cssi/SciSciGPT-SciSciNet huggingface dataset:
The role of tight junction proteins during Dengue virus entry

August 20-22, 2012 W more than one-third of the world’s population living in areas at risk of infection, dengue disease becomes a huge public health burden around the world. Considerable molecular, biochemical and structural virology information have been accumulated for Dengue virus (DENV), however, our understanding on its entry process remains ambiguous. We reported here that a group of cell surface proteins, including tight junction proteins claudin-1 and occludin, were involved in DENV entry process. In Huh 7.5 cells with claudin-1 or occludin knockdown, the amount of DENV entering into the cells was reduced. Consequently, the virus progeny productions were decreased and DENV-induced CPE/apoptosis were prevented. Furthermore, resuming the expression of claudin-1 in claudin-1-knockdown and occludin in occluding-knockdown cells facilitated DENV entry in respective cells. Using pulldown assay, we showed that claudin-1 interacted with DENV prM/M protein and occludin interacted with the E protein, respectively. Mutations on essential domains in claudin-1 and occludin disrupted such interactions. The critical domain and amino acids in claudin-1 were determined using various deletion mutations and point mutations, especially mutations on the extracellular loops (ECL) of claudin-1 and occludin. Since host and viral factors involving in virus entry are very promising therapeutic targets, and entry inhibitors may provide attractive therapeutics against DENV. Thus, the results reported will provide significant insights of DENV entry mechanisms and will lead, eventually, to the ability to describe completely the entry process and to moderate or inhibit it at will.
Examining Alphabet Writing Fluency in Kindergarten: Exploring the Issue of Time on Task

Curriculum-based measures (CBMs) are necessary for educators to quickly assess student skill levels and monitor progress. This study examined the use of the alphabet writing fluency task, a CBM of ...
In-Hospital Mortality in Patients With Periprosthetic Joint Infection

Abstract Background While periprosthetic joint infection (PJI) has a huge impact on patient function and health, only a few studies have investigated its impact on mortality. The purpose of this large-scale study was to (1) determine the rate and trends of in-hospital mortality for PJI and (2) compare the in-hospital mortality rate of patients with PJI and those undergoing revision arthroplasty for aseptic failure and patients undergoing other nonorthopedic major surgical procedures. Methods Data from the Nationwide Inpatient Sample from 2002 to 2010 were analyzed to determine the risk of in-hospital mortality for PJI patients compared with aseptic revision arthroplasty. The Elixhauser comorbidity index was used to obtain patient comorbidities. Multiple logistic regression analyses were used to examine whether PJI and other patient-related factors were associated with mortality. Results PJI was associated with an increased risk (odds ratio, 2.05; P Conclusion Patients undergoing treatment for PJI have a 2-fold increase in in-hospital mortality for each surgical admission compared to aseptic revisions. Considering that PJI cases often have multiple admissions and that this analysis is by surgical admission, the risk of mortality will accumulate for every additional surgery. Surgeons should be cognizant of the potentially fatal outcome of PJI and the importance of infection control to reduce the risk of mortality.
Thermal anisotropy enhanced by phonon size effects in nanoporous materials

While thermal anisotropy is a desirable materials property for many applications, including transverse thermoelectrics and thermal management in electronic devices, it remains elusive in practical natural compounds. In this work, we show how nanoporous materials with anisotropic pore lattices can be used as a platform for inducing strong heat transport directionality in isotropic materials. Using density functional theory and the phonon Boltzmann transport equation, we calculate the phonon-size effects and thermal conductivity of nanoporous silicon with different anisotropic pore lattices. Our calculations predict a strong directionality in the thermal conductivity, dictated by the difference in the pore-pore distances, i.e., the phonon bottleneck, along the two Cartesian axes. Using Fourier's law, we also compute the diffusive heat transport for the same geometries obtaining significantly smaller anisotropy, revealing the crucial role of phonon-size effects in tuning thermal transport directionality. Bes...
Contextual decision processes with low Bellman rank are PAC-learnable

This paper studies systematic exploration for reinforcement learning (RL) with rich observations and function approximation. We introduce contextual decision processes (CDPs), that unify most prior RL settings. Our first contribution is a complexity measure, the Bellman rank, that we show enables tractable learning of near-optimal behavior in CDPs and is naturally small for many well-studied RL models. Our second contribution is a new RL algorithm that does systematic exploration to learn near-optimal behavior in CDPs with low Bellman rank. The algorithm requires a number of samples that is polynomial in all relevant parameters but independent of the number of unique contexts. Our approach uses Bellman error minimization with optimistic exploration and provides new insights into efficient exploration for RL with function approximation.
Distance Verification for Classical and Quantum LDPC Codes

The techniques of distance verification known for general linear codes are first applied to the quantum stabilizer codes. Then, these techniques are considered for classical and quantum (stabilizer) low-density-parity-check (LDPC) codes. New complexity bounds for distance verification with provable performance are derived using the average weight spectra of the ensembles of LDPC codes. These bounds are expressed in terms of the erasure-correcting capacity of the corresponding ensemble. We also present a new irreducible-cluster technique that can be applied to any LDPC code and takes advantage of parity-checks’ sparsity for both the classical and quantum LDPC codes. This technique reduces complexity exponents of all existing deterministic techniques designed for generic stabilizer codes with small relative distances, which also include all known families of the quantum stabilizer LDPC codes.
The impact of minimum wages on population health: evidence from 24 OECD countries.

This study examines the relationship between minimum wages and several measures of population health by analyzing data from 24 OECD countries for a time period of 31 years. Specifically, I test for health effects as a result of within-country variations in the generosity of minimum wages, which are measured by the Kaitz index. The paper finds that higher levels of minimum wages are associated with significant reductions of overall mortality rates as well as in the number of deaths due to outcomes that have been shown to be more prevalent among individuals with low socioeconomic status (e.g., diabetes, disease of the circulatory system, stroke). A 10% point increase of the Kaitz index is associated with significant declines in death rates and an increase in life expectancy of 0.44 years. Furthermore, I provide evidence for potential channels through which minimum wages impact population health by showing that more generous minimum wages impact outcomes such as poverty, the share of the population with unmet medical needs, the number of doctor consultations, tobacco consumption, calorie intake, and the likelihood of people being overweight.
Mechanical Novel: Crowdsourcing Complex Work through Reflection and Revision

Crowdsourcing systems accomplish large tasks with scale and speed by breaking work down into independent parts. However, many types of complex creative work, such as fiction writing, have remained out of reach for crowds because work is tightly interdependent: changing one part of a story may trigger changes to the overall plot and vice versa. Taking inspiration from how expert authors write, we propose a technique for achieving interdependent complex goals with crowds. With this technique, the crowd loops between reflection, to select a high-level goal, and revision, to decompose that goal into low-level, actionable tasks. We embody this approach in Mechanical Novel, a system that crowdsources short fiction stories on Amazon Mechanical Turk. In a field experiment, Mechanical Novel resulted in higher-quality stories than an iterative crowdsourcing workflow. Our findings suggest that orienting crowd work around high-level goals may enable workers to coordinate their effort to accomplish complex work.
Ion flow and sheath structure near positively biased electrodes

What effect does a dielectric material surrounding a small positively biased electrode have on the ion flow and sheath structure near the electrode? Measurements of the ion velocity distribution function and plasma potential near positively biased electrodes were made using laser-induced fluorescence and an emissive probe. The results were compared with 2D particle-in-cell simulations. Both measurements and simulations showed that when the positive electrode was surrounded by the dielectric material, ions were accelerated toward the electrode to approximately 0.5 times the ion sound speed before being deflected radially by the electron sheath potential barrier of the electrode. The axial potential profile in this case contained a virtual cathode. In comparison, when the dielectric material was removed from around the electrode, both the ion flow and virtual cathode depth near the electrode were dramatically reduced. These measurements suggest that the ion presheath from the dielectric material surrounding...
Minimizing Multimodular Functions and Allocating Capacity in Bike‐Sharing Systems

The growing popularity of bike-sharing systems around the world has motivated recent attention to models and algorithms for the effective operation of these systems. Most of this literature focuses on their daily operation for managing asymmetric demand. In this work, we consider the more strategic question of how to allocate dock-capacity in such systems. Our main result is a practically fast polynomial-time allocation algorithm to compute optimal solutions for this problem, that can also handle a number of practically motivated constraints, such as a limit on the number of docks moved from a given allocation. Our work further develops connections between bike-sharing models and the literature on discrete convex analysis and optimization.
Mahalanobis distance for class averaging of cryo-EM images

Single particle reconstruction (SPR) from cryo-electron microscopy (EM) is a technique in which the 3D structure of a molecule needs to be determined from its contrast transfer function (CTF) affected, noisy 2D projection images taken at unknown viewing directions. One of the main challenges in cryo-EM is the typically low signal to noise ratio (SNR) of the acquired images. 2D classification of images, followed by class averaging, improves the SNR of the resulting averages, and is used for selecting particles from micrographs and for inspecting the particle images. We introduce a new affinity measure, akin to the Mahalanobis distance, to compare cryo-EM images belonging to different defocus groups. The new similarity measure is employed to detect similar images, thereby leading to an improved algorithm for class averaging. We evaluate the performance of the proposed class averaging procedure on synthetic datasets, obtaining state of the art classification.
Mechanism of ribosome rescue by ArfA and RF2.

ArfA rescues ribosomes stalled on truncated mRNAs by recruiting release factor RF2, which normally binds stop codons to catalyze peptide release. We report two 3.2 A resolution cryo-EM structures – determined from a single sample – of the 70S ribosome with ArfA•RF2 in the A site. In both states, the ArfA C-terminus occupies the mRNA tunnel downstream of the A site. One state contains a compact inactive RF2 conformation. Ordering of the ArfA N-terminus in the second state rearranges RF2 into an extended conformation that docks the catalytic GGQ motif into the peptidyl-transferase center. Our work thus reveals the structural dynamics of ribosome rescue. The structures demonstrate how ArfA ‘senses’ the vacant mRNA tunnel and activates RF2 to mediate peptide release without a stop codon, allowing stalled ribosomes to be recycled.
WHAT IS THE UNDERLYING MECHANISM FOR THE FAILURE MODE OBSERVED IN THE PROXIMAL FEMORAL LOCKING COMPRESSION PLATE? A BIOMECHANICAL STUDY

Summary Biomechanically, a 2° screw deviation from the nominal axis in the PFLCP leads to significantly earlier implant failure. Screw deviation relies on a technical error on insertion, but in our opinion cannot be controlled intraoperatively with the existing instrumentation devices. Background Several cases of clinical failure have been reported for the Proximal Femoral Locking Compression Plate (PFLCP). The current study was designed to investigate the failure mode and to explore biomechanically the underlying mechanism. Specifically, the study sought to determine if the observed failure was due to technical error on insertion or due to implant design. Methods To exclude patient and fracture type related factors, an abstract foam block model simulating an unstable pertrochanteric fracture was created for three study groups with six specimens each (n=6). Group 1 was properly instrumented according to the manufacturer's guidelines. In Group 2 and 3, the first or second screw was placed in a posterior or anterior off-axis orientation by 2° measured in the transversal plane, respectively. Each construct was tested cyclically until failure using a test setup and protocol simulating complex axial and torsional loading. Radiographs were taken prior to and after the tests. Force, number of cycles and failure mode were compared. Results The 2° screw deviation from the nominal axis led to significantly earlier construct failure in Group 2 and 3. The failure mode consisted of loosening of the off-axis screw due to disengagement with the plate, resulting in loss of construct stiffness and varus collapse of the fracture. Conclusions In our biomechanical test setup, a screw deviation of only 2° from the nominal axis consistently led to the failure mode observed clinically. In our opinion, screw deviation mostly relies on technical error on insertion. But, proper screw insertion may be difficult or impossible with the existing instrumentation devices, especially as it cannot be controlled or guaranteed intraoperatively.
Political reform and trade policy

Abstract The welfare effects of partial restrictions on political competition are investigated in a model in which two candidates receive campaign contributions from import-competing industries in return for tariff protection. Ceilings on allowable contributions per industry may be welfare-worsening, particularly if the “contributor elasticity” is high, because they induce candidates to seek additional contributors. Restrictions that reduce the number of industries allowed to contribute may also worsen welfare, because candidates respond by increasing contributions (and tariff protection) for each active contributor. The results suggest that the ability of candidates to circumvent partial restrictions may eliminate any potential benefits.
Polar Codes: Speed of Polarization and Polynomial Gap to Capacity

We prove that, for all binary-input symmetric memoryless channels, polar codes enable reliable communication at rates within an additive gap e > 0 to the Shannon capacity with a block length, construction complexity, and decoding complexity, all bounded by a polynomial in 1/e. Polar coding gives the first known explicit construction with rigorous proofs of all these properties; previous constructions were not known to achieve capacity with less than exp(1/e) decoding complexity except for erasure channels. We establish the capacity-achieving property of polar codes via a direct analysis of the underlying martingale of conditional entropies, without relying on the martingale convergence theorem. This step gives rough polarization (noise levels ≈ e for the good channels), which can then be adequately amplified by tracking the decay of the channel Bhattacharyya parameters. Our effective bounds imply that polar codes can have block length (and encoding/decoding complexity) bounded by a polynomial in 1/e. The generator matrix of such polar codes can be constructed in polynomial time by algorithmically computing an adequate approximation of the polarization process.
Human Information Interaction, Artificial Intelligence, and Errors

In a time of pervasive and increasingly transparent computing, humans will interact more with information objects, and less with the computing devices that define them. Artificial Intelligence (AI) will be the proxy for humans’ interaction with information. Because interaction creates opportunities for error, the trend towards AI-augmented human information interaction (HII) will mandate an increased emphasis on cognition-oriented information science research, and new ways of thinking about errors and error handling. In this chapter, a review of HII and its relationship to AI is presented, with a focus on errors in this context.
Crosstalk reduction by matrix matching

Based on the recognition that propagating near-end crosstalk is the primary source of crosstalk noise in short unterminated channels we describe and demonstrate an approach to improve the signal integrity on such channels significantly. The basic physics and Norton formulation of crosstalk reduction by matrix matching are described. We then show large potential gains for two on-package interconnect application examples. A nominal strip line configuration based on standard package design rules and including realistic modeling assumptions yields 50.4% reduced channel power at iso-performance. The same design can be converted to microstrip without degrading eye height and channel power.
Engaging patients in health research: identifying research priorities through community town halls.

The vision of Canada’s Strategy for Patient-Oriented Research is that patients be actively engaged as partners in health research. Support units have been created across Canada to build capacity in patient-oriented research and facilitate its conduct. This study aimed to explore patients’ health research priorities in the province of Newfoundland and Labrador (NL). Eight town halls were held with members of the general public in rural and urban settings across the province. Sessions were a hybrid information-consultation event, with key questions about health research priorities and outcomes guiding the discussion. Sixty eight members of the public attended town hall sessions. A broad range of health experiences in the healthcare system were recounted. Key priorities for the public included access and availability of providers and services, disease prevention and health promotion, and follow-up support and community care. In discussing their health research priorities, participants spontaneously raised a broad range of suggestions for improving the healthcare system in our jurisdiction. Public research priorities and suggestions for improving the provision of healthcare provide valuable information to guide Support Units’ planning and priority-setting processes. A range of research areas were raised as priorities for patients that are likely comparable to other healthcare systems. These create a number of health research questions that would be in line with public priorities. Findings also provide lessons learned for others and add to the evidence base on patient engagement methods.
Dural Closure in Confined Spaces of the Skull Base with Nonpenetrating Titanium Clips.

Background Dural repair in areas with limited operative maneuverability has long been a challenge in skull base surgery. Without adequate dural closure, postoperative complications, including cerebrospinal fluid (CSF) leak and infection, can occur. Objective To show a novel method by which nonpenetrating, nonmagnetic titanium microclips can be used to repair dural defects in areas with limited operative access along the skull base. Methods We reviewed 53 consecutive surgical patients in whom a dural repair technique utilizing titanium microclips was performed from 2013 to 2016 at our institution. The repairs primarily involved difficult-to-reach dural defects in which primary suturing was difficult or impractical. A detailed surgical technique is described in 3 selected cases involving the anterior, middle, and posterior fossae, respectively. An additional 5 cases are provided in more limited detail to demonstrate clip artifact on postoperative imaging. Rates of postoperative CSF leak and other complications are reported. Results The microclip technique was performed successfully in 53 patients. The most common pathology in this cohort was skull base meningioma (32/53). Additional surgical indications included traumatic dural lacerations (9/53), nonmeningioma tumors (8/53), and other pathologies (4/53). The clip artifact present on postoperative imaging was minor and did not interfere with imaging interpretation. CSF leak occurred postoperatively in 3 (6%) patients. No obvious complications attributable to microclip usage were encountered. Conclusion In our experience, intracranial dural closure with nonpenetrating, nonmagnetic titanium microclips is a feasible adjunct to traditional methods of dural repair.
Impacting Entry into Evidence-Based Supported Employment: A Population-Based Empirical Analysis of a Statewide Public Mental Health Program in Maryland

We use discrete-time survival regression to study two empirical issues relating to take-up of individual placement and support (IPS) supported employment (SE) services for persons with serious mental illness: (1) the influence of client characteristics on take-up probability, and (2) the possible impacts of a major recent initiative in one state (Maryland) to overcome barriers to IPS-SE expansion. Our longitudinal analysis of population-based Medicaid cohorts, during 2002–2010, provides tentative evidence of positive state initiative impacts on SE take-up rates, and evidence of effects on take-up for clients’ diagnoses, prior work-history, health and demographic characteristics, and geographic accessibility to SE providers.
Association of Insurance Expansion With Surgical Management of Thyroid Cancer.

Importance To our knowledge, thyroid cancer incidence is increasing faster than any other cancer type and is currently the fifth most common cancer among women. While this rise is likely multifactorial, there has been scarce consideration of the effect of insurance statuses on the treatment of thyroid cancer. Objective We evaluate the association of insurance expansion with thyroid cancer treatment using the 2006 Massachusetts health reform, which serves as a unique natural experiment. Design, Setting, and Participants We used the Agency for Healthcare Research and Quality State Inpatient Databases to identify patients with government-subsidized or self-pay insurance or private insurance who were admitted to a hospital with thyroid cancer and underwent a thyroidectomy between 2001 and 2011 in Massachusetts (n = 8534) and 3 control states (n = 48 047). Difference-in-differences models were used to evaluate an association between the 2006 Massachusetts health care reform and thyroid cancer treatment, and participants were controlled for age, sex, comorbidities, and secular trends. Main Outcomes and Measures Change in the thyroidectomy rate for thyroid cancer treatment was the primary outcome evaluated. Results The Massachusetts cohort consisted of 6443 women (75.5%) and 2091 men (24.5%), of whom 6388 (79.6%) were white, 391 (4.9%) were black, 527 (6.6%) were Hispanic, 424 (5.3%) were Asian/Pacific Islander, 63 (0.8%) were Native American, and 228 (2.8%) were other. The participants from control states included 36 818 women (76.6%) and 11 229 men (23.4%), of whom 30 432 (65.5%) were white, 3818 (8.2%) were black, 6462 (13.9%) were Hispanic, 2591 (5.6%) were Asian/Pacific Islander, 211 (0.5%) were Native American, and 2947 (6.3%) were other. Before the 2006 Massachusetts insurance expansion, patients with government-subsidized or self-pay insurance had lower thyroidectomy rates for thyroid cancer in Massachusetts and the control states compared with patients with private insurance. The Massachusetts insurance expansion was associated with a 26% increased rate of undergoing a thyroidectomy (incident rate ratio, 1.26; 95% CI, 1.04-1.52; P = .02) and a 22% increased rate of neck dissection (incident rate ratio, 1.22; 95% CI, 1.07-1.37; P = .002) for treating cancer compared with control states. Conclusions and Relevance The 2006 Massachusetts health reform, which is a model for the Affordable Care Act, was associated with a 26% increased rate of thyroidectomy for treating thyroid cancer. Our study suggests that insurance expansion may be associated with increased access to the surgical management of thyroid cancer. Further studies need to be conducted to evaluate the effect of healthcare expansion at a national level.
Government Regulation of International Corporate Social Responsibility in the US and the UK: How Domestic Institutions Shape Mandatory and Supportive Initiatives

While most scholarship on corporate social responsibility (CSR) focuses on company-level CSR initiatives, it increasingly also examines government programs for CSR. However, research on how governments contribute to CSR has mainly focused on domestic and not international CSR challenges. This literature also does not specify whether governments shape CSR through mandatory regulation or supportive initiatives. This article adopts a process-tracing approach to determine how governments regulate international CSR. It demonstrates that the legal and political systems in the liberal market economies of the UK and the US lead to different forms of public CSR regulation — notably in the areas of labour standards in apparel and tax transparency in extractives. The UK government has been more likely to support bottom-up collaborative multi-stakeholder initiatives, whereas the US government has favoured top-down mandatory regulation.
Preferential formation of sodium salts from frozen sodium-ammonium-chloride-carbonate brines – Implications for Ceres’ bright spots

Abstract Observations of bright deposits in Ceres’ Occator crater have revealed large quantities of natrite (Na 2 CO 3 ) and smaller amounts of NH 4 Cl or NH 4 HCO 3 . These materials have been suggested to originate from the crystallization of brines that reached the surface from below. Here we report a systematic study of the chemistry of frozen brines containing sodium, ammonium, chloride, and carbonate ions via micro-Raman spectroscopy. Natrite and hydrohalite (NaCl·2H 2 O) are found to form preferentially, even in ammonium-dominated solutions. Additionally, NH 4 Cl could only form when NH 4 + or Cl - (or both) are present in excess in the brine solutions. The detection of NH 4 Cl on Ceres’ surface may thus imply an early subsurface reservoir rich in ammonium and/or chloride, placing an important constraint on modeling of the liquid composition.
Some mixed character sum identities of Katz

Abstract A conjecture connected with quantum physics led N. Katz to discover some amazing mixed character sum identities over a field of q elements, where q is a power of a prime p > 3 . His proof required deep algebro-geometric techniques, and he expressed interest in finding a more straightforward direct proof. Such a proof has been given by Evans and Greene in the case q ≡ 3 ( mod 4 ) , and in this paper we give a proof for the remaining case q ≡ 1 ( mod 4 ) . Moreover, we show that the identities are valid for all characteristics p > 2 .
A taste for taxes: Minimizing distortions using political preferences

Abstract We conduct an experiment with online workers to assess whether the distortionary effect of a tax is sensitive to the ideological match between taxpayer and tax expenditures. We find that, among self-identified political moderates, the labor supply elasticity with respect to the net of tax wage is significantly smaller when individuals pay taxes to a favored government agency as compared to an unfavored one. While the tax has a significant distortionary effect in the latter case, with a point estimate for the labor supply elasticity of approximately 0.77, the elasticity point estimate is close to zero when taxes go to a favored agency. There is also an increase in total output for the matched population among moderates. There is no evidence that these effects hold for self-identified liberals or conservatives.
Tuning of Fermi contour anisotropy in GaAs (001) 2D holes via strain

We demonstrate tuning of the Fermi contour anisotropy of two-dimensional (2D) holes in a symmetric GaAs (001) quantum well via the application of in-plane strain. The ballistic transport of high-mobility hole carriers allows us to measure the Fermi wavevector of 2D holes via commensurability oscillations as a function of strain. Our results show that a small amount of in-plane strain, on the order of 10−4, can induce significant Fermi wavevector anisotropy as large as 3.3, equivalent to a mass anisotropy of 11 in a parabolic band. Our method to tune the anisotropy in situ provides a platform to study the role of anisotropy in phenomena such as the fractional quantum Hall effect and composite fermions in interacting 2D systems.
Contributing factors of frequent use of the emergency department: A synthesis.

Abstract Introduction Overcrowding in emergency departments is an issue that has a negative impact worldwide. As attendance in emergency departments has increased, the ability to provide critical services to patients suffering from actual medical emergencies in a timely manner has decreased as these departments are many times at or over capacity. One patient population whose negative influence has been researched with regard to their impact on the overcrowding issue is that of the frequent user. Methods A search of two electronic databases was conducted to identify factors that frequent users state as their reasoning for using an emergency department. Peer reviewed articles in English were searched for in CINAHL Plus and PubMed, as well as a review of reference lists. Results A review of the literature identified two predominant factors related to frequent users in the emergency department: a lack of awareness of medical necessity and issues of access. Discussion To address the frequent users in emergency departments, implications for practice need to be explored and implemented. Implications for practice include education of medical necessity for the frequent users, expansion of the pre-hospital role in primary care and inappropriate use prevention, and improvement of access to alternative healthcare services.
The EGLN-HIF O2-Sensing System: Multiple Inputs and Feedbacks

The EGLN (also called PHD) prolyl hydroxylase enzymes and their canonical targets, the HIFα subunits, represent the core of an ancient oxygen-monitoring machinery used by metazoans. In this review, we highlight recent progress in understanding the overlapping versus specific roles of EGLN enzymes and HIF isoforms and discuss how feedback loops based on recently identified noncoding RNAs introduce additional layers of complexity to the hypoxic response. Based on novel interactions identified upstream and downstream of EGLNs, an integrated network connecting oxygen-sensing functions to metabolic and signaling pathways is gradually emerging with broad therapeutic implications.
Management and Effects of In-Store Promotional Displays

Problem definition: We examine a brick-and-mortar retailer’s choice of which product to include in a promotional display (e.g., an “endcap” display). The display provides a visibility advantage to ...
Probabilistic Motion Planning Under Temporal Tasks and Soft Constraints

This paper studies motion planning of a mobile robot under uncertainty. The control objective is to synthesize a finite-memory control policy, such that a high-level task specified as a linear temporal logic formula is satisfied with a desired high probability. Uncertainty is considered in the workspace properties, robot actions, and task outcomes, giving rise to a Markov decision process that models the proposed system. Different from most existing methods, we consider cost optimization both in the prefix and suffix of the system trajectory. We also analyze the potential tradeoff between reducing the mean total cost and maximizing the probability that the task is satisfied. The proposed solution is based on formulating two coupled linear programs, for the prefix and suffix, respectively, and combining them into a multiobjective optimization problem, which provides provable guarantees on the probabilistic satisfiability and the total cost optimality. We show that our method outperforms relevant approaches that employ Round-Robin policies in the trajectory suffix. Furthermore, we propose a new control synthesis algorithm to minimize the frequency of reaching a bad state when the probability of satisfying the tasks is zero, in which case, most existing methods return no solution. We validate the above-mentioned schemes via both numerical simulations and experimental studies.
Advances in Femtosecond Fiber Lasers

Pulse-shaping based on filtering of chirped pulses enables construction of femtosecond lasers without intracavity dispersion control. The operation and performance of all-normal-dispersion fiber lasers will be described.
Performance evaluation of Web proxy cache replacement policies

Abstract The continued growth of the World-Wide Web and the emergence of new end-user technologies such as cable modems necessitate the use of proxy caches to reduce latency, network traffic and Web server loads. In this paper we analyze the importance of different Web proxy workload characteristics in making good cache replacement decisions. We evaluate workload characteristics such as object size, recency of reference, frequency of reference, and turnover in the active set of objects. Trace-driven simulation is used to evaluate the effectiveness of various replacement policies for Web proxy caches. The extended duration of the trace (117 million requests collected over 5 months) allows long term side effects of replacement policies to be identified and quantified. Our results indicate that higher cache hit rates are achieved using size-based replacement policies. These policies store a large number of small objects in the cache, thus increasing the probability of an object being in the cache when requested. To achieve higher byte hit rates a few larger files must be retained in the cache. We found frequency-based policies to work best for this metric, as they keep the most popular files, regardless of size, in the cache. With either approach it is important that inactive objects be removed from the cache to prevent performance degradation due to pollution.
Bayesian regression tree models for causal inference: regularization, confounding, and heterogeneous effects

This paper presents a novel nonlinear regression model for estimating heterogeneous treatment effects from observational data, geared specifically towards situations with small effect sizes, heterogeneous effects, and strong confounding. Standard nonlinear regression models, which may work quite well for prediction, have two notable weaknesses when used to estimate heterogeneous treatment effects. First, they can yield badly biased estimates of treatment effects when fit to data with strong confounding. The Bayesian causal forest model presented in this paper avoids this problem by directly incorporating an estimate of the propensity function in the specification of the response model, implicitly inducing a covariate-dependent prior on the regression function. Second, standard approaches to response surface modeling do not provide adequate control over the strength of regularization over effect heterogeneity. The Bayesian causal forest model permits treatment effect heterogeneity to be regularized separately from the prognostic effect of control variables, making it possible to informatively "shrink to homogeneity". We illustrate these benefits via the reanalysis of an observational study assessing the causal effects of smoking on medical expenditures as well as extensive simulation studies.
Faster Algorithms for the Geometric Transportation Problem

Let R, B be a set of n points in R^d, for constant d, where the points of R have integer supplies, points of B have integer demands, and the sum of supply is equal to the sum of demand. Let d(.,.) be a suitable distance function such as the L_p distance. The transportation problem asks to find a map tau : R x B --> N such that sum_{b in B}tau(r,b) = supply(r), sum_{r in R}tau(r,b) = demand(b), and sum_{r in R, b in B} tau(r,b) d(r,b) is minimized. We present three new results for the transportation problem when d(.,.) is any L_p metric: * For any constant epsilon > 0, an O(n^{1+epsilon}) expected time randomized algorithm that returns a transportation map with expected cost O(log^2(1/epsilon)) times the optimal cost. * For any epsilon > 0, a (1+epsilon)-approximation in O(n^{3/2}epsilon^{-d}polylog(U)polylog(n)) time, where U is the maximum supply or demand of any point. * An exact strongly polynomial O(n^2 polylog n) time algorithm, for d = 2.
Precision genome editing using synthesis-dependent repair of Cas9-induced DNA breaks

The RNA-guided DNA endonuclease Cas9 has emerged as a powerful tool for genome engineering. Cas9 creates targeted double-stranded breaks (DSBs) in the genome. Knockin of specific mutations (precision genome editing) requires homology-directed repair (HDR) of the DSB by synthetic donor DNAs containing the desired edits, but HDR has been reported to be variably efficient. Here, we report that linear DNAs (single and double stranded) engage in a high-efficiency HDR mechanism that requires only ∼35 nucleotides of homology with the targeted locus to introduce edits ranging from 1 to 1,000 nucleotides. We demonstrate the utility of linear donors by introducing fluorescent protein tags in human cells and mouse embryos using PCR fragments. We find that repair is local, polarity sensitive, and prone to template switching, characteristics that are consistent with gene conversion by synthesis-dependent strand annealing. Our findings enable rational design of synthetic donor DNAs for efficient genome editing.
2017 ACC/AAP/AHA Health Policy Statement on Opportunities and Challenges in Pediatric Drug Development: Learning From Sildenafil

T he STARTS-1 and -2 trials (Sildenafil in Treatment-Naive Children, Aged 1 to 17 Years, With Pulmonary Arterial Hypertension) and subsequent 2012 US Food and Drug Administration (FDA) product labeling for sildenafil use in pediatric patients with pulmonary hypertension highlight many of the challenges to the development and approval of medications for children. This experience served as the impetus for direct collaboration between FDA representatives and the Joint Council on Congenital Heart Disease (JCCHD) (representing the pediatric cardiology leadership of the American College of Cardiology, the American Heart Association, and the American Academy of Pediatrics) to improve communication and realign missions with regard to pediatric drug trials. These discussions led to the joint FDA/JCCHD development of this statement, which describes the current environment and identifies possible future directions for reducing barriers to pediatric drug trials. There are many challenges to the development and approval of medications for children. The STARTS-1 and -2 trials, which are described briefly in the next section, highlight many of the challenges in pediatric trial design and approval of medications for children, especially those with rare diseases. Through a series of conversations between the FDA and JCCHD that had their origin around review of the effect of the STARTS-1 and -2 trials and subsequent regulatory response on clinical practice, it became clear that better communication and alignment of goals surrounding pediatric drug trials were needed. This paper serves as unique opportunity to bring leaders of the pediatric cardiology community and FDA together as 1 voice. Fewer than 50% of drugs approved for use in the United States have sufficient data to support labeling for dosing, safety, and efficacy in children.1,2 Several studies estimate at least 40% and up to 100% of hospitalized children are prescribed at least 1 medication that is used “off-label.”3 …
Spermatic Cord Torsion: Diagnostic Limitations

To distinguish spermatic cord torsion from other intrascrotal pathology, scrotal ultrasound and radionuclide scanning have been highly recommended on the basis of both clinical and experimental studies. We review the data from six patients in whom ultrasound or nuclear medicine examination was misleading. We emphasize that history, physical examination, and urinalysis remain the cornerstones of the diagnosis of spermatic cord torsion. Scrotal ultrasound and nuclear medicine scans are useful adjuncts and are reassuring when in agreement with the clinical picture. However, they are not 100% sensitive or specific, and a negative study should not prevent emergency operative exploration of a clinically suspicious lesion.
Quality Control of Agar Diffusion Susceptibility Tests: Data From the Quality Assurance Service Microbiology Program of the College of American Pathologists

Over a 12-month period, between July 1981 and June 1982, 115 active participants in the Microbiology program of the College of American Pathologists Quality Assurance Service (QAS) submitted a total of 555,619 individual determinations on three quality control reference strains using the NCCLS standardized disc diffusion procedure. Data is presented for those antimicrobic agent/reference strain combinations for which NCCLS control limits have been changed since the last report of QAS microbiology data or that continue to show discrepancies with current NCCLS individual daily test control guidelines. Data for Escherichia coli versus cefoxitin, doxycycline, and nalidixic acid and for Staphylococcus aureus versus cefoxitin, nafcillin, and oxacillin show good compliance with the new NCCLS guidelines and distributions that are all approximately Gaussian. Significant discrepancies were noted for six combinations; cefamandole, cephalothin, neomycin, and nitrofurantoin versus E. coli and amikacin and clindamycin versus S. aureus. Of these discrepancies, only neomycin/E. coli and amikacin/S. aureus can be accounted for by a subpopulation of laboratories, which, when removed, corrects the data.
Communication With Imperfectly Shared Randomness

Communication complexity investigates the amount of communication needed for two or more players to determine some joint function of their private inputs. For many interesting functions, the communication complexity can be much smaller than basic information theoretic measures associated with the players’ inputs such as the input length, the entropy, or even the conditional entropy. Communication complexity of many functions reduces further when the players share randomness. Classical works studied the communication complexity of functions when the interacting players share randomness perfectly, i.e., they get identical copies of randomness from a common source. This paper considers the variant of this question when the players share randomness imperfectly, i.e., when they get noisy copies of the randomness produced by some common source. Our main result shows that any function that can be computed by a $k$ -bit protocol in the perfect sharing model has a $2^{k}$ -bit protocol in the setting of imperfectly shared randomness and such an exponential growth is necessary. Our upper bound relies on ideas from locality sensitive hashing, while lower bounds rely on hypercontractivity and a new invariance principle tailored for communication protocols.
Teaching Stats for Data Science

ABSTRACT“Data science” is a useful catchword for methods and concepts original to the field of statistics, but typically being applied to large, multivariate, observational records. Such datasets call for techniques not often part of an introduction to statistics: modeling, consideration of covariates, sophisticated visualization, and causal reasoning. This article re-imagines introductory statistics as an introduction to data science and proposes a sequence of 10 blocks that together compose a suitable course for extracting information from contemporary data. Recent extensions to the mosaic packages for R together with tools from the “tidyverse” provide a concise and readable notation for wrangling, visualization, model-building, and model interpretation: the fundamental computational tasks of data science.
Transcriptional Architecture of Synaptic Communication Delineates GABAergic Neuron Identity.

Understanding the organizational logic of neural circuits requires deciphering the biological basis of neuronal diversity and identity, but there is no consensus on how neuron types should be defined. We analyzed single-cell transcriptomes of a set of anatomically and physiologically characterized cortical GABAergic neurons and conducted a computational genomic screen for transcriptional profiles that distinguish them from one another. We discovered that cardinal GABAergic neuron types are delineated by a transcriptional architecture that encodes their synaptic communication patterns. This architecture comprises 6 categories of ∼40 gene families, including cell-adhesion molecules, transmitter-modulator receptors, ion channels, signaling proteins, neuropeptides and vesicular release components, and transcription factors. Combinatorial expression of select members across families shapes a multi-layered molecular scaffold along the cell membrane that may customize synaptic connectivity patterns and input-output signaling properties. This molecular genetic framework of neuronal identity integrates cell phenotypes along multiple axes and provides a foundation for discovering and classifying neuron types.
Unitary Embedding for Data Hiding with the SVD

Steganography is the study of data hiding for the purpose of covert communication. A secret message is inserted into a cover file so that the very existence of the message is not apparent. Most current steganography algorithms insert data in the spatial or transform domains; common transforms include the discrete cosine transform, the discrete Fourier transform, and discrete wavelet transform. In this paper, we present a data-hiding algorithm that exploits a decomposition representation of the data instead of a frequency-based transformation of the data. The decomposition transform used is the singular value decomposition (SVD). The SVD of a matrix A is a decomposition A = USV T in which S is a nonnegative diagonal matrix and U and V are orthogonal matrices. We show how to use the orthogonal matrices in the SVD as a vessel in which to embed information. Several challenges were presented in order to accomplish this, and we give effective solutions to these problems. Preliminary results show that information-hiding using the SVD can be just as effective as using transform-based techniques. Furthermore, different problems arise when using the SVD than using a transform-based technique. We have applied the SVD to image data, but the technique can be formulated for other data types such as audio and video.