cssi/SciSciGPT-SciSciNet huggingface dataset:
Eteplirsen for the treatment of Duchenne muscular dystrophy: Quality of evidence concerns – An alternative viewpoint

We read the paper by Reinig AM and colleagues entitled “Advances in the Treatment of Duchenne Muscular Dystrophy: New and Emerging Pharmacotherapies” with great interest.1 The authors discuss several novel therapies to increase production of dystrophin in myocytes, of which, eteplirsen (Exondys) is the only currently approved by the US Food & Drug Administration (FDA).2 Pharmacologic management of Duchenne muscular dystrophy (DMD) centers on the use of glucocorticoids which works by decreasing inflammation and reducing immune system activity. Steroid therapy only slows disease progression and therefore, there is a clear need for additional therapeutic options.3 This article is protected by copyright. All rights reserved.
Speciation in Metapopulations

Publisher Summary This chapter expands the previous approaches to speciation in metapopulation by developing a model incorporating multiple genetic loci underlying reproductive isolation and species differences. It starts by describing an approach for modeling speciation that is based on the classical Bateson–Dobzhansky–Muller (BDM) model. Then, this approach is incorporated into the metapopulation framework. The resulting model allows one to study the dynamics of both the overall diversity and the genetic structure of the system of populations undergoing radiation.
Improved threshold selection for the determination of volume of distribution of nanoparticles administered by convection-enhanced delivery

Abstract Nanotechnology, in conjunction with convection-enhanced delivery (CED), has gained traction as a promising method to treat many debilitating neurological diseases, including gliomas. One of the key parameters to evaluate the effectiveness of delivery is the volume of distribution (V d ) of nanoparticles within the brain parenchyma. Measurements of V d are commonly made using fluorescent reporter systems. However, reported analyses lack accurate and robust methods for determining V d . Current methods face the problems of varying background intensities between images, high intensity aggregates that can shift intensity distributions, and faint residual backgrounds that can occur as artifacts of fluorescent imaging. These problems can cause inaccurate results to be reported when a percentage of the maximum intensity is set as the threshold value. Here we show an implementation of Otsu’s method more reliably selects accurate threshold values than the fixed-threshold method. We also introduce a goodness of fit value η that quantifies the appropriateness of using Otsu’s method to calculate V d . Adoption of Otsu’s method and reporting of η may help standardize fluorescent image analysis of nanoparticles administered by convection-enhanced delivery.
Ultrastructural imaging of cell fusion in Caenorhabditis elegans

Caenorhabditis elegans is a well-established model system particularly suited for studying cell-cell fusion because of its highly predictable and rapid development and its known cell lineage. This chapter focuses on understanding the ultrastructural components of cell fusion through the use of transmission electron microscopy (TEM). Published TEM studies have described the initial demonstration of syncytial cells in the worm, the vesiculation of the bilayers between cells during widening of the normal fusion aperture, and the appearance of microfusion intermediates in the membranes of cells with fusion-defective mutations. Capturing events observed in embryos on the light microscope and preserving the integrity of cellular membranes for examination by TEM require some special considerations that differ from many ultrastructural studies of cells. The principles of different techniques for TEM and details of protocols that have been used to investigate cell fusion in the nematode are discussed in this chapter.
Dietary Glycation Products Regulate Immune Homeostasis: Early Glycation Products Promote Prostate Cancer Cell Proliferation through Modulating Macrophages.

cope : Well-controlled glycation (generally limited to the early stages) has been proposed as a strategy to improve the physiochemical properties of dietary proteins, but the functional studies of glycation products were mostly on advanced glycation end-products (AGEs) rather than early glycation products (EGPs). Since cytokines are important modulators of various biological processes, this study aimed to determine whether EGPs and AGEs affected immune homeostasis differentially and did so through modulating macrophage-derived factors. Methods and results : Two systems (glycine-glucose and whey protein isolate (WPI)-glucose) were established to generate glycation products. They were applied to human macrophages (PMA-differentiated U937 cells), and cell viability and cytokine production were measured. Furthermore, EGPs, AGEs and their conditioned medium (CM) from macrophages were applied to human prostate cancer (PCa) cells with different etiology (LNCaP and PC-3) and murine PCa cells (TRAMP-C2) to determine their direct and indirect effects on PCa cell proliferation. EGPs enhanced the production of anti-inflammatory and immunosuppressive cytokines, and this enhancement was associated with increased PCa cell proliferation. In contrast, AGEs inhibited macrophages to secret cytokines, but increased PCa cell proliferation directly. Conclusions : Our data suggest that EGPs promote the prostate tumor proliferation indirectly through modulating macrophages, while AGEs have a direct effect. This article is protected by copyright. All rights reserved
DNA sequencing at ultra-high fidelity

Built-in error-correction and novel fluorogenic chemistry open a path to perfect read quality.
Strength of silver brazed joints in mild steel

An investigation was made of the dependence of the strength of silver brazed, low carbon steel joints on the geometry of the joint. The experimental results indicate that for cylindrical test specimens having transverse brazed joints, the ultimate tensile strength is really a linear function of the thickness to diameter ratio rather than only of the thickness of the filler metal for constant specimen diameter.
Opportunities for Computer Support for Systematic Reviewing - A Gap Analysis

Systematic review is a type of literature review designed to synthesize all available evidence on a given question. Systematic reviews require significant time and effort, which has led to the continuing development of computer support. This paper seeks to identify the gaps and opportunities for computer support. By interviewing experienced systematic reviewers from diverse fields, we identify the technical problems and challenges reviewers face in conducting a systematic review and their current uses of computer support. We propose potential research directions for how computer support could help to speed the systematic review process while retaining or improving review quality.
A Compass at Weak Magnetic Fields Using Thymine Dimer Repair

How birds sense the variations in Earth’s magnetic field for navigation is poorly understood, although cryptochromes, proteins homologous to photolyases, have been proposed to participate in this magnetic sensing. Here, in electrochemical studies with an applied magnetic field, we monitor the repair of cyclobutane pyrimidine dimer lesions in duplex DNA by photolyase, mutants of photolyase, and a modified cryptochrome. We find that the yield of dimer repair is dependent on the strength and angle of the applied magnetic field even when using magnetic fields weaker than 1 gauss. This high sensitivity to weak magnetic fields depends upon a fast radical pair reaction on the thymines leading to repair. These data illustrate chemically how cyclobutane pyrimidine dimer repair may be used in a biological compass informed by variations in Earth’s magnetic field.
Development of a standard data structure for wastewater pipe performance management

The accurate prediction of wastewater pipe structural and functional deterioration plays an essential role in the utility asset management process and capital investment planning. The limitations of deterioration prediction capabilities are in the lack of accurate and consistent performance data, or not well-understood interdependencies of the pipeline performance parameters. Thus, the primary objective of this paper is to develop a standard data structure to support the performance prediction of wastewater pipe remaining life. This paper presents the life cycle, failure modes and mechanisms, and data structure of wastewater pipe that has been completed with results from intensive literature reviews, various interviews with utilities, consultants, and pipe associations. In this research, the authors investigated the lifecycle of wastewater pipes, identifying the causes of pipe failure in different phases, including design, manufacture, construction, operation and maintenance, and repair/rehabilitation/replacement. The data structure was classified into gold, silver, bronze, and wood standards.
Risk and risk aversion effects in contests with contingent payments

Contests by their very nature involve risk, winning and losing are both possible, and the gain from winning can itself be uncertain. The participants in a contest use resources to increase their chance of winning. The main focus of this analysis is on the effects of risk aversion and risk in contests where only winners pay for resources used to compete. When payment is contingent on winning, the effect of risk aversion is in the opposite direction of what occurs when costs are paid by both winners and losers. A number of contests observed in the marketplace that exhibit this contingent payment property are discussed.
Collagen shields as a vehicle for collecting and studying migratory cells on human corneas.

Collagen shields have been studied in the enhancement of the initial healing of epithelial defects, as an adjunct in the treatment of dry eye, and as a reservoir and delivery system for topical ocular medications. The authors used collagen shields to collect information on the numbers and types of free cells populating the normal and postoperative ocular surface. In addition, correlative microscopic techniques were used to study details of the mechanisms responsible for the dissolution of the shields when applied to the human eye. Collagen shields were applied as a bandage lens on the eyes of patients who underwent extracapsular cataract extraction (n = 10) or penetrating keratoplasty (n = 10) and on normal volunteers (n = 10). The shields were collected at the 1-day postoperative examination and fixed in aldehyde mixtures. Specimens then were processed for correlative light (LM), transmission (TEM), and scanning (SEM) microscopy. Cell accumulation was shown by SEM on both anterior and posterior shield surfaces. Cell adherence occurred primarily on the posterior shield periphery for approximately 2 mm, with the central zone relatively clean. Both LM and TEM evaluation revealed cell counts ranging from 0.066 cells/10 4 nm 2 (standard deviation, ± 0.256) in healthy eyes compared with shields placed on postoperative eyes (194.25 ± 7,32 cells/10 4 Mm 2 ). Various correlative microscopy techniques revealed that most cells were polymorphonuclear leukocytes with a low number of other hematogenous (lymphocytes and monocytes) and exfoliated epithelial cells. The ability of collagen shields to serve as a substrate for cellular accumulation may allow them to serve as a device for studying the dynamics of migratory cells on the ocular surfaces of healthy and inflamed eyes. It may also aid in documenting the role these cells play in the dissolution of the shields. Invest Ophthalmol Vis Sci 33:298-303,1992
Using subsurface flow barriers to reduce nitrate leaching

The relative effectiveness of different types of subsurface barriers on delaying and reducing anion leaching was examined using repacked soil columns. Further, the effect of the size of a barrier against chloride leaching was Investigated. All of the barriers tested delayed the Initial breakthrough of chloride and/or reduced the peak chloride concentration compared with the no-barrier case. Further, the emergence of the peak concentration was delayed when subsurface barriers were used Indicating that subsurface barriers prolonged the resident time of chloride In the soil column. Among subsurface barriers used, a compacted soil layer above the applied chloride was most effective on delaying and reducing chloride leaching. The initial breakthrough of chloride was delayed by 0.9 relative pore volumes and the peak concentration was reduced by more than 50% compared with the no-barrler case. The appearance of the peak concentration was delayed by 1.2 relative pore volumes compared with the no-barrier case. A 3-cm plastic disc, just large enough to cover the area with applied chloride reduced the peak concentration of chloride compared with the no-barrier case. A 5-cm diameter barrier, which had only an extra 2-cm cover to the applied chloride, started delaying the initial breakthrough of chloride and reduced the peak concentration by 40% compared with the no-barrier case. The emergence of the peak was also delayed by 0.6 relative pore volumes.
Internet futures

This paper describes the architectural principles and drivers behind the Internet protocol suite and identifies the fundamental differences when compared to the historical telco approach. The major Internet protocol enhancements of multicast routeing and quality of service (QoS) are then described and briefly compared to the related and developing solutions in the ITU and ATM forum. Finally, two major interworking scenarios are discussed for the Internet. The first outlines some of the fundamental architectural issues being addressed for the development of ATM within the internetworking paradigm. The second considers opportunities for the sharing of intelligence and data with the intelligent network.
Minimum-Margin Active Learning.

We present a new active sampling method we call min-margin which trains multiple learners on bootstrap samples and then chooses the examples to label based on the candidates' minimum margin amongst the bootstrapped models. This extends standard margin sampling in a way that increases its diversity in a supervised manner as it arises from the model uncertainty. We focus on the one-shot batch active learning setting, and show theoretically and through extensive experiments on a broad set of problems that min-margin outperforms other methods, particularly as batch size grows.
Opportunistic UAV Navigation With Carrier Phase Measurements From Asynchronous Cellular Signals

This article presents a framework for opportunistic unmanned aerial vehicle (UAV) navigation by exploiting carrier phase measurements from ambient cellular signals of opportunity. In the proposed framework, the cellular base transceiver stations (BTSs) are not assumed to be synchronous. A complete framework that employs an extended Kalman filter (EKF) is presented, including filter initialization and process and measurement noise covariance selection. The EKF estimates the position and velocity of the UAV, as well as the differences between the UAV-mounted receiver and each of the BTSs’ clock bias and clock drift. The observability of the estimation framework is analyzed, and the boundedness of the EKF's errors is studied. It is shown that the system is observable given a class of vehicle and receiver clock dynamics. A lower bound for the EKF estimation error covariance is derived, and it is shown that the covariance remains bounded. Monte Carlo simulations are conducted to study the effect of the number of BTSs, the initial UAV speed, and the receiver's oscillator quality, on the estimation performance. Two sets of experimental results are presented demonstrating UAVs navigating exclusively with cellular carrier phase measurements via the developed framework, achieving a total position root-mean-squared error of 2.94 and 5.99 m for UAV trajectories of 2.6 and 2.9 km, respectively.
What Is a Hybrid Regime

After decades of proliferation of democracy around the world as a part of the ‘Third Wave’, by the early 2000s, the democratization process stalled in many countries and a new form of governance emerged in some countries either by choice or by default. This new form, while having some democratic institutions, is essentially authoritarian in its nature. It became evident to researchers that these regimes are not in transition. They are neither subtypes of autocracy nor of democracy, but instead are a regime type of their own. They are called hybrid regimes. This chapter traces the emergence of the concept of hybrid regime, explores its defining features, and examines the spread of such regimes around the world.
Abandoning questions with unpredictable answers

This study investigated the types of questions that prospective teachers of mathematics asked their students during whole-class discussions, how these questions changed over time, and why. Four prospective teachers were interviewed at the beginning and end of a 10-week period of student teaching to elicit their views about the kinds of questions mathematics teachers should ask. One lesson per week, for eight lessons, was video recorded for each prospective teacher. These videos were analyzed for the kinds of questions the prospective teachers asked and the nature of the responses from their high-school students. We found that the prospective teachers initially expressed the view that it was important to ask questions that required students to explain their thinking—a view that aligned with what was promoted in their teacher-preparation program—and that they attempted to ask questions with unpredictable answers in the early weeks. Over time, however, they asked fewer questions overall, with an even greater reduction in the number of questions with unpredictable answers. Interviews revealed that the prospective teachers’ views about what kinds of questions to ask were influenced, over time, by the responses of their students. The videos offered additional insights into the nature of the students’ responses.
The anti-parasitic agent suramin and several of its analogues are inhibitors of the DNA binding protein Mcm10

Minichromosome maintenance protein 10 (Mcm10) is essential for DNA unwinding by the replisome during S phase. It is emerging as a promising anti-cancer target as MCM10 expression correlates with tumour progression and poor clinical outcomes. Here we used a competition-based fluorescence polarization (FP) high-throughput screening (HTS) strategy to identify compounds that inhibit Mcm10 from binding to DNA. Of the five active compounds identified, only the anti-parasitic agent suramin exhibited a dose-dependent decrease in replication products in an in vitro replication assay. Structure-activity relationship evaluation identified several suramin analogues that inhibited ssDNA binding by the human Mcm10 internal domain and full-length Xenopus Mcm10, including analogues that are selective for Mcm10 over human RPA. Binding of suramin analogues to Mcm10 was confirmed by surface plasmon resonance (SPR). SPR and FP affinity determinations were highly correlated, with a similar rank between affinity and potency for killing colon cancer cells. Suramin analogue NF157 had the highest human Mcm10 binding affinity (FP Ki 170 nM, SPR KD 460 nM) and cell activity (IC50 38 µM). Suramin and its analogues are the first identified inhibitors of Mcm10 and probably block DNA binding by mimicking the DNA sugar phosphate backbone due to their extended, polysulfated anionic structures.
EMI Sensing for Underwater Metallic Targets Detection and Classification

Electromagnetic induction (EMI) sensing phenomenon are investigated for a conducting and multilayer environment to aid in underwater unexploded ordnance (UXO) detection and classification. The marine environment introduces complexities, such salinity gradient, sharp conductivity changes at air-water-sediment etc., which adversely can affect targets EMI signals and make underwater targets classification more difficult problem than classifying the same buried targets on land. The sensitivity of a secondary EMI signal with respect the water/air and/or water/sediment boundaries and temporal (diffusive EM field propagation speed) variability of EMI fields in an underwater (UW) environment are studied and demonstrated using the unconditionally stable Crank-Nicolson finite different time domain method (FDTD).
Modulation of Bacterial Quorum Sensing by Eukaryotes

Bacterial quorum sensing (QS) mediated by small chemical signaling molecules is an important phenomenon that helps bacterial populations to synchronize and regulate their key cellular functions. Important to this behavior is employment of often unique signaling molecules that are recognized and bound by dedicated cognate receptors that result in modulation of gene expression. Well-documented examples are those of gram-negative bacterial N-acyl homoserine lactone (AHL) QS signaling pathways. The ability to disrupt or alter bacterial communication using signal analogues (agonist and antagonist) and other signal disruption mechanisms offers selective advantage to competitors and coinhabitants that share the environment with the bacterium. Such mechanisms are often found pervasive in both bacterial genre and higher eukaryotic hosts. Examples include employment of small molecular signals that target QS signaling and/or enzymes that inactivate QS signals. This report aims to highlight well-documented key mechanisms adapted by eukaryotes such as algae, fungi, plants, and animals both to sense bacterial QS signals and to employ bacterial QS modulators to regulate interkingdom interactions such as symbiosis, altered biofilm production, pathogenesis, etc. This knowledge could pave ways for developing nature-inspired non-antibiotic drugs, antifouling agents, and other bacterial fitness disruptor drugs that potentially bypasses bacterial drug resistance mechanisms, providing longer-term solutions for bacterial disease control.
GENVISAGE: Rapid Identification of Discriminative and Explainable Feature Pairs for Genomic Analysis

Motivation. A common but critical task in genomic data analysis is finding features that separate and thereby help explain differences between two classes of biological objects, e.g., genes that explain the differences between healthy and diseased patients. As lower-cost, high-throughput experimental methods greatly increase the number of samples that are assayed as objects for analysis, computational methods are needed to quickly provide insights into high-dimensional datasets with tens of thousands of objects and features. Results . We develop an interactive exploration tool called G ENVISAGE that rapidly discovers the most discriminative feature pairs that best separate two classes in a dataset, and displays the corresponding visualizations. Since quickly finding top feature pairs is computationally challenging, especially when the numbers of objects and features are large, we propose a suite of optimizations to make G ENVISAGE more responsive and demonstrate that our optimizations lead to a 400X speedup over competitive baselines for multiple biological data sets. With this speedup, G ENVISAGE enables the exploration of more large-scale datasets and alternate hypotheses in an interactive and interpretable fashion. We apply G ENVISAGE to uncover pairs of genes whose transcriptomic responses significantly discriminate treatments of several chemotherapy drugs. Availability. Free webserver at http://genvisage.knoweng.org:443/ with source code at https://github.com/KnowEnG/Genvisage
Electroconvulsive Therapy Pulse Amplitude and Clinical Outcomes.

ABSTRACT Introduction Electroconvulsive therapy (ECT) pulse amplitude, which determines the induced electric field magnitude in the brain, is currently set at 800–900 milliamperes (mA) on modern ECT devices without any clinical or scientific rationale. The present study assessed differences in depression and cognitive outcomes for three different pulse amplitudes during an acute ECT series. We hypothesized that the lower amplitudes would maintain the antidepressant efficacy of the standard treatment and reduce the risk of neurocognitive impairment. Methods This double-blind investigation randomized subjects to three treatment arms: 600, 700, and 800 mA (active comparator). Clinical, cognitive, and imaging assessments were conducted pre-, mid- and post-ECT. Subjects had a diagnosis of major depressive disorder, age range between 50 and 80 years, and met clinical indication for ECT. Results The 700 and 800 mA arms had improvement in depression outcomes relative to the 600 mA arm. The amplitude groups showed no differences in the primary cognitive outcome variable, the Hopkins Verbal Learning Test-Revised (HVLT-R) retention raw score. However, secondary cognitive outcomes such as the Delis Kaplan Executive Function System Letter and Category Fluency measures demonstrated cognitive impairment in the 800 mA arm. Discussion The results demonstrated a dissociation of depression (higher amplitudes better) and cognitive (lower amplitudes better) related outcomes. Future work is warranted to elucidate the relationship between amplitude, electric field, neuroplasticity, and clinical outcomes.
Accidental Feminism: Gender Parity and Selective Mobility among India’s Professional Elite

In India, elite law firms offer a surprising oasis for women within a hostile, predominantly male industry. Less than 10 percent of the country’s lawyers are female, but women in the most prestigious firms are significantly represented both at entry and partnership. Elite workspaces are notorious for being unfriendly to new actors, so what allows for aberration in certain workspaces? Drawing from observations and interviews with more than 130 elite professionals, Accidental Feminism examines how a range of underlying mechanisms—gendered socialization and essentialism, family structures and dynamics, and firm and regulatory histories—afford certain professionals egalitarian outcomes that are not available to their local and global peers. Juxtaposing findings on the legal profession with those on elite consulting firms, Swethaa Ballakrishnen reveals that parity arises not from a commitment to create feminist organizations, but from structural factors that incidentally come together to do gender differently. Simultaneously, their research offers notes of caution: while conditional convergence may create equality in ways that more targeted endeavors fail to achieve, “accidental” developments are hard to replicate, and are, in this case, buttressed by embedded inequalities. Ballakrishnen examines whether gender parity produced without institutional sanction should still be considered feminist. In offering new ways to think about equality movements and outcomes, Accidental Feminism forces readers to critically consider the work of intention in progress narratives. [enter Abstract Body]
Statistical shape modeling of the pelvic floor to evaluate women with obstructed defecation symptoms.

Obstructed defecation (OD) is common and may be related to compromised pelvic floor integrity. Magnetic resonance (MR) defecography and statistical shape modeling were used to define pelvic floor s...
Choices in networks: a research framework

Networks are ubiquitous in life, structuring options available for choice and influencing their relative attractiveness. In this article, we propose an integration of network science and choice theory beyond merely incorporating metrics from one area into models of the other. We posit a typology and framework for “network-choice models” that highlight the distinct ways choices occur in and influence networked environments, as well as two specific feedback processes that guide their mutual interaction, emergent valuation and contingent options. In so doing, we discuss examples, data sources, methodological challenges, anticipated benefits, and research pathways to fully interweave network and choice models.
Extracellular Matrix Enterocutaneous Fistula Plugs Show Promise for Low-Flow Colocutaneous and Enterocutaneous Fistulae

Abstract Purpose To evaluate extracellular matrix enterocutaneous fistula plugs (ECMFPs) in treatment of enteric fistulae at a single institution. Materials and Methods The study included 18 patients who had an ECMFP placed between 2012 and 2018 with treatment follow-up through July 2020. Median patient age was 52.5 years (interquartile range, 11.5 y). There were 28 ECMFP procedures performed on 19 separate fistulae. Fistulae locations were gastrocutaneous (n = 4), enterocutaneous (n = 9), and colocutaneous (n = 6). Descriptive statistics were used to define closure rates, recurrence rates, and complications. Results Fistula closure was achieved in 1 of 4 gastrocutaneous (25%), 4 of 9 enterocutaneous (44%), and 3 of 6 colocutaneous (50%) locations. The median time from procedure to fistula tract closure was 29 days interquartile range 25 days. The median time from ECMFP placement to fistula recurrence was 28 days (interquartile range 27 days). Of the fistulae that eventually closed, 6 of 8 closed after the first attempt (75%), and 2 closed after the second attempt (25%). Of the procedures that resulted in complete closure, 7 of 8 were categorized as low flow, and 1 of 8 was categorized as high flow. Complications were seen in 4 patients (23%), with major complications in 3 patients (17%). Conclusions Low-flow fistulae originating from the small bowel are most likely to have complete closure. High-flow and/or gastrocutaneous fistulae are less likely to benefit from this intervention. In patients who are not surgical candidates or who have failed surgical management, ECMFPs may provide a solution.
Supply and Demand Risks in Laboratory Forward and Spot Markets: Implications for Agriculture

Laboratory experimental methods are used to investigate the impacts of supply and/or demand risks on prices, quantities traded, and earnings within forward and spot market institutions. Random demand and/or supply shifts can be as much as 25 percent of the expected equilibrium outcome. Nevertheless, results suggest that the spot or forward trading institution itself has a greater influence on market outcomes than the presence of risk within the trading institution. Sellers tend to have relatively higher earnings in a spot market than buyers, regardless of the risk. Total surplus, however, generally is greater in a forward market. Key Words: Laboratory Markets, Forward Market, Spot Mmarket, Supply and/or Demand Risks
Variable-Switching Constant-Sampling Frequency Critical Soft Switching MPC for DC/DC Converters

A variable-switching constant-sampling frequency critical soft switching model predictive control (VSCS-MPC) method is proposed in this paper to improve the dynamic behavior, efficiency and power density of the DC/DC power converters. Firstly, this paper analyzes the boundary constraints of critical soft switching that are derived with the key parameters of the interlock time and threshold current for typical SiC and GaN devices. Then, the VSCS-MPC method is proposed for synchronous DC/DC converter. Both the current source load and resistive load converters are validated with the proposed MPC method. VSCS-MPC includes two controlling parts. First is the frequency controller to maintain the critical soft switching operation by adjusting the switching frequency based on the pre-defined boundary conditions with a constant sampling frequency. A discretized frequency controller is developed to improve the stability of the system by maintaining a fixed sampling frequency. Second part is the model predictive controller to track the output voltage/current and maintain critical soft switching during dynamic periods. The explicit optimization and oversampling methods are applied in the MPC controller to meet the high frequency demand. A large current ripple ( $\triangle i_L$ $\ge$ 200 %) is introduced to achieve the critical soft switching and reduce the inductance. The switching losses are decreased by the frequency controller and the critical soft switching is maintained especially in dynamic periods due to the fast response of MPC.
Multiple causal DNA variants in a single gene affect gene expression in trans

Abstract Identifying the specific causal DNA differences in a genome that contribute to variation in phenotypic traits is a key goal of genetic research. Trans-acting DNA variants that alter gene expression are important sources of genetic variation. Several genes are known to carry single causal variants that affect the expression of numerous genes in trans. Whether these single variants are representative of the architecture of trans-acting variation is unknown. Here, we studied the gene IRA2, which carries variants with broad, trans-acting effects on gene expression in two strains of the yeast Saccharomyces cerevisiae. We found that IRA2 contains at least seven causal nonsynonymous variants. The causal variants were located throughout the gene body and included a pair of neighboring variants with opposing effects that largely canceled each other out. The causal variants showed evidence for non-additive epistatic interactions, in particular among variants at the 5’ end of the gene. These results show that the molecular basis of trans-acting variation can involve considerable complexity even within a single gene.
Breaking the Privacy Gridlock: A Broader Look at Remedies

Divisions over two enforcement issues—private right of action and federal preemption—have long gridlocked the effort to enact federal consumer privacy legislation. A look at regulatory systems outside the privacy field, however, reveals a complex landscape of enforcement mechanisms and remedies, many of which have not yet received much attention in the privacy debate. Insights from financial services regulation, environmental law, labor law, and other fields may offer ideas for assembling an effective web of enforcement for a federal privacy law. In November 2020, we convened two workshops bringing together scholars from fields other than privacy to describe the enforcement and remedies structures in those other fields. In this paper, we offer some insights drawn from those workshops and further research, in the hope that they will generate creative thinking and expand the scope of the remedies and enforcement discussion in the privacy arena.
Cosa Nostra in the YouTube Comment Section: Visions of Tommaso Buscetta, the Mafia, and Italian History

When Tommaso Buscetta broke omerta in 1984 (only a decade after politicians were claiming that the mafia did not exist), one of his first statements in his depositions directly related to media dep...
SURREAL PLAY EXPERIENCE FOR TEACHING SALES: LEARNING HOW TO ASK THE RIGHT QUESTIONS

We introduce the surreal play experience (SPE) as an effective pedagogical method of experiential learning for teaching professional sales. Using a customer’s needs assessment as a skill to develop...
Huntington’s Disease: Anti-Neurotoxic Therapeutic Strategies

The dual roles of glutamate as excitatory neurotransmitter and potential neurotoxin have prompted anti-neurotoxic therapeutic strategies aimed at slowing the neuronal degeneration and clinical decline of Huntington’s disease. It is proposed that long-term pharmacologic attenuation of glutamatergic corticostriatal function in patients with Huntington’s disease will prevent or postpone the clinical and radiographic correlates of neuronal death. Baclofen, a drug which preferentially blocks the neuronal release of excitatory amino acids, is undergoing systematic evaluation in an effort to test this supposition.
Quantitative fluorescence nanoscopy for cancer biomedicine

Cancer is a major health threat worldwide. Options for targeted cancer therapy, however, are often limited, in a large part due to our incomplete understanding of how key processes including oncogenesis and drug response are mediated at the molecular level. New imaging techniques for visualizing biomolecules and their interactions at the nanometer and single molecule scales, collectively named fluorescence nanoscopy, hold the promise to transform biomedical research by providing direct mechanistic insight into cellular processes. We discuss the principles of quantitative single-molecule localization microscopy (SMLM), a subset of fluorescence nanoscopy, and their applications to cancer biomedicine. In particular, we will examine oncogenesis and drug resistance mediated by mutant Ras, which is associated with ~1/3 of all human cancers but has remained an intractable drug target. At ~20 nm spatial and single-molecule stoichiometric resolutions, SMLM clearly showed that mutant Ras must form dimers to activate its effector pathways and drive oncogenesis. SMLM further showed that the Raf kinase, one of the most important effectors of Ras, also forms dimers upon activation by Ras. Moreover, treatment of cells expressing wild type Raf with Raf inhibitors induces Raf dimer formation in a manner dependent on Ras dimerization. Together, these data suggest that Ras dimers mediate oncogenesis and drug resistance in tumors with hyperactive Ras and can potentially be targeted for cancer therapy. We also discuss recent advances in SMLM that enable simultaneous imaging of multiple biomolecules and their interactions at the nanoscale. Our work demonstrates the power of quantitative SMLM in cancer biomedicine.
Numerical Investigation of Transition in a Flared Cone Boundary Layer at Mach 6

Abstract Laminar–turbulent transition is investigated for a flared cone at Mach 6 using spatial Direct Numerical Simulations (DNS). The flow parameters used in the simulations discussed here closely match the laboratory conditions of the hypersonic transition ex- periments conducted at Purdue University. The objective of the present research is to make a contribution towards understanding of the nonlinear stages of transition in hypersonic boundary layers on a flared cone. Towards this end, the role of second–mode fundamental (K-type) and oblique breakdown is investigated using controlled transition simulations. For fundamental resonance, the parameter space was first explored by performing several low-resolution simulations in order to identify the cases that result in the strongest nonlinear interactions. Subsequently, a set of highly resolved fundamental and oblique breakdown simulations have been performed and the results are presented in this paper. Both fundamental and oblique breakdown lead to strong nonlinear interactions and were thus found to be viable candidates of nonlinear mechanisms that can lead to a fully turbulent boundary layer. The nonlinear interactions observed during these breakdown processes are discussed in detail. A detailed description of the flow structures that arise due to these nonlinear interactions is provided and the development of the skin friction and heat transfer during the breakdown is presented.
On the effects of thermally weakened ductile shear zones on postseismic deformation

[1] We present three-dimensional (3-D) numerical models of postseismic deformation following repeated earthquakes on a vertical strike-slip fault. Our models use linear Maxwell, Burgers, and temperature-dependent power law rheology for the lower crust and upper mantle. We consider effects of viscous shear zones that result from thermomechanical coupling and investigate potential kinematic similarities between viscoelastic models incorporating shear zones and elastic models incorporating rate-strengthening friction on a deep aseismic fault root. We find that the thermally activated shear zones have little effect on postseismic relaxation. In particular, the presence of shear zones does not change the polarity of vertical displacements in cases of rheologies that are able to generate robust postseismic transients. Stronger rheologies can give rise to an opposite polarity of vertical displacements, but the amplitude of the predicted transient deformation is generally negligible. We conclude that additional (to thermomechanical coupling) mechanisms of strain localization are required for a viscoelastic model to produce a vertical deformation pattern similar to that due to afterslip on a deep extension of a fault. We also investigate the discriminating power of models incorporating Burgers and power law rheology. These rheologies were proposed to explain postseismic transients following large (M7) earthquakes in the Mojave desert, Eastern California. Numerical simulations indicate that it may be difficult to distinguish between these rheologies even with high-quality geodetic observations for observation periods less than a decade. Longer observations, however, may potentially allow discrimination between the competing models, as illustrated by the model comparisons with available GPS and interferometric synthetic aperture radar data.
Abstract P032: Wine Consumption and Cognitive Function

Background: Regular modest wine consumption may be linked favorably or adversely to cognition. Goal: To assess the cross-sectional relation between wine consumption frequency ( WineF ) & cognitive indices. Method: Of 1018 adults age 20-85 without CVD or DM, 945 completed a food frequency questionnaire eliciting WineF. Frequency was of interest, since frequency of a food with antioxidant effects previously related favorably to cognitive indices in younger adults. Cognitive tests included grooved pegboard (time), Trails A & B (time), digit symbol, Elithorn mazes, Stroop color word. Memory and attention tests included digit span and recurrent words; and digit vigilance. (Table legend shows coding). Regression (robust standard errors) assessed how WineF predicted cognitive performance. Since two prior dietary predictors showed age-dependency in relation to cognition (selectively evident in younger adults), assessment included age-stratified analysis. Covariates adjusted were known cognitive predictors (per this sample and/or the literature): age, sex, education, exercise, diet variables linked to cognition in this sample, and metabolic variables (glucose, LDL, systolic blood pressure), recognizing that adjustment for the latter could attenuate associations if these variables are mediating. Results: More frequent WineF predicted significantly better performance, in younger adults and often in the full sample, for the tests shown in the Table (fully adjusted model). These tests involved timed performance and/or constructs such as executive function. WineF did not relate significantly to the tests above of memory or attention (data not shown). Limitations: Alcohol bears risks and findings are observational. Heavy drinkers were poorly represented and findings need not apply to them. Conclusion: More frequent WineF in a study sample (with few heavy wine drinkers) was favorably linked to performance on cognitive tests related to timed performance and executive function, particularly in younger adults.
The pH Dependence of the Steady State Kinetic Parameters for Staphylococcal Nuclease-catalyzed Hydrolysis of Deoxythymidine-3'-phosphate-5'-p-nitrophenylphosphate in H2O and D2O

Abstract Initial velocity studies over the pH range 7.5 to 10.5 have been utilized to derive kinetic constants for the hydrolysis of deoxythymidine-3'-phosphate-5'-p-nitrophenylphosphate catalyzed by staphylococcal nuclease. A pronounced decline in reaction rate at high substrate concentration has been attributed to multiple binding of the substrate to the enzyme. The pH dependence of the parameters κ2 and Km has been employed to derive kinetically apparent ionization constants for the processes of binding and reaction. This analysis also yielded the pH-independent kinetic constants κ2 in water and deuterium oxide with the ratio κ2h2o/κ2d2o = 0.95. The relationship of these data to the possible mechanism of catalysis has been considered.
Review: Higher vitamin D status and supplementation may be associated with risks

The prevalence of low vitamin D levels and associated risks has led to an increase in supplementation. However, a “U-shaped” relationship has been suggested between vitamin D status and adverse effects, with risks observed both in low and high levels. While risks associated with low levels of vitamin D have been extensively studied, the risks of higher levels of vitamin D have not been as widely circulated. We sought to describe key observed adverse risks with vitamin D supplementation and higher serum 25(OH)-D levels in healthy adult populations.
Muscarinic Receptor Agonists and Antagonists: Effects on Keratinocyte Functions

The stratified epithelium enveloping the skin and lining the surfaces of oral and vaginal mucosa is comprised by keratinocytes that synthesize, secrete, degrade, and respond to acetylcholine via muscarinic and nicotinic receptors. The two pathways may compete or synergize with one another, so that net biologic effect represents the biologic sum of the effects of distinct acetylcholine receptors expressed by a keratinocyte at a particular stage of its development. Keratinocytes express a unique combination of muscarinic receptor subtypes at each stage of their development. Experimental results indicate that muscarinic receptors expressed in human keratinocytes regulate their viability, proliferation, migration, adhesion, and terminal differentiation, hair follicle cycling, and secretion of humectants, cytokines, and growth factors. Learning the muscarinic pharmacology of keratinocyte development and functions has salient clinical implications for patients with nonhealing wounds, mucocutaneous cancers, and various autoimmune and inflammatory diseases. Successful therapy of pemphigus lesions with topical pilocarpine and disappearance of psoriatic lesions due to systemic atropine therapy illustrate that such therapeutic approach is feasible.
Network Quality of Service in Docker Containers

This poster presents an extension to the currently limited Docker's networks. Specifically, to guarantee quality of service (QoS) on the network, our extension allows users to assign priorities to Docker's containers and configures the network to service these containers based on their assigned priority. Providing QoS not only improves the user experience but also reduces the operation cost by allowing for the efficient use of resources. Our implementation ensures that time-sensitive and critical applications, hosted in high-priority containers, get a greater share of network bandwidth, without starving other containers.
Prefrontal Cortex in Motor Control

The sections in this article are: 1 Anatomy 1.1 Development and Comparative Anatomy 1.2 Connections 1.3 Summary 2 Lesion Studies 2.1 Motility 2.2 Task Performance 2.3 Emotional Behavior 2.4 Summary 3 Electrophysiology 3.1 Inputs and Outputs Electrically Traced 3.2 Inhibition From Orbital Prefrontal Cortex 3.3 Frontal Eye Fields and Oculomotor Control 3.4 Electrical Correlates of Performance 3.5 Summary 4 Discussion 4.1 Temporal Synthesis of Behavior 5 Summary and Conclusions
Distinct CDR3 Conformations in TCRs Determine the Level of Cross-Reactivity for Diverse Antigens, but Not the Docking Orientation

T cells are known to cross-react with diverse peptide MHC Ags through their αβ TCR. To explore the basis of such cross-reactivity, we examined the 2C TCR that recognizes two structurally distinct ligands, SIY-Kb and alloantigen QL9-Ld. In this study we characterized the cross-reactivity of several high-affinity 2C TCR variants that contained mutations only in the CDR3α loop. Two of the TCR lost their ability to cross-react with the reciprocal ligand (SIY-Kb), whereas another TCR (m67) maintained reactivity with both ligands. Crystal structures of four of the TCRs in complex with QL9-Ld showed that CDR1, CDR2, and CDR3β conformations and docking orientations were remarkably similar. Although the CDR3α loop of TCR m67 conferred a 2000-fold higher affinity for SIY-Kb, the TCR maintained the same docking angle on QL9-Ld as the 2C TCR. Thus, CDR3α dictated the affinity and level of cross-reactivity, yet it did so without affecting the conserved docking orientation.