gebhart/patrepeval huggingface dataset:
In vivo metabolism of epothilone B in tumor-bearing nude mice: identification of three new epothilone B metabolites by capillary high-pressure liquid chromatography/mass spectrometry/tandem mass spectrometry (2000)

Epothilone B is a 16-membered macrolide produced by the myxobacterium Sorangium cellulosum and is currently under clinical investigation. Experimentally, epothilone B demonstrates potent antiproliferative activity at the nanomolar level in vitro, and potent regression-producing antitumor activity in vivo, similar to paclitaxel (Taxol). In order to foster the design of improved derivatives, the potential biotransformation products of epothilone B formed in liver of tumor-bearing mice after intravenous administration of 10 mg/kg were characterized in an early stage of compound development. Solely on the basis of capillary high-performance liquid chromatography, combined either with electrospray tandem mass spectrometry (in precursor and product ion scan mode) and single analyzing time-of-flight mass spectrometry (H/D exchange and accurate mass measurement), three main metabolites could be detected. The three metabolites, formed by the liver, have in common that the epoxide ring was hydrolyzed and that the macrocyclic lactone ring was opened to the acid. In two cases it is assumed that open-chain intermediates re-cycled either to a lactone or, after conjugation with taurine, to the respective lactam. The proposed structures were additionally supported by the determination of the number of the exchangeable hydrogen atoms and by confirmation of the proposed elemental composition by exact mass measurement.
Growth Hormone Responses to Growth Hormone-Releasing Hormone and Clonidine before and after Erythropoietin Therapy in CAPD Patients (1996)

Correction of anemia with recombinant human erythropoietin (rhEPO) in patients with end-stage renal disease has been associated with improvement of several abnormalities in hypothalamo-hypophyseal functions. The aim of the present work was to evaluate the growth hormone (GH) responses to GH-releasing hormone (GHRH) and clonidine stimulation, as well as the baseline concentrations of insulin-like growth factor I(IGF-I), before and after the correction of anemia with rhEPO in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Nine clinically stable patients (1 male, 8 female; mean age 55.4 years; mean duration of CAPD 14.1 months) were studied. Twelve normal volunteers were studied as controls. GHRH and clonidine stimulation tests were performed prior to starting rhEPO and again after partial correction of anemia with rhEPO therapy (60-130 U/kg/week, s.c., for 12 weeks). Blood samples for GH were collected during 2 h after GHRH (100 micrograms i.v. in bolus) or clonidine (0.15 mg/m2, p.o.) administration. In basal plasma samples IGF-I concentrations were also measured. Mean (+/- SEM) blood hemoglobin concentration rose from 5.32 +/- 0.25 to 7.22 +/- 0.25 mmol/l (p < 0.001) after rhEPO treatment. GH responses to GHRH were characterized by marked differences in single patients when compared with the control group. However, the GH peak and the area under the secretory curves (AUC) of GH responses in CAPD patients (9.89 +/- 4.01 micrograms/l and 15.06 +/- 6.02 micrograms.h/l, respectively) did not differ from those obtained in control subjects (14.58 +/- 3.25 microgram/l and 16.94 +/- 4.31 microgram.h/l, respectively). The study after correction of anemia showed an evident potentiation of GH values that reached statistically significant values at 60 and 90 min. GH AUC after rhEPO therapy rose to 25.61 +/- 9.25 micrograms.h/l (p = 0.01). In control subjects, clonidine administration was followed by a GH release that reached a maximum at 90 min (7.67 +/- 2.24 micrograms/l). However, CAPD patients exhibited a blunted response to clonidine both before (2.00 +/- 0.78 microgram/l) and after (2.78 +/- 0.76 microgram/l, NS) correction of the anemia with rhEPO. On the other hand, IGF-I concentrations after rhEPO therapy (32.05 +/- 5.52 nmol/l) were not significantly different from those found prior to starting therapy (38.13 +/- 8.44 nmol/l). In conclusion, these results suggest that correction of the anemia with rhEPO therapy potentiates GH responses to direct pituitary stimulation with GHRH although it is unable to restore the blunted response of GH to clonidine that is found in CAPD patients.
Dendritic spine pathology and deficits in experience‐dependent dendritic plasticity in R6/1 Huntington's disease transgenic mice (2004)

Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion coding for an expanded polyglutamine tract in the huntingtin protein. Dendritic abnormalities occur in human HD patients and in several transgenic mouse models of the disease. In this study, we examine, for the first time, dendrite and spine pathology in the R6/1 mouse model of HD, which mimics neurodegeneration seen in human HD. Enriching the environment of HD transgenic mice delays the onset of symptoms, so we also examine the effects of enrichment on dendrite pathology. Golgi-impregnated tissue from symptomatic R6/1 HD mice reveals a decrease in dendritic spine density and dendritic spine length in striatal medium spiny neurons and cortical pyramidal neurons. HD also causes a specific reduction in the proportion of bifurcated dendritic spines on basal dendrites of cortical pyramidal neurons. No differences in soma size, recurving distal dendrites, or dendritic branching were observed. Although home-cage environmental enrichment from 1 to 8 months of age increases spine density in wild-type mice, it has no effect on the spine pathology in HD mice. These results show that dendritic spine pathology in R6/1 HD mice resembles degenerative changes seen in human HD and in other transgenic mouse models of the disease. We thus provide further evidence that the HD mutation disrupts the connectivity in both neostriatum and cerebral cortex, which will contribute to motor and cognitive disease symptoms. Furthermore, we demonstrate that Huntington's disease pathology interferes with the normal plastic response of dendritic spines to environmental enrichment.
Flow cytometric immunofluorescence assay for detection of antibodies to human immunodeficiency virus type 1 using insoluble precursor forms of recombinant polyproteins as carriers and antigens (1996)

A new serological assay, the recombinant flow cytometric immunofluorescence assay (r-FIFA), was developed for the early detection of human immunodeficiency virus type 1 (HIV-1) antibodies by using recombinant insoluble forms of HIV-1 Gag-p45, Gag-gp41 chimeric protein, gp160, Po197 polyprotein as antigens and autologous carriers through flow cytometry. These recombinant proteins were expressed in insect cells by a baculovirus expression system. Eight anti-HIV-1 seroconversion panels, a low-titer anti-HIV-1 panel from Boston Biomedica Inc. (BBI), and three HIV-1 seroconversion specimens from the Provincial Health Laboratory of Ontario, Toronto, Ontario, Canada (PHL), were tested and analyzed by r-FIFA. In sensitivity comparisons between r-FIFA and tests licensed by the U.S. Food and Drug Administration, which were used to test all of the HIV-1 panels from BBI, detection of HIV-1 antibody by r-FIFA was on average greater than 20 days earlier than that by enzyme immunoassay. The sensitivity of r-FIFA has permitted the detection of HIV-1-specific immunoglobulin G (IgG), IgM, and IgA antibodies during seroconversion. A kinetic analysis of HIV-1 antibody production of r-FIFA has shown that either IgG or IgM, or both, can be detected, depending on the phase and type of the immune response in the HIV-1-infected individual. Both primary and secondary immune responses were observed during this period. The r-FIFA results suggest that implementation of r-FIFA may significantly reduce the "window" period from the time of infection to the time of seroconversion, with earlier detection of antibodies after initial infection. This would also make it possible for us to understand the immune response and the precise mechanisms of immunopathogenesis in the early period of HIV-1 infection.
DNA-mediated Folding and Assembly of MyoD-E47 Heterodimers (1998)

Basic region helix-loop-helix (bHLH) transcription factors regulate key steps in early development by binding to regulatory DNA sites as heterodimers consisting of a tissue-specific factor and a widely expressed factor. We have examined the folding, dimerization, and DNA binding properties of the muscle-specific bHLH protein MyoD and its partner E47, to understand why these proteins preferentially associate in heterodimeric complexes with DNA. In the absence of DNA, the E47 bHLH domain forms a very stable homodimer, whereas MyoD is unfolded and monomeric. Fluorescence quenching experiments show that MyoD does not dimerize with E47 under dilute conditions in the absence of DNA. Residues in and around the loop of the E47 bHLH domain contribute to its markedly greater stability. An altered MyoD bHLH substituted with the loop segment from E47 folds in the absence of DNA, and it readily dimerizes with E47. In the presence of a specific DNA binding site, MyoD and E47 both form homodimeric complexes with DNA that have similar dissociation constants, despite the very different stabilities of these protein dimers off DNA. A 1:1 mixture of these bHLH domains forms almost exclusively heterodimeric complexes on DNA. Assembly of these bHLH-DNA complexes is apparently governed by the strength of each subunit's interaction with the DNA and not by the strength of protein-protein interactions at the dimer interface. These findings suggest that preferential association of MyoD with E47 in DNA complexes results from more favorable DNA contacts made by one or both subunits of the heterodimer in comparison with either homodimeric complex.
Description of the larva of Cordulegaster pekinensis Selys from China (Anisoptera: Cordulegastridae) (2007)

The 2 ultimate instar larva from Beijing area, China, is described and illustrated. It shares some characters with the Cordulegaster boltonii-group, C. bidentata-group, and others with the but the anal pyramid is longer than in both.
New Player on An Old Field; the Keap1/Nrf2 Pathway as a Target for Treatment of Type 2 Diabetes and Metabolic Syndrome (2013)

Nuclear erythroid factor 2 like 2 (Nrf2) has been described as a transcription factor that serves as a master regulator of the adaptive response to exogenous and endogenous oxidative and electrophilic stresses. Evidence of Nrf2 crosstalk with other molecular pathways is increasing; recent publications have proposed a role of Nrf2 in the development of obesity and in the highly regulated process of adipocyte differentiation through its interaction with other transcription factors and receptors implicated in metabolic regulation. In the present review, we discuss the available data on the possible role of Nrf2 in obesity and metabolic syndrome and the feasibility of using Nrf2 as a therapeutic target in the clinical setting.
Systemic Delivery of Modified mRNA Encoding Herpes Simplex Virus 1 Thymidine Kinase for Targeted Cancer Gene Therapy (2012)

Failure of clinical trials of nonviral vector-mediated gene therapy arises primarily from either an insufficient transgene expression level or immunostimulation concerns caused by the genetic information carrier (e.g., bacteria-generated, double-stranded DNA (dsDNA)). Neither of these issues could be addressed through engineering-sophisticated gene delivery vehicles. Therefore, we propose a systemic delivery of chemically modified messenger RNA (mRNA) as an alternative to plasmid DNA (pDNA) in cancer gene therapy. Modified mRNA evaded recognition by the innate immune system and was less immunostimulating than dsDNA or regular mRNA. Moreover, the cytoplasmic delivery of mRNA circumvented the nuclear envelope, which resulted in a higher gene expression level. When formulated in the nanoparticle formulation liposome-protamine-RNA (LPR), modified mRNA showed increased nuclease tolerance and was more effectively taken up by tumor cells after systemic administration. The use of LPR resulted in a substantial increase of the gene expression level compared with the equivalent pDNA in the human lung cancer NCI-H460 carcinoma. In a therapeutic model, when modified mRNA encoding herpes simplex virus 1-thymidine kinase (HSV1-tk) was systemically delivered to H460 xenograft-bearing nude mice, it was significantly more effective in suppressing tumor growth than pDNA.
pos-1 encodes a cytoplasmic zinc-finger protein essential for germline specification in C. elegans (1999)

Germ cells arise during early C. elegans embryogenesis from an invariant sequence of asymmetric divisions that separate germ cell precursors from somatic precursors. We show that maternal-effect lethal mutations in the gene pos-1 cause germ cell precursors to inappropriately adopt somatic cell fates. During early embryogenesis, pos-1 mRNA and POS-1 protein are present predominantly in the germ precursors. POS-1 is a novel protein with two copies of a CCCH finger motif previously described in the germline proteins PIE-1 and MEX-1 in C. elegans, and in the mammalian TIS11/Nup475/TTP protein. However, mutations in pos-1 cause several defects in the development of the germline blastomeres that are distinct from those caused by mutations in pie-1 or mex-1. The earliest defect detected in pos-1 mutants is the failure to express APX-1 protein from maternally provided apx-1 mRNA, suggesting that POS-1 may have an important role in regulating the expression of maternal mRNAs in germline blastomeres.
Compressed ultrafast photography by multi-encoding imaging (2018)

&lt;p&gt;Imaging ultrafast dynamic scenes has been long pursued by scientists. As a two-dimensional dynamic imaging technique, compressed ultrafast photography (CUP) provides the fastest receive-only camera to capture transient events. This technique is based on three-dimensional image reconstruction by combining streak imaging with compressed sensing (CS). However, the image quality and the frame rate of CUP are limited by the CS-based image reconstruction algorithms and the inherent temporal and spatial resolutions of the streak camera. Here, we report a new method to improve the temporal and spatial resolutions of CUP. Our numerical simulation and experimental verification show that by using a multi-encoding imaging method, both the image quality and the frame rate of CUP can be significantly improved beyond the intrinsic technical parameters. Importantly, the temporal resolution by our scheme can break the limitation of the streak camera. Therefore, this new technology has potential benefits in many applications that require the ultrafast dynamic scene image with high temporal and spatial resolutions.&lt;/p&gt;
In Situ Evidence of KRAS Amplification and Association With Increased p21 Levels in Non–Small Cell Lung Carcinoma (2009)

Recent advances in the characterization of the lung cancer genome have suggested that KRAS may frequently be amplified, although little is known regarding the significance of this finding. This is in contrast with activating mutations of KRAS, which occur in approximately 20% of non-small cell lung carcinomas (NSCLCs). We used fluorescence in situ hybridization to provide direct evidence of KRAS amplification for the first time in clinical specimens. We detected amplification in 7 of 100 consecutive NSCLCs, with a concurrent activating KRAS mutation in 4 cases. KRAS amplification was associated with greater expression of p21 as assessed by quantitative immunohistochemical analysis (P = .015). Our data indicate that a sizable subgroup of NSCLCs harbor KRAS amplification, some of which also contain point mutations, and suggest that an increased KRAS copy number may drive p21 overexpression. KRAS amplification may define a unique clinicopathologic subset of NSCLCs with potentially altered responsiveness to targeted therapies.
The Role of Hepatitis C Virus in Hepatocellular Carcinoma in Japan (1994)

Increasing numbers of patients with hepatocellular carcinoma (HCC) have been reported in Japan. In this paper, we investigated the role of hepatitis C virus (HCV) in HCC and the reason for the increase, using patients admitted to our university hospital from 1945 to 1992. 99 (73%) of 135 patients with HCC were positive for anti-HCV. Prospective studies demonstrated that 22 of 158 (14%) patients with chronic hepatitis C, and 31 of 70 (44%) cirrhotic patients with anti-HCV developed to HCC during the follow-up period (10.1 +/- 3.3 and 7.3 +/- 3.5 years, respectively). Prolonged survival of cirrhotic patients during past decades would also contribute to the increasing number of HCC cases as well as the number of HCV infections in Japan.
High-energy scissors mode (1995)

All the orbital M1 excitations, at both low and high energies, obtained from a rotationally invariant quasiparticle random-phase approximation, represent the fragmented scissors mode. The high-energy M1 strength is almost purely orbital and resides in the region of the isovector giant quadrupole resonance. In heavy deformed nuclei the high-energy scissors model is strongly fragmented between 17 and 25 MeV (with uncertainties arising from the poor knowledge of the isovector potential). The coherent scissors motion is hindered by the fragmentation and B(M1)0.25${\mathrm{\ensuremath{\mu}}}_{\mathit{N}}^{2}$ for single transitions in this region. The (e,e') cross sections for excitations above 17 MeV are one order of magnitude larger for E2 than for M1 excitations even at backward angles.
Mapping Genes Encoding Microsomal ω‐6 Desaturase Enzymes and Their Cosegregation with QTL Affecting Oleate Content in Soybean (2008)

The microsomal ω‐6 desaturase enzymes, which catalyze the desaturation of oleic acid to linoleic acid during fatty acid biosynthesis, are encoded by the FAD2‐1 and FAD2‐2 genes in soybean [ Glycine max (L.) Merr.]. Breeders aim to incorporate the high‐oleate trait into soybean germplasm in order to improve the nutritional value and oxidative stability of soybean oil. The objectives of this study were to map the isoforms of the FAD2‐1 and FAD2‐2 genes and investigate the association of these genetic loci with the oleate phenotype in three populations segregating for oleate content. The populations were grown in replicated multienvironment field trials. According to linkage analysis conducted for two of the populations, FAD2‐1A and FAD2‐1B mapped on Linkage Groups O and I, respectively, while the closely linked FAD2‐2A and FAD2‐2B isoforms mapped on Linkage Group L. Oleate quantitative trait loci with minor effects were detected in the proximity of FAD2‐1B and possibly FAD2‐2B on Linkage Groups I and L. Quantitative trait loci affecting maturity were also detected on chromosomal regions adjacent to the FAD2 genes. The genotyping assays developed for the FAD2‐1A , FAD2‐1B , and FAD2‐2B isoforms, as well as their linked simple sequence repeat markers, can be used in soybean breeding programs for the elevation of oleic acid seed content through marker‐assisted selection.
Tissue- and Tumor-Specific Targeting of Murine Leukemia Virus-Based Replication-Competent Retroviral Vectors (2006)

Replication-competent retrovirus vectors based on murine leukemia virus (MLV) have been shown to effectively transfer therapeutic genes over multiple serial infections in cell culture and through solid tumors in vivo with a high degree of genomic stability. While simple retroviruses possess a natural tumor selectivity in that they can transduce only actively dividing cells, additional tumor-targeting strategies would nevertheless be advantageous, since tumor cells are not the only actively dividing cells. In this study, we used the promiscuous murine cytomegalovirus promoter, a chimeric regulatory sequence consisting of the hepatitis B virus enhancer II and the human alpha1-antitrypsin (EII-Pa1AT) promoter, and a synthetic regulatory sequence consisting of a series of T-cell factor binding sites named the CTP4 promoter to generate replicating MLV vectors, whereby the last two are transcriptionally restricted to liver- and beta-catenin/T-cell factor-deregulated cells, respectively. When the heterologous promoters were used to replace almost the entire MLV U3 region, including the MLV TATA box, vector replication was inefficient since nascent virus particle production from infected cells was greatly decreased. Fusion of the heterologous promoters lacking the TATA box to the MLV TATA box, however, generated vectors which replicated with almost-wild-type kinetics throughout permissive cells while exhibiting low or negligible spread in nonpermissive cells. The genomic stability of the vectors was shown to be comparable to that of a similar vector containing wild-type MLV long terminal repeats, and tropism analysis over repeated infection cycles showed that the targeted vectors retained their original specificity.
Photovoltaics (PV) as an eligible measure in residential PACE programs: Benefits and challenges (2010)

Property Assessed Clean Energy (PACE) financing is one of several new financial models broadening access to clean energy by addressing the barrier of initial capital cost. The majority of the PACE programs in the market today include PV as an eligible measure. PV appeals to homeowners as a way to reduce utility bills, self-generate sustainable power, increase energy independence and demonstrate a commitment to the environment. If substantial state incentives for PV exist, PV projects can be economic under PACE, especially when partnered with good net metering policies. At the same time, PV is expensive relative to other eligible measures with a return on investment horizon that might exceed program targets. This fact sheet reviews the benefits and potential challenges of including PV in PACE programs.
Adoptive Immunotherapy of Patients with Metastatic Renal Cell Cancer Using Lymphokine‐Activated Killer Cells, lnterleukin‐2 and Cyclophosphamide: Long‐Term Results (1998)

Long-term effects of LAK/IL-2/CPM therapy were not correlated with the maximal response observed 4 weeks after therapy. Although LAK/IL-2/CPM therapy appears suitable for use as induction therapy in RCC, our data suggest that long-term suppression will require surgical removal of remnant tumors or more intensive maintenance therapy.
Exceptionally Potent Anti-Tumor Bystander Activity of an scFv:sTRAIL Fusion Protein with Specificity for EGP2 Toward Target Antigen-Negative Tumor Cells (2004)

Previously, we reported on the target cell-restricted fratricide apoptotic activity of scFvC54:sTRAIL, a fusion protein comprising human-soluble tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) genetically linked to the antibody fragment scFvC54 specific for the cell surface target antigen EGP2. In the present study, we report that the selective binding of scFvC54:sTRAIL to EGP2-positive target cells conveys an exceptionally potent pro-apoptotic effect toward neighboring tumor cells that are devoid of EGP2 expression (bystander cells). The anti-tumor bystander activity of scFvC54:sTRAIL was detectable at target-to-bystander cell ratios as low as 1:100. Treatment in the presence of EGP2-blocking or TRAIL-neutralizing antibody strongly inhibited apoptosis in both target and bystander tumor cells. In the absence of target cells, bystander cell apoptosis induction was abrogated. The bystander apoptosis activity of scFvC54:sTRAIL did not require internalization, enzymatic conversion, diffusion, or communication (gap junctional intracellular communication) between target and bystander cells. Furthermore, scFvC54:sTRAIL showed no detectable signs of innocent bystander activity toward freshly isolated blood cells. Further development of this new principle is warranted for approaches where cancer cells can escape from antibody-based therapy due to partial loss of target antigen expression.