cssi/SciSciGPT-SciSciNet huggingface dataset:
Understanding advanced concepts in atrioventricular block

Not all atrioventricular blocks occur in the atrioventricular node. Understanding the physiological concept behind the various blocks makes recognizing the relevant ECG indications easier. Furthermore, the implications to patients are clear when healthcare providers understand the level of the block and the dangers the block may impose. Until a more accurately descriptive classification system of conduction blocks becomes universally accepted, the current labels will continue to be used. It is imperative that nurses, particularly those caring for cardiac patients, recognize and understand the ECG indications of various degrees of block.
Toward Customer Needs Cultural Risk Indicator Insights for Product Development

As the availability and affordability of consumer products continues to increase around the world, consumers — especially those in developing countries and living on less than $10/day — will express more discerning in their tastes and preferences. Design teams have already been operating in design for the developing world contexts for many years and more are moving into the arena on a regular basis. Many designers do not have cultural knowledge of the customers cultures they are designing for. Cultural ignorance can lead to misinterpretation of customer needs that can lead to products that do not satisfy customer needs and results in disappointed customers, low sales figures, and a frustrated design team. The Customer Needs Cultural Risk Indicator (CNCRI) method introduced in this paper provides a method for design teams to rapidly analyze customer needs for “Risk Indicators” in customer needs based upon cultural differences between the customers and the design team. By understanding early on in the design process where a lack of cultural knowledge may be a risk to the design, the design team can make informed decisions on how to satisfy customer needs effectively.Copyright © 2015 by ASME
Dynamic Protein Acetylation in Plant–Pathogen Interactions

Pathogen infection triggers complex molecular perturbations within host cells that results in either resistance or susceptibility. Protein acetylation is an emerging biochemical modification that appears to play central roles during host-pathogen interactions. To date, research in this area has focused on two main themes linking protein acetylation to plant immune signaling. Firstly, it has been established that proper gene expression during defense responses requires modulation of histone acetylation within target gene promoter regions. Second, some pathogens can deliver effector molecules that encode acetyltransferases directly within the host cell to modify acetylation of specific host proteins. Collectively these findings suggest that the acetylation level for a range of host proteins may be modulated to alter the outcome of pathogen infection. This review will focus on summarizing our current understanding of the roles of protein acetylation in plant defense and highlight the utility of proteomics approaches to uncover the complete repertoire of acetylation changes triggered by pathogen infection.
Instrumental conditioning of the running-wheel response of food-deprived rats

Two experiments are cited in which it was found that body-weight deficit was the main contributor to the increase in running wheel activity by food-deprived rats. Both cited studies were unable to support any learning or associative effect in such an activity increase. The present study demonstrates that the wheel running behavior of food-deprived rats can be either increased or decreased when reinforcement contingencies are rigorously controlled in an operant conditioning paradigm. The possible time delay between response and reinforcement in the previously cited investigations is discussed.
Orientational Dynamics in Sum Frequency Spectroscopic Line Shapes

We present a general response function formalism describing the contribution of orientational dynamics of molecules at interfaces to spectroscopic line shapes in vibrational sum frequency generation (SFG). When reorientation occurs on the time scale comparable to vibrational dephasing, its dynamics can be extracted from polarization-selected SFG spectral line shapes. Unique features of orientational motion at interfaces are (1) the anisotropic case-specific equilibrium orientational distribution and (2) possible dynamic anisotropy (e.g., different in-plane versus out-of-plane relaxation rates), both of which must be taken into account. Within the small-step rotational diffusion model, we present solutions for two cases, the weak-confinement model, applicable when the deviations from the isotropic case are not severe, and the wobbling-in-a-cone model, which considers a hard-wall orienting potential. SFG line shapes are calculated for a rod-like chromophore as a function of the rotational diffusion rate. Fo...
Discussion the Effect of the Cooling Rate to the Mechanical Properties of Non Quenched and Tempered Steel Connecting Rod

This article present the effect and the importance of the air cooling rate of the connecting rod forging heat treatment.Then to do series test of air cooling rate to solve the mechanical function deviation problem of the connecting casting,and find out the most suitable cooling rate of heat treatment,to meet the connecting rod technical requirement.
Application of optical fiber gratings in a 3D probe

A novel 3D touch trigger probe is developed based on the fiber Bragg grating(FBG) sensing technology.From the perspective of principles of FBG,the selection criteria of the main technical parameters of the FBG sensor is analyzed.And the structure of the probe is designed according to the characteristics of the FBG sensor.Some key performance of the 3D probe is tested during the process of fabrication,such as the probe repeatability and positioning accuracy.The feasibility of fiber grating probe is analyzed theoretically and verified via experiments to some extent.
P-δ Effects on the Plastic Region of RC Bridge Columns: Closed-Form Solution

AbstractA closed-form solution to the effect of member deformations (δ) on the inelastic response of RC bridge columns is presented. The formulation is based on an equivalent elastic structure with a constant flexural stiffness for the cracked RC section that enables the solution to be independent of the structural global displacements (Δ). The ability of the proposed solution for predicting moment, curvature, and displacement profiles in RC columns is demonstrated and verified against experimental data from four half-scale test columns. The closed-form solution led to the identification of a dimensionless slenderness parameter that measures the susceptibility of RC columns to second-order effects. Simplified formulas for the spread of the plastic region (Lpr) and the magnitude of P-δ moment are proposed for use in seismic design. The design formulas, derived from the mechanics-based solution, are shown to be able to predict experimental data on the P-δ effects with satisfactory accuracy.
A new approach to an old problem: Gemination and constraint reranking in West Germanic

This paper presents an Optimality Theoretic (Prince and Smolensky1993; McCarthy and Prince 1995) analysis of diachronic phonological change as the reranking of violable constraints, taking thee mergence of word-medial geminates in West Germanic as a case study. West Germanic is characterized by, among other things, the gemination of all consonants – except *r – after a short vowel and before *j (Gmc. *skapjan > OS skeppian, OE scieppan vs. Got. skapjan, ON skepja ’tocreate‘) and the gemination of voiceless stops before *r and*l (*akr- > OHG akkar, OS akkar vs. Got. akrs, ON akr ’field‘). Evidence from versification and word division in original documents suggests that all Germanic dialects favored bimoraic stressed syllables, syllabifying *skapjan as *skap.jan, for example. This often resulted in faulty syllable contacts in which the coda consonant was less sonorous than the following onset. Murray and Vennemann (1983) propose that geminates arose in order to repair such faulty syllable contacts (e.g., *skap.jan > *skap.pjan),but their analysis fails to satisfactorily account for the full scope of the West Germanic Gemination. I propose here that while gemination before *r and *l was driven by unfavorable sonority differences at syllable margins, the more pervasive appearance of geminates before *j simply resulted from a well-attested Germanic dispreference for *j in onset-initial position.
Focus on Technology: Inspiring Students to Read With Online Book Collections

Today's young people, with greater access to the Internet, have more reading material to select from than in previous years. This increase in reading content provides more chances to find material ...
Chapter 14 – Principles of Biostatistics

Randomized controlled trials (RCTs) are considered a gold standard to measure an intervention's effect by random assignment of individuals to an intervention or a control arm. Specifically, the randomization process ensures that the differences between the groups, if observed at the end of the trial, are only due to the treatment administration. To fully appreciate the principles of RCTs, the investigators leading the studies should have basic understanding of the statistical principles. This chapter covers state-of-the-art statistical approaches that are commonly employed in the medical field for design and analysis of clinical trials.
A radar echo emulator for the evaluation of automotive radar sensors

Autonomous emergency braking (AEB) and Pre-Collision Systems (PCS) are beginning to be implemented by major automotive manufactures. AEB systems utilize automotive radar sensors operating in the 77 GHz frequency band for target detection, as well as other sensors such as camera, and infrared. Currently, the Euro NCAP Vehicle Target (EVT) is selected as the European standard target for evaluating PCS radar performance under defined AEB testing scenarios [1]-[3]. The main goal of this research effort was developing a compact 76–78 GHz radar echo emulator (REE) to replace the complex radar scattering and absorbing treatment inside EVT (Figure 6)[2]. The proposed REE receives signals transmitted from the PCS radar mounted on the training vehicle under test (VUT) and then transmits modified radar signals back to PCS radar bearing the similar range-dependent radar cross section (RCS) property as EVT. Additionally, this paper details a technique for characterizing the “near-field RCS” of a target at close range which is necessary for evaluating AEB performance.
Co‐surgeons in breast reconstructive microsurgery: What do they bring to the table?

Introduction Current research within other surgical specialties suggests that a co-surgeon approach may reduce operative times and complications associated with complex bilateral procedures, possibly leading to improved patient and surgical outcomes. We sought to evaluate the role of the co-surgery team and its development in free flap breast reconstruction. Methods A retrospective review of free-flap breast reconstruction by two surgeons from 2011 to 2016 was conducted. We analyzed 128 patients who underwent bilateral-DIEP breast. Surgical groups were: single-surgeon reconstruction (SSR; 35 patients), co-surgery where both surgeons are present for entire reconstruction (CSR-I; 69 patients), and co-surgery reconstruction where co-surgeons appropriately assist in two concurrent or staggered cases (CSR-II; 24 patients). Efficiency data collected was OR time and patient length-of-stay (LOS). The rate of flap-failure, return to OR, infection, wound breakdown, seroma, hematoma, and PE/DVT were compared. Results Single-surgeon reconstruction had significantly longer OR time (678 vs. 485 min, P < .0001), LOS (5 vs. 3.9 days, P < .001), higher wound occurrences of the umbilical site that required surgical correction [11.4 percent (n = 4) vs. 1.5% (n = 1); P < .043] compared to CSR-I. Similarly, SSR had significantly longer average OR time (678 vs. 527 min P < .0001), average LOS (5 vs. 4 days, P = .0005) when compared with CSR-II. There were no total increased patient related complications associated with co-surgery (CSR-I or II). Conclusion The addition of a co-surgeon, even with concurrent surgery, reduces operative time, average patient LOS, and postoperative complications. This work lends a strong credence that co-surgery model is associated with increased operative efficiency.
Real-world use of PCSK-9 inhibitors by early adopters: cardiovascular risk factors, statin co-treatment, and short-term adherence in routine clinical practice

BACKGROUND Inconsistency of real-world medication use with labeled indications may affect cost and clinical value of pharmacotherapy. PCSK-9 inhibitors are labeled in the US for use with statins to reduce low-density lipoprotein cholesterol in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH). OBJECTIVE To assess consistency with labeled indications and treatment persistency for early (first 5 post-launch months) adopters of PCSK-9 inhibitor pharmacotherapy. METHODS Retrospective analysis of commercially insured cohorts derived from the Truven Health MarketScan® database was performed. Subjects were aged 18-64 years, initiated PCSK-9 inhibitor or highest-intensity statin (rosuvastatin 40 mg/day or atorvastatin 80 mg/day) pharmacotherapy from August to December 2015, and were enrolled throughout 2015 and during separate baseline (pre-treatment) periods of 6 and 18 months. Baseline ASCVD, FH, and ASCVD events (myocardial infarction, transient ischemic attack, and cerebrovascular occlusion) were measured. Persistency was measured through December 2015 for subcohorts of patients initiating treatment from August to September 2015. RESULTS Baseline disease rates were higher for patients treated with PCSK-9 inhibitors (n=390) compared with highest-intensity statins (n=26,306): ASCVD (68.5% vs 33.4%, respectively); FH (39.7% vs 15.5%); both P<0.001. In 18 months pre-treatment, 35.6% of PCSK-9 inhibitor-treated patients had ≥1 ASCVD event, and 87.9% had a labeled indication. Rates of 60-day nonpersistency for PCSK-9 inhibitors and highest-intensity statins were 33.3% and 39.8%, respectively (P=0.207). During PCSK-9 inhibitor pharmacotherapy, 33.8% of patients had evidence of statin supply and, of those initiating treatment from August to September, 40.9% filled ≥1 statin prescription. Of those with sustained pre-treatment statin use, 34.8% had no statin supply during PCSK-9 inhibitor pharmacotherapy. CONCLUSION Among early-adopting PCSK-9 inhibitor-treated patients, the off-label diagnosis rate was 12%; a majority lacked statin co-treatment; and one third filled prescriptions for ≤60 days. Inconsistency with labeled uses may reflect prescriber/patient decisions, health-insurance coverage determinations, or statin intolerance not reported on claims.
Introducing Catalytic Diversity into Single-Site Chabazite Zeolites of Fixed Composition via Synthetic Control of Active Site Proximity

We report a synthesis–structure–function relation describing how different routes to crystallize single tetrahedral-site (T-site) zeolites of fixed composition lead to different arrangements of framework Al atoms and, in turn, of extraframework proton active site ensembles that markedly influence turnover rates of a Bronsted acid-catalyzed reaction. Specifically, synthetic routes are reported that result in systematic changes in the arrangement of aluminum atoms (Al–O(−Si-O)x–Al) in isolated (x > 2) and paired (x = 1, 2) configurations within chabazite (CHA) zeolite frameworks of effectively fixed composition (Si/Al = 14–17). Precursor solutions containing different structure-directing agents and aluminum sources crystallize CHA zeolites with one organic N,N,N-trimethyl-1-adamantylammonium cation occluded per CHA cage, and with amounts of occluded Na+ cations that increase linearly with paired framework Al content (0–44%). Ammonia and divalent cobalt ion titrations are used to quantify total and paired Br...
Stereoscopic PIV measurements of near-wall flow in a tightly packed rod bundle with wire spacers

Abstract In this study, we experimentally investigated the flow field characteristics in the complex geometry of a tightly packed 61-rod bundle with wire spacers by employing matched-index-of-refraction (MIR) and stereoscopic particle image velocimetry (SPIV) techniques. SPIV measurements were performed on a cross-flow plane at Reynolds numbers of 500, 2500, and 6300, and the measurement area covered the interior and edge sub-channels that were located near the enclosure wall. The SPIV results showed that peaks of the velocity magnitude occurred in the edge sub-channel, indicating the wall effects on the flow symmetry in the cross-flow plane. Mean velocities at the central areas of the edge and interior sub-channels showed flat profiles for Re = 500 and local peaks around 0.15 y / D rod 0.3 , due to the wire’s presence and near-wall location of the edge sub-channel. The rms fluctuating profiles velocities showed that local maximal peaks linearly shifted from y / D rod = - 0.44 to −0.36 and −0.28 as Re increased. Taylor’s hypothesis was applied to the SPIV velocity vector fields for reconstructing quasi-instantaneous three-dimensional (3D) vortical structures in the wire-wrapped rod bundle. The visualization of 3D vorticity iso-surfaces showed that vortical structures were generated from shear layers of neighboring rods and traveled in the streamwise direction. Finally, proper orthogonal decomposition (POD) analysis was applied to SPIV velocity snapshots taken at the edge and interior sub-channels to extract the most statistically dominant flow structures. The POD velocity decomposition revealed coherent structures with sizes and shapes comparable to instantaneous vortical structures identified by iso-surfaces. Energy fractions of the first POD modes were found to reduce from 46% and 31% to 26% and 18% when Reynolds numbers increased from Re = 500 to 6300, respectively. On the other hand, kinetic energy levels of low-order POD modes (modes 2, 3, 4, etc.) increased when the Reynolds number increased.
Reliability Enhancement of Smart Metering System Using Millimeter Wave Technology

Millimeter wave (mmWave) technology has been advocated as a promising infrastructure to provide reliable communications, both in indoor and outdoor environments. In this paper, we extend the application of mmWave to the uplink communication between smart meters (SMs) and a gateway. Such a communication is subject to interference from SMs belonging to adjacent networks and blockage caused by human bodies. Using a 3-D stochastic blockage model, we derive the outage probability. When human-body blockage is neglected, the high signal-to-noise-ratio (SNR) analysis shows a diversity gain of $(m_{L}M)$ , where $m_{L}$ is the Nakagami-fading parameter of the line of sight (LOS) of the reference transmitter’s channel, and $M$ is the number of receive antennas at the gateway. Accounting for human-body blockage, the diversity gain reduces to $(m_{N}M)$ , where $m_{N}$ is the Nakagami-fading parameter of the non LOS of the reference transmitter’s channel. Our analysis shows that the probability that an SM is in LOS decays exponentially with the link length and the density of blockages. Although at high SNR blockage reduces the diversity gain, our numerical results show that blockage may decrease the outage probability at finite SNR.
ASYNCHRONOUS ONSET OF MECHANICAL SYSTOLE STUDIED BY COMPUTER GENERATED THREE-DIMENSIONAL FUNCTIONAL IMAGES OF THE LEFT VENTRICLE

ABSTRACT Regional asynchrony in the onset of mechanical systole is defined as the physiological phenomenon that all regions of the left ventricle do not begin to contract at the same time. Three-dimensional left ventricular images of each set of biplane cine frames were generated to study this regional asynchrony. A discrete Fourier analysis on segmental volume versus time data was performed to obtain the phase relationship between the onset of global and segmental systole. Three different types of wall segments analyzed by this method were normal wall motion in subjects with normal coronary arteries (Group A), normal wall motion in subjects with coronary artery disease (Group B), and abnormal wall motion in subjects with coronary artery disease (Group C). Wall segments in all groups were found to have synchronous as well as early and late onset of mechanical systole. Group A had a significantly (p
Diet and Cancer Prevention in the United States

Human cancer risk is strongly influenced by life style choices, including diet; differences in diet contribute to international variations in cancer incidence. Dietary patterns in Japan are growing closer to those in the United States and most likely are contributing to the rising rates of colorectal, breast, and prostate cancers in Japan. Colorectal cancer research has investigated the effect of dietary fat, fiber, and calcium on the development of adenomatous polyps, precursor lesions with malignant potential. The potential role of dietary fat alone in the development of breast cancer remains controversial, but fat, calories, and obesity together most likely affect postmenopausal breast cancer risk. Both the amount and type of fat consumed may be important and perhaps the age at which fat is consumed. Research has hypothesized that prostate cancer may have hormonal connections; and fat, as well as genetic factors, may play a role in this hormonal etiology. NIH-sponsored large-scale trials—specifically, the Polyp Prevention Trial (PPT) and the Women’s Health Initiative (WHI)—are evaluating the effects of a diet low in fat and high in vegetables, fruits, and fiber on colorectal and breast cancer risk, respectively. Public health programs and new food technology applications, such as soy-based foods, fat substitutes, and genetically engineered foods, have been developed and could contribute to healthy dietary habits.
Right Upper Quadrant Pain, Fever, Nausea, and Vomiting

A 40-year-old female presents with a 24 h history of right upper quadrant (RUQ) and epigastric pain, associated with nausea and vomiting. She has had similar pain in the past, particularly after eating greasy foods. According to her family, over the last few hours, the patient has become slightly confused. Past medical history is negative. Physical examination reveals a temperature of 102.5 °F, a heart rate of 110 beats/min, respiratory rate of 16/min, and a blood pressure of 90/60 mmHg. She is moderately tender in the RUQ to deep palpation. She has slight scleral icterus. She has noted dark-colored urine. The remainder of her abdominal exam is negative. Laboratory examination is significant for a white blood count of 15 × 103/μL (normal 4.1–10.9 × 103/μL), a total bilirubin of 4.0 mg/dl (0.1–1.2 mg/dl), alkaline phosphatase (AP) of 350 μ/L (33–131 μ/L), aspartate aminotransferase (AST) of 300 μ/L (5–35 μ/L) and alanine aminotransferase (ALT) of 280 μ/L (7–56 μ/L), gamma-glutamyl transpeptidase (GGT) of 330 μ/L (8–88 μ/L), and an amylase of 100 μ/L (30–110 μ/L). Urine is positive for bilirubin.
Agent architectures for flexible, practical teamwork

Teamwork in complex, dynamic, multi-agent domains mandates highly flexible coordination and communication. Simply fitting individual agents with precomputed coordination plans will not do, for their inflexibility can cause severe failures in teamwork, and their domain-specificity hinders reusability. Our central hypothesis is that the key to such flexibility and reusability is agent architectures with integrated teamwork capabilities. This fundamental shift in agent architectures is illustrated via an implemented candidate: STEAM. While STEAM is founded on the joint intentions theory, practical operationalization has required it to integrate several key novel concepts: (i) team synchronization to establish joint intentions; (ii) constructs for monitoring joint intentions and repair; and (iii) decision-theoretic communication selectivity (to pragmatically extend the joint intentions theory). Applications in three different complex domains, with empirical results, are presented.
Bloodstream Infections Occurring in Patients With Percutaneously Implanted Bioprosthetic Pulmonary Valve A Single-center Experience

Background—Percutaneous pulmonary valve implantation using a stent-based bioprosthetic valve provides an alternative to surgery in select patients. Systemic infections in Melody valve–implanted patients with and without identified valve involvement have been reported, yet the incidence is unknown, and risk factors remain unidentified. Methods and Results—Between 2007 and 2012, a total of 147 consecutive patients with congenital heart disease underwent Melody percutaneous pulmonary valve implantation at our institution. Demographic and clinical variables were collected at baseline and at follow-up and analyzed as predictors. The occurrence of bloodstream infection (BSI), defined as a bacterial infection treated with ≥4 weeks of antibiotics, served as our primary outcome. The mean age at implantation for the study population was 21.5±11 years, and tetralogy of Fallot was the cardiac condition in 59%. During a median follow-up of 19 months, 14 patients experienced BSI (9.5%; 95% confidence interval, 5.3%–15%...
An Adaptive Interleaving Algorithm for Multi-Converter Systems

To integrate DC distributed generation (DG) with micro-source into the existing AC grid, a DC distribution bus can be used to couple on-site photovoltaics (PV), battery energy storage systems (BESS), and DC loads. If the converters connected to the DC bus are interleaved, the DC bus capacitor size could be minimized. In this paper, we propose an interleaving algorithm for multi-converter systems to minimize the current harmonics at switching frequency on the DC bus. The proposed algorithm is implemented using Resilient Information Architecture Platform for Smart Grid (RIAPS) platform. Hardware-in-the-Loop (HIL) simulation results based on Opal- RT are presented to validate its performance. The influence of synchronization frequency on the proposed algorithm are also considered.
High-dose chemotherapy (HDCT) plus peripheral-blood stem-cell transplant (PBSCT) for patients (pts) with relapsed germ-cell tumors (GCT) and active brain metastases (mets).

4558Background: The optimal management of progressive brain mets in pts with GCT remains unsettled. Treatment options include chemotherapy, stereotactic or whole brain radiation (XRT), surgery, or ...
Effects of a brief pain and smoking cessation intervention in adults with chronic pain: A randomized controlled trial

Tobacco cigarette smokers with comorbid chronic pain experience greater difficulty quitting smoking relative to those without chronic pain. A brief smoking cessation intervention was developed to address smoking in the context of chronic pain to increase the intention to engage in smoking cessation treatment. The primary aim of this randomized controlled trial was to investigate the effects of a brief pain and smoking (BPS) cessation intervention on the willingness to consider quitting smoking in adults with chronic pain seeking treatment in a pain specialty outpatient clinic. Subjects randomized to the BPS intervention were 7.5 times more likely to endorse willingness to consider quitting smoking. Subjects who received the BPS intervention were also greater than 2.5 times more likely to report an interest in learning about cessation programs, and nearly 5 times more likely to endorse willingness to consider participating in an intensive smoking cessation program. Moreover, subjects who received the BPS intervention evinced a trend-level reduction in perceived difficulty of quitting smoking. These results contribute to a growing multidisciplinary literature examining pain-smoking interrelations and suggest that smokers with chronic pain may become more willing to consider engaging a cessation attempt as awareness increases about how continued smoking may interfere with the clinical outcomes of pain treatment. These results are also consistent with clinical practice guidelines for promoting intention to quit among smokers currently unwilling to engage a quit attempt by incorporating strategies aimed at identifying ambivalence about the continued use of tobacco.
Forging Smarter Cities through CrowdLaw

Public officials are often ill-equipped when it comes to knowing how to regulate complex societal challenges, especially those that involve cutting-edge scientific and technological advances that raise myriad ethical, moral, political, legal, regulatory and social questions. But what if technology could be used to improve the quality of regulation and legislation? Online, tech-enabled participation methods, known as “CrowdLaw”, enable more individuals, not only interest groups, to inform the legislative and policymaking processes. In this brief commentary, I survey a handful of global examples which show CrowdLaw in use at each stage of the lawmaking process at the local level and exhibit how participation is improving outcomes.
Species of Cassida Linne, 1758 described by Thunberg and their present status (Coleoptera: Chrysomelidae: Cassidinae)

All species of Cassida Linne described by Thunberg are listed and commented. Lectotype designations are given for all species in order to fix names. Following new synonym is proposed: C. flaveola Thunberg, 1794 = C. pallida Thunberg, 1794, syn. nov. Author and year of publication in C. swartzii is corrected.
High Efficiency Drug Repurposing for New Antifungal Agents

There has been a persistent effort to improve efficacy of conventional antimycotic drugs. However, current antimycotic interventions have often limited efficiency in treating fungal pathogens, especially those resistant to drugs. Considering development of entirely new antimycotic drugs is a capital-intensive and time-consuming process, we investigated an alternative approach termed drug repurposing whereby new utility of various marketed, non-antifungal drugs could be repositioned as novel antimycotic agents. As a proof of concept, we applied chemosensitization as a new screening strategy, where combined application of a second compound, viz., chemosensitizer, with a conventional drug could enhance antifungal efficacy of the drug co-applied. Unlike the conventional combination therapy, a chemosensitizer itself does not necessarily have to possess an antifungal activity, but the chemosensitizer significantly debilitates defense systems of pathogens to drugs, enabling improved identification of antifungal activity of off-patent drugs. Of note, inclusion of fungal mutants, such as antioxidant mutants, could facilitate drug repurposing process by enhancing the sensitivity of antifungal screening. Altogether, our strategy could lead to high efficiency drug repurposing, which enhances the drug susceptibility of targeted fungal pathogens.
Donor-Derived Cytokine-Induced Killer Cell Infusion as Consolidation after Nonmyeloablative Allogeneic Transplantation for Myeloid Neoplasms.

ABSTRACT Non-myeloablative conditioning, such as with total lymphoid irradiation and antithymocyte globulin (TLI-ATG), has allowed allogeneic hematopoietic cell transplantation (allo-HCT) with curative potential for older patients and those with comorbid medical conditions with myeloid neoplasms. However, early achievement of full donor chimerism (FDC) and relapse remain challenging. Cytokine-induced killer (CIK) cells have been shown to have antitumor cytotoxicity. Infusion of donor-derived CIK cells has been studied for hematologic malignancies relapsed after allo-HCT but has not been evaluated as post-transplant consolidation. In this phase II study, we prospectively studied whether a one-time infusion of 1 × 108/kg CD3+ donor-derived CIK cells administered between day +21 and day +35 after TLI-ATG conditioning could improve achievement of FDC by day +90 and 2-year clinical outcomes in patients with myeloid neoplasms. CIK cells, containing predominantly CD3+CD8+NKG2D+ cells along with significantly expanded CD3+CD56+ cells, were infused in 31 of 44 patients. Study outcomes were compared to outcomes of a retrospective historical cohort of 100 patients. We found that this one-time CIK infusion did not increase the rate of FDC by day +90. On an intention-to-treat analysis, 2-year non-relapse mortality (6.8%; 95% confidence interval [CI], 0-14.5%), event-free survival (27.3%; 95% CI, 16.8-44.2%), and overall survival (50.6%; 95% CI, 37.5-68.2%) were similar to the values seen in the historical cohort. The cumulative incidence of grade II-IV acute graft-versus-host disease at 1-year was 25.1% (95% CI, 12-38.2%). On univariate analysis, the presence of monosomal or complex karyotype was adversely associated with relapse-free survival and overall survival. Given the favorable safety profile of CIK cell infusion, strategies such as repeat dosing or genetic modification merit exploration. This trial was registered at ClinicalTrials.gov (NCT01392989).
Improvements in the design of thermal-infrared radiation thermometers and sensors

A new design for thermal-infrared radiation thermometer and sensors is described. Critical optical elements, such as the field stop, Lyot stop, collimating lens, and detector, are placed inside a thermally stabilized assembly that is controlled using thermo-electric coolers and thermistors. The assembled radiation thermometer is calibrated using both variable-temperature fluid-bath and heat-pipe blackbodies from -45 °C to 75 °C and the use of a modified-Planck function and these blackbodies. The size-of-source effect both with and without the Lyot stop has been measured. This new design, during operations without the need for cryogenic cooling, demonstrates sub millikelvin temperature measurement resolution with few millikelvin, week-long stable operations while measuring room-temperature objects.
Hemimethylation of CpG dyads is characteristic of secondary DMRs associated with imprinted loci and correlates with 5-hydroxymethylcytosine at paternally methylated sequences.

In mammals, the regulation of imprinted genes is controlled by differential methylation at imprinting control regions which acquire parent of origin-specific methylation patterns during gametogenesis and retain differences in allelic methylation status throughout fertilization and subsequent somatic cell divisions. In addition, many imprinted genes acquire differential methylation during post-implantation development; these secondary differentially methylated regions appear necessary to maintain the imprinted expression state of individual genes. Despite the requirement for both types of differentially methylated sequence elements to achieve proper expression across imprinting clusters, methylation patterns are more labile at secondary differentially methylated regions. To understand the nature of this variability, we analyzed CpG dyad methylation patterns at both paternally and maternally methylated imprinted loci within multiple imprinting clusters. We determined that both paternally and maternally methylated secondary differentially methylated regions associated with imprinted genes display high levels of hemimethylation, 29–49%, in comparison to imprinting control regions which exhibited 8–12% hemimethylation. To explore how hemimethylation could arise, we assessed the differentially methylated regions for the presence of 5-hydroxymethylcytosine which could cause methylation to be lost via either passive and/or active demethylation mechanisms. We found enrichment of 5-hydroxymethylcytosine at paternally methylated secondary differentially methylated regions, but not at the maternally methylated sites we analyzed in this study. We found high levels of hemimethylation to be a generalizable characteristic of secondary differentially methylated regions associated with imprinted genes. We propose that 5-hydroxymethylcytosine enrichment may be responsible for the variability in methylation status at paternally methylated secondary differentially methylated regions associated with imprinted genes. We further suggest that the high incidence of hemimethylation at secondary differentially methylated regions must be counteracted by continuous methylation acquisition at these loci.
On implicit regularization: Morse functions and applications to matrix factorization

In this paper, we revisit implicit regularization from the ground up using notions from dynamical systems and invariant subspaces of Morse functions. The key contributions are a new criterion for implicit regularization---a leading contender to explain the generalization power of deep models such as neural networks---and a general blueprint to study it. We apply these techniques to settle a conjecture on implicit regularization in matrix factorization.
Powertrain distribution based on total cost of ownership for privately owned vehicles and TNC in the Chicago metropolitan area

From a Total Cost of Ownership (TCO) standpoint, the lowest-cost powertrain option depends on driving conditions and number of miles driven over the lifetime of the vehicle. Studies looking at the value proposition of powertrain options traditionally assess the energy consumption based on standardized drive cycles. TCO is then calculated using average yearly Vehicle Miles Travelled (VMT). This approach which looks at TCO at the aggregate level, does not take into consideration the variations in driving patterns and the spread of VMT that exist in the vehicle population. In this study, we first determine the driving pattern of each vehicle in the Chicago metropolitan area. We then consider different powertrain options for each vehicle, calculate its associated TCO and provide a powertrain distribution based on lowest TCO. Vehicles under consideration are Privately Owned Vehicles (POV) and vehicles used by Transportation Network Companies (TNC).
An mTORC1-dependent switch orchestrates the transition between mouse spermatogonial stem cells and clones of progenitor spermatogonia.

Summary Spermatogonial stem cells (SSCs) sustain spermatogenesis by balancing self-renewal and initiation of differentiation to produce progenitor spermatogonia committed to forming sperm. To define the regulatory logic among SSCs and progenitors, we performed single-cell RNA velocity analyses and validated results in vivo. A predominant quiescent SSC population spawns a small subset of cell-cycle-activated SSCs via mitogen-activated protein kinase (MAPK)/AKT signaling. Activated SSCs form early progenitors and mTORC1 inhibition drives activated SSC accumulation consistent with blockade to progenitor formation. Mechanistically, mTORC1 inhibition suppresses transcription among spermatogonia and specifically alters expression of insulin growth factor (IGF) signaling in early progenitors. Tex14−/− testes lacking intercellular bridges do not accumulate activated SSCs following mTORC1 inhibition, indicating that steady-state mTORC1 signaling drives activated SSCs to produce progenitor clones. These results are consistent with a model of SSC self-renewal dependent on interconversion between activated and quiescent SSCs, and mTORC1-dependent initiation of differentiation from SSCs to progenitor clones.
Childhood Outcomes Following Parechovirus Infections in a US Young Infant Cohort.

Background Parechovirus A type 3 (PeV-A3) is associated with central nervous system infection in young infants. There are limited data regarding long-term outcomes, mostly reported from Australia and European populations. The objective of this study was to assess frequency of neurodevelopmental impairment (NDI) following PeV-A3 infection in our US cohort. Methods Infants hospitalized during the 2014 outbreak with laboratory-confirmed PeV-A3 infection were evaluated with medical history, neurologic examination, parental completion of Ages and Stages Questionnaire and developmental assessment using Bayley Scales of Infant and Toddler Development, Third Edition cognitive, motor and language quotients. Determination of NDI was based on published criteria. Relationship of severity of PeV disease to outcome measures was determined using Fisher exact, χ2 and Mann-Whitney U test as appropriate. Results Nineteen children, term gestation, were evaluated at ~3 years of age; PeV-A3 illness was uncomplicated for 6 (32%), complex, non-neurologic for 9 (47%) and encephalitis/seizures for 4 (21%). No differences were noted in mean Bayley Scales of Infant and Toddler Development, Third Edition quotients between infants by clinical presentation. Quotients for all were within 1 SD of population norms. Two (11%) children had mild NDI; 1 with mild cerebral palsy. Ages and Stages Questionnaire results included 11% at referral level and 37% suspect concern. Parents of 6 (32%) noted behavior concerns. These findings were unrelated to severity of the PeV-A3 illness. Conclusions Parent concerns were identified frequently following infant PeV-A3 disease. Eleven percent had neurodevelopmental impairment at 3 years of age. Severity at presentation did not correlate with adverse childhood outcomes. Longitudinal developmental monitoring following infantile PeV-A3 disease is warranted.
New Dimensions of Nonprofit Responsiveness: The Application and Promise of Internet-Based Technologies

The incredible diffusion of the Internet is ushering in a new era of possibilities for nonprofit organizations to engage with and be responsive to their core stakeholders, yet little is known of the range and extent of such practices. To enhance our understanding of these increasingly important yet understudied phenomena, we conduct a comprehensive study of 117 community foundations' Web-based stakeholder responsiveness practices. Our examination of four key dimensions of online responsiveness reveals a number of best practices and areas of untapped potential. We argue that online stakeholder responsiveness is increasingly a strategic concern; to successfully fulfill their mission, organizations thus need to consider seriously the amount and interactivity of the content they target at each of their core constituents.
Dynamo and the Adiabatic Invariant

The paper considers dynamo generated by a shallow fluid layer in a celestial body (planet or star). This dynamo is based on the extra invariant for interacting magnetic Rossby waves. The magnetohydrodynamics (MHD) is linearized on the background of strong toroidal magnetic field. The extra invariant is used to show that the background field is maintained.
Optical and Electrical Properties of ITO Coated Willow Glass for Upscaling Perovskite Solar Cell Manufacturing Using Photonic Curing

Indium tin oxide (ITO) coated Willow glass is an excellent substrate for roll-to-roll manufacturing of perovskite solar cells (PSCs) but can have large variability in its optical and electrical properties. Photonic curing uses intense light pulses instead of heat to process materials and has the potential to facilitate faster processing speeds in roll-to-roll manufacturing to upscale the production of PSCs. The substrate materials’ properties play an integral role in the photonic curing outcome. Here, we present the effect of ITO transmission on the photonic curing of NiO sol-gel precursors into metal oxide and consequently the PSC performance.
Deep Generative Models in Engineering Design: A Review.

Automated design synthesis has the potential to revolutionize the modern human design process and improve access to highly optimized and customized products across countless industries. Successfully adapting generative Machine Learning to design engineering may be the key to such automated design synthesis and is a research subject of great importance. We present a review and analysis of Deep Generative Learning models in engineering design. Deep Generative Models (DGMs) typically leverage deep networks to learn from an input dataset and learn to synthesize new designs. Recently, DGMs such as Generative Adversarial Networks (GANs), Variational Autoencoders (VAEs), feedforward Neural Networks (NNs) and certain Deep Reinforcement Learning (DRL) frameworks have shown promising results in design applications like structural optimization, materials design, and shape synthesis. The prevalence of DGMs in Engineering Design has skyrocketed since 2016. Anticipating continued growth, we conduct a review of recent advances with the hope of benefitting researchers interested in DGMs for design. We structure our review as an exposition of the algorithms, datasets, representation methods, and applications commonly used in the current literature. In particular, we discuss key works that have introduced new techniques and methods in DGMs, successfully applied DGMs to a design-related domain, or directly supported development of DGMs through datasets or auxiliary methods. We further identify key challenges and limitations currently seen in DGMs across design fields, such as design creativity, handling complex constraints and objectives, and modeling both form and functional performance simultaneously. In our discussion we identify possible solution pathways as key areas on which to target future work.
Myosin purification and characterization.

Publisher Summary This chapter describes and evaluates the methods for purifying and characterizing myosin from muscle and nonmuscle cells. Myosin is an energy-transducing enzyme responsible for muscle contraction. During its interaction with actin, myosin converts the chemical energy stored in adenosine triphosphate (ATP) into mechanical force. Myosin is also the only energy-transducing enzyme known to participate in cytoplasmic streaming and contractility. Various procedures are described in the chapter, and a few examples of how they can be combined to purify myosin are given. The first prerequisite in the purification of any protein is reliable, simple assays. The rationale for this approach is that myosins from various cells differ sufficiently that no single procedure is generally useful for myosin purification. However, a suitable combination of the procedures now available makes it possible to purify any myosin type. During the characterization of a new myosin, it is usually essential to examine the structure of myosin filaments and of the complex of myosin with actin filaments. Extraction of myosin from the cell requires lysis of the cell into a buffer that solubilizes myosin. Three general types of extracting solutions have been used to solubilize myosin: high ionic strength, sucrose, or pyrophosphate buffers. Precipitation of the specific combination of myosin filaments with actin filaments is one of the original methods for purifying myosin.
A Contralateral Esophagus-Sparing Technique to Limit Severe Esophagitis Associated With Concurrent High-Dose Radiation and Chemotherapy in Patients With Thoracic Malignancies

Purpose Severe (Radiation Therapy Oncology Group [RTOG] grade 3 or greater) esophagitis generally occurs in 15% to 25% of non–small cell lung cancer (NSCLC) patients undergoing concurrent chemotherapy and radiation therapy (CCRT), which may result in treatment breaks that compromise local tumor control and pose a barrier to dose escalation. Here, we report a novel contralateral esophagus-sparing technique (CEST) that uses intensity modulated radiation therapy (IMRT) to reduce the incidence of severe esophagitis. Methods and Materials We reviewed consecutive patients with thoracic malignancies undergoing curative CCRT in whom CEST was used. The esophageal wall contralateral (CE) to the tumor was contoured as an avoidance structure, and IMRT was used to guide a rapid dose falloff gradient beyond the target volume in close proximity to the esophagus. Esophagitis was recorded based on the RTOG acute toxicity grading system. Results We identified 20 consecutive patients treated with CCRT of at least 63 Gy in whom there was gross tumor within 1 cm of the esophagus. The median radiation dose was 70.2 Gy (range, 63-72.15 Gy). In all patients, ≥99% of the planning and internal target volumes was covered by ≥90% and 100% of prescription dose, respectively. Strikingly, no patient experienced grade ≥3 esophagitis (95% confidence limits, 0%-16%) despite the high total doses delivered. The median maximum dose, V45, and V55 of the CE were 60.7 Gy, 2.1 cc, and 0.4 cc, respectively, indicating effective esophagus cross-section sparing by CEST. Conclusion We report a simple yet effective method to avoid exposing the entire esophagus cross-section to high doses. By using proposed CE dose constraints of V45