gebhart/patrepeval huggingface dataset:
A wafer-scale digital integrator using restructurable VSLI (1985)

Wafer-scale integration has been demonstrated by fabricating a digital integrator on a monolithic 20-cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> silicon chip, the first laser-restructured digital logic system. Large-area integration is accomplished by laser programming of metal interconnect for defect avoidance. This paper describes the technology for laser welding and cutting, the design methodology and CAD tools developed for wafer-scale integration, and the integrator itself.
N-Terminal Mutant Huntingtin Associates with Mitochondria and Impairs Mitochondrial Trafficking (2008)

Huntington's disease (HD) is caused by polyglutamine (polyQ) expansion in huntingtin (htt), a large (350 kDa) protein that localizes predominantly to the cytoplasm. Proteolytic cleavage of mutant htt yields polyQ-containing N-terminal fragments that are prone to misfolding and aggregation. Disease progression in HD transgenic models correlates with age-related accumulation of soluble and aggregated forms of N-terminal mutant htt fragments, suggesting that multiple forms of mutant htt are involved in the selective neurodegeneration in HD. Although mitochondrial dysfunction is implicated in the pathogenesis of HD, it remains unclear which forms of cytoplasmic mutant htt associate with mitochondria to affect their function. Here we demonstrate that specific N-terminal mutant htt fragments associate with mitochondria in Hdh(CAG)150 knock-in mouse brain and that this association increases with age. The interaction between soluble N-terminal mutant htt and mitochondria interferes with the in vitro association of microtubule-based transport proteins with mitochondria. Mutant htt reduces the distribution and transport rate of mitochondria in the processes of cultured neuronal cells. Reduced ATP level was also found in the synaptosomal fraction isolated from Hdh(CAG)150 knock-in mouse brain. These findings suggest that specific N-terminal mutant htt fragments, before the formation of aggregates, can impair mitochondrial function directly and that this interaction may be a novel target for therapeutic strategies in HD.
Measurement of real-time digital signals in a silicon bipolar junction transistor using a noninvasive optical probe (1986)

We report optical charge sensing of real-time 0.8 V digital signals in a silicon bipolar transistor in a 20 MHz bandwidth using a 1.3 μm semiconductor laser, and in a 100 MHz bandwidth using a 1.3 μm Nd:YAG laser. The probe is noninvasive, inducing a transistor base current of less than 10 nA.
[New drugs at the horizon for men with prostate cancer]. (2010)

Despite major progress in the understanding of biological mechanisms underlying metastatic prostate cancer, the treatment of men with advanced prostate cancer remains challenging. Several randomized controlled trials with promising or positive results are underway or just released. Here we discuss new treatments which might be used in clinic in the near future: hormonal treatments (Abiraterone and MDV3100), a new chemotherapy (Cabazitaxel), a cellular vaccine (Sipuleucel-T), anti-angiogenic drugs (Bevacizumab, Aflibercept), a new radioactive treatment (Alpharadin) and a new bone-protective agent (Deno-sumab).
Hypertensive heart disease and heart failure (1995)

Hypertension is associated with the remodeling of left ventricular geometry and abnormalities of function that may precede geometric changes. Rather than a specific disease, "hypertensive heart failure" is a spectrum of disorders that result from left ventricular geometric changes and comorbid conditions. Heart failure may present as abnormalities of diastolic or systolic function, although symptoms (dyspnea, fatigue) and physical findings (edema, rales) may be similar.
Ultrastructural changes in goat interspecies and intraspecies reconstructed early embryos (2008)

The low efficiency of somatic cell nuclear transfer may be related to the ultrastructural deviations of reconstructed embryos. The present study investigated ultrastructural differences between in vivo-produced and cloned goat embryos, including intra- and interspecies embryos. Goat ear fibroblast cells were used as donors, while the enucleated bovine and goat oocytes matured in vitro as recipients. Goat-goat (GG), goat-cattle (GC) and goat in vivo-produced embryos at the 2-cell, 4-cell, 8-cell and 16-cell stages were compared using transmission electron microscopy. These results showed that the three types of embryos had a similar tendency for mitochondrial change. Nevertheless, changes in GG embryos were more similar to changes in in vivo-produced embryos than were GC embryos, which had more extreme mitochondrial deviation. The results indicate the effects of the cytoplast on mitochondria development. The zona pellucida (ZP) in all three types of embryos became thinner and ZP pores in both GC and GG embryos showed an increased rate of development, especially for GC embryos, while in vivo-produced embryos had smooth ZP. The Golgi apparatus (Gi) and rough endoplasmic reticulum (RER) of the two reconstructed embryos became apparent at the 8-cell stage, as was found for in vivo embryos. The results showed that the excretion of reconstructed embryos was activated on time. Lipid droplets (LD) of GC and GG embryos became bigger, and congregated. In in vivo-produced embryos LD changed little in volume and dispersed gradually from the 4-cell period. The nucleolus of GC and GG embryos changed from electron dense to a fibrillo-granular meshwork at the 16-cell stage, showing that nucleus function in the reconstructed embryos was activated. The broken nuclear envelope and multiple nucleoli in one blastomere illuminated that the nucleus function of reconstructed embryos was partly changed. In addition, at a later stage in GC embryos the nuclear envelope displayed infoldings and the chromatin was concentrated, implying that the blastomeres had an obvious trend towards apoptosis. The gap junctions of the three types of embryos changed differently and GG and GC embryos had bigger perivitelline and intercellular spaces than did in vivo-produced embryos. These results are indicative of normal intercellular communication at an early stage, but this became weaker in later stages in reconstructed embryos. In conclusion, inter- and intraspecies reconstructed embryos have a similar pattern of developmental change to that of in vivo-produced embryos for ZP, rough ER, Gi and nucleolus, but differ for mitochondria, LD, vesicles, nucleus and gap junction development. In particular, the interspecies cloned embryos showed more severe destruction. These ultrastructural deviations might contribute to the compromised developmental potential of reconstructed embryos.
The effect of feeding salmon oil during pregnancy on causes of piglet deaths prior to weaning (2000)

Pre-weaning mortality is a major source of economic loss to the pig industry which despite improvements in husbandry and farrowing crate design remains about 10% of piglets borne alive. The causes of death are multi-factorial (Varley, 1995) but a large proportion may be due to low neonatal vigor. Commercial pig diets do not normally contain long chain n-3 fatty acids, a deficiency of which has been implicated in reduced visual and neural development in premature human babies and in experimental animals. The objectives of the present experiment were to quantify the causes of piglet mortality in sows of modern genotype and to determine the effects of salmon oil supplementation of the diet of the sow, providing long-chain n-3 fatty acids, on this mortality.
Pharmacodynamic study of Bay41-4109 in HBV transgenic mouse model (2011)

Objective To study the pharmacodynamics of Bay41-4109,a novel anti-HBV compound,in HBV transgenic mouse model.Methods specific pathogen frce(SPF) level TgM(HBV D1.3)mice were divided into 3 groups: Bay41-4109 group [30mg/(kg·d)],lamivudine group [30mg/(kg·d)] and vehicle group(0.5% sodium carboxymethycellulose),with 32 in each.Antiviral effect of Bay41-4109 was tested in HBV transgenic mice including the analysis of HBcAg changes in liver tissue by immunohistochemistry,and changes in HBV DNA in liver and serum by quantitative real time PCR analysis.Serum transaminase(ALT and AST) and body weight were assayed to evaluate the safety of the compound.Results Oral Bay41-4109 significantly reduced the number of HBV core antigen(HBcAg) positive cell nucleus,average area of HBcAg positive cell nucleus and the rate of OD compared with vehicle group after 50 days treatment(P 0.05).However,Bay41-4109 could not significantly reduce HBV-specific DNA in HBV transgenic mice,both in liver and plasma.No significant impact was found on ALT,AST and body weigh of Bay41-4109-treated mice.Conclusions Bay41-4109 can more effectively reduce cytoplasmic HBcAg in liver sections than lamivudine.It is suggested that Bay41-4109,a different mode of action from lamivudine,represents a promising anti-HBV drug candidate with good antiviral effect and safety.
Über einige Abkömmlinge des 2.4.6‐Kollidins und des 2.4‐Lutidins (1955)

Abstract Bei der katalytischen Oxydation des 2.4.6‐Kollidins und des 2.4‐Lutidins mit Luft in der Gasphase ließen sich fast alle Stufen der Umwandlung der Methyl‐ in Aldehydgruppen verwirklichen. Die entstandenen Aldehyde wurden zum Konstitutionsbeweis in die Carbonsäuren übergeführt. Hierbei wurden die Angaben über die Eigenschaften einiger spärlich beschriebener Carbonsäuren präzisiert und eine Dimethyl‐isonicotinsäure aufgefunden.
Cortical network from human embryonic stem cells (2011)

The connection of embryonic stem cell technology and developmental biology provides valuable tools to decipher the mechanisms underlying human brain development and diseases, especially among neuronal populations, that are not readily available in primary cultures. It is obviously the case of neurons forming the human cerebral cortex. In the images that are presented, the neurons were generated in vitro from human embryonic stem cells via forebrain-like progenitors. Maintained in culture for prolonged time, they acquired a mainly glutamatergic phenotype and morphological characteristics of cortical pyramidal neurons, including dendritic spines, and formed spectacular networks.
Multiple Low-Dose Challenges in a Rhesus Macaque AIDS Vaccine Trial Result in an Evolving Host Response That Affects Protective Outcome (2014)

Using whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque AIDS vaccine trial. Samples were collected from animals prior to and after vaccination with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig loaded with simian immunodeficiency virus (SIV) peptides, either alone or in combination with a SIV-gp120 protein boost. Additional samples were collected following multiple low-dose rectal challenges with SIVmac251. Animals in the boosted group had a 73% reduced risk of infection. Surprisingly, few changes in gene expression were observed during the vaccination phase. Focusing on postchallenge comparisons, in particular for protected animals, we identified a host response signature of protection comprised of strong interferon signaling after the first challenge, which then largely abated after further challenges. We also identified a host response signature, comprised of early macrophage-mediated inflammatory responses, in animals with undetectable viral loads 5 days after the first challenge but with unusually high viral titers after subsequent challenges. Statistical analysis showed that prime-boost vaccination significantly lowered the probability of infection in a time-consistent manner throughout several challenges. Given that humoral responses in the prime-boost group were highly significant prechallenge correlates of protection, the strong innate signaling after the first challenge suggests that interferon signaling may enhance vaccine-induced antibody responses and is an important contributor to protection from infection during repeated low-dose exposure to SIV.
Pramipexole Augmentation of a Selective Serotonin Reuptake Inhibitor in the Treatment of Depression (2000)

DeBattista, Charles DMH, MD; Solvason, H. Brent MD, PhD; Breen, Jeanne Anne Heilig MS; Schatzberg, Alan F. MD Author Information
Osmoregulation of gene expression. II. DNA sequence of the envZ gene of the ompB operon of Escherichia coli and characterization of its gene product. (1982)

The envZ gene together with the ompR gene is located in the ompB operon of Escherichia coli and is known to be responsible for the regulation of osmolarity-sensitive expression of genes for the major outer membrane proteins, OmpF and OmpC.The DNA sequence of a 1.6kilobase-pair fragment carrying the entire e n d gene was determined.Together with the DNA sequence of the ompR gene determined in the preceding paper (Wurtzel, E.
Inhibitory effect of monoclonal antibodies on Alzheimer's β-amyloid peptide aggregation (1996)

In vitro aggregation of β-amyloid peptide induced by incubating the peptide for 3 h at 37°C, was investigated via immunocomplexation with a panel of monoclonal anti-bodies raised against various β-amyloid fragments Some of these monoclonal antibodies prevented the formation of β-amyloid and this effect may be related to the localization of the antibody binding sites. Monoclonal antibodies 6C6 and 10D5, and AMY-33, which recognize epitopes spanning the amino acid residues 1–28 of β-amyloid peptide, inhibited its aggregation by 40%–90% when compared with aggregation occurring in the absence of the respective antibodies. The antibodies, 2H3 and 1C2, directed to the regions comprisingpeptides 1–12 and 13–28, respectively, had a considerably low effect. Identifying the “aggregating epitopes” as sequences that are related to the sites where protein aggregation is initiated and preparing monoclonal antibodies against these regions may facilitate the under-standing and prevention of protein aggregation processes. This study may provide a factual basis for using monoclonal antibodies to prevent the β-amyloid formation that is associated with Alzheimer's disease.
Low Detection Rate and Maternal Provenance of Hepatitis B Virus S Gene Mutants in Cases of Failed Postnatal Immunoprophylaxis in England and Wales (1997)

Hepatitis B virus (HBV) infection occurred despite full passive-active immunoprophylaxis in 20 of 321 infants born to mothers seropositive for hepatitis B e antigen. In 2 (12%) of 17 infected infants, mother-infant DNA sequence mismatches were found in a segment of the HBV S gene coding for antigenic determinants of the HBV surface antigen (HBsAg) amplified from sera by polymerase chain reaction (PCR). Point substitutions occurred in codons 120, 134, and 144 of the HBsAg polypeptide in the variant sequence of 1 infant and in codon 126 in the other; all were missense mutations. Mutant sequences could not be recovered from maternal sera by PCR cloning but were selectively generated using an amplification refractory mutation system. The frequency of potential vaccine escape mutants is therefore low, and these preexist maternally as minor variants.
The Analytical Reduction of Porphyrins to Pyrroles (1971)

When porphyrins or related pigments are reduced by HI–AcOH, their meso-substituents (R = H or alkyl) appear as α-CH 2 R groups in the resulting pyrroles. The identification of the pyrroles, as by g.l.p.c., defines and orders the meso-substituents flanking each pair of peripheral substituents in the porphyrin. If one meso-substituent differs from the others, all the substituents about the two adjacent pyrrole nuclei are then ordered.The pyrroles can be reductively alkylated in situ, and symmetry then reduces their number when the aldehyde used (R.CHO) corresponds to a bridge and its meso-substituent. This may simplify the pyrrole mixtures, identify meso-substituents, or make pyrroles distinguishable by g.l.p.c.The critical pyrrole – propionic acids are separable as methyl esters by g.l.p.c. Desoxophylloerythrin and pyrophaeophorbides (the latter first reduced with potassium borohydride) are reduced to cyclo-penteno-pyrroles which reveal the isocyclic rings and the 5-substituents. The r.r.t.'s of relevant pyrroles are reported.
Location and dynamics of anthracyclines bound to unilamellar phosphatidylcholine vesicles (1985)

We have exploited the intrinsic fluorescence properties of the anthracycline antitumor antibiotics to study the dependence on drug structure of relative drug location and dynamics when the anthracyclines were bound to sonicated dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) vesicles at 27.5 degrees C. Iodide quenching experiments at constant ionic strength were used to evaluate the relative accessibilities of the bound fluorophores to membrane-impermeable iodide. Iodide was found to quench the fluorescence of anthracyclines in free solution by both static and dynamic mechanisms, whereas quenching of membrane-bound fluorophores was predominantly due to the dynamic mechanism. Modified Stern-Volmer plots of anthracyclines bound to fluid-phase DMPC bilayers were linear, and the biomolecular rate constant (kq) values ranged from 0.6 X 10(9) to 1.3 X 10(9) M-1 s-1. Modified Stern-Volmer plots of anthracyclines bound to solid-phase DPPC bilayers were curved, indicative of a heterogeneous-bound drug population. A strong correlation between drug hydrophobicity and penetration of the fluorophore into the bilayer was observed for the daunosamine-containing anthracyclines. Steady-state fluorescence anisotropy measurements under iodide quenching conditions were used to investigate the diffusive motions of anthracyclines in isotropic solvent and in fluid-phase DMPC bilayers. Anthracycline derivatives free in solution exhibited limiting anisotropy (alpha infinity) values which decayed to zero at times long compared to the excited-state lifetime, in contrast to anthracyclines bound to fluid-phase DMPC bilayers, which showed nonzero alpha infinity values. Steady-state anisotropies of membrane-bound anthracyclines were found to be governed principally by alpha infinity and not by the mean rotational rate (R).(ABSTRACT TRUNCATED AT 250 WORDS)
Profiling the Native Specific Human Humoral Immune Response to Sudan Ebola Virus Strain Gulu by Chemiluminescence Enzyme-Linked Immunosorbent Assay (2012)

Ebolavirus, a member of the family Filoviridae, causes high lethality in humans and nonhuman primates. Research focused on protection and therapy for Ebola virus infection has investigated the potential role of antibodies. Recent evidence suggests that antibodies can be effective in protection from lethal challenge with Ebola virus in nonhuman primates. However, despite these encouraging results, studies have not yet determined the optimal antibodies and composition of an antibody cocktail, if required, which might serve as a highly effective and efficient prophylactic. To better understand optimal antibodies and their targets, which might be important for protection from Ebola virus infection, we sought to determine the profile of viral protein-specific antibodies generated during a natural cycle of infection in humans. To this end, we characterized the profile of antibodies against individual viral proteins of Sudan Ebola virus (Gulu) in human survivors and nonsurvivors of the outbreak in Gulu, Uganda, in 2000-2001. We developed a unique chemiluminescence enzyme-linked immunosorbent assay (ELISA) for this purpose based on the full-length recombinant viral proteins NP, VP30, and VP40 and two recombinant forms of the viral glycoprotein (GP(1-294) and GP(1-649)) of Sudan Ebola virus (Gulu). Screening results revealed that the greatest immunoreactivity was directed to the viral proteins NP and GP(1-649), followed by VP40. Comparison of positive immunoreactivity between the viral proteins NP, GP(1-649), and VP40 demonstrated a high correlation of immunoreactivity between these viral proteins, which is also linked with survival. Overall, our studies of the profile of immunorecognition of antibodies against four viral proteins of Sudan Ebola virus in human survivors may facilitate development of effective monoclonal antibody cocktails in the future.
Treatment of Respiratory Infections with Fosfomycin (1977)

Evaluation was made of the clinical-bacteriological results of treatment with fosfomycin on a group of 27 patients with infectious respiratory pathology. The group is made up of patients with respiratory infections diagnosed as pneumonias, bronchopneumonias, acute bronchitis and chronic bronchopneumopathies. The doses of fosfomycin used varied between 4 and 12 g/day, administered during a period of 1 or 2 weeks. The results of the treatment expressed in clinical and bacteriological parameters have been successful in 15 and 21 cases for their bacteriological response and their clinical response respectively.
Mechanical Tissue Resuscitation at the Site of Traumatic Brain Injuries Reduces the Volume of Injury and Hemorrhage in a Swine Model (2014)

Application of mechanical tissue resuscitation to TBI was efficacious in the large-animal model. Application of -100 mm Hg for 5 days resulted in significantly improved outcomes. Delays of up to 3 hours between injury and the initiation of treatment did not diminish the efficacy of the mechanical tissue resuscitation treatment.
Effects of a Melanotropic Peptide on Melanoma Cell Growth, Metastasis, and Invasion (1992)

Melanocyte stimulating hormone (alpha-MSH, alpha-melanotropin),Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Ly-Pro-Va l-NH2, regulates melanogenesis within epidermal melanocytes of many animals. An MSH analogue ([Nle4,D-Phe7]alpha-MSH) that exhibits superpotency and prolonged biological activity has been synthesized, biologically characterized, and is presently in clinical trials to determine its possible clinical use in tanning of the skin. It also has potential for the diagnosis, localization, and chemotherapy of melanoma. The effects of this analogue on the growth, metastatic behavior, and invasive potential of a melanotic variant of Cloudman S-91 murine melanoma are reported here. In an intracutaneous murine model of melanoma cell tumor growth, the analogue did not increase primary tumor growth (size) after the period of administration of the peptide hormone analogue and did not affect spontaneous lung metastases. Survival times for the control and melanotropin-treated groups were similar, suggesting that overall tumor burden was not affected by treatment with the hormone analogue. Last, melanoma cell invasion through a human amniotic basement membrane in vitro was not enhanced compared to untreated cells.
Antitumor effect of IL-2, p53, and bax gene transfer in C6 glioma cells. (2000)

The use of interleukin-2 (IL-2) and p53 for immunotherapy and gene therapy for cancer has shown promising results. In this study, we examined the efficacy of plasmid gene therapy utilizing murine IL-2, the wild-type (wt) human p53 gene, the combination of these genes, and the murine bax gene, which are under the control of the cytomegalovirus (CMV) immediate-early promoter, in nude mice bearing established subcutaneous C6 glioma. In vitro assays and immunocytochemical analysis for therapeutic genes demonstrated expression of the proteins in C6 transfected cells. In animal studies, significant antitumor activity was observed for the IL-2, p53/IL-2, and bax treated groups. However, no synergistic effect was observed in the p53/IL-2 combination group. Demonstrating for the first time, bax showed a significant reduction of tumor volume when compared to p53 (p < 0.02). Thus, our in vivo studies show that delivery of naked therapeutic genes is safe and results in significantly slower progression of glioma in athymic rodents.