cssi/SciSciGPT-SciSciNet huggingface dataset:
Anticipatory Control of Voltage Regulator Modules

Fast load transient response and tight regulation are two strict specifications of voltage regulator module (VRM) design for powering desktop and mobile microprocessors. This paper presents a VRM topology for microprocessor applications. In this topology, instead of conventional bulky capacitors, small metal-oxide-semiconductor field-effect transistors (MOSFETs) utilized to provide fast transient requirements of the system. VRM topology based on anticipatory control tightly maintains output voltage of the converter within the required output voltage ripple band during transients. In anticipatory control, since there is no need to instantaneous changes in the inductor current, therefore, the dynamic response of the converter to the load changes is ultra-fast. A 12/1.5-V, 25-A, and 300 kHz VRM, based on anticipatory control is designed, built and tested. The proposed topology is validated with detailed simulation and a hardware prototype.
The singular and bounded parts of dyadic Green's function in a rectangular waveguide

A systematic derivation of singular and bounded parts of the electric and magnetic dyadic Green's functions of electric and magnetic current inside a rectangular waveguide using Poisson's summation formula is given in this paper. The rectangular waveguide of dimensions (a, b) is assumed to be oriented such that the “a” dimension is in the x-direction, and “b” dimension in the y-direction. Integrals of singular parts of these functions over rectangles arbitrarily oriented in the waveguide, useful in the computation of electric and magnetic fields in the source region of uniform distribution of electric and magnetic currents are also presented. Numerical results verifying the correctness and accuracy of these expressions are presented.
On the role of adhesion in single-file dynamics

Abstract For a one-dimensional interacting system of Brownian particles with hard-core interactions (a single-file model), we study the effect of adhesion on both the collective diffusion (diffusion of the entire system with respect to its center of mass) and the tracer diffusion (diffusion of the individual tagged particles). For the case with no adhesion, all properties of these particle systems that are independent of particle labeling (symmetric in all particle coordinates and velocities) are identical to those of non-interacting particles (Lebowitz and Percus, 1967). We clarify this last fact twice. First, we derive our analytical predictions that show that the probability-density functions of single-file ( ρ s f ) and ordinary ( ρ o r d ) diffusion are identical, ρ s f = ρ o r d , predicting a nonanomalous (ordinary) behavior for the collective single-file diffusion, where the average second moment with respect to the center of mass, 〈 x ( t ) 2 〉 , is calculated from ρ for both diffusion processes. Second, for single-file diffusion, we show, both analytically and through large-scale simulations, that 〈 x ( t ) 2 〉 grows linearly with time, confirming the nonanomalous behavior. This nonanomalous collective behavior comes in contrast to the well-known anomalous sub-diffusion behavior of the individual tagged particles (Harris, 1965). We introduce adhesion to single-file dynamics as a second inter-particle interaction rule and, interestingly, we show that adding adhesion does reduce the magnitudes of both 〈 x ( t ) 2 〉 and the mean square displacement per particle Δ x 2 ; but the diffusion behavior remains intact independent of adhesion in both cases. Moreover, we study the dependence of both the collective diffusion constant D and the tracer diffusion constant D T on the adhesion coefficient α .
A Supervisory (Expert) Adaptive Control Scheme

Abstract A supervisory scheme is presented, aimed at stabilizing adaptive controllers. The scheme works on the basis of heuristic (expert) rules and includes a monitor, a detuner and a structure identifier. The monitor detects onsetting instability based on the analysis of the amplitude and trend of the error signal. Upon detecting instability, the contoller is detuned, to a safer algorithm, recursively until stability is restored. Simultaneously, new data is gathered and the plant structure is re-identified. Based on the new structure, a new controller is designed and normal adaptation is finally restored. 15.1. Expert Systems for Automatic Control
Comparing active learning techniques: The effect of clickers and discussion groups on student perceptions and performance

Instructors often implement technology-based active learning pedagogies, such as clickers, to maximise student engagement and facilitate learning outcomes. Despite the abundance of clicker research, no work has directly compared student performance as well as student perceptions of clickers to a distinct, non-technological active learning pedagogy. Using a mixed methods quasi-experimental design, the current research compared clickers to a collaborative active learning pedagogy, student discussion groups. As predicted, clickers were evaluated more favourably than discussion groups. Qualitative analysis of students’ open-ended evaluations augmented these quantitative findings. Secondary analyses suggested that student performance was equivalent for clicker and discussion sections. Together, these results suggest that incorporating clickers into introduction courses may improve students’ attitudes towards the instructor’s pedagogy without any negative consequences for performance.
A Synthesis of Spelling Interventions for Secondary Students with Disabilities.

This synthesis examined the effects of spelling interventions on spelling outcomes for students with disabilities in Grades 6 through 12. Thirteen single-case design studies were identified for inc...
Three-body Forces in Photoreactions on 3He

We have measured the three-body photobreakup of {sup 3}He with the tagged photon beam and the CEBAF Large Acceptance Spectrometer in Hall B at the Thomas Jefferson National Accelerator Facility, in the photon energy range between 0.35 GeV and 1.55 GeV. This measurement constitutes a wide-ranging survey of two- and three-body processes in the gamma{sup 3}He {yields} ppn reaction channel, thanks to the high statistics and large kinematic coverage obtained with the CLAS. Total and partially integrated differential cross sections for the full ppn data set and for selected kinematics were extracted and are compared to theoretical predictions of Laget (up to 1.0 GeV). At low photon energies, the calculations are generally in fair agreement with the data. The comparison shows evidence of strong contributions of three-body absorption mechanisms, especially in the star kinematics, a symmetric configuration of the three final-state nucleons. Mostly the effects of two-body absorption mechanisms are se en, as expected, in the pp-pair-breakup kinematics, where the neutron does not participate in the reaction. The quasi-two-body breakup shows angular distributions consistent with preliminary gamma{sup 3}He --> pd results, extracted from our experiment. The ratio of cross sections for the star configuration and for the two-body kinematics, showsmore » a maximum for three-body effects at a photon energy of about 0.5 GeV, corresponding to a reduced photon wavelength of 0.4 fm. The 4pi-integrated cross section is in excellent agreement with previous experimental results from DAPHNE up to 800 MeV; no previous results have been obtained above this energy.« less
Scheuermann’s Kyphosis Surgery Complication

Scheuermann’s kyphosis (SK) presents as increased thoracic kyphosis or loss of lumbar lordosis with pathognomonic irregularities of the vertebral end plates. The majority of patients can be managed nonoperatively with bracing, short-term courses of NSAIDs, and physical therapy to address muscular discomfort. Surgical intervention should be considered for symptomatic patients with kyphosis exceeding 75°; however, smaller magnitude curves are also considered surgical if located in the thoracolumbar spine, if they are progressive, or if associated with significant pain or neurologic symptoms. A posterior approach with multilevel posterior column osteotomies at the apex of the deformity, segmental instrumentation, and fusion is the workhorse procedure. Junctional kyphosis is a complication that can often be avoided through careful selection of the upper (UIV) and lower instrumented vertebrae (LIV). In SK, the UIV should be the end vertebra; however, this is often difficult to visualize on lateral films, and therefore a line of best-fit technique may be used to aid selection. LIV is identified as the sagittal stable vertebra. Surgical correction of thoracic kyphosis and lumbar lordosis to values that are harmonious with the pelvic incidence (PI) is also important in preventing junctional kyphosis. In general terms, patients with high PI should be left with a larger thoracic kyphosis, while patients with relatively low PI should have a straighter sagittal profile. Asymptomatic, nonprogressive proximal junctional kyphosis (PJK) may be managed expectantly. The presence of progressive kyphosis, instability, or neurologic symptoms would mandate revision surgery with extension of the fusion proximally to a neutral or lordotic level.
An Aging Workforce and Work Environment: A Hotel Case Study in China

ABSTRACT The demographic trends of decreasing fertility rate and increasing life expectancy result in many older people remaining in the workforce. The biggest challenge for organizations is to est...
ReGAN: a pipelined ReRAM-based accelerator for generative adversarial networks

Generative Adversarial Networks (GANs) have recently drawn tremendous attention in many artificial intelligence (AI) applications including computer vision, speech recognition, and natural language processing. While GANs deliver state-of-the-art performance on these AI tasks, it comes at the cost of high computational complexity. Although recent progress demonstrated the promise of using ReRMA-based Process-In-Memory for acceleration of convolutional neural networks (CNNs) with low energy cost, the unique training process required by GANs makes them difficult to run on existing neural network acceleration platforms: two competing networks are simultaneously co-trained in GANs, and hence, significantly increasing the need of memory and computation resources. In this work, we propose ReGAN - a novel ReRAM-based Process-In-Memory accelerator that can efficiently reduce off-chip memory accesses. Moreover, ReGAN greatly increases system throughput by pipelining the layer-wise computation. Two techniques, namely, Spatial Parallelism and Computation Sharing are particularly proposed to further enhance training efficiency of GANs. Our experimental results show that ReGAN can achieve 240× performance speedup compared to GPU platform averagely, with an average energy saving of 94×.
Fibroblast Growth Factor 23 is Associated With Adiposity in Patients Receiving Hemodialysis: Possible Cross Talk Between Bone and Adipose Tissue

OBJECTIVE:Fibroblast growth factor 23 (FGF-23) may be involved in signaling between bone and adipose tissue in dialysis patients, but its role is uncertain. We sought to examine the association between FGF-23 and adiposity and whether this association is mediated in part by leptin. DESIGN/SETTING:We performed univariate and multivariate linear regression analyses using data from 611 participants in a cohort of prevalent hemodialysis patients recruited from dialysis centers in Atlanta, GA and San Francisco, CA from 2009 to 2011. We also investigated the role of leptin in these relationships. SUBJECTS:Participants were aged ≥18 years, English or Spanish speaking, and receiving hemodialysis for at least 3 months. MAIN OUTCOME MEASURES:Outcome measures of adiposity included body mass index, waist circumference, and body fat measured by bioelectrical impedance spectroscopy. RESULTS:Mean age was 56 ± 14 years, 39.8% were female, and median serum FGF-23 was 807 pg/mL. In fully adjusted models, FGF-23 was inversely associated with body mass index (-0.24 kg/m2 per 50% higher FGF-23, 95% confidence interval [CI]: -0.38 to -0.10), waist circumference (-0.44 cm per 50% higher FGF-23, 95% CI: -0.79 to -0.08), and percent body fat (-0.58% per 50% higher FGF-23, 95% CI: -0.79 to -0.37). Leptin was inversely associated with FGF-23. Addition of leptin to body composition models attenuated the associations between FGF-23 and measures of adiposity, but FGF-23 remained significantly associated with percent body fat (-0.17% per 50% higher FGF-23, 95% CI: -0.32 to -0.02). CONCLUSION:We found a negative association between FGF-23 and adiposity that appears to be mediated in part by leptin. As adipose tissue provides a "protective energy depot" for patients with chronic illness, a decrease in adipose tissue may be one mechanism in which higher FGF-23 levels may contribute to increased mortality in dialysis patients.
Direct analysis of textile dyes from trace fibers by automated microfluidics extraction system coupled with Q-TOF mass spectrometer for forensic applications.

Abstract Textile fiber is a common form of transferable trace evidence at the crime scene. Different techniques such as microscopy or spectroscopy are currently being used for trace fiber analysis. Dye characterization in trace fiber adds an important molecular specificity during the analysis. In this study, we performed a direct trace fiber analysis method via dye characterization by a novel automated microfluidics device (MFD) dye extraction system coupled with a quadrupole-time-of-flight (Q-TOF) mass spectrometer (MS). The MFD system used an in-house made automated procedure which requires only 10 μL of organic solvent for the extraction. The total extraction and identification time by the system is under 12 min. A variety of sulfonated azo and anthraquinone dyes were analyzed from ∼1 mm length nylon fiber samples. This methodology successfully characterized multiple dyes (≥3 dyes) from a single fiber thread. Additionally, it was possible to do dye characterization from single fibers with a diameter of ∼10 μm. The MFD-MS system was used for elemental composition and isotopic distribution analysis where MFD-MS/MS was used for structural characterization of dyes on fibers.
De panzas y prejuicios: la historia y la comida

espanolEste articulo proporciona un resumen de los textos del presente numero de HIb Revista de Historia Iberoamericana e identifica puntos de dialogo entre estos y algunos estudios de reciente publicacion, que representan importantes corrientes dentro de la historia de los alimentos. Hace enfasis en que el estudio historico de los alimentos se encuentra en la interseccion de lo material y lo social, lo que permite interpretaciones innovadoras sobre temas establecidos dentro la historiografia, a la vez que abre el panorama a nuevos sujetos de estudio. EnglishThis article provides a brief summary of the texts included in the current issue of HIb Revista de Historia Iberoamericana and identifies punts of dialogue between them and some recently published studies that represent important tendencies within the history of food. It emphasizes that since material and social dynamics intersect in food its study allows for innovative interpretations of established topics while opening the panorama to new historical subjects. portuguesEste texto fornece um resumo dos textos neste numero de HIb Revista de Historia Iberoamericana e identifica os focos de dialogo entre eles e alguns estudos de recente publicacao que representam importantes correntes dentro da historia dos alimentos. Ele enfatiza o fato do estudo historico dos alimentos encontrar-se na interseccao entre o material e o social, porque permite interpretacoes inovadoras de questoes estabelecidas dentro da historiografia ao mesmo tempo que abre o panorama para novos objetos de estudo.
Refractive Index Gradients in Sunfish Cones

Jay Enoch’s pioneering work with whole-mounted retinas established that vertebrate photoreceptors behave as dielectric waveguides. Theoretical analyses lead to the expectation that the distribution of refractive index in the photoreceptor inner segment will affect its waveguiding behavior. To determine the distribution of refractive indices in isolated photoreceptors, we examined them with a scanning microinterferometer. Our measurements of cones from green sunfish (Lepomis cyanellus) reveal systematic gradients of refractive index within the inner segments. For example, the refractive index of single cones (averaged over transverse cross-sections) increases from ca. 1.38 to ca. 1.42 along the inner segment longitudinal axis. Such gradients are large enough to affect waveguiding properties. Interferometric measurements and analysis of subcellular variations in refractive index will allow us to address a variety of unresolved issues in photoreceptor optics.
The seagrass ( Zostera marina [zosteraceae]) industry of Nova Scotia (1907–1960)

Wild gathering of the leaves of the submerged marine monocotyledon Zostera marina L. once formed the basis of a vigorous insulation industry in North America. Since European colonization, fishing communities used detached leaves, deposited on the beach by tide and wind, as green manure and domestic insulation, but beginning in the late 1800s, these leaves were utilized in a commercial insulating product. Two companies manufactured seagrass “quilts” that were installed in many buildings of the period including some of the first skyscrapers. We here describe the importance of seagrass gathering for the coastal community of Yarmouth County, Nova Scotia, Canada. Interviews with older residents and analysis of county and company archives facilitate the reconstruction of what was once a seasonally important activity. Our findings have direct application to global seagrass protection initiatives.
Multi-step Training of a Generalized Linear Classifier

We propose a multi-step training method for designing generalized linear classifiers. First, an initial multi-class linear classifier is found through regression. Then validation error is minimized by pruning of unnecessary inputs. Simultaneously, desired outputs are improved via a method similar to the Ho-Kashyap rule. Next, the output discriminants are scaled to be net functions of sigmoidal output units in a generalized linear classifier. This classifier is trained via Newton’s algorithm. Performance gains are demonstrated at each step. Using widely available datasets, the final network’s tenfold testing error is shown to be less than that of several other linear and generalized linear classifiers reported in the literature.
Ideal telestroke time targets: Telestroke-based treatment times in the United States stroke belt.

BackgroundStudying critical time interval requirements can enhance thrombolytic treatment for stroke patients in telestroke networks. We retrospectively examined 12 concurrent months of targeted ti...
Implementation of Oral Health Screening and Referral Guidelines in Primary Health Care

Objectives:To determine the oral health screening and referral practices of pediatric providers, their adherence to American Academy of Pediatrics oral health guidelines, and barriers to adherence....
Problems in International Protection of Intellectual Property Rights

Intellectual property rights are policies that assign and protect the rights to earn income from innovative and creative activity. These rights provide legal authority to control the dissemination ...
Writeback-Aware LLC Management for PCM-Based Main Memory Systems

With the increase in the number of data-intensive applications on today's workloads, DRAM-based main memories are struggling to satisfy the growing data demand capacity. Phase Change Memory (PCM) is a type of non-volatile memory technology that has been explored as a promising alternative for DRAM-based main memories due to its better scalability and lower leakage energy. Despite its many advantages, PCM also has shortcomings such as long write latency, high write energy consumption, and limited write endurance, which are all related to the write operations. In this article, we propose a novel writeback-aware Last Level Cache (LLC) management scheme named WALL to reduce the number of LLC writebacks and consequently improve performance, energy efficiency, and lifetime of a PCM-based main memory system. First, we investigate the writeback behavior of LLC sets and show that writebacks are not uniformly distributed among sets; some sets observe much higher writeback rates than others. We then propose a writeback-aware set-balancing mechanism, which employs the underutilized LLC sets with few writebacks as an auxiliary storage for the evicted dirty lines from sets with frequent writebacks. We also propose a simple and effective writeback-aware replacement policy to avoid the eviction of the dirty blocks that are highly reused after being evicted from the cache. Our experimental results show that WALL achieves an average of 30.9% reduction in the total number of LLC writebacks, compared to the baseline scheme, which uses the LRU replacement policy. As a result, WALL can reduce the memory energy consumption by 23.1% and enhance PCM lifetime by 1.29×, on average, on an 8-core system with a 4GB PCM main memory, running memory-intensive applications.
Rigorous policies ensure integrity of NLM literature databases.

We read with interest the article titled “How predatory journals leak into PubMed,” by Dr. Manca and colleagues published in CMAJ .[1][1] We thank the authors for their interest in PubMed and PubMed Central and provide clarification on which journals the US National Library of Medicine has
Sensitivity of the Power Spectra of Magnetization Fluctuations in Low Barrier Nanomagnets to Barrier Height Modulation and Defects

Nanomagnets with small shape anisotropy energy barriers on the order of the thermal energy have unstable magnetization that fluctuates randomly in time. They have recently emerged as promising hardware platforms for stochastic computing and machine learning because the random magnetization states can be harnessed for probabilistic bits. Here, we have studied how the statistics of the magnetization fluctuations (e.g. the power spectral density) is affected by (i) moderate variations in the barrier height of the nanomagnet and (ii) the presence of structural defects, in order to assess how robust the computing platform is. We found that the power spectral density is relatively insensitive to moderate barrier height change and also relatively insensitive to the presence of small localized defects. However, extended (delocalized) defects, such as thickness variations over a significant fraction of the nanomagnet, affect the power spectral density very noticeably. As a result, small variations in the shape (causing small variations in the barrier height), or small localized defects, are relatively innocuous and tolerable, but significant variation of the nanomagnet thickness is not. Consequently, tight control over the nanomagnet thickness must be maintained for stochastic computing applications.
Systematic method for modeling and characterizing multilayer light field displays

Conventional stereoscopic displays are subject to the well-known vergence-accommodation conflict (VAC) problem due to their lack of the ability to render correct focus cues of a 3D scene. A computational multilayer light field display has been explored as one of the approaches that can potentially overcome the VAC problem owing to the promise of rendering a true 3D scene by sampling the directions of the light rays apparently emitted by the 3D scene. Several pioneering works have demonstrated working prototypes of multilayer light field displays and the potential capability of rendering nearly correct focus cues. However, there is no systematic investigation upon methods for modeling and analyzing such a display, which is essential for further optimization and development of high-performance multilayer light field display systems. In this paper, we proposed a systemic analysis method for the multilayer light field displays by simulating the perceived retinal image which takes the display factors, the view-dependency of the reference light field, the diffraction effect, and the visual factors into consideration. Then we applied this model to investigate the accommodative response when observing the display engine.
Effect of Insurance Type on Access to Orthopedic Care for Pediatric Trigger Thumb.

Purpose To assess the effect of type of insurance coverage on the ability of a pediatric patient to obtain an outpatient orthopedic appointment for trigger thumb. Methods A list of 200 orthopedic practices in 4 states were contacted and presented with a fictitious 3-year-old patient with trigger thumb. The patient was presented as having Blue Cross Blue Shield Insurance during the first call and Medicaid during the second call. Data regarding whether an appointment was offered or denied were recorded. Results Of the 200 practices, 81 were excluded, 22 because they did not answer the calls, 25 needed the patient’s social security number, 19 needed medical records, 5 had no hand surgeon in the practice, and 10 would not see any children at all. Of the 119 practices included in the analysis, the private insurance patient was able to get an appointment 51.3% of the time whereas the Medicaid patient was able to get an appointment in 26.9% of instances. Conclusions There is a significant effect of insurance status on the ability of pediatric patients with trigger thumb to obtain outpatient orthopedic appointments. Clinical relevance Pediatric patients with Medicaid face greater barriers to accessing proper care for trigger thumb than patients with private insurance.
Defective Trafficking of Annexins to the Site of Injury in ANO5-Knockout Muscle Fibers

Mutations in ANO5 (TMEM16E) cause limb-girdle muscular dystrophy R12 (limb-girdle muscular dystrophy type 2L). Recent evidence implicates defective plasma membrane repair as a likely mechanism for the disorder. Here, we probe the ANO5-dependency of the membrane repair pathway using a laser wounding assay in Ano5 knockout mouse muscle fibers. Wounded myofibers from Ano5 knockout mice exhibit delayed membrane resealing relative to wild type fibers as revealed by an increased uptake of the membrane-impermeant FM1-43 dye and a prolonged elevation of intracellular Ca2+. The trafficking of several annexin proteins, which together form a cap at the site of injury, is altered in Ano5 knockout fibers. Annexin A2 accumulates at the wound to nearly twice the level observed in WT fibers, while annexin A6 accumulation is substantially inhibited in the absence of ANO5. Furthermore, trafficking of annexins A1 and A5 to the cap is decreased in the Ano5 knockout. These changes are correlated with an alteration in the fine structure of the annexin repair cap and the shedding of annexin-positive extracellular vesicles. Our results suggest that the meticulous coordination of the annexin repair machinery required to effectively reseal wounded sarcolemma is disrupted in Ano5 knockout mice. ANO5 is a putative phospholipid scramblase, responsible for exposure of intracellular phospholipids to the extracellular leaflet of the plasma membrane. However, because the membrane repair defect is rescued by overexpression of wild type ANO5 or a scramblase-defective mutant, we suggest that ANO5-mediated phospholipid scrambling is not essential for membrane repair.
Trends in Breast Cancer Treatment De-Implementation in Older Patients with Hormone Receptor-Positive Breast Cancer: A Mixed Methods Study

Guidelines allow for the omission of sentinel lymph node biopsy (SLNB) and post-lumpectomy radiotherapy in women ≥ 70 years of age with hormone receptor-positive (HR +) breast cancer. Despite this, national data suggest these procedures have not been widely de-implemented. Our objectives were to evaluate trends in SLNB and post-lumpectomy radiotherapy utilization in patients who are eligible for omission, and evaluate patient preferences as a target for de-implementation of low-value care. We performed a sequential explanatory mixed-methods study by first analyzing an institutional database of patients ≥ 70 years of age with HR + breast cancer who received surgical treatment from 2014 to 2018. Based on the quantitative data, we conducted semi-structured interviews with women identified as high or low utilizers of breast cancer treatments to elicit patient perspectives on de-implementation. SLNB and post-lumpectomy radiotherapy were performed in 68% and 43% of patients, respectively, who met the criteria for omission. There was a significant decrease in SLNB rates from 2014 to 2018. Forty-nine percent of patients were classified as high utilizers and 26% were classified as low utilizers. Qualitative analysis found that the most important factors influencing decision making regarding SLNB and post-lumpectomy radiotherapy omission for both high and low utilizers were trust in their provider and a desire for peace of mind. Despite efforts to de-implement low-value care, older women with HR + breast cancer remain at risk of overtreatment. Patient perspectives suggest that multi-level de-implementation strategies will need to target provider practice patterns and patient-provider communication to promote high-quality decision making and reduction in breast cancer overtreatment.
How to Overturn Employment Division v. Smith: A Historical Approach

Over the last decade, justices on both sides of the Roberts Court have demonstrated a growing willingness to give the Free Exercise Clause substantive power: a trend that stands in stark contrast with the Rehnquist Court’s decision in Employment Division v. Smith. The Court’s references to Smith have also become visibly — and fittingly — awkward and halting. In this article, I argue that the time has come to push for an explicit reversal of Smith, and that such a decision would not only be joined by Chief Justice Roberts, but likely by Justice Kagan as well. Exploring the history of the Free Exercise Clause, I argue that Smith contradicted the Clause’s original intent, and that the nineteenth-century decisions on which Smith relied were little more than brazen codifications of anti-Mormon bigotry. I conclude that Justice Scalia’s majority opinion in Smith fails every metric of sound jurisprudence, and that a bipartisan coalition of justices can be persuaded to discard it as an aberration.
Some thermodynamic effects of varying nonpolar surfaces in protein-ligand interactions.

Abstract Understanding how making structural changes in small molecules affects their binding affinities for targeted proteins is central to improving strategies for rational drug design. To assess the effects of varying the nature of nonpolar groups upon binding entropies and enthalpies, we designed and prepared a set of Grb2-SH2 domain ligands, Ac–pTyr–Ac6c–Asn–(CH2)n–R, in which the size and electrostatic nature of R groups at the pTyr+3 site were varied. The complexes of these ligands with the Grb2-SH2 domain were evaluated in a series of studies in which the binding thermodynamics were determined using isothermal titration calorimetry, and binding interactions were examined in crystallographic studies of two different complexes. Notably, adding nonpolar groups to the pTyr+3 site leads to higher binding affinities, but the magnitude and energetic origins of these effects vary with the nature of the R substituent. For example, enhancements to binding affinities using aliphatic R groups are driven by more favorable changes in binding entropies, whereas aryl R groups improve binding free energies through a combination of more favorable changes in binding enthalpies and entropies. However, enthalpy/entropy compensation plays a significant role in these associations and mitigates against any significant variation in binding free energies, which vary by only 0.8 kcal•mol−1, with changes in the electrostatic nature and size of the R group. Crystallographic studies show that differences in ΔG° or ΔH° correlate with buried nonpolar surface area, but they do not correlate with the total number of polar or van der Waals contacts. The relative number of ordered water molecules and relative order in the side chains at pTyr+3 correlate with differences in –TΔS°. Overall, these studies show that burial of nonpolar surface can lead to enhanced binding affinities arising from dominating entropy- or enthalpy-driven hydrophobic effects, depending upon the electrostatic nature of the apolar R group.
Microarray Profiling Reveals Distinct Circulating miRNAs in Aged Male and Female Mice Subjected to Post-stroke Social Isolation.

Social isolation (SI) increases ischemic injury and significantly delays recovery after experimental stroke. Changes in circulating microRNAs (miRNAs) have been implicated in several neurological disorders, including stroke. However, potential biomarkers to elucidate the mechanisms that underlie the detrimental effects of post-stroke isolation are unknown. Aged C57BL/6 male and female mice (18–20 months) were subjected to a 60-min middle cerebral artery occlusion followed by reperfusion and were assigned to either isolation (SI) or continued pair housing (PH) immediately after stroke. On day 15, mice were sacrificed, and plasma samples were collected for miRNAome analysis. Top candidate miRNAs and their biological functions were identified using integrated bioinformatics. The miRNAome analysis revealed a total of 21 differentially expressed miRNAs across both sexes with fold change of 3 or higher. Within the female cohort, miR-206-3p, -376a-3p, -34b-5p, -133a-5p, -466f, and -671-3p were highly altered relative to the PH housing condition. Similarly in males, miR-376c-3p, -181d-5p, -712-5p, -186-5p, -21a-3p, -30d-3p, -495-3p, -669c-5p, -335-5p, -429-3p, -31-3p, and -217-5p were identified. Following Kyoto Encyclopedia of Genes and Genomes analysis, the identified miRNAs effected distinct subset of pathways within sexes. Interactional network analysis revealed miR-495-3p (male) and miR-34b-5p (female) as pivotal nodes that targeted the largest subset of genes. We identified several sex-specific miRNAs as candidate biomarkers for post-stroke SI in aged male and female mice. Additionally, these results suggest that there is potential to use plasma-based circulating miRNAs as a source of novel biomarkers to identify biological pathways involved in post-stroke SI.
Distributed and Localized Closed Loop Model Predictive Control via System Level Synthesis

We present the Distributed and Localized Model Predictive Control (DLMPC) algorithm for large-scale structured linear systems, a distributed closed loop model predictive control scheme wherein only local state and model information needs to be exchanged between subsystems for the computation and implementation of control actions. We use the System Level Synthesis (SLS) framework to reformulate the centralized MPC problem as an optimization problem over closed loop system responses, and show that this allows us to naturally impose localized communication constraints between sub-controllers. We show that the structure of the resulting optimization problem can be exploited to develop an Alternating Direction Method of Multipliers (ADMM) based algorithm that allows for distributed and localized computation of distributed closed loop control policies. We conclude with numerical simulations to demonstrate the usefulness of our method, in which we show that the computational complexity of the subproblems solved by each subsystem in DLMPC is independent of the size of the global system. To the best of our knowledge, DLMPC is the first MPC algorithm that allows for the scalable distributed computation of distributed closed loop control policies.
Multispectral Imaging for Metallic Biopsy Marker Detection During MRI-Guided Breast Biopsy: A Feasibility Study for Clinical Translation.

Purpose To assess the feasibility and diagnostic accuracy of multispectral MRI (MSI) in the detection and localization of biopsy markers during MRI-guided breast biopsy. Methods This prospective study included 20 patients undergoing MR-guided breast biopsy. In 10 patients (Group 1), MSI was acquired following tissue sampling and biopsy marker deployment. In the other 10 patients (Group 2), MSI was acquired following tissue sampling but before biopsy marker deployment (to simulate deployment failure). All patients received post-procedure mammograms. Group 1 and Group 2 designations, in combination with the post-procedure mammogram, served as the reference standard. The diagnostic performance of MSI for biopsy marker identification was independently evaluated by two readers using two-spectral-bin MR and one-spectral-bin MR. The κ statistic was used to assess inter-rater agreement for biopsy marker identification. Results The sensitivity, specificity, and accuracy of biopsy marker detection for readers 1 and 2 using 2-bin MSI were 90.0% (9/10) and 90.0% (9/10), 100.0% (10/10) and 100.0% (10/10), 95.0% (19/20) and 95.0% (19/20); and using 1-bin MSI were 70.0% (7/10) and 80.0% (8/10), 100.0% (8/8) and 100.0% (10/10), 85.0% (17/20) and 90.0% (18/20). Positive predictive value was 100% for both readers for all numbers of bins. Inter-rater agreement was excellent: κ was 1.0 for 2-bin MSI and 0.81 for 1-bin MSI. Conclusion MSI is a feasible, diagnostically accurate technique for identifying metallic biopsy markers during MRI-guided breast biopsy and may eliminate the need for a post-procedure mammogram.
Clenbuterol Attenuates Immune Reaction to Lipopolysaccharide and Its Relationship to Anhedonia in Adolescents

While inflammation has been implicated in depression, little is known of immune-inhibitory agents for individuals with depression. This study sought to assess whether β2-agonist clenbuterol (CBL) would attenuate increased cytokine secretion in adolescents with mood and anxiety symptoms following ex vivo exposure of whole blood to lipopolysaccharide (LPS). Our focus on adolescents aimed to target a critical developmental period when psychiatric conditions often emerge and prior to chronicity effects. Participants (15.25 ± 2.16 years old, 59% female) were 97 psychotropic-medication free adolescents with mood and anxiety symptoms and 33 healthy controls. All had comprehensive evaluations and dimensional assessments of psychiatric symptoms. Fasting whole-blood samples were collected and stimulated with LPS in the presence and absence of CBL for 6 hours and analyzed for 41 cytokines. Comparison analyses used Bonferroni-corrected nonparametric tests. Exploratory factor analysis reduced 41 cytokines into 5 cytokine factors in each experimental condition, and their relationships with psychiatric symptoms were examined. Levels of nine cytokines were significantly reduced by CBL treatment compared to LPS alone. A cytokine factor in the LPS+CBL condition significantly correlated with anticipatory (rho = −0.39, p = 7.4 × 10-5) and consummatory anhedonia (rho = −0.36, p = 3.3 × 10-4), which remained significant when controlling for depression. This study supports the possible inhibitory effect of CBL on immune activation. Using a data-driven method, distinctive relationships between CBL-affected cytokines and dimensional anhedonia were reported, further elucidating the role of β2-agonism in adolescent affective symptomatology.
Organohalogen Contaminants and Vitamins in Northern Fur Seals ( Callorhinus ursinus ) Collected During Subsistence Hunts in Alaska

During native subsistence hunts from 1987 to 2007, blubber and liver samples from 50 subadult male northern fur seals (Callorhinus ursinus) were collected on St. Paul Island, Alaska. Samples were analyzed for legacy persistent organic pollutants (POPs), recently phased-out/current-use POPs, and vitamins. The legacy POPs measured from blubber samples included polychlorinated biphenyl congeners, DDT (and its metabolites), chlorobenzenes, chlordanes, and mirex. Recently phased-out/current-use POPs included in the blubber analysis were the flame retardants, polybrominated diphenyl ethers, and hexabromocyclododecanes. The chemical surfactants, perfluorinated alkyl acids, and vitamins A and E were assessed in the liver samples. Overall, concentrations of legacy POPs are similar to levels seen in seal samples from other areas of the North Pacific Ocean and the Bering Sea. Statistically significant correlations were seen between compounds with similar functions (pesticides, flame retardants, vitamins). With sample collection spanning two decades, the temporal trends in the concentrations of POPs and vitamins were assessed. For these animals, the concentrations of the legacy POPs tend to decrease or stay the same with sampling year; however, the concentrations of the current-use POPs increased with sampling year. Vitamin concentrations tended to stay the same across the sampling years. With the population of northern fur seals from St. Paul Island on the decline, a detailed assessment of exposure to contaminants and the correlations with vitamins fills a critical gap for identifying potential population risk factors that might be associated with health effects.
Grounded situation models for situated conversational assistants

A Situated Conversational Assistant (SCA) is a system with sensing, acting and speech synthesis/recognition abilities, which engages in physically situated natural language conversation with human partners and assists them in carrying out tasks. This thesis addresses some prerequisites towards an ideal truly cooperative SCA through the development of a computational model of embodied, situated language agents and implementation of the model in the form of an interactive, conversational robot. The proposed model produces systems that are capable of a core set of situated natural language communication skills, and provides leverage for many extensions towards the ideal SCA, such as mind reading skills. The central idea is to endow agents with a sensor-updated "structured blackboard" representational structure called a Grounded Situation Model (GSM), which is closely related to the cognitive psychology notion of situation models. The GSM serves as a workspace with contents similar to a "theatrical stage" in the agent's "mind". The GSM may be filled either with the contents of the agent's present here-and-now physical situation, or a past situation that is being recalled, or an imaginary situation that is being described or planned. Furthermore, the GSM contains descriptions of both physical (such as objects) as well as mental aspects of situations (such as beliefs of others). Most importantly, the proposed GSM design enables bidirectional translation between linguistic descriptions and perceptual data/expectations. To demonstrate viability, an instance of the model was implemented on a manipulator robot with touch, vision, and speech synthesis/ recognition. The robot grasps the semantics of a range of words and speech acts related to cooperative manipulation of objects on a table top situated between the robot and human. The robot's language comprehension abilities are comparable to those implied by a standard and widely used test of children's language comprehension (the Token Test), and in some directions also surpass those abilities. Not only the viability but also the effectiveness of the GSM proposal is thus demonstrated, through a real-world autonomous robot that performs comparably to those capabilities of a normally-developing three-year old child which are assessed by the token test. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)
Transition to Turbulence in Thermal Convection with and without Rotation

Publisher Summary This chapter discusses the transition to turbulence in thermal convection with and without rotation. Thermal convection in a layer heated from below and Taylor vortices between differentially rotating coaxial cylinders are the classical examples of fluid systems that exhibit a slow onset of turbulence. A fluid layer heated from below is horizontally isotropic and homogenous at least in the limit when a layer of infinite extent is approached. This causes an infinite degeneracy of the solutions even at the onset of convection. The physical conditions on flow between rotating cylinders are anisotropic and the onset of Taylor vortices can be described by a simple bifurcation from the basic state. In the case of convection, this behavior can be modeled by using layers in which height and width are comparable. This permits a removal of the degeneracy to an experimentally relevant extent. Mathematical models for the description of the onset of turbulence have usually been developed on the basis of the theory of ordinary differential equations. The concept of a mathematical description of turbulence by a large manifold of solutions, each of which is unstable with respect to some other solution of the manifold, is not a new one. Convection in a rotating layer offers the simplest example of such a model of turbulence with the additional advantage of a weak nonlinearity of the basic equations.
Global Software Development with Cloud Platforms

Offshore and outsourced distributed software development models and processes are facing challenges, previously unknown, with respect to computing capacity, bandwidth, storage, security, complexity, reliability, and business uncertainty. Clouds promise to address these challenges by adopting recent advances in virtualization, parallel and distributed systems, utility computing, and software services. In this paper, we envision a cloud-based platform that addresses some of these core problems. We outline a generic cloud architecture, its design and our first implementation results for three cloud forms - a compute cloud, a storage cloud and a cloud-based software service- in the context of global distributed software development (GSD). Our ”compute cloud” provides computational services such as continuous code integration and a compile server farm, ”storage cloud” offers storage (block or file-based) services with an on-line virtual storage service, whereas the on-line virtual labs represent a useful cloud service. We note some of the use cases for clouds in GSD, the lessons learned with our prototypes and identify challenges that must be conquered before realizing the full business benefits. We believe that in the future, software practitioners will focus more on these cloud computing platforms and see clouds as a means to supporting a ecosystem of clients, developers and other key stakeholders.
Poly(ethylene glycol) Hydrogels with Adaptable Mechanical and Degradation Properties for Use in Biomedical Applications

Requirements of hydrogels for drug delivery, wound dressings, and surgical implantation can be extensive, including suitable mechanical properties and tailorable degradation time frames. Herein, an adaptable PEG-based hydrogel, whose mechanical properties and degradation rate can be systematically adjusted to meet these criteria by altering simple variables such as the PEG molecular weight, is described. The performance of these hydrogels in three physical manipulations (pushing, pulling, and folding), representative of manipulations that they may undergo during typical biomedical use, is also assessed. While not all of these formulations can withstand these manipulations, a subset did, and it is intended to further optimize these formulations for specific clinical applications. Additionally, the outcomes of the physical manipulation tests indicate that simply having a high modulus does not correlate with biomedical applicability.