gebhart/patrepeval huggingface dataset:
Resolving the Coffey Paradox: what does the androgen receptor do in normal vs. malignant prostate epithelial cells? (2018)

Donald Straley Coffey completed his 85 year life's journey on November 9, 2017. In his wake, he left a legion of inspired and loyal students, fellows, and faculty colleagues from all over the world to carry on his passion both for life in general and his 50 year quest to conquer cancer. Early in his career, Dr. Coffey developed a series of animal models to study how androgen regulates the growth of both normal and abnormal prostatic epithelium. As part of these early studies, Dr. Coffey uncovered a paradox in that anti-androgen treatment given at the "wrong" time paradoxically enhanced, not inhibited, normal prostate growth. Advances over the last several years concerning the paracrine-dependent stem cell organization of the prostate provide a mechanistic explanation for this "Coffey Paradox". This is based upon the realization that the normal function of the Androgen Receptor (AR) in the paracrine-dependent stem cell organization of the prostate is to induce terminal differentiation of normal prostate epithelial cells while suppressing their growth, despite the presence of high levels of stromal cell-derived paracrine growth factors. Such growth suppression involves ligand-dependent AR binding to the Tcf-4/β-catenin 3'c-Myc enhancer in prostate epithelial cells, which inhibits c-Myc transcription needed for proliferation. Therefore, if anti-androgen is given at the wrong time, it prevents such AR-dependent c-Myc down regulation, and thus paradoxically enhances epithelial regrowth (i.e. the Coffey Paradox) induced by exogenous androgen replacement in the castration regressed prostate. In contrast to the normal prostate epithelium, in prostate cancer cells retaining AR expression, androgen-induced AR signaling no longer reduces c-Myc transcription but instead up-regulates c-Myc translation and protein stability to stimulate malignant growth. Thus, in these AR expressing prostate cancer cells, AR signaling is converted from a growth suppressor to an oncogene, which involves a gain of function to upregulate c-Myc protein expression. Such a gain of function "addicts" these prostate cancer cells to AR signaling for their proliferation and survival, which provides the rationale for therapy targeted at inhibiting such AR signaling. While therapies targeted at maximally decreasing the level of androgen ligand are the most commonly used, recent studies have documented that a subset of patients progressing on such androgen ablation (i.e. castration-resistant disease) due to their adaptive increase in AR protein expression respond positively to rapid cycling between pharmacologically high and castration low levels of circulating androgen. [i.e. Bipolar Androgen Therapy (BAT)].
Sequential causal inference in a single world of connected units (2021)

We consider adaptive designs for a trial involving N individuals that we follow along T time steps. We allow for the variables of one individual to depend on its past and on the past of other individuals. Our goal is to learn a mean outcome, averaged across the N individuals, that we would observe, if we started from some given initial state, and we carried out a given sequence of counterfactual interventions for $τ$ time steps. We show how to identify a statistical parameter that equals this mean counterfactual outcome, and how to perform inference for this parameter, while adaptively learning an oracle design defined as a parameter of the true data generating distribution. Oracle designs of interest include the design that maximizes the efficiency for a statistical parameter of interest, or designs that mix the optimal treatment rule with a certain exploration distribution. We also show how to design adaptive stopping rules for sequential hypothesis testing. This setting presents unique technical challenges. Unlike in usual statistical settings where the data consists of several independent observations, here, due to network and temporal dependence, the data reduces to one single observation with dependent components. In particular, this precludes the use of sample splitting techniques. We therefore had to develop a new equicontinuity result and guarantees for estimators fitted on dependent data. We were motivated to work on this problem by the following two questions. (1) In the context of a sequential adaptive trial with K treatment arms, how to design a procedure to identify in as few rounds as possible the treatment arm with best final outcome? (2) In the context of sequential randomized disease testing at the scale of a city, how to estimate and infer the value of an optimal testing and isolation strategy?
Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans (2015)

Neural stem cells (NSCs) continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR) 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs), VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.
Adenoviral Vector-Mediated Gene Therapy in the Mouse Lung: No Role of Fas-Fas Ligand Interactions for Elimination of Transgene Expression in Bronchioepithelial Cells (1999)

The early successes of adenoviral vector-mediated gene therapies in the lung have been hampered by the immune response directed against viral proteins and transgene product. Intratracheal administration of adenovirus vector in immune-competent mice transduces bronchioepithelial cells of lung extremely efficiently; however, transgene expression is eliminated within 2 weeks. Extinction of transgene expression has been attributed to infiltrating cytotoxic T lymphocytes (CTLs). Fas-Fas ligand (Fas-FasL) interactions play a critical role in the effector function of the CTL killing. We have previously demonstrated that this interacting pair of molecules plays a critical role in elimination of transgene expression in mouse liver. In this study we investigated the role of Fas-FasL interactions in CTL effector functions in vivo in mouse lung. Analyses of these molecules in lung showed constitutive expression of Fas in bronchiooepithelial cells. On the other hand, FasL was inducible in the bronchioepithelial cells after adenovirus vector treatment. The in vivo role of the Fas-FasL interactions was determined by adoptive transfer of splenocytes from normal immune-competent mice to Fas-deficient mice (B6-lpr); likewise, the function of FasL on CTLs was analyzed by the ability of splenocytes from FasL-deficient mice (B6-gld) to eliminate transgene expression in Rag1-deficient mice. These studies demonstrate that despite expression of Fas and FasL in bronchioepithelial cells and CTLs, these interacting molecules do not play a critical role in elimination of transgene expression in the lung.
Synchronous Speech Recognition and Speech-to-Text Translation with Interactive Decoding (2020)

Speech-to-text translation (ST), which translates source language speech into target language text, has attracted intensive attention in recent years. Compared to the traditional pipeline system, the end-to-end ST model has potential benefits of lower latency, smaller model size, and less error propagation. However, it is notoriously difficult to implement such a model without transcriptions as intermediate. Existing works generally apply multi-task learning to improve translation quality by jointly training end-to-end ST along with automatic speech recognition (ASR). However, different tasks in this method cannot utilize information from each other, which limits the improvement. Other works propose a two-stage model where the second model can use the hidden state from the first one, but its cascade manner greatly affects the efficiency of training and inference process. In this paper, we propose a novel interactive attention mechanism which enables ASR and ST to perform synchronously and interactively in a single model. Specifically, the generation of transcriptions and translations not only relies on its previous outputs but also the outputs predicted in the other task. Experiments on TED speech translation corpora have shown that our proposed model can outperform strong baselines on the quality of speech translation and achieve better speech recognition performances as well.
Real usage-based precise reliability test by extracting read/write/retention-mixed real-life access of NAND flash memory from system-level SSD emulator (2017)

Real usage-based precise reliability test for NAND flash of SSDs and reliability boost guidelines are proposed. Conventional simple reliability tests of data-retention and read-disturb cannot reproduce the real-life V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">TH</sub> shift and memory cell errors. The proposed reliability test method precisely reproduces the real memory cell failures by emulating the complicated read, write, and data-retention with SSD emulator. Based on the proposed reliability test, the guidelines of the read reference voltage shift are proposed to achieve the highest memory cell reliability for two kinds of real workloads.
<title>Vibrating surface actuators for active flow control</title> (2002)

Current research has shown that aircraft can gain significant aerodynamic performance benefits from active flow control (AFC). AFC seeks to control large scale flows by exploiting natural response triggered by small energy inputs. The principal target application is download alleviation of the V-22 Osprey under the DARPA sponsored Boeing Active Flow Control System program. One method of injecting energy into the flow over the V22 wings is to use an active vibrating surface on the passive seal between the wing and flapperon. The active surface is an oscillating cantilevered beam which injects fluid into the flow, similar to a synthetic jet, and interacts with the flow field. Two types of actuators, or flipperons, are explored. The first is a multilayer piezoelectric polyvinylidene fluoride cantilevered bender. The second is a single crystal piezoelectric (SCP)d<SUB>31</SUB> poled wafer mounted on a cantilevered spring steel substrate. This paper details the development effort including fabrication, mechanical and electrical testing, and modeling for both types of actuators. Both flipperons were mounted on the passive seal between a 1/10th scale V22 wing and flapperon and the aerodynamic performance evaluated in low speed wind tunnel. The SCP flipperon demonstrated significant cruise benefits, with increase of 10 percent lift and 20 percent angle of attack capability. The PVDF flipperon provided a 16 percent drag reduction in the hover mode.
Suppression of renal cell carcinoma growth and metastasis with sustained antiangiogenic gene therapy (2007)

B151 INTRODUCTION AND OBJECTIVE: Renal Cell Carcinoma (RCC) is the third most common urologic neoplasm. This aggressive malignancy has proven refractory to conventional treatment options. Recently, antiangiogenic agents have shown early success in treating metastatic disease. The highly vascular nature of RCC appears particularly susceptible to this approach. This study investigates the potential of sustained expression of an endostatin-angiostatin fusion protein in an early-stage model of RCC to inhibit tumor growth and metastasis.  METHODS: Subcutaneous RCC-29 tumors were induced in 7-week old athymic nude male mice by injecting 2x106 cells bilaterally into each flank region. Mice were divided into two groups. Once tumors reached volumes of 10 mm3 and 25 mm3 respectively, subjects received intratumoral injections in the right flank only of a non-replicating adenoviral vector every 20 days until the conclusion of the trial. The mice were randomly assigned to three treatment groups: saline control, viral Ad-GFP control and Ad-EndoAngio, encoding a chimeric endostatin-angiostatin fusion protein. Tumor volumes were measured twice weekly for 80 days. During days 40-50 of the trial, subjects were administered fluorescent rhodamine-BSA dye and underwent dual-photon optical imaging of the tumor vasculature to ascertain antiangiogenic effects of treatment. All animals underwent post-mortem histopathological analysis to assess for metastatic disease in the kidney, lung, liver, brain, lymph nodes and spleen.  RESULTS: The 10 mm3 and 25 mm3 tumor arms when treated with Ad-EndoAngio displayed 97% and 92% growth reduction respectively (p
Slater model applied to polarization graded ferroelectrics (1997)

Ferroelectric thin films of BaxSr1−xTiO3 with compositional gradients normal to the growth surface have been formed by the successive deposition and annealing of films having step-variable Ba to Sr ratios. By suitably tailoring the magnitude and sense of the gradient in Ba to Sr ratio, directional potentials can be built into the structures yielding a new, but controllable, hysteresis phenomenon. Slater’s empirical model for ferroelectric materials has been extended to also describe thin films with polarization gradients normal to the growth surface, i.e., graded ferroelectric devices. This model accounts for several aspects of these structures, including: the broadness of the permittivity plots with temperature, the formation of a spontaneous potential upon oscillatory field excitation, offsets in the hysteresis graphs along the displacement axis with directions which are gradient dependent, and the electric field dependence of that offset.
Imaging Venus' surface at night in the near-IR from above its clouds: New analytical models for the effective spatial resolution, illustrated with new Parker Solar Probe data (2022)

There are a handful of spectral windows in the near-IR through which we can see down to Venus' surface on the night side of the planet. The surface of our sister planet has thus been imaged by sensors on Venus-orbiting platforms (Venus Express, Akatsuki) and during fly-by with missions to other planets (Galileo, Cassini). The most tantalizing finding, so far, is the hint of possible active volcanism. However, the thermal radiation emitted by Venus' searing surface (c. 475 degrees C) has to get through the opaque clouds between 50 and 70 km altitude, as well as the sub-cloud atmosphere. In the clouds, the light is not absorbed but scattered, indeed, many times. This results in blurring the surface imagery to the point where the smallest discernible feature is roughly 100 km in size, full-width half-max (FWHM), and this has been reproduced using numerical models. We propose a new analytical modeling framework for predicting the width of the atmospheric point-spread function (APSF) that determines the effective resolution of surface imaging from space. Our best estimates of the APSF width for the 1-to-1.2 micron spectral range are clustered around 130 km FWHM. Interestingly, this is somewhat larger than the accepted value of 100 km based on both visual image inspection and detailed numerical simulations. Lastly, we apply the new modeling framework to the fly-by imaging by the Parker Solar Probe in a somewhat shorter wavelength band.
CCDC 756407: Experimental Crystal Structure Determination (2010)

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Stability of La0.6Sr0.4Co0.2Fe0.8O3-δas SOFC Cathode (2012)

The stability of La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF6428) was studied by long-term annealing of the sintered pellets with and without oxygen potential gradients. The heat treatments at 1073–1273 K under uniform oxygen partial pressure of 10−4 − 0.21 bar for one week did not make any notable changes in the composition of the pellets. However, significant changes were observed in the morphology and the composition at the surface of the high p(O2) side (1 bar oxygen side) when the pellet was placed under oxygen potential gradient between 1 bar oxygen and diluted oxygen from 10−4 to 10−1 bar. On the high p(O2) side, many particles containing cobalt and strontium, possibly cobalt oxides and strontium oxides, were found along the grain boundary by the scanning electron microscopic observation and the energy dispersive X-ray analysis. The amount as well as size of the deposited particles increased with decreasing oxygen potential on the low oxygen partial pressure side, i.e. increasing the oxygen potential gradient, and/or with increasing temperature. The results indicated that kinetic decomposition took place since the diffusions of cobalt and strontium ions are faster than those of the other cations.
Biophysically inspired model for functionalized nanocarrier adhesion to cell surface: roles of protein expression and mechanical factors (2016)

In order to achieve selective targeting of affinity-ligand coated nanoparticles to the target tissue, it is essential to understand the key mechanisms that govern their capture by the target cell. Next-generation pharmacokinetic (PK) models that systematically account for proteomic and mechanical factors can accelerate the design, validation and translation of targeted nanocarriers (NCs) in the clinic. Towards this objective, we have developed a computational model to delineate the roles played by target protein expression and mechanical factors of the target cell membrane in determining the avidity of functionalized NCs to live cells. Model results show quantitative agreement with in vivo experiments when specific and non-specific contributions to NC binding are taken into account. The specific contributions are accounted for through extensive simulations of multivalent receptor-ligand interactions, membrane mechanics and entropic factors such as membrane undulations and receptor translation. The computed NC avidity is strongly dependent on ligand density, receptor expression, bending mechanics of the target cell membrane, as well as entropic factors associated with the membrane and the receptor motion. Our computational model can predict the in vivo targeting levels of the intracellular adhesion molecule-1 (ICAM1)-coated NCs targeted to the lung, heart, kidney, liver and spleen of mouse, when the contributions due to endothelial capture are accounted for. The effect of other cells (such as monocytes, etc.) do not improve the model predictions at steady state. We demonstrate the predictive utility of our model by predicting partitioning coefficients of functionalized NCs in mice and human tissues and report the statistical accuracy of our model predictions under different scenarios.
The Fram Strait Tomography Experiment 2008 (2008)

Two field experiments have been carried out in connection with the tomography experiment in the Fram Strait. In the first Cruise, during 14-18 August 2008, the acoustic tomography system was successfully deployed from RV Håkon Mosby. In addition we deployed 7 transponders, a McLane profiling CTD mooring near the tomographic source mooring, and 9 CTD stations were taken between the source and the receiver mooring. During the second cruise 19-26 September 2008 using the KV Svalbard it was confirmed that the tomography system is working, 20 acoustic listening stations were obtained, 16 XBTs were obtained along the acoustic track,<br> AWIs sea glider was recovered, UPMC Moored Ocean Profiler (MOP) mooring and AWI winch mooring were recovered, and finally 3 ice stations were visited. The two cruises were successfully carried out with the exception that we were not able to download the acoustic<br> data using acoustic modems.
Control of a small robot using a hybrid optical modulating retro-reflector/RF link (2014)

Tele-operated robots used for Explosive Ordnance Disposal (EOD) are ordinarily controlled using a radio frequency (RF) link. Use of RF links on the battlefield presents several challenges including spectrum allocation and jamming effects (both by the enemy and friendly forces). Several solutions have been attempted including electrical or fiber optic umbilicals and spread spectrum radios with varying degrees of success. Modulating Retro-reflector Free Space Optical (MRR-FSO) communications links avoid these effects entirely but are limited to line of sight operation. We have developed a system consisting of an MRR-FSO link with a tracking optical terminal, a conventional RF link and a deployable pod to provide a relay node bridging the FSO link to the operator and the RF link to the robot. The MRRFSO link provides the capability to operate the robot in the presence of jamming while the RF link allows short range non line of sight operation. The operator uses the MRR-FSO link to drive the robot to a position downrange outside the influence of the jammer or other interference. Once the robot is positioned downrange near the area of operation the pod is deployed. This allows the robot to maneuver freely including venturing beyond line of sight using the short range RF link to maintain communications between the vehicle and pod while the FSO link maintains connectivity between the pod and the operator.
Diagram Method for Resolution Limit Calculation in Laser Microscopy (2017)

In 1873, Ernst Abbe established the modem theory of image formation in optical microscopy and derived the well-known formula for optical resolution, d=λ /2 NA , which corresponds to frequency cutoff (resolution limit) of 2 NA/λ . Recently many kinds of laser microscopy have been developed by means of a variety of light-matter interactions. Although the Abbe’s definition of resolution limit is still used as the standard, it is relatively unknown that 2 NA/λ can be applied only to the microscopy utilizing χ (1) -derived light-matter interaction such as linear absorption. If taking advantage of higher order χ (1) -derived interactions ( i ≧2), the resolution limit may surpass 2 NA/λ. In this study, we formulated the rules for the calculation of resolution limit in all laser microscopy that employ arbitrary interactions.
Quelques applications cliniques de l'électrophorèse capillaire (1999)

Several applications of capillary electrophoresis using laser-induced fluorescence or indirect UV detection were realised in biological sciences; analysis of ribonucleic acid involved in atherosclerosis, amino acids and biogenic amines in serae or cerebrospinal fluids, anthracycline in tumors and the analysis of organic acids for bacterial taxonomy.