gebhart/patrepeval huggingface dataset:
Mistranslation Drives Alterations in Protein Levels and the Effects of a Synonymous Variant at the Fibroblast Growth Factor 21 Locus (2021)

Fibroblast growth factor 21 (FGF21) is a liver-derived hormone with pleiotropic beneficial effects on metabolism. Paradoxically, FGF21 levels are elevated in metabolic diseases. Interventions that restore metabolic homeostasis reduce FGF21. Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor in altering FGF21 levels and function in humans is unknown. A genetic approach is used to help resolve this paradox. The authors demonstrate that the primary event in dysmetabolic phenotypes is the elevation of FGF21 secretion. The latter is regulated by translational reprogramming in a genotype- and context-dependent manner. To relate the findings to tissues outcomes, the minor (A) allele of rs838133 is shown to be associated with increased hepatic inflammation in patients with metabolic associated fatty liver disease. The results here highlight a dominant role for translation of the FGF21 protein to explain variations in blood levels that is at least partially inherited. These results provide a framework for translational reprogramming of FGF21 to treat metabolic diseases.
Multiphasic Collagen Scaffolds for Engineered Tissue Interfaces (2018)

Abstract Hard–soft tissue interfaces pose unique challenges for regeneration due to architectural, mechanical, and compositional changes between tissues, which are difficult to incorporate into tissue engineering scaffolds. Multiphasic scaffolds are needed to better mimic structural and chemical changes through the incorporation of layers with distinct properties. A particular challenge in the production of multilayered constructs is achieving cohesion between layers. Herein, a novel system is developed, which combines sequential collagen self‐assembly and diffusion gradients in mineralization to produce multiphasic collagen scaffolds that have intrinsic connectivity and porosity between layers, with no need for adhesives or heat treatments. The scaffolds incorporate mineralized layers, wherein the mineralized collagen fibrils have intrafibrillar oriented mineral resembling bone, alongside unmineralized layers. The interface between mineralized and unmineralized layers is sharp and well defined, with nonmineralized fibrils inserting into the mineralized layer to create mechanical interlock and cohesion. Inspired by the complex architecture of the periodontal attachment apparatus (bone–ligament–cementum), it is demonstrated that the model system can be applied to the development of a trilayered collagen scaffold with potential for periodontal regeneration.
La maladie de Tchekhov : écriture, thématiques, enjeux (2022)

de la scne
CYP2C9 genotype and ibuprofen (IBU) pharmacokinetics (PK) in cystic fibrosis (CF)1 (1999)

Clinical Pharmacology & Therapeutics (1999) 65, 140–140; doi:
64Cu Labeled AmBaSar-RGD2 for micro-PET Imaging of Integrin αvβ3 Expression (2011)

Integrin αvβ3 plays a critical role in tumor-induced angiogenesis and metastasis. Previously, a 64Cu-AmBaSar- RGD monomer with high in vivo stability compared with 64Cu-DOTA-RGD was developed for integrin αvβ3 PET imaging. It has been established that dimeric RGD peptides have higher receptor-binding affinity and superior in vivo kinetics compared with monomeric RGD peptides due to the polyvalency effect. In this context, we synthesized and evaluated 64Cu-labeled AmBaSar dimeric RGD conjugates (64Cu-AmBaSar-RGD2) for PET imaging of integrin αvβ3 expression. The dimeric RGD peptide was conjugated with a cage-like chelator AmBaSar and labeled with 64Cu. Cell binding, microPET imaging, receptor blocking, and biodistribution studies of 64Cu-AmBaSar-RGD2 were conducted in the U87MG human glioblastoma xenograft model. AmBaSar-RGD2 conjugate was obtained in reasonable yield (45.0 ± 2.5%, n= 4) and the identity was confirmed by HPLC and MS (found 1779.8, calculated m/z for [M+H]+ M: C81H125N27O19 1779.9). 64Cu-AmBaSar-RGD2 was obtained with high radiochemical yield (92.0 ± 1.3%) and purity (≥ 98.0%) under mild conditions (pH 5.0~5.5, 23~37 °C) in 30 min. The specific activity of 64Cu-AmBaSar-RGD2 was estimated to be 15-22 GBq/µmol at the end of synthesis. Based on microPET imaging and biodistribution studies, 64Cu-AmBaSar-RGD2 has demonstrated higher tumor uptake at selected time points than 64Cu-AmBaSar-RGD. At 20 h p.i., the tumor uptake reached 0.65 ± 0.05 %ID/g for 64Cu-AmBaSar-RGD and 1.76 ± 0.38 %ID/g for 64Cu-AmBaSar-RGD2, respectively. The integrin αvβ3 targeting specificity was confirmed by blocking experiments. Therefore, the new tracer 64Cu-AmBaSar- RGD2 exhibited better tumor-targeting efficacy and more favorable in vivo pharmacokinetics than the 64Cu labeled RGD monomer due to the polyvalency effect.
A Robust Deflation based Demultiplexing Algorithm for PSK/QAM Coherent Optical Systems (2011)

We propose an adaptation of the CMA algorithm in order to ensure singularity-free transmission independently of the channel characteristics. This adaptation is implemented using a blockwise approach in 112Gbit/s context and valid for PSK/QAM formats.
Questionable Efficacy of Extracorporeal Shock Wave Therapy for Peyronie’s Disease:: Results of a Prospective Approach (2004)

According to our data ESWT does not appear to be significantly effective for decreasing penile curvature and plaque size or improving sexual function in the total population of patients with Peyronie's disease despite improvements in individuals. Penile pain seems to resolve earlier than during the natural course. Regarding the results of this study and previous reports with exact documentation of the clinical findings it can be concluded that ESWT cannot be recommended as a standard procedure for Peyronie's disease. To evaluate the exact efficacy of ESWT a controlled, single-blind, multicenter study with exact documentation of symptoms is urgently required.
64CuCl2 PET/CT in Prostate Cancer Relapse (2017)

Our objective was to evaluate the biodistribution, kinetics, and radiation dosimetry of <sup>64</sup>CuCl<sub>2</sub> in humans and to assess the ability of <sup>64</sup>CuCl<sub>2</sub> PET/CT to detect prostate cancer (PCa) recurrence in patients with biochemical relapse. <b>Methods:</b> We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external-beam radiation therapy. All patients underwent <sup>64</sup>CuCl<sub>2</sub> PET/CT, <sup>18</sup>F-choline PET/CT, and multiparametric MRI within 15 d of each other. Experienced readers interpreted the images, and the detection rate (DR) of each imaging modality was calculated. Histopathology, when available; clinical or laboratory response; and multidisciplinary follow-up were used to confirm the site of disease. In parallel, biodistribution, kinetics of the lesions, and radiation dosimetry of <sup>64</sup>CuCl<sub>2</sub> were evaluated. <b>Results:</b> From a dosimetric point of view, an administered dose of 200 MBq for <sup>64</sup>CuCl<sub>2</sub> translated into a 5.7-mSv effective dose. Unlike <sup>18</sup>F-choline, <sup>64</sup>CuCl<sub>2</sub> was not excreted or accumulated in the urinary tract, thus allowing thorough pelvic exploration. The maximum <sup>64</sup>CuCl<sub>2</sub> uptake at the sites of PCa relapse was observed 1 h after tracer injection. In our cohort, <sup>64</sup>CuCl<sub>2</sub> PET/CT proved positive in 41 of 50 patients, with an overall DR of 82%. The DRs of <sup>18</sup>F-choline PET/CT and multiparametric MRI were 56% and 74%, respectively. The difference between the DRs of <sup>64</sup>CuCl<sub>2</sub> PET/CT and <sup>18</sup>F-choline PET/CT was statistically significant (<i>P</i> < 0.001). Interestingly, on considering prostate-specific antigen (PSA) value, <sup>64</sup>CuCl<sub>2</sub> PET/CT had a higher DR than <sup>18</sup>F-choline PET/CT in patients with a PSA of less than 1 ng/mL. <b>Conclusion:</b> The biodistribution of <sup>64</sup>CuCl<sub>2</sub> is more suitable than that of <sup>18</sup>F-choline for exploring the pelvis and prostatic bed. The <sup>64</sup>CuCl<sub>2</sub> effective dose is like those of other established PET tracers. In patients with biochemical relapse and a low PSA level, <sup>64</sup>CuCl<sub>2</sub> PET/CT shows a significantly higher DR than <sup>18</sup>F-choline PET/CT.
Mechanistic Difference in Photoreduction of Phenacyl Halides by NADH Model Compounds (1988)

Abstract Photoreduction of phenacyl halides by an NADH model compound, 10-methylacridan (AcrH2), in MeCN proceeds via photoinduced electron transfer from the singlet excited state of AcrH2 to phenacyl halides without the contribution of radical chain reactions, while the photoreduction by another NADH model compound, 1-benzyl-1,4-dihydronicotinamide (BNAH), proceeds via photoinduced radical chain reactions. The origin of the mechanistic difference between AcrH2 and BNAH has been discussed.
ChemInform Abstract: VINYLCYCLOHEXATRIENEIRON TRICARBONYL COMPLEXES OF THE DIENE TYPE VIA OLEFIN ISOMERIZATION OF ALLYL‐AROMATICS (1978)

Abstract Der Versuch mit Allylbenzol (V) eine zu Allylnaphthalin (I) analoge Reaktion mit Eisencarbonylen durchzuführen, lieferte statt des erhofften, (III) entsprechenden Vinylkomplexes das zweikernige Produkt (VI).
The UK10K project identifies rare variants in health and disease (2015)

The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7x) or exomes (high read depth, 80x) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.
Induction of Vascular Endothelial Growth Factor by IGF-I in Osteoblast-Like Cells Is Mediated by the PI3K Signaling Pathway through the Hypoxia-Inducible Factor-2α (2002)

IGF-I is known to stimulate the expression of oxygen- and nutrient-sensitive genes in several cell types. In this study we investigated the signaling pathways and transcriptional mechanisms that mediate IGF-I induction of vascular endothelial growth factor (VEGF) expression in human osteoblast-like cells. IGF-I (50 ng/ml) induced a rapid increase (3-fold) in VEGF mRNA in osteoblasts that was accompanied by an increase in the level of hypoxia-inducible factor-2alpha (HIF-2alpha) protein without changes in HIF-2alpha mRNA expression. These effects were mimicked by chemical inhibition of proteosomal degradation of HIF-2alpha. Transcriptional activation of a proximal VEGF promoter-luciferase construct was greatly enhanced by cotransfection with an HIF-2alpha, but not an HIF-1alpha, construct. IGF-I acutely stimulated Akt phosphorylation, which was abolished by pretreatment of cells with the PI3K inhibitor LY294002. Pretreatment of the cells with LY294002 also greatly attenuated IGF-I induction of HIF-2alpha and blunted IGF-I-induced VEGF promoter activity. Finally, forced expression of a constitutively active PI3K expression construct induced VEGF promoter to levels similar to those observed with IGF-I alone. These data indicate that IGF-I, by activation of the PI3K pathway, induces VEGF expression in osteoblasts through a transcriptional control mechanism common to those that activate VEGF and other hypoxia response genes.
p53 tumor suppressor gene mutation in early esophageal precancerous lesions and carcinoma among high-risk populations in Henan, China. (1994)

To understand whether p53 gene mutation is an early or late event in esophageal carcinogenesis, biopsy samples of esophageal epithelium from symptom-free subjects in a high incidence area, Huixian county of Henan Province, China, were analyzed. Mutations in exons 5, 6, 7, and 8 of p53 were analyzed by single-strand conformation polymorphism analysis and DNA sequencing. Among the 37 biopsy samples showing accumulation of p53 protein in immunohistochemical staining, missense mutations of p53 gene were detected in 1 of 3 samples with normal epithelia, 3 of 23 samples with basal cell hyperplasia, and 4 of 11 samples with dysplasia. All mutations occurred at exon 5 with 3 at codon 175, 2 at codon 176, and 1 each at codons 159, 135, and codon 132. Of the 8 mutations, there were 3 G to A transitions and 3 G to T transversions. To understand the mutation spectrum and possible causative factors of esophageal cancer in this area, surgically resected human primary esophageal carcinomas from Linxian county were analyzed for p53 gene mutations in exons 5, 6, 7, and 8. Mutations were detected in 16 of 29 samples (55%). Twelve samples contained different missense point mutations, with 75% transitions (7 G to A and 2 A to G) and 25% transversions (2 G to T and 1 G to C). Most of the mutations were located at either exon 5 or exon 7. A deletion and an insertion of nucleotides leading to frame-shift mutations were detected in each of two other samples. The results demonstrate that p53 protein accumulation and gene mutation may occur at very early stages of esophageal carcinogenesis. In carcinomas, there was a higher frequency of p53 gene mutations, which accounts for most of the cases with p53 protein accumulation.
Fluorescence Probes in Oncology (2002)

The Nature of Light Introduction to Photophysics Basic Approaches to the Experimental Study of Chemical and Biological Luminescence Methods and Instrumentation New Methods. Theoretical Basis and Potential Applications to Biology Fluorescent Probes Applications of Fluorescence Techniques to Study Biological Processes in Normal and Pathological Cells Cell Physiopathology.
Cep55/c10orf3, a Tumor Antigen Derived From a Centrosome Residing Protein in Breast Carcinoma (2009)

Identification of tumor-associated antigens may facilitate vaccination strategies to treat patients with malignant diseases. We have found that the centrosomal protein, Cep55/c10orf3 acts as a novel breast carcinoma-associated tumor-associated antigen. Cep55/c10orf3 mRNA was detectable in a wide variety of tumor cell lines. Expression was barely detectable in normal tissues except for testis and thymus. Moreover, Cep55/c10orf3 protein could be detected by a monoclonal anti-Cep55/c10orf3 antibody (# 11-55) in 69.8% of breast carcinoma, 25% of colorectal carcinoma, and 57.8% of lung carcinoma tissues. The expression of Cep55/c10orf3 protein did not show any relationship with the hormone receptors such as estrogen receptor and progesterone receptor or expression patterns of p185 HER2/neu. We designed 11 peptides which displayed a human leukocyte antigen-A24 binding motif. One Cep55/c10orf3-peptide, Cep55/c10orf3_193(10) (VYVKGLLAKI), induced cytotoxic T lymphocytes (CTLs) in 3 of 3 patients with Cep55/c10orf3 (# 11-55)-positive breast carcinoma. A Cep55/c10orf3_193(10)-specific CTL clone could also recognize Cep55/c10orf3 (+) displayed on human leukocyte antigen-A24 (+) cancer cell lines. These data indicate that Cep55/c10orf3 peptides were naturally presented by breast cancer cells and can cause CTL clonal expansion in vivo. Monoclonal antibody # 11-55 and the Cep55/c10orf3_193(10) peptides may be useful as part of a therapeutic strategy for hormonal therapy or anti-p185 HER2/neu monoclonal antibody therapy-resistant breast carcinoma patients.
Aberrant expression of the glycolytic enzymes aldolase B and type II hexokinase in hepatocellular carcinoma are predictive markers for advanced stage, early recurrence and poor prognosis (2008)

Cancer cells with a high glycolytic rate have an advantage in tumor growth. Hepatocellular carcinoma (HCC) often exhibits an aberrant expression of glycolytic enzymes, particularly type II hexokinase (HKII) and aldolase B (ALDOB). This study examined the aberrant expression of HKII and ALDOB in 203 surgically resected HCCs. A dramatic down-regulation of ALDOB was found in 116 HCCs (57%), while 43% of HCCs maintained the expression. HKII mRNA was overexpressed in 70 (35%) primary HCCs. The ALDOB down-regulation and HKII overexpression correlated with high-grade (grade II-IV) HCC (all ps<0.0001), portal vein invasion (stage IIIB-IV) (ps<1x10(-6)), early tumor recurrence (ETR) (p<0.001 and p<0.01, respectively) and a lower 5-year survival (p=0.000001 and p=0.0062, respectively). Notably, in stage II HCC which had no vascular invasion, the ALDOB down-regulation was associated with ETR (p<0.05) and a lower 5-year survival (p=0.015). The down-regulation of ALDOB correlated with a high AFP (p=1x10(-8)), whereas the overexpression of HKII, which has two functional motifs for the mutant p53, correlated with the p53 mutation, p<0.01. The three factors (ALDOB down-regulation, HKII overexpression and p53 mutation) not only correlated with tumor progression, but also interacted with one another, leading to a more aggressive HCC with a portal vein invasion and various extent of intrahepatic metastasis by more than four-fold (ps<1x10(-6)) and frequent ETR by more than two-fold (ps<0.0001) compared with HCCs without the events. In conclusion, the aberrant expression of ALDOB and HKII is associated with advanced disease, ETR and poor prognosis, and ALDOB down-regulation in stage II HCC is a predictive marker of ETR and an unfavorable outcome.
Efficient Boolean function matching (1992)

We propose efficient new algorithms for performing the matching step in technology mapping. Our main result is an algorithm for matching under input negations that takes time polynomial in the size of the BDDs representing the functions to be matched. This algorithm is the basis for efficient methods for matching under permutations, bridging and constant inputs. We implemented a simple mapper based on our algorithms, and tested it on a suite of combinational circuits. Using the Actel type 1 mother cell, our mapper required an average of 8.5% fewer cells than mispga. When integrated into a more sophisticated technology mapper, we believe our matching algorithms could provide even better performance.
The Small Noncoding DsrA RNA Is an Acid Resistance Regulator inEscherichia coli (2004)

DsrA RNA is a small (87-nucleotide) regulatory RNA of Escherichia coli that acts by RNA-RNA interactions to control translation and turnover of specific mRNAs. Two targets of DsrA regulation are RpoS, the stationary-phase and stress response sigma factor (sigmas), and H-NS, a histone-like nucleoid protein and global transcription repressor. Genes regulated globally by RpoS and H-NS include stress response proteins and virulence factors for pathogenic E. coli. Here, by using transcription profiling via DNA arrays, we have identified genes induced by DsrA. Steady-state levels of mRNAs from many genes increased with DsrA overproduction, including multiple acid resistance genes of E. coli. Quantitative primer extension analysis verified the induction of individual acid resistance genes in the hdeAB, gadAX, and gadBC operons. E. coli K-12 strains, as well as pathogenic E. coli O157:H7, exhibited compromised acid resistance in dsrA mutants. Conversely, overproduction of DsrA from a plasmid rendered the acid-sensitive dsrA mutant extremely acid resistant. Thus, DsrA RNA plays a regulatory role in acid resistance. Whether DsrA targets acid resistance genes directly by base pairing or indirectly via perturbation of RpoS and/or H-NS is not known, but in either event, our results suggest that DsrA RNA may enhance the virulence of pathogenic E. coli.
Neural Substrates of Word Generation during Stroke Recovery: The Influence of Cortical Hypoperfusion (2007)

Several studies have demonstrated reorganization of cognitive and motor function caused by stroke. This study examined the influence of hypoperfused brain regions, in addition to the area of the infarct itself, on reorganization of the cognitive processes underlying word generation in stroke patients. In addition, we also sought to determine the influence of hypoperfusion on the blood oxygen level dependent/(BOLD) effect. Subjects with left and right subacute or chronic subcortical strokes, along with normal controls, were imaged while performing a verbal fluency task (word generation). The study population included six normal subject and six stroke patients with subcortical infarcts and cortical hypoperfusion in the middle cerebral artery territory who had recovered or improved markedly in word fluency. While normal subjects displayed a left-lateralized fronto-temporo-parietal and bilateral cingulo-striatal-thalamic-cerebellar network, the activation pattern of stroke patients was determined both by the hypoperfused regions and infarcted areas of the brain. Specifically, patients showed diminished BOLD effect in the cortical regions that were hypoperfused, even though their infarcts were subcortical, and showed increased BOLD effect in the homologous regions of the normal hemisphere. This finding raises the possibility that cortical hypoperfusion in the absence of infarct can cause shift of language functions to the opposite, intact hemisphere. However, reduced BOLD effect in the task relative to rest was found in hypoperfused regions in two patients, raising the possibility that regional function persisted, even though vascular reactivity was impaired. Results illustrate the complexities of functional imaging studies of recovery in patients with vascular lesions.