gebhart/patrepeval huggingface dataset:
Application and Verification of Local Nonsemantic-Preserving Transformations in System Design (2008)

Due to the increasing abstraction gap between the initial system model and a final implementation, the verification of the respective models against each other is a formidable task. This paper addresses the verification problem by proposing a stepwise application of combined refinement and verification activities in the context of synchronous model of computation. An implementation model is developed from the system model by applying predefined design transformations which are as follows: 1) semantic preserving or 2) nonsemantic preserving. Nonsemantic-preserving transformations introduce lower level implementation details, which are necessary to yield an efficient implementation. Our approach divides the verification tasks into two activities: 1) the local correctness of a refined block is checked by using formal verification tools and predefined properties, which are developed for each nonsemantic-preserving transformation, and 2) the global influence of the refinement to the entire system is studied through static analysis. We illustrate the design refinement and verification approach with three transformations: 1) a communication refinement mapping a synchronous channel to an asynchronous one including a handshake mechanism; 2) a computation refinement, which introduces resource sharing in a combinational computation block; and 3) a synchronization demanding refinement, where an algorithm analyzes the influence of a local refinement to the temporal properties of the entire system and restores the system's correct temporal behavior if necessary.
Economic analysis of solar home sysstems: a case study for the philippines (2003)

This paper deals with the economic analysis of solar photovoltaic home systems for off-grid application in the Philippines. Solar homes systems financing is one of several components of the proposed Philippines Rural Project. A detailed reconciliation of economic and financial flows is provided, which indicates the basis for an assessment of the rationale for, and impact of, alternative levels of subsidy. The conventional switching value sensitivity analysis is augmented by a probabilistic risk assessment using Monte Carlo simulation. Risk factors assessed include shorter than expected system lives, capital costs, market penetration, kerosene prices, and uncertainty in the demand curve parameters. Additional benefits from carbon reduction further enhance the economic rate of return. A range of further environmental benefits - such as the reduction of burn injuries and deaths from kerosene lamps, and indoor air pollution benefits are noted, though not quantified. The paper concludes that solar home systems provide high economic returns for areas with low load density for which grid extension is uneconomic, with very small risk of hurdle rates not being achieved.
Comparative Genomics of Two Closely Related Unicellular Thermo-Acidophilic Red Algae, Galdieria sulphuraria and Cyanidioschyzon merolae, Reveals the Molecular Basis of the Metabolic Flexibility of Galdieria sulphuraria and Significant Differences in Carbohydrate Metabolism of Both Algae (2005)

Unicellular algae serve as models for the study and discovery of metabolic pathways, for the functional dissection of cell biological processes such as organellar division and cell motility, and for the identification of novel genes and gene functions. The recent completion of several algal genome sequences and expressed sequence tag collections and the establishment of nuclear and organellar transformation methods has opened the way for functional genomics approaches using algal model systems. The thermo-acidophilic unicellular red alga Galdieria sulphuraria represents a particularly interesting species for a genomics approach owing to its extraordinary metabolic versatility such as heterotrophic and mixotrophic growth on more than 50 different carbon sources and its adaptation to hot acidic environments. However, the ab initio prediction of genes required for unknown metabolic pathways from genome sequences is not trivial. A compelling strategy for gene identification is the comparison of similarly sized genomes of related organisms with different physiologies. Using this approach, candidate genes were identified that are critical to the metabolic versatility of Galdieria. Expressed sequence tags and high-throughput genomic sequence reads covering >70% of the G. sulphuraria genome were compared to the genome of the unicellular, obligate photoautotrophic red alga Cyanidioschyzon merolae. More than 30% of the Galdieria sequences did not relate to any of the Cyanidioschyzon genes. A closer inspection of these sequences revealed a large number of membrane transporters and enzymes of carbohydrate metabolism that are unique to Galdieria. Based on these data, it is proposed that genes involved in the uptake of reduced carbon compounds and enzymes involved in their metabolism are crucial to the metabolic flexibility of G. sulphuraria.
State Estimation in Electric Power Grids: Meeting New Challenges Presented by the Requirements of the Future Grid (2012)

This article provides a survey on state estimation (SE) in electric power grids and examines the impact on SE of the technological changes being proposed as a part of the smart grid development. Although SE at the transmission level has a long history, further research and development of innovative SE schemes, including those for distribution systems, are needed to meet the new challenges presented by the requirements of the future grid. This article also presents some example topics that signal processing (SP) research can contribute to help meet those challenges.
Formation Permeability Determination by Micro or Mini-Hydraulic Fracturing (1994)

This paper presents a theory and its application for post-fracture pressure-transient analyses. The proposed procedure, known as “impulse fracture test,” is an injection/falloff test designed for the determination of formation permeability and reservoir pressure. The hydraulically induced fracture can pass the near wellbore damaged zone and expose a larger formation area to flow. The permeability and reservoir pressure determined are therefore more representative of the reservoir. The theory is based on the distribution of sources with variable intensity along the fracture trajectory. For field applications, asymptotic solutions are derived to give the “type-curve” capability for the estimation of formation permeability and reservoir pressure. Assorted slope behaviors, such as −1, −2, +1/2 and +1 slopes, are predicted from various pressure and pressure derivative plots. Analyses of data from two wells which were inadvertently fractured support these behaviors.
Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity. (1993)

Chronic intracerebroventricular (icv) administration of neuropeptide-Y (NPY; 10 micrograms/day) was performed in normal female rats to investigate its hormonal and metabolic consequences. Intracerebroventricular NPY produced hyperphagia, increased basal insulinemia, as well as liver and adipose tissue lipogenic activity. It also increased basal morning corticosteronemia. When NPY-induced hyperphagia was prevented by pair-feeding, the icv NPY treatment resulted in the same increases in basal insulinemia and corticosteronemia, and liver and white adipose tissue lipogenesis was still higher than that in respective controls. Under the ad libitum and pair-feeding conditions, icv NPY stimulated glucose uptake as well as total lipoprotein lipase activity in white adipose tissue; it resulted in an increase total activity of hepatic and white adipose tissue acetyl coenzyme-A-carboxylase. As all hormonal and metabolic changes elicited by icv NPY remained present (at the same or to a lesser extent depending upon the parameter considered) when hyperphagia was prevented by pair-feeding, it was, thus, shown that icv NPY per se induces peripheral hormonal and metabolic alterations via efferent routes, which remain to be determined. The effects of icv NPY reported in this study are similar to the defects observed in the early phase of genetic obesity in rodents, the hypothalamus of which has increased NPY levels. NPY could, thus, be of relevance in the occurrence of genetically induced obesity.
JNK1 Physically Interacts with WW Domain-containing Oxidoreductase (WOX1) and Inhibits WOX1-mediated Apoptosis (2003)

Transient activation of c-Jun N-terminal kinase (JNK) promotes cell survival, whereas persistent JNK activation induces apoptosis. Bovine testicular hyaluronidase PH-20 activates JNK1 and protects L929 fibroblasts from staurosporine-mediated cell death. PH-20 also induces the expression of a p53-interacting WW domain-containing oxidoreductase (WOX1, also known as WWOX or FOR) in these cells. WOX1 enhances the cytotoxic function of tumor necrosis factor and mediates apoptosis synergistically with p53. Thus, the activated JNK1 is likely to counteract WOX1 in mediating apoptosis. Here it is demonstrated that ectopic JNK1 inhibited WOX1-mediated apoptosis of L929 fibroblasts, monocytic U937 cells, and other cell types. Also, JNK1 blocked WOX1 prevention of cell cycle progression. By stimulating cells with anisomycin or UV light, JNK1 became activated, and WOX1 was phosphorylated at Tyr(33). The activated JNK1 physically interacted with the phosphorylated WOX1, as determined by co-immunoprecipitation. Alteration of Tyr(33) to Arg(33) in WOX1 abrogated its binding interaction with JNK1 and its activity in mediating cell death, indicating that Tyr(33) phosphorylation is needed to activate WOX1. A dominant negative WOX1 was developed and shown to block p53-mediated apoptosis and anisomycin-mediated WOX1 phosphorylation but could not inhibit JNK1 activation. This mutant protein bound p53 but could not interact with JNK1, as determined in yeast two-hybrid analysis. Taken together, phosphorylation of JNK1 and WOX1 is necessary for their physical interaction and functional antagonism.
Type‐specific identification of human adenovirus 3, 7, and 21 by a multiplex PCR assay† (2001)

Human adenovirus (Ad) serotypes 3, 7, and 21 of DNA cluster B:1 are often associated with severe respiratory illness, particularly in infants and young children and, in addition to Ad4, are among the most important causes of acute respiratory disease syndrome in new military recruits. To address the inherent problems associated with classic typing methods, we developed a multiplex PCR assay for the rapid, specific identification of Ad3, Ad7, and Ad21 field isolates. To design type-specific primers for our assay, we sequenced the Ad21 hexon gene and compared this sequence with previously published sequences of Ad3, Ad7, and Ad16. The overall nucleotide (nt) and amino acid (aa) identities between Ad21 and Ad3, Ad7, and Ad16 were similar (ranges 78.3-80.8% nt; 84.1-86.2% aa), with significantly greater variability in the regions of the hexon that encode surface loops 1 and 2. Type-specific primers designed to the hypervariable regions correctly identified Ad3, Ad7, and Ad21 prototype strains and 53 previously typed Ad field isolates. No cross-reactions with other Ad serotypes were identified. Our multiplex PCR assay for type-specific identification of Ad3, Ad7, and Ad21 isolates will provide a rapid and convenient tool for the epidemiologic investigation of Ad-associated respiratory illness.
STAT5 Activation by BCR-Abl Contributes to Transformation of K562 Leukemia Cells (1999)

Signal transducers and activators of transcription (STATs) belong to a family of transcription factors that were originally identified as mediators of cytokine-induced gene expression. Recent evidence, however, has shown that certain members of the STAT family, including STAT3, are also involved in cellular transformation. Here we show that STAT5 also plays a role in cellular transformation by the BCR-Abl oncogene. In BCR-Abl transformed K562 cells, STAT5A and 5B are constitutively phosphorylated on tyrosine and are transcriptionally active. Moreover, expression of a dominant negative form of STAT5 shows that active STAT5 is necessary for the growth in soft agar of these cells. These results show that besides STAT3, STAT5 can also be involved in cellular transformation.
Expression of Vascular Endothelial Growth Factor (VEGF) Family Members in Breast Cancer (1999)

Vascular endothelial growth factor (VEGF)-A is known to play an important role in tumor angiogenesis. Three additional members of the VEGF family, VEGF-B, -C and -D, have recently been discovered. VEGF-C and VEGF-D are ligands for VEGF receptor-3, which is expressed in the endothelium of lymphatic vessels. The expression of VEGF-C is known to be associated with the development of lymphatic vessels. Therefore, it is conceivable that VEGF-C and VEGF-D might play a role in the development of lymphatic vessels in solid tumors. To obtain some clue as to this role, we developed a semi-quantitative reverse transcription-polymerase chain reaction method to investigate the mRNA expression levels of each VEGF family member in breast cancer. All the VEGF family members were expressed at different levels in seven human breast cancer cell lines explored. Although VEGF-A and VEGF-B expressions were detected in both node-positive and node-negative breast tumors, VEGF-C expression was detected only in node-positive tumors. VEGF-D expression was detected only in an inflammatory breast cancer and a tumor which developed an inflammatory skin metastasis. These findings suggest a possible relationship between the expression level of VEGF-C and/or VEGF-D and the development of lymphatic tumor spread.
Metabolism in the F344 rat of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, a tobacco-specific carcinogen. (1980)

The metabolism of the tobacco-specific carcinogen, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), was studied in the F344 rat, in which it induces tumors of the nasal cavity, liver, and lung. When NNK was incubated with rat liver microsomes and a reduced nicotinamide adenine dinucleotide phosphate-generating system, metabolites resulting from alpha-hydroxylation, carbonyl reduction, and N-oxidation were isolated. alpha-Hydroxylation at the methylene carbon gave 4-oxo-4-(3-pyridyl)butanal, whereas alpha-hydroxylation at the methyl carbon gave myosmine and 4-hydroxyl-1-(3-pyridyl)butan-1-one. The formation of these products involved the intermediacy of electrophilic diazohydroxides or carbonium ions which may be proximate or ultimate carcinogens of NNK. Carbonyl reduction gave 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)butan-1-ol and N-oxidation yielded 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone. When rats were gavaged with NNK, the microsomal products of alpha-hydroxylation were not detected in the 48-hr urine. Compounds which presumably resulted from further oxidation or reduction of these products, 4-oxo-4-(3-pyridyl)butyric acid, 4-hydroxy-4-(3-pyridyl)butyric acid, and 4-hydroxy-1-(3-pyridyl)butan-1-ol, were isolated. 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)butan-1-ol and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl-N-oxide)-1 butanone were also urinary metabolites.
Preparing Unbiased T-Cell Receptor and Antibody cDNA Libraries for the Deep Next Generation Sequencing Profiling (2013)

High-throughput sequencing has the power to reveal the nature of adaptive immunity as represented by the full complexity of T-cell receptor (TCR) and antibody (IG) repertoires, but is at present severely compromised by the quantitative bias, bottlenecks, and accumulated errors that inevitably occur in the course of library preparation and sequencing. Here we report an optimized protocol for the unbiased preparation of TCR and IG cDNA libraries for high-throughput sequencing, starting from thousands or millions of live cells in an investigated sample. Critical points to control are revealed, along with tips that allow researchers to minimize quantitative bias, accumulated errors, and cross-sample contamination at each stage, and to enhance the subsequent bioinformatic analysis. The protocol is simple, reliable, and can be performed in 1-2 days.
Pulmonary Pathology of the Rheumatic Diseases (2007)

Thoracic manifestations of the rheumatic diseases (RDs) are a significant cause of morbidity and mortality worldwide. The five RDs most frequently associated with pleuropulmonary disease are (1) rheumatoid arthritis (RA), (2) systemic lupus erythematosus (SLE), (3) progressive systemic sclerosis (PSS), (4) polymyositis/dermatomyositis (PM/DM), and (5) Sjögren syndrome (SS). The clinical presentation is highly variable, ranging from pleuritic pain alone to slowly progressive breathlessness accompanied by cough. On occasion RD may present acutely with overwhelming respiratory failure as the first pulmonary manifestation. In all of the RDs, the pathology is dominated by either or both inflammation and fibrosis, but the anatomical distribution in each varies somewhat. For example, airway-associated lymphoid hyperplasia is a common manifestation of SS, PM/DM preferentially involves the alveolar parenchyma, and pleural inflammation is most commonly seen in RA. Such changes may be detected radiologically as peribronchovascular disease in SS, ground-glass infiltrates in PM/DM, and pleural disease with effusion in RA. Some RDs are more commonly associated with distinctive histopathology, such as rheumatoid nodules in RA, or lymphoid hyperplasia in both RA and SS. Patients with PSS are at particular risk for pulmonary hypertension when the lung is involved. Also, statistically, acute lung injury occurs more commonly in some, such as SLE and PM/DM. The very common use of immunosuppressive agents in the treatment of RD creates additional diagnostic problems related to drug toxicity and infection. Finally, a major confounding factor occurs when preclinical RD presents first as pulmonary disease (particularly PM/DM), an occurrence that may invoke one of the so-called idiopathic interstitial pneumonias. The most common pleuropulmonary pathological manifestations of the five major RDs are presented and discussed with brief radiological correlations.
Animal models of schizophrenia (2011)

Developing reliable, predictive animal models for complex psychiatric disorders, such as schizophrenia, is essential to increase our understanding of the neurobiological basis of the disorder and for the development of novel drugs with improved therapeutic efficacy. All available animal models of schizophrenia fit into four different induction categories: developmental, drug-induced, lesion or genetic manipulation, and the best characterized examples of each type are reviewed herein. Most rodent models have behavioural phenotype changes that resemble 'positive-like' symptoms of schizophrenia, probably reflecting altered mesolimbic dopamine function, but fewer models also show altered social interaction, and learning and memory impairment, analogous to negative and cognitive symptoms of schizophrenia respectively. The negative and cognitive impairments in schizophrenia are resistant to treatment with current antipsychotics, even after remission of the psychosis, which limits their therapeutic efficacy. The MATRICS initiative developed a consensus on the core cognitive deficits of schizophrenic patients, and recommended a standardized test battery to evaluate them. More recently, work has begun to identify specific rodent behavioural tasks with translational relevance to specific cognitive domains affected in schizophrenia, and where available this review focuses on reporting the effect of current and potential antipsychotics on these tasks. The review also highlights the need to develop more comprehensive animal models that more adequately replicate deficits in negative and cognitive symptoms. Increasing information on the neurochemical and structural CNS changes accompanying each model will also help assess treatments that prevent the development of schizophrenia rather than treating the symptoms, another pivotal change required to enable new more effective therapeutic strategies to be developed.
A radioiodinated, intracellularly trapped ligand for determining the sites of plasma protein degradation in vivo (1983)

We recently developed a general method for determining tissue sites of degradation of plasma proteins in vivo that made use of covalently attached radioactive sucrose. On degradation of the protein, the sucrose remained trapped in the cells as a cumulative marker of protein degradation. The method described here depends on the same principles, but uses an adduct of cellobiose and tyramine that is radioiodinated to high specific radioactivity and then covalently attached to protein. Use of the radioiodinated ligand increases the sensitivity of the method at least 100-fold and allows simplified tissue analysis. Proteins derivatized with the radioiodinated ligand were recognized as underivatized proteins both in vitro and in vivo. On degradation of derivatized low-density lipoprotein, the rate of leakage from cultured fibroblasts was only 5% during 24 h. Similarly, on injection of labelled proteins into rats and rabbits, urinary excretion of the label was in all cases less than 10% of total labelled catabolic products recovered 24 h after injection. Examination of the tissue contents of label at two times after injection of labelled asialofetuin or apolipoprotein A1 in rats, and asialotransferrin in rabbits showed that the label did not detectably redistribute between tissues after initial uptake and catabolism; a significant leakage from liver was quantitatively accounted for by label appearing in gut contents and faeces. A simple double-label method was devised to provide a correction for intact protein in trapped plasma, the extravascular spaces, and within cells. By using this method it becomes unnecessary to fractionate tissue samples.
High resolution pHe imaging of rat glioma using pH‐dependent relaxivity (2006)

Previous studies using MR spectroscopy have shown that the extracellular pH (pH(e)) of tumors is acidic compared to normal tissues. This has a number of important sequelae that favor the emergence of more aggressive and therapy-resistant tumors. New MRI methods based on pH-sensitive T1 relaxivity are an attractive alternative to previous spectroscopic methods, as they allow improvements in spatial and temporal resolution. Recently, pH-dependent GdDOTA-4AmP5- and a pH-independent analog, GdDOTP5-, were used to image renal pH in mice. The current study has used a similar approach to image pH(e) in rat gliomas. Significant differences were observed compared to the renal study. First, the relaxivity of GdDOTP5- was found to be affected by the higher extracellular protein content of tumors. Second, the pixel-by-pixel analysis of the GdDOTP5- and GdDOTA-4AmP5- pharmacokinetics showed significant dispersion, likely due to the temporal fluctuations in tumor perfusion. However, there was a robust correlation between the maximal enhancements produced by the two boluses. Therefore, to account for the local time-courses differences, pH(e) maps were calculated at the time of maximal enhancement in each pixel. Finally, the comparison of the pH(e) and the time to maximal intensity maps revealed an inverse relationship between pH(e) and tumor perfusion.