gebhart/patrepeval huggingface dataset:
Transport Phenomena That Control Electroplated Copper Filling of Submicron Vias and Trenches (1999)

Scaling analysis and finite element modeling of the governing transport equations are used to show that in the submicron features of damascene ultralarge scale integrated interconnect structures, diffusion of cupric ion and trace additives is the only transport process that affects plating uniformity. Potential variations in solution or in the metal film, while important on wafer (dm) length scales, are completely negligible on feature (μm) length scales. Convection is also unimportant in submicron features. As a result, changes in process parameters such as fluid flow rate, barrier film conductivity or thickness, or solution conductivity are unlikely to result in significant changes in plating uniformity or void formation inside trenches and vias. On the other hand, changes in plating current density, feature geometry, or additive concentration in the plating bath will have a large impact on filling profiles. The impact of diffusive limitations on feature filling is described by a dimensionless parameter . Low values of indicate that for typical damascene structures and plating conditions, cupric ion depletion is only on the order of a few percent, indicating that copper plating is essentially conformal. Only very deep or high‐aspect features will pinch off as a result of cupric ion depletion. For additives that are depleted at the metal surface, values of can be large, indicating the potential for substantial additive depletion inside trenches and vias. scales with . As a result, deeper features (larger L) plate less uniformly, as do more narrow features (smaller w). However, if aspect ratios (L/w) are held constant as critical dimensions decrease, beneficial effects of additive depletion will diminish in future device generations. © 1999 The Electrochemical Society. All rights reserved.
Mechanism of Prebeta-HDL Formation and Activation (2006)

The mechanism of formation of functional high-density lipoprotein (HDL) from secreted lipid-free apolipoprotein A1 (apo A1) was determined using human liver-derived (HepG2) cells, human intestine-derived (CaCO2) cells, and CHO cells stably expressing full-length human apo A1 (CHO-A1 cells). In each cell line, a significant proportion of secreted apo A1 had a Stokes radius of 2.6 nm and was inactive in binding phospholipids (PL) or free cholesterol (FC). Extracellularly, in a reaction dependent on membrane transporter ABCA1, prealpha-migrating 2.6 nm apo A1 was converted to a prebeta-migrating product that was able to bind PL. Both forms were reactive with mAb55201, a monoclonal antibody specific for native plasma lipid-poor (prebeta1) HDL [Nakamura, Y., et al. (2004) Biochemistry 43, 14311-14318]. The physical properties of precursor and product apo A1 suggested that both are monomers, with Stokes radii of 2.6 and 3.6 nm, respectively, consistent with the absence of intermolecular cross-linking of apo A1 in lipid-poor HDL, reported previously. Product but not precursor apo A1 promoted reverse cholesterol transport (RCT) from human aortic smooth muscle cells. These studies suggest an important contribution of secreted lipid-free apo A1 to HDL formation.
Food and Globalization (2006)

This review takes two key approaches for exploring the theme of food and globalization: first, how food has been mobilized as a commodity in global production and trade systems and governed through global institutions; and second, how the idea of globalization has been nourished through food, particularly with the mobility of people and of ideas about cuisine and nutrition. Stark global inequalities are also noted, and the review calls for attention to policy-based research and to the analytical connections between governance, food politics, and food citizenship in future studies.
Sequence organization and transcription at two heat shock loci in Drosophila. (1978)

The heat shock loci of Drosophila melanogaster chromosome subdivisions 87A and 87C have been studied by using cloned DNA. Both sites contain a number of copies of a 2,4-kilobase (kb) region homologous to mRNA for the 70,000-dalton heat shock protein. In situ hybridization to chromosomal RNA shows that transcripts of this sequence accumulate at both sites after temperature elevation. At 87C there is a 1.5-kb repeated sequence homologous to another heat shock RNA. One cloned segment includes two to three tandem copies of this sequence located 0.8 kb from the beginning of a 2.4-kb message region. RNA complementary to the 1.5-kb repeat acccumulates at 87C after temperature elevation, but does not code for any known heat shock protein. In the sibling species D. simulans, there are sequences located and transcribed at 87A and 87C that are homologous to the melanogaster 2.4-kb message sequence. The 1.5-kb repeat, however, is absent from 87C in simulans and no heat shock RNA homologous to it can be detected.
Viral Etiology for Parkinson's Disease (1999)

Some clinical reports and epidemiological data suggest that a virus may play a role in the etiology of Parkinson's disease (PD). Once a certain strain of influenza A virus has adapted to the central nervous system, it will gain infectivity to neurons, especially in the substantia nigra, cerebellum and hippocampus, both in human cases and experimental models. Although efforts to detect virus particles in the brains, or antibodies in the serum or cerebrospinal fluid of patients with PD have been generally unsuccessful, recent immunohistochemical work has revealed the presence of complement proteins and the interferon-induced MxA in association with Lewy bodies and swollen neuronal process. We propose a hypothesis that neurovirulent influenza A virus and other potent viruses may be responsible for the formation of Lewy bodies and the later death of nigral neurons, to constitute a viral etiology for PD.
Estimation of boundary value processes applied to shape determination of a circular antenna from observations on the boundary (2002)

An estimation algorithm for shape determination of a circular antenna is described. A space-based antenna would require light-weight materials, making it difficult to place sensors in the interior of the antenna. Hence, sensors on the outer rim are considered. Due to its rapid dynamics, the antenna achieves an equilibrium shape quickly. Therefore, static models for the antenna shape are considered. The antenna deformations are modeled as elliptic stochastic partial differential equations (PDEs) with boundary conditions that describe a noncausal system. A smoothing algorithm is developed for antenna shape estimation using a homogenized antenna model, described by a single PDE. Approximate Green functions used in the smoother are calculated, and digital simulation methods can be applied.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Pulmonary Administration of Interferon Beta-1a-Fc Fusion Protein in Non-Human Primates Using an Immunoglobulin Transport Pathway (2011)

Currently, products containing interferon beta (IFNβ) are injected either intramuscularly or subcutaneously. To avoid the necessity of injection, we developed a novel monomeric Fc fusion protein of IFNβ (IFNβFc) that is absorbed via an immunoglobulin transport system present in the upper and central airways upon administration of the drug as an inhaled aerosol. The systemic absorption of IFNβFc through the lung in non-human primates, at deposited doses of 1, 3, and 10 μg/kg, was compared to the absorption of a single 3 μg/kg dose of IFNβ-1a (Avonex®) subcutaneously administered. IFNβFc was well absorbed through the lung, displaying dose proportional increases in serum concentrations, and was biologically active, as shown by increases in plasma neopterin levels. The circulating half-life of IFNβFc was ∼3 times longer (∼30 h) than that of IFNβ-1a, (8-9 h). At approximately equimolar doses of IFNβFc (10 μg/kg) and IFNβ-1a (3 μg/kg), the stimulation of neopterin over background levels was approximately equivalent, demonstrating that the longer half-life of IFNβFc compensated for the lower relative specific antiviral activity of IFNβFc measured in vitro. In conclusion, IFNβFc was efficiently absorbed after pulmonary delivery in non-human primates, retained its biological activity, and may offer a convenient alternative to injectable IFNβ.
Emergence and genetic evolution of HIV-1 variants with mutations conferring resistance to multiple reverse transcriptase and protease inhibitors (1999)

The emergence of genotypic resistance in protease and reverse transcriptase (RT) gene regions was longitudinally evaluated in plasma samples from a group of 12 HIV-1-infected patients treated with different combination of antiretroviral therapies and selected on the basis of their clinical failure. Complex mutational patterns in the reverse transcriptase gene were observed. In particular, combinations of AZT (41L, 67N, 70R, 210W, and 219Q/E) and 3TC (184M) were seen in 10 patients. Two patients presented codon 151 multinucleoside analogue resistance (MNR). Additionally, seven patients harbored RT nonnucleoside analogue-related resistance substitutions (98G, 103N, and 181C). Multiple protease-selected mutations were found in each patient with an average of six substitutions per patient, with 10I/F/V, 63P, 71V, 82A/T, 84V, and 90M being the most prevalent substitutions. Overall, these results showed that for most patients virological failure was coupled with detectable genotypic resistance. Furthermore, most patients exhibited genotypic resistance to almost all available anti-HIV-1 drugs. The high viral loads found in most patients at the end of the study suggest that the replication of these multidrug resistant viruses are not severely compromised. Phylogenetic analysis of these pol sequences revealed that a specific HIV-1 genotype prone to develop multidrug resistance was not found.
CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings (2014)

Our findings indicate that CNS clinical involvement occurs in ATTR-V30M patients regardless of LT. Longer disease duration after LT can provide the necessary time for transthyretin amyloidosis to progress until it becomes clinically relevant. Highly sensitive imaging methods are needed to identify and monitor brain ATTR. Disease modifying therapies should consider brain TTR as a target.
Structural Analysis of Arabidopsis thaliana Chromosome 5. VII. Sequence Features of the Regions of 1,013,767 bp Covered by Sixteen Physically assigned P1 and TAC Clones (1998)

Sixteen PI and TAC clones assigned to Arabidopsis thaliana chromosome 5 were sequenced, and their sequence features were analyzed using various computer programs. The total length of the sequences determined was 1,013,767 bp. Together with the nucleotide sequences of 109 clones previously reported, the regions of chromosome 5 sequenced so far now total 9,072,622 bp, which presumably covers approximately one-third of the chromosome. A similarity search against the reported gene sequences predicted the presence of a total of 225 protein-coding genes and/or gene segments in the newly sequenced regions, indicating an average gene density of one gene per 4.5 kb. Introns were identified in 72.4% of the potential protein genes for which the entire gene structure was predicted, and the average number per gene and the average length of the introns were 3.3 and 163 bp, respectively. These sequence features are essentially identical to those in the previously reported sequences. The sequence data and gene information are available on the World Wide Web database KAOS (Kazusa Arabidopsis data Opening Site) at http://www.kazusa.or.jp/arabi/.
Overexpression of the met/HGF receptor in renal cell carcinomas (1996)

The c-met oncogene encodes the receptor for hepatocyte growth factor/scatter factor (HGF/SF), a multifunctional cytokine able to mediate morphogenesis as well as mitogenesis, motogenesis and invasiveness of epithelial cells. HGF/SF has been implicated in branching tubulogenesis of the developing kidney and in regeneration after renal injury and nephrectomy. We have examined the expression of the met/HGF receptor in normal human kidney and tissues of the genito-urinary tract, and in 50 kidney neoplasms of different histotypes, using monoclonal antibodies (MAbs) against the met/HGF receptor and immunohistochemistry. In normal kidneys, weak staining restricted to the distal tubules was observed. Transitional cell carcinomas were consistently negative, whereas increased expression at various levels was found in 87% of renal cell carcinomas with different cytological features and histological patterns. Western blot analysis of samples showed that the met/HGF receptor found in the malignant cells exhibits features of the normal receptor. The met/HGF receptor is also overexpressed in a renal cell carcinoma cell line, whose motility is triggered by HGF/SF. Our data suggest that expression of the met/HGF receptor may be involved in the onset and progression of renal cell carcinomas.
Controlled Study in Diabetic Children Comparing Insulin-Dosage Adjustment by Manual and Computer Algorithms (1990)

A controlled trial of a new microprocessor device for insulin-dosage adjustment was undertaken in two matched groups of a priori well-controlled diabetic children. A prospective study design with three equal 8-wk periods was used. In the first period, both groups used manual methods for insulin-dosage adjustment after manual criteria. In the second period, one group of children adjusted insulin dosage by computer algorithms, whereas the other continued to use manual methods. In the third period, both groups again adjusted insulin by traditional methods. Mean premeal glycemia and glycosylated hemoglobin levels did not change in either group throughout the study. During the second period, episodes of hypoglycemia were more frequent in children without the computer than in those who used the device. In keeping with the latter outcome, the group that used the microprocessor device was given less insulin in the second period than the first (0.88 +/- 0.02 vs. 0.94 +/- 0.02 U.kg-1.day-1, P less than 0.0001) and in comparison to the control group of patients who concurrently were given an increased insulin dose in the second period compared with the first. This study showed that insulin treatment through specific computer-mediated dosage-adjusting algorithms was safe and minimized hypoglycemia by effectively accommodating seasonally changing insulin requirements. We recommend the device to help diabetic children and their families in the care of insulin-dependent diabetes.
Exon-specific RNAi: A tool for dissecting the functional relevance of alternative splicing (2002)

The goal of functional genomics is to determine the function of each protein encoded by an organism. Typically, this is done by inactivating individual genes and, subsequently, analyzing the phenotype of the modified organisms. In higher eukaryotes, where a tremendous amount of alternative splicing occurs, such approaches are not feasible because they have the potential to simultaneously affect multiple proteins that could have quite distinct and important functions. Thus, it is necessary to develop techniques that inactivate only a subset of proteins synthesized from genes encoding alternatively spliced mRNAs. Here we demonstrate that RNA interference (RNAi) can be used to selectively degrade specific alternatively spliced mRNA isoforms in cultured Drosophila cells. This is achieved by treating the cells with double-stranded RNA corresponding to an alternatively spliced exon. This technique may prove to be a powerful tool to assess the function of proteins synthesized from alternatively spliced mRNAs. In addition, these results have implications regarding the mechanism of RNAi in Drosophila.
Flight control of a spin stabilised axi-symmetric disc-wing (2001)

A review of air-vehicles with circular planform ie discwings includes examples of mid-20 th century innovation and recent developments in UAV (unnamed air vehicle) technology. A spin stabilised axi-symmetric disc-wing has potential application as a highly manoeuvrable, unpowered unmanned air vehicle or guided projectile. This paper considers the means by which aerodynamic control moments can be generated on such a disc-wing. The present experimental investigation outlines the aerodynamics of a spin stabilised axi-symmetric discwing and documents the aerodynamic differences of a disc-wing with forced transition strips installed on the disc rim. It is proposed that these differences are achievable by a similar active flow control method such as active turbulent strips, vortex generators or synthetic (massless) jets as a means to aerodynamic control of the disc in flight. A simple analysis of disc-wing flight manoeuvres predicts the turning radius and time period of a 90° banked turn based on experimental data. Nomenclature
DEco‐TILLING: an inexpensive method for single nucleotide polymorphism discovery that reduces ascertainment bias (2007)

Abstract Genetic markers that measure DNA variation are important for population genetics research, resource management and other applications. Single nucleotide polymorphisms (SNP) are becoming a popular marker because they are abundant and because rapid and efficient assays can be developed to detect them. However, with the exception of a few organisms, most species have little DNA sequence information available and relatively few SNPs have been developed for species that lack sequence data. Methods to find SNPs can be expensive and incorporate substantial ascertainment bias, which may result in failure to discover SNPs that are useful or efficient for addressing specific questions. We have developed a system to detect SNPs that we call DEco‐TILLING, which is derived from Eco‐TILLING (targeting induced local lesions in genomes). The DEco‐TILLING method facilitates the development of useful genotyping assays rapidly and inexpensively and can reduce ascertainment bias.
Single-chain mono- and bispecific antibody derivatives with novel biological properties and antitumour activity from a COS cell transient expression system. (1994)

Single-chain antibody molecules were expressed from modified eukaryotic expression vectors as individual protein domains encoded on interchangeable cDNA cassettes. Two different single-chain antibody derivatives were constructed by linking individual light- and heavy-chain variable domains. The first was specific for the L6 tumour-associated antigen and the second was specific for human CD3. Each single-chain variable domain was genetically fused with an Fc 'tag' and expressed as a fusion protein in a COS cell transient transfection system. These single-chain antibody derivatives demonstrated specific binding to cells expressing appropriate antigen and bound with affinities similar to native antibody. The CD3 single chain molecule mediated stronger activation of PLC gamma 1 and similar levels of T-cell proliferation compared with native antibody. A bispecific Fv single-chain cassette was created by fusing the expression cassettes encoding the binding domains for L6 and CD3 single-chain molecules using oligonucleotide primers encoding a short 27-residue 'helical' peptide linker. The CD3-L6 variable domains were fused to the Fc tag and expressed in COS cells. The CD3-L6FvIg bispecific fusion protein mediated adhesion between T cells and L6-positive tumour cells, and stimulated potent T-cell proliferation and cytotoxicity against tumour cells expressing the L6 antigen.
Base5, a versatile, highly integrated high-throughput methylation profiling platform for methylation specific PCR based marker identification applied to colorectal cancer (2007)

A61 Testing the methylation status of one or more genomic loci is a new principle applicable to diagnosis and prognosis of disease, as well as prediction of therapeutic response. In an attempt to increase the success rate of marker discovery work in the field of methylation a new integrated system including bioinformatics, high throughput marker testing and data analysis has been created. The newly devised ‘Base5’ system is described and proof of principle data from studies in the field of colorectal cancer are presented.  Materials and Methods:  The Base5 methylation profiling platform (Base5) currently comprises several different modules:  The first module is a set of bioinformatics tools which allow the design of Methylation Specific PCR (MSP) assays in a highly efficient way, based on any annotated or known genomic DNA sequence. With this tool 224 different MSP assays in the promoter region of 145 different genes have been newly designed. In addition to these new candidates, several already known methylation markers for colorectal cancer were included in a “design list”. This list was used for manufacturing high throughput arrays capable of analyzing 12 different samples in parallel with all the assays of interest.  The second module of the Base5 system, a high throughput real time detection system was used to determine the methylation status of the genes processed in module 1. The equivalent of 200ng of genomic, bisulphite converted DNA from 90 samples (60 colorectal cancer samples and 30 normal colorectal tissue samples) was tested for the presence of methylated alleles.  The third module of the Base5 system was used to analyze and present the results in “methylation tables” which indicate the methylation status of each sample tested for each of the assays. Using the methylation tables, sensitivity and specificity for each gene was calculated and genes were ranked by specificity and sensitivity. In a final step, the performance of known colorectal cancer markers (CHFR, MGMT and others) included in the design was compared to the new candidate markers screened with the system.  Results:  Using the Base5 system it was possible to design 224 different MSP assays within two workdays. A total of 20160 MSP assays was performed by one technical staff within four workdays including genomic DNA isolation, bisulphite conversion, real-time detection and data interpretation.  Known methylation markers of colorectal cancer included in the list of designs were confirmed among the best performing assays. New markers, so far not associated with colorectal cancer, could be determined which perform as well or even better than the known markers, with a relatively small effort.
Structural Basis for Promoting and Preventing Decarboxylation in Glutaryl-Coenzyme A Dehydrogenases (2010)

Glutaryl-coenzyme A dehydrogenases (GDHs) involved in amino acid degradation were thought to catalyze both the dehydrogenation and decarboxylation of glutaryl-coenzyme A to crotonyl-coenzyme A and CO(2). Recently, a structurally related but nondecarboxylating, glutaconyl-coenzyme A-forming GDH was characterized in the obligately anaerobic bacteria Desulfococcus multivorans (GDH(Des)) which conserves the free energy of decarboxylation by a Na(+)-pumping glutaconyl-coenzyme A decarboxylase. To understand the distinct catalytic behavior of the two GDH types on an atomic basis, we determined the crystal structure of GDH(Des) with and without glutaconyl-coenzyme A bound at 2.05 and 2.1 A resolution, respectively. The decarboxylating and nondecarboxylating capabilities are provided by complex structural changes around the glutaconyl carboxylate group, the key factor being a Tyr --> Val exchange strictly conserved between the two GDH types. As a result, the interaction between the glutaconyl carboxylate and the guanidinium group of a conserved arginine is stronger in GDH(Des) (short and planar bidentate hydrogen bond) than in the decarboxylating human GDH (longer and monodentate hydrogen bond), which is corroborated by molecular dynamics studies. The identified structural changes prevent decarboxylation (i) by strengthening the C4-C5 bond of glutaconyl-coenzyme A, (ii) by reducing the leaving group potential of CO(2), and (iii) by increasing the distance between the C4 atom (negatively charged in the dienolate transition state) and the adjacent glutamic acid.