cssi/SciSciGPT-SciSciNet huggingface dataset:
Benefit-risk tradeoff preferences for chronic hand eczema treatments

Hand eczema affects approximately 16% of the US population. The long-term prognosis is poor, and 5-7% experience severe chronic hand eczema (sCHE) that interferes with daily activities. Treatments for CHE may be ineffective or associated with adverse events (AEs) that may dissuade patients from pursuing or continuing treatment. For quantification of patient experiences and benefit-risk preferences for outcomes associated with CHE treatments, a web-based discrete choice experiment survey was administered to patients in the United States with a self-reported physician diagnosis of CHE and severe symptoms not resolved with topical agents. Respondents answered a series of treatment choice questions, each requiring evaluation of a pair of hypothetical profiles of medications for sCHE defined by efficacy and risk of several AEs. Improvement in CHE clearing of 25-50% was rated from 1.5 to 3.1 times as important as eliminating a 5% risk of permanent bone problems. The mean maximum acceptable risk of permanent vision problems in exchange for an improvement in CHE clearing of 25-50% ranged from 3.4% to 4.8%. This study demonstrated that patients with CHE rated efficacy improvements associated with treatment of sCHE as more important than eliminating the risks of specific AEs.
Pre-orthotopic heart transplant estimated glomerular filtration rate predicts post-transplant mortality and renal outcomes: An analysis of the UNOS database.

Background Pre-orthotopic heart (OHT) serum creatinine correlates with post-OHT outcomes, but there is limited information on the relationship between pre-OHT estimated glomerular filtration rate (eGFR) and adjusted short- and long-term survival and renal outcomes post-OHT. Methods Using the United Network of Organ Sharing (UNOS) database we estimated pre-OHT eGFR using the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in patients aged ≥18 years who underwent OHT between 1988 and 2013. Patients were stratified into 5 eGFR categories (≥90, 60 to 89, 45 to 59, 30 to 44 and 2 ) using each equation. The primary outcome was to determine whether pre-OHT eGFR independently predicted post-OHT mortality. Results A total of 30,090 patients were included in the study; of these, 46.1% and 39.9% had an eGFR 2 by MDRD and CKD-EPI, respectively. Compared with eGFR ≥90 ml/min/1.73 m 2 , the adjusted hazard ratio of mortality was 1.09 (95% confidence interval [CI] 1.02 to 1.26) for eGFR 45 to 59 ml/min/1.73 m 2 , 1.22 (95% CI –1.23 to 1.31) for eGFR 30 to 44 ml/min/1.73 m 2 and 1.55 (95% CI 1.41 to 1.70) for eGFR 2 by MDRD. There was no advantage for CKD-EPI over MDRD in determining post-OHT mortality. Pre-OHT eGFR by either equation was predictive of post-OHT end-stage renal disease (ESRD) and the need for kidney transplantation, with the highest risk in those with pre-OHT eGFR 2 by either equation. Conclusions Pre-OHT eGFR was independently associated with mortality, ESRD and kidney transplantation after OHT. There was no advantage of CKD-EPI over MDRD in determining post-OHT mortality or renal outcomes.
tRNA Primer Sequestration as an Antiviral Strategy

From retroviral initiation to eukaryotic genome replication, priming cDNA is a challenging task. An underlying problem is that the template lacks a 3′-OH substrate required for faithful initiation of RNA or DNA synthesis by the replicative enzyme, whether it is HIV-1 reverse transcriptase (RT) or eukaryotic pol α. The solutions to this problem are various – in the case of hepadnaviruses, the replicase itself uses a tyrosine residue for the substrate to mimic a primer’s 3′-OH (reviewed in (Salas 1991)), and in the case of eukaryotic replication, a second enzyme, the pol α-primase domain, serves the role of synthesizing a primer for use by the replicase pol α. Retroviruses best exemplify genomic brevity by their ability to accomplish so many activities in so few nucleotides (nt). Thus, retroviruses and retrotransposons have solved the priming problem by co-opting an abundant highly conserved cellular factor to serve as the primer for reverse transcriptase and adapting their genomic viral RNA (vRNA) sequences to be complementary to their primers (Dahlberg et al. 1974; Harada et al. 1975; Kikuchi et al. 1986; Peters and Glover 1980). Although the primer is always a tRNA for retroviruses, the specific primer used by a retrovirus subgroup is unique, with all lentiviruses including HIV-1 using solely tRNALys3 in vivo (reviewed in (Mak and Kleiman 1997; Marquet et al. 1995)).
Preliminary Data from Worldwide Legume Inoculation Trials

The International Network of Legume Inoculation Trials (INLIT) is funded by the United States Agency for International Development (USAID), with the organization, promotion and coordination of the Network assigned to NifTAL. The program was initiated in 1980. The first year, of necessity, was devoted mostly to identifying potential cooperators for the Network, so 1981 was the first year with substantial planting of INLIT experiments. In 1982, results from cooperators started arriving at NifTAL in sufficient quantity for composite analysis.
Cloud Computing in Managing Big Data

As the world becomes technologically advanced, so has the collection and accumulation of big data. With this comes the perceived vision that cloud computing will become inevitable in the near future. The purpose of this paper is to evaluate ways and means of how Cloud Computing in Managing Big Data can be advantageous in storing, analyzing and extracting useful information. The outcome is seen to favorably impact sustainability of enterprises while at the same time facilitate executives with the ability to making predictive decisions in business models and improving customer satisfaction.
A mosquito hemolymph odorant-binding protein family member specifically binds juvenile hormone

Juvenile hormone (JH) is a key regulator of insect development and reproduction. In adult mosquitoes, it is essential for maturation of the ovary and normal male reproductive behavior, but how JH distribution and activity is regulated after secretion is unclear. Here, we report a new type of specific JH-binding protein, given the name mosquito juvenile hormone-binding protein (mJHBP), which circulates in the hemolymph of pupal and adult Aedes aegypti males and females. mJHBP is a member of the odorant-binding protein (OBP) family, and orthologs are present in the genomes of Aedes, Culex, and Anopheles mosquito species. Using isothermal titration calorimetry, we show that mJHBP specifically binds JH II and JH III but not eicosanoids or JH derivatives. mJHBP was crystallized in the presence of JH III and found to have a double OBP domain structure reminiscent of salivary "long" D7 proteins of mosquitoes. We observed that a single JH III molecule is contained in the N-terminal domain binding pocket that is closed in an apparent conformational change by a C-terminal domain-derived α-helix. The electron density for the ligand indicated a high occupancy of the natural 10R enantiomer of JH III. Of note, mJHBP is structurally unrelated to hemolymph JHBP from lepidopteran insects. A low level of expression of mJHBP in Ae. aegypti larvae suggests that it is primarily active during the adult stage where it could potentially influence the effects of JH on egg development, mating behavior, feeding, or other processes.
Novel Bis(indole) Alkaloid Dragmacidin D: Synthetic Quest for the Last 13 Years

Dragmacidin D, a bis(indole) alkaloid was isolated from deep water marine sponge in 1992 and 1998. The structural feature consists...
Synthesis and Assessment of Peptide Gd-DOTA Conjugates Targeting Extradomain B Fibronectin for Magnetic Resonance Molecular Imaging of Prostate Cancer

Contrast enhanced MRI is commonly used in imaging and treatment planning of prostate cancer. However, no tumor targeting contrast agent is commercially available for accurate detection and characterization of prostate cancer with MRI. Extradomain B fibronectin (EDB-FN), an oncoprotein present in aggressive tumors, is a promising molecular target for detection and stratification of high-risk prostate cancer. In this work, we have identified four small peptides (GVK, IGK, SGV, and ZD2) specific to EDB-FN for tumor targeting. In silico simulations of the binding patterns and affinities of peptides to the EDB protein fragment revealed different binding site to different peptide in the ligand–receptor interactions. Tumor specificity and organ distribution of the peptides were assessed using fluorescence imaging in male mice bearing PC-3 human prostate cancer xenografts. Targeted contrast agents were synthesized by conjugating tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to the peptides in the solid p...
An Overview of Time-Based Computing with Stochastic Constructs

Computing on time-based data is a recent evolution of research in stochastic computing. As with stochastic computing, complex functions can be computed with remarkably low area cost. Unlike stochastic computing, the latency and energy efficiency are very favorable compared to computations on conventional binary radix. In this article, the authors review and evaluate the design and implementation of arithmetic operations on time-encoded signals, with a particular focus on low power. The advantages, challenges, and potential applications are discussed.
Blocking CD13 in combination with a toll like receptor agonist increases the efficacy of cancer vaccine adjuvants

Vaccines have been an extraordinary tool in the fight against human disease. Recent cancer research has revealed promising results leading to approved cervical and prostate cancer vaccines. Despite the success, a major downfall of these vaccines remains poor immunogenicity. MPLA (monophosphorylated lipid A) is a synthetic analog of LPS that binds to TLR4 leading to activation of the adaptive immune response without triggering deleterious inflammatory consequences. As such, MPLA has recently been FDA approved as an adjuvant of the prophylactic vaccine against HPV-driven (Human Papilloma Virus) cervical cancer. However, this vaccine is limited to non-preexisting HPV cases while protecting against only two out of the dozen HPV strains that can potentially lead to cervical cancer. Pertinent to this subject, we have found that the absence of CD13 in antigen presenting cells (APCs), leads to increased TLR4 endocytosis and bias toward the same endocytic-signaling pathway triggered by MPLA. CD13 is a large, multifunctional cell surface peptidase constitutively expressed on all lineages of myeloid cells. We have previously shown that lack of CD13 increases tumor antigen uptake and presentation, resulting in enhanced activation of tumor-specific cytotoxic T cells. The combination of these facts has led to the intriguing possibility that blocking CD13 may amplify the efficacy of MPL as an adjuvant and ameliorate the efficacy of prophylactic and therapeutic cancer vaccines. Therefore, we hypothesize that CD13-blocking agents will act as dual-action adjuvants by enhancing MPL-TLR4 endocytosis, and as a delivery system through increased endocytic antigen uptake and subsequent cytotoxic T cell activation.
Can volumes of cortical and subcortical structures predict pre and post-laser ablation psychiatric symptoms in patients with temporal lobe epilepsy? (P6.265)

Objective: To investigate an association between mesial temporal, thalamic and orbitofrontal cortical volumes and history of pre-surgical and/or post-surgical mood and anxiety disorders in subjects with TLE who underwent laser ablation (LA) of mesial temporal structures. Background: Larger volumes of the amygdala have been associated with symptoms of depression and anxiety in TLE. Whether smaller cortical thickness and smaller volume of thalamic nuclei have the same effect is yet to be established. Design/Methods: 26 patients who underwent a LA, had a psychiatric evaluation before and at 1, 4, 12, 24 and 52 weeks after surgery. Automated quantitative volumetric measurements of hippocampi, amygdalae, thalamic nuclei, insula and orbitofrontal cortices as well as manual measurements of amygdala and hippocampus were performed in 3 Tesla high-resolution brain MRI studies. Results: Among the 26 (12 females) their mean age was 45 years old (range: 25 to 72) and the mean post-surgical follow-up period was 21 months (range 7 to 42 months). In 14 patients, the ablation was in the left side. Pre-surgical psychiatric symptoms were identified in 15 patients (58%); 9 had a left ablation. Post-surgical exacerbation in the initial 4 weeks occurred in 13 patients (66% of symptomatic patients pre-surgically). Persistent psychiatric symptomatology at last contact was present in 8 patients (31%), while 10 patients (66% of symptomatic patients pre-surgically) had a complete remission of psychiatric symptoms. A significant association was found between pre-surgical mood/anxiety disorders and a larger amygdala volume in the left side (p = 0.03). A greater asymmetry index between amygdalae, was associated with persistent psychiatric symptomatology postsurgically (p=0.022). Conclusions: Volumes of amygdalae can be associated with pre and post-surgical depressive and anxiety disorders. A larger number of patients may be necessary to identify the impact of grey matter volume changes in other structures. Disclosure: Dr. Millan has nothing to disclose. Dr. Saporta has nothing to disclose. Dr. Ribot has nothing to disclose. Dr. Stoub has nothing to disclose. Dr. Bermudez has nothing to disclose. Dr. Lowe has nothing to disclose. Dr. Palomeque has nothing to disclose. Dr. Rey has nothing to disclose. Dr. Serrano has nothing to disclose. Dr. Velez-Ruiz has nothing to disclose. Dr. Jagid has nothing to disclose. Dr Kanner has nothing to disclose.
Viscoelastic Fluid Flow: Critical Parameters and Asymptotics

This article discusses critical parameters and the use of asymptotic analysis in viscoelasticity. The discussion centers on two specific problems: the first examines the entrance layer structure that accounts for memory effects of a fluid with “small elasticity” as it moves through the inlet into a channel; the second examines secondary flows and stability of the flow of a viscoelastic fluid in a cone-plate apparatus of small angle.
Arduino as a platform for a computer organization course

The goal of this paper is to describe a set of projects we have used in the Computer Organization course at Kalamazoo College involving embedded software development on the Arduino hardware platform. These projects are motivated by the idea that programming microcontrollers moves students beyond the black box view of computation. Working with physical devices makes the content more concrete, while also providing students with a useful set of skills not covered in most computer science programs.
Complete Coupled Binding-Folding Pathway of the Intrinsically Disordered Transcription Factor Protein Brinker Revealed by Molecular Dynamics Simulations and Markov State Modeling.

Intrinsically disordered proteins (IDPs) make up a large class of proteins that lack stable structures in solution, existing instead as dynamic conformational ensembles. To perform their biological...
Water uncertainty, ritual predictability and agricultural canals at Chaco Canyon, New Mexico

The Pueblo population of Chaco Canyon during the Bonito Phase (AD 800–1130) employed agricultural strategies and water-management systems to enhance food cultivation in this unpredictable environment. Scepticism concerning the timing and effectiveness of this system, however, remains common. Using optically stimulated luminescence dating of sediments and LiDAR imaging, the authors located Bonito Phase canal features at the far west end of the canyon. Additional ED-XRF and strontium isotope (87Sr/86Sr) analyses confirm the diversion of waters from multiple sources during Chaco’s occupation. The extent of this water-management system raises new questions about social organisation and the role of ritual in facilitating responses to environmental unpredictability.
Extending the osmometer method for assessing drought tolerance in herbaceous species

Community-scale surveys of plant drought tolerance are essential for understanding semi-arid ecosystems and community responses to climate change. Thus, there is a need for an accurate and rapid methodology for assessing drought tolerance strategies across plant functional types. The osmometer method for predicting leaf osmotic potential at full turgor (πo), a key metric of leaf-level drought tolerance, has resulted in a 50-fold increase in the measurement speed of this trait; however, the applicability of this method has only been tested in woody species and crops. Here, we assess the osmometer method for use in herbaceous grassland species and test whether πo is an appropriate plant trait for understanding drought strategies of herbaceous species as well as species distributions along climate gradients. Our model for predicting leaf turgor loss point (πTLP) from πo (πTLP = 0.80πo–0.845) is nearly identical to the model previously presented for woody species. Additionally, πo was highly correlated with πTLP for graminoid species (πtlp = 0.944πo–0.611; r2 = 0.96), a plant functional group previously flagged for having the potential to cause erroneous measurements when using an osmometer. We report that πo, measured with an osmometer, is well correlated with other traits linked to drought tolerance (namely, leaf dry matter content and leaf vulnerability to hydraulic failure) as well as climate extremes linked to water availability. The validation of the osmometer method in an herb-dominated ecosystem paves the way for rapid community-scale surveys of drought tolerance across plant functional groups, which could improve trait-based predictions of ecosystem responses to climate change.
Enjoy it again: Repeat experiences are less repetitive than people think.

What would it be like to revisit a museum, restaurant, or city you just visited? To rewatch a movie you just watched? To replay a game you just played? People often have opportunities to repeat hedonic activities. Seven studies (total N = 3,356) suggest that such opportunities may be undervalued: Many repeat experiences are not as dull as they appear. Studies 1-3 documented the basic effect. All participants first completed a real-world activity once in full (Study 1, museum exhibit; Study 2, movie; Study 3, video game). Then, some predicted their reactions to repeating it whereas others actually repeated it. Predictors underestimated Experiencers' enjoyment, even when experienced enjoyment indeed declined. Studies 4 and 5 compared mechanisms: neglecting the pleasurable byproduct of continued exposure to the same content (e.g., fluency) versus neglecting the new content that manifests by virtue of continued exposure (e.g., discovery), both of which might dilute uniform dullness. We found stronger support for the latter: The misprediction was moderated by stimulus complexity (Studies 4 and 5) and mediated by the amount of novelty discovered within the stimulus (Study 5), holding exposure constant. Doing something once may engender an inflated sense that one has now seen "it," leaving people naive to the missed nuances remaining to enjoy. Studies 6 and 7 highlighted consequences: Participants incurred costs to avoid repeats so to maximize enjoyment, in specific contexts for which repetition would have been as enjoyable (Study 6) or more enjoyable (Study 7) as the provided novel alternative. These findings warrant a new look at traditional assumptions about hedonic adaptation and novelty preferences. Repetition too could add an unforeseen spice to life. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Subcutaneous Transposition of the Flexor Pollicis Longus: Does It Provide Increased Length for Tendon Repair? A Cadaveric Study.

Background: Flexor pollicis longus (FPL) tendon lacerations typically occur via sharp mechanisms such as knife injury. When the injury is chronic, it may be difficult to perform a tension free repa...
Effects of vitamin D supplementation on salivary immune responses during Marine Corps basic training.

Vitamin D's role in regulating immune responses may increase during periods of elevated psychological and physiological stress. Due to the high demands placed on US Marine Corps recruits undergoing 12 weeks of basic military training, we hypothesized that vitamin D status would be related to markers of innate mucosal immunity, and daily vitamin D supplementation would augment immune responses during training. Males (n = 75) and females (n = 74) entering recruit basic training during the summer and winter volunteered to participate in a randomized, double-blind, placebo-controlled study. Subjects received either 1000 IU vitamin D3 + 2000 mg calcium/d (n = 73) or placebo (n = 76) for 12 weeks. Saliva samples were collected pre-training, during (weeks 4 and 8), and post-training (week 12) in order to determine salivary SIgA and cathelicidin (indices of mucosal immunity) and α-amylase (indicator of stress). Initial (baseline) and post-training serum 25(OH)D levels were measured. Results were as follows: serum 25(OH)D levels were 37% higher in recruits entering training in summer compared with winter. A positive relationship was observed between baseline 25(OH)D levels and SIgA secretion rates (-SR). When stress levels were high during summer training, baseline 25(OH)D levels contributed to an increase in salivary secretory immunoglobulin A secretion rates (SIgA-SR) and cathelicidin-SR, the latter only in males. Vitamin D supplementation contributed to the changes in SIgA-SR and cathelicidin-SR, specifically SIgA-SR was higher in the treatment group. These data highlight the importance of vitamin D and mucosal immune responses during arduous basic military training when stress levels are increased.
Frontal and parietal neurons encode reward prediction errors in multiple reference frames

Abstract Anticipated and experienced rewards modulate cognitive control and attention, but the mechanisms of these modulations are poorly understood. We compared neuronal responses in monkey dorsolateral prefrontal cortex and parietal area 7A, two areas strongly implicated in visual attention and working memory, related to probabilistic rewards signaled by familiar visual cues. Neurons in both areas encoded the magnitude, probability and expected value (EV) of the reward signaled by the cue. Strikingly, neurons also encoded across-trial memories of recent rewards, which, although statistically irrelevant to a trial’s expectations, correlated with the monkeys’ behavioral sensitivity to reward history. Finally, upon outcome delivery, neurons combined responses to the experienced outcome with renewed sensitivity to EV and reward history, allowing for population-level decoding of reward prediction errors (RPEs) relative to the trial’s EV and reward history. Frontal and parietal areas explicitly encode expected and experienced outcomes and provide information relevant to computing model-free and model-based RPEs.
Periodic Riesz and Gauss-Type Potentials

In this chapter, we consider kernels of the form \(K(x, y):=F(x-y)\) for some F periodic with respect to a given lattice \(\varLambda \subset \mathbb {R}^d\); that is, \(F(x+v)=F(x)\) for all \(v\in \varLambda \). In Section 10.1, we consider periodic F defined by lattice sums of the form \(F(x)=\sum _{v\in \varLambda }f(x+v), \) for some lattice \(\varLambda \) and f with sufficient decay (see Definition 10.1.1) for the sum to converge absolutely (or to \(\infty \) unconditionally). Such sums represent the energy required to place a unit charge at x in the presence of unit charges located on \(\varLambda \) with pairwise interactions given by f. In this section, we also define and relate several notions of energy related to these periodic potentials.
The digital rock analysis of biogenically induced reservoir heterogeneities in Cretaceous reservoirs of Saudi Arabia

The characterization of the fluid-flow properties in biogenically altered formations is a key for successful exploration campaigns. This study assessed reservoir quality and evaluated permeability of the biogenically-modified Cretaceous carbonate section in Saudi Arabia. When dealing with these bioturbated carbonates, characterization of sedimentary heterogeneities is often overprinted by the complex spatial geometries of burrows. The high-resolution 3D X-ray microscopy imaging and analysis of these bioturbated sections lead to a better understanding of the interconnectivity between permeable burrows and tight matrix. The analysis deploys multiscale imaging from whole core to sub-micron scale. The coarse imaging at 20-50 microns resolution helped to identify bioturbated sections to select samples for higher resolution tomography. The 3D sample tomograms were segmented to define burrows and matrix distributions, where samples were extracted for thin-sections, scanning electronic microscopy (SEM) and mercury injection capillary pressure (MICP) analyses to refine the pore sizes and rock types. The analysis showed an intricate, highly connected, mixed horizontal and inclined burrow system dominated by Thalassinoides . Intergranular porosity, associated with the fill of Thalassinoides, constitutes a mechanism for permeability enhancement in a tight matrix. Increased permeability is associated with higher dolomite content that might be used as a sweet spot identifier from wireline logs.
On “A New Look At Entropy And The Life Table”

The author comments on a recent paper by Noreen Goldman and Graham Lord concerning the entropy of the life table. A reply by Goldman and Lord (pp. 441-2) is also included. (ANNOTATION)
Suppression of cavitation-induced nucleation in systems under isochoric confinement

This work explores the effects of constant volume confinement on cavitation-induced ice nucleation by marrying fluid dynamics, thermodynamics, and nucleation kinetics into a single approach. The authors find that confinement at even macroscopic volumes can suppress cavitation-induced nucleation from single microscale bubbles, suggesting that macroscale confinement may provide an effective method of suppressing this nucleation pathway in supercooled aqueous systems.
Elevated prevalence of nodal positivity in carcinoid tumours of the appendix smaller than 2 cm has a negative impact on overall survival

Aim The current standard of care for clinically node-negative carcinoid tumours of the appendix Method A retrospective database review of the 2019 US National Cancer Database for appendiceal cancer identified 2007 cases of clinically node-negative appendiceal carcinoid tumours based on SEER histology codes 8240, 8241, 8242, 8243, 8243, 8244, 8245, 8246 and 8249. Kaplan-Meier with log-rank testing and multivariate Cox regression analysis evaluated the impact of occult nodal positivity on overall survival following resection for clinically node-negative appendiceal carcinoma. Results The prevalence of occult nodal positivity increased from 1.9% for sub-centimetre tumours to 7% for tumours between 1.0 and 1.5 cm, 16.5% for tumours between 1.5 and 2.0 cm and to >29.5% for tumours > 2.0 cm. Rates of metastatic spread were similar for tumours Conclusion Clinically node-negative carcinoid tumours of the appendix bigger than 1.5 cm have an increased rate of occult nodal spread which has a negative impact on overall survival.
Detecting parkinsonian degeneration in lateroventral tier of substantia nigra pars compacta with MRI

Abstract Dopaminergic neurons in substantia nigra pars compacta contain neuromelanin. Parkinson's disease causes profound depigmentation of substantia nigra pars compacta. At the time of parkinsonian symptom onset, approximately 50% of melanized dopaminergic neurons in substantia nigra pars compacta have died. Multiple histopathology studies dating back to the 1930s observed a loss of these melanized neurons occurring in the lateroventral tier of substantia nigra pars compacta. Delineation of substantia nigra pars compacta in images from magnetic resonance imaging (MRI) scanners has been hampered by a lack of sensitivity to neuromelanin. The creation of neuromelanin-sensitive MRI has allowed for accurate delineation of substantia nigra pars compacta. In this chapter, we provide an overview of neuromelanin-sensitive MRI and detail studies using neuromelanin-sensitive MRI to study cell loss in the lateroventral tier of substantia nigra.
The molecular features of normal and atopic dermatitis skin in infants, children, adolescents, and adults

Background Although atopic dermatitis (AD) often presents in infancy and persists into adulthood, comparative characterization of AD skin among different pediatric age groups is lacking. Objective We sought to define skin biopsy profiles of lesional and nonlesional AD across different age groups (0-5-year-old infants with disease duration Methods We performed gene expression analyses by RNA-sequencing and real-time PCR (RT-PCR) and protein expression analysis using immunohistochemistry. Results TH2/TH22 skewing, including IL-13, CCL17/thymus and activation-regulated chemokine, IL-22, and S100As, characterized the common AD signature, with a global pathway-level enrichment across all ages. Nevertheless, specific cytokines varied widely. For example, IL-33, IL-1RL1/IL-33R, and IL-9, often associated with early atopic sensitization, showed greatest upregulations in infants. TH17 inflammation presented a 2-peak curve, with highest increases in infants (including IL-17A and IL-17F), followed by adults. TH1 polarization was uniquely detected in adults, even when compared with adolescents, with significant upregulation in adults of IFN-γ and CXCL9/CXCL10/CXCL11. Although all AD age groups had barrier abnormalities, only adults had significant decreases in filaggrin expression. Despite the short duration of the disease, infant AD presented robust downregulations of multiple barrier-related genes in both lesional and nonlesional skin. Clinical severity scores significantly correlated with TH2/TH22-related markers in all pediatric age groups. Conclusions The shared signature of AD across ages is TH2/TH22-skewed, yet differential expression of specific TH2/TH22-related genes, other TH pathways, and barrier-related genes portray heterogenetic, age-specific molecular fingerprints.
Provable Hierarchy-Based Meta-Reinforcement Learning.

Hierarchical reinforcement learning (HRL) has seen widespread interest as an approach to tractable learning of complex modular behaviors. However, existing work either assume access to expert-constructed hierarchies, or use hierarchy-learning heuristics with no provable guarantees. To address this gap, we analyze HRL in the meta-RL setting, where a learner learns latent hierarchical structure during meta-training for use in a downstream task. We consider a tabular setting where natural hierarchical structure is embedded in the transition dynamics. Analogous to supervised meta-learning theory, we provide "diversity conditions" which, together with a tractable optimism-based algorithm, guarantee sample-efficient recovery of this natural hierarchy. Furthermore, we provide regret bounds on a learner using the recovered hierarchy to solve a meta-test task. Our bounds incorporate common notions in HRL literature such as temporal and state/action abstractions, suggesting that our setting and analysis capture important features of HRL in practice.
UniTS: Short-Time Fourier Inspired Neural Networks for Sensory Time Series Classification

Discovering patterns in time series data is essential to many key tasks in intelligent sensing systems, such as human activity recognition and event detection. These tasks involve the classification of sensory information from physical measurements such as inertial or temperature change measurements. Due to differences in the underlying physics, existing methods for classification use handcrafted features combined with traditional learning algorithms, or employ distinct deep neural models to directly learn from raw data. We propose here a unified neural architecture, UniTS, for sensory time series classification in various tasks, which obviates the need for domain-specific feature, model customization or polished hyper-parameter tuning. This is possible as we believe that discriminative patterns in sensory measurements would manifest when we combine information from both the time and frequency domains. In particular, to reveal the commonality of sensory signals, we integrate Short-Time Fourier Transform (STFT) into neural networks by initializing convolutional filter weights as the Fourier coefficients. Instead of treating STFT as a static linear transform with fixed coefficients, we make these weights optimizable during network training, which essentially learns to weigh each frequency channel. Recognizing that time-domain signals might represent intuitive physics such as temperature and acceleration, we combine linearly transformed time-domain hidden features with the frequency components within each time chunk. We further extend our model to multiple branches with different time-frequency resolutions to avoid the need of hyper-parameter search. We conducted experiments on four public datasets containing time-series data from various IoT systems, including motion, WiFi, EEG, and air quality, and compared UniTS with numerous recent models. Results demonstrate that our proposed method achieves an average F1 score of 91.85% with a 2.3-point improvement over the state of the art. We also verified the efficacy of STFT-inspired structures through numerous quantitative studies.
Ovine Corticotropin-Releasing Hormone (oCRH) Stimulation Test

This test is performed to differentiate Cushing’s disease from ectopic and adrenal Cushing’s syndrome.
A learning algorithm for localizing people based on wireless signal strength that uses labeled and unlabeled data

This paper summarizes a probabilistic approach for localizing people through the signal strengths of a wireless IEEE 802.1 lb network. Our approach uses data labeled by ground truth position to learn a probabilistic mapping from locations to wireless signals, represented by piecewise linear Gaussians. It then uses sequences of wireless signal data (without position labels) to acquire motion models of individual people, which further improves the localization accuracy. The approach has been implemented and evaluated in an office environment.
TIM-4, a Receptor for Phosphatidylserine, Controls Adaptive Immunity by Regulating the Removal of Antigen-Specific T Cells

Adaptive immunity is characterized by the expansion of an Ag-specific T cell population following Ag exposure. The precise mechanisms, however, that control the expansion and subsequent contraction in the number of Ag-specific T cells are not fully understood. We show that T cell/transmembrane, Ig, and mucin (TIM)-4, a receptor for phosphatidylserine, a marker of apoptotic cells, regulates adaptive immunity in part by mediating the removal of Ag-specific T cells during the contraction phase of the response. During Ag immunization or during infection with influenza A virus, blockade of TIM-4 on APCs increased the expansion of Ag-specific T cells, resulting in an increase in secondary immune responses. Conversely, overexpression of TIM-4 on APCs in transgenic mice reduced the number of Ag-specific T cells that remained after immunization, resulting in reduced secondary T cell responses. There was no change in the total number of cell divisions that T cells completed, no change in the per cell proliferative capacity of the remaining Ag-specific T cells, and no increase in the development of Ag-specific regulatory T cells in TIM-4 transgenic mice. Thus, TIM-4–expressing cells regulate adaptive immunity by mediating the removal of phosphatidylserine-expressing apoptotic, Ag-specific T cells, thereby controlling the number of Ag-specific T cells that remain after the clearance of Ag or infection.
Computational identification of potential multi-drug combinations for reduction of microglial inflammation in Alzheimer disease

Like other neurodegenerative diseases, Alzheimer Disease (AD) has a prominent inflammatory component mediated by brain microglia. Reducing microglial inflammation could potentially halt or at least slow the neurodegenerative process. A major challenge in the development of treatments targeting brain inflammation is the sheer complexity of the molecular mechanisms that determine whether microglia become inflammatory or take on a more neuroprotective phenotype. The process is highly multifactorial, raising the possibility that a multi-target/multi-drug strategy could be more effective than conventional monotherapy. This study takes a computational approach in finding combinations of approved drugs that are potentially more effective than single drugs in reducing microglial inflammation in AD. This novel approach exploits the distinct advantages of two different computer programming languages, one imperative and the other declarative. Existing programs written in both languages implement the same model of microglial behavior, and the input/output relationships of both programs agree with each other and with data on microglia over an extensive test battery. Here the imperative program is used efficiently to screen the model for the most efficacious combinations of 10 drugs, while the declarative program is used to analyze in detail the mechanisms of action of the most efficacious combinations. Of the 1024 possible drug combinations, the simulated screen identifies only 7 that are able to move simulated microglia at least 50% of the way from a neurotoxic to a neuroprotective phenotype. Subsequent analysis shows that of the 7 most efficacious combinations, 2 stand out as superior both in strength and reliability. The model offers many experimentally testable and therapeutically relevant predictions concerning effective drug combinations and their mechanisms of action.
Foreign Direct Investment, Economic Growth, and the Human Capital Threshold: Evidence from US States*

The United States has experienced a dramatic increase in foreign direct investment (FDI) in recent years. While foreign firms bring immediate benefits of high-paying jobs, data limitations have prevented detailed study on FDI's long-term effects on the states receiving it. By creating a new stock measure of FDI based on employment, we are able to capture these long-term effects. Results demonstrate that FDI has a greater impact on per capita output growth than domestic investment for US states that meet a minimum human capital threshold. Ironically, the most active states in the recruitment of FDI tend to fall below this threshold.
Why one example is not enough for an image query

For over a decade, query-by-one-example has been a popular query paradigm for multimedia information retrieval. We show, by analyzing feature-to-semantics mapping, that such a paradigm cannot realistically lead to a scalable, satisfactory query performance. More specifically, we cluster a small image dataset based on the images' perceptual features, and show that these image clusters are not coherent to the semantic categories of the images. Though some image categories are well separated from the others in the input space formed by the perceptual features, most categories are colocated in more than one cluster. For a query-concept that is mixed with others in a number of clusters, the query-by-one-example paradigm simply lacks information to identify clearly the target query-concept, and hence cannot achieve satisfactory query results.
Early kick detection and well control decision-making for managed pressure drilling automation

Abstract Early kick detection and blowout prevention is a major concern in any drilling operation. Usually, conventional well control procedures rely merely on the pit gain and variations in pump pressure as the primary indicators to detect and handle a kick. These indicators are rudimentary and unreliable for drilling costly offshore wells while advanced well control techniques demand more reliable indicators for early detection of kicks. For instance, early kick detection plays a vital role in deploying Managed Pressure Drilling (MPD) techniques successfully. Moreover, in conventional drilling, the only widely accepted response to a gas influx is to shut the well in on the BOPs. The Constant Bottom Hole Pressure (CBHP) variation of MPD allows for circulating small and medium-sized influxes out without the need to shut in the well, either by increasing casing backpressure and/or by adjusting pump flow rate. Evident benefits include a faster response to the kick (with clear safety benefits) and a considerable time and cost savings compared to the conventional approach. Unfortunately, there is currently no method available to decide upon the best MPD-CBHP response during an influx, because such a response depends on many parameters, such as Maximum Allowable Surface Pressure (MASP), wellbore geometry, fracture pressure of any weak zones exposed in open hole, type of drilling fluid, influx size, etc. To remedy this situation, we present a fast and accurate decision-making method that overcomes the traditional difficulties and automatically selects a best well control response. The method incorporates a transient multi-phase model based on mass and momentum conservation. A numerical simulator was developed for this purpose. Comparing the actual well response with simulated results during an influx event and following the proposed algorithm allows the best response to be taken in a quick, convenient, and accurate manner. Moreover, the approach lends itself well to fully automated well control. Here, we describe the new method and its validation using available two-phase experimental data for annular air–water and air-mud flow for a wide range of flow rates and flow regimes. We believe that the method provides a powerful new decision-making and design tool in MPD operations that ensures delivery of safer wells with lower non-productive time and associated trouble cost spent on well control operations.
Temporal video segmentation using unsupervised clustering and semantic object tracking

This paper proposes a content-based temporal video segmentation system that integrates syntactic (domain- independent) and semantic (domain-dependent) features for auto- matic management of video data. Temporal video segmentation in- cludes scene change detection and shot classification. The proposed scene change detection method consists of two steps: detection and tracking of semantic objects of interest specified by the user, and an unsupervised method for detection of cuts, and edit effects. Object detection and tracking is achieved using a region matching scheme, where the region of interest is defined by the boundary of the object. A new unsupervised scene change detec- tion method based on two-class clustering is introduced to eliminate the data dependency of threshold selection. The proposed shot classification approach relies on semantic image features and ex- ploits domain-dependent visual properties such as shape, color, and spatial configuration of tracked semantic objects. The system has been applied to segmentation and classification of TV programs col- lected from different channels. Although the paper focuses on news programs, the method can easily be applied to other TV programs with distinct semantic structure. © 1998 SPIE and IS&T. (S1017-9909(98)00803-4)
Superficial Epidermolytic Ichthyosis: A Report of Two Families

Superficial epidermolytic ichthyosis (SEI), previously known as ichthyosis bullosa of Siemens, is a rare genetic skin condition, characterized by blisters and hyperkeratosis. It can be easily confused with epidermolytic hyperkeratosis, known now as epidermolytic ichthyosis, and genetic testing can be helpful in differentiating between the two conditions. We describe two children with SEI confirmed by genetic testing, including one with a novel mutation. We also describe other affected family members with SEI.
On the unsteady-state species separation of a binary liquid mixture in a rectangular thermogravitational column

This paper investigates the unsteady-state species segregation of binary liquid mixtures in rectangular thermogravitational columns. The analysis leads to a procedure to obtain both molecular and thermal diffusion coefficients from transient separation measurements. Two models are presented: first, an ideal model where buoyancy only depends on temperature and second, a general model where buoyancy also varies with composition. Steady-state measurements are not required regardless of which model is chosen. As a result, the new procedure is faster than steady-state procedures. When either the molecular or thermal diffusion coefficient is known a priori, the other can be obtained without knowledge of fluid properties such as density, viscosity, thermal expansion, and compositional coefficients.
Corrigendum to “Recent Progress in Discovery of Small–Molecule CCR5 Chemokine Receptor Ligands as HIV-1 Inhibitors” [Bioorg. Med. Chem. 2003, 11, 2663–2676]

Wieslaw Kazmierski,* Neil Bifulco, Hanbiao Yang, Larry Boone, Felix DeAnda, Chris Watson and Terry Kenakin Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA Department of Virology, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA Computational, Analytical and Structural Sciences, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA Systems Research, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA
Relationships between Spring Snow Mass and Summer Precipitation in the Southwestern United States Associated with the North American Monsoon System

This paper provides a detailed description of the relationship between spring snow mass in the mountain areas of the western United States and summertime precipitation in the southwestern United States associated with the North American monsoon system and examines the hypothesis that antecedent spring snow mass can modulate monsoon rains through effects on land surface energy balance. Analysis of spring snow water equivalent (SWE) and July‐August (JA) precipitation for the period of 1948‐97 confirms the inverse snow‐monsoon relationship noted in previous studies. Examination of regional difference in SWE‐JA precipitation associations shows that although JA precipitation in New Mexico is significantly correlated with SWE over much larger areas than in Arizona, the overall strength of the correlations are just as strong in Arizona as in New Mexico. Results from this study also illustrate that the snow‐monsoon relationship is unstable over time. In New Mexico, the relationship is strongest during 1965‐92 and is weaker outside that period. By contrast, Arizona shows strongest snow‐monsoon associations before 1970. The temporal coincidence between stronger snow‐monsoon associations over Arizona and weaker snow‐monsoon associations over New Mexico (and vice versa) suggests a common forcing mechanism and that the variations in the strength of snow‐monsoon associations are more than just climate noise. There is a need to understand how other factors modulate monsoonal rainfall before realistic predictions of summertime precipitation in the Southwest can be made.