gebhart/patrepeval huggingface dataset:
Development of Bisphosphonate-Conjugated Antibiotics to Overcome Pharmacodynamic Limitations of Local Therapy: Initial Results with Carbamate Linked Sitafloxacin and Tedizolid (2021)

The use of local antibiotics to treat bone infections has been questioned due to a lack of clinical efficacy and emerging information about <i>Staphylococcus aureus</i> colonization of the osteocyte-lacuno canalicular network (OLCN). Here we propose bisphosphonate-conjugated antibiotics (BCA) using a "target and release" approach to deliver antibiotics to bone infection sites. A fluorescent bisphosphonate probe was used to demonstrate bone surface labeling adjacent to bacteria in a <i>S. aureus</i> infected mouse tibiae model. Bisphosphonate and hydroxybisphosphonate conjugates of sitafloxacin and tedizolid (BCA) were synthesized using hydroxyphenyl and aminophenyl carbamate linkers, respectively. The conjugates were adequately stable in serum. Their cytolytic activity versus parent drug on MSSA and MRSA static biofilms grown on hydroxyapatite discs was established by scanning electron microscopy. Sitafloxacin <i>O</i>-phenyl carbamate BCA was effective in eradicating static biofilm: no colony formation units (CFU) were recovered following treatment with 800 mg/L of either the bisphosphonate or α-hydroxybisphosphonate conjugated drug (<i>p</i> < 0.001). In contrast, the less labile tedizolid <i>N</i>-phenyl carbamate linked BCA had limited efficacy against MSSA, and MRSA. CFU were recovered from all tedizolid BCA treatments. These results demonstrate the feasibility of BCA eradication of <i>S. aureus</i> biofilm on OLCN bone surfaces and support in vivo drug development of a sitafloxacin BCA.
ChemInform Abstract: Total Synthesis of (+)‐Dihydromevinolin. (1986)

Abstract The synthesis of the title compound (XII) is carried out as shown in the scheme starting from the tricyclic ketone (I).
The Heck Reaction under Ball‐Milling Conditions. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Caspase-3 dependent nitrergic neuronal apoptosis following cavernous nerve injury is mediated via RhoA and ROCK activation in major pelvic ganglion (2016)

Axonal injury due to prostatectomy leads to Wallerian degeneration of the cavernous nerve (CN) and erectile dysfunction (ED). Return of potency is dependent on axonal regeneration and reinnervation of the penis. Following CN injury (CNI), RhoA and Rho-associated protein kinase (ROCK) increase in penile endothelial and smooth muscle cells. Previous studies indicate that nerve regeneration is hampered by activation of RhoA/ROCK pathway. We evaluated the role of RhoA/ROCK pathway in CN regulation following CNI using a validated rat model. CNI upregulated gene and protein expression of RhoA/ROCK and caspase-3 mediated apoptosis in the major pelvic ganglion (MPG). ROCK inhibitor (ROCK-I) prevented upregulation of RhoA/ROCK pathway as well as activation of caspase-3 in the MPG. Following CNI, there was decrease in the dimer to monomer ratio of neuronal nitric oxide synthase (nNOS) protein and lowered NOS activity in the MPG, which were prevented by ROCK-I. CNI lowered intracavernous pressure and impaired non-adrenergic non-cholinergic-mediated relaxation in the penis, consistent with ED. ROCK-I maintained the intracavernous pressure and non-adrenergic non-cholinergic-mediated relaxation in the penis following CNI. These results suggest that activation of RhoA/ROCK pathway mediates caspase-3 dependent apoptosis of nitrergic neurons in the MPG following CNI and that ROCK-I can prevent post-prostatectomy ED.
Modular inverter system (2023)

A system connected to an AC power grid having an AC phase signal includes an inverter module including a first inverter coupled to a DC voltage, actuated based on the AC phase signal. The first inverter provides a first voltage signal having predetermined harmonic components. A second inverter includes second switch elements coupled to the DC voltage and actuated by a second set of control signals phase delayed with respect to the first control signals. A transformer module has first and second primary windings coupled to the first and second inverters. The transformer module further includes a secondary winding coupled to first primary winding, the second primary winding, and the AC power grid. The secondary winding is configured to provide a secondary output voltage to the AC power grid by combining the first voltage signal and the second voltage signal such that the predetermined harmonic components are substantially cancelled.
Data from Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism (2023)

&lt;div&gt;Abstract&lt;p&gt;Metformin inhibits cancer cell proliferation, and epidemiology studies suggest an association with increased survival in patients with cancer taking metformin; however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation, whereas increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer. &lt;i&gt;Cancer Res; 73(14); 4429–38. ©2013 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Hand-grip impact on range-based cooperative positioning (2014)

In this paper we present experimental evaluations of cooperative ranging-based approaches in mobile positioning. Our main contribution is represented by experimental investigations of the errors introduced by the hand-grip effect on cooperative schemes among peer devices, demonstrating that by knowing in real-time the particular orientation of the MS in a controlled experimental environment, it is possible to mitigate and filter out the effect of the hand-grip on RSS measurements and consequently to maintain the beneficial effect of the cooperation in the final position estimation.
Evaluation of a nanophosphor lateral-flow assay for self-testing for herpes simplex virus type 2 seropositivity (2019)

Herpes Simplex Virus Type 2 (HSV-2) is a common human pathogen that causes life-long illness. The US prevalence of HSV-2 infection is 11.9% for individuals between 15 and 49 years of age. Individuals with HSV-2 infection are more likely to contract and spread other sexually-transmitted infections. Eighty percent of individuals with HSV-2 are unaware of their infection, in part because of the social stigma associated with in-clinic testing for sexually-transmitted infections. We conducted an initial evaluation of a prototype smartphone-based serological lateral-flow immunoassay (LFA) for HSV-2 infection that uses strontium aluminate persistent luminescent nanoparticles (nanophosphors) as reporters. When applied to a test panel of 21 human plasma/serum samples varying in anti-HSV titer, the nanophosphor HSV-2 LFA had 96.7% sensitivity and 100% specificity for detection of HSV-2 infection. The sensitivity of the nanophosphor HSV-2 LFA was higher than that of commercially-available rapid HSV-2 assays tested with the same panel. Analysis of the iPhone nanophosphor HSV-2 LFA strip images with our custom smartphone app gave greater reproducibility compared to ImageJ analysis of strip images. The smartphone-based nanophosphor LFA technology shows promise for private self-testing for sexually-transmitted infections (STI).
Costimulation blockade in combination with IL-2 permits regulatory T cell sparing immunomodulation that inhibits autoimmunity (2022)

Blockade of CD28 costimulation with CTLA-4-Ig/Abatacept is used to dampen effector T cell responses in autoimmune and transplantation settings. However, a significant drawback of this approach is impaired regulatory T cell homeostasis that requires CD28 signaling. Therefore, strategies that restrict the effects of costimulation blockade to effector T cells would be advantageous. Here we probe the relative roles of CD28 and IL-2 in maintaining Treg. We find provision of IL-2 counteracts the regulatory T cell loss induced by costimulation blockade while minimally affecting the conventional T cell compartment. These data suggest that combining costimulation blockade with IL-2 treatment may selectively impair effector T cell responses while maintaining regulatory T cells. Using a mouse model of autoimmune diabetes, we show combined therapy supports regulatory T cell homeostasis and protects from disease. These findings are recapitulated in humanised mice using clinically relevant reagents and provide an exemplar for rational use of a second immunotherapy to offset known limitations of the first.
Cytokines and Biocompatibility (1990)

Issues in biocompatibility have traditionally focused on the interaction of membranes or materials with the activation of complement, red blood cell destruction, clotting dysfunctions, and platelet activation. Other studies are concerned with the replacement fluid formulations and host responses. Recent attention has examined the interaction of the blood monocyte with either complement or membrane surfaces. Activation of monocytes leads to the synthesis of cytokines, namely interleukin 1, tumor necrosis factor, and interleukin 6. These potent polypeptide 'cytokines' affect biological functions in nearly every tissue. Understanding the mechanisms by which gene expression of these cytokines is triggered will help in the better design of membrane material or substitution fluids. These are discussed in the context of increased cytokine synthesis during hemodialysis and continuous ambulatory peritoneal dialysis.
Supplementary Table 1 from BAD Phosphorylation Determines Ovarian Cancer Chemosensitivity and Patient Survival (2023)

&lt;p&gt;PDF file - 3931KB, Genes/probe sets.&lt;/p&gt;
Education on vehicle electrification: Battery Systems, Fuel Cells, and Hydrogen (2010)

A new education program is under development at the University of Michigan to educate engineers in the fundamentals of electrochemical propulsion systems for vehicle electrification. This paper describes two courses that are part of this larger program: “Battery Systems & Control” and “Fuel Cell Vehicles & Hydrogen Infrastructure.” These courses seek to educate undergraduate, graduate, and professional (i.e. distance learning) students in the fundamentals of modeling, control, and design of batteries, fuel cells, and hydrogen storage systems. These courses apply a systems-level approach to electrochemical propulsion systems with particular emphasis placed on modeling, design, and control issues encountered in practice. In the battery course students are introduced to electrochemical-based models, model reduction techniques, simulation procedures, and real-life control problems such as state-of-charge estimation. Topics covered in the fuel cell course include: PEM fuel cell operating fundamentals, hydrogen production pathways, hydrogen storage, and well-to-wheels CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> and efficiency analyses. This paper broadly outlines the curriculum for both courses using specific assignments as illustrative examples of the program's content. Together these two courses provide fundamental skills directed at developing engineering leadership and knowledge in sustainable transportation systems.
ChemInform Abstract: SYNTHESIS AND PROPERTIES OF BIS(PENTAMETHYLCYCLOPENTADIENYL) ACTINIDE HYDROCARBYLS AND HYDRIDES. A NEW CLASS OF HIGHLY REACTIVE F‐ELEMENT ORGANOMETALLIC COMPOUNDS (1982)

Abstract Die Reaktionen zwischen den Bis‐[pentamethylcyclopentadienyl]‐Th‐ und ‐U‐dichloriden (II), Produkte der Grignardierung von Th‐ bzw. U‐tetrachlorid mit (I), und entsprechenden Li‐Reagenzien führen abhängig von der Stöchiometrie zu den Mono‐ oder Disubstitutionsprodukten (III).
[Bortezomib-induced tumor lysis syndrome with a remarkable elevation of LDH in a case of relapsed and therapy-resistant multiple myeloma]. (2006)

A 60-year-old female patient with a therapy-resistant Bence-Jones (BJ) lambda-type multiple myeloma was treated with bortezomib. She had been treated with tandem autologous stem cell transplantations and achieved complete remission before her disease relapsed. Sixteen hours after the first administration of bortezomib, an episode of fever, slight consciousness disturbance and vomiting occurred, which was accompanied by a remarkable elevation of LDH (3608 IU/l). Serum levels of creatinine, uric acid, and AST were also transiently elevated. Serum interleukin-6 level was also increased after the administration of bortezomib. The symptoms disappeared rapidly within 48 hours. Bortezomib at a 25%-reduced dose was administered again along with dexamethasone 26 days later, which caused a moderate increase in LDH levels, but no other symptoms. Further treatment caused no increase in LDH. The treatment was very effective and eradicated both urinary BJ protein and bone marrow myeloma cells after 8 sessions of bortezomib administration. These findings suggest that a bortezomib-induced rapid reduction in tumor burden led to tumor lysis syndrome, for which caution is needed when treating myeloma patients with this very effective agent.
Single valproic acid treatment inhibits glycogen and RNA ribose turnover while disrupting glucose-derived cholesterol synthesis in liver as revealed by the [U-13C6]-d-glucose tracer in mice (2009)

Previous genetic and proteomic studies identified altered activity of various enzymes such as those of fatty acid metabolism and glycogen synthesis after a single toxic dose of valproic acid (VPA) in rats. In this study, we demonstrate the effect of VPA on metabolite synthesis flux rates and the possible use of abnormal 13C labeled glucose-derived metabolites in plasma or urine as early markers of toxicity. Female CD-1 mice were injected subcutaneously with saline or 600 mg/kg) VPA. Twelve hours later, the mice were injected with an intraperitoneal load of 1 g/kg [U-13C]-d-glucose. 13C isotopomers of glycogen glucose and RNA ribose in liver, kidney and brain tissue, as well as glucose disposal via cholesterol and glucose in the plasma and urine were determined. The levels of all of the positional 13C isotopomers of glucose were similar in plasma, suggesting that a single VPA dose does not disturb glucose absorption, uptake or hepatic glucose metabolism. Three-hour urine samples showed an increase in the injected tracer indicating a decreased glucose re-absorption via kidney tubules. 13C labeled glucose deposited as liver glycogen or as ribose of RNA were decreased by VPA treatment; incorporation of 13C via acetyl-CoA into plasma cholesterol was significantly lower at 60 min. The severe decreases in glucose-derived carbon flux into plasma and kidney-bound cholesterol, liver glycogen and RNA ribose synthesis, as well as decreased glucose re-absorption and an increased disposal via urine all serve as early flux markers of VPA-induced adverse metabolic effects in the host.
Non-heparin hemodialysis with oral administration of newly developed antiplatelet agent. (1991)

Non-heparin hemodialysis (HD) was successfully done in anuric dogs with the oral administration of a newly developed antiplatelet agent, 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid, (E5510, Eisai Pharmaceutical Co., Japan). In the current study, the antithrombotic effect of E5510 during HD was investigated. Eleven mongrel dogs with bilateral ureteral ligation were given 0.1 mg/kg of E5510 orally 1 hr before undergoing 4 hr HD using hollow fiber dialyzers, (PMMA 5, regenerated cellulose 6) without heparin and under general anesthesia. Blood samples were taken before the administration of E5510 and before and 1, 2, 3, and 4 hr after starting HD; blood counts, hematocrits, blood chemistries, and plasma thromboxane levels (TxB2) were examined. Platelet aggregation, activated clotting times (ACT), and activated partial thrombin times (APTT) were also measured, and sequential plasma E5510 concentrations were determined. In 10 of 11 anuric dogs, non-heparin HD was successfully done with minimal clotting in the dialyzer and drip chambers. The maximum aggregation rate was depressed to less than 20% of the initial value throughout HD. Plasma TxB2 concentration was depressed, and ACT and APTT were mildly, but not significantly prolonged. Neither hemorrhagic complications nor other side effects of E5510 were observed.
Development of SiGe Indentation Process Control for Gate-All-Around FET Technology Enablement (2022)

Methodologies for characterization of the lateral indentation of silicon-germanium (SiGe) nanosheets using different non-destructive and in-line compatible metrology techniques are presented and discussed. Gate-all-around nanosheet device structures with a total of three sacrificial SiGe sheets were fabricated and different etch process conditions used to induce indent depth variations. Scatterometry with spectral interferometry and x-ray fluorescence in conjunction with advanced interpretation and machine learning algorithms were used to quantify the SiGe indentation. Solutions for two approaches, average indent (represented by a single parameter) as well as sheet-specific indent, are presented. Both scatterometry with spectral interferometry as well as x-ray fluorescence measurements are suitable techniques to quantify the average indent through a single parameter. Furthermore, machine learning algorithms enable a fast solution path by combining x-ray fluorescence difference data with scatterometry spectra, therefore avoiding the need for a full optical model solution. A similar machine learning model approach can be employed for sheet-specific indent monitoring; however, reference data from cross-section transmission electron microscopy image analyses are required for training. It was found that scatterometry with spectral interferometry spectra and a traditional optical model in combination with advanced algorithms can achieve a very good match to sheet-specific reference data.
Altered membrane physiology in Müller glial cells after transient ischemia of the rat retina (2004)

Inwardly rectifying K+ (Kir) channels have been implicated in the mediation of retinal K+ homeostasis by Muller glial cells. To assess possible involvement of altered glial K+ channel expression in ischemia-reperfusion injury, transient retinal ischemia was induced in rat eyes. Acutely isolated Muller cells from postischemic retinae displayed a fast downregulation of their Kir currents, which began within 1 day and reached a maximum at 3 days of reperfusion, with a peak decrease to 20% as compared with control. This strong decrease of Kir currents was accompanied by an increase of the incidence of cells which displayed depolarization-evoked fast transient (A-type) K+ currents. While no cell from untreated control rats expressed A-type K+ currents, all cells investigated from 3- and 7-day postischemic retinae displayed such currents. An increased incidence of cells displaying fast transient Na+ currents was observed at 7 days after ischemia. These results suggest a role of altered glial Kir channel expression in postischemic neuronal degeneration via disturbance of retinal K+ siphoning.
Combination of quantitative features from H&E biopsies and CT scans predicts response to chemotherapy and overall survival in small cell lung cancer (SCLC). (2021)

8572 Background: Small Cell Lung Cancer (SCLC) is an aggressive malignancy with a rapid growth, and Chemotherapy remains mainstay of treatment. Identifying therapeutic targets in SCLC presents a challenge, partially due to a lack of accurate and consistently predictive biomarkers. In this study we sought to evaluate the utility of a combination of computer-extracted radiographic and pathology features from pretreatment baseline CT and H&amp;E biopsy images to predict sensitivity to platinum-based chemotherapy and overall survival (OS) in SCLC. Methods: Seventy-eight patients with extensive and limited-stage SCLC who received platinum-doublet chemotherapy were selected. Objective response to chemotherapy (RECIST criteria) and overall survival (OS) as clinical endpoints were available for 51 and 78 patients respectively. The patients were divided randomly into two sets (Training (Sd), Validation (Sv)) with a constraint (equal number of responders and nonresponders in Sd)—Sd comprised twenty-one patients with SCLC. Sv included thirty patients. CT scans and digitized Hematoxylin Eosin-stained (H&amp;E) biopsy images were acquired for each patient. A set of CT derived (46%) and tissue derived (53%) image features were captured. These included shape and textural patterns of the tumoral and peritumoral regions from CT scans and of tumor regions on H&amp;E images. A random forest feature selection and linear regression model were used to identify the most predictive CT and H&amp;E derived image features associated with chemotherapy response from Sd. A Cox proportional hazard regression model was used with these features to compute a risk score for each patients in Sd. Patients in Sv were stratified into high and low-risk groups based on the median risk score. Kaplan-Meier survival analysis was used to assess the prognostic ability of the risk score on Sv. Results: The risk score comprised nine CT (intra and peri-tumoral texture) and six H&amp;E derived (cancer cell texture and shape) features. A linear regression model in conjunction with these 15 features was significantly associated with chemo-sensitivity in Sv (AUC = 0.76, PRC = 0.81). A multivariable model with these 15 features was significantly associated with OS in Sv (HR = 2.5, 95% CI: 1.3-4.9, P = 0.0043). Kaplan-Meier survival analysis revealed a significantly reduced OS in the high-risk group compared to the low-risk group. Conclusions: A combined CT and H&amp;E tissue derived image signature model predicted response to chemotherapy and improved OS in SCLC patients. Image features from baseline CT scans and H&amp;E tissue slide images may help in better risk stratification of SCLC patients. Additional independent validation of these quantitative image-based biomarkers is warranted.
Low-Power Deep Learning Inference using the SpiNNaker Neuromorphic Platform (2021)

n this presentation we will discuss recent results on using the SpiNNaker neuromorphic platform (48-chip model) for deep learning neural network inference. We use the Sandia Labs developed Whet stone spiking deep learning library to train deep multi-layer perceptrons and convolutional neural networks suitable for the spiking substrate on the neural hardware architecture. By using the massively parallel nature of SpiNNaker, we are able to achieve, under certain network topologies, substantial network tiling and consequentially impressive inference throughput. Such high-throughput systems may have eventual application in remote sensing applications where large images need to be chipped, scanned, and processed quickly. Additionally, we explore complex topologies that push the limits of the SpiNNaker routing hardware and investigate how that impacts mapping software-implemented networks to on-hardware instantiations.
Spectrometer-Free Graphene Plasmonics Based Refractive Index Sensor (2020)

We propose a spectrometer-free refractive index sensor based on a graphene plasmonic structure. The spectrometer-free feature of the device is realized thanks to the dynamic tunability of graphene's chemical potential, through electrostatic biasing. The proposed sensor exhibits a 1566 nm/RIU sensitivity, a 250.6 RIU<sup>-1</sup> figure of merit in the optical mode of operation and a 713.2 meV/RIU sensitivity, a 246.8 RIU<sup>-1</sup> figure of merit in the electrical mode of operation. This performance outlines the optimized operation of this spectrometer-free sensor that simplifies its design and can bring terahertz sensing one step closer to its practical realization, with promising applications in biosensing and/or gas sensing.