gebhart/patrepeval huggingface dataset:
Effects of Depression on Working Memory in Presymptomatic Huntington's Disease (2001)

Cognitive decline may precede motor symptoms in Huntington's disease (HD). Depression is common in HD and has also been linked with cognitive impairment. The contribution of depression to cognition in individuals presymptomatic for HD (N=15) was investigated. Tests from the Cambridge Automated Neuropsychological Assessment Battery measured visual and working memory. Depression was assessed with the Beck Depression Inventory and the Unified Huntington's Disease Rating Scale. Depressed mood and estimated time to disease onset, calculated by using DNA mutation length, both were significant predictors of working memory performance. Findings are consistent with and contribute to existing research with individuals presymptomatic for HD, identifying a potentially remediable contribution to cognitive decline (i.e., depressed mood).
N-Linked Glycosylation Is Critical for the Plasma Membrane Localization of Nephrin (2002)

The expression pattern, subcellular localization, and the role of glycosylation of the human nephrin was examined in transfected cells. Stable cell lines, constitutively expressing a full-length human nephrin cDNA construct, were generated from transfected immortalized mouse podocytes (IMP) and a human embryonic kidney cell line (HEK-293). Immunofluorescence confocal microscopy of transfected cells showed plasma membrane localization of the recombinant nephrin. Immunoblotting showed that the recombinant nephrin expressed in transfected cell lines migrated as a double band with a molecular weight of 185 kD. When cells were treated with the N-glycosylation inhibitor, tunicamycin, the molecular weight of nephrin was decreased to a single immunoband of 150 kD, indicating that the shift in the electrophoretic migration of nephrin is due to N-linked carbohydrate moieties. It was further shown that this glycosylation process is highly sensitive to inhibition by tunicamycin, which is a naturally occurring antibiotic, leading to retention of nonglycosylated nephrin molecules in the endoplasmic reticulum. It was concluded that N-glycosylation of nephrin is crucial for its proper folding and thereby plasma membrane localization; therefore, inhibition of this process might be an important factor in the onset of pathogenesis of some acquired glomerular diseases.
Targeting Random Mutations to Hotspots in Antibody Variable Domains for Affinity Improvement (2003)

The potential of Fvs as magic bullets for targeting therapeutic drugs or imaging agents is well-documented. However, the conversion of whole antibodies (Abs) into Fvs (scFvs or dsFvs) is often associated with a drastic reduction in antigen (Ag)-binding affinity. For efficient use of Fvs as targeting agents, this property must be improved.
Identification of phosphate oxygens that are important for self-cleavage activity of the HDV ribozyme by phosphorothioate substitution interference analysis (1994)

A phosphorothioate substitution interference assay was used to investigate the role of the pro-Rp oxygens of phosphate groups in the self-cleavage reaction of the genomic human hepatitis delta virus (HDV) ribozyme. Incorporation of several different phosphorothioates (NTP alpha S) into the HDV ribozyme inhibited the self-cleavage activity. Incorporation of uridine 5' phosphorothioate or adenosine 5' phosphorothioate maintained 72% of the original self-cleavage activity whereas incorporation of guanosine 5' phosphorothioate or cytosine 5' phosphorothioate into the precursor reduced self-cleavage activity to about 20% in each case. Using partially substituted phosphorothioate-modified transcripts, we identified the pro-Rp oxygens that are important for the ribozyme activity, and they are located at positions 0, 1, 4, 5, 21, 24, 25, 27, 28, 30-34, 40, 43 and 75. In particular, the pro-Rp oxygens at positions 0, 1 and 21 are appear to be critical for the self-cleavage activity of the HDV ribozyme.
Early Clinical Trials (2005)

This chapter contains sections titled: Introduction Pharmacokinetic Studies Phase I Trials Phase II Trials Practicalities Technical Details
Bacterial Interference Between Clostridium difficile and Normal Fecal Flora (1981)

Clostridium difficile has been shown to be the cause of virtually all cases of pseudomembranous colitis related to the administration of antimicrobial agents. It is possible that some antimicrobial agents alter the normal bacterial flora of the gastrointestinal tract so as to permit colonization and/or proliferation by C. difficile. The inhibitory activity of representative fecal bacteria from 23 anaerobic and aerobic genera against C. difficile was examined using two in vitro procedures. Strains of bacteria in six of the genera inhibited the multiplication of C. difficile, with Lactobacillus organisms and group D enterococci displaying the most antagonistic activity. C. difficile was examined for its ability to inhibit the multiplication of several fecal strains of anaerobic and aerobic bacteria. All eight strains of C. difficile tested inhibited the growth of particular strains of bacteria in the genera Bacteroides, Peptococcus, and Peptostreptococcus.
Free acid gel form of β-hydroxy-β-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt (2010)

The leucine metabolite, β-hydroxy-β-methylbutyrate (HMB), is a nutritional supplement that increases lean muscle and strength with exercise and in disease states. HMB is presently available as the Ca salt (CaHMB). The present study was designed to examine whether HMB in free acid gel form will improve HMB availability to tissues. Two studies were conducted and in each study four males and four females were given three treatments in a randomised, cross-over design. Treatments were CaHMB (gelatin capsule, 1 g), equivalent HMB free acid gel swallowed (FASW) and free acid gel held sublingual for 15 s then swallowed (FASL). Plasma HMB was measured for 3 h following treatment in study 1 and 24 h with urine collection in study 2. In both the studies, the times to peak plasma HMB were 128 (sem 11), 38 (sem 4) and 38 (sem 1) min (P < 0·0001) for CaHMB, FASW and FASL, respectively. The peak concentrations were 131 (sem 6), 249 (sem 14) and 239 (sem 14) μmol/l (P < 0·0001) for CaHMB, FASW and FASL, respectively. The areas under the curve were almost double for FASW and FASL (P < 0·0001). Daily urinary HMB excretion was not significantly increased resulting in more HMB retained (P < 0·003) with FASW and FASL. Half-lives were 3·17 (sem 0·22), 2·50 (sem 0·13) and 2·51 (sem 0·14) h for CaHMB, FASW and FASL, respectively (P < 0·004). Free acid gel resulted in quicker and greater plasma concentrations (+185%) and improved clearance (+25%) of HMB from plasma. In conclusion, HMB free acid gel could improve HMB availability and efficacy to tissues in health and disease.
Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. (1994)

The p53 tumor suppressor gene product is a transcriptional activator that may be associated with its ability to suppress tumor cell growth. The acidic amino terminus of the p53 protein has been shown to contain this trans-activation activity as well as the domains for mdm-2 and adenovirus 5 E1B 55-kD protein binding. An extensive genetic analysis of this amino-terminal p53 domain has been undertaken using site-specific mutagenesis. The results demonstrate that the acidic residues in the amino terminus of p53 may contribute to, but are not critical for, this trans-activation activity. Rather, the hydrophobic amino acid residues Leu-22 and Trp-23 of human p53 are both required for trans-activation activity, binding to the adenovirus E1B 55-kD protein and the human mdm-2-p53 protein in vitro. In addition, hydrophobic residues Leu-14 and Phe-19 are crucial for the interactions between p53 and human mdm-2 (hdm-2). Hydrophobic residues Trp-23 and Pro-27 are also important for binding to the adenovirus 5 (Ad5) E1B 55-kD protein in vitro. These mutations have no impact on the ability of the p53 protein to bind to a p53-specific DNA element. These results suggest that 2-4 critical hydrophobic residues in the amino-terminal domain of the p53 protein interact with the transcriptional machinery of the cell resulting in transcriptional activation. These very same hydrophobic residues contact the hdm-2 and Ad5 E1B 55-kD oncogene products.
Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model (2013)

Extension of survival and dense T-cell infiltrates emphasize the translational potential of combinational immunotherapy strategies for hepatocellular carcinoma. Clin Cancer Res; 19(22); 6151-62. ©2013 AACR.
Hologram–Moiré Interferometry for Transparent Objects (1967)

A modification of hologram interferometry applicable to the study of transparent objects of moderate optical quality has been devised which combines hologram and moiré techniques and allows the observation of high contrast, relatively unlocalized, interferometric fringes under conditions less critical than those of the conventional hologram interferometer. By spatially modulating one beam of the interferometer during exposure, moiré fringes may be obtained in the reconstruction which distort and move with optical phase changes in either beam of the interferometer. An analysis of the origin and nature of these distortions is given and experimental verification of the analysis is presented.
Multiplexed in Vivo His-Tagging of Enzyme Pathways for in Vitro Single-Pot Multienzyme Catalysis (2012)

Protein pathways are dynamic and highly coordinated spatially and temporally, capable of performing a diverse range of complex chemistries and enzymatic reactions with precision and at high efficiency. Biotechnology aims to harvest these natural systems to construct more advanced in vitro reactions, capable of new chemistries and operating at high yield. Here, we present an efficient Multiplex Automated Genome Engineering (MAGE) strategy to simultaneously modify and co-purify large protein complexes and pathways from the model organism Escherichia coli to reconstitute functional synthetic proteomes in vitro. By application of over 110 MAGE cycles, we successfully inserted hexa-histidine sequences into 38 essential genes in vivo that encode for the entire translation machinery. Streamlined co-purification and reconstitution of the translation protein complex enabled protein synthesis in vitro. Our approach can be applied to a growing area of applications in in vitro one-pot multienzyme catalysis (MEC) to manipulate or enhance in vitro pathways such as natural product or carbohydrate biosynthesis.
Initiation and termination of phage f1 plus-strand synthesis. (1982)

The origin of DNA replication of bacteriophage f1 contains a nucleotide sequence that is used both for the initiation of viral (plus) strand synthesis and for its termination. With chimeric plasmids containing two f1 functional origins in the same orientation, synthesis of chimeric plus-strand DNA is initiated, after f1 infection, at either one of the two f1 origins and is terminated at the other. Thus, the chimeric plasmids segregate into two replicons, each of them containing only one f1 origin. This system has been used to test several fragments of the f1 origin varying in size or in nucleotide sequence for their ability to function in either initiation or termination of viral strand synthesis. Our data show that the f1 origin is composed of two overlapping but distinct domains (signals), one for initiation and the other for termination of plus-strand synthesis.
Molecular mechanisms underlying selective cytotoxic activity of BZL101, an extract of Scutellaria barbata, towards breast cancer cells (2008)

We studied the mechanism of the cytotoxic activity of BZL101, an aqueous extract from the herb Scutellaria barbata D. Don, which is currently in phase II clinical trial in patients with advanced breast cancer. The phase I trial showed favorable toxicity profile and promising efficacy. We report here that BZL101 induces cell death in breast cancer cells but not in non-transformed mammary epithelial cells. This selective cytotoxicity is based on strong induction by BZL101 of reactive oxygen species (ROS) in tumor cells. As a consequence, BZL101 treated cancer cells develop extensive oxidative DNA damage and succumb to necrotic death. Data from the expression profiling of cells treated with BZL101 are strongly supportive of a death pathway that involves oxidative stress, DNA damage and activation of death-promoting genes. In breast cancer cells oxidative damage induced by BZL101 leads to the hyperactivation of poly (ADP-ribose) polymerase (PARP), followed by a sustained decrease in levels of NAD and depletion of ATP, neither of which are observed in non-transformed cells. The hyperactivation of PARP is instrumental in the necrotic death program induced by BZL101, because inhibition of PARP results in suppression of necrosis and activation of the apoptotic death program. BZL101 treatment leads to the inhibition of glycolysis selectively in tumor cells, evident from the decrease in the enzymatic activities within the glycolytic pathway and the inhibition of lactate production. Because tumor cells frequently rely on glycolysis for energy production, the observed inhibition of glycolysis is likely a key factor in the energetic collapse and necrotic death that occurs selectively in breast cancer cells. The promising selectivity of BZL101 towards cancer cells is based on metabolic differences between highly glycolytic tumor cells and normal cells.
Immunoaffinity Chromatography: An Introduction to Applications and Recent Developments (2010)

Immunoaffinity chromatography (IAC) combines the use of LC with the specific binding of antibodies or related agents. The resulting method can be used in assays for a particular target or for purification and concentration of analytes prior to further examination by another technique. This review discusses the history and principles of IAC and the various formats that can be used with this method. An overview is given of the general properties of antibodies and of antibody-production methods. The supports and immobilization methods used with antibodies in IAC and the selection of application and elution conditions for IAC are also discussed. Several applications of IAC are considered, including its use in purification, immunodepletion, direct sample analysis, chromatographic immunoassays and combined analysis methods. Recent developments include the use of IAC with CE or MS, ultrafast immunoextraction methods and the use of immunoaffinity columns in microanalytical systems.
Performance of neural network basecalling tools for Oxford Nanopore sequencing (2019)

Abstract Basecalling, the computational process of translating raw electrical signal to nucleotide sequence, is of critical importance to the sequencing platforms produced by Oxford Nanopore Technologies (ONT). Here we examine the performance of different basecalling tools, looking at accuracy at the level of bases within individual reads and at majority-rules consensus basecalls in an assembly. We also investigate some additional aspects of basecalling: training using a taxon-specific dataset, using a larger neural network model and improving consensus basecalls in an assembly via additional signal-level analysis with Nanopolish. Training basecallers on taxon-specific data resulted in a significant boost in consensus accuracy, mostly due to the reduction of errors in methylation motifs. A larger neural network was able to improve both read and consensus accuracy, but at a cost to speed. Improving consensus sequences (‘polishing’) with Nanopolish somewhat negates the accuracy differences in basecallers, but pre-polish accuracy does have an effect on post-polish accuracy, so basecaller choice is still relevant even when Nanopolish is used.
고광도 빛이 시설내 여성 치매 노인의 수면에 미치는 효과 (1999)

Sleep impairment with agitated behavior is common in the demented elderly. The gravity of sleep and behavioral disturbances is evident from the fact that night time agitation is the primary cause of institutionalization of the demented elderly. Both problems are related to circadian rhythm changes and decreased exposure to zeitgebers. Bright light is known to be a strong zeitgeber of human circadian rhythm. Consequently, bright light has been emerged as a possible therapeutic alternative for the problems of sleep and behavioral disturbances. The purpose of this study was to examine the effect of evening bright light delivered by fluorescent lamps on female demented elderly with disturbed sleep patterns, accompanied by agitated behavior, in a community care facility. The study was conducted in cross-over trial with twenty-one subjects and outcome variables derived from tympanic temperature, sleep, agitation and cognition were analyzed. The results were as follows : 1. Temperature : Treatment effect was not statistically significant for the mean, peak, nadir, and amplitude (P>0.10). No statistically significant changes of the occurrence numbers of peak 4PM were found after treatment, but the occurrence numbers of nadir at 4 AM increased significantly (P=0.09) after treatment. 2. Sleep : Treatment effect was not statistically significant for the sleep period at night, total sleep time, wake after sleep onset, percentage of sleep during night, sleep time at night, wake up time in the morning. Nap time (P=0.01) and nap numbers(P=0.02) decreased significantly after treatment. 3. Agitation scores decreased significantly after treatment(P=0.00). 4. Cognition scores were not changed significantly after treatment(P=0.82). Evening bright light has significantly decreased the agitated behavior of the demented elderly, but were found to be effective on only a few outcome measures of temperature and sleep-activity rhythm, and ineffective on cognition. It can be concluded tat bright light is a potent therapeutic intervention for the sleep and behavioral disturbances of the demented elderly.
Neurotensin, a brain and gastrointestinal peptide. (1982)

Abstract : This volume contains the proceedings of the first conference on neurotensin, a peptide discovered almost ten years ago and now known to be present within the central nervous system and the gastrointestinal tract of a variety of mammals. The conference was organized along two major themes: (1) the localization and effects of neurotensin n the periphery, including its endocrine and cardiovascular actions, and (2) the localization, behavioral and neurochemical effects of neurotensin in the central nervous system.
The reciprocal pool model for the measurement of gluconeogenesis by use of [U-13C]glucose (2000)

To improve upon the [U- 13 C]glucose method to estimate “gluconeogenesis” as described by J. Katz and J. A. Tayek ( Am. J. Physiol. Endocrinol. Metab. 272: E476–E484, 1997, and 275: E537–E542, 1998), we describe the reciprocal pool model by using only the isotopomer data of plasma glucose during infusion of [U- 13 C]glucose. The glucose pool serves as both precursor and product for the calculation of the fraction of molecules generated by gluconeogenesis and to correct for exchange and loss of labeled carbon at the level of the tricarboxylic acid cycle. We have applied this model to both our own data and those of other investigators using [U- 13 C]glucose and have demonstrated excellent agreement between the Katz and Tayek model and our reciprocal pool model. When we compare the results of the reciprocal pool model with those of Hellerstein ([2- 13 C]glycerol) and Landau ( 2 H 2 O-glucose-C-5), the results are similar in short- and long-term fasted adult humans. Finally, when we apply the reciprocal pool model to our data from premature infants, it is clear that we account for the inflow of unlabeled glycerol and presumably amino acids. This is not surprising, because the vast majority of gluconeogenesis is the result of recycling of glucose and pyruvate carbon.
CMOS-Analogous Wafer-Scale Nanotube-on-Insulator Approach for Submicrometer Devices and Integrated Circuits Using Aligned Nanotubes (2008)

Massive aligned carbon nanotubes hold great potential but also face significant integration/assembly challenges for future beyond-silicon nanoelectronics. We report a wafer-scale processing of aligned nanotube devices and integrated circuits, including progress on essential technological components such as wafer-scale synthesis of aligned nanotubes, wafer-scale transfer of nanotubes to silicon wafers, metallic nanotube removal and chemical doping, and defect-tolerant integrated nanotube circuits. We have achieved synthesis of massive aligned nanotubes on complete 4 in. quartz and sapphire substrates, which were then transferred to 4 in. Si/SiO(2) wafers. CMOS analogous fabrication was performed to yield transistors and circuits with features down to 0.5 mum, with high current density approximately 20 muA/mum and good on/off ratios. In addition, chemical doping has been used to build fully integrated complementary inverter with a gain approximately 5, and a defect-tolerant design has been employed for NAND and NOR gates. This full-wafer approach could serve as a critical foundation for future integrated nanotube circuits.
Preferentially Expressed Antigen of Melanoma (PRAME) in the Development of Diagnostic and Therapeutic Methods for Hematological Malignancies (2003)

PRAME (Preferentially expressed antigen of melanoma), highly expressed in various solid tumor cells and normal testis, was first isolated as a human melanoma antigen recognized by cytotoxic T cells (CTL). This gene was also expressed in some of the hematological malignancies, including acute myelogenous leukemia (AML) and multiple myeloma. We and others have extensively evaluated the PRAME expression in various hematological malignancies and demonstrated high expression of the PRAME gene in subsets of AML, chronic myelogenous leukemia, acute lymphocytic leukemia, lymphoma and multiple myeloma. In addition, we have demonstrated that PRAME was a useful marker for detection of minimal residual disease (MRD) in patients with leukemia, particularly those leukemias in which tumor specific markers are currently unavailable. Since PRAME was first identified as a tumor antigen recognized by T cells, the possibility that PRAME is a leukemia antigen recognized by T cells was evaluated, and it was found that PRAME-positive leukemia cell lines and fresh leukemia cells were susceptible to lysis by the PRAME-specific CTL. Five CTL epitopes associated with either HLA-A*0201 or HLA-A*2402 have recently been identified. It is, therefore, an attractive strategy to apply PRAME specific immunotherapy on patients with PRAME positive leukemia in MRD condition.