gebhart/patrepeval huggingface dataset:
An Integrated Computational/Experimental Model of Lymphoma Growth (2013)

Non-Hodgkin's lymphoma is a disseminated, highly malignant cancer, with resistance to drug treatment based on molecular- and tissue-scale characteristics that are intricately linked. A critical element of molecular resistance has been traced to the loss of functionality in proteins such as the tumor suppressor p53. We investigate the tissue-scale physiologic effects of this loss by integrating in vivo and immunohistological data with computational modeling to study the spatiotemporal physical dynamics of lymphoma growth. We compare between drug-sensitive Eμ-myc Arf-/- and drug-resistant Eμ-myc p53-/- lymphoma cell tumors grown in live mice. Initial values for the model parameters are obtained in part by extracting values from the cellular-scale from whole-tumor histological staining of the tumor-infiltrated inguinal lymph node in vivo. We compare model-predicted tumor growth with that observed from intravital microscopy and macroscopic imaging in vivo, finding that the model is able to accurately predict lymphoma growth. A critical physical mechanism underlying drug-resistant phenotypes may be that the Eμ-myc p53-/- cells seem to pack more closely within the tumor than the Eμ-myc Arf-/- cells, thus possibly exacerbating diffusion gradients of oxygen, leading to cell quiescence and hence resistance to cell-cycle specific drugs. Tighter cell packing could also maintain steeper gradients of drug and lead to insufficient toxicity. The transport phenomena within the lymphoma may thus contribute in nontrivial, complex ways to the difference in drug sensitivity between Eμ-myc Arf-/- and Eμ-myc p53-/- tumors, beyond what might be solely expected from loss of functionality at the molecular scale. We conclude that computational modeling tightly integrated with experimental data gives insight into the dynamics of Non-Hodgkin's lymphoma and provides a platform to generate confirmable predictions of tumor growth.
Energy Efficiency Analysis of Comb Source Carrier-Injection Ring-Based Silicon Photonic Link (2019)

Current electronic interconnections in high performance computing (HPC) systems are reaching their limit in supporting high data traffic demands. Dense wavelength-division multiplexed (DWDM) links have gained interest as they can potentially alleviate these interconnect bandwidth demands while also lowering the cost and energy consumption compared to traditional electronic links. In this article we present an analysis of a ring-based DWDM silicon photonic (SiP) link architecture with a comb laser source and p-i-n photodetectors. Specifically, we consider microring resonators (MRRs) with narrow bus waveguides and carrier-injection ring modulators. We propose a new method to select the optimal comb source setting to minimize the laser power consumption at a particular data rate. Additionally, we leverage power penalty models supported by measurements to estimate the effective received optical power at the receiver input of each of the DWDM channels which yields a bit error rate (BER) of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-12</sup> or lower. We show that the analyzed comb source has the lowest power consumption per channel for 24 consecutive lines. For these comb settings, the maximum channel data rate of non-return to zero on-off keying (NRZ-OOK) signals is 22 Gbps, and the minimum energy consumption is 3.28 pJ/bit.
Detection and removal of rain from videos (2004)

The visual effects of rain are complex. Rain consists of spatially distributed drops falling at high velocities. Each drop refracts and reflects the environment, producing sharp intensity changes in an image. A group of such falling drops creates a complex time varying signal in images and videos. In addition, due to the finite exposure time of the camera, intensities due to rain are motion blurred and hence depend on the background intensities. Thus, the visual manifestations of rain are a combination of both the dynamics of rain and the photometry of the environment. In this paper, we present the first comprehensive analysis of the visual effects of rain on an imaging system. We develop a correlation model that captures the dynamics of rain and a physics-based motion blur model that explains the photometry of rain. Based on these models, we develop efficient algorithms for detecting and removing rain from videos. The effectiveness of our algorithms is demonstrated using experiments on videos of complex scenes with moving objects and time-varying textures. The techniques described in this paper can be used in a wide range of applications including video surveillance, vision based navigation, video/movie editing and video indexing/retrieval.
Performance Impact Analysis of Beam Switching in Millimeter Wave Vehicular Communications (2021)

Millimeter wave wireless spectrum deployments will allow vehicular communications to share high data rate vehicular sensor data in real-time. The highly directional nature of wireless links in millimeter spectral bands will require continuous channel measurements to ensure the transmitter (TX) and receiver (RX) beams are aligned to provide the best channel. Using real-world vehicular mmWave measurement data at 28 GHz, we determine the optimal beam sweeping period, i.e. the frequency of the channel measurements, to align the RX beams to the best channel directions for maximizing the vehicle-to-infrastructure (V2I) throughput. We show that in a realistic vehicular traffic environment in Austin, TX, for a vehicle traveling at an average speed of 10.5 mph, a beam sweeping period of 300 ms in future V2I communication standards would maximize the V2I throughput, using a system of four RX phased arrays that scanned the channel 360 degrees in the azimuth and 30 degrees above and below the boresight. We also investigate the impact of the number of active RX chains controlling the steerable phased arrays on V2I throughput. Reducing the number of RX chains controlling the phased arrays helps reduce the cost of the vehicular mmWave hardware while multiple RX chains, although more expensive, provide more robustness to beam direction changes at the vehicle, allowing near maximum throughput over a wide range of beam sweep periods. We show that the overhead of utilizing one RX chain instead of four leads to a 10% drop in mean V2I throughput over six non-line-of-sight runs in real traffic conditions, with each run being 10 to 20 seconds long over a distance of 40 to 90 meters.
Biased M 1 receptor–positive allosteric modulators reveal role of phospholipase D in M 1 -dependent rodent cortical plasticity (2019)

Highly selective, positive allosteric modulators (PAMs) of the M<sub>1</sub> subtype of muscarinic acetylcholine receptor have emerged as an exciting new approach to potentially improve cognitive function in patients suffering from Alzheimer's disease and schizophrenia. Discovery programs have produced a structurally diverse range of M<sub>1</sub> receptor PAMs with distinct pharmacological properties, including different extents of agonist activity and differences in signal bias. This includes biased M<sub>1</sub> receptor PAMs that can potentiate coupling of the receptor to activation of phospholipase C (PLC) but not phospholipase D (PLD). However, little is known about the role of PLD in M<sub>1</sub> receptor signaling in native systems, and it is not clear whether biased M<sub>1</sub> PAMs display differences in modulating M<sub>1</sub>-mediated responses in native tissue. Using PLD inhibitors and PLD knockout mice, we showed that PLD was necessary for the induction of M<sub>1</sub>-dependent long-term depression (LTD) in the prefrontal cortex (PFC). Furthermore, biased M<sub>1</sub> PAMs that did not couple to PLD not only failed to potentiate orthosteric agonist-induced LTD but also blocked M<sub>1</sub>-dependent LTD in the PFC. In contrast, biased and nonbiased M<sub>1</sub> PAMs acted similarly in potentiating M<sub>1</sub>-dependent electrophysiological responses that were PLD independent. These findings demonstrate that PLD plays a critical role in the ability of M<sub>1</sub> PAMs to modulate certain central nervous system (CNS) functions and that biased M<sub>1</sub> PAMs function differently in brain regions implicated in cognition.
Opportunities in metabolic engineering to facilitate scalable alkaloid production (2009)

Numerous drugs and drug precursors in the current pharmacopoeia originate from plant sources. The limited yield of some bioactive compounds in plant tissues, however, presents a significant challenge for large-scale drug development. Metabolic engineering has facilitated the development of plant cell and tissue systems as alternative production platforms that can be scaled up in a controlled environment. Nevertheless, effective metabolic engineering approaches and the predictability of genetic transformations are often obscured due to the myriad cellular complexities. Progress in systems biology has aided the understanding of genome-wide interconnectivities in plant-based systems. In parallel, the bottom-up assembly of plant biosynthetic pathways in microorganisms demonstrated the possibilities of a new means of production. In this Perspective, we discuss the opportunities and challenges of implementing metabolic engineering in various platforms for the synthesis of natural and unnatural plant alkaloids.
Hydroacoustic measurements of the radiated noise from Wave Energy Converters in the Lysekil project and project WESA (2013)

Field measurements of the hydroacoustic noise from Wave Energy Converters (WECs) in the Lysekil project at Uppsala University and the Project WESA (joint effort between Uppsala University (Lead Partner), Ålands Teknikkluster r.f. and University of Turku) are presented. Anthropogenic noise is increasing in the oceans world wide and wave energy conversion may contribute to this noise, but to what extent? The main objective in this study is to examine the noise from full scale operating WECs in the Lysekil and project WESA. Acoustic measurements were made in order to be able to estimate potential environmental impact. Submersible recording devices (SRD) were deployed at 1 m from WECs at a depth of approximately 24 meters. Both WECs are a full scale point absorber with a directly driven linear generator, placed on gravitation foundations at the seabed with a connected buoy at the surface that absorbs energy from the heaving waves. The SRDs used to measure the noise from the WECs, consists of a SM2-recorder from Wildlife Acoustics and hydrophones from High Tech Inc. (HTI 96 MIN and HTI 99 HF). Measurements at in the Lysekil project were carried out in the spring of 2013 and in the project WESA in Jan-Feb of 2012. Preliminary results show that the main operating noise radiated from the WEC are short transients with instant rise time when the translator moves past the stator and when the stator hits the end stop springs of the generator. Most of the power in the noise is between 20 – 1000 Hz.
Long-Term Outcomes From a Randomized Dose Optimization Study of Chimeric Antigen Receptor Modified T Cells in Relapsed Chronic Lymphocytic Leukemia (2020)

In patients with advanced CLL, a 5 × 10<sup>8</sup> dose of CART-19 may be more effective than 5 × 10<sup>7</sup> CART-19 at inducing CR without excessive toxicity. Attainment of a CR after CART-19 infusion, regardless of cell dose, is associated with longer OS and progression-free survival in patients with relapsed CLL.
Antibody-mediated platelet destruction by quinine, quinidine, and their metabolites. (1988)

Metabolites of quinine and quinidine, along with the parent compounds, were investigated for their ability to promote complement-mediated platelet destruction when combined with drug-dependent platelet antibodies from five patients with quinine- and quinidine-induced thrombocytopenia. In all, eight metabolites and four closely related structural analogues were studied. These included the desmethyl, 2'-oxo, 10,11-dihydroxy, N-oxide, N'-oxide, and diN,N'-oxide derivatives. When we used the cytotoxic chromium 51 release assay, the parent compounds were typically from 10 to greater than 300 times more effective than the corresponding metabolites and structural analogues in promoting antibody-mediated platelet lysis. Reaction patterns varied significantly among all antibodies and compounds studied, strengthening previous evidence that drug-dependent platelet antibodies are extremely heterogeneous in their reactions with platelets. Although most of the metabolites were much less potent than the parent compounds in promoting antibody-mediated platelet lysis, one quinidine-induced antibody was significantly inhibited in its quinidine-mediated lytic activity by the addition of desmethylquinidine, an essentially nonreactive metabolite with this particular antibody. These findings support the hypothesis that the native structures of quinine and quinidine are sufficient to provoke drug-dependent antibody formation and subsequent platelet destruction independently of their metabolites. They also suggest a possible protective role for some of these metabolites in certain individuals who are susceptible to this allergic drug reaction.
Well plate microfluidic system for investigation of dynamic platelet behavior under variable shear loads (2011)

Abstract The study of platelet behavior in real‐time under controlled shear stress offers insights into the underlying mechanisms of many vascular diseases and enables evaluation of platelet‐focused therapeutics. The two most common methods used to study platelet behavior at the vessel wall under uniform shear flow are parallel plate flow chambers and cone‐plate viscometers. Typically, these methods are difficult to use, lack experimental flexibility, provide low data content, are low in throughput, and require large reagent volumes. Here, we report a well plate microfluidic (WPM)‐based system that offers high throughput, low reagent consumption, and high experimental flexibility in an easy to use well plate format. The system consists of well plates with an integrated array of microfluidic channels, a pneumatic interface, an automated microscope, and software. This WPM system was used to investigate dynamic platelet behavior under shear stress. Multiple channel designs are presented and tested for shear loads with whole blood to determine their applicability to study thrombus formation. Normal physiological shear (0.1–20 dyn/cm 2 ) and pathological shear (20–200 dyn/cm 2 ) devices were used to study platelet behavior in vitro under various shear, matrix coating, and monolayer conditions. The high physiological relevance, low blood consumption, and increased throughput create a valuable technique available to vascular biology researchers. The approach also has extensibility to other research areas including inflammation, cancer biology, and developmental/stem cell research. Biotechnol. Bioeng. 2011;108: 2978–2987. © 2011 Wiley Periodicals, Inc.
The Critical Role of IL-15 in the Antitumor Effects Mediated by the Combination Therapy Imatinib and IL-2 (2008)

The synergistic antitumor effects of the combination therapy imatinib mesylate (IM) and IL-2 depended upon NK1.1- expressing cells and were associated with the accumulation of CD11c(int)B220(+)NK1.1(+) IFN-producing killer dendritic cells (IKDC) into tumor beds. In this study, we show that the antitumor efficacy of the combination therapy was compromised in IL-15 and IFN-type 1R loss-of-function mice. IL-15Ralpha was required for the proliferation of IKDC during IM plus IL-2 therapy. Trans-presentation of IL-15/IL-15Ralpha activated IKDC to express CCR2 and to respond to type 1 IFN by producing CCL2. Moreover, the antitumor effects of the combination therapy correlated with a CCL2-dependent recruitment of IKDC, but not B220(-) NK cells, into tumor beds. Altogether, the IL-15-driven peripheral expansion and the CCL-2-dependent intratumoral chemoattraction of IKDC are two critical parameters dictating the antitumor efficacy of IM plus IL-2 in mice.
Active foamy virus proteinase is essential for virus infectivity but not for formation of a Pol polyprotein (1995)

To analyze proteolytic processing of foamy (spuma) retroviruses, two mutations were generated in the presumed active-site triplet Asp-Ser-Gly in the predicted proteinase (PR) region of the human foamy virus (HSRV). The mutations changed either the presumed catalytic aspartic acid residue to a catalytically incompetent alanine or the adjacent serine to a threonine found in most cellular and retroviral proteases at this position. Both mutations were cloned into the full-length infectious HSRV DNA clone. Wild-type and S/T mutant genomes directed the synthesis of particles with similar infectious titers, while the HSRV D/A PR mutant was noninfectious. Immunoblot analysis of transfected cells revealed identical patterns for the wild-type and for the S/T PR mutant. HSRV D/A mutant-transfected cells expressed only a single Gag polyprotein of 78 kDa instead of the 78-kDa-74-kDa doublet found in HSRV-infected or wild-type-transfected cells. Analysis with pol-specific antisera yielded a protein of approximately 120 kDa reactive with antisera against pol- but not gag-specific domains. No Gag-Pol polyprotein was detected in this study. Electron microscopy analysis of transfected cells showed heterogeneous particle morphology in the case of the D/A mutant, with particles of normal appearance and particles of aberrant size and shape. These results indicate that foamy viruses have an aspartic PR that is essential for infectivity but not for formation of the 120-kDa Pol polyprotein.
Benchmarking Delay and Energy of Neural Inference Circuits (2019)

Neural network circuits and architectures are currently under active research for applications to artificial intelligence and machine learning. Their physical performance metrics (area, time, and energy) are estimated. Various types of neural networks (artificial, cellular, spiking, and oscillator) are implemented with multiple CMOS and beyond-CMOS (spintronic, ferroelectric, and resistive memory) devices. A consistent and transparent methodology is proposed and used to benchmark this comprehensive set of options across several application cases. Promising architecture/device combinations are identified.
Volumetric capnography for monitoring lung recruitment and PEEP titration (2011)

Capnography and capnometry provide useful information that may help improve decision-making and reduce complications during transport. This chapter reviews specific clinical applications of capnography and capnometry: assuring proper endotracheal tube placement, monitoring airway circuit integrity, monitoring the consistency of mechanical ventilation, improving safety in procedural sedation, assessing cardiac output, and evaluating patients in cardiac arrest. Capnometry and capnography aid in the confirmation of correct endotracheal tube placement. End-tidal CO2 (ETCO2) measurement can accurately detect esophageal intubation because CO2 is exhaled through the trachea, and not the esophagus. Once an airway device is in place, continuous monitoring is important to assure ventilator circuit patency, including that of the endotracheal tube, and to assure consistent levels of ventilation. Capnography is the gold standard for monitoring patients on airway appliances and ventilator circuits, and there are useful roles for the technology during procedural sedation and evaluating patients in the time surrounding arrest states.
Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines (2018)

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Author response: Inverse regulation of Vibrio cholerae biofilm dispersal by polyamine signals (2021)

The global pathogen Vibrio cholerae monitors environmental polyamines to garner information about numbers of ‘self’ versus ‘other’ in the vicinity, and in response, to remain or disperse from biofilms.
Stimuli‐Driven Control of the Helical Axis of Self‐Organized Soft Helical Superstructures (2018)

Supramolecular and macromolecular functional helical superstructures are ubiquitous in nature and display an impressive catalog of intriguing and elegant properties and performances. In materials science, self-organized soft helical superstructures, i.e., cholesteric liquid crystals (CLCs), serve as model systems toward the understanding of morphology- and orientation-dependent properties of supramolecular dynamic helical architectures and their potential for technological applications. Moreover, most of the fascinating device applications of CLCs are primarily determined by different orientations of the helical axis. Here, the control of the helical axis orientation of CLCs and its dynamic switching in two and three dimensions using different external stimuli are summarized. Electric-field-, magnetic-field-, and light-irradiation-driven orientation control and reorientation of the helical axis of CLCs are described and highlighted. Different techniques and strategies developed to achieve a uniform lying helix structure are explored. Helical axis control in recently developed heliconical cholesteric systems is examined. The control of the helical axis orientation in spherical geometries such as microdroplets and microshells fabricated from these enticing photonic fluids is also explored. Future challenges and opportunities in this exciting area involving anisotropic chiral liquids are then discussed.
Surface Reactivity of the Quinone/Hydroquinone Redox Center Tethered to Gold: Comparison of Delocalized and Saturated Bridges (2008)

We found that when a quinone headgroup, present in a mixed self-assembled monolayer on gold, reacts with a nucleophile, dissolved in the bulk phase, the reaction rate widely depends on the chemical nature of the tether, being 7 times faster for quinones attached via a delocalized bridge as compared to a saturated alkane chain. Cyclic voltammetry (CV) of the quinone/hydroquinone redox couple was used to monitor the nucleophilic addition, while simulated CVs compared to experimental runs permitted the determination of rate constants. Analysis of CV data also suggests that the delocalized oligo(phenylene ethynylene) bridge facilitates the addition of two mercaptoethanol molecules as compared to the alkane bridge, where only one molecule is being added. The use of delocalized bridges for tethering quinones to electrodes is of great potential in electrochemically controlled "tuning" of surfaces needed in biosensor applications.