gebhart/patrepeval huggingface dataset:
Novel druggable mechanism of Parkinson's disease: Potential therapeutics and underlying pathogenesis based on ferroptosis (2023)

Genetics, age, environmental factors, and oxidative stress have all been implicated in the development of Parkinson's disease (PD); however, a complete understanding of its pathology remains elusive. At present, there is no cure for PD, and currently available therapeutics are insufficient to meet patient needs. Ferroptosis, a distinctive iron-dependent cell death mode characterized by lipid peroxidation and oxidative stress, has pathophysiological features similar to those of PD, including iron accumulation, reactive oxygen species-induced oxidative damage, and mitochondrial dysfunction. Ferroptosis has been identified as a specific pathway of neuronal death and is closely related to the pathogenesis of PD. Despite the similarities in the biological targets involved in PD pathogenesis and ferroptosis, the relationship between novel targets in PD and ferroptosis has been neglected in the literature. In this review, the mechanism of ferroptosis is discussed, and the potential therapeutic targets implicated in both PD and ferroptosis are compared. Furthermore, the anti-PD effects of several ferroptosis inhibitors, as well as clinical studies thereof, and the identification of novel lead compounds for the treatment of PD and the inhibition of ferroptosis are reviewed. It is hoped that this review can promote research to further elucidate the relationship between ferroptosis and PD and provide new strategies for the development of novel ferroptosis-targeting PD therapy.
Measure of Forming Limit Strain on the Aluminum Sheets Passed Through Draw-Bead by Digital Image Correlation (2015)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;Accurate determination of the forming limit strain of aluminum sheet metal is an important topic which has not been fully solved by industry. Also, the effects of draw beads (enhanced forming limit behaviors), normally reported on steel sheet metals, on aluminum sheet metal is not fully understood. This paper introduces an experimental study on draw bead effects on aluminum sheet metals by measuring the forming limit strain zero (FLD&lt;sub&gt;0&lt;/sub&gt;) of the sheet metal. Two kinds of aluminum, AL 6016-T4 and AL 5754-0, are used. Virgin material, 40% draw bead material and 60% draw bead material conditions are tested for each kind of aluminum. Marciniak punch tests were performed to create a plane strain condition. A dual camera Digital Image Correlation (DIC) system was used to record and measure the deformation distribution history during the punch test. The on-set necking timing is determined directly from surface shape change. The FLD&lt;sub&gt;0&lt;/sub&gt; of each test situation is reported in this article. From the results of this study, the draw bead effects (enhanced forming limit behaviors) are found in both aluminums tested. Basic theory, experiment plan, experimental setup, test results and data analysis are shown in detail in this paper.&lt;/div&gt;&lt;/div&gt;
ChemInform Abstract: Total Synthesis of UK‐1. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Total syntheses of (+)-hypusine and its (2S,9S)-diastereomer (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal syntheses of (+)-hypusine and its (2S,9S)-diastereomerRaymond J. Bergeron, Michael X. B. Xia, and Otto Phanstiel IVCite this: J. Org. Chem. 1993, 58, 24, 6804–6806Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://pubs.acs.org/doi/10.1021/jo00076a048https://doi.org/10.1021/jo00076a048research-articleACS PublicationsRequest reuse permissionsArticle Views284Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Nanoparticle assembly and sintering towards all-copper flip chip interconnects (2015)

The current feed capability of typical flip chip electrical interconnects is constrained by the solder alloy, as it is more susceptible to electromigration than the copper used for the pads and wires. Hence, interconnects formed by copper only mitigate the electromigration risk and/or allow to increase the current limit of the all-copper interconnect. In this work, two methods to form all-copper flip chip interconnects at an annealing temperature of 250 °C are presented. The interconnects in the contact region between Cu pillars and Cu pads with a pitch down to 150 μm are formed by Cu nanoparticle self-assembly and sintering. In the first method, the entire gap between a Cu pillar chip and a substrate was filled with a Cu nano-suspension. The formation of capillary bridges during the evaporation of the dispersant directed the self-assembly of the nanoparticles towards the contact region between Cu pillars and Cu pad. In the second method, the Cu pillar chip was dipped into a film of the Cu nano-suspension, followed by a transfer, placement and release with a die bonder onto pads on a substrate. The annealing of the Cu nanoparticles is performed in both cases in a reducing formic acid atmosphere. The first method was more susceptible to the formation of shorts between pillars, whereas the second method resulted in electrical functional chip to substrate assemblies. Interconnects with a mean electrical resistance of 26 ± 3 mΩ and a shear strength ranging from 4.6 to 12.3 MPa were achieved. The sintered Cu nanoparticles bridged gaps up to 10 μm between copper pillars and pads, demonstrating the potential to apply the joint also on non-planar substrates. Nevertheless, imperfections such as voids and cracks are still present in the joints and need further process development, to improve the quality and process robustness further.
Free-standing mesoporous silica films; morphogenesis of channel and surface patterns (1997)

Extraordinary channel patterns have been observed in an oriented mesoporous silica film that is synthesized at the boundary between air and water. The basic channel designs comprise concentric circles, herringbones, fingerprints and hairpins. It is suggested that these patterns are spatio-temporal silicified recordings of the polymerization and growth of a silicate liquid-crystal seed emerging in two spatial dimensions at the air/water interface. The origin of the channel patterns may be from defects, such as disclinations and dislocations, that spontaneously form in a surface confined precursor silicate liquid-crystal film to give a liquid-crystalline texture to the resulting mesoporous silica film. The reaction–diffusion processes and defects that are believed to contribute to the curved three-dimensional morphologies and channel patterns of mesoporous silica free to grow in solution, may also occur in the surface version, except that the isotropy of solution is replaced by the anisotropy of the air/water interface together with proximity effects from neighboring growth centers. Polymerization induced radial stresses produced in the as-synthesized mesoporous silica film before drying, are relieved through warping of the film into micrometer-scale hillock-shaped protuberances. These mounds are arranged into patterns that appear to reflect the channel designs within the film. A linear radial stress model is found to successfully account for the warp patterns. A possible connection between the two-dimensional channel patterns in mesoporous silica films and the two-dimensional stripe domain patterns found in modulated phases is discussed.
Human Molecular Genetics and Genomics — Important Advances and Exciting Possibilities (2021)

Human Molecular Genetics and Genomics Genomic research has evolved from seeking to understand the fundamentals of the human genetic code to examining the ways in which this code varies among people...
Orally administered CCR2 selective inhibitor CCX872-b clinical trial in pancreatic cancer. (2017)

276 Background: CCR2 inhibition decreases tumor-associated macrophages and Treg cells, and increases CD8+ and CD4+ T cells in pancreatic tumors. Single oral doses of 150 mg CCX872-B were well tolerated in patients with pancreatic cancer. The first stage results of the multiple dose part of this study are presented. Methods: Patients with locally advanced or metastatic pancreatic cancer, ECOG score ≤ 2 were studied. Patients received FOLFIRINOX (fluorouracil [5-FU], leucovorin, irinotecan, oxaliplatin) q2weeks for up to 24 wks plus 150 mg CCX872-B once or twice daily until disease progression or intolerance to CCX872-B. The primary efficacy endpoint is progression-free survival (PFS) at 24 wks. Tumor control rate (TCR) and the objective response rate (ORR), a secondary endpoint, are presented. Results: Fifty patients were enrolled. Baseline: Mean ± SD age: 60 ± 8.6 years, male 52%; primary tumor location: head 57%, body/tail 41%, local recurrence 2%; metastatic disease 78%, ECOG score 0: 62%, ECOG score 1: 38%. Thirty five of 50 patients completed week 12. Most common reasons for early withdrawal were subject request (5 pts) and adverse events typically associated with FOLFIRINOX (4 pts). In the pre-specified analysis population, i.e., those with ≥ 1 post baseline CT scan, tumor control at wk 12 was achieved in 32 of 41 (78%) patients, with 15 of 41 (37%) partial responders, and 17 of 41 (41%) with stable disease. The ORR was 37% (all partial responders) in the primary analysis population (30% when all enrolled patients were included). Thirteen of 21 patients with available CT scan results at week 24 were progression-free. Mean trough CCX872 plasma level was ~8 μg/mL. CCR2 was covered 88% on average by CCX872-B based on receptor occupancy assays. CCX872-B appeared to be well tolerated and the incidence of ≥ Gr 3 AEs was not increased with CCX872-B plus FOLFIRINOX vs historical data with FOLFIRINOX alone. The complete set of PFS data will be available by the end of 2016. Conclusions: CCX872-B plus FOLFIRINOX resulted in a TCR of 78% and an ORR of 30 to 37% with no safety issues ascribed to CCX872-B use. Clinical trial information: NCT02345408.
Gastrointestinal secretory, motor, circulatory, and metabolic effects of prosomatostatin. (1981)

This study compares the gastrointestinal effects of somatostatin (SS) and its putative prohormone, prosomatostatin (Pro-SS), a 28-amino acid peptide isolated from the hypothalamus and the gut, in conscious dogs with chronic gastric and pancreatic fistulae. Pro-Ss suppressed the release of serum gastrin, insulin, and pancreatic polypeptide that occurs in response to feeding a meat meal in a manner similar to that seen with SS. However, in contrast to SS, which strongly reduced intestinal blood flow and oxygen consumption and stimulated intestinal motility, Pro-SS, at the doses tested, had no influence on mesenteric circulation, oxygen uptake, and intestinal motility. We conclude that Pro-SS mimics most of the gastrointestinal secretory actions of SS, but does not exhibit the intestinal circulatory, metabolic, and motor effects of SS.
Implementation of a DPU-Based Intelligent Thermal Imaging Hardware Accelerator on FPGA (2021)

Thermal imaging has many applications that all leverage from the heat map that can be constructed using this type of imaging. It can be used in Internet of Things (IoT) applications to detect the features of surroundings. In such a case, Deep Neural Networks (DNNs) can be used to carry out many visual analysis tasks which can provide the system with the capacity to make decisions. However, due to their huge computational cost, such networks are recommended to exploit custom hardware platforms to accelerate their inference as well as reduce the overall energy consumption of the system. In this work, an energy adaptive system is proposed, which can intelligently configure itself based on the battery energy level. Besides achieving a maximum speed increase that equals 6.38×, the proposed system achieves significant energy that is reduced by 97.81% compared to a conventional general-purpose CPU.
Mechanisms of vascular dysfunction in mice with endothelium-specific deletion of the PPAR-δ gene (2014)

Peroxisome proliferator-activated receptor (PPAR)-δ is a nuclear hormone receptor that is mainly involved in lipid metabolism. Recent studies have suggested that PPAR-δ agonists exert vascular protective effects. The present study was designed to characterize vascular function in mice with genetic inactivation of PPAR-δ in the endothelium. Mice with vascular endothelial cell-specific deletion of the PPAR-δ gene (ePPARδ(-/-) mice) were generated using loxP/Cre technology. ePPARδ(-/-) mice were normotensive and did not display any sign of metabolic syndrome. Endothelium-dependent relaxations to ACh and endothelium-independent relaxations to the nitric oxide (NO) donor diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate were both significantly impaired in the aorta and carotid arteries of ePPARδ(-/-) mice (P < 0.05). In ePPARδ(-/-) mouse aortas, phosphorylation of endothelial NO synthase at Ser(1177) was significantly decreased (P < 0.05). However, basal levels of cGMP were unexpectedly increased (P < 0.05). Enzymatic activity of GTP-cyclohydrolase I and tetrahydrobiopterin levels were also enhanced in ePPARδ(-/-) mice (P < 0.05). Most notably, endothelium-specific deletion of the PPAR-δ gene significantly decreased protein expressions of catalase and glutathione peroxidase 1 and resulted in increased levels of H2O2 in the aorta (P < 0.05). In contrast, superoxide anion production was unaltered. Moreover, treatment with catalase prevented the endothelial dysfunction and elevation of cGMP detected in aortas of ePPARδ(-/-) mice. The findings suggest that increased levels of cGMP caused by H2O2 impair vasodilator reactivity to endogenous and exogenous NO. We speculate that chronic elevation of H2O2 predisposes PPAR-δ-deficient arteries to oxidative stress and vascular dysfunction.
ChemInform Abstract: Selective and Potent β2‐Adrenoceptor Agents within the Tetrahydroisoquinoline Class; Effect of Methyl Substitution at the Benzylic Carbon of the 1‐(3,4,5‐Trimethoxybenzyl) Group of Trimetoquinol. (1982)

Abstract Auf den im Formelschema skizzierten Wegen werden die Trimetoquinol‐Analoga (V) dargestellt.
Fitting Curves to Human Respiratory Data (1997)

SUMMARY Records of gas flow during breathing are cyclical, with the cycles varying in duration. The shape of these cycles may change with the intensity of respiratory stimulation or the development of respiratory disease, but currently research is hampered by the lack of a fully satisfactory technique for determining the shape of a typical cycle. The approach adopted here is to replace the time series by a ‘phase diagram’, plotting the time integral of flow against flow itself. Principal curves are then fitted. These are curves ‘through the middle of the data’ which were introduced by Hastie and Stuetzle. The shapes of these curves are compared, either directly or after reconstructing an average cycle corresponding to each fitted curve. This has the advantage that the shape of the waveform is separated from the amplitude, and from the duration of the breath. A disadvantage is that periods of zero flow are lost, and the reconstructed average cycle may show irregularities at points near zero flow as a result. In practice, the methodology showed clear differences in shape between the protocols, gave reasonable average cycles and ordered the waveform shapes according to the hardness of breathing induced by the protocols.
The almost magical world of photonic crystals (2003)

An innovative and exciting new class of materials has emerged called photonic band gap materials, or photonic crystals. The specific applications, needed performance, and overall fabrication costs will dictate the gap properties of the photonic crystal. In this regard a very significant and attractive difference between photonic crystals and electronic semiconductor crystals is the former's inherent ability to provide complete tunability to the desired performance specifications. In recent years, work in the field of photonic crystals has focused primarily on designing and fabricating crystals with 2D and 3D omnidirectional band gaps and on studying the properties of defects in these crystals. Given a photonic crystal with a complete band gap, light with a frequency inside the gap is forbidden to exist within the material unless there is a defect (or a break in the periodic dielectric function) in the otherwise perfect photonic crystal. Such a defect will act like an internal surface within which a photon is confined or localized. A point-like defect will act like a cavity, a line-defect will act like a waveguide, and a planar-defect or surface will act like a perfectly reflecting mirror. Moreover, the structural and material properties of these defects (unlike electronic defects in semiconductors) can be completely and continuously tuned to provide whatever photon properties are desired. Using this great flexibility, researchers could design photonic crystal structures to control and mold the properties of light in new and important ways.
Design and Performance of a Miniaturized High-Speed Continuous-Flow Analyzer (1974)

Abstract Design features and performance of a miniaturized high-speed continuous-flow analyzer are described. Special emphasis is made in the design towards a system that is free from the operational and mechanical complexities found in most of today’s advanced systems. Depending on the particular analyses, sample size varies from 3 to 25 µl and reagent consumption is less than 180 µl per sample. Analyses are performed under steady-state conditions at sampling rates of 150 samples per hour with a 2:1 or 3:1 sample-to-wash ratio. The marked reduction in sample size makes the system ideal for microanalyses, especially in the pediatric clinical laboratory, in small animal research, and in any other cases where small sample volume is especially important.
Quantum Computational Quantification of Protein-Ligand Interactions (2021)

We have demonstrated a prototypical hybrid classical and quantum computational workflow for the quantification of protein-ligand interactions. The workflow combines the Density Matrix Embedding Theory (DMET) embedding procedure with the Variational Quantum Eigensolver (VQE) approach for finding molecular electronic ground states. A series of $β$-secretase (BACE1) inhibitors is rank-ordered using binding energy differences calculated on the latest superconducting transmon (IBM) and trapped-ion (Honeywell) Noisy Intermediate Scale Quantum (NISQ) devices. This is the first application of real quantum computers to the calculation of protein-ligand binding energies. The results shed light on hardware and software requirements which would enable the application of NISQ algorithms in drug design.
EPCO-25. MULTI-OMICS DISEASE STRATIFICATION IN PATIENTS WITH IDH-WILDTYPE GLIOBLASTOMA: SYNERGISTIC VALUE OF CLINICAL MEASURES, CONVENTIONAL AND DEEP RADIOMICS, AND GENOMICS FOR PREDICTION OF OVERALL SURVIVAL (2021)

Abstract PURPOSE Multi-omics data integration captures tumor characteristics at multiple scales [i.e., microscopic (genomics and epigenetics), macroscopic (radiomics), clinical manifestation], provides a more comprehensive assessment of patient’s risk, and facilitates personalized therapies. In this work, we investigated the synergistic value of such multiple data sources for risk stratification and prediction of overall survival in IDH-wildtype glioblastoma tumors. METHODS Quantitative conventional and deep radiomics were extracted from pre-operative multi-parametric structural MRI (T1, T1Gd, T2, T2-FLAIR) of 501 patients with newly diagnosed glioblastoma. 389/501 and 112/501 patients formed our discovery and replication cohorts, respectively. Conventional radiomics were extracted from CaPTk, and deep radiomics from a pre-trained VGG-19 model. Multivariate SVM classification was performed on the discovery cohort to stratify patients in high, medium, and low-risk groups, using recursive feature elimination and 5-fold cross-validation. This model was independently tested on the replication cohort, and a radiomic-based survival prediction index (SPIradiomics) was calculated for each patient. Multi-stage integration of omics data, i.e., clinical (age, gender, extent of resection (EOR)), SPIradiomics, epigenetics (MGMT promoter methylation), and genomics (27 clinically relevant gene mutations via next-generation sequencing (NGS)), was performed using multivariate Cox proportional hazards (Cox-PH) model for stratification of the risk in the replication cohort. RESULTS Cox-PH modeling resulted in a concordance index (c-index) of 0.65 (95% CI:0.6–0.7) for clinical data, 0.67 (95% CI:0.62–0.72) for clinical and epigenetics, 0.70 (95% CI:0.65–0.75) for clinical and radiomics, 0.72 (95% CI:0.68–0.77) for clinical, epigenetics, and radiomics, and 0.75 (95% CI:0.71 – 0.78) for the multi-omics combination of all data; highlighting the added value of each layer of information in prediction of the patient’s risk. CONCLUSION Our results reinforce the synergistic value of integrated diagnostic methods for improving risk assessment of patients with glioblastoma that may pave the path towards a more personalized treatment planning.
An R248C mutation of FGFR3 leading to thanatophoric dysplasia type I. (1999)

Thanatophoric dysplasia (TD) is the most common form of lethal neonatal dwarfism with micromelic shortening of the limbs, macrocephaly, platyspondyly, and reduced thoracic cavity. R248C mutation in the extracellular domain of fibrobast growth factor receptor 3 (FGFR3) was common in TD type I. Two TD type I patients were examined for R248C mutation by use of restriction digestion and direct sequencing. The results showed that both patients carried R248C mutation. Because of the homogeneity of R248C mutation among different ethnic populations, all TD patients should be analysed using this PCR-based method presented in this work.