gebhart/patrepeval huggingface dataset:
The Ratio of Exhausted to Resident Infiltrating Lymphocytes Is Prognostic for Colorectal Cancer Patient Outcome (2021)

Immunotherapy success in colorectal cancer is mainly limited to patients whose tumors exhibit high microsatellite instability (MSI). However, there is variability in treatment outcomes within this group, which is in part driven by the frequency and characteristics of tumor-infiltrating immune cells. Indeed, the presence of specific infiltrating immune-cell subsets has been shown to correlate with immunotherapy response and is in many cases prognostic of treatment outcome. Tumor-infiltrating lymphocytes (TIL) can undergo distinct differentiation programs, acquiring features of tissue-residency or exhaustion, a process during which T cells upregulate inhibitory receptors, such as PD-1, and lose functionality. Although residency and exhaustion programs of CD8<sup>+</sup> T cells are relatively well studied, these programs have only recently been appreciated in CD4<sup>+</sup> T cells and remain largely unknown in tumor-infiltrating natural killer (NK) cells. In this study, we used single-cell RNA sequencing (RNA-seq) data to identify signatures of residency and exhaustion in colorectal cancer-infiltrating lymphocytes, including CD8<sup>+</sup>, CD4<sup>+</sup>, and NK cells. We then tested these signatures in independent single-cell data from tumor and normal tissue-infiltrating immune cells. Furthermore, we used versions of these signatures designed for bulk RNA-seq data to explore tumor-intrinsic mutations associated with residency and exhaustion from TCGA data. Finally, using two independent transcriptomic datasets from patients with colon adenocarcinoma, we showed that combinations of these signatures, in particular combinations of NK-cell activity signatures, together with tumor-associated signatures, such as TGFβ signaling, were associated with distinct survival outcomes in patients with colon adenocarcinoma.
Prize Collecting Multiagent Orienteering: Price of Anarchy Bounds and Solution Methods (2020)

We propose and address a new variation of the team orienteering problem (TOP) in which all members of the team are independent self-interested agents. The prize-collecting nature emanates from the fact that the prize available at a node of the traversal graph can be collected only by a single visiting agent. The problem is motivated by situations in which team members (agents) must accomplish tasks toward a common goal but are unable to communicate, such as a fleet of surveillance drones operating in a communication denied area or with remote pilots operating independently. We explore three policies for minimizing the amount of inefficiency these self-interested agents can bring into the situation. We analyze these policies in a game-theoretic framework and show upper bounds on the Price of Anarchy (PoA) ranging from <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\approx 1.582$ </tex-math></inline-formula> to unbounded depending on the policy, network type, and the number of players <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$k$ </tex-math></inline-formula> . This is done by extending well-known PoA bounds for valid utility systems to a leader–follower setting. The PoA also depends on the behavior of the agents, which could not have goodwill toward other agents. In many cases, we are able to provide examples that establish the tightness of the bounds. Finally, solution methods are provided for each of these policies. Numerical results computed by these solution methods are then presented and compared with the optimal centrally coordinated solutions. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Note to Practitioners</i> —Unmanned aerial vehicles (UAVs) are becoming increasingly popular for information collection tasks in defense and civilian applications alike. When the collection area is large, it is not unusual that a fleet of UAVs is deployed. Routing of a fleet can be performed in a centralized or decentralized manner. Decentralized routing might be the only possibility when centralized situational awareness is not possible due to bandwidth limitations and when centralized optimal routes for each UAV are too complex to compute. For managers of UAV systems, our work provides a theoretical bound on how bad decentralized routing could be in the context of a prize-collecting game. Under a game-theoretic framework, we prove that the fleet will collect at least 50% of the prizes collected by the optimal centralized solution. Empirically, we show that the performance of the fleet is much better, usually providing at least 90% of the optimal centralized solution. Our routing strategies provide valuable guidance to the practicing engineer or manager of a UAV fleet.
The UCSC repeat browser allows discovery and visualization of evolutionary conflict across repeat families (2020)

The UCSC Repeat Browser allows easy and intuitive visualization of genomic data on consensus repeat elements, circumventing the problem of multi-mapping, in which sequencing reads of repeat elements map to multiple locations on the human genome. By developing a reference consensus, multiple datasets and annotation tracks can easily be overlaid to reveal complex evolutionary histories of repeats in a single interactive window. Specifically, we use this approach to retrace the history of several primate specific LINE-1 families across apes, and discover several species-specific routes of evolution that correlate with the emergence and binding of KZNFs.
Green and Red Emissions at Room Temperature on Er-Doped GaN Submicrometer Rods Synthesized by a Simple Chemical Vapor Deposition Technique (2007)

Er-doped GaN submicron rods have been synthesized on silicon (001) by the direct reaction of gallium and ammonia in a CVD system. Green and red emissions at room temperature coming from the rods with excitation below the energy of the bandgap of the semiconductor have been recorded.
Differential growth of U and M type infectious haematopoietic necrosis virus in a rainbow trout–derived cell line, RTG‐2 (2010)

Infectious haematopoietic necrosis virus (IHNV) is one of the most important viral pathogens of salmonids. In rainbow trout, IHNV isolates in the M genogroup are highly pathogenic, while U genogroup isolates are significantly less pathogenic. We show here that, at a multiplicity of infection (MOI) of 1, a representative U type strain yielded 42-fold less infectious virus than an M type strain in the rainbow trout-derived RTG-2 cell line at 24 h post-infection (p.i.). However, at an MOI of 10, there was only fivefold difference in the yield of infectious virus between the U and M strains. Quantification of extracellular viral genomic RNA suggested that the number of virus particles released from cells infected with the U strain at a MOI of 1 was 47-fold lower than from M-infected cells, but U and M virions were equally infectious by particle to infectivity ratios. At an MOI of 1, U strain intracellular viral genome accumulation and transcription were 37- and 12-fold lower, respectively, than those of the M strain at 24 h p.i. Viral nucleocapsid (N) protein accumulation in U strain infections was fivefold lower than in M strain infections. These results suggest that the block in U type strain growth in RTG-2 cells was because of the effects of reduced genome replication and transcription. The reduced growth of the U strain does not seem to be caused by defective genes, because the U and M strains grew equally well in the permissive epithelioma papulosum cyprini cell line at an MOI of 1. This suggests that host-specific factors in RTG-2 cells control the growth of the IHNV U and M strains differently, leading to growth restriction of the U type virus during the RNA synthesis step.
Different localizations of hydrophobic magnetic nanoparticles within vesicles trigger their efficiency as magnetic nano-heaters (2011)

The reverse phase evaporation (REV) and the multiple emulsion (ME) process are used to encapsulate hydrophobic magnetic nanoparticles (MNPs) within vesicles. The effect of the size distribution of the nanoparticles on their location in the liposomes has been observed by transmission electron microscopy: the small ones are in the inner core of the vesicles while the larger ones are found to be located at the membrane level. The influence of the confinement of hydrophobic nanoparticles inside vesicles on their subsequent magnetic properties (relaxometry, heating capacity) has been studied.
DNA-SIP and repeated isolation corroborate Variovorax as a key organism in maintaining the genetic memory for linuron biodegradation in an agricultural soil (2021)

The frequent exposure of agricultural soils to pesticides can lead to microbial adaptation, including the development of dedicated microbial populations that utilize the pesticide compound as a carbon and energy source. Soil from an agricultural field in Halen (Belgium) with a history of linuron exposure has been studied for its linuron-degrading bacterial populations at two time points over the past decade and Variovorax was appointed as a key linuron degrader. Like most studies on pesticide degradation, these studies relied on isolates that were retrieved through bias-prone enrichment procedures and therefore might not represent the in situ active pesticide-degrading populations. In this study, we revisited the Halen field and applied, in addition to enrichment-based isolation, DNA stable isotope probing (DNA-SIP), to identify in situ linuron-degrading bacteria in linuron-exposed soil microcosms. Linuron dissipation was unambiguously linked to Variovorax and its linuron catabolic genes and might involve the synergistic cooperation between two species. Additionally, two novel linuron-mineralizing Variovorax isolates were obtained with high 16S rRNA gene sequence similarity to strains isolated from the same field a decade earlier. The results confirm Variovorax as a prime in situ degrader of linuron in the studied agricultural field soil and corroborate the genus as key for maintaining the genetic memory of linuron degradation functionality in that field.
Multiple-Time-Scale Motion in Molecularly Linked Nanoparticle Arrays (2012)

We explore the transport of electrons between electrodes that encase a two-dimensional array of metallic quantum dots linked by molecular bridges (such as α,ω alkaline dithiols). Because the molecules can move at finite temperatures, the entire transport structure comprising the quantum dots and the molecules is in dynamical motion while the charge is being transported. There are then several physical processes (physical excursions of molecules and quantum dots, electronic migration, ordinary vibrations), all of which influence electronic transport. Each can occur on a different time scale. It is therefore not appropriate to use standard approaches to this sort of electron transfer problem. Instead, we present a treatment in which three different theoretical approaches-kinetic Monte Carlo, classical molecular dynamics, and quantum transport-are all employed. In certain limits, some of the dynamical effects are unimportant. But in general, the transport seems to follow a sort of dynamic bond percolation picture, an approach originally introduced as formal models and later applied to polymer electrolytes. Different rate-determining steps occur in different limits. This approach offers a powerful scheme for dealing with multiple time scale transport problems, as will exist in many situations with several pathways through molecular arrays or even individual molecules that are dynamically disordered.
Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel (2022)

These findings suggest that exposure of personnel to high numbers of low-level blast over a career may result in enduring central inflammation that is associated with chronic neurological symptoms. The data also suggest that peripheral markers of inflammation are not necessarily adequate surrogates for central neuroinflammation.
The Simple Empirics of Optimal Online Auctions (2018)

We study reserve prices computed to maximize the expected profit of the seller based on historical observations of incomplete bid data typically available to the auction designer in online auctions for advertising or e-commerce. This direct approach to computing reserve prices circumvents the need to fully recover distributions of bidder valuations. We derive asymptotic results and also provide a new bound, based on the empirical Rademacher complexity, for the number of historical auction observations needed in order for revenue under the estimated reserve price to approximate revenue under the optimal reserve arbitrarily closely. This simple approach to estimating reserves may be particularly useful for auction design in Big Data settings, where traditional empirical auctions methods may be costly to implement. We illustrate the approach with e-commerce auction data from eBay. We also demonstrate how this idea can be extended to estimate all objects necessary to implement the Myerson (1981) optimal auction.
New Persistent Opioid Use Following Common Forefoot Procedures for Treatment of Hallux Valgus (2018)

Category: Bunion Introduction/Purpose: Chronic opioid use and abuse is one of the greatest public health challenges in the United States and continues to worsen. Orthopaedic surgeons stand at #4 on the list of top prescribers of opioid analgesics by specialty and are squarely positioned to have an impact on the problem. A recent study revealed an 8% prevalence of new persistent opioid usage following abdominal surgery. At present, the incidence of persistent opioid use after foot and ankle surgery is largely unknown. Operative bunion correction is one of the most commonly performed elective foot and ankle surgeries in this country. We sought to determine the incidence of new persistent opioid use following surgical treatment of hallux valgus and to identify patient factors associated with persistent opioid use. Methods: A nationwide insurance claims data set from January 2010 to June 2015 was used to identify opioid naive patients (defined as patients with no prior opioid use 12 months prior to injury) who underwent surgical treatment of hallux valgus with either a proximal or distal first metatarsal osteotomy. The incidence of new persistent opioid use, defined by opioid prescription fulfillment between 90 and 180 days after surgery was then calculated. Data were assessed for patient factors which may be predictors of new persistent opioid use including surgery type, health insurance type, age, gender, household income, and comorbidities. Results: A total of 38,312 patients underwent surgical treatment of hallux valgus with either a distal or proximal first metatarsal osteotomy and filled a perioperative opioid prescription. The rate of new persistent opioid use among all patients was 5.6%. The majority of patients (90%) underwent treatment with a distal metatarsal osteotomy. Patients who underwent treatment with a proximal metatarsal osteotomy were more likely to have new persistent opioid use (aOR: 1.16; p=0.04). Logistic regression analysis demonstrated that patient factors independently associated with new persistent opioid use included depression, anxiety, alcohol and substance abuse disorders, and certain preoperative pain disorders. Age, gender, and income were not associated with new persistent opioid use. Conclusion: Despite rising national attention, opioid abuse continues to be a growing epidemic. In order for foot and ankle surgeons to help solve this problem, it must first be better defined. New persistent opioid use following surgical treatment of hallux valgus affects a substantial, growing number of patients. Fifty percent of patients using opioids for 3 months will be using them at 5 years. Understanding patient factors associated with persistent opioid use can help clinicians identify and counsel at-risk patients and ultimately focus strategies and interventions aimed at mitigating and eliminating this massive public health problem.
Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study (2016)

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines) and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5) induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID) mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.
Palladium-Catalyzed Alkoxycarbonylation of Unactivated Secondary Alkyl Bromides at Low Pressure (2020)

Catalytic carbonylations of organohalides are important C-C bond formations in chemical synthesis. Carbonylations of unactivated alkyl halides remain a challenge and currently require the use of alkyl iodides under harsh conditions and high pressures of CO. Herein we report a palladium-catalyzed alkoxycarbonylation of secondary alkyl bromides that proceeds at low pressure (2 atm CO) under mild conditions. Preliminary mechanistic studies are consistent with a hybrid organometallic-radical process. These reactions efficiently deliver esters from unactivated alkyl bromides across a diverse range of substrates and represent the first catalytic carbonylations of alkyl bromides with carbon monoxide.
The landscape of management: Creating the context for understanding social complexity (2004)

This report and opinion piece seeks to establish a model in which complexity can be positioned in the context of other management disciplines, in such a way as to effectively communicate to executives in industry and their equivalents in government the importance of applying complexity thinking. It also seeks to differentiate what is termed ‘social complexity’ from ‘mathematical complexity’ in the context of the development of management science. The background to this
ON THE POWER TO DETECT SNP/PHENOTYPE ASSOCIATION IN CANDIDATE QUANTITATIVE TRAIT LOCI GENOMIC REGIONS: A SIMULATION STUDY (2002)

We use coalescent methods to investigate the ability of linked neutral "markers" to reveal in simulated population samples the presence of one or more single nucleotide polymorphisms that is contributing to a trait having a complex genetic basis (QTN: quantitative trait nucleotide). Realistic mutation and recombination rates in our simulations allow us to generate SNP data appropriate for analyzing human variation across short chromosomal intervals corresponding to approximately 100 kilobases. We investigate the performance of both single marker and multiple-marker (haplotype) data for several ad hoc procedures. Our results with single SNP markers indicate that (1) the density of SNP markers need not be much higher than 10% in order to achieve near-maximal detection of a QTN; (2) a higher density of markers does not improve much on the ability to localize a QTN within an interval unless the recombination rate is high. Haplotype-based tests were investigated for the case in which more than one QTN is present in the studied interval. Larger sample sizes improve both the probability of detecting the haplotype with the largest number of QTNs, as well as the ability to infer correct haplotypes from genotypic data. Testing a series of short haplotypes across a longer interval can also be beneficial. The rate of false positives (i.e., when the most significant haplotype does not contain the greatest number of QTNs in the sample) can be very high when the contribution of individual QTNs to a trait is small. The elimination of low-frequency haplotypes does not substantially reduce the probability of detecting the haplotype with the largest number of QTNs but it can reduce the rate of false positives.
Highly integrated VO2-based antenna for frequency tunability at millimeter-wave frequencies (2016)

We report the monolithic integration of a metal-insulator material (vanadium dioxide, VO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) for realizing a frequency tunable antenna operating around 30 GHz. The design of the device is based on a slot antenna excited by a microstrip line having a length that can be conveniently varied using a VO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> -based switch. Compared to existing commercial solutions, the proposed switches show better electrical properties at high frequencies, with low losses (<;1 dB) and high isolation (>20 dB) up to 40 GHz. The simulation shows that the antenna can be tunable around 30 GHz, with discrete frequency operation while being highly integrated.
A method for stability analysis of vegetated hillslopes: an energy approach (1999)

Stability analyses of vegetated hillslopes are usually carried out by the limit equilibrium (LE) method where shear displacement is not taken into account. Experiments show that soil with roots produces a shear stress - displacement curve with higher peak shear stress at larger shear displacements than fallow soil. If the safety factor is obtained by the LE method, the ability of soil with roots to resist large shear strains due to soil-root interaction may be underestimated. A new approach is proposed that incorporates, within the stability analysis, the ability of soil with roots to withstand strain. It is based on a consideration of the energy consumed during the shearing process of the soil-root system. This is developed using characteristics of the shear stress - displacement curve of a soil-root system obtained from in situ direct shear tests under simulated overburden pressure and pore-water pressure conditions. The method is limited to vegetated hillslopes where the stability analysis can be approximated by a simplified infinite slope model. Shear stress - displacement data for two tree species were obtained from hillslopes where shallow landslides commonly occur in rainstorms under near-saturated conditions. Using these results the energy approach (EA) and LE methods are compared. A procedure is also outlined to predict the safety factor for hillslopes with different plant densities. Extension of the EA method for general two-dimensional slope stability analysis involving nonlinear shear planes is also explained.