gebhart/patrepeval huggingface dataset:
Ligand-dependent interactions of coactivators steroid receptor coactivator-1 and peroxisome proliferator-activated receptor binding protein with nuclear hormone receptors can be imaged in live cells and are required for transcription (2000)

Members of the nuclear receptor superfamily are thought to activate transcription by recruitment of one or more recently identified coactivator complexes. Here we demonstrate that both peroxisome proliferator-activated receptor binding protein (PBP) and steroid receptor coactivator-1 (SRC-1) are required for ligand-dependent transcription of transiently transfected and chromosomally integrated reporter genes by the estrogen receptor (ER) and retinoic acid receptor (RAR). To examine ligand-dependent interactions between nuclear receptors and specific coactivators in living cells, these proteins were tagged with cyan (CFP) and yellow (YFP) mutants of the green fluorescent protein. Fluorescence resonance energy transfer (FRET) from the CFP to the YFP indicated interaction between the receptor and coactivator. CFP fusions to RAR or its ligand-binding domain exhibited rapid ligand-dependent FRET to YFP-tagged nuclear receptor interaction domains of the coactivators SRC-1 and PBP. The ER-ligand-binding domain, unlike RAR, also exhibited some basal interaction with coactivators in unstimulated cells that was abolished by the receptor antagonists tamoxifen or ICI182,780. Inhibition of FRET by tamoxifen but not ICI182,780 could be reversed by estradiol, whereas estradiol-enhanced FRET could not be inhibited by either antagonist, indicating that ligand effects can show varying degrees of hysteresis. These findings suggest that ligand-dependent transcriptional activities of the RAR and ER require concurrent or sequential recruitment of SRC-1 and PBP-containing coactivator complexes.
Low frequency variability in fall precipitation across the United States (2008)

Precipitation and streamflow have increased across the United States during the 20th century, with the largest increases observed in the fall. In this study, we apply the multitaper method with singular value decomposition (MTM‐SVD) multivariate spectral analysis to characterize the space‐time variability of fall precipitation over the United States from 1895 to 2004. MTM‐SVD analysis of precipitation demonstrates the presence of statistically significant secular and decadal signals. The decadal signal in fall precipitation, with a period of approximately 12 years, is large and spatially correlated across most of the central United States. The secular signal, with a period greater than 55 years, is weaker, much less spatially correlated and is strongest in the eastern United States. The decadal and secular variations increased in magnitude after 1950, the period when many previous studies have identified large linear trends. Linear trends in fall precipitation are found to be more spatially consistent with the pattern of decadal variations than the secular variations, suggesting that increasing decadal variations in precipitation after 1950 have contributed to large linear trends reported by several previous studies. Our results suggest that the strong spatial correlation in decadal precipitation variations across the central United States are associated with a large SLP gradient across North America that is conducive for southerly flow from the Gulf of Mexico. Secular variations in SLP associated with precipitation over the United States are located primarily in the high latitudes, and are not consistent with correlated variations in precipitation across the central United States.
Patient‑derived xenograft mouse models: A high fidelity tool for individualized medicine (Review) (2018)

Patient-derived xenograft (PDX) mouse models involve the direct transfer of fresh human tumor samples into immunodeficient mice following surgical resection or other medical operations. Gene expression in tumors may be maintained by serial passages of tumors from mouse to mouse. These models aid research into tumor biology and pharmacology without manual manipulation of cell cultures <i>in vitro</i>. and are widely used in individualized cancer therapy/translational medicine, drug development and coclinical trials. PDX models exhibit higher predictive values for clinical outcomes than cell line-derived xenograft models and genetically engineered mouse models. However, PDX models are associated with certain challenges in clinical application. The present study reviewed current collections of PDX models and assessed the challenges and future directions of this field.
Landmark-based autonomous navigation in sewerage pipes (2002)

We describe a method for an autonomous mobile robot to navigate through a system of sewerage pipes. Landmarks signalling positions in the pipe system have to be detected and classified, where classification is allowed do be unreliable. Self localization is interpreted as a partially observable Markov decision problem and solved accordingly. The method is implemented and used on a prototype robot platform operating in a dry sewage pipe test network.
T Cell Proliferation Induced by Autologous Non-T Cells Is a Response to Apoptotic Cells Processed by Dendritic Cells (2002)

Self-reactive T cells are present in the mature immune repertoire as demonstrated by T cell proliferation induced by autologous non-T cells in the autologous mixed lymphocyte reaction. This reaction generates regulatory T cells in vitro and may reflect immune regulatory pathways in vivo, but the antigenic peptides recognized remain uncharacterized. We revisited this issue in light of the importance of apoptosis in immune regulation. We found that apoptosis among peripheral blood non-T stimulator cells is associated with augmented induction of autologous T cell proliferation. Our data show that caspase activity in the non-T stimulator population is essential for induction of autologous T cell proliferation, suggesting that cellular components in the non-T cell fraction are enzymatically modified, most likely by effector caspases, and have a direct or indirect effect on autoreactive T cell activation. Furthermore, exposure of macrophage-derived dendritic cells to apoptotic non-T cells augments autologous T cell proliferation, and blockade of alpha(v)beta(5) integrin, but not alpha(v)beta(3), inhibits the capacity of irradiated non-T cells or dendritic cells to stimulate autologous T cell proliferation. These experiments, using an entirely autologous system, suggest the interpretation that autoreactive T cells may recognize self-Ags modified through the actions of caspases and presented to T cells by dendritic cells. Induction of an in vivo autologous mixed lymphocyte reaction by caspase-modified self-Ags present in apoptotic cells may represent a mechanism to maintain peripheral immune tolerance.
A Unified Theory of Two-Stage Adaptive Designs (2002)

Adaptation of a clinical trial occurs when there is a change from the planned course of action in design, sample size, or method of analysis. There are many proposed adaptations in the literature, but no comprehensive mathematical theory to support them. The standard Neyman–Pearson theory is not suitable for the setting, and its use may result in invalid inference. This article provides a general formulation of adaptation, under which its validity can be broadly and rigorously established. The basic theory on distribution, stochastic independence, point estimation, confidence intervals, hypothesis testing, and asymptotics is developed. Various examples are given to illustrate applications of the theory. The goal is to provide a solid theoretical foundation to aid the development of adaptive methods for clinical investigations.
Mining logic gates in prokaryotic transcriptional regulation networks (2008)

Prokaryotic transcriptional networks possess a large number of regulatory modules that formally implement many of the logic gates that are typical of digital, Boolean circuits. Yet, natural regulatory elements appear most often compressed and exaggeratedly context-dependent for any reliable circuit engineering barely comparable to electronic counterparts. To overcome this impasse, we argue that designing new functions with biological parts requires (i) the recognition of logic gates not yet assigned but surely present in the meta-genome, (ii) the orthogonalization and disambiguation of natural regulatory modules and (iii) the development of ways to tackle the connectivity and the definition of boundaries between minimal biological components.
Contribution of the tonic vibration reflex to muscle stress and muscle fatigue. (1993)

The aim of the investigation was to determine the influence of vibration displacement amplitude (200, 300 microns peak-to-peak), as opposed to acceleration effects at selected frequencies (40, 80, 100, 120, 150, 200 Hz), on a commonly observed but often undesired motor response elicited by local vibratory stimulation, that is, the tonic vibration reflex (TVR). Vibration was applied to the distal tendons of the hand flexor muscles. Changes in the activity of hand flexor and extensor muscles were analyzed as a function of both their initial contraction level (0, 10, 20% of maximal voluntary contraction) and the vibration parameters. The main results indicate that TVR increases with the initial muscle contraction and increases with vibration frequency up to 100-150 Hz but decreases beyond. High-frequency vibration seems to induce less muscle and tendon stress. This result is particularly important for the design of handheld vibrating tools.
A sensitive method for the determination of protein-DNA binding specificities (1990)

We describe a sensitive and rapid method for determination of the sequence specificity of DNA binding proteins. The method allows recovery of specific sites using the small amounts of protein present in crude cell extracts or produced by cell-free translation reactions. Extract proteins are incubated with a pool of random sequence oligonucleotides, complexes purified by immunoprecipitation, and bound DNA amplified by the Polymerase Chain Reaction (PCR). This DNA is then used in further rounds of binding, immunoprecipitation, and amplification, until specific binding is detectable. With the transcription factor SRF as a model system, we demonstrate that authentic high affinity binding sites are recovered, and show that epitope tagging can be used to allow recovery of sites when specific antibodies are unavailable. We also show that specific sites bound by the Fos protein, which binds DNA with high affinity only when complexed with other polypeptides, are easily recovered by this technique.
Biosensor based on force microscope technology (1996)

We are developing a sensor capable of detecting biological species such as cells, proteins, toxins, and DNA at concentrations as low as 10−18 M. The force amplified biological sensor will take advantage of the high sensitivity of force microscope cantilevers to detect the presence of as little as one superparamagnetic particle bound to a cantilever by a sandwich immunoassay technique. The device, which will ultimately be small enough for hand-held use, will perform an assay in about 10 min. Lock-in detection and use of a reference cantilever will provide a high degree of vibration immunity. An array of ten or more cantilevers will provide greater sensitivity and the capability to detect multiple species simultaneously. The force amplified biological sensor also offers the potential of distinguishing and studying chemical species via its ability to measure binding forces.
The adenosine analog prodrug ATV006 is orally bioavailable and has preclinical efficacy against parental SARS-CoV-2 and variants (2022)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus driving the ongoing coronavirus disease 2019 (COVID-19) pandemic, continues to rapidly evolve. Because of the limited efficacy of vaccination in prevention of SARS-CoV-2 transmission and continuous emergence of variants of concern (VOCs), orally bioavailable and broadly efficacious antiviral drugs are urgently needed. Previously, we showed that the parent nucleoside of remdesivir, GS-441524, has potent anti-SARS-CoV-2 activity. Here, we report that esterification of the 5'-hydroxyl moieties of GS-441524 markedly improved antiviral potency. This 5'-hydroxyl-isobutyryl prodrug, ATV006, demonstrated excellent oral bioavailability in rats and cynomolgus monkeys and exhibited potent antiviral efficacy against different SARS-CoV-2 VOCs in vitro and in three mouse models. Oral administration of ATV006 reduced viral loads and alleviated lung damage when administered prophylactically and therapeutically to K18-hACE2 mice challenged with the Delta variant of SARS-CoV-2. These data indicate that ATV006 represents a promising oral antiviral drug candidate for SARS-CoV-2.
Resting Cell Neutralization Assay for HIV-1 Primary Isolates (1997)

A technique is described for detecting the activity of neutralizing polyclonal or monoclonal antibodies against HIV-1 primary isolates. Most commonly, neutralizing antibody activity for HIV-1 is assessed by quantifying the ability of antibodies to inhibit virus infection in mitogen-activated peripheral blood mononuclear cells or transformed lymphocytes. Because the target of HIV infection in vivo is neither a mitogen-activated nor a transformed cell, an assay using unstimulated peripheral blood mononuclear cells as a more physiologic target cell was developed. This "resting cell assay" mainly utilizes primary HIV-1 isolates that have been carried for only a few passages in vitro. The result is an assay that is more efficient to perform and that detects neutralizing activity with comparable or greater sensitivity than that previously described for assays of primary HIV-1 isolates.
Capacitive micromachined ultrasonic transducers: next-generation arrays for acoustic imaging? (2002)

Piezoelectric materials have dominated the ultrasonic transducer technology. Recently, capacitive micromachined ultrasonic transducers (CMUTs) have emerged as an alternative technology offering advantages such as wide bandwidth, ease of fabricating large arrays, and potential for integration with electronics. The aim of this paper is to demonstrate the viability of CMUTs for ultrasound imaging. We present the first pulse-echo phased array B-scan sector images using a 128-element, one-dimensional (1-D) linear CMUT array. We fabricated 64- and 128-element 1-D CMUT arrays with 100% yield and uniform element response across the arrays. These arrays have been operated in immersion with no failure or degradation in performance over the time. For imaging experiments, we built a resolution test phantom roughly mimicking the attenuation properties of soft tissue. We used a PC-based experimental system, including custom-designed electronic circuits to acquire the complete set of 128 x 128 RF A-scans from all transmit-receive element combinations. We obtained the pulse-echo frequency response by analyzing the echo signals from wire targets. These echo signals presented an 80% fractional bandwidth around 3 MHz, including the effect of attenuation in the propagating medium. We reconstructed the B-scan images with a sector angle of 90 degrees and an image depth of 210 mm through offline processing by using RF beamforming and synthetic phased array approaches. The measured 6-dB lateral and axial resolutions at 135 mm depth were 0.0144 radians and 0.3 mm, respectively. The electronic noise floor of the image was more than 50 dB below the maximum mainlobe magnitude. We also performed preliminary investigations on the effects of crosstalk among array elements on the image quality. In the near field, some artifacts were observable extending out from the array to a depth of 2 cm. A tail also was observed in the point spread function (PSF) in the axial direction, indicating the existence of crosstalk. The relative amplitude of this tail with respect to the mainlobe was less than -20 dB.
Experimental verification of electro-refractive phase modulation in graphene (2015)

Abstract Graphene has been considered as a promising material for opto-electronic devices, because of its tunable and wideband optical properties. In this work, we demonstrate electro-refractive phase modulation in graphene at wavelengths from 1530 to 1570 nm. By integrating a gated graphene layer in a silicon-waveguide based Mach-Zehnder interferometer, the key parameters of a phase modulator like change in effective refractive index, insertion loss and absorption change are extracted. These experimentally obtained values are well reproduced by simulations and design guidelines are provided to make graphene devices competitive to contemporary silicon based phase modulators for on-chip applications.
Advances in mesenchymal stem cell-mediated gene therapy for cancer (2010)

Mesenchymal stem cells have a natural tropism for tumours and their metastases, and are also considered immunoprivileged. This remarkable combination of properties has formed the basis for many studies investigating their potential as tumour-specific delivery vehicles for suicide genes, oncolytic viruses and secreted therapeutic proteins. The aim of the present review is to discuss the range of approaches that have been used to exploit the tumour-homing capacity of mesenchymal stem cells for gene delivery, and to highlight advances required to realize the full potential of this promising approach.
Microfluidic Bubble Logic (2007)

We demonstrate universal computation in an all-fluidic two-phase microfluidic system. Nonlinearity is introduced into an otherwise linear, reversible, low-Reynolds number flow via bubble-to-bubble hydrodynamic interactions. A bubble traveling in a channel represents a bit, providing us with the capability to simultaneously transport materials and perform logical control operations. We demonstrate bubble logic AND/OR/NOT gates, a toggle flip-flop, a ripple counter, timing restoration, a ring oscillator, and an electro-bubble modulator. These show the nonlinearity, gain, bistability, synchronization, cascadability, feedback, and programmability required for scalable universal computation. With increasing complexity in large-scale microfluidic processors, bubble logic provides an on-chip process control mechanism integrating chemistry and computation.
Cognate DNA Stabilizes the Tumor Suppressor p53 and Prevents Misfolding and Aggregation (2009)

The tumor suppressor protein p53 is a nuclear protein that serves as an important transcription factor. The region responsible for sequence-specific DNA interaction is located in its core domain (p53C). Although full-length p53 binds to DNA as a tetramer, p53C binds as a monomer since it lacks the oligomerization domain. It has been previously demonstrated that two core domains have a dimerization interface and undergo conformational change when bound to DNA. Here we demonstrate that the interaction with a consensus DNA sequence provides the core domain of p53 with enhanced conformational stability at physiological salt concentrations (0.15 M). This stability could be either increased or abolished at low (0.01 M) or high (0.3 M) salt concentrations, respectively. In addition, interaction with the cognate sequence prevents aggregation of p53C into an amyloid-like structure, whereas binding to a nonconsensus DNA sequence has no effect on p53C stability, even at low ionic strength. Strikingly, sequence-specific DNA binding also resulted in a large stabilization of full-length p53, whereas nonspecific sequence binding led to no stabilization. The effects of cognate DNA could be mimicked by high concentrations of osmolytes such as glycerol, which implies that the stabilization is caused by the exclusion of water. Taken together, our results show an enhancement in protein stability driven by specific DNA recognition. When cognate DNA was added to misfolded protein obtained after a pressurization cycle, the original conformation was mostly recovered. Our results may aid the development of therapeutic approaches to prevent misfolded species of p53.
Adenoviral Interleukin-2 Gene Transfer into P815 Tumor Cells Abrogates Tumorigenicity and Induces Antitumoral Immunity in Mice (1993)

The murine mastocytoma cell line P815 was used as a model to evaluate the effect on its tumorigenic capacity following interleukin-2 (IL-2) gene transfer into the tumor cells using a replication-defective adenovirus vector. The data show that P815 cells infected in vitro with this recombinant adenovirus secreted significant amounts of functional IL-2 as tested on CTL-L2 cells. Furthermore, when injected into syngeneic DBA/2 mice, the tumorigenic phenotype is lost in up to 80% of the animals. The rejection of the infected cells was host dependent, because co-injection at the same site or concomitant injection at the opposite side of the animal with a tumorigenic dose of noninfected P815 cells did not lead to tumor development in 50-70% of the mice. Moreover, protected animals developed a long-lasting state of immunization against the P815 tumor cells and their splenocytes were able to transfer the immunity to syngeneic naive recipients.
Studies on Glycosidase Inhibitors: Synthesis of 2,6-Dideoxy-2,6-imino-L-gulonic Acid and Its 3-Deoxy Analog (1995)

2,6-Dideoxy-2,6-imino-L-gulonic acid (1) with inhibitory activity against β-D-glucuronidase and α-L-iduronidase was stereoselectively synthesized from 2,3-di-O-benzyl-N-benzyloxycarbonyl-6-O-t-butyldiphenylsilyl-1,5- dideoxy-1 ,5-imino-D-glucitol (4). Through a deoxygenation reaction at the C-4 position of the latter, 2,3,6-trideoxy-2,6-imino-L-gulonic acid (2) was also prepared.
Novel lymphocyte-specific CC chemokines and their receptors (1997)

Abstract By using a cloning method termed the signal sequence trap as well as by searching for chemokine homologous sequences in the database of expressed sequence tags, cDNA fragments potentially encoding novel CC chemokines were initially identified. Using these sequences, we have cloned five novel human CC chemokines termed TARC, LARC, ELC, SLC, and PARC. These chemokines are constitutively expressed especially in some lymphoid tissues with individually unique expression patterns. The recombinant proteins are all found to be selectively chemotactic for lymphocytes but not for monocytes or neutrophils. Each chemokine appears to interact with a class of receptors on lymphocytes that is not shared by any other chemokines so far tested. Furthermore, we have identified CCR4 as the specific receptor for TARC, GPR-CY4/DRY6/CKR-L3/STRL22 as that for LARC (CCR6), and EBI1/BLR2 as that for ELC (CCR7). Only the gene for PARC is mapped to the traditional CC chemokine gene cluster at chromosome 17q11.2, whereas those for TARC, LARC, ELC, and SLC are localized at different loci. Collectively, these five CC chemokines may constitute a new category of CC chemokines that are involved in trafficking and homing of particular subsets of lymphocytes in particular lymphoid tissue microenvironments.
Design Parameters of a Miniaturized Piezoelectric Underwater Acoustic Transmitter (2012)

PZT ceramics have been widely used in underwater acoustic transducers. However, literature available discussing the design parameters of a miniaturized PZT-based low-duty-cycle transmitter is very limited. This paper discusses some of the design parameters--the backing material, driving voltage, PZT material type, power consumption and the transducer length of a miniaturized acoustic fish tag using a PZT tube. Four different types of PZT were evaluated with respect to the source level, energy consumption and bandwidth of the transducer. The effect of the tube length on the source level is discussed. The results demonstrate that ultralow-density closed-cell foam is the best backing material for the PZT tube. The Navy Type VI PZTs provide the best source level with relatively low energy consumption and that a low transducer capacitance is preferred for high efficiency. A 35% reduction in the transducer length results in 2 dB decrease in source level.