cssi/SciSciGPT-SciSciNet huggingface dataset:
Enzymatic conjugation using branched linkers for constructing homogeneous antibody–drug conjugates with high potency

Antibody–drug conjugates (ADCs) are emerging therapeutic agents in the treatment of cancer, and various conjugation strategies and chemical linkers have been developed to efficiently construct ADCs. Despite previous extensive efforts for improving conjugation efficiency and ADC homogeneity, most ADC linkers developed to date load only single payloads. Branched linkers that can load multiple payload molecules have yet to be fully explored. It is logical to envisage that a multi-loading strategy allows for increase in drug-to-antibody ratio (DAR) with less chemical or enzymatic modification to the antibody structure compared to traditional linear linkers, leading to efficient ADC construction, minimal destabilization of the antibody structure, and enhanced ADC efficacy. Herein, we report that the branched linkers we designed can be quantitatively installed on an anti-HER2 monoclonal antibody by microbial transglutaminase (MTGase)-mediated conjugation without impairing its antigen binding affinity, enabling modular installation of payload molecules and construction of homogeneous ADCs with increased DARs (up to 8). An anti-HER2 antibody–monomethyl auristatin F conjugate constructed using our branched linkers showed greater in vitro cytotoxicity against HER2-expressing breast cancer cell lines than that consisting of linear linkers, demonstrating the effectiveness of the branched linker-based payload delivery. Our finding demonstrates that enzymatic ADC construction using branched linkers is a promising strategy, which may lead to innovative cancer therapeutics.
Prospective evaluation of surgical management of sliding hiatal hernia and gastroesophageal reflux in dogs.

OBJECTIVE To evaluate response to surgical management of sliding hiatal hernia (SHH) and gastroesophageal reflux (GER) in dogs using standardized clinical scoring, videofluoroscopic swallow studies, and impedance planimetry. STUDY DESIGN Prospective clinical trial. ANIMALS A total of 17 client-owned dogs. METHODS Dogs were included if they had clinical signs and videofluoroscopic evidence of SHH and/or GER. Owners were asked to complete a standardized canine dysphagia assessment tool (CDAT) preoperatively and postoperatively. Conscious videofluoroscopic swallowing studies and impedance planimetry (IP) were used to evaluate esophageal function and lower esophageal sphincter location and geometry preoperatively and in a subsection of dogs postoperatively. RESULTS Preoperatively, 13/17 dogs included in the study had a history of regurgitation, and 4/17 had radiographic evidence of aspiration pneumonia. Postprandial regurgitation improved in 8/10 dogs with preoperative regurgitation, and for which completed preoperative and postoperative CDAT questionnaires were available (P < .01). The hiatal hernia severity score improved postoperatively (P = .046) in dogs with preoperative and postoperative videofluoroscopic swallowing studies (n = 12). However, hernia frequency score (P = .2) and IP parameters did not differ significantly between time points. CONCLUSION Clinical signs of SHH generally improved with surgery but did not consistently resolve. Videofluoroscopic studies provide evidence that GER and SHH can persist postoperatively in some patients. Based on IP findings, clinical improvement may be attributed to a mechanism independent of lower esophageal sphincter attenuation.
Laboratory validation of a point velocity probe for measuring horizontal flow from any direction

The point-velocity probe (PVP) quantifies groundwater speed and flow direction, i.e., velocity, at the centimeter scale. The first probe designs required that the flow direction be known a priori, within about 100° in order to position the probe during installation. This study introduces and assesses a '360° PVP' that measures flow from any direction without foreknowledge of the groundwater velocity. In tests conducted in a Nested Storage Tank (NeST) aquifer simulator packed with sand, PVP-measured velocities matched expected velocities within ±9° in direction and ±15% in magnitude, on average, consistent with previously reported PVP performances in laboratory studies. In tests involving 17 repacked NeSTs, the measured and expected velocities were within ±30° and ±30% on average, illustrating the sensitivity of flow to porous medium packing, and the probes' ability to sense these changes; the porosity was found to vary considerably between packings i.e., n=0.34±0.2. For flow directions between 0° and 80° of an injection port, the experimental error on velocity magnitude was within the ranges reported above. At higher flow angles, experimental sources of error contributed to greater uncertainties. Fortunately, in these cases there were always alternative injection ports (with lower angles to flow) that could be used to circumvent any biases. At low experimental flow angles (<10°) the calculated values tended to overestimate the actual flow angles. Fortunately, these cases were identifiable by the detection of tracer at detectors on either side of the active injection port. In several tests designed with an expected flow direction of 0°, averaging the calculated directions from each side of the injection port resulted in improved matches to the expected flow direction.
Fabrication and X-ray Photoelectron Spectroscopy of Nanostructured Semiconductor Thin Films and Particles

Nanostructured Ge granular films and freestanding InP nanoparticles have been prepared by physical vapor deposition and chemical methods, respectively. These samples were analyzed by x-ray diffraction and transmission electron microscopy (TEM) for structural characterization and by x-ray photoelectron spectroscopy for chemical characterization. Ge-M films, where M is the matrix in which Ge nanoparticles are embedded, prepared by physical vapor deposition were used as an example of the granular films and the oxidation of Ge in various matrices was studied. The matrices included metallic Al and ceramic AI2O3, SiO2 and MgO. InP nanoparticles prepared by the chemical route were the example for freestanding nanoparticles. Core level and plasmon loss peaks were utilized in order to properly identify the chemical constituents of these nanoparticles.
Credit market imperfection, minimum investment requirement, and endogenous income inequality

Abstract The main goal of this paper is to describe an endogenous feedback mechanism through which imperfection in the credit market may amplify income inequality. When entrepreneurs are subject to a minimum investment requirement and entrepreneurs’ future revenue is not fully pledgeable for debt repayment, then the highest interest rate entrepreneurs can credibly offer to depositors depends not only on the marginal product of capital but also on entrepreneurs’ net wealth. This dependence creates an entrepreneurial rent which has both direct and indirect impacts on income inequality. On the one hand, entrepreneurial rent magnifies income inequality because it changes the balance between marginal product on capital (collected by entrepreneurs) and the interest rate (collected by depositors) and alters young agents saving decision. Entrepreneurial rent indirectly affects the labor income inequality because it distorts young agents’ labor supply decision and thus indirectly affects labor income earned by borrowers and lenders. Under some configuration of parameter values, the model predicts a Kuznets curve, i.e., an inverted-U relationship between per capita income and income inequality.
Tracking of activity and sedentary behaviors in childhood: the Iowa Bone Development Study.

Background Physical activity tracking studies can determine when children settle into activity patterns and their risk for maintaining sedentary behaviors. This study examined the tracking of activity and sedentary behavior in relation to adiposity during middle childhood. Methods Activity intensities and patterns were examined during a 3-year interval in a population-based study of children using accelerometry and survey methods. Data were collected and analyzed from 1998 to 2004. Participants (n=379) were, on average, 5.6 (standard deviation [SD]±0.5) years at baseline and 8.6 (SD ±0.5) years at follow-up. Adiposity was measured with whole-body, dual-energy x-ray absorptiometry. Correlation coefficients and odds ratios were used to assess tracking. The association of activity with adiposity was tested using the Wilcoxon rank-sum test. Results Over the 3-year interval, Spearman rank-order correlation coefficients between baseline and follow-up activity measures were low to moderate (r=0.18 to 0.39). Sedentary behavior was more predictable than overall activity, and tended to be more stable (r=0.37 to 0.52), with the exception of video playing in boys (r=0.18). Children maintaining a high degree of vigorous activity and low levels of TV viewing were less likely than peers to be in the upper quartile for adiposity at follow-up, and were less likely to gain adiposity during the study period. Conclusions Sedentary behavior, including TV viewing, is moderately stable during middle childhood. Health promotion programs that specifically target maintaining high levels of vigorous activity and low levels of TV viewing may help reduce the increasing prevalence of childhood obesity.
Abstract 4483: Functional implications of PRDM16 loss in kidney cancer

The most common genetic aberration associated with inherited or sporadic renal cell carcinoma (RCC) is the loss or nonfunctional mutations in the von Hippel-Lindau (VHL) tumor suppressor gene. The mutations lead to the stabilization of hypoxia inducible factor (HIF-1α and 2α), thereby promoting the expression of HIF target genes. HIF target genes are reported to induce tumor phenotypes by altering cellular metabolism and upregulating the expression of protumorigenic/angiogenic factors as well. We report here tissue microarray data and histology-based analyses demonstrating that the gene PRDM16 (PRD1-BF1-RIZ1 homologous domain containing 16) is silenced in many RCC tumors regardless of their VHL status. Bioinformatics analysis demonstrates a role for promoter methylation in silencing PRDM16. We investigated the role of PRDM16 in the context of VHL loss in kidney cancer. PRDM16 is known to regulate brown fat mitochondrial metabolism by inducing expressions of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PPARGC1A) and estrogen-related receptor-gamma (ESRRG). Altered cellular metabolism, in particular, decreased mitochondrial respiration is a hallmark of RCC, which is in attributed to VHL alterations. Analysis of TCGA data demonstrates that PRDM16 expression strongly correlates with PPARGC1A expression in RCC. Ectopic expression of PRDM16 in RCC cells can induce PPARGC-1α and ESRRG mRNA expression but fails to increase mitochondrial respiration. However, ectopic expression of PRDM16 in RCC cell lines can suppress both in vitro and in vivo tumor phenotypes. These data suggest that the tumor-suppressive activity of PRDM16 may be independent from its effects on mitochondrial metabolism. RNA-seq based analysis of a VHL mutated RCC line re-expressing PRDM16 demonstrates that a transcription suppressive role of PRDM16 predominates in RCC. PRDM16 suppresses genes involved in cell migration and proliferation. In particular, PRDM16 downregulates the expression of semaphorin 5B (SEMA5B). q-PCR analysis validates high-throughput data in a panel of RCC and embryonic kidney cell lines. SEMA5B knock down significantly decreases RCC proliferation supporting the protumorigenic function of SEMA5B in RCC. Given the central role of VHL loss in renal tumor initiation, we demonstrate that the VHL/HIF axis regulates the expression of SEMA5B in RCC. Collectively, these data suggest that transcription suppressive activity of PRDM16 and VHL controls expression of the protumorigenic factor SEMA5B and that epigenetic silencing of PRDM16 thus amplifies this consequence of VHL loss. Citation Format: Anirban Kundu, Eun-Young Kho, Sandeep B. Shelar, Hyeyoung Nam, Garret Brinkley, Shimoga Darshan, Yawen Tang, Richard Kirkman, David K. Crossman, Sooryanarayana Varambally, Glenn C. Rowe, Shi Wei, Phillip Buckhaults, Sunil Sudarshan. Functional implications of PRDM16 loss in kidney cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4483.
Strategies for Appropriate Selection of SGLT2-i vs. GLP1-RA in Persons with Diabetes and Cardiovascular Disease

This review will serve to highlight the clinical rationale used in the selection of sodium-glucose cotransporter 2 inhibitors (SGLT2-i) or glucagon-like peptide 1 receptor agonists (GLP1-ra). SGLT2-i and GLP1-ra are the first anti-hyperglycemics to demonstrate significant cardiovascular benefit in multiple cardiovascular outcomes trials (CVOTs), with benefits that are consistent across class of medication. Diabetes is a major risk factor for morbidity and mortality from cardiovascular disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) and glucagon-like peptide 1 receptor agonists (GLP1-ra) are the first anti-hyperglycemics to demonstrate significant cardiovascular benefit. Given the unique side effect and benefit profiles, appropriate consideration of these agents with a focus on cardiovascular risk reduction requires an individualized approach.
Building an International Community of Paediatric Anaesthesiologists: An interview with Dr Edward Sumner

Dr Edward Sumner (1940) enjoyed a remarkably productive career as consultant pediatric anesthetist at the Great Ormond Street Hospital for Children. His leadership in clinical care helped his department rise to eminence. He trained hundreds of registrars in pediatric anesthesia and educated thousands more through invited lectures and by co-editing leading textbooks of neonatal and pediatric anesthesia. During his long tenure as Editor-in-Chief of Pediatric Anesthesia, he led the growth of the young journal to prominence. Based on an interview and a long-standing professional and personal friendship of forty-four years, this article reviews Ted Sumner's outstanding contributions to the specialty of pediatric anesthesia and to the development of a strong international community of pediatric anesthesiologists.
Opioid Use During the Six Months After an Emergency Department Visit for Acute Pain: A Prospective Cohort Study.

Study objective Despite the frequent use of opioids to treat acute pain, the long-term risks and analgesic benefits of an opioid prescription for an individual emergency department (ED) patient with acute pain are still poorly understood and inadequately quantified. Our objective was to determine the frequency of recurrent or persistent opioid use during the 6 months after the ED visit Methods This was a prospective, observational cohort study of opioid-naive patients presenting to 2 EDs for acute pain who were prescribed an opioid at discharge. Patients were followed by telephone 6 months after the ED visit. Additionally, we reviewed the statewide prescription monitoring program database. Outcomes included frequency of recurrent and persistent opioid use and frequency of persistent moderate or severe pain 6 months after the ED visit. Persistent opioid use was defined as filling greater than or equal to 6 prescriptions during the 6-month study period. Results During 9 months beginning in November 2017, 733 patients were approached for participation. Four hundred eighty-four met inclusion criteria and consented to participate. Four hundred ten patients (85%) provided 6-month telephone data. The prescription monitoring database was reviewed for all 484 patients (100%). Most patients (317/484, 66%; 95% confidence interval 61% to 70%) filled only the initial prescription they received in the ED. One in 5 patients (102/484, 21%; 95% confidence interval 18% to 25%) filled at least 2 prescriptions within the 6-month period. Five patients (1%; 95% confidence interval 0% to 2%) met criteria for persistent opioid use. Of these 5 patients, all but 1 reported moderate or severe pain in the affected body part 6 months later. Conclusion Although 1 in 5 opioid-naive ED patients who received an opioid prescription for acute pain on ED discharge filled at least 2 opioid prescriptions in 6 months, only 1% had persistent opioid use. These patients with persistent opioid use were likely to report moderate or severe pain 6 months after the ED visit.
The Effect of Diversity Climate on Institutional Affiliation/Pride and Intentions to Stay and Graduate: A Comparison of Latinx and Non-Latinx White Students.

This study analyzed student perceptions of diversity climate factors in a Hispanic Serving Institution (HSI). The climate of respect, perceived value of diversity on campus, and interracial interac...
College Food Insecurity: Implications on Student Success and Applications for Future Practice

Assessing basic needs of students at colleges and universities is gaining traction across the United States. Our research examined the prevalence of food and housing insecurity at a land-grant inst...
High Dimensional Normality of Noisy Eigenvectors

We study joint eigenvector distributions for large symmetric matrices in the presence of weak noise. Our main result asserts that every submatrix in the orthogonal matrix of eigenvectors converges to a multidimensional Gaussian distribution. The proof involves analyzing the stochastic eigenstate equation (SEE) which describes the Lie group valued flow of eigenvectors induced by matrix valued Brownian motion. We consider the associated colored eigenvector moment flow defining an SDE on a particle configuration space. This flow extends the eigenvector moment flow first introduced in Bourgade and Yau (2017) to the multicolor setting. However, it is no longer driven by an underlying Markov process on configuration space due to the lack of positivity in the semigroup kernel. Nevertheless, we prove the dynamics admit sufficient averaged decay and contractive properties. This allows us to establish optimal time of relaxation to equilibrium for the colored eigenvector moment flow and prove joint asymptotic normality for eigenvectors. Applications in random matrix theory include the explicit computations of joint eigenvector distributions for general Wigner type matrices and sparse graph models when corresponding eigenvalues lie in the bulk of the spectrum, as well as joint eigenvector distributions for Levy matrices when the eigenvectors correspond to small energy levels.
Chronic Obstructive Pulmonary Disease and Dysphagia: A Synergistic Review

Chronic obstructive pulmonary disease (COPD) is a leading global cause of death and disability. The literature has previously established clear physiological characteristics of COPD-related dysphagia (swallowing difficulties). However, COPD and dysphagia are both also intimately tied to breathing and contribute to a cascade of secondary physio-psycho-emotional sequalae, such as COPD exacerbation, anxiety, depression, increased economic burden, social isolation, and decreased quality of life. Further, the collective impact of these comorbidities may magnify disease impact, resulting in a downward spiral of well-being. Thus, the clinical relevance of COPD’s and dysphagia’s frequently occurring and overlapping sequelae cannot be overlooked, as the disease-related burden of both disorders is deeply rooted in the presence of concomitant physiological and psycho-emotional consequences. The current review explores the complex network of interactions between COPD, dysphagia, and their outcomes, framing this relationship within a mind-body-breath framework. Ultimately, we propose a model that more comprehensively captures the constellation of interrelated disease characteristics and consequences, highlighting a need for researchers and healthcare providers to consider disease impact more broadly in order to maximize treatment outcomes.
The MD/PhD Essay

The second essay required in the AMCAS primary application asks applicants to articulate why they want to pursue the MD/PhD combined degree. In other words, it is asking the question: “How have your clinical and research experiences shaped your career goals, and why are clinical medicine and academic research both indispensable to these aspirations?” This chapter provides several suggestions regarding how to approach this essay and what content is appropriate to include and discuss within the essay.
Hyperfine Filtering of an Electro-Optic Modulated Comb

We present a new architecture for generating low noise electro-optic modulated combs by simultaneously stabilizing and filtering all generated comb lines to a 100,000 finesse etalon. The comb exhibits an instrument limited >60 dB OSNR and ~1.7 ps FWHM pulses.
Earnings Momentum and Bank Loan Quality

In the aftermath of the financial crisis, bankers, regulators, lawmakers, and others claimed that bank CEOs’ incentives to sustain high past earnings growth (earnings momentum) led banks to originate lower quality loans, which subsequently defaulted at high rates in the financial crisis. We examine this claim. Using a sample of 267 U.S. bank holding companies from 2001 to 2009, we find banks with high earnings momentum have more future non-performing loans (NPLs). In contrast, neither CEO compensation incentives nor benchmark beating metrics are associated with future NPLs. Consistent with career concerns, the effect of earnings momentum on future NPLs is concentrated in banks with younger CEOs. We also find earnings momentum is positively associated with bank failures. Further analyses show results are independent of competition pressures and earnings guidance. Our study contributes to the literature on factors associated with the dramatic collapse of the banking system during the financial crisis.
Autosegmentation of cardiac substructures in respiratory-gated, non-contrasted computed tomography images.

Background Radiation dose to specific cardiac substructures can have a significant on treatment related morbidity and mortality, yet definition of these structures is labor intensive and not standard. Autosegmentation software may potentially address these issues, however it is unclear whether this approach can be broadly applied across different treatment planning conditions. We investigated the feasibility of autosegmentation of the cardiac substructures in four-dimensional (4D) computed tomography (CT), respiratory-gated, non-contrasted imaging. Aim To determine whether autosegmentation can be successfully employed on 4DCT respiratory-gated, non-contrasted imaging. Methods We included patients who underwent stereotactic body radiation therapy for inoperable, early-stage non-small cell lung cancer from 2007 to 2019. All patients were simulated via 4DCT imaging with respiratory gating without intravenous contrast. Generated structure quality was evaluated by degree of required manual edits and volume discrepancy between the autocontoured structures and its edited sister structure. Results Initial 17-structure cardiac atlas was generated with 20 patients followed by three successive iterations of 10 patients using MIM software. The great vessels and heart chambers were reliably autosegmented with most edits considered minor. In contrast, coronary arteries either failed to be autosegmented or the generated structures required major alterations necessitating deletion and manual definition. Similarly, the generated mitral and tricuspid valves were poor whereas the aortic and pulmonary valves required at least minor and moderate changes respectively. For the majority of subsites, the additional samples did not appear to substantially impact the quality of generated structures. Volumetric analysis between autosegmented and its manually edited sister structure yielded comparable findings to the physician-based assessment of structure quality. Conclusion The use of MIM software with 30-sample subject library was found to be useful in delineating many of the heart substructures with acceptable clinical accuracy on respiratory-gated 4DCT imaging. Small volume structures, such as the coronary arteries were poorly autosegmented and require manual definition.
Chasing the Trends: How does IT Knowledge Impact Individuals’ Career Development?

With the growing importance of information technology in the world, extensive evidence has shown the pivotal role of IT in businesses at the industry and firm level. However, little is known about the value of “personal IT knowledge acquisition” in individual career development. This paper aims to bridge this gap. Towards this end, we obtained a unique data set covering 1 million randomly selected individuals’ career records between 2000 and 2016 from a leading online employment service company in China. We identified individuals’ IT knowledge in both the generalized and specialized IT domains over time. We then employed extensive econometric analyses to identify the nuanced effects of IT knowledge acquisition on an individual’s career development. In particular, we examined the average effects, time-varying effects, and the moderating effects with three potential bias factors, including home bias, big-city bias, and gender bias indicators. Our empirical results suggest that acquiring specialized IT knowledge would increase an individual’s annual salary, on average, by 2.59%, ceteris paribus. The value of specialized IT knowledge has accelerated since 2010, with annual increases ranging from 5% to over 12%. Further, it is important to acquire the “right” knowledge at the “right” time: there is a significant time-varying effect of different types of specialized IT knowledge over time (e.g., AI and deep learning in recent years). Lastly, we observe that having specialized IT knowledge can help individuals reduce common biases (i.e., home bias, big-city bias, and gender bias) in the labor market. In particular, we observe that the acquisition of specialized IT knowledge would mitigate the salary gaps resulting from the home bias and big-city bias (by 1.11% and 5.92%, respectively). Interestingly, females benefit more from having specialized IT knowledge – it helps reduce gender biases by 12.7%. Our analyses further reveal an interesting trade-off - while having specialized IT knowledge helps workers obtain salary increases, having generalized IT knowledge helps workers extend their tenure with the firm. Our paper offers significant managerial implications for both the individual career development and the policymakers.
Tangent fields, intrinsic stationarity, and self-similarity (with a supplement on Matheron Theory)

This paper studies the local structure of continuous random fields on $\mathbb R^d$ taking values in a complete separable linear metric space ${\mathbb V}$. Extending seminal work of Falconer, we show that the generalized $(1+k)$-th order increment tangent fields are self-similar and almost everywhere intrinsically stationary in the sense of Matheron. These results motivate the further study of the structure of ${\mathbb V}$-valued intrinsic random functions of order $k$ (IRF$_k$,\ $k=0,1,\cdots$). To this end, we focus on the special case where ${\mathbb V}$ is a Hilbert space. Building on the work of Sasvari and Berschneider, we establish the spectral characterization of all second order ${\mathbb V}$-valued IRF$_k$'s, extending the classical Matheron theory. Using these results, we further characterize the class of Gaussian, operator self-similar ${\mathbb V}$-valued IRF$_k$'s, generalizing results of Dobrushin and Didier, Meerschaert and Pipiras, among others. These processes are the Hilbert-space-valued versions of the general $k$-th order operator fractional Brownian fields and are characterized by their self-similarity operator exponent as well as a finite trace class operator valued spectral measure. We conclude with several examples motivating future applications to probability and statistics. In a technical Supplement of independent interest, we provide a unified treatment of the Matheron spectral theory for second-order stationary and intrinsically stationary processes taking values in a separable Hilbert space. We give the proofs of the Bochner-Neeb and Bochner-Schwartz theorems.
Behavior of Liquids in Free Fall

Recent rocket and satellite activities have brought into focus a number of important problems involving the behavior of liquids under weightless conditions. Study of the behavior of liquids in free fall can give considerable insight into the behavior of liquids in space. A photographic study of boiling during 8 ft. of free fall1 clearly demonstrated the existence of differences between earth bound and and weightless fluid behavior. An analysis of the relative orders of magnitudes of surface tensile, viscous, and inertia forces acting on weightless liquid2 allows estimation of the approximate time required for deformation due to surface tension after removal of gravity forces. In the present note, some photographs of fluids in free fall are included. It should be noted that this study was entirely qualitative and of a very preliminary nature. For these experiments, a free-fall vehicle consisting of a 2-in. square lucite box and a heavy steel weight was constructed. The vehicle was dropped from heights up to 16 ft. and caught by an arresting system. Liquids placed in the lucite box were photographed at the bottom of their fall by a 3-microsecond exposure flash camera. While the container was dropped from successively greater heights, a series of photographs was taken which show the progress of the fluid in free fall.
Characterization of discrete decoupling capacitors for high-speed digital systems

This paper describes frequency-dependent characterization of multi-terminal decoupling capacitors (2, 8, 14, and any arbitrary number of terminals) by using a full-wave tool developed at Intel. This tool can capture high frequency effects with fast CPU run time, which enables accurate modeling of the power delivery system. The full-wave S-parameters have been validated with the measurements and the modeled data obtained from a commercial tool (HFSS). Based on its fast and accurate solution, different design configurations of capacitors have been studied to identify the optimal configuration which maximizes the performance of the decoupling capacitor. To capture the frequency-dependent behavior of capacitor impedance, a higher order representation made up with 7 or 9 elements of RLGC was developed. This circuit representation was used to assess the accuracy of the conventional series lumped RLC capacitor model. Finally, the responses were incorporated into a high performance microprocessor power delivery network to investigate system performance.
Uptake of Selenium-75 by Human Lymphocytes in Vitro

Selenite uptake by human lymphocytes was studied both in whole blood and in isolated cells. When 75Se-selenite (75Se-SeO3-2--) is supplied to whole blood, it is converted by the erythrocytes to a form which rapidly becomes bound to plasma proteins. Studies with a variety of inhibitors indicated that the process is not energy dependent but that sulfhydryl groups are required. The 75Se bound to plasma proteins is absorbed by lymphocytes in preference to 75SeO3-2-. By the use of selective inhibitors (respiratory, sulfhydryl, protein biosynthetic) it was demonstrated that the uptake of either form of 75Se requires neither energy nor protein synthesis; however, all the sulfhydryl inhibitors cause a decrease of absorption. A scheme which summarizes the pathway of selenite conversion in human blood and uptake by lymphocytes is presented; the data indicate that plasma proteins function as carriers of selenium to lymphocytes.
External-Focus Feedback Benefits Free-Throw Learning in Children

Purpose: Considerable research supports the motor-learning advantage associated with an external focus of attention; however, very few studies have attempted to generalize these findings to children especially with attentional focus feedback. Therefore, the purpose of this study was to determine the effect of attentional focus feedback on motor learning in children. Method: Boys (n = 14) and girls (n = 14) aged 9 to 11 years old were randomly assigned to 1 of 2 gender-stratified groups: (a) internal-focus feedback or (b) external-focus feedback. Following initial instructions and task demonstration, participants performed 100 modified free throws over 2 days while receiving feedback statements respective to their attentional focus condition. Approximately 24 hr later, participants performed a retention test consisting of 20 additional free throws. Participants were also asked to respond to a retrospective verbal report at the end of each day to serve as a manipulation check. Results: Results of the analys...
Constructing Recombinant DNA Molecules by the Polymerase Chain Reaction

This unit describes the use of PCR to construct hybrid DNA molecules. The main objective is to give an overview of how PCR can be exploited to accomplish numerous cloning strategies; it is assumed that the reader is already familiar with basic molecular biology techniques including PCR amplification and subcloning. The Basic Protocol outlines the PCR amplification and cloning strategies. A troubleshooting guide for problems most frequently encountered in PCR cloning, and three specific examples of this technique--for creating (1) in-frame fusion proteins, (2) recombinant DNA products, and (3) deletions and inversions by inverse PCR--are also presented.
Composable Algorithms for Interdependent Cyber Physical Systems

Cyber-Physical Systems (CPS) applications are being increasingly used to provide services in domains such as health-care, transportation, and energy. Providing such services may require interactions between applications, some of which may be unpredictable. Understanding and mitigating such interactions require that CPSs be designed as open and composable systems. Composition has been studied extensively in the literature. To complement this work, this paper studies composition of cyber algorithms with user behaviors in a CPS. Traditional middleware algorithms have been designed by abstracting away the underlying system and providing users with high-level APIs to interact with the physical system. In a CPS, however, users may interact directly with the physical system and may perform actions that are part of the services provided. We find that by accounting for user interactions and including them as part of the solution, one can design algorithms that are more efficient, predictable and resilient. To accomplish this, we propose a framework to model both the physical and the cyber systems. This framework allows specification of both physical algorithms and cyber algorithms. We discuss how such specifications can be composed to design middleware that leverages user actions. We show that such composite solutions preserve invariants of the component algorithms such as those related to functional properties and fault-tolerance. Our future work involves developing a comprehensive framework that uses compositionality is a key feature to address interdependent behavior of CPSs.
Total Knee Arthroplasty Following High Tibial Osteotomy

Valgus high tibial osteotomy has been advocated for the treatment of isolated medial compartment osteoarthritis. Successful results have been obtained in eighty to ninety percent of patients in the short term (1). However, with longer follow-up progressive arthritic deterioration has developed in more patients requiring conversion to total knee arthroplasty (1). Conversion of a high tibial osteotomy to a total knee arthroplasty introduces unique challenges not typically encountered during primary total knee arthroplasty
Gene Genealogies in Geographically Structured Populations

Population genetics theory has dealt only with the spatial or geographic pattern of degrees of relatedness or genetic similarity separately for each point in time. However, a frequent goal of experimental studies is to infer migration patterns that occurred in the past or over extended periods of time. To fully understand how a present geographic pattern of genetic variation reflects one in the past, it is necessary to build genealogy models that directly relate the two. For the first time, space-time probabilities of identity by descent and coalescence probabilities are formulated and characterized in this article. Formulations for general migration processes are developed and applied to specific types of systems. The results can be used to determine the level of certainty that genes found in present populations are descended from ancient genes in the same population or nearby populations vs. geographically distant populations. Some parameter combinations result in past populations that are quite distant geographically being essentially as likely to contain ancestors of genes at a given population as the past population located at the same place. This has implications for the geographic point of origin of ancestral, "Eve," genes. The results also form the first model for emerging "space-time" molecular genetic data.
3D thermal analysis of AlGaN/GaN high power ultraviolet light-emitting diodes

We report 3D simulation of AlGaN/GaN high power (λ ∼ 350 nm) light emitting diodes (LEDs) for their advance thermal management. Theoretical transit thermal analysis study has been carried out for an efficient heat distribution and dissipation from the junction layer. The designed package was mainly consists of three layers namely, thermal interfacial materials (TIM), specialty designed submount and high conductivity heat-sink. Efficient non-metallic and inter-metallic material layers such as, single layer carbon nano-tubes (CNT), Au 20 Sn 80 , and Ag 3.5 Sn 96.5 as TIMs, high thermal conductivity AlN, SiC, and diamond (C) as submounts and Al, & Cu as heat-sinks were employed. Finite element analysis was performed to investigate the heat distribution and dissipation profile through junction layer. Calculated data was analyzed using transient temperature profile to find a suitable combination of TIM, sbmount and heat sink for an efficient thermal management of high power UV LEDs. Comparative study showed that CNT, C and Cu were among the best suited choice as TIM, submount and heat-sink. The estimated average temperature of Cu as heat-sink was ∼ 60 °C for Au 20 Sn 80 , and ∼ 50 °C for Ag 3.5 Sn 96.5 , whereas, the transient temperature profile of CNT was ∼ 160 °C respectively.
Wind and trees: Air infiltration effects on energy in housing

Abstract A series of wind tunnel tests have been conducted to examine the ways in which wind influences air infiltration energy losses in residential housing. A quantitative model for air infiltration has been developed that is based upon a linear relationship between air flow and pressure difference across walls and roof surfaces. With the model, a variety of windhouse orientations are tested, and the sheltering effects provided by solid fences, adjacent houses, and tall evergreen trees are assessed and compared.
Effect on food intake by rats of day-night cycle control and increment in deprivation.

Additional data on the relation between food intake and deprivation were provided by incorporating Siegel's day-night cycle control and extending the small increments in deprivation. Ten male hooded rats were housed in individual translucen cages and exposed to a constant illumination from a 25-w light. on the last day of a 10-day base period 10 Ss were assigned to 10 deprivation levels: 0, 8, 16, 24, 36, 48, 60, 72, 84, and 96 hr., but each S began a sequence at each of the 10 levels and then began another at the next level so that each level preceded and followed each other level an equal number of times. Before each deprivation Ss were weighed, deprived, and then given a 3-hr. food-intake period. At the end of this period remaining food pellets were removed and weighed. Ss were maintained on a continuous food schedule for at least twice as long as the last deprivation in order to regain lost weight. Food intake increased steadily and reached constant maximum after 16 hr., not the usual 24 hr.
(528) The influence of fear of pain on activity-induced exacerbation of delayed onset muscle pain

Little is known regarding the influence of fear of pain on acute exacerbations of pain during activity, which is reported in several chronic pain conditions. Thus, the purpose of this study was to investigate the influence of fear of pain on pain perception during activity and at rest after induced delayed onset muscle pain (DOMP) of the bicep. Forty-two young healthy adults completed 2 consecutive days of testing. On Day 1, subjects completed the State-Trait Anxiety Inventory –Trait version (STAI-T), the Pain Catastrophizing Scale (PCS), and the Fear of Pain Questionnaire (FPQ-III). Then, subjects performed an eccentric exercise protocol of the non-dominant elbow flexors to induce DOMP. At baseline and 24 hours after the eccentric exercise protocol, bicep pain was assessed at rest and during elbow flexion, and extension. Subjects were then randomly assigned to perform 20 minutes of either standardized activity of the painful muscles (elbow flexion/extension with a 1lb dumbbell), non-standardized activity of the painful muscles (elbow flexion/ extension while playing Nintendo Wii Boxing), or quiet rest. Subjects rated their worst pain during the activity/rest. Step-wise regression models considered baseline pain measures and scores on the STAI-T, PCS, and FPQ-III as predictors of DOMP at rest and elbow flexion/extension 24 hours later. Bivariate correlations examined the relationship between fear of pain and worst pain during 20 minutes of activity or rest. FPQ-III scores significantly predicted DOMP at rest (b=.481) and pain during elbow extension (b=.445), and were significantly related to worst pain during 20 minutes of rest (r=.853) and standardized elbow flexion/extension activity (r=.733). These results confirm the influence of fear of pain on DOMP while at rest and provide novel evidence showing that greater fear of pain is also associated with greater activityinduced exacerbations of DOMP, with the exception of pain reported while playing Wii Boxing.
Domain structure in epitaxial metastable zinc-blende (GaAs)1-x(Ge2)x(001) alloys.

Plane-view and cross-sectional transmission electron microscopy have been used to examine the structure of epitaxial metastable zinc-blende (GaAs)/sub 1-//sub x/(Ge/sub 2/)/sub x/ alloys grown by rf sputter deposition on GaAs(001) substrates. An analysis of bright-field and dark-field images obtained from both fundamental and superstructure reflections showed, in addition to (111) microtwins and (a/2) line dislocations, the existence of ordered antiphase regions. However, the domain boundaries were not composed of Ga: Ga and As: As antisite bonds, as in III-V films grown on group-IV substrates, but formed stochastically due to the presence of Ge in agreement with previously published theoretical growth kinetic models. The Ge-mediated boundaries were planar and gave rise to an additional contrast in dark-field images obtained with /002/ superstructure reflections. From cross-sectional micrographs and plane-view images obtained with samples tilted away from the (001) zone axis, the antiphase regions were shown to extend primarily parallel to the growth direction but with random off-axis components weaving through the matrix. The spatial extent and number density of these domains increased with increasing Ge concentrations.
Ethics in Health Education: The Need to Include a Model Course in Professional Preparation Programs

Abstract The study of ethics is not new to the field of health education. Trends in today's society have resulted in a renewed emphasis on studying ethics in a variety of disciplines. Society is asking for greater accountability from all professions. The health education profession involves content areas which provide a plethora of opportunities for discussing ethics and ethical reasoning. The purpose of this article is to describe a proposed model course for the study of ethics in professional preparation programs of health education. Specifically, this paper includes a review of related literature, a discussion on the importance to include ethics instruction in professional preparation programs and a description of proposed course goals, as well as suggested content areas, teaching methods, and student activities to incorporate in a course on ethics instruction as a part of professional preparation programs for health educators. This proposed course outline is an attempt to suggest a curriculum which wi...
Finding Surface Correspondences Using Symmetry Axis Curves

In this paper, we propose an automatic algorithm for finding a correspondence map between two 3D surfaces. The key insight is that global reflective symmetry axes are stable, recognizable, semantic features of most real-world surfaces. Thus, it is possible to find a useful map between two surfaces by first extracting symmetry axis curves, aligning the extracted curves, and then extrapolating correspondences found on the curves to both surfaces. The main advantages of this approach are efficiency and robustness: the difficult problem of finding a surface map is reduced to three significantly easier problems: symmetry detection, curve alignment, and correspondence extrapolation, each of which has a robust, polynomial-time solution (e.g., optimal alignment of 1D curves is possible with dynamic programming). We investigate of this approach on a wide range of examples, including both intrinsically symmetric surfaces and polygon soups, and find that it is superior to previous methods in cases where two surfaces have different overall shapes but similar reflective symmetry axes, a common case in computer graphics. © 2012 Wiley Periodicals, Inc.
A computationally efficient inverse modelling approach of inherent optical properties for a remote sensing model

Inverse modelling of inherent optical properties (IOP) is an alternative to the in situ measurements of IOP requiring specialized instruments. However, inverse modelling using Monte Carlo models may require very large computational time due to a large number of dynamic model runs needed to search the optimum parameter values. We present a new approach to reduce this computational time. Mathematical relationships were developed for wavelength and concentration dependence of IOP values of suspended mineral based on four parameters. Optimal values of these four parameters were calculated by minimizing the mean sum of error between the physical hyperspectral optical-Monte Carlo (PHO-MC) model predicted reflectance to measured reflectance values for selected 33 reflectance measurements for a set of 11 wavelengths and three suspended sediment concentrations. The computation time was significantly reduced by several orders of magnitude by: (1) replacing the PHO-MC model with 11 wavelengths specific pseudo-simulator models developed by applying artificial neural network approach; and (2) using a nondominated sorted genetic algorithm -II (NSGA II) to search the global optimal solution of four parameters of IOP equations. Determined IOP values of suspended minerals were then successfully validated by using them as input to PHO-MC model to predict reflectance values for an independent set of 287 combinations of 41 wavelengths and seven suspended sediment concentrations.