore, it was suggested that the angiogenic properties of this agent might be consequent to the production of secondary mediators. Since TNF-alpha stimulates the synthesis of platelet-activating factor (PAF) by monocytes and endothelial cells, we investigated the possible involvement of PAF in the angiogenic effect of TNF-alpha. Angiogenesis was studied in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model the angiogenesis induced by TNF-alpha was shown to be inhibited by WEB 2170, a specific PAF receptor antagonist. Moreover, in mice injected with TNF-alpha, PAF was detected within the Matrigel, 6 and 24 h after TNF-alpha injection. The synthesis of PAF within the Matrigel was concomitant with the early migration of endothelial cells and infiltration of monocytes. No infiltration of lymphocytes or polymorphonuclear leukocytes was observed. Synthetic PAF as well as PAF extracted and purified from mice challenged with TNF-alpha induced a rapid angiogenic response, inhibited by WEB 2170. These results suggest that the angiogenic effect of TNF-alpha is, at least in part, mediated by PAF synthesized from monocytes and/or endothelial cells infiltrating the Matrigel plug.
Metal‐Catalyzed Olefin Cyclopropanation with Ethyl Diazoacetate: Control of the Diastereoselectivity (2009)

Abstract The control of the cis / trans diastereoselectivity by catalyst design in the olefin cyclopropanation reaction with ethyl diazoacetate is reviewed. Catalysts based on ruthenium, copper, rhodium, iron, osmium and cobalt are discussed. The degree of stereocontrol achieved for styrene and related aryl‐containing olefins is higher than that for terminal alkenes with no aryl substituents.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)
Slalom chromatography: size-dependent separation of DNA molecules by a hydrodynamic phenomenon (1990)

Slalom chromatography, a size-dependent DNA fractionation method based on a new principle [Hirabayashi, J., & Kasai, K. (1989) Anal. Biochem. 178, 336-341], was systematically studied in detail. In this method, larger DNA fragments are eluted much later than smaller ones from columns packed with spherical microbeads. Elution of a series of DNA fragments was systematically examined by using columns packed with polymer-based packings of different diameter and different pore size for high-performance gel permeation chromatography. Packings of smaller diameter proved to be superior for resolving the smaller size range of DNA, while the reverse was the case for larger DNAs. Application of a faster flow rate led to larger retardation of every DNA fragment, while at the lowest flow rate applied (0.067 cm/min), all the fragments were eluted almost at the void volume. When the column temperature was lowered, retardation of DNA became larger. On the other hand, differences in the chemical nature and the pore size of packings, or in the hydrophobicity of the eluting solvent, had little effect on DNA retardation. Size-dependent fractionation of DNA was also achieved even on columns packed with nonporous packings having anionic groups (cation exchangers). In conclusion, these results confirmed the previous conclusion that slalom chromatography is not based on an adsorption or equilibrium phenomenon but should be attributed to a hydrodynamic phenomenon.
Phosphorothioates, Essential Components of Therapeutic Oligonucleotides (2014)

Phosphorothioates have found their usefulness in the general area of oligonucleotide therapeutic applications. Initially this modification was introduced into the antisense methodology because of the nuclease resistance of the phosphorothioate linkage in comparison with that of the phosphate linkage. However, as experimental data accumulated, it was detected that this chemical modification also facilitates cellular uptake and bioavailibity in vivo. Thus, today the majority of therapeutic oligonucleotides contain this modification. This review will discuss the historical development of this modification and present some of its chemical properties where they differ from those of the phosphate group. The antisense application will be discussed in the original context with cleavage of the target mRNA, but other target RNAs such as microRNAs and long noncoding RNAs will also be covered. It continues with applications where the target RNA should not be cleaved. A brief presentation of decoy oligonucleotides will be included, as well as some miscellaneous applications. Cellular uptake is a crucial step for oligonucleotides to reach their target and will be briefly reviewed. Lastly, a most surprising recent observation is the presence of phosphorothioate groups in bacterial DNA where functions still remain to be fully determined.
Pan-S replication patterns and chromosomal domains defined by genome-tiling arrays of ENCODE genomic areas (2007)

In eukaryotes, accurate control of replication time is required for the efficient completion of S phase and maintenance of genome stability. We present a high-resolution genome-tiling array-based profile of replication timing for approximately 1% of the human genome studied by The ENCODE Project Consortium. Twenty percent of the investigated segments replicate asynchronously (pan-S). These areas are rich in genes and CpG islands, features they share with early-replicating loci. Interphase FISH showed that pan-S replication is a consequence of interallelic variation in replication time and is not an artifact derived from a specific cell cycle synchronization method or from aneuploidy. The interallelic variation in replication time is likely due to interallelic variation in chromatin environment, because while the early- or late-replicating areas were exclusively enriched in activating or repressing histone modifications, respectively, the pan-S areas had both types of histone modification. The replication profile of the chromosomes identified contiguous chromosomal segments of hundreds of kilobases separated by smaller segments where the replication time underwent an acute transition. Close examination of one such segment demonstrated that the delay of replication time was accompanied by a decrease in level of gene expression and appearance of repressive chromatin marks, suggesting that the transition segments are boundary elements separating chromosomal domains with different chromatin environments.
Distribution of oncofetal fibronectin isoforms in normal, hyperplastic and neoplastic human breast tissues (1994)

Two different oncofetal fibronectins (FN) have been reported: one, generated by O-glycosylation in the splicing region IIICS that is recognized by monoclonal antibody (MAb) FDC-6, and another, recognized by MAb BC-I, generated by the alternative splicing of the FN pre-mRNA which includes an extra type-III repeat called ED-B. Using these and 2 other MAbs (IST-4 which recognizes all different FN isoforms and IST-6 which recognizes only the FN molecules that do not include the ED-B sequence) we have immunohistochemically studied 171 normal, hyperplastic and neoplastic breast-tissue specimens. Although all normal specimens reacted strongly with MAbs IST-4 and IST-6, they did not show the presence of oncofetal FNs as established by the use of BC-I and FDC-6. In contrast, out of the 97 cases of invasive ductal carcinomas studied, 90 (93%) and 96 (99%) reacted positively with BC-I and FDC-6, respectively, the reaction being observed in the tumoral stroma connective tissue and in tumoral vessels. Furthermore, invasive lobular carcinoma showed less intense and less frequent staining with BC-1 and FDC-6 (10 and 11 out of 14, respectively). We found differences in the distribution of the 2 oncofetal fibronectin isoforms within the same specimens. The most remarkable difference was observed in the tumoral vessels: in invasive ductal carcinoma MAb BC-1 revealed a positive reaction with vessels in 78% of cases while FDC-6 showed such a reaction in only 59% of cases.
Renal Extraction of Endogenous Gastrin in Patients with Normal Renal Function (1977)

Renal extraction of gastrin in patients with normal clearance of inulin and p-aminohippuric acid was assessed by gastrin radioimmunoassay. In 23 fasting patients there was no significant difference in arterial gastrin (37.7 pg/ml serum ±25.1 S.D.) and the renal vein gastrin (35.9 ± 24.6), resulting in a renal extraction ratio for gastrin not significantly different from zero (p>0.5). The results in three patients indicated no extraction of gastrin for two consecutive periods after a protein-rich meal.
Identification and Characterization of the CYP52 Family of Candida tropicalis ATCC 20336, Important for the Conversion of Fatty Acids and Alkanes to α,ω-Dicarboxylic Acids (2003)

Candida tropicalis ATCC 20336 excretes alpha,omega-dicarboxylic acids as a by-product when cultured on n-alkanes or fatty acids as the carbon source. Previously, a beta-oxidation-blocked derivative of ATCC 20336 was constructed which showed a dramatic increase in the production of dicarboxylic acids. This paper describes the next steps in strain improvement, which were directed toward the isolation and characterization of genes encoding the omega-hydroxylase enzymes catalyzing the first step in the omega-oxidation pathway. Cytochrome P450 monooxygenase (CYP) and the accompanying NADPH cytochrome P450 reductase (NCP) constitute the hydroxylase complex responsible for the first and rate-limiting step of omega-oxidation of n-alkanes and fatty acids. 10 members of the alkane-inducible P450 gene family (CYP52) of C. tropicalis ATCC20336 as well as the accompanying NCP were cloned and sequenced. The 10 CYP genes represent four unique genes with their putative alleles and two unique genes for which no allelic variant was identified. Of the 10 genes, CYP52A13 and CYP52A14 showed the highest levels of mRNA induction, as determined by quantitative competitive reverse transcription-PCR during fermentation with pure oleic fatty acid (27-fold increase), pure octadecane (32-fold increase), and a mixed fatty acid feed, Emersol 267 (54-fold increase). The allelic pair CYP52A17 and CYP52A18 was also induced under all three conditions but to a lesser extent. Moderate induction of CYP52A12 was observed. These results identify the CYP52 and NCP genes as being involved in alpha,omega-dicarboxylic acid production by C. tropicalis and provide the foundation for biocatalyst improvement.