gebhart/patrepeval huggingface dataset:
Parallel Synthesis of a Biased Library of Thiazolidinones as Novel Sodium Channel Antagonists (2003)

A biased chemical library containing 91 differentially substituted thiazolidinones was prepared in an effort to improve the pharmacology of a known anticonvulsant agent V102862. The collection was prepared in a single step multi-component condensation reaction that produced good yields and very high crude purity (75%-85%). Seven compounds, identified within the library were shown to be more potent than V102862, our parent reference compound, in an electrophysiological assay measuring sodium channel antagonism. The most potent compound, 3-(2-piperidinylethyl)-2-(3-(3-trifluoromethylphenoxy)phenyl)thiazolidinone, has a Ki of 90 nM.
Immunolocalization of Periostin-like Factor and Periostin During Embryogenesis (2007)

Periostin-like factor (PLF) and Periostin are alternatively spliced mRNAs. Our findings are the first to show similarities and differences between PLF and Periostin location using isoform-specific antibodies. The differences in when and where they are present during mouse embryogenesis suggest that they may have different functions. Using immunostaining techniques, we observed that PLF was highly expressed at 12.5 days postconception (dpc) in the intermediate and outer zones of most brain regions, spinal cord, cranial and spinal nerves, and chondrocytes in developing bone and in the heart wall. By 16.5 dpc, PLF was also present in ameloblasts and odontoblasts in developing teeth, and by 19.5 dpc, PLF was present at low levels only in vagal nerve bundles, discrete white matter bundles in the brain, and chondrocytes of developing ribs. Periostin, on the other hand, was absent at 12.5 dpc from dorsal spinal cord and from cranial and spinal nerves. By 16.5 dpc, Periostin was present in many spinal nerves, but absent thereafter, and at 19.5 dpc, Periostin was present in chondrocytes in developing bone but not in neural tissues. The different spatial and temporal location of PLF and Periostin in cartilage and bone cells suggests different roles for these proteins in endochondral bone formation. The early expression of PLF in brain differentiation zones and in developing axon bundles and nerves suggests that it may facilitate axon growth.
Preparation of poly(fluorene)s using trans‐bis(dicyclohexylamine)palladium diacetate as a catalyst: Scope and limitations (2006)

trans-Bis(dicyclohexylamine)palladium diacetate was tested in a Suzuki-type poly(fluorene) synthesis. Poly(9,9-dihexylfluorene) was prepared in only 2 h with alcohols as the solvent and KOH as the base. The concomitant occurrence of Suzuki coupling, debromination, hydrolytic deboronation, and hydroxy deboronation reactions was demonstrated and used in a such way that either dihydrogen-terminated or partly hydroxy-terminated poly(fluorene)s could be obtained.
Iron-streptomycin derived catalyst for efficient oxygen reduction reaction in ceramic microbial fuel cells operating with urine (2019)

In recent years, the microbial fuel cell (MFC) technology has drawn the attention of the scientific community due to its ability to produce clean energy and treat different types of waste at the same time. Often, expensive catalysts are required to facilitate the oxygen reduction reaction (ORR) and this hinders their large-scale commercialisation. In this work, a novel iron-based catalyst (Fe-STR) synthesised from iron salt and streptomycin as a nitrogen-rich organic precursor was chemically, morphologically and electrochemically studied. The kinetics of Fe-STR with and without being doped with carbon nanotubes (CNT) was initially screened through rotating disk electrode (RDE) analysis. Then, the catalysts were integrated into air-breathing cathodes and placed into ceramic-type MFCs continuously fed with human urine. The half-wave potential showed the following trend Fe-STR > Fe-STR-CNT ≫ AC, indicating better kinetics towards ORR in the case of Fe-STR. In terms of MFC performance, the results showed that cathodes containing Fe-based catalyst outperformed AC-based cathodes after 3 months of operation. The long-term test reported that Fe-STR-based cathodes allow MFCs to reach a stable power output of 104.5 ± 0.0 μW cm<sup>-2</sup>, 74% higher than AC-based cathodes (60.4 ± 3.9 μW cm<sup>-2</sup>). To the best of the Authors' knowledge, this power performance is the highest recorded from ceramic-type MFCs fed with human urine.
Full-wave PEEC time-domain method for the modeling of on-chip interconnects (2001)

With the advances in the speed of high-performance chips, inductance effects in some on-chip interconnects have become significant. Specific networks such as clock distributions and other highly optimized circuits are especially impacted by inductance. Several difficult aspects have to be overcome to obtain valid waveforms for problems where inductances contribute significantly. Mainly, the geometries are very complex and the interactions between the capacitive and inductive currents have to be taken into account simultaneously. In this paper, we show that a full-wave partial element equivalent circuit method, which includes the delays among the partial elements, leads to an efficient solver enabling the analysis of large meaningful problems. Applying this method to several examples leads to helpful insights for realistic very large scale integration wiring problems. It is shown in this paper that the impact overshoot, reflections, and inductive coupling are critical for the design of critical on-chip interconnects.
Blockade of NAALADase: A Novel Neuroprotective Strategy Based on Limiting Glutamate and Elevating NAAG (1999)

Excessive glutamate receptor activation is thought to be involved in the neuronal injury caused by stroke. Based on the hypothesis that N-acetyl-aspartyl-glutamate (NAAG) is a modulatory neurotransmitter or storage form of glutamate, we have pursued a novel strategy of therapeutic intervention, blockade of N-acetylated alpha-linked acidic dipeptidase (NAALADase), the enzyme that hydrolyzes NAAG to liberate glutamate. Using the suture model of transient middle cerebral artery occlusion (MCAO) in rats, the prototype NAALADase inhibitor 2-(phosphonomethyl)pentanedioic acid (2-PMPA) dramatically reduced extracellular glutamate accumulation measured by microdialysis both during a 2-hour occlusion and during reperfusion, consistent with an effect on glutamate supply. During reperfusion, the decrease in glutamate was accompanied by an equimolar, reciprocal rise in extracellular NAAG. NAALADase inhibition may prove to be a well tolerated therapy for cerebral ischemia. In addition, NAALADase inhibitors should prove to be important tools in understanding the physiological role of NAAG in the brain.
Clinical characteristics and molecular features of non-small cell lung cancers (NSCLCs) following disease progression on immune checkpoint inhibitors (ICIs). (2022)

e21178 Background: ICIs are cornerstones of therapy for advanced NSCLC. Despite dramatic and sometimes durable responses to therapy, most patients (pts) either (i) do not respond to therapy (intrinsic resistance), or (ii) subsequently progress after initial clinical benefit (acquired resistance). Currently, insights into the molecular mechanisms of resistance to ICIs in NSCLC are lacking. Methods: To investigate clinical and molecular features of pts progressing on ICIs, we identified pts who underwent repeat tumor biopsies on and/or after disease progression on ICIs and were included in the Stand Up 2 Cancer (SU2C)/Mark Foundation multi-institutional cohort. Biopsy specimens underwent whole-exome sequencing (WES) and/or whole transcriptome sequencing (RNAseq). Results: We identified 37 pts who underwent a total of 47 repeat biopsies on or after ICIs. Six pts underwent multiple post-ICI biopsies (range 2-4). Twenty-five pts (68%) received PD-(L)1 inhibitor monotherapy, 6 (16%) received PD-(L)1 plus CTLA-4 inhibitors, and 6 (16%) received other PD-1 inhibitor-based combinations. Overall, the objective response rate was 46% among pts undergoing repeat biopsies (complete response 2 [5%], partial response 15 [41%], stable disease 14 [38%], progressive disease 5 [14%] and not evaluable 1 [3%]). Median progression-free survival (PFS) was 8.1 months. In total, pre-ICI biopsy specimens were available in 20 pts. WES and RNAseq were performed on 67 and 44 specimens, respectively. Median tumor mutation burden (TMB) in pre-ICI specimens was 5.0 mutations/Mb versus 4.9 mutations/Mb in post-ICI specimens ( p= 0.3, Mann-Whitney U test). Among 20 paired pre/post-ICI specimens, there was no significant difference in TMB (pre-treatment median 3.9 mutations/Mb; post-treatment median 4.3 mutations/Mb; p= 0.7, Wilcoxon signed-rank test). One pt with a complete response acquired a nonsense mutation in B2M, and one pt with a partial response acquired a nonsense mutation in JAK1. Among 10 paired pre/post-ICI specimens that underwent RNAseq, we observed significant decreases in granzyme B and perforin in post-ICI specimens ( p= 4×10 -5 and p= 2×10 -3 , respectively, limma-voom analysis). Conclusions: Genomic alterations impairing antigen presentation (e.g., B2M) or immune activation (e.g., JAK1) may enable resistance to ICIs in a small subset of cases. However, the majority of repeat biopsies obtained from pts progressing on ICIs lacked clear genetic mediators of resistance, suggesting the presence of additional tumor-intrinsic and/or tumor-extrinsic factors underlying resistance to ICIs in NSCLC.
Activation of NMDA receptors induces protein kinase A‐mediated phosphorylation and degradation of matrin 3. Blocking these effects prevents NMDA‐induced neuronal death (2005)

Activation of NMDA receptors leads to activation of cAMP-dependent protein kinase (PKA). The main substrates phosphorylated by PKA following NMDA receptor activation remain unidentified. The aim of this work was to identify a major substrate phosphorylated by PKA following NMDA receptor activation in cerebellar neurones in culture, and to assess whether this phosphorylation may be involved in neuronal death induced by excessive NMDA receptor activation. The main PKA substrate following NMDA receptor activation was identified by MALDI-TOFF fingerprinting as the nuclear protein, matrin 3. PKA-mediated phosphorylation of matrin 3 is followed by its degradation. NMDA receptor activation in rat brain in vivo by ammonia injection also induced PKA-mediated matrin 3 phosphorylation and degradation in brain cell nuclei. Blocking NMDA receptors in brain in vivo with MK-801 reduced basal phosphorylation of matrin 3, suggesting that it is modulated by NMDA receptors. Inhibition of PKA with H-89 prevents NMDA-induced phosphorylation and degradation of matrin 3 as well as neuronal death. These results suggest that PKA-mediated phosphorylation of matrin 3 may serve as a rapid way of transferring information from synapses containing NMDA receptors to neuronal nuclei under physiological conditions, and may contribute to neuronal death under pathological conditions.
Efficient graphical-processor-unit parallelization algorithm for computing Eigen values (2020)

Several leading-edge applications such as pathology detection, biometric identification, and face recognition are based mainly on blob and line detection. To address this problem, Eigen value computing has been commonly employed due to its accuracy and robustness. However, Eigen value computing requires a raised computational processing, intensive memory data access, and data overlapping, which involve higher execution times. To overcome these limitations, we propose in this paper a new parallel strategy to implement Eigen value computing using a graphics processing unit (GPU). Our contributions are (1) to optimize instruction scheduling to reduce the computation time, (2) to efficiently partition processing into blocks to increase the occupancy of streaming multiprocessors, (3) to provide efficient input data splitting on shared memory to benefit from its lower access time, and (4) to propose new data management of shared memory to avoid access memory conflict and reduce memory bank accesses. Experimental results show that our proposed GPU parallel strategy for Eigen value computing achieves speedups of 27 compared with a multithreaded implementation, of 16 compared with a predefined function in the OpenCV library, and of eight compared with a predefined function in the Cublas library, all of which are performed into a quad core multi-central-processing unit platform. Next, our parallel strategy is evaluated through an Eigen value-based method for retinal thick vessel segmentation, which is essential for detecting ocular pathologies. Eigen value computing is executed in 0.017 s when using Structured Analysis of the Retina database images. Accordingly, we achieved real-time thick retinal vessel segmentation with an average execution time of about 0.039 s.
Hybrid Technologies for Water Heating Applications: A Review (2023)

The over-reliance on fossil resources necessitates the development of a sustainable energy system. Renewable energy and efficient hybrid water heating technologies are viable net-zero energy options. The economic benefits of these hybrid technologies offer a promising prospect for widespread adoption in developing countries as a means of increasing the hot water production. These hybrid technologies are becoming increasingly popular for domestic thermal applications in remote areas to compensate for energy shortages. This paper provides an overview of hybrid renewable water heating technologies with a focus on hybrid configurations, optimization techniques, mono-particle, and hybrid nanofluids and modelling. This paper also highlights the prospects for increasing the economic attractiveness and public acceptance of such systems.
Beyond spectral gap: The role of the topology in decentralized learning (2022)

In data-parallel optimization of machine learning models, workers collaborate to improve their estimates of the model: more accurate gradients allow them to use larger learning rates and optimize faster. We consider the setting in which all workers sample from the same dataset, and communicate over a sparse graph (decentralized). In this setting, current theory fails to capture important aspects of real-world behavior. First, the 'spectral gap' of the communication graph is not predictive of its empirical performance in (deep) learning. Second, current theory does not explain that collaboration enables larger learning rates than training alone. In fact, it prescribes smaller learning rates, which further decrease as graphs become larger, failing to explain convergence in infinite graphs. This paper aims to paint an accurate picture of sparsely-connected distributed optimization when workers share the same data distribution. We quantify how the graph topology influences convergence in a quadratic toy problem and provide theoretical results for general smooth and (strongly) convex objectives. Our theory matches empirical observations in deep learning, and accurately describes the relative merits of different graph topologies.
Multimodal motion guidance (2012)

The ability to guide human motion through automatically generated feedback has significant potential for applications in areas, such as motor learning, human-computer interaction, telepresence, and augmented reality.
IPv6 Support for Generic Routing Encapsulation (GRE) (2015)

Generic Routing Encapsulation (GRE) can be used to carry any network-
layer payload protocol over any network-layer delivery protocol.
Currently, GRE procedures are specified for IPv4, used as either the
payload or delivery protocol. However, GRE procedures are not
specified for IPv6. This document specifies GRE procedures for IPv6,
used as either the payload or delivery protocol.
Potent Antiviral Effect of Reverset™ in HIV-1-Infected Adults following a Single Oral Dose (2004)

Reverset™ (2′,3′-didehydro-2′,3′-dideoxy-5-fluorocyti-dine, RVT) is a potent inhibitor of HIV-1 replication in cell culture, with a 90% effective concentration at or below 1 μM. In vitro, RVT retains its activity against isolates harbouring mutations in the reverse transcriptase (RT) gene that otherwise confer resistance to lamivudine and/or zidovudine. The pharmacokinetics and safety of single oral doses of RVT (10–200 mg) were evaluated in an initial Phase I clinical trial. The viral load changes were determined on 18 HIV-1-infected antiretroviral therapy-naive subjects that were randomized into three cohorts, each cohort consisting of three study periods. The subjects received up to two oral doses of active drug and one placebo dose with a 1-week washout period separating the three study periods. Quantification of viral RNA was performed on the pre-dose, 12, 24 and 48 h post-dose plasma samples. A single oral dose of RVT to antiretroviral-naive subjects significantly reduced plasma viral load by 0.45 ±0.10 log 10 copies/ml ( P=0.0003). A mean drop of 0.37 ±0.12 log 10 copies/ml ( P=0.001) was obtained at the lowest dose of 10 mg. Sequence analysis of the HIV-1 RT gene performed before and after RVT dosing detected no genotypic changes in this short-term study. The viral RT gene of one subject had at predose the following genotype: L41 + N103 + C181 + W210 + D215, indicating prior exposure to zidovudine and non-nucleoside analogues, and anticipating high-level resistance against these agents. A single 10 mg RVT dose resulted in a viral load drop of 0.61 ±0.05 log 10 providing evidence that a viral strain with the indicated genotype is susceptible to RVT.
Phosphoramidates as Steering Elements for Highly Selective Access to Complementary Imidazo[1,2-a]pyrimidine Isomers (2019)

We report that selective <i>N</i>-phosphorylation of aminoimidazoles results in a key steering element that controls isomeric selectivity in the condensation of β-ethoxy acrylamides and aminoimidazoles to furnish imidazo[1,2-<i>a</i>]pyrimidines. We identified conditions that provide highly selective (99:1) phosphorylation at the endo- or exocyclic nitrogen. Either the 2-amino or 4-amino isomer of the (benzo)imidazo[1,2-<i>a</i>]pyrimidine products could be isolated in 64-95% yield. Mass spectrometric analysis and computational studies give insight into the mechanism of this exceptionally selective transformation.
Global Workforce Bolsters U.S. Science (2004)

B eginning in the 1930s and continuing through the 1950s, the United States gradually earned a dominant position in science and engineering. Those gains were made in part through the influx of foreign-born scientists from Europe, and later from the developing world, who were attracted by the
Smectic Liquid‐Crystalline Colloids by Miniemulsion Techniques (2005)

The preparation of liquid-crystalline colloids with diameters in the range of about 100 to 300 nm is reported. Different preformed smectic polysiloxanes have been transferred into colloids by a miniemulsion process with ionic surfactants. Microscopy of unstained colloids clearly show the smectic layer structure within them (see Figure) and are prove the model of a microphase separation between mesogens and polysiloxane chains in liquid-crystalline polysiloxanes.
Binding affinity and inhibitory potency of neomycin and streptomycin on the Tat peptide interaction with HIV-1 TAR RNA detected by on-line acoustic wave sensor (2003)

The binding of two aminoglycoside antibiotics, neomycin and streptomycin, to a segment of the transactivation responsive region (TAR) RNA of the human immunodeficiency virus, and their inhibitory potency to disrupt the interaction of the RNA with a regulatory Tat protein-derived peptide, have been studied using a flow-through acoustic wave detector system. Binding affinity is directly correlated with the inhibitory potency of these molecules and the acoustic wave detection system shows that neomycin exhibits at least a ten-fold greater affinity for TAR RNA and that it is also a more potent inhibitor than streptomycin. These results are in agreement with previous studies. However, unlike the time-consuming batch-based assays, use of the flow-through format offers considerable potential for the rapid screening of the chemistry of relatively small-molecule-nucleic acid binding events.
Cover Picture: Chemical and (Photo)‐Catalytical Transformations in Photonic Crystal Fibers (ChemCatChem 3/2013) (2013)

Photonic crystal fibers as photocatalytic microreactors! The cover picture shows a photonic crystal fiber (PCF), which can guide light in a hollow core filled with reactants and catalysts. In their Concept paper on p. 641 ff., researchers from the Excellence Cluster Engineering of Advanced Materials in Erlangen describe recent progress on using PCFs as reactors with nL volumes, and discuss the further opportunities raised by the unique technology. The excellent overlap between guided light and fluids in the core allows for in situ spectroscopy and photochemical activation. Compared to spectroscopy using conventional cuvettes of centimeter dimensions, interaction lengths up to several meters can easily be achieved, making it possible to detect compounds in ultra-low concentrations. In addition, the small core diameter means that ultra-high power densities can be reached at moderate laser powers, which is advantageous for photochemical activation.
IC‐P‐045: PET IMAGING OF SYNERGISTIC, BUT MODALLY DISTINCT, OBESITY‐ AND Aβ‐TRIGGERED ABNORMALITIES IN CEREBRAL GLUCOSE METABOLISM AND GLIOSIS IN MICE (2014)

High sucrose, high saturated fat western diets are increasingly leading to health issues such as obesity, metabolic syndrome and diabetes. Growing evidence also suggests that the western diet, and resulting metabolic abnormalities such as chronic hyperglycemia and inflammation, may increase the risk of cognitive decline and Alzheimer's disease (AD). The aim of this study was to assess changes in cerebral glucose metabolism and glial TSPO expression in response to obesity and intracerebroventricular Aβ infusion in vivo using PET. Three month old C57BL/J6 mice were fed either a standard (non-obese group) or high fat diet (obese group) for 3 months, and intracerebroventricularly infused with vehicle or Aβ-42. Fasting levels of blood glucose and insulin were measured as a marker of peripheral hyperglycemia, while brain [18 F]FDG uptake was assessed by PET a marker of cerebral metabolism. As a marker of deleterious gliosis, brain uptake of a TSPO ligand, [11 C]PBR-28, was assessed by PET. In vivo [11 C]PBR-28 uptake was confirmed by autoradiography of brain sections obtained from scanned mice. TSPO expression in glial subpopulations was confirmed by immunohistochemistry, co-staining with the glial markers CD-11b and GFAP. Obesity combined with A β infusion synergistically increased cerebral glucose metabolism and TSPO signals as assessed by PET. In autoradiographic sections, increased TSPO signals were associated with A β -infusion, but not obesity, although severe gliosis was observed by immunohistochemistry in both models of inflammation. In contrast, obesity-induced inflammation alone was associated with reduced TSPO signals detected by PET and autoradiography. FDG and TSPO may be useful imaging biomarkers for the identification of early-stage metabolic and inflammatory pathogenic changes in obesity associated with cognitive decline and AD risk. Increased brain [18 F]FDG uptake observed A β -infused mice may reflect increased metabolic demand resulting from gliosis or seizure activity. Surprisingly, obesity-induced inflammation was associated with decreased TSPO signals, which could potentially indicate qualitative differences in glial function between the two models of inflammation.