gebhart/patrepeval huggingface dataset:
Phenotypic Identification of the Redox Dye Methylene Blue as an Antagonist of Heat Shock Response Gene Expression in Metastatic Melanoma Cells (2013)

Repurposing approved and abandoned non-oncological drugs is an alternative developmental strategy for the identification of anticancer therapeutics that has recently attracted considerable attention. Due to the essential role of the cellular heat shock response in cytoprotection through the maintenance of proteostasis and suppression of apoptosis, small molecule heat shock response antagonists can be harnessed for targeted induction of cytotoxic effects in cancer cells. Guided by gene expression array analysis and a phenotypic screen interrogating a collection of 3,7-diamino-phenothiazinium derivatives, we have identified the redox-drug methylene blue (MB), used clinically for the infusional treatment of methemoglobinemia, as a negative modulator of heat shock response gene expression in human metastatic melanoma cells. MB-treatment blocked thermal (43 °C) and pharmacological (celastrol, geldanamycin) induction of heat shock response gene expression, suppressing Hsp70 (HSPA1A) and Hsp27 (HSPB1) upregulation at the mRNA and protein level. MB sensitized melanoma cells to the apoptogenic activity of geldanamycin, an Hsp90 antagonist known to induce the counter-regulatory upregulation of Hsp70 expression underlying cancer cell resistance to geldanamycin chemotherapy. Similarly, MB-cotreatment sensitized melanoma cells to other chemotherapeutics (etoposide, doxorubicin). Taken together, these data suggest feasibility of repurposing the non-oncological redox drug MB as a therapeutic heat shock response antagonist for cancer cell chemosensitization.
Comprehensive geriatric assessment prior to autologous stem cell transplant as a predictor of patient outcomes: A retrospective review. (2019)

e23023 Background: While autologous stem cell transplant (ASCT) has been shown to be safe and effective in the geriatric population, age alone is not a sufficient predictor of outcomes. Minimal data exists regarding the use of a comprehensive geriatric assessment (CGA) tool prior to ASCT as a predictor of patient outcomes. This study aims to assess our institution’s pre-ASCT CGA on its ability to predict transplant-related outcomes in the elderly. Methods: We retrospectively analyzed all patients age 65 years of age and older (n = 68) who received ASCT at Thomas Jefferson University Hospital between 2012 and 2018 for multiple myeloma (MM) (n = 52), AL amyloidosis (n = 1), combined MM/amyloidosis (n = 2), B-NHL (n = 11), T cell lymphoma (n = 2), and Hodgkin lymphoma (n = 1). The CGA consists of 13 components, culminating in an overall frailty status. Kaplan-Meier survival estimates were used to assess overall survival (OS) and progression free survival (PFS), and multivariable logistic regression and Cox proportional hazard regression were used to determine associations between CGA variables and relevant post-ASCT outcomes. Results: Among the 68 patients (43 males, 25 females) who received ASCT, the median age was 68 years (range 65-78). Fifty-one patients (75%) underwent pre-transplant CGA. Among the entire cohort, 2-year OS and PFS were 95.4% and 79.6%, respectively. Median OS was not reached, and median PFS was 48.5 months. There was no difference in OS between patients who underwent CGA and those who did not (P = 0.937). Multivariate analysis revealed that none of the variables in the CGA were predictive of patient outcomes, such as OS, length of stay on ASCT admission, 30-day readmissions, and falls. Conclusions: This single-institution data suggests that ASCT is safe and highly effective in geriatric patients. Undergoing a CGA was not associated with improved outcomes, and none of the CGA components including frailty status were predictive of outcomes in this preliminary data set. Our data suggest that further refinement of the CGA may improve its predictive ability. Future studies examining additional outcomes, including patient-reported quality-of-life outcomes, are warranted.
High performance liquid chromatography analysis of tetrahydrozoline hydrochloride in ophthalmic solution by silica column eluted with aqueous solvent mixtures (2020)

A HPLC method using bared silica column eluted with aqueous solvent mobile phase was developed for determination of tetrahydrozoline hydrochloride in ophthalmic preparations. A mixture of methanol and water (70:30, v/v) containing 0.03% triethylamine and 0.02% acetic acid was used as mobile phase, and chlorpheniramine maleate as an internal standard. The flow rate was 1 mL/min and the detection was at 254 nm. The quantitation limit was 1.0, μg/mL. Average recoveries range from 98.9 to 99.9%. The linearity of the calibration curve of tetrahydrozoline hydrochloride was well correlated (r 2 = 0.9996) within the range from 12.5 to 500 μg/mL as well as from 1.0 to 20 μg/mL (r 2 = 0.9997). This study further reports a simple and quick method for routine quantitative analysis of tetrahydrozoline hydrochloride in an ophthalmic solution that contains a relatively high concentration of sulfamethoxazole sodium and methyl paraben.
Application and Methodology of the Non-destructive <sup>19</sup>F Time-domain NMR Technique to Measure the Content in Fluorine-containing Drug Products (2017)

Here, we describe a protocol developed by our group that uses low-field fluorine-19 (<sup>19</sup>F) time-domain (TD) nuclear magnetic resonance (NMR) to measure the average content of fluorinated drugs in their formulated drug product forms: tablets or capsules. This method is specific to fluorinated drugs because it detects only the content of fluorine, avoiding interference from the excipients that lack fluorine. The advantages of measuring the active content of fluorinated drugs using low-field <sup>19</sup>F TD-NMR versus high-field <sup>19</sup>F solid-state (SS) NMR are the simplicity of the method; the low cost; and the non-destructive nature of the technique, with all samples recoverable in intact forms (e.g., powders, tablets, and capsules), making this technique affordable for any laboratory. We have tested the method with three fluorinated drug products available on the market - cinacalcet, lansoprazole, and ciprofloxacin - with doses ranging from 15 to 500 mg. The results of the analyses, measured by low-field <sup>19</sup>F TD-NMR, supported the reported label claims for the average drug content. Based on the simplicity and reproducibility of the analysis, we envision this methodology being implemented in any laboratory, including manufacturing plants, as a process analytical technology (PAT) tool in the pharmaceutical industry.
There Is No Simple Model of the Plasma Membrane Organization (2016)

Ever since technologies enabled the characterization of eukaryotic plasma membranes, heterogeneities in the distributions of its constituents were observed. Over the years this led to the proposal of various models describing the plasma membrane organization such as lipid shells, picket-and-fences, lipid rafts, or protein islands, as addressed in numerous publications and reviews. Instead of emphasizing on one model we in this review give a brief overview over current models and highlight how current experimental work in one or the other way do not support the existence of a single overarching model. Instead, we highlight the vast variety of membrane properties and components, their influences and impacts. We believe that highlighting such controversial discoveries will stimulate unbiased research on plasma membrane organization and functionality, leading to a better understanding of this essential cellular structure.
Identification of the synaptic vesicle glycoprotein 2 receptor binding site in botulinum neurotoxin A (2014)

Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by hydrolysing SNARE proteins. The most important serotype BoNT/A employs the synaptic vesicle glycoprotein 2 (SV2) isoforms A-C as neuronal receptors. Here, we identified their binding site by blocking SV2 interaction using monoclonal antibodies with characterised epitopes within the cell binding domain (HC). The site is located on the backside of the conserved ganglioside binding pocket at the interface of the HCC and HCN subdomains. The dimension of the binding pocket was characterised in detail by site directed mutagenesis allowing the development of potent inhibitors as well as modifying receptor binding properties.
Perlecan a multifunctional extracellular proteoglycan scaffold (2007)

Perlecan is a large multidomain heparan sulfate proteoglycan of the extracellular matrix. Expression of this proteoglycan changes dynamically during embryo implantation and placentation. Perlecan is expressed by various cells of the embryo including trophectoderm and trophoblast as well as the maternal compartment, including basal lamina underlying uterine epithelia and endothelia and, most dynamically, in developing decidua. Perlecan supports various biological functions, including cell adhesion, growth factor binding, and modulation of apoptosis. Moreover, studies in other systems demonstrate that perlecan expression and activity can be controlled at many levels, including transcription, alternative splicing, and extracellular proteolysis. This review will discuss changes in perlecan expression that occur during embryo implantation and placentation. Furthermore, we propose a model in which perlecan represents an extracellular scaffold protein that supports complex, distinct functions in its full-length form or smaller forms generated by alternative mRNA splicing, extracellular proteolysis, or glycosidase action.
High power IPT stage lighting controller (2011)

This paper introduces a modified IPT pickup AC topology for stage lighting applications. The topology improves on previous work enabling lower switch ratings and improved waveform quality across the pick-up and at the light. Circuit analysis, simulations and measurements are presented that establish the relationship between the switch and the reactive elements for design. The circuit is shown to provide sinusoidal output waveforms across the load with lower peak values for a given RMS voltage or current level reducing noise and THD significantly while also improving efficiency. The new controller is implemented and used to power a 1.2 kW 240 V Philips Broadway lamp. Either feedback or feed-forward voltage control can used to control the output within 1% of that desired.
Fabrication and experimental characterization of d 31 telescopic piezoelectric actuators (2000)

Stacks are a popular form of piezoelectric actuation. Unfortunately with this type of actuation architecture the long lengths normally required to obtain necessary displacements can pose packaging and buckling problems. To overcome these limitations, a new architecture for piezoelectric actuators has been developed called telescopic. The basic design consists of concentric shells interconnected by end-caps which alternate in placement between the two axial ends of the shells. This leads to a linear displacement amplification at the cost of force; yet the force remains at the same magnitude as a stack and significantly higher than bender type architectures. This paper describes the fabrication and experimental characterization of three different telescopic prototypes. The actuator prototypes discussed in this paper mark a definitive step forward in fabrication techniques for complex piezoceramic structures. Materials Systems Inc. has developed an injection molding process that produced a functional, five-tube, monolithic telescopic actuator. A three-tube, monolithic actuator was fabricated using a novel polymerization technique developed at the University of Michigan. As a benchmark, a third actuator was built from off-the-shelf tubes that were joined with aluminum end-caps. Each prototype's free deflection behavior was experimentally characterized and the results of the testing are presented within this paper.
Soft recovery diodes with snappy behavior (2015)

This paper illustrates several issues that a user of high voltage PiN diodes may encounter in actual application conditions. It shows that high-voltage power diodes require specifiable on-time prior to entering their reverse recovery phase and offers 1D device simulations and measurements taken on several actual high power diodes to illustrate and explain all the concepts introduced.
RF-Photonic Deep Learning Processor with Shannon-Limited Data Movement (2022)

Edholm's Law predicts exponential growth in data rate and spectrum bandwidth for communications and is forecasted to remain true for the upcoming deployment of 6G. Compounding this issue is the exponentially increasing demand for deep neural network (DNN) compute, including DNNs for signal processing. However, the slowing of Moore's Law due to the limitations of transistor-based electronics means that completely new paradigms for computing will be required to meet these increasing demands for advanced communications. Optical neural networks (ONNs) are promising DNN accelerators with ultra-low latency and energy consumption. Yet state-of-the-art ONNs struggle with scalability and implementing linear with in-line nonlinear operations. Here we introduce our multiplicative analog frequency transform ONN (MAFT-ONN) that encodes the data in the frequency domain, achieves matrix-vector products in a single shot using photoelectric multiplication, and uses a single electro-optic modulator for the nonlinear activation of all neurons in each layer. We experimentally demonstrate the first hardware accelerator that computes fully-analog deep learning on raw RF signals, performing single-shot modulation classification with 85% accuracy, where a 'majority vote' multi-measurement scheme can boost the accuracy to 95% within 5 consecutive measurements. In addition, we demonstrate frequency-domain finite impulse response (FIR) linear-time-invariant (LTI) operations, enabling a powerful combination of traditional and AI signal processing. We also demonstrate the scalability of our architecture by computing nearly 4 million fully-analog multiplies-and-accumulates for MNIST digit classification. Our latency estimation model shows that due to the Shannon capacity-limited analog data movement, MAFT-ONN is hundreds of times faster than traditional RF receivers operating at their theoretical peak performance.
Snowmass 2021 CMB-S4 White Paper (2022)

This Snowmass 2021 White Paper describes the Cosmic Microwave Background Stage 4 project CMB-S4, which is designed to cross critical thresholds in our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. We provide an overview of the science case, the technical design, and project plan.
Extremely short high-energy UV pulses from a high-pressure gas: Understanding the physical limits (2009)

Nonlinear-optical processes in the gas phase have long been used for efficient broadband frequency upconversion of high-power laser radiation [1]. Extension of these strategies to high-peak-power few-cycle laser pulses is one of the most challenging tasks in the modern era of laser science and technologies. Recent experiments [2, 3] have demonstrated that gas-phase harmonic-generation techniques can produce few-cycle pulses with a pulse width less than 1 fs in the UV/DUV range.
Effects of Hydroxyethyl‐Starch‐Bound Deferoxamine on Ischemia/Reperfusion Injury in Chronic Nerve Compression (1998)

The authors have demonstrated previously that pretreatment with deferoxamine, an iron chelator and antioxidant, at the time of release in acute nerve compression, provided protection against ischemia/reperfusion (I/R) injury. In the present study, they evaluated whether therapeutic intervention with hydroxyethyl-starch-bound deferoxamine (HES-DFO) at the time of release of the chronically-compressed peripheral nerve protects the nerve from I/R injury. The sciatic nerves of 43 male Sprague-Dawley rats, weighing 325 to 350 g, were subjected to 8 weeks of compression with Silastic tubing. The treatment group received intravenous HES-DFO (70 mg/kg) at the time of decompression, while the control group received an equal volume of intravenous hetastarch vehicle at the same time schedule and route. Nerve-tissue samples from the compression site, as well as contralateral noncompressed nerves, were assayed for malondialdehyde (MDA), a marker of I/R injury. The control group exhibited MDA levels up to five times normal, and did not return to normal for 21 days. In contrast, the HES-DFO group had MDA levels that were not statistically significantly different from normal levels. The results confirm that pretreatment with HES-DFO prior to the surgical decompression of chronically-compressed nerve provides marked protection against I/R injury.
Effect of Imidazolium Nitrate Ionic Liquids on Conformational Changes of Poly(N-vinylcaprolactam) (2022)

Detailed information about molecular interactions and conformational changes of polymeric components in the presence of ionic liquids (ILs) is essential for designing novel polymeric ionic liquid-based biomaterials. In biomaterials science and technology, thermoresponsive polymers (TRPs) are widely viewed as potential candidates for the fabrication of biorelated medical devices. Here, we synthesized thermoresponsive poly(<i>N</i>-vinyl-caprolactam) (PVCL) polymer and investigated the effects of imidazolium-based ILs (1-ethyl-3-methyl imidazolium nitrate and 1-butyl-3-methylimidazolium nitrate) with common anion and different cations on the phase transition behavior of PVCL aqueous solution. The impact of ILs on the phase transition behavior of PVCL was monitored by using UV-visible absorption spectra, steady-state fluorescence spectroscopy, thermal fluorescence spectroscopy, and temperature dependent dynamic light scattering. Results showed significant changes in the absorbance, molecular interactions, agglomeration, and coil to globule transition behaviors of PVCL in the presence of two ILs. PVCL aqueous solution showed significant conformational changes after the addition of ILs.
Melanin: A Greener Route To Enhance Energy Storage under Solar Light (2019)

The development of technologies integrating solar energy conversion and energy storage functions is critical for limiting the anthropogenic effects on climate change and preventing possible energy shortages related to the increase of the world population. In our work, we explored the possibility to integrate the conversion and storage functions within the same multifunctional biosourced material. We identified the redox-active, quinone-based, melanin pigment, featuring a broadband absorption in the UV-vis region, as the ideal candidate for such an exploration. Electrodes of melanin on carbon paper were investigated for their morphological, optical, and voltammetric characteristics prior to being assembled into symmetric supercapacitors operating in aqueous electrolytes. We observed that, under solar light, the capacity and capacitance of melanin electrodes significantly increase with respect to the dark conditions (by 22 and 39%, respectively). Once in a supercapacitor configuration, besides featuring a Coulombic efficiency close to 100% after 5000 cycles, the capacitance and capacity of the electrodes, rated by the initial values, improve after prolonged illumination, as it is the case for the energy and power density.
Cyclin D2 overexpression drives B1a-derived MCL-like lymphoma in mice (2021)

Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with poor long-term overall survival. Currently, MCL research and development of potential cures is hampered by the lack of good in vivo models. MCL is characterized by recurrent translocations of CCND1 or CCND2, resulting in overexpression of the cell cycle regulators cyclin D1 or D2, respectively. Here, we show, for the first time, that hematopoiesis-specific activation of cyclin D2 is sufficient to drive murine MCL-like lymphoma development. Furthermore, we demonstrate that cyclin D2 overexpression can synergize with loss of p53 to form aggressive and transplantable MCL-like lymphomas. Strikingly, cyclin D2-driven lymphomas display transcriptional, immunophenotypic, and functional similarities with B1a B cells. These MCL-like lymphomas have B1a-specific B cell receptors (BCRs), show elevated BCR and NF-κB pathway activation, and display increased MALT1 protease activity. Finally, we provide preclinical evidence that inhibition of MALT1 protease activity, which is essential for the development of early life-derived B1a cells, can be an effective therapeutic strategy to treat MCL.
Kernel Smoothing of the Treatment Effect CDF (2018)

The strata-specific treatment effect or so-called blip for a randomly drawn strata of confounders defines a random variable and a corresponding cumulative distribution function. However, the CDF is not pathwise differentiable, necessitating a kernel smoothing approach to estimate it at a given point or perhaps many points. Assuming the CDF is continuous, we derive the efficient influence curve of the kernel smoothed version of the blip CDF and a CV-TMLE estimator. The estimator is asymptotically efficient under two conditions, one of which involves a second order remainder term which, in this case, shows us that knowledge of the treatment mechanism does not guarantee a consistent estimate. The remainder term also teaches us exactly how well we need to estimate the nuisance parameters (outcome model and treatment mechanism) to guarantee asymptotic efficiency. Through simulations we verify theoretical properties of the estimator and show the importance of machine learning over conventional regression approaches to fitting the nuisance parameters. We also derive the bias and variance of the estimator, the orders of which are analogous to a kernel density estimator. This estimator opens up the possibility of developing methodology for optimal choice of the kernel and bandwidth to form confidence bounds for the CDF itself.
Functional ultrasound imaging of intrinsic connectivity in the living rat brain with high spatiotemporal resolution (2014)

Long-range coherences in spontaneous brain activity reflect functional connectivity. Here we propose a novel, highly resolved connectivity mapping approach, using ultrafast functional ultrasound (fUS), which enables imaging of cerebral microvascular haemodynamics deep in the anaesthetized rodent brain, through a large thinned-skull cranial window, with pixel dimensions of 100 μm × 100 μm in-plane. The millisecond-range temporal resolution allows unambiguous cancellation of low-frequency cardio-respiratory noise. Both seed-based and singular value decomposition analysis of spatial coherences in the low-frequency (<0.1 Hz) spontaneous fUS signal fluctuations reproducibly report, at different coronal planes, overlapping high-contrast, intrinsic functional connectivity patterns. These patterns are similar to major functional networks described in humans by resting-state fMRI, such as the lateral task-dependent network putatively anticorrelated with the midline default-mode network. These results introduce fUS as a powerful novel neuroimaging method, which could be extended to portable systems for three-dimensional functional connectivity imaging in awake and freely moving rodents.