gebhart/patrepeval huggingface dataset:
Expression of trk in MAH cells lacking the p75 low-affinity nerve growth factor receptor is sufficient to permit nerve growth factor-induced differentiation to postmitotic neurons. (1994)

We have transfected MAH cells, an immortalized sympathoadrenal progenitor cell line, with a plasmid encoding the 140-kDa Trk protein, a nerve growth factor (NGF) receptor with protein-tyrosine kinase activity. NGF promotes neurite outgrowth and proliferation from such cells, indicating that Trk is sufficient to mediate such responses in the absence of significant levels of the endogenous 75-kDa low-affinity NGF receptor (p75). These initial NGF responses are indistinguishable from those evoked by basic fibroblast growth factor (bFGF). However, NGF is sufficient to promote terminal differentiation of a approximately 8% of trk-transfected MAH cells to postmitotic, NGF-dependent neurons, whereas all cells eventually die in medium with bFGF. Other environmental signals (such as depolarization or ciliary neurotrophic factor) can cooperate with NGF to enhance production of postmitotic NGF-dependent neurons in trk-transfected MAH cells. The terminal differentiation of sympathetic neurons thus involves sequential and cooperative actions of different growth and neurotrophic factors, as well as cell-intrinsic changes in the response to these factors.
Catheter-based acoustic interrogation device for real-time monitoring of the dynamics of the lower esophageal sphincter:in vitroand pilot canine studies (2015)

This paper presents a novel minimally-invasive catheter-based acoustic interrogation device for real-time monitoring the dynamics of the lower esophageal sphincter (LES). Dysfunction of the LES could result gastrointestinal (GI) diseases, such as gastroesophageal reflux disease (GERD). A micro-oscillator actively emitting sound wave at 16 kHz is located at one side of the LES, and a miniature microphone is located at the other side of the LES to capture the sound generated from the oscillator. Thus, the dynamics of the opening and closing of the LES can be monitored. The device was tested in vitro by utilizing a custom-designed LES simulator, as well as in vivo in a pilot canine model. In the in vitro test, the sound was captured by the microphone and its strength was correlated with the level of LES opening and closing which was controlled by the simulator. The measurements showed statistically significant (p < 0.05) Pearson correlation coefficients (0.905 on the average in quiet environment and 0.736 on the average in noisy environment, DOF = 9). In the in vivo test, the LES was forced open and closed by a transoral endoscope, which was monitored in real-time by a transpyloric endoscope inserted from the duodenum and positioned into the distal stomach. Frame-by-frame video analysis validated the interrelation between the sound strength and the LES opening and closing. The LES dynamics monitored by the proposed device has the potential to become a valuable minimally-invasive technique for understanding LES dysfunction.
PI3K/PTEN/Akt pathway status affects the sensitivity of high-grade glioma cell cultures to the insulin-like growth factor-1 receptor inhibitor NVP-AEW541 (2010)

IGF-1 receptor signaling contributes to the growth of many solid tumors, including glioblastoma. This study analyzed the sensitivity of 8 glioblastoma cultures to the IGF-1 receptor inhibitor NVP-AEW541. Growth reduction, caused by a combination of antiproliferative and proapoptotic effects, varied between 20% and 100%. Growth-inhibitory effects of IGF-1 receptor siRNA were also demonstrated in 2 of the cultures. Activating mutations in PIK3CA were found in 2 cultures, and 2 other cultures displayed ligand-independent Akt phosphorylation. Growth inhibition was significantly reduced in cultures with PIK3CA mutations or ligand-independent Akt phosphorylation. PTEN siRNA experiments supported the notion that the status of the PI3K/PTEN/Akt pathway is involved in determining NVP-AEW541 sensitivity. Combination treatments with either PI3 kinase or mTOR inhibitors together with NVP-AEW541 were performed. These experiments demonstrated the effects of NVP-AEW541 in cells not responding to mono-treatment with the IGF-1 receptor inhibitor, when used together with either of the 2 other inhibitors. Together, the studies support continued clinical development of IGF-1 receptor antagonists for glioblastomas and identify links between PI3K/PTEN/Akt status and sensitivity to mono-treatment with NVP-AEW541. Furthermore, the studies suggest that NVP-AEW541 is also active together with PI3 kinase and mTOR inhibitors in cultures with a dysregulated PI3K/PTEN/Akt pathway. These studies should assist in future clinical development of IGF-1 receptor antagonists for glioblastoma and other tumors.
Reliability and performance of commercial RNA and DNA extraction kits for FFPE tissue cores (2017)

Cancer biomarker studies often require nucleic acid extraction from limited amounts of formalin-fixed, paraffin-embedded (FFPE) tissues, such as histologic sections or needle cores. A major challenge is low quantity and quality of extracted nucleic acids, which can limit our ability to perform genetic analyses, and have a significant influence on overall study design. This study was aimed at identifying the most reliable and reproducible method of obtaining sufficient high-quality nucleic acids from FFPE tissues. We compared the yield and quality of nucleic acids from 0.6-mm FFPE prostate tissue cores across 16 DNA and RNA extraction protocols, using 14 commercially available kits. Nucleic acid yield was determined by fluorometry, and quality was determined by spectrophotometry. All protocols yielded nucleic acids in quantities that are compatible with downstream molecular applications. However, the protocols varied widely in the quality of the extracted RNA and DNA. Four RNA and five DNA extraction protocols, including protocols from two kits for dual-extraction of RNA and DNA from the same tissue source, were prioritized for further quality assessment based on the yield and purity of their products. Specifically, their compatibility with downstream reactions was assessed using both NanoString nCounter gene expression assays and reverse-transcriptase real-time PCR for RNA, and methylation-specific PCR assays for DNA. The kit deemed most suitable for FFPE tissue was the AllPrep kit by Qiagen because of its yield, quality, and ability to purify both RNA and DNA from the same sample, which would be advantageous in biomarker studies.
Laboratory Evaluation of I-129 and Tc-99 Removal at the F-Area Water Treatment Units (2003)

The results from this study suggest that the silver-modified carbons and the commercially available anion exchange resin, SIR-1200, were effective in removing I-129 from the feed water to low levels.
Resection and surgically targeted radiation therapy for locally recurrent GBM. (2021)

2054 Background: Recurrent GBM (rGBM) is a diffuse disease, and resection (R) alone does not provide durable local control (LC) or prolong overall survival (OS). Hypothesizing R plus immediate radiation (RT) may achieve durable LC and secondarily improve OS by permitting time for subsequent potentially effective but biologically slower treatments to have an impact, we prospectively evaluated R combined with a novel surgically targeted radiation therapy (STaRT) device utilizing Cs-131 embedded in bioresorbable collagen tiles. Methods: From 2/13-2/18 patients (pts) with locally recurrent GBM were treated on a prospective single arm trial (ClinicalTrials.gov, NCT#03088579) of maximum safe resection and immediate RT (GammaTile, GT Medical Technologies, Tempe AZ). Upon resection the at-risk areas of the surgical bed were lined with the GammaTile (GT) device, delivering 60-80 Gy at 5 mm. Follow up treatments were not specified but captured; no pt. underwent additional local therapy without progression, and no pt. was lost to follow up. We present study specified endpoints of local control (LC), overall survival (OS), and adverse events (AE), and a post hoc, hypothesis-generating analysis of outcomes by receipt of systemic (Sys) therapy. Results: 28 locally recurrent GBM were treated, 20 at first progression (range 1-3). Median age was 58 years (yrs.) (range 21-80), KPS 80 (60-100), female: male ratio 10:18 (36/64%). MGMT was methylated in 11%, unmethylated in 18%, and unknown in 71%. For all pts., median OS was 10.7 months (mo.) (range.1-42.3), and radiographic LC was 8.8 mo. (range.01-34.5). LC (defined as &lt; 15 mm from surgical bed) was maintained in 50% of pts., and no first failure was local. 12 mo. OS was 75% for pts. &lt; 50 yrs. vs. 43% for &gt; 50 yrs. (HR.46, p =.009). MGMT, KPS, and sex were non-predictive. After R+GT, 17 pts. received &gt; 1 cycle of systemic therapy (Sys), either as adjuvant or salvage, alone or in combination . Sys was bevacizumab (BEV) in 15 pts., temozolomide (TMZ) in 12, and lomustine (CCNU) in 8 (N &gt; 17 as some pts. received &gt; 1 Sys). Post hoc analysis disclosed a 15.1 mo. OS for pts. receiving &gt; 1 cycle of Sys (Sys+, N = 17) vs. 6.5 mo. for no Sys (Sys-, N = 11) (hazard ratio (HR).38, p =.017)). LC was 11.4 mo. for Sys+ and 2.1 mo. for Sys- (HR.44; p =.16)). Median OS (mo.) for BEV+ vs. BEV- was 16.7/4.5 (HR.38, p =.017), for TMZ+ vs. TMZ- 17.5/6.7 (HR.40, p =.025) and for CCNU+ vs. CCNU- 17.5/7.9 (HR.61, p =.25), respectively. Three attributed AE occurred, 1 dehiscence requiring surgery and 2 radiation brain effects, medically treated. 4 unrelated deaths occurred &lt; 60 days post-op, all in the Sys- cohort, impacting their opportunity for subsequent treatment. Conclusions: In this study local treatment alone was insufficient to achieve prolonged OS. Post hoc analysis suggests R+GT coupled with Sys may have potential to impact OS in rGBM patients. GT was FDA cleared in 2020 for use in newly diagnosed malignant and all recurrent intracranial neoplasms. Clinical trial information: NCT#03088579.
Styryl Dye Photosensitizer for Laser-Induced Photopolymerization. (1995)

フォトポリマー用増感色素の開発を目的として, 新規な分子内電荷移動型スチリル系色素を合成し, その光増感特性について検討した. これらの色素は可視レーザー光記録用波長 (488 nm) で高い吸収効率を示した. また, 酸化電位が低いので光重合開始系において, 既知の色素に比べて高い増感効果を示した. そしてこの色素は溶剤に対する溶解度が高いので可視アルゴンレーザー用増感色素として有望であることが分かった.
Elongated Copper Nanoparticles Coated with a Zwitterionic Surfactant (2000)

A sonochemical approach to the preparation of elongated copper nanoparticles coated with a zwitterionic surfactant, cetyltrimethylammonium p-toluene sulfonate (CTAPTS) is reported. A shape transition of the copper nanoparticles is found to occur due to the presence of an organized medium, consisting of a cylindrical, interconnected network of threadlike micelles. Transmission electron micrographs (TEM) show the presence of elongated copper nanoparticles coated with the surfactant. UV−visible spectroscopic studies point to the elongation of the copper nanoparticles and to the adsorption of the CTAPTS on the surface of the copper nanoparticles, which is corroborated by IR and NMR spectral studies. A monolayer coating of the surfactant is formed on the surface of the elongated copper nanoparticles. This is confirmed by comparing the weight loss obtained in thermogravimetric analysis with that obtained theoretically.
Expression Analysis of Taste Signal Transduction Molecules in the Fungiform and Circumvallate Papillae of the Rhesus Macaque, Macaca mulatta (2012)

The molecular mechanisms of the mammalian gustatory system have been examined in many studies using rodents as model organisms. In this study, we examined the mRNA expression of molecules involved in taste signal transduction in the fungiform papillae (FuP) and circumvallate papillae (CvP) of the rhesus macaque, Macaca mulatta, using in situ hybridization. TAS1R1, TAS1R2, TAS2Rs, and PKD1L3 were exclusively expressed in different subsets of taste receptor cells (TRCs) in the FuP and CvP. This finding suggests that TRCs sensing different basic taste modalities are mutually segregated in macaque taste buds. Individual TAS2Rs exhibited a variety of expression patterns in terms of the apparent level of expression and the number of TRCs expressing these genes, as in the case of human TAS2Rs. GNAT3, but not GNA14, was expressed in TRCs of FuP, whereas GNA14 was expressed in a small population of TRCs of CvP, which were distinct from GNAT3- or TAS1R2-positive TRCs. These results demonstrate similarities and differences between primates and rodents in the expression profiles of genes involved in taste signal transduction.
Rotatory Brownian motion of a rigid dumbbell (1974)

The frictional torque on a dumbbell rotating with time-dependent angular velocity is calculated from the hydrodynamic interaction between the two ends of the dumbbell. This leads to the correlation function for the random torque in rotatory Brownian motion. Although the motion of each dumbbell end has the characteristics of a translational motion, the correlation function at large times decays like t −5/2 , as in the case of a solid sphere. The correlation function may be calculated for the limiting case of very small angular displacements. The results for displacements of arbitrary magnitude are the same provided that terms quadratic in the angular velocity are negligible.
Inhibition of cytotoxicity and amyloid fibril formation by a D-amino acid peptide that specifically binds to Alzheimer's disease amyloid peptide (2008)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. The 'amyloid cascade hypothesis' assigns the amyloid-beta-peptide (Abeta) a central role in the pathogenesis of AD. Although it is not yet established, whether the resulting Abeta aggregates are the causative agent or just a result of the disease progression, polymerization of Abeta has been identified as a major feature during AD pathogenesis. Inhibition of the Abeta polymer formation, thus, has emerged as a potential therapeutic approach. In this context, we identified peptides consisting of d-enantiomeric amino acid peptides (d-peptides) that bind to Abeta. D-peptides are known to be more protease resistant and less immunogenic than the respective L-enantiomers. Previously, we have shown that a 12mer D-peptide specifically binds to Abeta amyloid plaques in brain tissue sections from former AD patients. In vitro obtained binding affinities to synthetic Abeta revealed a K(d) value in the submicromolar range. The aim of the present study was to investigate the influence of this d-peptide to Abeta polymerization and toxicity. Using cell toxicity assays, thioflavin fluorescence, fluorescence correlation spectroscopy and electron microscopy, we found a significant effect of the d-peptide on both. Presence of D-peptides (dpep) reduces the average size of Abeta aggregates, but increases their number. In addition, Abeta cytotoxicity on PC12 cells is reduced in the presence of dpep.
Increased copy number at 17q22-q24 by CGH in breast cancer is due to high-level amplification of two separate regions (1997)

Studies by comparative genomic hybridization (CGH) have defined a chromosomal site at 17q22-q24 that is often overrepresented in breast cancer, neuroblastoma, and several other tumor types. Due to the limited resolution and dynamic range of CGH, it remain unclear whether this gain reflects high-level amplification of small subregion(s) or low-level gain of most of the distal 17q. We used 32 physically mapped 17q probes to construct more accurate copy number profiles for 14 breast cancer cell lines by interphase fluorescence in situ hybridization (FISH). Six cell lines (43%) showed an increased copy number of the 17q-22q24 region by CGH, and seven (50%) by FISH. FISH copy number profiles had a substantially higher dynamic range than did CGH profiles. FISH revealed two independent, highly amplified regions (A and B) at 17q23, separated by about 5 Mb of non-amplified DNA. These regions were distinctly telomeric from the ERBB2 gene locus. However, region A was often co-amplified with ERBB2, whereas B was amplified in cell lines that showed no ERBB2 amplification. We conclude that distal 17q gains recently discovered in breast cancer by CGH are due to high-level amplifications of two different regions at 17q23. This chromosomal region has previously been reported to undergo allelic loss and therefore was thought to harbor a tumor suppressor gene. The present FISH data provide support for the presence, and a starting point for the positional isolation, of 17q23 genes whose upregulation by amplification may play a role in the progression of breast cancer and many other tumor types.
Mitochondrial genome copy number measured by DNA sequencing in human blood is strongly associated with metabolic traits via cell-type composition differences (2020)

Abstract Mitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell type composition. Here, we studied MT-CN variation in blood-derived DNA from 19,184 Finnish individuals using a combination of genome (N = 4,163) and exome sequencing (N = 19,034) data as well as imputed genotypes (N = 17,718). We identified two loci significantly associated with MT-CN variation: a common variant at the MYB-HBS1L locus (P = 1.6×10 −8 ), which has previously been associated with numerous hematological parameters; and a burden of rare variants in the TMBIM1 gene (P = 3.0×10 −8 ), which has been reported to protect against non-alcoholic fatty liver disease. We also found that MT-CN is strongly associated with insulin levels (P = 2.0×10 −21 ) and other metabolic syndrome (metS) related traits. Using a Mendelian randomization framework, we show evidence that MT-CN measured in blood is causally related to insulin levels. We then applied an MT-CN polygenic risk score (PRS) derived from Finnish data to the UK Biobank, where the association between the PRS and metS traits was replicated. Adjusting for cell counts largely eliminated these signals, suggesting that MT-CN affects metS via cell type composition. These results suggest that measurements of MT-CN in blood-derived DNA partially reflect differences in cell-type composition and that these differences are causally linked to insulin and related traits.
Effect of Capsaicin as a Neuropeptide-Releasing Substance on Sneezing Reflex in a Type I Allergic Animal Model (1992)

To elucidate the effect of capsaicin-sensitive nerve fibers, which are known to contain substance P (SP) and other sensory neuropeptides, on the sneezing reflex, we have investigated the effect of capsaicin on this reflex provoked in guinea pigs passively sensitized with anaphylactic antibody followed by specific antigen challenge. It has already been established that histamine released from mast cells is a reliable inducer of the sneezing reflex in type I allergy. Our experimental results indicated that the frequency of sneezing provoked by antigen challenge as well as histamine application was significantly reduced by pretreatment with capsaicin in a dose-dependent fashion. SP is considered to be one of the main neurotransmitters in sensory nerves. When the amount of SP in animal nasal mucosa was measured 12 h after capsaicin treatment, a marked reduction was noted. However, the histamine content in the nasal mucosa was not changed by capsaicin treatment. These data suggest that neuropeptides, especially SP, which are released or depleted from sensory nerves by capsaicin treatment, probably play an important role as neurotransmitters of the stimulant histamine in the development of sneezing in type I allergy.
Application of the Chiral Bis(phosphine) Monoxide Ligand to Catalytic Enantioselective Addition of Dialkylzinc Reagents to β-Nitroalkenes (2006)

[reaction: see text] Me-DuPHOS monoxide is shown to be a very effective ligand in the enantioselective copper-catalyzed addition of dialkylzinc reagents to beta-nitroalkenes providing access to chiral nitroalkanes. The major advantages of this process are high yields, broad and complementary substrate scope, and high enantioselectivities. The effect of achiral dummy ligands as an additive has also been documented.
Anomalous increase in modulus upon hydration in random copolymers with hydrophobic segments and hydrophilic blocks (2012)

The polymers with hydrophilic moieties typically become soft upon hydration. Here we report an exception to this rule. The modulus was found to increase upon water uptake in polymers in which hydrophilic poly(ethylene glycol) (PEG) segments were incorporated randomly into a chain of hydrophobic segments of 3,5-diiodo desaminotyrosyl-tyrosine ethyl ester. The Young's modulus of the copolymer increased by as much as 15-fold upon hydration with 30 to 60 vol% of PEG. This increase in modulus was fully reversible and was observed at both 22 °C and the physiological temperature of 37 °C. A degree of hydration of ∼3 water molecules per ethylene glycol and hydration-induced phase separation of hydrophilic domains appear to be essential for the observed increase in modulus. This stiffening effect is attributed to the PEG segments in the hydrated domains that no longer participate in the transfer of stress through the polymer matrix as they do when they are molecularly dispersed along the polymer chain in the dry state.
Theory of genus reduction in alkali-induced graphitization of nanoporous carbon (2007)

Exposure to elemental Cs generates graphitic domains within nanoporous carbon at only $50\phantom{\rule{0.2em}{0ex}}\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$, well below the typical graphitization temperatures of $&gt;1000\phantom{\rule{0.2em}{0ex}}\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$. We present a model of nanoporous carbon, the wormhole, which can express the fundamental topological elements of graphitization: a negative-curvature analog to ${\mathrm{C}}_{60}$ fullerene. The pathway to wormhole annihilation comprises an initial Stone-Wales transformation and a subsequent unzipping of the defect. This complex $\ensuremath{\sim}100$-atom collective defect disintegrates with the formation of only two dangling bonds. Our ab initio calculations show that while the activation barrier against reduction in topological genus is indeed lowered by interaction with alkali, an additional chemical constituent must be involved to account for this remarkable local graphitization of nanoporous carbons at near-room temperature.
Neuroprotective effects of granulocyte‐colony stimulating factor in a novel transgenic mouse model of SCA17 (2011)

J. Neurochem. (2011) 118 , 288–303. Abstract Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant inherited disorder characterized by degeneration of spinocerebellar tracts and selected brainstem neurons owing to the expansion of a CAG repeat of the human TATA‐binding protein ( hTBP ) gene. To gain insight into the pathogenesis of this hTBP mutation, we generated transgenic mice with the mutant hTBP gene driven by the Purkinje specific protein (Pcp2/L7) gene promoter. Mice with the expanded hTBP allele developed ataxia within 2–5 months. Behavioral analysis of L7‐hTBP transgenic mice showed reduced fall latency in a rotarod assay. Purkinje cell degeneration was identified by immunostaining of calbindin and IP3R1. Reactive gliosis and neuroinflammation occurred in the transgenic cerebellum, accompanied by up‐regulation of GFAP and Iba1. The L7‐hTBP transgenic mice were thus confirmed to recapitulate the SCA17 phenotype and were used as a disease model to explore the potential of granulocyte‐colony stimulating factor in SCA17 treatment. Our results suggest that granulocyte‐colony stimulating factor has a neuroprotective effect in these transgenic mice, ameliorating their neurological and behavioral deficits. These data indicate that the expression of the mutant hTBP in Purkinje cells is sufficient to produce cell degeneration and an ataxia phenotype, and constitutes a good model for better analysis of the neurodegeneration in SCA17.
Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass (2017)

A correction to this article has been published and is linked from the HTML version of this article.