gebhart/patrepeval huggingface dataset:
Modeling, simulation, and verification of photonic-integrated circuits using VHDL (1996)

Optical links and photonic integrated circuits require integration of photonic and electronic devices at chip, module, or board level. The complexity of such systems is motivating a need for system level CAD tools which can simulate electronic and photonic devices and circuits simultaneously and at multiple levels of abstraction. Furthermore integrating photonic devices into conventional electronic computer and communication systems needs to be justified in terms of cost, performance, and portability of existing computer software and hardware. Thus system level analysis of optoelectronic interconnect system is clearly necessary to ensure that an overall functional and performance requirements are met. The proposed approach for system level modeling is to integrate photonic device simulations into the established electronic design automation environment, particularly VHDL-based one. VHDL description of photonic devices will provide benefits such as portability of individual design, system level performance analysis before building a real system, and synthesis capability for a rapid- prototyping. This paper demonstrates the use of basic VHDL entities of various passive optical waveguide components and a special VHDL package (`Optical_Package') defining physical photonic parameters to verify the feasibility of this approach. It includes modeling and simulation of global signal distribution network on MCMs using optical interconnect and wavelength division (de)multiplexing-based optical link.
MEK-ERK pathway modulation ameliorates disease phenotypes in a mouse model of Noonan syndrome associated with the Raf1L613V mutation (2011)

Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden death in children and young adults. Abnormalities in several signaling pathways are implicated in the pathogenesis of HCM, but the role of the RAS-RAF-MEK-ERK MAPK pathway has been controversial. Noonan syndrome (NS) is one of several autosomal-dominant conditions known as RASopathies, which are caused by mutations in different components of this pathway. Germline mutations in RAF1 (which encodes the serine-threonine kinase RAF1) account for approximately 3%-5% of cases of NS. Unlike other NS alleles, RAF1 mutations that confer increased kinase activity are highly associated with HCM. To explore the pathogenesis of such mutations, we generated knockin mice expressing the NS-associated Raf1(L613V) mutation. Like NS patients, mice heterozygous for this mutation (referred to herein as L613V/+ mice) had short stature, craniofacial dysmorphia, and hematologic abnormalities. Valvuloseptal development was normal, but L613V/+ mice exhibited eccentric cardiac hypertrophy and aberrant cardiac fetal gene expression, and decompensated following pressure overload. Agonist-evoked MEK-ERK activation was enhanced in multiple cell types, and postnatal MEK inhibition normalized the growth, facial, and cardiac defects in L613V/+ mice. These data show that different NS genes have intrinsically distinct pathological effects, demonstrate that enhanced MEK-ERK activity is critical for causing HCM and other RAF1-mutant NS phenotypes, and suggest a mutation-specific approach to the treatment of RASopathies.
Synthesis and hybridization properties of inverse oligonucleotides (1997)

The synthesis of adenine and thymine cyclopentylethyl nucleosides is presented. This novel constrained monomeric building block is very difficult to incorporate into oligonucleotides. It was introduced in 13mer oligodeoxynucleotide sequences at a single position using H-phosphonate chemistry. Phosphoramidite chemistry completely failed in this particular case. The H-phosphonate building blocks were obtained starting from the corresponding phosphoramidites. Stability of duplexes with RNA and DNA is significantly reduced.
Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV‐infected patients receiving highly active antiretroviral therapy (2007)

Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV-infected patients, reflecting possibly a low-grade pro-inflammatory state. Low-grade inflammation has been implicated in insulin resistance and other features of dysmetabolism. Accordingly it is hypothesized that circulating suPAR is associated with the metabolic status of HIV-infected patients on HAART. Fasting plasma suPAR was determined in 36 normoglycaemic HIV-infected patients on HAART (n = 18 lipodystrophic, and n = 18 non-lipodystrophic) who had estimated insulin sensitivity (Rd) and non-oxidative glucose disposal (NOGM) by euglycaemic hyperinsulinaemic clamps, indirect calorimetry, and glucose tracer infusion. Five patients had circadian suPAR concentrations measured (24 hr, 20 min-intervals). suPAR and non-HDL-cholesterol were higher and Rd, NOGM, and limb fat were lower in lipodystrophic patients than in non-lipodystrophic patients (P < 0.05). suPAR correlated positively with non-HDL-cholesterol and inversely with Rd, NOGM and limb fat (P < 0.005, n = 36). suPAR also correlated positively with leukocyte count and TNF-alpha (P < 0.01, n = 36) but not with IL-6. In multiple regression analyses suPAR was a stronger predictor of dysmetabolism than TNF-alpha and IL-6. Circadian suPAR did not systematically fluctuate. In conclusion, suPAR may reflect the metabolic status of the HIV-infected patient on HAART, thus linking low-grade inflammation, immune constitution, lipid and glucose metabolism, and fat redistribution. Circadian suPAR concentration appeared stable, suggesting that sampling schedule does not affect measurement. Further studies addressing whether suPAR predicts lipodystrophy and dysmetabolism in HIV-infected patients are warranted.
Assessing hopelessness in terminally ill cancer patients: Development of the Hopelessness Assessment in Illness Questionnaire. (2011)

Hopelessness has become an increasingly important construct in palliative care research, yet concerns exist regarding the utility of existing measures when applied to patients with a terminal illness. This article describes a series of studies focused on the exploration, development, and analysis of a measure of hopelessness specifically intended for use with terminally ill cancer patients. The 1st stage of measure development involved interviews with 13 palliative care experts and 30 terminally ill patients. Qualitative analysis of the patient interviews culminated in the development of a set of potential questionnaire items. In the 2nd study phase, we evaluated these preliminary items with a sample of 314 participants, using item response theory and classical test theory to identify optimal items and response format. These analyses generated an 8-item measure that we tested in a final study phase, using a 3rd sample (n = 228) to assess reliability and concurrent validity. These analyses demonstrated strong support for the Hopelessness Assessment in Illness Questionnaire providing greater explanatory power than existing measures of hopelessness and found little evidence that this assessment was confounded by illness-related variables (e.g., prognosis). In summary, these 3 studies suggest that this brief measure of hopelessness is particularly useful for palliative care settings. Further research is needed to assess the applicability of the measure to other populations and contexts.
Why are there so few resistance–associated mutations in insecticide target genes? (1998)

The genes encoding the three major targets of conventional insecticides are: Rdl, which encodes a gamma-aminobutyric acid receptor subunit (RDL); para, which encodes a voltage-gated sodium channel (PARA); and Ace, which encodes insect acetylcholinesterase (AChE). Interestingly, despite the complexity of the encoded receptors or enzymes, very few amino acid residues are replaced in different resistant insects: one within RDL, two within PARA and three or more within AChE. Here we examine the possible reasons underlying this extreme conservation by looking at the aspects of receptor and/or enzyme function that may constrain replacements to such a limited number of residues.
Application of Padlock Probe Based Nucleic Acid Analysis In Situ (2010)

The great variation displayed by nucleic acid molecules in human cells, and the continuous discovery of their impact on life, consequently require continuous refinements of molecular analysis techniques. Padlock probes and rolling circle amplification offer single nucleotide discrimination in situ, a high signal-to-noise ratio and localized detection within cells and tissues. In this thesis, in situ detection of nucleic acids with padlock probes and rolling circle amplification was applied for detection of DNA in the single cell gel electrophoresis assay to detect nuclear and mitochondrial DNA. This assay is used to measure DNA damage and repair. The behaviour of mitochondrial DNA in the single cell gel electrophoresis assay has earlier been controversial, but it was shown herein that mitochondrial DNA diffuses away early in the assay. In contrast, Alu repeats remain associated with the nuclear matrix throughout the procedure. A new twelve gel approach was also developed with increased throughput of the single cell gel electrophoresis assay. DNA repair of three genes OGG1, XPD and HPRT and of Alu repeats after H2O2 induced damage was further monitored. All three genes and Alu repeats were repaired faster than total DNA. Finally, padlock probes and rolling circle amplification were applied for detection of the single stranded RNA virus Crimean Congo hemorrhagic fever virus. The virus was detected by first reverse transcribing RNA into cDNA.. The virus RNA together with its complementary RNA and the nucleocapsid protein were detected in cultured cells. The work presented here enables studies of gene specific damage and repair as well as viral infections in situ. Detection by ligation offers high specificity and makes it possible to discriminate even between closely related molecules. Therefore, these techniques will be useful for a wide range of applications within research and diagnostics.
Antioxidant effect and antimicrobial activity of phenolic sulfides (1989)

Abstract Some phenolic compounds containing both phenolic hydroxyl groups and sulfide groups in the molecules were prepared by Michael addition and radical addition reactions of ethanethiol and ethanedithiol with o‐, m ‐ and p ‐vinylphenol. The antioxidant effect of these products on the autoxidation of lard was examined by an oven test at 60°C. The antimicrobial activities of these products were evaluated by an agar dilution method. Three kinds of gram‐positive and three kinds of gram‐negative bacterial strains, as well as six kinds of fungal strains were used for the test. It was found that the Michael addition products showed considerably better antioxidant effects than BHT, whereas the radical addition products did not show any antioxidant effect. The antioxidant effects of these compounds were influenced by the positions of the sulfide groups in their molecules. The phenolic sulfides tested in this report showed good antimicrobial activities against bacteria and fungi.
IL-5 Is Required for Eosinophil Recruitment, Crystal Deposition, and Mononuclear Cell Recruitment During a Pulmonary <i>Cryptococcus neoformans</i> Infection in Genetically Susceptible Mice (C57BL/6) (1998)

CBA/J (highly resistant), BALB/c (moderately resistant), and C57BL/6 (susceptible) mice displayed three resistance patterns following intratracheal inoculation of Cryptococcus neoformans 52. The inability to clear the infection correlated with the duration of the eosinophil infiltrate in the lungs. The role of IL-5 in promoting the pulmonary eosinophilia and subsequent inflammatory damage in susceptible C57BL/6 mice was investigated. C57BL/6 mice developed a chronic alveolar, peribronchiolar, and perivascular eosinophilia following C. neoformans infection. This resulted in the accumulation of intracellular Charcot-Leyden-like crystals in alveolar macrophages by wk 4 and the extracellular deposition of these crystals in the bronchioles with associated destruction of airway epithelium by wk 6. IL-5 mRNA was expressed in the lungs, and injections of anti-IL-5 mAb prevented eosinophil recruitment and crystal deposition but did not alter cryptococcal clearance. Depletion of CD4+ T cells (but not CD8+) ablated IL-5 production by lung leukocytes in vitro and eosinophil recruitment in vivo. Neutralization of IL-5 also inhibited the recruitment of macrophages, CD8+ T lymphocytes, and B lymphocytes by 47 to 57%. Anti-IL-5 mAb inhibited CD4+ T lymphocyte recruitment by 30% but did not affect neutrophil recruitment. Thus, the development of a chronic eosinophil infiltrate in the lungs of C. neoformans-infected C57BL/6 mice is a nonprotective immune response that causes significant lung pathology. Furthermore, IL-5 promotes the recruitment and activation of eosinophils, resulting in the recruitment of additional macrophages and lymphocytes into the lungs.
Thalidomide in the treatment of lepra reactions (1965)

In 6 consecutive cases of lepromatous leprosy, acute severe lepra reactions were qUickly resolved with disappearance of symptoms as well as signs after the use of thalidomide as a sedative. No exceptions were noted. Concurrent therapy with sulfones and arsenicals did not appear to be involved. The cases are reported at this early stage because of the obvious importance of corroborating these findings.
Common migraine ("migraine without aura"): localization of the initial pain of attack. (1993)

In classical migraine ("migraine with aura"), the attack pain is usually initially felt in the oculo-fronto-temporal area (around 90% of the cases). A fronto-temporal onset of pain is in other words a typical trait of classic migraine. The initial location of pain in common migraine ("migraine without aura") is not so well known. In the present study, 32 migraine patients and 29 cervicogenic headache patients were compared as for localization of pain onset. Twenty-four of 32 migraine patients (75%) felt the initial pain in the oculo-fronto-temporal area; in 28 of 32 cases the onset was in the "anterior" parts (88%). The corresponding figures in the cervicogenic group were: 5 of 29 (17%) and 6 of 29 (21%) respectively. There is thus a clear-cut difference between the two groups in this respect. The initial localization of pain can probably also be used for diagnostic purposes. The similarity between classic and common migraine in this respect is striking.
Privatization in Tunisia (1993)

This paper is an attempt to provide a comprehensive overview of the privatization experience in Tunisia, focusing upon the respective roles of the public and private sectors, the relationship between them, and how this has changed over time. First, a historical background is presented to give perspective on the rationale for and the specific difficulties encountered in privatization in Tunisia. Issues discussed include key factors accounting for the growth of public sector enterprises, the country's overall economic performance and problems, the debt crisis and decline in the terms of trade during the 1980s, and the need for structural adjustment of the Tunisian economy. In order to tackle Tunisia's current account deficit (109 percent of GDP) and set the stage for renewed growth, the Government of Tunisia embarked on a major economic structural adjustment program in 1986. In this context, reducing the role of the public sector became a specific government objective. This paper details how this was accomplished through a multi-phased program for economic and social development. To create an environment in which substantial reforms could be introduced, legal and organizations changes were necessary. The paper discusses the relevant laws passed by the government in support of the privatization effort. The process of privatization in Tunisia is a complex one, involving eight steps which are discussed in the report. So far, privatization has taken place on a case by case basis and covered only small and medium-size enterprises. Finally, the paper examines the major factors affecting the success of the privatization process in Tunisia and identifies lessons that can be applied to other countries. Paramount among these is the sustained commitment to privatization at the highest levels of government. Although Tunisia has successfully achieved the privatization of small and medium enterprises, this program will now have to tackle large enterprises and the utilities sector whose privatizations pose more complex problems.
Arrayed electrowetting microwells (2008)

Colored oils and aqueous solutions have been electromechanically pumped in and out of arrayed microwells. The microwells comprised pyramidal pits in Si substrates that were coated with an aluminum electrode and a hydrophobic dielectric. These substrates were then suspended between volumes of water and oil. When colored oil was placed behind the substrate, surface tension forces caused the oil to completely fill the microwells and provide brilliant red coloration to the array. With application of ∼30–50V, electrowetting drove the colored oil behind the substrate and the reflection was made dominantly white.
Significance of long term components of heart rate variability for the further prognosis after acute myocardial infarction (1990)

Whilst the maximum value of short term heart rate variability is sufficient for stratification of the high risk post-myocardial infarction patients, an arbitrarily selected short term ECG recording is unlikely to register the maximum heart rate variability. It is concluded that the heart rate variability assessed from arbitrary 1 h electrocardiographic records is not as prognostically important as the variability estimated from 24 h recordings.
Recovery of Acutely Transforming Viruses from Myeloid Leukosis Induced by the HPRS-103 Strain of Avian Leukosis Virus (1993)

Viruses rapidly able to transform cultured chicken bone marrow cells have been isolated from cases of myelocytic myeloid leukosis (MML) induced experimentally by the HPRS-103 strain of avian leukosis virus, and from field cases of MML. HPRS-103 virus itself did not acutely transform cultured bone-marrow cells. These findings suggest that during myeloid leukemogenesis by HPRS-103 virus, recombinant viruses are generated with transduced cellular oncogenes. The transformed cell appeared to be a macrophage precursor cell. Transformed cells in culture lost their proliferative capacity after a few weeks and then tended to resemble more differentiated macrophages. This change could be reversed temporarily by addition of a myelomonocytic growth factor, cMGF, to the culture medium. In oncogenicity tests, a selection of the virus strains induced MML, nephroblastomas, renal adenomas/adenocarcinomas, and other tumors in line 21 meat-type chickens but not in line 0 chickens. This difference may have been related to a propensity for the virus strains to induce persistent tolerant viremic infections in the line 21 chickens following infection at 1 day of age. The oncogenic pattern was not clearly related to the ability of the viruses to transform cultured bone-marrow cells. The generation of acutely transforming viruses during myeloid leukemogenesis may be relevant to the occurrence of MML in the field.
Symptoms of obsessive-compulsive disorder (1997)

Obsessive-compulsive disorder is a multidimensional and etiologically heterogeneous condition. The four symptom dimensions identified in this study are largely congruent with those identified in earlier reports. These factors may be of value in future genetic, neurobiological, and treatment response studies.
IRDye800CW-anti-CD105 TRC105 chimeric monoclonal antibody (2012)

Angiogenesis is an essential process in the development of new blood vessels both in normal physiological states and diseases (1, 2). Targeting of tumor vasculature is a promising strategy for tumor imaging and therapy because tumor growth and metastasis largely depend on angiogenesis (3-5). Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that modulates blood vessel development, angiogenesis, and tumor progression (6). There are three isoforms of TGF-β (β1, β2, and β3). TGF-β1 inhibits proliferation and migration of endothelial cells and their ability to form capillaries. CD105 (endoglin, EDG) is a homodimeric transmembrane glycoprotein (180 kDa) with disulfide-linked subunits of 95,000. CD105 is a component of the TGF-β receptor complex that specifically binds TGF-β1 and TGF-β3 with high affinity (7). CD105 is important for blood vessel development. The expression of CD105 on different cells affects cellular response to TGF-β1. CD105 is overexpressed in proliferating endothelial cells of tumor vessels, and CD105 prevents TGF-β1–mediated inhibition of endothelial cell proliferation (8, 9).Radiolabeled monoclonal antibodies (mAbs) have been developed for both the diagnosis and treatment of tumors (10-12). Quiescent human endothelial cells express CD105 only weakly, but the expression of CD105 is strongly upregulated on the endothelial cells of tumor tissues undergoing angiogenesis (9, 13). The high level of expressed CD105 (up to 106 molecules/proliferating cell) appears to be ideal for in vivo imaging and therapy. Anti-CD105 mAbs, such as MAEND3, E9, and MJ7/18 with radioisotopes (e.g., 111In, 99mTc, and 125I) have been studied as single-photon emission computed tomography (SPECT) probes for imaging CD105 expression (9, 14). TRC105 is a human/murine chimeric IgG1 mAb that binds with higher affinity to human CD105 than to murine CD105 (15). TRC105 inhibits angiogenesis and tumor growth and is now in clinical trials in cancer patients. Binding of TRC105 to CD105 allows TGF-β1–mediated inhibition of endothelial cell proliferation. Hong et al. (16) showed that 64Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-anti-CD105 TRC105 (64Cu-DOTA-TRC105) mAb could efficiently image 4T1 murine breast tumor in mice with positron emission tomography (PET) imaging. Hong et al. (17) have evaluated 89Zr-desferrioxamine-TRC105 (89Zr-Df-TRC105) as an 89Zr-based PET agent in the same 4T1 murine breast tumor model. For near-infrared (NIR) fluorescence optical imaging, Yang et al. (18) conjugated IRDye800CW to TRC105 to form IRDye800CW-TRC105 to assess CD105 expression in mice bearing 4T1 murine breast tumors.