gebhart/patrepeval huggingface dataset:
Androgen receptor (AR) antagonism triggers acute succinate‐mediated adaptive responses to reactivate AR signaling (2021)

Treatment-induced adaptive pathways converge to support androgen receptor (AR) reactivation and emergence of castration-resistant prostate cancer (PCa) after AR pathway inhibition (ARPI). We set out to explore poorly defined acute adaptive responses that orchestrate shifts in energy metabolism after ARPI and identified rapid changes in succinate dehydrogenase (SDH), a TCA cycle enzyme with well-known tumor suppressor activity. We show that AR directly regulates transcription of its catalytic subunits (SDHA, SDHB) via androgen response elements (AREs). ARPI acutely suppresses SDH activity, leading to accumulation of the oncometabolite, succinate. Succinate triggers calcium ions release from intracellular stores, which in turn phospho-activates the AR-cochaperone, Hsp27 via p-CaMKK2/p-AMPK/p-p38 axis to enhance AR protein stabilization and activity. Activation of this pathway was seen in tissue microarray analysis on prostatectomy tissues and patient-derived xenografts. This adaptive response is blocked by co-targeting AR with Hsp27 under both in vitro and in vivo studies, sensitizing PCa cells to ARPI treatments.
Tissue Engineering: Scaffold‐Mediated 2D Cellular Orientations for Construction of Three Dimensionally Engineered Tissues Composed of Oriented Cells and Extracellular Matrices (Adv. Funct. Mater. 7/2009) (2009)

Novel technology for fabrication of 3D-engineered tissues consisting of oriented cells and extracellular matrices (ECM) is described by Yoshida and co-workers on page 1001. They prepare disulfide-crosslinked hydrogels with oriented pores to induce cellular orientations on and in the scaffolds. Finally, 3D-oriented engineered tissues with 2D-cell and ECM orientation are successfully obtained by decomposing template gel with reductant agent.
Efficient signal multiplexing scheme based on optical signal processing (2015)

Distributed signals undergo multiplexing/de-multiplexing in which many signals are sequentially multiplexed by subcarrier multiplexing on a single optical carrier. Precise and dense packing is achieved by cross-phase modulation in nonlinear fibers with locally defined subcarriers.
Engineering a Cytidine Aminotransferase for Biocatalytic Production of the Antiviral Molnupiravir (2021)

The COVID-19 pandemic highlights the urgent need for cost-effective processes to rapidly manufacture antiviral drugs at scale. Here we report a concise biocatalytic process for Molnupiravir, a nucleoside analogue currently in phase 3 clinical trials as an orally available treatment for SARS-CoV-2. Key to the success of this process was the development of a cytidine aminotransferase for the production of N-hydroxy-cytidine through evolutionary adaption of the hydrolytic enzyme cytidine deaminase. This engineered biocatalyst performs &gt;100,000 turnovers in less than 30 minutes, operates at 180 g/L substrate loading and benefits from in situ crystallization of the N-hydroxy-cytidine product (&gt;90% yield), which can be converted to Molnupiravir by a selective 5’-acylation using Novozym® 435.
Neuronal entry and high neurotoxicity of botulinum neurotoxin A require its N-terminal binding sub-domain (2017)

Botulinum neurotoxins (BoNTs) are the most toxic proteins known, due to inhibiting the neuronal release of acetylcholine and causing flaccid paralysis. Most BoNT serotypes target neurons by binding to synaptic vesicle proteins and gangliosides via a C-terminal binding sub-domain (H<sub>CC</sub>). However, the role of their conserved N-terminal sub-domain (H<sub>CN</sub>) has not been established. Herein, we created a mutant form of recombinant BoNT/A lacking H<sub>CN</sub> (rAΔH<sub>CN</sub>) and showed that the lethality of this mutant is reduced 3.3 × 10<sup>4</sup>-fold compared to wild-type BoNT/A. Accordingly, low concentrations of rAΔH<sub>CN</sub> failed to bind either synaptic vesicle protein 2C or neurons, unlike the high-affinity neuronal binding obtained with <sup>125</sup>I-BoNT/A (K<sub>d</sub> = 0.46 nM). At a higher concentration, rAΔH<sub>CN</sub> did bind to cultured sensory neurons and cluster on the surface, even after 24 h exposure. In contrast, BoNT/A became internalised and its light chain appeared associated with the plasmalemma, and partially co-localised with vesicle-associated membrane protein 2 in some vesicular compartments. We further found that a point mutation (W985L) within H<sub>CN</sub> reduced the toxicity over 10-fold, while this mutant maintained the same level of binding to neurons as wild type BoNT/A, suggesting that H<sub>CN</sub> makes additional contributions to productive internalization/translocation steps beyond binding to neurons.
CellFIT: A Cellular Force-Inference Toolkit Using Curvilinear Cell Boundaries (2014)

Mechanical forces play a key role in a wide range of biological processes, from embryogenesis to cancer metastasis, and there is considerable interest in the intuitive question, "Can cellular forces be inferred from cell shapes?" Although several groups have posited affirmative answers to this stimulating question, nagging issues remained regarding equation structure, solution uniqueness and noise sensitivity. Here we show that the mechanical and mathematical factors behind these issues can be resolved by using curved cell edges rather than straight ones. We present a new package of force-inference equations and assessment tools and denote this new package CellFIT, the Cellular Force Inference Toolkit. In this approach, cells in an image are segmented and equilibrium equations are constructed for each triple junction based solely on edge tensions and the limiting angles at which edges approach each junction. The resulting system of tension equations is generally overdetermined. As a result, solutions can be obtained even when a modest number of edges need to be removed from the analysis due to short length, poor definition, image clarity or other factors. Solving these equations yields a set of relative edge tensions whose scaling must be determined from data external to the image. In cases where intracellular pressures are also of interest, Laplace equations are constructed to relate the edge tensions, curvatures and cellular pressure differences. That system is also generally overdetermined and its solution yields a set of pressures whose offset requires reference to the surrounding medium, an open wound, or information external to the image. We show that condition numbers, residual analyses and standard errors can provide confidence information about the inferred forces and pressures. Application of CellFIT to several live and fixed biological tissues reveals considerable force variability within a cell population, significant differences between populations and elevated tensions along heterotypic boundaries.
Double Integral involving the Product of the Bessel Function of the First Kind and Modified Bessel Function of the Second Kind: Derivation and Evaluation (2022)

A double integral whose kernel involves the Bessel functions Kv(xβ) and Jv(yα) is derived. This integral is expressed in terms of the Hurwitz-Lerch zeta function and evaluated for various values of the parameters involved. Some examples are evaluated and expressed in terms of fundamental constants. All the results in this work are new.
Index (2013)

A thorough musculoskeletal and sensory exam is required for any patient prior to TMR surgery (see Chapter 5). Special attention should be given to the proximal shoulder on the injured side, as proximal kinetic chain injury is very common with traumatic arm amputation. A thorough evaluation of the patient’s overall posture and core conditioning is also important, as postural musculature plays a significant role in the control of upper limb myoelectric prostheses. In addition, an assessment should be made of the patient’s enthusiasm for using a prosthesis, compliance with past treatment, and understanding of the TMR process. If the patient has already been fit with a prosthesis, the patient’s functional ability with the device should be thoroughly assessed before surgery to provide an indication of prosthesis control prior to TMR surgery and allow comparison to functional control after TMR. This baseline assessment cannot be performed after surgery, as prosthesis control may degrade before the final TMR fitting, due to denervation of original control muscles.
Use of Trifluoromethyl Groups for Catalytic Benzylation and Alkylation with Subsequent Hydrodefluorination (2015)

Abstract The electrophilic organofluorophosphonium catalyst [(C 6 F 5 ) 3 PF][B(C 6 F 5 ) 4 ] is shown to effect benzylation or alkylation by aryl and alkyl CF 3 groups with subsequent hydrodefluorination, thus resulting in a net transformation of CF 3 into CH 2 –aryl fragments. In the case of alkyl CF 3 groups, Friedel–Crafts alkylation by the difluorocarbocation proceeded without cation rearrangement, in contrast to the corresponding reactions of alkyl monofluorides.
Regulated and controlled liberalisation: a means to reconcile market efficiency and social cohesion? (2002)

The opening up of the public sector by a strategy of regulated liberalisation is a controversial policy area for the EU. The article provides an introduction to the political, economic and social considerations on which European liberalisation is based, namely the need for a balance between economic efficiency and ensuring the provision of public goods. The most important elements in the practical implementation of EU liberalisation policy, with their weaknesses and deficiencies, are explained. In conclusion the changes implied for trade unions are discussed: while liberalisation undoubtedly confronts unions with new challenges and dangers, it also offers them opportunities, provided they Europeanise their interest representation structures.
Effect of a supplement containing trans-10,cis-12 conjugated linoleic acid on the performance of dairy ewes fed 2 levels of metabolizable protein and at a restricted energy intake (2011)

Trans-10,cis-12 conjugated linoleic acid (CLA) inhibits milk fat synthesis in dairy ewes, but the effects under varying dietary metabolizable protein (MP) levels when energy-limited diets are fed have not been examined. The objectives of the study were to evaluate the response of lactating dairy ewes to CLA supplementation when fed diets limited in metabolizable energy (ME) and with either a low or high MP content. Twelve multiparous ewes in early lactation were randomly allocated to 1 of 4 dietary treatments: a high MP (110% of daily MP requirement) or low MP (93% of daily MP requirement) diet unsupplemented or supplemented with a lipid-encapsulated CLA to provide 2.4 g/d of trans-10,cis-12 CLA, in each of 4 periods of 25 d each in a 4×4 Latin square design. All diets were restricted to supply each ewe with 4.6 Mcal of ME/d (equivalent to 75% of ME requirement). Supplementation with CLA decreased milk fat percentage and yield by 33% and 24%, respectively, and increased milk, milk protein, and lactose yields by 16, 13, and 17%, respectively. Feeding the high MP diet increased the yields of milk, fat, protein, and lactose by 18, 15, 19, and 16%, respectively. Milk fat content of trans-10,cis-12 CLA (g/100g) was 0.09 and <0.01 for the CLA-supplemented and unsupplemented ewes, respectively. Ewes supplemented with CLA had a reduced yield (mmol/d) of fatty acids of <C16, C16, and >C16, although the effect was greatest for <C16. Feeding a high MP level increased the yield of fatty acids of C16 and >C16. Plasma urea concentrations were lowest in ewes supplemented with CLA compared with those unsupplemented (6.5 vs. 7.4 mmol/L, respectively) and receiving low compared with high MP diets (5.6 vs. 8.3 mmol/L, respectively). In conclusion, dairy ewes fed energy-limited diets and supplemented with CLA repartitioned nutrients to increase yields of milk, protein, and lactose, with the response to CLA supplementation and additional MP intake being additive.
High-Resolution Computed Tomographic Bronchiolography Using Perfluoroctylbromide (PFOB) (1993)

The use of perfluoroctylbromide (PFOB), a liquid ventilatory agent, was evaluated as a computed tomographic contrast agent to visualize small airway anatomy to the level of the centrilobular bronchiole, normally not visible on high-resolution computed tomography (HRCT). A freshly excised neonatal lamb heart-lung preparation was tracheally intubated, suspended in a saline bath, and mechanically ventilated with gas. After obtaining HRCT control images with suspended respiration using continuous positive airway pressure, 30 ml of perfluorocytlbromide was instilled into the trachea and repeat scans were obtained. These images demonstrated PFOB filling and distending the airways to the level of the centrilobular bronchioles and their first order branches. There was only minimal spillage into air spaces, allowing excellent anatomic detail of the bronchiolar structures. A liquid ventilatory agent, PFOB is a superb candidate as a bronchographic contrast agent due to its promotion of gas exchange, low toxicity, low surface tension, radiopacity, and vaporized excretion via the lung. It has great potential to evaluate small airway disease when used in conjunction with HRCT.
Sparse-Push: Communication- &amp; Energy-Efficient Decentralized Distributed Learning over Directed &amp; Time-Varying Graphs with non-IID Datasets (2021)

Current deep learning (DL) systems rely on a centralized computing paradigm which limits the amount of available training data, increases system latency, and adds privacy and security constraints. On-device learning, enabled by decentralized and distributed training of DL models over peer-to-peer wirelessly connected edge devices, not only alleviate the above limitations but also enable next-gen applications that need DL models to continuously interact and learn from their environment. However, this necessitates the development of novel training algorithms that train DL models over time-varying and directed peer-to-peer graph structures while minimizing the amount of communication between the devices and also being resilient to non-IID data distributions. In this work we propose, Sparse-Push, a communication efficient decentralized distributed training algorithm that supports training over peer-to-peer, directed, and time-varying graph topologies. The proposed algorithm enables 466x reduction in communication with only 1% degradation in performance when training various DL models such as ResNet-20 and VGG11 over the CIFAR-10 dataset. Further, we demonstrate how communication compression can lead to significant performance degradation in-case of non-IID datasets, and propose Skew-Compensated Sparse Push algorithm that recovers this performance drop while maintaining similar levels of communication compression.
Exploring intercity regional similarity using worldwide location-based social network data (demo paper) (2022)

Finding out similar regions between cities is important to a variety of real-world applications, such as point-of-interest recommendations, site selection, and travel guidance. With the help of the increasing number of location-based social network users, we can measure the intercity similarity from a new perspective of spatiotemporal characteristics of human mobility. In this paper, we developed an interactive intercity regional similarity explorer (IRSE) that 1) visualizes regional spatiotemporal human mobility features, 2) searches similar region candidates in the target city, and 3) explores the regional similarity from different views in a quantitative and illustrative way. In this paper, we show how our system can be useful in exploring regional similarity across cities in the world by use cases, which will interest various users from different countries in the demonstration session. Demo available at: https://bit.ly/3OjwnGu
Recognition of hypermethylated triplet repeats in vitro by cationic nanoparticles (2001)

Genomic DNA contains many higher-order structural deviations from the Watson-Crick global average. The massive expansion and hypermethylation of the duplex triplet repeat (CCG)(n)(CGG)(n) has characteristic higher-order structures that are associated with the fragile X syndrome. We have used luminescent mineral nanoparticles of protein-sized cadmium sulfide in optical assays to detect anomalous DNA structures. The photoluminescence of these particles is sensitive to the presence and nature of adsorbates. We previously found that our nanoparticles bind the fragile X repeat well but do not bind to normal double-helical DNA. In this study, we have determined that these particles are also able to detect the hypermethylated forms of these triplet repeats. Therefore, these nanoparticles may form the basis for future optical assays of higher-order DNA structures, especially those associated with human disease.
Thin Films of Two Functional Oxides Patterned Laterally by Soft Lithography (2011)

Thin films of two laterally patterned functional oxides of uniform thickness were obtained in a two-step soft-lithographic micromolding process. CoFe(2)O(4)/ZnO and CoFe(2)O(4)/BaTiO(3) dual-phase patterns were fabricated. The films showed good replication of the pattern that was defined in the first patterning step. X-ray diffraction showed that the films consisted of two distinct phases, and magnetic force microscopy showed that the compounds were laterally separated, the separation pattern being the same as that of the initial soft-lithographic process. The films exhibited slight height variations near the edges of the phases, which were introduced in the first deposition step and were not fully compensated in the second deposition step. The films are sufficiently smooth to allow fabrication of multilayer structures.
Optimization of ultrashort pulse written volume-Bragg-gratings in fused silica for high power applications (Conference Presentation) (2019)

The ongoing increase of peak and average power of diode lasers makes the consideration of thermo-optical effects due to absorption in the optical system necessary. Otherwise, this local increase in temperature might lead to a significant reduction of the entire functionality or a complete failure. Here, we consider this issue in volume Bragg gratings (VBG) as they are typically used for wavelength stabilization of the laser diodes. Conventionally, these gratings are fabricated very effectively by inscription using ultraviolet light into special photosensitive glasses. However, the use of these special glasses might compromise the transmission and, thus, limit the application. As an alternative, we inscribe VBGs in pure fused silica using ultrashort laser pulses and the phase mask scanning technique. Applying these gratings for external stabilization of high power diode lasers already demonstrated an outstanding performance in sense of spectral drift due to load change compared to conventional VBGs. Here, we present investigations to further optimize the residual absorption of the gratings especially in the NIR. Apart from analyzing the influence of the processing parameters on the residual absorption, we also studied the possibility for a thermal post-processing to anneal absorbing defects. The resulting gratings exhibit a residual absorption close to the intrinsic absorption of fused silica, making them ideally suited for high power applications. Further applications in ultrashort pulse laser systems for pulse stretching and compression are discussed.
Translating Neurobehavioral Toxicity Across Species From Zebrafish to Rats to Humans: Implications for Risk Assessment (2021)

There is a spectrum of approaches to neurotoxicological science from high-throughput <i>in vitro</i> cell-based assays, through a variety of experimental animal models to human epidemiological and clinical studies. Each level of analysis has its own advantages and limitations. Experimental animal models give essential information for neurobehavioral toxicology, providing cause-and-effect information regarding risks of neurobehavioral dysfunction caused by toxicant exposure. Human epidemiological and clinical studies give the closest information to characterizing human risk, but without randomized treatment of subjects to different toxicant doses can only give information about association between toxicant exposure and neurobehavioral impairment. <i>In vitro</i> methods give much needed high throughput for many chemicals and mixtures but cannot provide information about toxicant impacts on behavioral function. Crucial to the utility of experimental animal model studies is cross-species translation. This is vital for both risk assessment and mechanistic determination. Interspecies extrapolation is important to characterize from experimental animal models to humans and between different experimental animal models. This article reviews the literature concerning extrapolation of neurobehavioral toxicology from established rat models to humans and from zebrafish a newer experimental model to rats. The functions covered include locomotor activity, emotion, and cognition and the neurotoxicants covered include pesticides, metals, drugs of abuse, flame retardants and polycyclic aromatic hydrocarbons. With more complete understanding of the strengths and limitations of interspecies translation, we can better use animal models to protect humans from neurobehavioral toxicity.
Ral Overactivation in Malignant Peripheral Nerve Sheath Tumors (2009)

Ras leads an important signaling pathway that is deregulated in neurofibromatosis type 1 and malignant peripheral nerve sheath tumor (MPNST). In this study, we show that overactivation of Ras and many of its downstream effectors occurred in only a fraction of MPNST cell lines. RalA, however, was overactivated in all MPNST cells and tumor samples compared to nontransformed Schwann cells. Silencing Ral or inhibiting it with a dominant-negative Ral (Ral S28N) caused a significant reduction in proliferation, invasiveness, and in vivo tumorigenicity of MPNST cells. Silencing Ral also reduced the expression of epithelial mesenchymal transition markers. Expression of the NF1-GTPase-related domain (NF1-GRD) diminished the levels of Ral activation, implicating a role for neurofibromin in regulating RalA activation. NF1-GRD treatment caused a significant decrease in proliferation, invasiveness, and cell cycle progression, but cell death increased. We propose Ral overactivation as a novel cell signaling abnormality in MPNST that leads to important biological outcomes with translational ramifications.
Gas flow characteristics of GCL under distortions, wet-dry cycles, and hydrating fluids (2023)

Geosynthetic clay liner (GCL) is commonly used in cover system of engineered landfill to limit migration of gases and infiltration of water. In engineered landfill, gas transfer occurs by advection and diffusion, which may take place at different time frames or simultaneously depending on placement conditions. Hence, efficacy of GCL as a gas barrier under advection and diffusion needs to be assessed at various geoenvironmental settings. In the present study, the gas flow response of GCL under advection and diffusion were evaluated at various apparent degrees of saturation, distortion levels, hydrating fluids, and wet-dry cycles using custom-designed test apparatus. Gas permeability and gas diffusion coefficient of GCL were found to decrease by four and three orders of magnitude respectively with an increase in apparent degree of saturation from 7% to 80%. Gas permeability and gas diffusion coefficient were increased with an increase in distortion levels. With an increase in wet-dry cycles 1 to 5, gas permeability and gas diffusion of GCL were increased marginally when hydrated with distilled water while increased by one order of magnitude for hydrated with 0.0125 M CaCl 2 solution. The obtained results were compared with published results and found to be in good agreement.