cssi/SciSciGPT-SciSciNet huggingface dataset:
Novel cancer antigens for personalized immunotherapies: latest evidence and clinical potential.

The clinical success of monoclonal antibody immune checkpoint modulators such as ipilimumab, which targets cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and the recently approved agents nivolumab and pembrolizumab, which target programmed cell death receptor 1 (PD-1), has stimulated renewed enthusiasm for anticancer immunotherapy, which was heralded by Science as ‘Breakthrough of the Year’ in 2013. As the potential of cancer immunotherapy has been recognized since the 1890s when William Coley showed that bacterial products could be beneficial in cancer patients, leveraging the immune system in the treatment of cancer is certainly not a new concept; however, earlier attempts to develop effective therapeutic vaccines and antibodies against solid tumors, for example, melanoma, frequently met with failure due in part to self-tolerance and the development of an immunosuppressive tumor microenvironment. Increased knowledge of the mechanisms through which cancer evades the immune system and the identific...
Interaction between endotoxic lipopolysaccharides (LPS) and the complement (C) system: solubilization of C-consuming substances during brief absorbtions at 0 degrees.

SummaryAttempts were made to remove antibodies and other serum factors involved in the interaction between endotoxic lipopolysaccharides (LPS) and the complement system by brief absorbtions of guinea pig serum with LPS at 0°. However, in addition to removal of serum factors, this procedure also resulted in the solubilization or “imbibation” of LPS constituents into the fluid phase, such that when the absorbed sera were subsequently incubated at 37°, or hyperimmune rabbit anti-LPS serum was added to them at either 0 or 37°, LPS constitutents which initiated C consumption were found. C consumption upon addition of LPS to absorbed sera persisted, even as bactericidal activity against the parent Veillonella organisms was reduced. While the importance of solubilization of LPS to its interaction with the C system is not yet known, these experiments show the difficulty of evaluating the factors in serum which initiate C consumption upon addition of LPS and their relationship to “natural” bactericidal antibodies.
Revisiting Fee Policies

Charging for missed sessions is presented as part of an ethical flexible fee policy that is being challenged and will require continued appraisal.
On Velázquez's Working Method

Sir Nikolaus Pevsner's masterly essay, “Richard Payne Knight,” in this journal (XXXI, 1949, 293–320), and more recent writings have illuminated the aesthetic theory of that celebrated English dilettante. To them may now be added new information upon Knight's reactions to the Elgin Marbles and his relations with that other noted amateur, Sir Uvedale Price (1747–1849), thanks to the discovery of a series of hitherto unpublished letters in the correspondence of a mutual friend, George, Fourth Earl of Aberdeen (1784–1860) (Figs. 1–2).1
THEORETICAL MODEL AND ANALYSIS OF SOFT REDUCTION GRADIENT FOR CONTINUOUS CASTING SLAB

Based on the analysis of continuous casting slab soft reduction process,a theoretical model to solve soft reduction gradient was deduced,and the effect of casting speed on reduction gradient was investigated.The results show that the reduction gradient is the biggest at the entry of soft reduction zone,and decreases linearly along the strand.As the casting speed increased by 0.2m/min,the average reduction gradient decreased by 0.04mm/m.It seems that the casting speed has no effect on the range of reduction rate which changed linearly from 0.36 to 0.22mm/min,and the average reduction rate,which also is independent of casting speed,keeps the value of 0.29mm/min.
Courting the Women’s Vote: The Emotional, Cognitive, and Persuasive Effects of Gender-Based Appeals in Campaign Advertisements

In this paper, we examine the ways in which citizens emotionally react to and cognitively process campaign advertisements that contain group-based appeals. Specifically, we focus on the emotional, cognitive, and persuasive effects of three campaign ads aired during the 2012 election campaign that contained explicit appeals to women voters. We analyze differences across women and men in their emotional responses to the ads, in their reports of the memorability of the ads, in their cognitive engagement with the ads, and in how persuasive the ads were for vote choice. In so doing, we add nuance to studies of gender and campaigns and contribute to the expanding literature on the impact of strategic campaign communications.
A Beating Worse Than Death: Imagining and Contesting Violence in the U.S.-Mexico Borderlands

Between 1995 and 2005, it is conservatively estimated that over 3,600 migrants died while trying to cross clandestinely into the United States from Mexico. Unsanctioned crossings of the U.S.-Mexico boundary have long been dangerous. But the number of deaths has increased significantly over the last several years. Despite the large and rapidly growing death toll, these fatalities have received little critical public scrutiny--especially when compared with other acts of violence involving unauthorized immigrants and state authorities. In trying to ascertain why, this paper compares and contrasts the reaction to two incidents in southern California in early April 1996: the beating of two migrants by police officers, and the deaths of several migrants killed while fleeing the U.S. Border Patrol. This paper argues that the reasons for the unevenness in terms of response relate to hegemonic and interrelated notions regarding national territory, the "illegal" immigrant, and violence. These assumptions reflect and reproduce particular notions of security and rights that conflict with those of migrant, and thus make it difficult to perceive and challenge the factors ultimately responsible for the deaths.
Borderline personality disorder diagnosis, diagnostic criteria, and criterion count as predictors of regularly drinking alcohol before sex among adults in the United States

a satisfaction measure not only collects data on participants’ attitudes about the treatment provided, but provides an unspoken message that participants’ opinions are valued. The current study examines results of a treatment satisfaction survey administered to participants enrolled in the multi-center NIDA CTN Cocaine Use Reduction with Buprenorphine (CURB) trial to assess opinions about study participation. Methods: This secondary analysis utilizes a 9-item satisfaction survey self-administered by cocaine-dependent participants at the endof the 8-week study. All participants received extended-release injectable naltrexone and were randomly assigned to 1 of 3 daily sublingual buprenorphine/naloxone (BUP) conditions: 16mg BUP (BUP16), 4mg BUP (BUP4), 0mg BUP (placebo, PLB), plus weekly CBT. Satisfaction ratings were based on a 5-point Likert Scale. Results: 278 surveys were collected for a 92% completion rate. Most participants (93.5%) reported being satisfied or very satisfied with their overall experience in the study, and 84.9% reported that they would definitely participate again if given the opportunity. No difference in overall satisfaction was found between the BUP groups and the PLB group (BUP4 vs PLB, p=0.08; BUP16 vs PLB, p=0.43). Satisfaction was not associated with retention, CBT attendance, or cocaine use outcomes. Participants were also asked to what medication group they thought they were assigned, and 56.8% had an opinion whereas 43.2% were unsure. Of those with an opinion, 26.3% correctly guessed their group assignment. Additional analyses of items addressing participant opinion of the study medication and counseling will be presented. Conclusions: Given the high rates of treatment satisfaction reported by study participants, it is not surprising that satisfaction is not related to treatmentperformanceandoutcome. Interestingly, participant guesses about assigned treatment were no better than chance. This seems to demonstrate the effectiveness of the study blinding process. Financial Support: DA013045.
A system dynamics model of the standards development process

An overall dynamic model of the standards development process that was developed to document savings potentially obtainable from standards improvements in the Defense Information System (DIS) is presented. DIS is defined as the aggregation of all US Department of Defense information systems, including sensors, data entry devices, displays, communications networks, and computer resources. The model provides a 20-yr view of the application of standards to DIS programs. Quantitative measures of performance are calculated, and standards resource allocation is optimized. >
Ensuring that Ecological Science Contributes to Natural Resource Management Using a Delphi-Derived Approach

This chapter approaches participatory modeling in environmental decision making from an atypical perspective. It broadly addresses the question of how to assure that science conducted to assist practitioners improves resource management. More specifically, it describes a case involving environmental science and natural resource management at Fort Benning, a United States (US) Army installation in the southeastern US where disparate environmental research projects were funded by a single federal agency to enhance the ability of Fort Benning’s resource managers to achieve their resource management goals. The role of our effort was to integrate the scientific studies in a manner that would be meaningful and useful for resource managers. Hence we assembled a team consisting of an anthropologist, ecologist, microbiologist, statistician, and geographic information systems specialist who developed a common framework that served as the basis for this integration. The team first used a Delphi expert elicitation, which evolved into an approach more akin to facilitated negotiation. This second approach arose organically, particularly when our team took advantage of an opportunity for face-to-face interaction. Although the shift in our approach was unplanned, it proved to be highly productive. We discuss the potential utility of our approach for other situations and suggest that it would be useful to initiate at the beginning of research where the aim is to produce scientific results that meet practitioners’ needs, specifically in the realm of environmental science and resource management.
Absence of remote earthquake triggering within the Coso and Salton Sea geothermal production fields

Geothermal areas are long recognized to be susceptible to remote earthquake triggering, probably due to the high seismicity rates and presence of geothermal fluids. However, anthropogenic injection and extraction activity may alter the stress state and fluid flow within the geothermal fields. Here we examine the remote triggering phenomena in the Coso geothermal field and its surrounding areas to assess possible anthropogenic effects. We find that triggered earthquakes are absent within the geothermal field but occur in the surrounding areas. Similar observation is also found in the Salton Sea geothermal field. We hypothesize that continuous geothermal operation has eliminated any significant differential pore pressure between fractures inside the geothermal field through flushing geothermal precipitations and sediments out of clogged fractures. To test this hypothesis, we analyze the pore-pressure-driven earthquake swarms, and they are found to occur outside or on the periphery of the geothermal production field. Therefore, our results suggest that the geothermal operation has changed the subsurface fracture network, and differential pore pressure is the primary controlling factor of remote triggering in geothermal fields.
Effects of Selection for Seedling Vigor on the Genetic Variation in Leymus cinereus

Basin wildrye (Leymus cinereus [Scribn. & Merr. A. Love]) is a perennial grass native to western regions of North America. Despite its importance for rangelands, stand establishment of basin wildrye is difficult due to its poor seedling vigor. We undertook to increase the seedling vigor of the basin wildrye cultivar “Trailhead” by using selection for emergence from deep seeding depth. We carried out two cycles of selection in two select populations and included two random populations, in which no direct selection occurred. We characterized the indirection effect of the selection on biomass, seed production, and stand percentage in these populations under field conditions. We used amplified fragment length polymorphic (AFLP) markers to identify regions of the genome associated with the selection by identifying allele frequency changes between the base population and the select and random populations. The second cycle select population and the first cycle random population possessed the highest total emergence from deep seeding (60% and 59%, respectively) compared with the base population (26%). The field evaluations showed no differences in genetic variation among the base, select, and random populations for biomass, seed production, and stand percentage. On the basis of the analysis of the AFLP markers, diversity increased slightly among the random populations and decreased slightly among the select populations. In the select populations, band frequencies increased for aggcac403, actcag185, and aggcac208. The band frequencies of aggctg212 and actctc66 decreased in both random and selected cycles. The results indicate that targeted selection for trait improvement in this native grass can be successfully completed with minimal effect on population genetic diversity.
Secondary Stabilizers of the Anterior Cruciate Ligament—Deficient Knee

Eliminating rotatory knee instability during anterior cruciate ligament (ACL) reconstruction surgery is crucial to ensure patients return to normal function after ACL injury. Although the ACL is generally considered the primary soft tissue restraint to anteroposterior laxity of the knee, several additional structures, such as the anterolateral complex of the knee, lateral and medial menisci and their capsular attachments, posterolateral corner structures, and collateral ligaments, also play important roles in knee stability. The primary goal of ACL reconstruction surgery should be to recreate the anatomical location and function of the native ACL, and injuries to these other secondary restraints should also be evaluated and addressed surgically if necessary.
Assessing temperature pattern projections made in 1989

Successful projection of the distribution of surface temperature change increases our confidence in climate models. Here we evaluate projections of global warming from almost 30 years ago using the observations made during the past half century.
The Natural History and Outcomes of Endovascular Therapy for Claudication

Background The natural history of claudication is well-characterized and traditional therapy includes risk factor modification and exercise protocols with revascularization reserved for patients who are severely impaired. However, the reduced periprocedural morbidity with endovascular therapy has led physicians to broaden the indications for intervention for peripheral artery disease, and more claudicants are undergoing procedures for disease that is moderately limiting to their lifestyle. This study sought to assess the natural history of patients who have undergone peripheral vascular intervention for claudication. Methods All patients who underwent at least 1 peripheral vascular intervention (PVI) for claudication at a single institution from January 2007 to December 2013 were identified. Patient demographics were assessed using the hospital record. Outcomes included secondary endovascular intervention, secondary bypass intervention, amputation, and survival. Cox proportional hazards models were created to assess risk factors for further intervention. Results Five hundred fifteen patients were identified as having undergone PVI for claudication during the study period. Forty-three percent were female, 37% had diabetes, 31% had coronary artery disease, 26% were current smokers, 6.6% had congestive heart failure, 8.2% had a tibial lesion that was intervened upon, and 35% had a Trans-Atlantic Inter-Society Consensus Document (TASC) II C/D lesion. Actuarial survival at 5 years was 79.9% and 62.5% of patients had primary patency. The limb salvage rate was 97.2%. Over the follow-up period, 21.8% required some type of further intervention: either endovascular (17.7%) or open bypass (7.2%). A Cox proportional hazards model adjusting for age, sex, and other comorbidities showed that the two largest risk factors for requiring reintervention were angioplasty only (no stent; hazard ratio [HR] 1.36, P = 0.02) and TASC C/D lesion (HR 1.52, P = 0.03). Conclusions With 5-year follow-up, patients have a primary patency that is comparable to an open prosthetic bypass to an above knee target. In addition, the secondary patency rate was over 90% and the major amputation rate as less than 3%. The presence of a TASC C/D lesion was predictive of failure of endovascular therapy, and surgical bypass should be considered in these patients.
Trends in Surgical Management of Shoulder Instability

Background:Optimal surgical management of anterior shoulder instability remains controversial. There is a need to assess the most recent trends for primary and revision shoulder stabilization surge...
Construal-level Mindsets Enhance Behavioral Persistence in Response to Incentive Valence

In this research, we find that incentive valence and construal-level mindsets can interact to influence behavioral persistence on challenging tasks. An abstract mindset improves persistence in response to positively framed incentives whereas a concrete mindset improves persistence in response to negatively framed incentives. This interaction effect can be observed even when the cues inducing construal-level mindsets are not related to the incentives or the incentivized tasks. Participants in our studies were either positively or negatively incentivized to solve a set of difficult anagrams, and were primed with an abstract or a concrete mindset using spatial (Study 1) and social (Study 2) cues. The participants persisted longer in response to the positively framed incentive when primed with spatially or socially remote cues. In contrast, for the negatively framed incentive, participants persisted longer when primed with spatially or socially proximal cues. Copyright © 2017 John Wiley & Sons, Ltd.
Retinal thinning in amyotrophic lateral sclerosis patients without ophthalmic disease.

Importance Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease that primarily affects motor neurons. Recently, three causative genes have been implicated in both ALS and glaucoma. However, it is still uncertain whether patients with ALS have neurodegeneration in their retinas. If so, retinal thickness measurements might be a useful biomarker for ALS progression. Previous work in this area has been inconclusive, as it has not taken into account the effect of ophthalmic diseases on retinal thinning. Objective To determine whether there are differences in retinal neurons in ALS patients utilizing spectral-domain optical coherence tomography (SD-OCT). We tested the hypothesis that ALS patients exhibit retinal neurodegeneration that is not associated with ophthalmic diseases. Design, settings and participants Observational, comparative, cross-sectional study performed on patients recruited from the Duke University Medical Center ALS clinic. Patients underwent a comprehensive ophthalmologic examination to rule out ocular pathology. 21 patients met inclusion criteria. Two eyes with ocular pathology were excluded, leading to a total of 40 eyes of 21 patients included in the study. Retinal neurodegeneration was assessed by retinal nerve fiber layer (RNFL) thickness measurement using SD-OCT (Spectralis; Heidelberg Engineering). Main outcomes and measures ALS disease severity, determined through the ALS Functional Rating Scale (ALSFRS-R); mean and six sector RNFL thickness values compared to age-adjusted values in the normative database provided by Heidelberg Engineering; RNFL thickness correlation with ALSFRS-R, ALSFRS-R progression rate, forced vital capacity (FVC), and visual acuity. Results ALSFRS-R mean score was 30+/-10. Mean RNFL thickness in ALS patients was 88.95 +/- 10.8 microns, significantly thinner than values in the normative database (95.81 +/- 0.8). These RNFL thickness values did not demonstrate correlation to ALSFRS-R score, ALSFRS-R progression rate, FVC, intraocular pressure, or visual acuity. Conclusions Using SD-OCT, our study shows that ALS patients without ocular pathology exhibit thinned retinal layers. Future studies are warranted to clarify the clinical relationship between retinal thinning and motor neuron loss in ALS.
On non-local energy transfer via zonal flow in the Dimits shift

The two-dimensional Terry–Horton equation is shown to exhibit the Dimits shift when suitably modified to capture both the nonlinear enhancement of zonal/drift-wave interactions and the existence of residual Rosenbluth–Hinton states. This phenomenon persists through numerous simplifications of the equation, including a quasilinear approximation as well as a four-mode truncation. It is shown that the use of an appropriate adiabatic electron response, for which the electrons are not affected by the flux-averaged potential, results in an nonlinearity that can efficiently transfer energy non-locally to length scales of the order of the sound radius. The size of the shift for the nonlinear system is heuristically calculated and found to be in excellent agreement with numerical solutions. The existence of the Dimits shift for this system is then understood as an ability of the unstable primary modes to efficiently couple to stable modes at smaller scales, and the shift ends when these stable modes eventually destabilize as the density gradient is increased. This non-local mechanism of energy transfer is argued to be generically important even for more physically complete systems.
Plasmonic nano-arrays for enhanced photoemission and photodetection

Efficient conversion of photons to electrical energy has a wide variety of applications including imaging, energy harvesting, and infrared detection. The coupling of electromagnetic radiation to free electron oscillations at a metal interface results in enhanced electric fields tightly confined to the surface. Taking advantage of this nonlinear light–matter interaction, this work presents resonant surfaces optimized for combining electrical and photonic excitations in order to liberate electrons in a vacuum-channel device for applications ranging from enhanced photoemission to infrared photodetection.
Problem of qualitative changes in the time course of chronic disease

Chronical, multifactorial diseases are characterized by qualitative changes in the time course of their development. The changes have diagnostic and therapeutic implications.
Paying Attention to the Trees in the Forest, or a Call to Examine Agency-Specific Stories:

Public administration scholarship needs to strike a better balance between large sample studies and in-depth case studies. The availability of large data sets has led us to engage in empirical rese...
Documenting an epidemic of suffering: low health-related quality of life among transgender youth

Purpose To quantify HRQOL of TGN patients using the PedsQL 4.0 generic core scales, and to compare reported HRQOL of TGN adolescents with published data from comparison populations.
Blue Light Enhances Bacterial Clearance and Reduces Organ Injury During Sepsis.

OBJECTIVES The physiology of nearly all mammalian organisms are entrained by light and exhibit circadian rhythm. The data derived from animal studies show that light influences immunity, and these neurophysiologic pathways are maximally entrained by the blue spectrum. Here, we hypothesize that bright blue light reduces acute kidney injury by comparison with either bright red or standard, white fluorescent light in mice subjected to sepsis. To further translational relevance, we performed a pilot clinical trial of blue light therapy in human subjects with appendicitis. DESIGN Laboratory animal research, pilot human feasibility trial. SETTING University basic science laboratory and tertiary care hospital. SUBJECTS Male C57BL/6J mice, adult (> 17 yr) patients with acute appendicitis. INTERVENTIONS Mice underwent cecal ligation and puncture and were randomly assigned to a 24-hour photoperiod of bright blue, bright red, or ambient white fluorescent light. Subjects with appendicitis were randomized to receive postoperatively standard care or standard care plus high-illuminance blue light. MEASUREMENTS AND MAIN RESULTS Exposure to bright blue light enhanced bacterial clearance from the peritoneum, reduced bacteremia and systemic inflammation, and attenuated the degree of acute kidney injury. The mechanism involved an elevation in cholinergic tone that augmented tissue expression of the nuclear orphan receptor REV-ERBα and occurred independent of alterations in melatonin or corticosterone concentrations. Clinically, exposure to blue light after appendectomy was feasible and reduced serum interleukin-6 and interleukin-10 concentrations. CONCLUSIONS Modifying the spectrum of light may offer therapeutic utility in sepsis.
The General Random Walk

WHAT IS this mathematical model called a random walk? Let {X n, n ≥ 1} be iid real valued random variables. Define S0 = 0, and for n ≥ 1 define S n = X 1 + … + X n. Then {S n , n ≥ 0} is a random walk. The random variables {X i } are called the steps of the random walk, and the distribution F(x) = P{X1 ≤ x} is called the step distribution.
Risk Adjustment for Health Plan Payment

Abstract Risk adjustment for health plan payment is a bundled payment strategy in which payments are based on mathematical formulas that predict health plan obligations for spending on each enrollee. The risk adjustment formula quantifies the relationship between spending and explanatory variables called risk adjusters. The selection of risk adjusters involves tradeoffs between cost saving and selection incentives. Exogenous variables like age and sex that are independent of spending choices and utilization maximize cost-saving incentives but leave strong incentives for selection, while endogenous, more gameable variables that reflect utilization and taste choices may better reduce selection incentives but weaken cost control. Estimation requires selecting a population, the types of spending to be adjusted, an objective function, and choosing a statistical approach for estimation, for which machine learning is a promising direction. Implementation of risk adjustment formulas requires a choice of enrollee data, adjustments to deal with time lags, accommodation of other payment system features such as risk sharing and premiums, and specifying how funds are to be reallocated from the sources of funds selected.
Properties and material models for modern construction materials at elevated temperatures

Abstract The construction industry has adopted a number of new building materials over the past few years. While these materials are specifically designed to achieve improved strength and durability characteristics at ambient conditions, the performance of modern construction materials (MCMs) under extreme conditions such as fire is still not understood. Under elevated temperatures, MCMs not only undergo a series of physio-chemical degradations, but these degradations are often of a much severe magnitude than that in traditional construction materials (TCMs). Despite ongoing efforts, there continues to be a lack of guidance/provisions on how to account for such temperature-induced degradations in MCMs. This adds another dimension of complexity to researchers and engineers seeking to carry out fire resistance evaluation and also presents a major challenge towards promoting standardization and performance-based solutions for fire engineering applications. In order to bridge this knowledge gap, this paper presents a methodology to develop temperature-dependent material models for MCMs such as high strength/performance concrete (HSC/HPC), high/very high strength steels (HSS/VHSS), and fiber-reinforced polymer (FRP) composites, using two techniques of artificial intelligence (AI) namely: artificial neural networks (ANNs) and evolutionary genetic algorithms (GAs). The outcome of this study showcases the merit of integrating AI into understanding the complex behavior of MCMs under fire conditions as well as in deriving temperature-dependent material models for these materials.
Thoracic Radiologists' Versus Computer Scientists' Perspectives on the Future of Artificial Intelligence in Radiology.

BACKGROUND There is intense interest and speculation in the application of artificial intelligence (AI) to radiology. The goals of this investigation were (1) to assess thoracic radiologists' perspectives on the role and expected impact of AI in radiology, and (2) to compare radiologists' perspectives with those of computer science (CS) experts working in the AI development. METHODS An online survey was developed and distributed to chest radiologists and CS experts at leading academic centers and societies, comparing their expectations of AI's influence on radiologists' jobs, job satisfaction, salary, and role in society. RESULTS A total of 95 radiologists and 45 computer scientists responded. Computer scientists reported having read more scientific journal articles on AI/machine learning in the past year than radiologists (mean [95% confidence interval]=17.1 [9.01-25.2] vs. 7.3 [4.7-9.9], P=0.0047). The impact of AI in radiology is expected to be high, with 57.8% and 73.3% of computer scientists and 31.6% and 61.1% of chest radiologists predicting radiologists' job will be dramatically different in 5 to 10 years, and 10 to 20 years, respectively. Although very few practitioners in both fields expect radiologists to become obsolete, with 0% expecting radiologist obsolescence in 5 years, in the long run, significantly more computer scientists (15.6%) predict radiologist obsolescence in 10 to 20 years, as compared with 3.2% of radiologists reporting the same (P=0.0128). Overall, both chest radiologists and computer scientists are optimistic about the future of AI in radiology, with large majorities expecting radiologists' job satisfaction to increase or stay the same (89.5% of radiologists vs. 86.7% of CS experts, P=0.7767), radiologists' salaries to increase or stay the same (83.2% of radiologists vs. 73.4% of CS experts, P=0.1827), and the role of radiologists in society to improve or stay the same (88.4% vs. 86.7%, P=0.7857). CONCLUSIONS Thoracic radiologists and CS experts are generally positive on the impact of AI in radiology. However, a larger percentage, but still small minority, of computer scientists predict radiologist obsolescence in 10 to 20 years. As the future of AI in radiology unfolds, this study presents a historical timestamp of which group of experts' perceptions were closer to eventual reality.
Three-Dimensional Structure of RNA Monomeric G-Quadruplex Containing ALS and FTD Related G4C2 Repeat and Its Binding with TMPyP4 Probed by Homology Modeling based on Experimental Constraints and Molecular Dynamics Simulations

The G-quadruplex-forming hexanucleotide repeat expansion (HRE), d(G4C2)n, within the human C9orf72 gene is the root cause for familial amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD). A recent study has shown that TMPyP4 has good potential to work as a RNA G-quadruplex binder in treating ALS and FTD. Although the high-resolution structure of the monomeric DNA antiparallel G-quadruplex form of the monomeric hexanucleotide repeat was recently solved, the RNA parallel G-quadruplex structure and its complex with TMPyP4 are not available yet. In this study, we first constructed the homology model for the parallel monomeric RNA G-quadruplex of r(G4C2)3G4 based on experimental constraints and the parallel monomeric G-quadruplex DNA crystal structure. Although the G-tetra core of the homology model was stable observed in 15 μs molecular dynamics (MD) simulations, we observed that the loops adopt additional conformations besides the initial crystal conformation, where TMPyP4 binding was found to reduce the loop fluctuation of the RNA monomeric G-quadruplex. Next, we probed the elusive binding behavior of TMPyP4 to the RNA monomeric G-quadruplex. Encouragingly, the binding modes observed are similar to the modes observed in two experimental complexes of a parallel DNA G-quadruplex with TMPyP4. We also constructed a Markov state model to provide insights into the binding pathways. Together, the findings from our study may assist future development of G-quadruplex-specific ligands in the treatment of neurodegenerative diseases like ALS and FTD.
10 "THE IBM WAY": WHAT THE WORLD SAW, 1964–1993

In an interdependent organization, a community of effort is imperative. Thomas J. Watson Jr. 1 IBM Became a large firm along with other American and international ones. Each employee learned how to do that as they went along, from senior executives to the newest IBM salesperson, sharing insights with each other, so much so that part of IBM's success can be attributed to its creation and dominance of an information technology ecosystem in the 1960s to the 1980s involving most large businesses and many democratic government agencies. Its influence and behavior expanded and changed, driven by such nontechnical issues as strategy development, accounting and financial strategies, and managerial worldviews, often in response to regulatory and legal regimes. The greatest number of large firms were headquartered in the United States, within easy reach of over half of IBM's employees. By 1973, IBM ranked among the ten largest corporations, along with General Electric, Chrysler, Mobil Oil, Texaco, ITT, Royal Dutch Shell, General Motors, Exxon, and Unilever. 2 Historians observed that part of the success of IBM and other firms was their ability to leverage emerging technologies, while the Chandlerian model of how large enterprises worked endured. 3
Thiopental Does Not Produce Hyperalgesia: A Laboratory Study Using Two Human Experimental Pain Models.

OBJECTIVE Past investigations assessing the effects of thiopental on pain are conflicting. Although several studies demonstrate hyperalgesia as a result of barbiturate administration, others show analgesia. Our objective was to assess the effects of an infusion of the GABAA agonist thiopental, compared with placebo, in healthy participants on two subjective experimental pain paradigms: noxious electrical stimulation and intradermal capsaicin. METHODS For electrical stimulation, the milliamps required to achieve pain threshold and tolerance were recorded, and the percent change from baseline was determined for each infusion condition. In the intradermal capsaicin condition, the area of hyperalgesia was determined by von Frey technique pre- and postinfusion, and the percent change in the area of hyperalgesia was calculated. RESULTS Though thiopental infusion resulted in an increase in the electrical stimulation current required to elicit pain threshold or reach pain tolerance when compared with baseline, this finding was not statistically significant. In the intradermal capsaicin condition, there was a statistically significant difference in overall pre- and postinfusion pain interpretation, as measured by the McGill Pain Questionnaire (P < 0.05), but there was no significant difference in area of hyperalgesia. CONCLUSIONS In this human study of thiopental's effects on two experimental pain models, our results show that thiopental does not induce hyperalgesia.
Design of Experiments in Metrology

One of the topics that has received relatively little attention in the metrology literature is the statistical design of experiments (DOEx). A premise of statistical DOEx is that efficiency is paramount in terms of the resources (cost, time, personnel, equipment, etc.…) used to perform an experiment. In the case of metrology studies, individual runs in an experiment may be very costly, and the experiment must be designed in such a way that information regarding the measurement process is obtained efficiently. In this chapter we present a variety of experimental designs and approaches to efficiently developing, evaluating, and optimizing a measurement process.
Vortex-Induced Vibrations of a square prism free to oscillate in the inline direction

Abstract We study the response of a prism placed in flow and free to oscillate in the direction of flow (the inline direction) for different possible angles of attack. The tests were conducted in a water tunnel for a range of reduced velocities of 2.4 ≤ α ≤ 45°, where α = 0° corresponded to the case where one of the square’s sides was perpendicular to the incoming flow. We observed Vortex-Induced Vibrations in the inline direction for angles of attack of α = 0°, 2.5°, 5°, 7.5°, and we showed that lock-in has occurred in the cases where oscillations are observed, by showing that the shedding frequency and the oscillation frequency were equal in this range. Throughout the lock-in range, the fluctuating force and the displacement remained in phase as well. The width of the lock-in range and the maximum amplitude of oscillations decreased with increasing angles of attack, and no oscillations were observed for α > 7.5°. The wake structures were found to be predominantly symmetric for α = 0°, and transitioned toward asymmetry with increasing α . By calculating the ratio of the fluctuating lift force to the fluctuating drag force, we quantified how the asymmetry in fluid forces increased with increasing both the angle of attack and the reduced velocity. We also showed how for larger angles of attack where oscillations were not observed, giving an initial disturbance to the prism resulted in formation of vortices for only few cycles and the prism’s oscillations decayed and were damped by the fluid forces.
Non — Perturbative Up — Conversion Techniques: Ultrafast Meets X—Rays

Femtosecond laser pulses are now available from the ultraviolet (200 nm) all the way to the mid-infrared (12 µm) in compact (often commercially available) systems. This tunability is achieved through “perturbative” nonlinear optical wavelength conversion techniques in crystals. To reach further into the ultraviolet and X—ray regions of the spectrum, a new set of techniques becomes necessary. In this paper, we will review some of these “non-perturbative” nonlinear optical methods. Specifically, we will consider the high harmonic generation process in detail, and go through the essentials of the semi-classical theory. Next, we will review a new technique, based on Thomson scattering, which has produced 0.4-Angstrom, 300-fs radiation. Finally we will consider means of measuring femtosecond pulses in this short wavelength regime.
An algebraic approach to the subset selection problem

The need for decomposing a signal into its optimal representation arises in many applications. In such applications, one can usually represent the signal as a combination of an over-complete dictionary elements. The non-uniqueness of signal representation, in such dictionaries, provides us with the opportunity to adapt the signal representation to the signal. The adaptation is based on sparsity, resolution and stability of the signal representation. In this paper, we propose an algebraic approach for identifying the sparsest representation of a given signal in terms of a given over-complete dictionary. Unlike other current techniques, our approach is guaranteed to find the solution, given that certain conditions apply. We explain these conditions.
Institutional Change as Strategy: The Role of Decentralization in Party Competition

Why do governing parties voluntarily transfer significant political and/or fiscal powers to subnational authorities? Contributing to the literature on the origins of institutions, this paper views decentralization as an electoral strategy. Unlike existing strategic explanations, however, I argue that decentralization is a means to bolster a governing party’s national-level electoral strength. It is a tool, akin to policy appeasement, used to co-opt pro-decentralization regionalist party voters. By conceiving of decentralization in this manner, we can understand why parties propose devolution reforms that would sabotage their control of the newly created subnational bodies. Because the costs of this institutional strategy are disproportionately concentrated at the subnational level, the policy will only be adopted and implemented by centralized parties that prioritize national-level power. I examine the power of the institutional appeasement theory by analyzing intranational variation in the degree and timing of decentralizing reforms across the regions of Great Britain.
Digital Logic Circuit Analysis and Design

0. Introduction. 1. Number Systems and Codes. 2. Algebraic Methods for Analysis and Synthesis of Logic Circuits. 3. Simplification of Switching Functions. 4. Modular Combinational Logic. 5. Combinational Circuit Design with Programmable Logic Devices. 6. Introduction to Sequential Devices. 7. Modular Sequential Logic. 8. Analysis and Synthesis of Synchronous Sequential Circuits. 9. Simplification of Sequential Circuits. 10. Asychronous Sequential Circuits. 11. Sequential Circuits with Programmable Logic Devices. 12. Logic Circuit Testing and Testable Design. 13. Design Examples.
Stability Analysis for Discrete Time Learning Systems: Sufficiency by Lyapunov and Necessity by Z Domain

The stability of learning systems for linear time invariant discrete time plants is studied. A standard Lyapunov function for sufficiency in the time domain is proposed. An equivalent condition in the Z domain is also presented to show necessity.
LIGHT (a Cellular Ligand for Herpes Virus Entry Mediator and Lymphotoxin Receptor)-Mediated Thymocyte Deletion Is Dependent on the Interaction Between TCR and MHC/Self-Peptide

Negative selection serves as a major mechanism to maintain self-tolerance. We previously reported that LIGHT (a cellular ligand for herpes virus entry mediator and lymphotoxin receptor), a TNF family member, plays an important role in thymocyte development via promoting apoptosis of double-positive thymocytes. Here, we demonstrated that LIGHT-mediated deletion of thymocyte requires the strong interaction of TCR with MHC/self-peptide. Transgenic mice overexpressing LIGHT in thymocytes were bred with a transgenic mouse line expressing a TCR recognizing the H-Y male Ag in the context of H-2b class I MHC molecules. In male H-Y/LIGHT double-transgenic mice, more efficient negative selection of H-Y T cells occurred, and total thymocyte number was further reduced compared with H-Y/negative littermates. In contrast, the presence of LIGHT transgene had no evident impact on the thymocyte development of female H-Y/LIGHT double-transgenic mice. Taken together, LIGHT plays a role in negative selection of thymocytes via inducing the apoptosis of thymocytes bearing high affinity TCR during negative selection.
Parameter Estimation for Groundwater Models under Uncertain Irrigation Data

The success of modeling groundwater is strongly influenced by the accuracy of the model parameters that are used to characterize the subsurface system. However, the presence of uncertainty and possibly bias in groundwater model source/sink terms may lead to biased estimates of model parameters and model predictions when the standard regression-based inverse modeling techniques are used. This study first quantifies the levels of bias in groundwater model parameters and predictions due to the presence of errors in irrigation data. Then, a new inverse modeling technique called input uncertainty weighted least-squares (IUWLS) is presented for unbiased estimation of the parameters when pumping and other source/sink data are uncertain. The approach uses the concept of generalized least-squares method with the weight of the objective function depending on the level of pumping uncertainty and iteratively adjusted during the parameter optimization process. We have conducted both analytical and numerical experiments, using irrigation pumping data from the Republican River Basin in Nebraska, to evaluate the performance of ordinary least-squares (OLS) and IUWLS calibration methods under different levels of uncertainty of irrigation data and calibration conditions. The result from the OLS method shows the presence of statistically significant (p < 0.05) bias in estimated parameters and model predictions that persist despite calibrating the models to different calibration data and sample sizes. However, by directly accounting for the irrigation pumping uncertainties during the calibration procedures, the proposed IUWLS is able to minimize the bias effectively without adding significant computational burden to the calibration processes.
Maximizing Reward in a Non-Stationary Mobile Robot Environment

The ability of a robot to improve its performance on a task can be critical, especially in poorly known and non-stationary environments where the best action or strategy is dependent upon the current state of the environment. In such systems, a good estimate of the current state of the environment is key to establishing high performance, however quantified. In this paper, we present an approach to state estimation in poorly known and non-stationary mobile robot environments, focusing on its application to a mine collection scenario, where performance is quantified using reward maximization. The approach is based on the use of augmented Markov models (AMMs), a sub-class of semi-Markov processes. We have developed an algorithm for incrementally constructing arbitrary-order AMMs on-line. It is used to capture the interaction dynamics between a robot and its environment in terms of behavior sequences executed during the performance of a task. For the purposes of reward maximization in a non-stationary environment, multiple AMMs monitor events at different timescales and provide statistics used to select the AMM likely to have a good estimate of the environmental state. AMMs with redundant or outdated information are discarded, while attempting to maintain sufficient data to reduce conformation to noise. This approach has been successfully implemented on a mobile robot performing a mine collection task. In the context of this task, we first present experimental results validating our reward maximization performance criterion. We then incorporate our algorithm for state estimation using multiple AMMs, allowing the robot to select appropriate actions based on the estimated state of the environment. The approach is tested first with a physical robot, in a non-stationary environment with an abrupt change, then with a simulation, in a gradually shifting environment.
Dedication: Henry A. Jones (1889–1981) Plant Breeder Extraordinaire

It is fitting that the first volume of Plant Breeding Reviews be dedicated to the memory of Dr. Henry A. Jones, plant breeder extraordinaire.