gebhart/patrepeval huggingface dataset:
Local gene transfection in the cochlea (Review) (2013)

There is much interest in the potential application of vector-induced gene therapeutic approaches to several forms of hearing disorders due to the poor efficacy of existing treatments. The cochlea is an ideal site for local gene transfection due to its anatomical encapsulation and fluid flow within its ducts. However, this requires the development of novel technologies in materials science and microbial supply vectors for target gene delivery. This review focuses on the introduction of various viral and non-viral vectors as well as injection approaches to transfecting cochlear cells in vivo. Finally, the perspective of local gene therapy was discussed. Therapeutic approaches using local gene transfection may provide a means of cochlear cell and tissue protection and treatment in cases of exogenous hearing loss and endogenous disorders.
An 18-channel multifrequency laser (1996)

A multifrequency laser (MFL) is demonstrated that runs simultaneously CW on 18 channels spaced by 103 GHz. The laser emits -14.6-dBm power per wavelength channel into single-mode fiber. Each wavelength channel can be modulated at 1.24 Gb/s. The MFL exhibits a stable and reproducible optical channel spacing owing to the reproducibility of the waveguide grating router that serves as the intracavity filter element.
Mediation of Oxidative DNA Damage by Nickel(II) and Copper(II) Complexes with the N-Terminal Sequence of Human Protamine HP2 (1997)

The potential of Ni(II) and Cu(II) complexes with Arg-Thr-His-Gly-Gln-Ser-His-Tyr-Arg-Arg-Arg-His-Cys-Ser-Arg-amide (HP2(1-15)), a peptide modeling the N-terminal amino acid sequence of human protamine HP2, to mediate oxidative DNA damage was studied by measurements of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) generation from 2'-deoxyguanosine (dG) and calf thymus DNA and by formation of double-strand breaks in calf thymus DNA. The concentrations of reagents were 0.1 mM dG and the metal-HP2(1-15) complex, 1 mM H2O2, 1.5 mM DNA (per phosphate group), 100 mM phosphate buffer, pH 7.4, ambient O2. Samples were incubated at 37 degrees C for 16-24 h. The Cu(II)-HP2(1-15) complex was found to be an effective promoter of the formation of 8-oxo-dG from both dG and DNA with ambient O2 (approximately 13- and 3-fold increase versus the oxidant alone, respectively) and H2O2 (approximately 25-fold increase in either case). The Ni(II)-HP2(1-15) complex was ineffective with O2 versus 8-oxo-dG production from both substrates but markedly enhanced the attack of H2O2 on dG and DNA (approximately 5-fold increase of 8-oxo-dG production in either case). Both Cu(II)- and Ni(II)-HP2(1-15) equally promoted double-strand scission by H2O2 in calf thymus DNA. The promotion by the complexes of dG and DNA oxidation with H2O2 was accompanied by oxidative damage to the complexes themselves, consisting of decreasing contents of their His (to approximately 50% of control in either complex) and especially Tyr (down to 48% of control in Cu(II)- and 19% in Ni(II)-HP2[1-15]) residues, as well as appearance of aspartic acid, the known oxidation product of His residues in peptides (up to 22% vs Gly for Cu(II)- and 10% for Ni(II)-HP2(1-15)). The above results provide a novel chemical mechanism of Cu(II) and Ni(II) toxicity and may have wide implications for reproductive and transgenerational effects of metal exposure.
A Logic-Compatible Embedded Flash Memory for Zero-Standby Power System-on-Chips Featuring a Multi-Story High Voltage Switch and a Selective Refresh Scheme (2013)

Embedded flash memory implemented using standard I/O devices can open doors to new applications and system capabilities, as it can serve as a secure on-chip non-volatile storage for VLSI chips built in standard logic processes. For example, it is indispensable for adaptive self-healing techniques targeted for mitigating process variation and circuit aging related issues where system information must be retained during power down periods. Embedded non-volatile memory can also enable zero-standby power systems by allowing them to completely power down without losing critical data. There has been numerous device and circuit level research on high-density non-volatile memories such as flash, STT-MRAM, PRAM, and RRAM. However, only few attempts have been made to develop a cost effective moderate-density non-volatile solution using standard I/O devices. In this paper, a logic-compatible embedded flash memory that uses no special devices other than standard core and I/O transistors is demonstrated in a generic logic process having a 5 nm tunnel oxide. An overstress-free high voltage switch and a selective WL refresh scheme are employed for improved cell threshold voltage window and higher endurance cycles.
Two Nonoverlapping Domains on the Norwalk Virus Open Reading Frame 3 (ORF3) Protein Are Involved in the Formation of the Phosphorylated 35K Protein and in ORF3-Capsid Protein Interactions (2003)

Expression of the Norwalk virus open reading frame 3 (ORF3) in Spodoptera frugiperda (Sf9) cells yields two major forms, the predicted 23,000-molecular-weight (23K) form and a larger 35K form. The 23K form is able to interact with the ORF2 capsid protein and be incorporated into virus-like particles. In this paper, we provide mass spectrometry evidence that both the 23K and 35K forms are composed only of the ORF3 protein. Two-dimensional gel electrophoresis and phosphatase treatment showed that the 35K form results solely from phosphorylation and that the 35K band is composed of several different phosphorylated forms with distinct isoelectric points. Furthermore, we analyzed deletion and point mutants of the ORF3 protein. Mutants that lacked the C-terminal 33 amino acids (ORF3(1-179), ORF3(1-152), and ORF3(1-107)) no longer produced the 35K form. An N-terminal truncation mutant (ORF3(51-212)) and a site-directed mutant (ORF3(T201V)) were capable of producing the larger form, which was converted to the smaller form by treatment with protein phosphatase. These data suggest that the region between amino acids 180 and 212 is phosphorylated, and mass spectrometry showed that amino acids Arg196 to Arg211 are not phosphorylated; thus, phosphorylation of the serine-threonine-rich region from Thr181 to Ser193 must be involved in the generation of the 35K form. Studies of the interaction between the ORF2 protein and full-length and mutated ORF3 proteins showed that the full-length ORF3 protein (ORF3(FL)), ORF3(1-179), ORF3(1-152), and ORF3(51-212) interacted with the ORF2 protein, while an ORF3(1-107) protein did not. These results indicate that the region of the ORF3 protein between amino acids 108 and 152 is responsible for interaction with the ORF2 protein.
A PNP-triggered SCR with improved trigger techniques for high-speed I/O ESD protection in deep sub-micron CMOS LSIs (2005)

A PNP-triggered SCR with improved trigger techniques is proposed for high-speed I/O ESD protection. By using these techniques, a high trigger voltage, VTRIG, for latch-up immunity during normal operating conditions, together with a low trigger voltage, Vt1, during ESD stress conditions, can be realized with simple design. Moreover, I/O circuits including the ESD protection are operable at a higher voltage than an on-chip core VDD. The PNP-triggered SCR is demonstrated in our 90 nm CMOS technology, suitable trigger voltages at both conditions (VTRIG = 4.0 V@125degC/ Vt1 = 2.0 V), and good ESD performances (HBM: 3500 V/ MM: 200 V) are achieved.
Regulation of Polar Auxin Transport by AtPIN1 in Arabidopsis Vascular Tissue (1998)

Polar auxin transport controls multiple developmental processes in plants, including the formation of vascular tissue. Mutations affecting the PIN-FORMED (PIN1) gene diminish polar auxin transport in Arabidopsis thaliana inflorescence axes. The AtPIN1gene was found to encode a 67-kilodalton protein with similarity to bacterial and eukaryotic carrier proteins, and the AtPIN1 protein was detected at the basal end of auxin transport-competent cells in vascular tissue. AtPIN1 may act as a transmembrane component of the auxin efflux carrier.
Diabetes and the Mediterranean diet: a beneficial effect of oleic acid on insulin sensitivity, adipocyte glucose transport and endothelium-dependent vasoreactivity (2000)

Abnormalities in endothelial function may be associated with increased cardiovascular risk in diabetic patients. We examined the effect of an oleic-acid-rich diet on insulin resistance and endothelium-dependent vasoreactivity in type 2 diabetes. Eleven type 2 diabetic patients were changed from their usual linoleic-acid-rich diet and treated for 2 months with an oleic-acid-rich diet. Insulin-mediated glucose transport was measured in isolated adipocytes. Fatty acid composition of the adipocyte membranes was determined by gas-liquid chromatography and flow-mediated endothelium-dependent and -independent vasodilatation were measured in the superficial femoral artery at the end of each dietary period. There was a significant increase in oleic acid and a decrease in linoleic acid on the oleic-acid-rich diet (p<0.0001). Diabetic control was not different between the diets, but there was a small but significant decrease in fasting glucose/insulin on the oleic-acid-rich diet. Insulin-stimulated (1 ng/ml) glucose transport was significantly greater on the oleic- acid-rich diet (0.56+/-0.17 vs. 0.29+/-0.14 nmol/10(5) cells/3 min, p<0.0001). Endothelium-dependent flow-mediated vasodilatation (FMD) was significantly greater on the oleic-acid-rich diet (3.90+/-0.97% vs. 6.12+/-1.36% p<0.0001). There was a significant correlation between adipocyte membrane oleic/linoleic acid and insulin-mediated glucose transport (p<0.001) but no relationship between insulin-stimulated glucose transport and change in endothelium-dependent FMD. There was a significant positive correlation between adipocyte membrane oleic/linoleic acid and endothelium-dependent FMD (r=0.61, p<0.001). Change from polyunsaturated to monounsaturated diet in type 2 diabetes reduced insulin resistance and restored endothelium-dependent vasodilatation, suggesting an explanation for the anti-atherogenic benefits of a Mediterranean-type diet.
Brain Size and Folding of the Human Cerebral Cortex (2008)

During evolution, the mammalian cerebral cortex has expanded disproportionately to brain volume. As a consequence, most mammals with large brains have profusely convoluted cortices. The human cortex is a good example of this trend, however, given the large variability in human brain size, it is not clear how cortical folding varies from the smallest to the largest brains. We analyzed cortical folding in a large cohort of human subjects exhibiting a 1.7-fold variation in brain volume. We show that the same disproportionate increase of cortical surface relative to brain volume observed across species can be also observed across human brains: the largest brains can have up to 20% more surface than a scaled-up small brain. We introduce next a novel local measure of cortical folding, and we show that the correlation between cortical folding and size varies along a rostro-caudal gradient, being especially significant in the prefrontal cortex. The expansion of the cerebral cortex, and in particular that of its prefrontal region, is a major evolutionary landmark in the emergence of human cognition. Our results suggest that this may be, at least in part, a natural outcome of increasing brain size.
Influenza Pandemics of the 20th Century (2006)

Three worldwide (pandemic) outbreaks of influenza occurred in the 20th century: in 1918, 1957, and 1968. The latter 2 were in the era of modern virology and most thoroughly characterized. All 3 have been informally identified by their presumed sites of origin as Spanish, Asian, and Hong Kong influenza, respectively. They are now known to represent 3 different antigenic subtypes of influenza A virus: H1N1, H2N2, and H3N2, respectively. Not classified as true pandemics are 3 notable epidemics: a pseudopandemic in 1947 with low death rates, an epidemic in 1977 that was a pandemic in children, and an abortive epidemic of swine influenza in 1976 that was feared to have pandemic potential. Major influenza epidemics show no predictable periodicity or pattern, and all differ from one another. Evidence suggests that true pandemics with changes in hemagglutinin subtypes arise from genetic reassortment with animal influenza A viruses.
Augmented TLR9-induced Btk activation in PIR-B–deficient B-1 cells provokes excessive autoantibody production and autoimmunity (2009)

Pathogens are sensed by Toll-like receptors (TLRs) expressed in leukocytes in the innate immune system. However, excess stimulation of TLR pathways is supposed to be connected with provocation of autoimmunity. We show that paired immunoglobulin (Ig)-like receptor B (PIR-B), an immunoreceptor tyrosine-based inhibitory motif-harboring receptor for major histocompatibility class I molecules, on relatively primitive B cells, B-1 cells, suppresses TLR9 signaling via Bruton's tyrosine kinase (Btk) dephosphorylation, which leads to attenuated activation of nuclear factor kappaB p65RelA but not p38 or Erk, and blocks the production of natural IgM antibodies, including anti-IgG Fc autoantibodies, particularly rheumatoid factor. The autoantibody production in PIR-B-deficient (Pirb(-/-)) mice was further augmented in combination with the Fas(lpr) mutation, which might be linked to the development of autoimmune glomerulonephritis. These results show the critical link between TLR9-mediated sensing and a simultaneously evoked, PIR-B-mediated inhibitory circuit with a Btk intersection in B-1 cells, and suggest a novel way toward preventing pathogenic natural autoantibody production.
Effects of Methyl and Fluorine Substitution on the Metabolic Activation and Tumorigenicity of Polycyclic Aromatic Hydrocarbons (1985)

The effects of methyl and fluorine substitution on the metabolic activation and tumorigenicity of polycyclic aromatic hydrocarbons (PAH) are reviewed. The structural requirements favoring tumorigenicity of methylated PAH are a bay region methyl group and a free peri position, both adjacent to an unsubstituted angular ring. The enhancing effect of a bay region methyl group on PAH tumorigenicity appears to be due to the relatively high reactivity with DNA and exceptional tumorigenicity of a dihydrodiol epoxide metabolite having a methyl group and epoxide ring in the same bay region. The inhibiting effect of a peri methyl substituent on tumorigenicity can be due to either the diaxial conformation of the trans dihydrodiol at the adjacent double bond, or to inhibition of dihydrodiol formation. Substitution of fluorine in the angular ring of PAH can prevent bay region dihydrodiol epoxide formation and can thereby diminish tumorigenicity. Fluorine substitution at the peri position adjacent to the angular ring also inhibits tumorigenicity, by mechanisms similar to those observed in peri-methyl substituted PAH.
The virulence gene cluster of Listeria monocytogenes is also present in Listeria ivanovii, an animal pathogen, and Listeria seeligeri, a nonpathogenic species (1994)

Most known Listeria monocytogenes virulence genes cluster within a 9.6-kb chromosomal region. This region is flanked on one end by two uncharacterized open reading frames (ORF A and ORF B) and ldh, an ORF presumably encoding the L. monocytogenes lactate dehydrogenase (J.-A. Vazquez-Boland, C. Kocks, S. Dramsi, H. Ohayon, C. Geoffroy, J. Mengaud, and P. Cossart, Infect. Immun. 60:219-230, 1992). We report here that the other end is flanked by prs, and ORF homologous to phosphoribosyl PPi synthetase genes. ORF B and prs were detected in all Listeria species and thus delimit the virulence region. This virulence gene cluster was detected exclusively in hemolytic Listeria species, Listeria ivanovii, an animal pathogen, and Listeria seeligeri, a nonpathogenic species.
Transformation of Atmospheric CO2 Catalyzed by Protic Ionic Liquids: Efficient Synthesis of 2‐Oxazolidinones (2015)

Protic ionic liquids (PILs), such as 1,8-diazabicyclo[5.4.0]-7-undecenium 2-methylimidazolide [DBUH][MIm], can catalyze the reaction of atmospheric CO2 with a broad range of propargylic amines to form the corresponding 2-oxazolidinones. The products are formed in high yields under mild, metal-free conditions. The cheaper and greener PILs can be easily recycled and reused at least five times without a decrease in the catalytic activity and selectivity. A reaction mechanism was proposed on the basis of a detailed DFT study which indicates that both the cation and anion of the PIL play key synergistic roles in accelerating the reaction.
Monoclonal antibodies specific for the outer surface protein A (OspA) of Borrelia burgdorferi prevent Lyme borreliosis in severe combined immunodeficiency (scid) mice. (1990)

We have recently shown that viable Borrelia burgdorferi organisms induce a chronic infection associated with arthritis and carditis in severe combined immunodeficiency (scid) mice but not in immunocompetent mice. The disease is similar to that found in patients suffering from Lyme disease. We now show that B. burgdorferi-specific immune mouse sera as well as a monoclonal antibody to the spirochetal outer surface antigen A (31 kDa) but not monoclonal antibodies specific for the 41-kDa antigenic component of the periplasmic flagella are able to prevent (or mitigate) the development of the disease in scid mice when passively transferred at the time of the bacterial inoculation. The identification of a B. burgdorferi-associated protective antigen suggests that the corresponding spirochetal protein should be tested as a vaccine against Lyme disease.
Purification of cell culture‐derived human influenza A virus by size‐exclusion and anion‐exchange chromatography (2006)

A process comprising of size-exclusion chromatography (SEC) and anion-exchange chromatography (AEC) was investigated for downstream processing of cell culture-derived influenza A virus. Human influenza virus A/PR/8/34 (H1N1) was propagated in serum-free medium using MDCK cells as a host. Concentrates of the virus were prepared from clarified and inactivated cell culture supernatants by cross-flow ultrafiltration as described before. SEC on Sepharose 4 FF resulted in average product yields of 85% based on hemagglutination (HA) activity. Productivity was maximized to 0.15 column volumes (cv) of concentrate per hour yielding a reduction in total protein and host cell DNA (hcDNA) to 35 and 34%, respectively. AEC on Sepharose Q XL was used to separate hcDNA from virus at a salt concentration of 0.65 M sodium chloride. Product yields >80% were achieved for loads >160 kHAU/mL of resin. The reduction in hcDNA was 67-fold. Split peak elution and bimodal particle volume distributions suggested aggregation of virions. Co-elution with hcDNA and constant amounts of hcDNA per dose indiciated association of virions to hcDNA. An overall product yield of 52% was achieved. Total protein was reduced more than 19-fold; hcDNA more than 500-fold by the process. Estimation of the dose volume from HA activity predicted a protein content at the limit for human vaccines. Reduction of hcDNA was found insufficient (about 500 ng per dose) requiring further optimization of AEC or additional purification steps. All operations were selected to be scalable and independent of the virus strain rendering the process suitable for vaccine production.
Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress (2014)

Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS) and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH), respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome.
Visible broadband, wide-angle, thin-film multilayer polarizing beam splitter (1996)

A method is described for the design of a thin-film all-dielectric polarizing beam splitter in which the transmittances for p- and s-polarized light are greater than 0.96 and less than 0.03, respectively, throughout the spectral region extending from 0.40 to 0.70 µm, and for an angular field of 12° measured in air.
Optical vernier filter with fiber grating Fabry–Perot resonators (1995)

A simple optical vernier filter with fiber grating Fabry-Perot resonators is proposed. This vernier filter comprises two isolated Fabry-Perot fiber resonators in tandem; each is formed with two parallel fiber reflection gratings. A comparison between this vernier filter and one that uses fiber (or waveguide) ring resonators is made. It is found that this vernier grating filter is simpler and usually has better output characteristics than the others.
Passive mode locking by using nonlinear polarization evolution in a polarization-maintaining erbium-doped fiber (1993)

By using a new simple cavity design, in which both linear and nonlinear polarization evolution are reproducibly controlled, we demonstrate passive mode locking in a Fabry–Perot-type erbium fiber laser. The laser generates stable trains of pulses as short as 200 fs with an energy content of 70 pJ at repetition rates as high as 100 MHz.
Integrating the spare parts supply chain: an inter‐disciplinary account (2010)

Purpose This paper aims to substantiate the need for additional research into a more holistic and multidisciplinary approach to managing the supporting supply chains that may also capture contextual information, also pointing out emerging avenues for further scholarly contributions. Design/methodology/approach The supply chain is viewed from a spare part consumer as well as from a supplier perspective. Key to the discussion is an accurate description of the maintenance demand pattern (MDP) known at the consumer's side as a valuable information source for the entire supply chain. Findings Solving the spare parts supply chain puzzle exceeds the realms of a single scientific discipline and involves hard and soft sciences. Besides, extending on the quantitative modelling aspects of MDPs, soft modelling and analysis is needed to define cooperative settings in which the supply chain parties can operate effectively. Practical implications In this paper, the authors argue for the sharing of the appropriately balanced combination of quantitative and qualitative information that is currently hidden, or exists in isolation, within supply chains. Debatably, such information sharing may potentially generate substantial benefits for all “players” within a given supply chain. Originality/value This contribution is unique in the sense that it provides a most accurate characterization of MDPs based on the proven maintenance concept design theory. In addition, the supply chain problem is analysed in a realistic context, with an open and broad mindset rather than approaching this issue from a single hard science perspective.