gebhart/patrepeval huggingface dataset:
An Introduction to Middle Classes, Discipline, and Development (2004)

One of the most commonly held assumptions in the field of development is that middle classes are the bounty of economic modernization and growth. As countries gradually transcend their agrarian past and become urbanized and industrialized, so the logic goes, middle classes emerge and gain in number, complexity, cultural influence, social prominence, and political authority. Yet this is only half the story. Middle classes shape industrial and economic development, rather than being merely its product; and the particular ways in which middle classes shape themselves – and the ways historical conditions shape them – influence development trajectories in multiple ways. This is especially true in late industrializers. Whether they choose rapid and successful export-oriented industrialization (EOI) grounded in an integrated and robust sectoral development based on strong forward and backward linkages, or whether they remain overly wedded to industrial policies that protect import-substitution activities (ISI) and reinforce sectoral imbalances and a disarticulated domestic economy careening from one economic crisis to the next, will depend on the alliances, character, composition, and political sway of their middle classes, both rural and urban, and the extent to which these forces and conditions engender strong state disciplining of capitalists and laborers in the service of national development.
GAMMA-HYDROXYBUTYRIC ACID IN THE TREATMENT OF ALCOHOL DEPENDENCE (1992)

*“Bernard B. Brodie” Department of Neuroscience, University of Cagliari, Cagliari, Italy; **Drug Abuse Unit, USSL 21, Padova, Italy.
Antivascular Endothelial Growth Factor in Diabetic Retinopathy (2010)

Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) represent the most common causes of vision loss in patients affected by diabetes mellitus. Diabetic retinopathy (DR) needs special attention because of its high public health impact and impact on quality of life of patients. Actually, laser retinal photocoagulation is the standard of care for the treatment of DR. However, laser treatment reduces the risk of moderate visual loss by approximately 50%, without a remarkable vision recovery. Thus, new approaches in the treatment of DR have been taken into account and, more specifically, the therapy employing antivascular endothelial growth factor (anti-VEGF) drugs could play a meaningful role. VEGF is a pluripotent growth factor that functions as an endothelial cell-specific mitogen and vasopermeability factor. Through these mechanisms VEGF plays a critical role in promoting angiogenesis and vascular leakage. A high level of VEGF has been detected in eyes presenting DME and PDR, and thereby VEGF is an attractive candidate as therapeutic target of pharmacological treatment in the management of DR. In the current chapter, the concepts and results of anti-VEGF therapy in the treatment of the DME and PDR are presented.
Is on‐demand sacral neuromodulation in patients with OAB syndrome a feasible therapy regime? (2011)

Possible benefits for patients could be: more autonomy, longer battery life of the implanted INS, decreasing the chance of adaptation by the nervous system.
Oncofetal Protein IMP3, a New Cancer Biomarker (2014)

IMP3 is a member of a family of RNA-binding proteins that consists of IMP1, IMP2 and IMP3. These proteins contain 2 RNA recognition motifs and 4 K-homology domains that allow them to bind RNAs strongly and specifically. IMP3 is an oncofetal protein involved in embryogenesis and its expression is associated with a number of malignant neoplasms. IMP3 is associated with aggressive and advanced cancers and is specifically expressed in malignant tumors but is not found in adjacent benign tissues. Moreover, in vitro studies have shown that IMP3 promotes tumor cell proliferation, adhesion, and invasion. This review focuses on the studies of IMP3 expression in different cancers and emphasizes the potential utility of IMP3 in routine surgical pathology practice. We also discuss IMP3 as a prognostic biomarker for cancer patients' outcomes.
Cytotoxicity of Antiviral Nucleotides Adefovir and Cidofovir Is Induced by the Expression of Human Renal Organic Anion Transporter 1 (2000)

The transport of organic anions in proximal convoluted tubules plays an essential role in the active secretion of a variety of small molecules by the kidney. In addition to other anionic substrates, the human renal organic anion transporter 1 (hOATI) is capable of transporting the nucleotide analogs adefovir and cidofovir. To investigate the involvement of hOATI in the mechanism of nephrotoxicity associated with these two clinically important antiviral agents, Chinese hamster ovary (CHO) cells were stably transfected with hOATI cDNA. The resulting CHOhOAT cells showed probenecid-sensitive and pH-dependent uptake of p-aminohippurate (Km = 15.4 FtM, V,,, ..ax = 20.6 pmol/106 cells min), a prototypical organic anion substrate. In addition, the stably expressed hOATI mediated efficient transport of adefovir (Km, = 23.8 tLM, V, a,, = 46.0 pmol/106 cells min) and cidofovir (K, = 58.0 /iM, Vt,ax = 103 pmol/106 cells * min) such that the levels of intracellular metabolites of both nucleotides were > 1 00-fold higher in CHOh OAT cells than in parental CHO. Consequently, adefovir and cidofovir were approximately 500-fold and 400-fold more cytotoxic, respectively, in CHOh OAT cells compared to CHO. The cytotoxicity of both drugs in CHOh OAT cells was markedly reduced in the presence of hOATI inhibitors. The cyclic prodrug of cidofovir, which exhibits reduced in vivo nephrotoxicity, was a poor substrate for hOATI and showed only marginally increased cytotoxicity in CHOh OAT cells. In conclusion, these studies demonstrate that hOATI plays a critical role in the organ-specific toxicity of adefovir and cidofovir, and indicates that CHOh OAT cells may represent a useful in vitro model to investigate the potential nephrotoxicity of clinically relevant organic anion agents.
Complement genetics, deficiencies, and disease associations (2012)

The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.
Genetic Transformation Systems in Insects (2001)

The past 5 years have witnessed the emergence of techniques that permit the stable genetic transformation of a number of non-drosophilid insect species. These transposable-element-based strategies, together with virus-based techniques that allow the expression of genes to be quickly examined in insects, provide insect scientists with a first generation of genetic tools that can begin to be harnessed to further increase our understanding of gene function and regulation in insects. We review and compare the characteristics of these gene transfer systems and conclude that, although significant progress has been made, these systems still do not meet the requirements of robust genetic tools. We also review risk assessment issues arising from the generation and probable release of genetically engineered insects.
Increased levels of KL‐6 and subsequent mortality in patients with interstitial lung diseases (2006)

Elevated KL-6 level may provide simple, yet valuable information by which to identify patients with ILDs who are at increased risk for subsequent mortality.
A 1.4 GHz differential low-noise CMOS frequency synthesizer using a wideband PLL architecture (2002)

The growing importance of wireless media for voice and data communications is driving a need for higher integration in personal communications transceivers to achieve lower cost, smaller form factor, and lower power dissipation. One approach to this problem is to integrate the RF functionality in low-cost CMOS technology together with the baseband transceiver functions. This in turn requires integration of the frequency synthesizer with enough isolation from supply noise to allow it to coexist with other on-chip transceiver circuitry and still meet the phase noise performance requirements of the application. This differential synthesizer for block-down-convert receivers achieves improved levels of phase noise and supply rejection performance through the use of fully-differential architecture and a wide-bandwidth PLL.
Design and synthesis of novel FKBP inhibitors (1992)

Small molecule FKBP inhibitors were prepared with inhibitory activity ranging from micromolar to nanomolar. The design of these inhibitors derives from a structural analysis of the substrates for FKBP and cyclophilin. As a consequence of this analysis two key observations were made, namely: (1) amino ketone moieties are suitable as FKBP recognition elements at the P1-P1' site and (2) the P3'-P4' site will accept a trans-olefin as a suitable mimetic of a peptide moiety. The preparation of these non-peptide inhibitors is readily accomplished by a protocol which includes the synthesis of chiral propargylic amines and their subsequent conversion into vinyl zirconium reagents.
Comparison of an inflammation-based prognostic score (GPS) with performance status (ECOG) in patients receiving platinum-based chemotherapy for inoperable non-small-cell lung cancer (2004)

The value of an inflammation-based prognostic score (GPS) was compared with performance status (ECOG) in patients (n=109) receiving platinum-based chemotherapy for inoperable non-small-cell lung cancer. On multivariate analysis with ECOG, white cell count and the GPS entered as covariates, only the GPS was a significant independent predictor of survival (HR 1.88, 95% CI 1.25-2.84, P=0.002).
Role of myristoylation and N-terminal basic residues in membrane association of the human immunodeficiency virus type 1 Nef protein (2006)

Human immunodeficiency virus type 1 Nef protein is N-terminally myristoylated, a modification reported to be required for the association of Nef with cytoplasmic membranes. As myristate alone is not sufficient to anchor a protein stably into a membrane, it has been suggested that N-terminal basic residues contribute to Nef membrane association via electrostatic interactions with acidic phospholipids. Here, data are presented pertaining to the role of the myristate and basic residues in Nef membrane association, subcellular localization and function. Firstly, by using a biochemical assay for membrane association it was shown that, whereas myristoylation of Nef was not essential, mutation of a cluster of four arginines between residues 17 and 22 reduced membrane association dramatically. Mutation of two lysines at residues 4 and 7 had negligible effect alone, but when combined with the arginine substitutions, abrogated membrane association completely. By using indirect immunofluorescence, it was demonstrated that mutation of either of the two basic clusters altered the subcellular distribution of Nef dramatically. Thirdly, the requirement of the arginine and lysine clusters for Nef-mediated CD4 down modulation was shown to correlate precisely with membrane association. These data suggest that membrane localization and subcellular targeting of Nef are controlled by a complex interplay of signals at the N terminus of the protein.
HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients (2005)

In non-small-cell lung cancer (NSCLC), sensitivity to tyrosine kinase inhibitors (TKIs) is associated with activating mutations and genomic gain of the epidermal growth factor receptor (EGFR). Preclinical data suggested that HER3 overexpression increases sensitivity to TKIs. A total of 82 NSCLC patients treated with gefitinib (250 mg), and previously evaluated for EGFR and HER2 status by fluorescence in situ hybridisation (FISH) and DNA sequencing, and for Phospho-Akt status by immunohistochemistry, were investigated for HER3 genomic gain by FISH. Patients with high polysomy and gene amplification were considered as HER3 FISH positive (+). HER3 FISH+ pattern was significantly associated with female gender (P=0.02) and never smoking history (P=0.02). Patients with HER3+ tumours (26.8%) had a significantly longer time to progression (3.7 vs 2.7, P=0.04) than patients with HER3- tumours, but not a significantly better response rate or survival. Patients with EGFR+/HER3+ tumours had higher objective response rate (36.4 vs 9.9%, P=0.03) and time to progression (7.7 vs 2.7 months, P=0.03) than patients with EGFR- and/or HER3- tumours, but no significantly longer survival. No difference in response was observed according to HER3 status in patients with EGFR+ tumours. Patients with HER2+/HER3+ tumours had similar outcome as patients with HER2- and/or HER3- tumours. Significantly different clinical end points were not observed between patients with HER3+/P-Akt+ and HER3- and/or P-Akt- tumours. Genomic gain for HER3 is not a marker for response or resistance to TKI therapy in advanced NSCLC patients.
Mechanisms for steep pulse irreversible electroporation technology to kill human large cell lung cancer cells L9981. (2014)

To explore the mechanisms for steep pulse irreversible electroporation technology to kill the lung cancer cell L9981. The apoptosis, cells mitochondrial membrane potential, internal PH changes and the intra-cellular calcium ions concentration were detected after steep pulses acted on the human large cell lung cancer cell L9981. Apoptosis test results indicated that cancer cells mainly experienced necrosis and apoptosis. Along with the increase of electric parameters, the proportion of the necrotic cells increased rapidly; the detection of cells mitochondrial membrane potential indicated that membrane potential occurred depolarization. Steep pulse can cause cancer cells to produce death and apoptosis .The PH value indicated that intracellular PH level down jumped. Internal PH became more acidic and led to cell death. The detection of intra-cellular calcium ions concentration showed that the number of free calcium significantly increased, and this change had killing effects on cell death and apoptosis. Steep pulse could induce cell apoptosis.
BLOC-3, a Protein Complex Containing the Hermansky-Pudlak Syndrome Gene Products HPS1 and HPS4 (2003)

The Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by defective lysosome-related organelles. HPS results from mutations in either one of six human genes named HPS1 to HPS6, most of which encode proteins of unknown function. Here we report that the human HPS1 and HPS4 proteins are part of a complex named BLOC-3 (for biogenesis of lysosome-related organelles complex 3). Co-immunoprecipitation experiments demonstrated that epitope-tagged and endogenous HPS1 and HPS4 proteins assemble with each other in vivo. The HPS1.HPS4 complex is predominantly cytosolic, with a small amount being peripherally associated with membranes. Size exclusion chromatography and sedimentation velocity analyses of the cytosolic fraction indicate that HPS1 and HPS4 form a moderately asymmetric protein complex with a molecular mass of approximately 175 kDa. HPS4-deficient fibroblasts from light ear mice display normal distribution and trafficking of the lysosomal membrane protein, Lamp-2, in contrast to fibroblasts from AP-3-deficient pearl mice (HPS2), which exhibit increased trafficking of this lysosomal protein via the plasma membrane. Similarly, light ear fibroblasts display an apparently normal accumulation of Zn2+ in intracellular vesicles, unlike pearl fibroblasts, which exhibit a decreased intracellular Zn2+ storage. Taken together, these observations demonstrate that the HPS1 and HPS4 proteins are components of a cytosolic complex that is involved in the biogenesis of lysosomal-related organelles by a mechanism distinct from that operated by AP-3 complex.
Improving the performance of industrial ethanol‐producing yeast by expressing the aspartyl protease on the cell surface (2010)

The yeasts used in fuel ethanol manufacture are unable to metabolize soluble proteins. The PEP4 gene, encoding a vacuolar aspartyl protease in Saccharomyces cerevisiae, was either secretively or cell-surface anchored expressed in industrial ethanol-producing S. cerevisiae. The obtained recombinant strains APA (expressing the protease secretively) and APB (expressing the protease on the cell wall) were studied under ethanol fermentation conditions in feed barley cultures. The effects of expression of the protease on product formation, growth and cell protein content were measured. The biomass yield of the wild-type was clearly lower than that of the recombinant strains (0.578 ± 0.12 g biomass/g glucose for APA and 0.582 ± 0.08 g biomass/g glucose for APB). In addition, nearly 98-99% of the theoretical maximum level of ethanol yield was achieved (relative to the amount of substrate consumed) for the recombinant strains, while limiting the nitrogen source resulted in dissatisfactory fermentation for the wild-type and more than 30 g/l residual sugar was detected at the end of fermentation. In addition, higher growth rate, viability and lower yields of byproducts such as glycerol and pyruvic acid for recombinant strains were observed. Expressing acid protease can be expected to lead to a significant increase in ethanol productivity.
Phage Response to CRISPR-Encoded Resistance in Streptococcus thermophilus (2007)

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated genes are linked to a mechanism of acquired resistance against bacteriophages. Bacteria can integrate short stretches of phage-derived sequences (spacers) within CRISPR loci to become phage resistant. In this study, we further characterized the efficiency of CRISPR1 as a phage resistance mechanism in Streptococcus thermophilus. First, we show that CRISPR1 is distinct from previously known phage defense systems and is effective against the two main groups of S. thermophilus phages. Analyses of 30 bacteriophage-insensitive mutants of S. thermophilus indicate that the addition of one new spacer in CRISPR1 is the most frequent outcome of a phage challenge and that the iterative addition of spacers increases the overall phage resistance of the host. The added new spacers have a size of between 29 to 31 nucleotides, with 30 being by far the most frequent. Comparative analysis of 39 newly acquired spacers with the complete genomic sequences of the wild-type phages 2972, 858, and DT1 demonstrated that the newly added spacer must be identical to a region (named proto-spacer) in the phage genome to confer a phage resistance phenotype. Moreover, we found a CRISPR1-specific sequence (NNAGAAW) located downstream of the proto-spacer region that is important for the phage resistance phenotype. Finally, we show through the analyses of 20 mutant phages that virulent phages are rapidly evolving through single nucleotide mutations as well as deletions, in response to CRISPR1.
Phase encryption of biometrics in diffractive optical elements (1996)

A new technique for the optical encoding of images is presented. The method of generalized projections is used to design diffractive optical elements for the phase encryption of biometrics for security applications. The encryption algorithm converges rapidly, and the decryption is seen to be secure and tolerant to additive noise.
Robust Device Independent Randomness Amplification (2013)

In randomness amplification a slightly random source is used to produce an improved random source. Perhaps surprisingly, a single source of randomness cannot be amplified at all classically. However, the situation is different if one considers correlations allowed by quantum mechanics as an extra resource. Here we present a protocol that amplifies Santha-Vazirani sources arbitrarily close to deterministic into fully random sources. The protocol is device independent, depending only on the observed statistics of the devices and on the validity of the no-signaling principle between different devices. It improves previously-known protocols in two respects. First the protocol is tolerant to noise so that even noisy quantum-mechanical systems give rise to good devices for the protocol. Second it is simpler, being based on the violation of a four-party Bell inequality and on the XOR as a hash function. As a technical tool we prove a new de Finetti theorem where the subsystems are selected from a Santha-Vazirani source.
Do Extra-Platelet Sources Contribute to the Plasma Level of Thrombospondin? (1988)

Thrombospondin, a trimeric glycoprotein contained in the platelet alpha-granules, has been proposed as a marker of in vivo platelet activation. However, it is also synthesised by a range of other cells. The extraplatelet contribution to plasma levels of thrombospondin was therefore estimated by investigating the relationship between plasma thrombospondin levels and platelet count in samples from profoundly thrombocytopenic patients with marrow hypoplasia, using the platelet-specific alpha-granule protein beta-thromboglobulin as control. Serum concentrations of both proteins were highly correlated with platelet count, but while plasma beta-thromboglobulin levels and platelet count also correlated, there was no relationship between the number of platelets and thrombospondin concentrations in plasma. Serial sampling of patients recovering from bone marrow depression indicated that the plasma thrombospondin contributed by platelets is superimposed on a background concentration of at least 50 ng/ml probably derived from a non-platelet source, and plasma thrombospondin levels do not simply reflect platelet release.