gebhart/patrepeval huggingface dataset:
Solvolytic rearrangement of 1,2,3-tri-tert-butyl-3-dichloromethylcyclopropene and cis-3,4-dichloro-1,2,3-tri-tert-butylcyclobutene (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolvolytic rearrangement of 1,2,3-tri-tert-butyl-3-dichloromethylcyclopropene and cis-3,4-dichloro-1,2,3-tri-tert-butylcyclobuteneAndrew E. Feiring and Joseph. CiabattoniCite this: J. Am. Chem. Soc. 1973, 95, 16, 5266–5272Publication Date (Print):August 1, 1973Publication History Published online1 May 2002Published inissue 1 August 1973https://pubs.acs.org/doi/10.1021/ja00797a029https://doi.org/10.1021/ja00797a029research-articleACS PublicationsRequest reuse permissionsArticle Views31Altmetric-Citations13LEARN 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
Central Role of α-Synuclein Oligomers in Neurodegeneration in Parkinson Disease (2008)

Selective death of nigrostriatal neurons, which leads to Parkinson disease, is explained by misfolding of brain protein alpha-synuclein. Herein, we review the data supporting this concept, propose a scheme of events leading to synuclein-induced neuronal death, and discuss protein deacetylase sirtuins as new potential therapeutic targets involved in this process.
A Components Based Framework for Quantum Key Distribution Networks (2020)

The difficulties related to operating basic quantum communication technologies and the inherent limitations of their direct transmission distances, be these be a consequence of absorption or optical aperture, leads to the fact that current generations of Quantum Key Distribution (QKD) systems are essentially designed to work in a stand-alone mode on a single link. This limits their utility and the potential impact on the market. To avoid these barriers, it is necessary to advance towards systems built for a network. QKD systems have to perform as network devices, and ideally on an equal footing with other telecom devices, without requiring any specialized or ad hoc tuning. To achieve this “zero-touch” integration, it is necessary to build a software ecosystem. This software should take a bare QKD system and provide all the information, so that the network can manage and the applications use the system. Here we present a SW architecture, based on components with a well-defined functionality, to build the SW ecosystem needed to deploy QKD systems in networks. The components support traditional and Software Defined Networks (SDN), as well as separated or integrated (sharing infrastructure) networks to improve their industrialization.
TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Metastatic Prostate Cancer (2021)

This randomized trial establishes meaningful clinical activity and safety of BAT and supports additional study to determine its optimal clinical integration. BAT can sensitize CRPC to subsequent antiandrogen therapy. Further study is required to confirm whether sequential therapy with BAT and enzalutamide can improve survival in men with CRPC.
Estimation of Pediatric Dosage of Antimalarial Drugs, Using Pharmacokinetic and Physiological Approach (2023)

Most of the individuals who die of malaria in sub-Saharan Africa are children. It is, therefore, important for this age group to have access to the right treatment and correct dose. Artemether-lumefantrine is one of the fixed dose combination therapies that was approved by the World Health Organization to treat malaria. However, the current recommended dose has been reported to cause underexposure or overexposure in some children. The aim of this article was, therefore, to estimate the doses that can mimic adult exposure. The availability of more and reliable pharmacokinetic data is essential to accurately estimate appropriate dosage regimens. The doses in this study were estimated using the physiological information from children and some pharmacokinetic data from adults due to the lack of pediatric pharmacokinetic data in the literature. Depending on the approach that was used to calculate the dose, the results showed that some children were underexposed, and others were overexposed. This can lead to treatment failure, toxicity, and even death. Therefore, when designing a dosage regimen, it is important to know and include the distinctions in physiology at various phases of development that influence the pharmacokinetics of various drugs in order to estimate the dose in young children. The physiology at each time point during the growth of a child may influence how the drug is absorbed, gets distributed, metabolized, and eliminated. From the results, there is a very clear need to conduct a clinical study to further verify if the suggested (i.e., 0.34 mg/kg for artemether and 6 mg/kg for lumefantrine) doses could be clinically efficacious.
Suuplementary Movie SM2 from Tumor-Penetrating iRGD Peptide Inhibits Metastasis (2023)

&lt;p&gt;Suuplementary Movie SM2. Collapse of cellular protrusions upon interaction with iRGD silver nanoparticles&lt;/p&gt;
Private independence testing across two parties (2022)

We introduce $π$-test, a privacy-preserving algorithm for testing statistical independence between data distributed across multiple parties. Our algorithm relies on privately estimating the distance correlation between datasets, a quantitative measure of independence introduced in Székely et al. [2007]. We establish both additive and multiplicative error bounds on the utility of our differentially private test, which we believe will find applications in a variety of distributed hypothesis testing settings involving sensitive data.
Activation of Human Endothelial Cells via S-Endo-1 Antigen (CD146) Stimulates the Tyrosine Phosphorylation of Focal Adhesion Kinase p125FAK (1998)

S-Endo-1 antigen (CD146), a transmembrane receptor also known as MUC18/MCAM, is a member of the immunoglobulin superfamily and belongs to a group of cell adhesion molecules. CD146 is highly expressed on the whole vascular tree. We demonstrate here that engagement of CD146 on human endothelial cells isolated from cord blood results in tyrosine phosphorylation of a large panel of cellular proteins, although no tyrosine phosphorylation of CD146 was detected. In particular, CD146 cross-linking induces the tyrosine phosphorylation of the protein tyrosine kinase p125(FAK) as well as p125(FAK) association with paxillin, both events being inhibited by cytochalasin D. No direct association of CD146 with p125(FAK) was observed. Consistent with these data, CD146 associates with p59(fyn), a Src family kinase known to phosphorylate p125(FAK). The identification of a signaling pathway initiated by CD146 engagement and which includes p59(fyn), p125(FAK), and paxillin indicates that CD146 participates in outside-in signaling in endothelial cells.
Fully Orthogonally Protected 2-Deoxystreptamine from Kanamycin (2008)

A fully orthogonally protected and enantiopure 2-deoxystreptamine derivative is prepared in a few straightforward steps from commercially available kanamycin. Resolution of a sterically hindered diacetate was effected by a Verenium esterase and was followed by a chemoselective Staudinger reduction-acylation protocol.
Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis (2017)

Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the eNOS mRNA 3'-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3'-UTR activity of eNOS mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and N-acetylcysteine prevented H<sub>2</sub>O<sub>2</sub>-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.
Medical diagnostic-based sensor selection (2011)

Wearable sensing systems have facilitated a variety of applications in Wireless Health. Due to the considerable number of sensors and their constant monitoring these systems are often expensive and power hungry. Traditional approaches to sensor selection in large multisensory arrays attempt to alleviate these issues by removing redundant sensors while maintaining overall sensor predictability. However, predicting sensors is unnecessary if ultimately the system needs only to quantify diagnostic measurements specific to the application domain. We propose a new method for optimizing the design of medical sensor systems through diagnostic-based bottom-up sensor selection. We reduce the original sensor array from ninety nine to twelve sensors while maintaining a prediction error rate of less than 5% over all diagnostic metrics in our testing dataset.
611. Promoter Evaluation of AAV Gene Therapy in the Central Nervous System for Feline Niemann-Pick Type C Disease (2016)

Niemann-Pick type C1 (NPC1) disease is characterized by progressive cerebellar ataxia, dementia, and death in adolescence. It is caused by mutations that result in deficient function of lysosomal, membrane-bound NPC1, resulting in the intralysosomal accumulation of cholesterol and sphingolipids. There are no FDA-approved therapies for NPC1 disease, however, we have previously shown that administration of 2-hydroxypropyl-beta-cyclodextrin (HPßCD) via the cerebromedullary cistern (CBMC) in presymptomatic cats with NPC1 disease prevented the onset of cerebellar tremor and resulted in Purkinje cell (PC) survival and near normal concentrations of cerebral cortex and cerebellar cholesterol and sphingolipids. Remarkably, these cats remained alive for greater than three years of age, in contrast to untreated NPC1 cats that died before six months of age. This therapy has advanced to clinical trials where patients receive biweekly HPßCD. In an attempt to both reduce the number of HPßCD injections and to treat uncorrected brain regions, we studied the feasibility of viral gene therapy, providing a one-time injection, in NPC1 cats. Preliminary studies utilized administration of an adeno-associated virus serotype 9 carrying the feline NPC1 transgene (fNPC1) via the CBMC of pre-symptomatic NPC1 cats. These treated cats showed reduced ataxia compared to untreated cats. Histologic evaluation of the brains revealed that NPC1 expression had been restored to some PCs and that this was associated with increased PC survival. This initial success prompted us to further explore the potential of various promoters to express functional NPC1 protein in the brain. In this study we evaluated the ability of four different promoters, three ubiquitous (CB7, GUSB, and JeTi) and one neuron-specific (CamKII), to drive GFP expression in the central nervous system of normal cats. Our preliminary therapeutic studies used the GUSB promoter (pGUSB) to mediate fNPC1 expression. Expression of both fNPC1 and a GFP reporter under pGUSB were low in PCs, and in cerebrocortical neurons and astrocytes. Overall, the CB7 promoter drove the highest level of expression in similar regions; however, this large promoter (~970bp) limits transgene size (where NPC is ~4.3Kbp) and led us to examine a smaller exogenous promoter based on CB7, termed JeTi. This promoter was similar in expression levels to the pGUSB, leading to low-level expression at our limit of detection using DAB-based immunohistochemistry. Interestingly, a six-month therapeutic study using the JeTi promoter had a similar outcome as pGUSB where treated cats had reduced clinical signs at the end of study. Expression driven by the neuron-specific promoter CamKII produced levels similar to the CB7 promoter, although PCs of the cerebellum had low to undetectable expression levels. These data and preliminary therapeutic data in AAV-treated NPC1 cats will be further explained in this presentation.
Chinese Herbal Medicine (MaZiRenWan) Improves Bowel Movement in Functional Constipation Through Down-Regulating Oleamide (2020)

In a prospective, randomized, three-arms, controlled clinical study, Chinese Herbal Medicine MaZiRenWan (MZRW, also known as Hemp Seed Pill) demonstrates comparable efficacy with Senna for functional constipation (FC) during an 8-week treatment period. Both MZRW and Senna are better than a placebo; relative to Senna and a placebo, MZRW displayed a more sustained effect during the 8-week follow-up period. The characteristic pharmacological mechanism responsible for this observation is still unclear. To explore this, we collected pre- and post-treatment serum samples of 85 FC patients from MZRW/Senna/placebo treatment groups for pharmacometabolomic analysis. An ultrahigh-performance liquid chromatography-mass spectrometer (UPLC-MS) was used for metabolic profiling and quantification. <i>In vivo</i> studies were conducted in constipated C57BL/6J mice to verify the effects and corresponding mechanism(s) of the action of MZRW. Pearson correlation analysis, paired t-test, one-way ANOVA analysis, χ2 test, and Student t-test were used to interpret the clinical and preclinical data. Changes in levels of circulating oleamide and its derivatives negatively correlate with improvement in complete spontaneous bowel movement (CSBM) in the MZRW group (Pearson r = -0.59, <i>p</i> = 0.00057). The same did not hold true for either Senna or placebo groups. Oleamide is a known regulator of intestinal motility. MZRW treatment resulted in reduced levels of circulating oleamide in FC patients. Experimental verification showed that MZRW attenuated oleamide-induced slow intestinal motility in mice. MZRW decreased oleamide levels in serum, ileum, and colon in normal mice, but increased expression of colonic fatty acid amide hydrolase (FAAH). In conclusion, MZRW improved bowel movement in FC by down-regulating oleamide, possibly by enhancing FAAH-mediated degradation. Our findings suggest a novel therapeutic strategy for FC.
New Position-Sensing Concept for Miniature Lateral-Stator Machines (2016)

Lateral-stator machine (LSM) is an unconventional permanent-magnet electrical machine type that enables direct drive for micromachining applications where the space in the tool head is limited. In such applications, standard position sensors cannot be used due to the space limits. The back electro-motive force (EMF) cannot be used for position estimation as the rotor position is needed over the full-speed range, including very low speeds. Moreover, the load-dependent saturation of the stator core hinders an impedance-tracking-based self-sensing approach. Therefore, this paper presents integrated position sensors comprising sensing coils wound on the shielding iron, which is a part specific to the mentioned type of machine. Using this approach, the challenge introduced by the specific machine geometry is turned into an opportunity to realize highly compact and robust position sensors that can operate from standstill up to 200 000 r/min. Measurement results prove the validity of the design procedure. Even though developed for a specific type of electric machine, the presented approach can be used for position sensing of other types of electromechanical actuators.
Two-particle azimuthal correlations in photonuclear ultraperipheral Pb+Pb collisions at 5.02 TeV with ATLAS (2021)

Two-particle long-range azimuthal correlations are measured in photonuclear collisions using $1.7\phantom{\rule{4pt}{0ex}}{\mathrm{nb}}^{\ensuremath{-}1}$ of 5.02 TeV $\mathrm{Pb}+\mathrm{Pb}$ collision data collected by the ATLAS experiment at the CERN Large Hadron Collider. Candidate events are selected using a dedicated high-multiplicity photonuclear event trigger, a combination of information from the zero-degree calorimeters and forward calorimeters, and from pseudorapidity gaps constructed using calorimeter energy clusters and charged-particle tracks. Distributions of event properties are compared between data and Monte Carlo simulations of photonuclear processes. Two-particle correlation functions are formed using charged-particle tracks in the selected events, and a template-fitting method is employed to subtract the nonflow contribution to the correlation. Significant nonzero values of the second- and third-order flow coefficients are observed and presented as a function of charged-particle multiplicity and transverse momentum. The results are compared with flow coefficients obtained in proton-proton and proton-lead collisions in similar multiplicity ranges, and with theoretical expectations. The unique initial conditions present in this measurement provide a new way to probe the origin of the collective signatures previously observed only in hadronic collisions.
Synthesis of Multi-Protein Complexes through Charge-Directed Sequential Activation of Tyrosine Residues (2021)

Site-selective protein-protein coupling has long been a goal of chemical biology research. In recent years, that goal has been realized to varying degrees through a number of techniques, including the use of tyrosinase-based coupling strategies. Early publications utilizing tyrosinase from Agaricus bisporus showed the potential to convert tyrosine residues into ortho-quinone functional groups, but this enzyme is challenging to produce recombinantly and suffers from some limitations in substrate scope. Initial screens of several tyrosinase candidates revealed that the tyrosinase from Bacillus megaterium (megaTYR) as an enzyme that possesses a broad substrate tolerance. We use the expanded substrate preference as a starting point for protein design experiments and show that single point mutants of megaTYR are capable of activating tyrosine residues in various sequence contexts. We leverage this new tool to enable the construction of protein trimers via a charge-directed sequential activation of tyrosine residues (CDSAT).
Method of making a small inlet optical panel (2023)

An optical panel having a small inlet, and a method of making a small inlet optical panel, are disclosed, which optical panel includes a individually coating, stacking, and cutting a first plurality of stacked optical waveguides to form an outlet face body with an outlet face, individually coating, stacking, and cutting a second plurality of stacked optical waveguides to form an inlet face body with an inlet face, and connecting an optical coupling element to the first plurality and second plurality of stacked optical waveguides, wherein the optical coupling element redirects light along a parallel axis of the inlet face to a parallel axis of the outlet face. In the preferred embodiment of the present invention, the inlet face is disposed obliquely with and askew from the outlet face.
A Microscopic, Continous, Optical Monitor for Interstitial Electrolytes and Glucose (2003)

Ions, such as hydrogen (pH), sodium, or potassium, as well as metabolites, such as glucose or lactate, diffuse easily between blood in the capillaries and the interstitial fluid (ISF) residing between cells, and tissues. This work represents a synthesis of several unique concepts to achieve accurate, continuous, in vivo monitoring of critical ions and glucose in the ISF under the human skin. Ionic levels are monitored using optode technology that translates the respective concentrations into variable colors of ionophore/dye/polymeric liquid membranes. Glucose is monitored indirectly, by coupling through immobilized glucose oxidase with pH, that is then detected using a similar color scheme. The monitor consists of a tiny plastic bar ("sliver sensor"), 100-300 microns wide and 1-15 mm long, placed just under the skin, with optical spots or stripes for each analyte as well as blanks for calibration. The colors are read and translated into concentration values by a watchlike device placed above the skin. Direct optical coupling between the in vivo sensing bar and the ex vivo detector device requires negligible power, and eliminates the need for wires or optical fibers crossing the skin. The microminiature sliver penetrates the skin easily and painlessly, so that the user could insert it him- or herself. No risk of track infection exists. We are reporting here on the first successful in vitro tests of this approach.
Faculty Opinions recommendation of Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. (2002)

The malaria parasite Plasmodium falciparum infects 5-10% of the world's population and kills two million people annually. Fatalities are thought to result in part from pathological reactions initiated by a malarial toxin. Glycosylphosphatidylinositol (GPI) originating from the parasite has the properties predicted of a toxin; however, a requirement for toxins in general and GPI in particular in malarial pathogenesis and fatality remains unproven. As anti-toxic vaccines can be highly effective public health tools, we sought to determine whether anti-GPI vaccination could prevent pathology and fatalities in the Plasmodium berghei/rodent model of severe malaria. The P. falciparum GPI glycan of the sequence NH(2)-CH(2)-CH(2)-PO(4)-(Man alpha 1-2)6Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcNH(2)alpha 1-6myo-inositol-1,2-cyclic-phosphate was chemically synthesized, conjugated to carriers, and used to immunize mice. Recipients were substantially protected against malarial acidosis, pulmonary oedema, cerebral syndrome and fatality. Anti-GPI antibodies neutralized pro-inflammatory activity by P. falciparum in vitro. Thus, we show that GPI is a significant pro-inflammatory endotoxin of parasitic origin, and that several disease parameters in malarious mice are toxin-dependent. GPI may contribute to pathogenesis and fatalities in humans. Synthetic GPI is therefore a prototype carbohydrate anti-toxic vaccine against malaria. PMID: 12181569
Design of dynamic trajectories for efficient and data-rich exploration of flow reaction design spaces (2021)

Sinusoidal variations of operative parameters in flow chemistry allows the fast exploration of chemical design spaces through inline measurements of an objective function.