cssi/SciSciGPT-SciSciNet huggingface dataset:
New frontiers in cloud computing research

Cloud computing is challenging conventional wisdom and practices in the management of IT resources and capabilities; at the same time, the technical underpinnings of cloud computing offer unique opportunities and levers for addressing these challenges. In this talk, I will talk about a number of new research thrusts brought forth by the cloud computing paradigm. First, the large magnitude of a typical virtual machine (VM) image and the large volume of common VM libraries have major performance implications for many cloud operations. Fortunately, content similarity that often exists across distinct VM images may be exploited to optimize the transfer and storage of VM images. Second, resource virtualization in the cloud is at odds with the assumptions in traditional software license models, which must be adapted or extended for virtualized environments. There is also a critical need for new license management techniques to help cloud-based software users achieve cost-effectiveness and compliance. Third, cloud infrastructure is evolving towards heterogeneity and is becoming programmable and composable. The so-called Software-Defined Infrastructure promises agility, flexibility, efficiency, and resilience through continuous and proactive optimization of heterogeneous resources to meet the changing requirements of a wide variety of workloads. For each of these research thrusts, I will discuss the specific technical issues and some initial work conducted at IBM Research.
Size and confinement effects on the glass transition behavior of polystyrene/ o -terphenyl polymer solutions

Polystyrene $(\mathrm{PS})/o\ensuremath{-}\mathrm{terphenyl} (o\mathrm{TP})$ solutions confined to nanometer scale pores were studied by differential scanning calorimetry to investigate size and confinement effects on the glass transition. We observed two glass transitions ${T}_{g}$ in all thermograms for materials confined in the controlled pore glasses. One was at a lower temperature than the bulk state ${T}_{g}$ and the other was at a higher temperature. The lower transition temperature decreases with decreasing pore size, which is consistent with previous reports from this laboratory on small molecule glass formers and some other reports in similar systems. Although $o\mathrm{TP}$ and $o\mathrm{T}\mathrm{P}/\mathrm{P}\mathrm{S}$ are not hydrogen bonding materials, we interpret the higher temperature transition as due to the existence of an interacting layer at the pore surface. A two-layer model in which there exists a ``core'' liquid in the center surrounded by the interacting layer at the pore surface is consistent with our observations.
Pushing Patriotism: Why Flag Encouragement Doesn't Fly

The federal Freedom to Display the American Flag Act of 2005 prohibits homeowners' associations (HOAs) from forbidding the display of the American flag. At least twenty states also have such laws, most of which have not been challenged in court. This article suggests that these “flag-encouragement laws” would not withstand challenges by either residents of HOAs or by HOAs themselves. HOA residents may use the state action doctrine to apply traditional First Amendment jurisprudence to these content-based laws, and HOAs may attack the laws using other precedents of the Supreme Court of the United States.
Absorption pathways of amino acids in the midgut of Manduca sexta larvae

Abstract The unidirectional transport of leucine and aspartic acid by midgut epithelium cells of the tobacco ornworm, Manduca sexta , was investigated using brush border membrane vesicles. Both K + -stimulated and K + -insensitive transport pathways for these two amino acids were identified. Kinetic analyses and profiles of cis-inhibition by other amino acids demonstrated that leucine and aspartic acid are transported by separate pathways and exhibit different sensitivity to potassium ion.
11 paper place

A love story about two 8.5 x 11 sheets of paper that magically transform into paper people as they are spit out of a malfunctioning printer into a recycling bin.
The timed-pregnant baboon animal model can be used for determining the role of soluble vascular endothelial growth factor receptors 1 and 2 during development.

Background During pregnancy, mechanisms that allow for regulation of continuous fetal and placental vasculogenesis with prevention of maternal neo-vascularization remain elusive. The vascular endothelial growth factor (VEGF) biological system has a key role during vasculogenesis. The aims of this study were to validate a bioassay for soluble vascular endothelial growth factor receptors 1 and 2 (sVEGFR-1 and sVEGFR-2) in baboon plasma and to determine the maternal and fetal plasma concentration of these receptors at the end of the baboon pregnancy. Methods Maternal peripheral blood samples were obtained from eight baboons (Papio anubis) prior to elective cesarean section and from the umbilical cord after the fetuses were delivered. Spike and recovery experiments at various concentrations in pooled baboon maternal plasma were used to validate a human quantitative sandwich immunoassay for sVEGFR-1 and -2. Concentrations of sVEGFR-1 and -2 were then determined in maternal and fetal plasma samples. Results No significant correlations were observed between sVEGFR-1 or -2 concentrations in maternal and fetal circulations. The concentration of sVEGFR-1 was at least 30 times greater and that of sVEGFR-2 approximately two times greater, in maternal than in cord plasma (both P < 0.01). Conclusions These findings suggest that baboons can be used to study the regulation of vasculogenesis during pregnancy.
Isolation of Temperature-Sensitive Conditional Lethal Mutants of “Fixed” Rabies Virus

Abstract In an attempt to induce temperature-sensitive (ts) conditional lethal mutants of rabies virus, stocks of a plaque-purified substrain of strain CVS fixed rabies virus were subjected to mutagenesis by HNO2, 5-fluorouracil, or 5-azacytidine. It was necessary to prepare virus stocks from clones of mutagenized virus selected at random and to test subsequently each stock for possible ts characteristics by measuring its relative capacity for growth at permissive (33 C) and nonpermissive (40.5 C) temperatures. Five ts mutants were detected in tests of 161 clones of mutagenized virus. Each of the mutants exhibited a remarkably low incidence of reversion and little demonstrable “leakiness.” One of the five ts mutants (ts2), which formed formed very small plaques, and another (ts1), which formed plaques of only slightly reduced size, were further characterized. Virus ts1 was more thermostable at 40.5 C than the parental virus, but the ts2 mutant was unchanged in this respect. The ts1 virus exhibited normal pathogenicity for mice, but ts2 virus caused a very irregular death pattern. Both deaths and survivors immune to rabies virus challenge were noted in all groups of mice inoculated with ts2 virus, regardless of the virus dose.
The Maternal Description of Child (MDoC): A New Audiotaped Measure of Maternal Affect

We report on a new measure of maternal affect from an ongoing multi-site birth cohort study with primarily low-income families, the Fragile Families and Child Wellbeing Study. At child age of 5 years, mothers were asked to describe their child in a short, semi-structured home interview. One innovation of this measure - called the Maternal Description of Child (MDoC) - is that it captured maternal affect via audiotape rather than videotape. Based on mothers' talk about their child, coders scored mothers on Positive Affect, Negative Affect, and Detachment. Evidence is presented to support the convergent and predictive validity of these scales. Given that objective measures of parenting are generally preferable to self-reported measures, further research should determine whether the MDoC can be successfully administered by phone. If it can, the MDoC would allow large-scale phone surveys to measure maternal affect for the first time.
Empirical analysis of CK metrics for object-oriented design complexity: implications for software defects

To produce high quality object-oriented (OO) applications, a strong emphasis on design aspects, especially during the early phases of software development, is necessary. Design metrics play an important role in helping developers understand design aspects of software and, hence, improve software quality and developer productivity. In this paper, we provide empirical evidence supporting the role of OO design complexity metrics, specifically a subset of the Chidamber and Kemerer (1991, 1994) suite (CK metrics), in determining software defects. Our results, based on industry data from software developed in two popular programming languages used in OO development, indicate that, even after controlling for the size of the software, these metrics are significantly associated with defects. In addition, we find that the effects of these metrics on defects vary across the samples from two programming languages-C++ and Java. We believe that these results have significant implications for designing high-quality software products using the OO approach.
Re-thinking the Foundation of Primary Care Nursing

The University at Buffalo (UB), Family Nurse Practitioner (FNP) program was recently funded by a Health Resources Service Administration (HRSA), Bureau of Health Professions, Advanced Nurse Trainin...
Pleural effusion accumulating in the epidural space: recurrent cord compression in a patient with progressive lung adenocarcinoma.

Pleural effusions are common in patients with advanced carcioma, particularly of the lung and breast. While the spinal column ies adjacent to the pleura, to our knowledge there is no reported ase of a pleural effusion causing cord compression. The epidural pace is normally isolated from the pleural space by the parietal leura, spinal column, ribs, and associated soft tissue. Here we describe a patient with lung carcinoma and a prior horacic laminectomy for epidural metastasis who presented with ecurrent cord compression. She was found to have a large epidural uid collection in the region of the prior laminectomy, as well as large pleural effusion which had developed simultaneously. The pidural collection was thin in consistency and under high pressure, onsistent with pleural fluid. The pleural effusion became smaller fter drainage of the epidural collection, suggesting the presence f a pleural–epidural fistula.
NESTED FISCAL IMPACT MEASURES USING THE NEW THEORY OF LOCAL PUBLIC GOODS

In this paper, we use recent advances in the theory of local public goods to develop more-complete measures of the fiscal impacts of population change. Each fiscal impact measure extends the average-cost-based simple multiplier. The service-based impact measure accounts for the public service production function. The local welfare measure further allows the size of the public budget to vary. The global welfare measure additionally introduces interneighborhood substitution of public services. These four nested measures are calculated for police servims in Vancouver. We demonstrate that the commonly used simple multiplier is an unreliable estimator of fiscal impacts.
Structure-activity relationship of conformationally constrained peptidomimetics for antiproliferative activity in HER2-overexpressing breast cancer cell lines

Human epidermal growth factor receptor 2 (HER2) is a member of the human epidermal growth factor receptor kinases and is involved in a signaling cascade for cell growth and differentiation. It is well established that HER2-mediated heterodimerization has important implications in cancer. Deregulation of signaling pathways and overexpression of HER2 are known to occur in cancer cells, indicating the role of HER2 in tumorigenesis. Therefore, blocking HER2-mediated signaling has potential therapeutic value. We have designed several peptidomimetics to inhibit HER2-mediated signaling for cell growth. One of the compounds (compound 5, Arg-[3-amino-3(1-naphthyl)-propionic acid]-Phe) exhibited antiproliferative activity with IC50 values in the nanomolar to micromolar range in breast cancer cell lines. To further investigate the structure–activity relationship of the compounds, various analogs of compound 5 were designed. Conformational constraints were initiated in the peptidomimetic with introduction of a Pro residue in the peptidomimetic sequence. Results of antiproliferative activity indicated that analogs of compound 5 with C-and N-terminal ends capped compound 16 and compound 9 with Asp at the C-terminal exhibited antiproliferative activity in the lower micromolar range against breast cancer cell lines. Introduction of conformational constraints such as Pro residue in the sequence or cyclization did not enhance the activity of the peptidomimetic. Competitive binding studies were carried out to evaluate the binding of potent peptidomimetics to HER2-overexpressing cancer cell lines. Results indicated that compounds exhibiting antiproliferative activity in breast cancer cell lines bind to the cells that overexpress HER2 protein.
Peak antibody production is associated with increased oxidative metabolism in an industrially relevant fed‐batch CHO cell culture

Cell metabolism can vary considerably over the course of a typical fed-batch antibody production process. However, the intracellular pathway alterations associated with various phases of growth and antibody production have yet to be fully elucidated using industrially relevant production hosts. Therefore, we performed (13)C labeling experiments and metabolic flux analysis (MFA) to characterize CHO cell metabolism during four separate phases of a fed-batch culture designed to closely represent industrial process conditions. First, we found that peak specific growth rate was associated with high lactate production and minimal TCA cycling. Conversely, we found that lactate metabolism switched from net production to net consumption as the culture transitioned from peak growth to peak antibody production. During the peak antibody production phase, energy was primarily generated through oxidative phosphorylation, which was also associated with elevated oxidative pentose phosphate pathway (oxPPP) activity. Interestingly, as TCA cycling and antibody production reached their peaks, specific growth rate continued to diminish as the culture entered stationary phase. However, TCA cycling and oxPPP activity remained high even as viable cell density began to decline. Overall, we found that a highly oxidative state of metabolism corresponded with peak antibody production, whereas peak cell growth was characterized by a highly glycolytic metabolic state.
A Diffusion Approximation for the G/GI/n/m Queue

We develop a diffusion approximation for the queue-length stochastic process in theG/GI/n/m queueing model (having a general arrival process, independent and identically distributed service times with a general distribution,n servers, andm extra waiting spaces). We use the steady-state distribution of that diffusion process to obtain approximations for steady-state performance measures of the queueing model, focusing especially upon the steady-state delay probability. The approximations are based on heavy-traffic limits in whichn tends to infinity as the traffic intensity increases. Thus, the approximations are intended for largen.For theGI/M/n/8 special case, Halfin and Whitt (1981) showed that scaled versions of the queue-length process converge to a diffusion process when the traffic intensity? napproaches 1 with (1 -? n )v n ? I for 0 <I < 8. A companion paper, Whitt (2005), extends that limit to a special class ofG/GI/n/m nmodels in which the number of waiting places depends onn and the service-time distribution is a mixture of an exponential distribution with probabilityp and a unit point mass at 0 with probability 1 -p. Finite waiting rooms are treated by incorporating the additional limitm n/vn ? ? for 0 <? = 8. The approximation for the more generalG/GI/n/m model developed here is consistent with those heavy-traffic limits. Heavy-traffic limits for theGI/PH/n/8 model with phase-type service-time distributions established by Puhalskii and Reiman (2000) imply that our approximating process is not asymptotically correct for nonexponential phase-type service-time distributions, but nevertheless, the heuristic diffusion approximation developed here yields useful approximations for key performance measures such as the steady-state delay probability. The accuracy is confirmed by making comparisons with exact numerical results and simulations.
Control Data Corporation: the Norris era

From a modest start in 1957, Control Data Corporation under the leadership of its founder, William C. Norris, grew rapidly to become a worldwide, multibillion dollar enterprise, the major producer of the world's most powerful computers and peripheral products and provider of a wide range of vital computer services. Along the way the company explored means for applying digital technologies to aid in the solution of critical problems of contemporary society. From a pinnacle of achievement by the early 1980s, Control Data slipped into a series of technological and financial crises, from which it is still struggling to emerge. >
Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma is an aggressive non-Hodgkin's lymphoma without a standard therapy for patients who relapse after or are not eligible for salvage autologous stem cell transplantation. In vitro analysis of lymphoma cell lines has shown that everolimus can inhibit cell cycle progression in vitro and inhibitors of the mammalian target of rapamycin have already demonstrated single-agent activity in relapsed non-Hodgkin's lymphomas including diffuse large B-cell lymphoma, validating mammalian target of rapamycin as a viable therapeutic target. We performed an open label phase II study of everolimus, an inhibitor of mammalian target of rapamycin, in combination with rituximab to examine efficacy and tolerability in patients with relapsed/refractory diffuse large B-cell lymphoma. Eligible patients were treated with everolimus 10 mg by mouth once daily on days 1-28 of a 28-day cycle with rituximab administered weekly during cycle one and then on day one of subsequent cycles. Patients were treated for a total of 12 cycles or until disease progression. The primary end-point was objective response rate, with secondary end-points being toxicity, progression-free survival, duration of response, and overall survival. Twenty-six patients (24 evaluable) were enrolled and had an overall response rate of 38% [90% CI (21%-56%)] with three complete responses and six partial responses among these 24 patients. The median duration of response among responders was 8.1 months. At a median follow-up of 12 months, the overall survival rate was 37% [90% CI (20%-54%)]. The most common grade 3 to 4 toxicities were neutropenia, anemia, and thrombocytopenia. In conclusion, everolimus in combination with rituximab is well tolerated and demonstrates activity in relapsed diffuse large B-cell lymphoma. Further studies of this combination are warranted. Clinicaltrials.gov identifier: NCT00869999
Life, genes, and death in Ph- MPNs.

In this issue of Blood , Tefferi et al make the important observations that polycythemia vera (PV) is not a continuum from essential thrombocythemia (ET), that survival in ET is less than matched controls but of longer duration than in patients with PV and primary myelofibrosis (PMF), and that “
Graduate-undergraduate interaction in wireless applications research and development

The School of Electrical and Computer Engineering at Purdue University is offering a new mobile communications project class for junior and senior undergraduate students. Students work in teams to design real-world applications for different mobile communications technologies. The wireless application development group is composed of several teams that aim to develop state-of-the-art wireless applications for IEEE 802.11 based mobile devices. Each of these undergraduate teams in this group is led by a graduate student, under the supervision of the professor. The research and development projects conducted in this group have led to a couple of conference papers and a journal paper in the past semesters. This paper describes the projects done in this group by the undergraduate students, presents the graduate student advisory experience, and the graduate-undergraduate interaction throughout the process, and suggests methods for such interactivity to be productive. It also discusses the impact of such interactions on the undergraduate students as well as on the graduate mentors.
Direction finding using spatial polarimetric time-frequency distributions

In this paper, we introduce the spatial polarimetric time-frequency distribution (SPTFD) as a platform to process nonstationary array signals with two orthogonal polarization components, such as horizontal and vertical. The use of dual polarization empowers the STFDs and improves the robustness of the respective signal and noise subspaces. With the additional polarimetric information, improved direction finding performance can be achieved. To demonstrate such advantages, the polarimetric time-frequency MUSIC (PTF-MUSIC) method is proposed based on the SPTFD platform and is shown to outperform the MUSIC techniques based on the time-frequency, polarimetric, and conventional methods.
Welfare Reform and Older Immigrants' Health Insurance Coverage

Objectives. I examined changes in older immigrants' health insurance coverage after welfare reform in the United States to determine whether the reform measures achieved their goal of saving money by reducing Medicaid participation without increasing the number of uninsured people.Methods. Data were obtained from older adults who participated in the Current Population Survey's Annual Social and Economic Supplement from 1994 to 1996 and 2001 to 2005. I used logistic regression to estimate changes in the sample's Medicaid and health insurance coverage after welfare reform, paying special attention to noncitizens and recent immigrants.Results. Older immigrants' health insurance status was associated with their citizenship status and length of stay in the United States. Medicaid participation significantly decreased among noncitizens and recent immigrants but increased among naturalized citizens. Private health insurance and employer-sponsored insurance coverage significantly increased among recent immigrants...
Low-cost routing in selfish and rational wireless ad hoc networks

Numerous routing protocols have been proposed for wireless networks. A common assumption made by the majority of these protocols is that each wireless node will follow the prescribed protocol without any deviation. This may not be true in practice since wireless nodes could be owned by users who perform in their own interests. We then have to design routing protocols that still work properly even for networks composed of selfish nodes. In this paper, we propose a unicast routing protocol to address this issue under the assumption that all networking nodes are rational. Here, a node is rational if it always chooses a strategy that maximizes its benefit. We assume that each node has a privately known cost of relaying a unit of data for other nodes. In our protocol, each wireless node has to declare a cost for forwarding a unit of data. When a node wants to send data to the access point, it first computes the least cost path to the access point and then computes a payment to each node on this path. We present a pricing mechanism such that the profit of each relay node is maximized when it declares its true cost. We also give a time optimal method to compute the payment in a centralized manner. We then discuss in detail how to implement the routing protocol in the distributed manner. We conduct extensive simulations to study the ratio of the total payment over the total cost incurred by all relay nodes. We find that this ratio is small in practice. Our protocol works when the wireless nodes will not collude and we show that no truthful mechanism can avoid the collusion of any pair of two nodes. We also give a truthful mechanism when a node only colludes with its neighbors.
Improving Pediatric Health Care Delivery by Engaging Residents in Team-Based Quality Improvement Projects

The goal was to implement and evaluate an experimental and longitudinal team-based curriculum in quality improvement (QI) for pediatric residents that would increase their ability to apply QI methodology while improving clinical processes and outcomes. The curriculum evolved over 3 years based on resident feedback. Working in teams, residents and faculty apply QI principles to systematically design and implement QI projects. Residents increased their level of comfort with key QI concepts. They showed an increase in QI skills by meaningful integration of the following QI concepts into their projects: establishing the magnitude of the problem, developing focused aims for improvement, identifying areas to change, using QI tools, collecting data, and assessing if changes were successful. The 10 resident-led projects conducted over the past 3 years also resulted in improvements in measures of multiple clinical processes and outcomes. This curriculum was effective and feasible within the constraints of residency work hours.
Genomic organization of the gene for mouse PIASγ and analysis of its promoter

Signal transducer and transcriptional activator (STAT) proteins are latent cytoplasmic transcription factors that are activated in response to stimulation by various cytokines. Protein Inhibitors of Activated STAT (PIAS) proteins comprise a family of five mammalian proteins which have been identified as potentially important downregulators of the STAT signaling pathway. We have previously reported the identification and expression of the mouse homologue of PIAS family member PIASgamma. Here we report the isolation by genomic 5'-RACE PCR and in vitro analysis of the mouse PIASgamma promoter region and the genomic structure and organization of the mouse and human PIASgamma genes. Human PIASgamma spans approximately 23 kb on chromosome 19 and is organized into ten exons. The size of mouse PIASgamma is 16 kb and also organized into ten exons with the intron/exon structure of the two genes conserved in both species. As a result, considerable conservatism of the mouse and human intron sequences was observed. Analysis of a 1.4 kb genomic fragment containing the mouse PIASgamma promoter allowed us to map the transcription 'Start' site of the gene, determine the sequences essential for the activity of this promoter and to define a minimal promoter region.
Exurban Industrialization: Implications for Economic Development Policy

Manufacturing is moving into the exurban countryside, away from central cities and their suburbs. However; manufacturing firms remain attracted to markets, labor, and transportation facilities and, therefore, tend to avoid remote areas. Increasing numbers of firms and employment are locating outside developed urban areas but not necessarily in the rural hinterlands. We call this middle area exurbia, and we call the process of manufacturing growth in this area exurban industrialization. It will fuel further population deconcentration and thus presents new opportunities for formerly rural communities within expanding urban territory. It also presents new challenges to communities competing for manufacturing firms. Finally, it presents fundamental challenges to manufacturing policy at all levels of government. This article uses economic base analysis to characterize exurban industrialization trends, discusses the nature of competition for new manufacturing jobs in this context, and reviews important policy i...
An Investigation of the Mechanics of Tactile Sense Using Two-Dimensional Models of the Primate Fingertip

Tactile information about an object in contact with the skin surface is contained in the spatio-temporal load distribution on the skin, the corresponding stresses and strains at mechanosensitive receptor locations within the skin, and the associated pattern of electrical impulses produced by the receptor population. At present, although the responses of the receptors to known stimuli can be recorded, no experimental techniques exist to observe either the load distribution on the skin or the corresponding stress-state at the receptor locations. In this paper, the role of mechanics in the neural coding of tactile information is investigated using simple models of the primate fingertip. Four models that range in geometry from a semi-infinite medium to a cylindrical finger with a rigid bone, and composed of linear elastic media, are analyzed under plane strain conditions using the finite element method. The results show that the model geometry has a significant influence on the surface load distribution as well as the subsurface stress and strain fields for a given mechanical stimulus. The elastic medium acts like a spatial low pass filter with the property that deeper the receptor location, the more blurred the tactile information. None of the models predicted the experimentally observed surface deflection profiles under line loads as closely as a simple heterogeneous waterbed model that treated the fingerpad as a membrane enclosing an incompressible fluid (Srinivasan, 1989). This waterbed model, however, predicted a uniform state of stress inside the fingertip and thus failed to explain the spatial variations observed in the neural response. For the cylindrical model indented by rectangular gratings, the maximum compressive strain and strain energy density at typical receptor locations emerged as the two strain measures that were directly related to the electrophysiologically recorded response rate of slowly adapting type I (SAI) mechanoreceptors. Strain energy density is a better candidate to be the relevant stimulus for SAIs, since it is a scalar that is invariant with respect to receptor orientations and is a direct measure of the distortion of the receptor caused by the loads imposed on the skin.
Diagnosis and management of genitourinary stone in vesicovaginal fistula tract

We present a case of a stone discovered in a vesicovaginal fistula after a total abdominal hysterectomy.CaseA 53-year-old woman presented with complaints of severe urinary incontinence, dyspareunia, and post-coital bleeding after hysterectomy. Her partner reported pain with intercourse as well. Physical examination revealed urinary stone wrapped around permanent suture within the vesicovaginal fistula tract. Patient was taken to the operating room for repair of the vesicovaginal fistula, anterior colporrhaphy and cystoscopy.
PAST AND FUTURE OF CONCRETE QUALITY EVALUATION

This paper examines the current practice, the recent developments, and the future prospects of various methods and techniques used for the quality evaluation of representative concrete and in-place concrete. Special attention is given to trends that will dominate the field in the future. Recent advances in accelerated test methods, ultrasonic testing, radioactivity methods, probe tests, pull-out tests, and rapid analysis of fresh concrete have been reviewed. The maturity concept, and its future role in the evaluation of concrete quality are mentioned. There is a great potential in the concrete industry for accelerated test methods and various nondestructive and partially destructive methods of testing in-place concrete.
Southwestern Internal Medicine Conference: The Arts of War and Medicine: A Study in Symbiosis

ABSTRACT Practitioners of warfare and medicine have both considered their respective disciplines part art and part science. Each has seen dramatic advances over the past several centuries, and the histories of progress in warfare and medical practice are inextricably intertwined. For example, the congregation of large armies inspired the development of epidemiologic analysis and preventive medicine, which forestalled the disastrous loss of life that typified all wars through the U.S. Civil War. Warfare also helped to clarify the critical distinction between medicine and health in several ways. Battles generate tremendous demands on the trauma surgeon, which triggers advances in understanding of trauma, surgery, fluid and electrolyte management, first aid, and triage. Similarly, the health of soldiers before and after combat is a result of public health measures that physicians have been ill-suited to manage. The dramatic severity of epidemics in armies progressively forced health professionals and politicians to seek solutions to illnesses that had plagued the general population to lesser degrees for millennia. The exigencies of war inspired creation of the nursing profession, with the burden and opportunity falling on women. Women were not allowed to hold positions of responsibility in caring for the sick until the enormity of the Civil War prevented men from occupying all such positions. Because each generation tends to view itself as “modern,” its inherent weaknesses often go uncorrected and even unobserved. The interconnected histories of war and medicine provide a warning to remain open to discovering those practices that need radical reform to prevent the current generation of physicians from appearing utterly ridiculous to physicians 100 years hence. This treatise focuses, therefore, on the symbiotic advances in warfare on health before this century because death in war due to trauma was statistically far less important than death due to disease.
Systematic Optimism in Financial Analysts' Earnings Forecasts

This study examines forecast errors in financial analysts' annual earnings forecasts and finds that analysts exhibit systematic optimism for a specific subset of companies. The magnitude of the analysts' optimistic forecast bias increases with the difficulty of the forecasting task, which is represented by statistical characteristics of a firm's earnings as well as the overall economic activity. We find that both the mean and median forecast errors are largest for companies with the most volatile earnings that move against or independently of the market earnings. We also develop a model of the analysts' forecasting behavior and provide evidence that the analysts' optimistic forecast error increases in periods of economic downturns, and somewhat slowly decreases throughout the forecast horizon. In contrast to most of the existing literature, which deals with samples, we analyze all available consensus as well as timely constructed forecasts for the 1987-2004 period.
Electron spin polarization transfer from photogenerated spin-correlated radical pairs to a stable radical observer spin.

A series of donor–chromophore–acceptor–stable radical (D–C–A–R•) molecules having well-defined molecular structures were synthesized to study the factors affecting electron spin polarization transfer from the photogenerated D+•–C–A–• spin-correlated radical pair (RP) to the stable radical R•. Theory suggests that the magnitude of this transfer depends on the spin–spin exchange interaction (2JDA) of D+•–C–A–•. Yet, the generality of this prediction has never been demonstrated. In the D–C–A–R• molecules described herein, D is 4-methoxyaniline (MeOAn), 2,3-dihydro-1,4-benzodioxin-6-amine (DioxAn), or benzobisdioxole aniline (BDXAn), C is 4-aminonaphthalene-1,8-dicarboximide, and A is naphthalene-1,8:4,5-bis(dicarboximide) (1A,B–3A,B) or pyromellitimide (4A,B–6A,B). The terminal imide of the acceptors is functionalized with either a hydrocarbon (1A–6A) or a 2,2,6,6-tetramethyl-1-piperidinyloxyl radical (R•) (1B–6B). Photoexcitation of C with 416-nm laser pulses results in two-step charge separation to yield D...
Systemic Inflammatory Biomarkers and Their Association With Periodontal and Diabetes-Related Factors in the Diabetes and Periodontal Therapy Trial, A Randomized Controlled Trial.

Background: The present study evaluates effects of non-surgical periodontal treatment on serum biomarkers in patients with type 2 diabetes mellitus (t2DM) and chronic periodontitis who participated in the Diabetes and Periodontal Therapy Trial (DPTT); and associations among diabetes markers, serum biomarkers, and periodontal measures in these patients.Methods: DPTT participants randomized to receive immediate or delayed non-surgical periodontal therapy were evaluated at baseline and 6 months. Serum samples from 475 participants with 6-month data were analyzed for the following biomarkers: 1) high sensitivity C-reactive protein; 2) E-selectin; 3) tumor necrosis factor (TNF)-α; 4) vascular cell adhesion molecule (VCAM); 5) interleukin (IL)-6; 6) IL-8; 7) intercellular adhesion molecule; and 8) IL-10. Changes in biomarker levels from baseline and correlations among biomarker levels and clinical findings were analyzed.Results: No differences between treatment and control groups were observed for any biomarker...
DDEL-09QUANTIFICATION OF TRANSIENT BLOOD BRAIN BARRIER DISRUPTION FOLLOWING THE SYSTEMIC ADMINISTRATION OF REGADENOSON

BACKGROUND: The blood brain barrier (BBB) makes it difficult for oral or intravenous chemotherapy to achieve therapeutic concentrations in brain parenchyma. Regadenoson is an adenosine receptor agonist which transiently disrupts the BBB, allowing systemically administered high molecular weight dextran (MW 70kD) to enter normal rodent brain. Our recent studies with this compound suggest that temozolomide concentrations in rodent brain are also increased by regadenoson. This FDA approved agent is used routinely for cardiac stress tests in patients unable to exercise along with visipaque and cardiac computed tomography (CT) imaging. Visipaque (MW 1550) typically only enters brain where there is significant disruption of the BBB. This study is being conducted to determine if regadenoson will allow more contrast to enter normal human brain. METHODS: Patients without known intracranial disease who were undergoing clinically indicated pharmacologic cardiac stress tests (visipaque with cardiac CT followed by visipaque with regadenoson and cardiac CT) were eligible. This IRB approved study only added brain CT pre- and post-regadenoson. Contrast delivery was measured in hounsfield units (HU), at the level of the basal ganglia, within the cortex, deep gray and white matter. A total of 27 patients are required to assist in comparison analysis of regional contrast uptake. A matched-pairs t-test was performed to determine if the difference was significant. RESULTS: Five of the 27 patients have been accrued and analyzed. There was no difference in contrast following visipaque alone and visipaque with regadenoson (29.3HU vs 30.2HU respectively, P = 0.06). CONCLUSION: Early results from this ongoing study suggest that even accounting for the additional visipaque dose there is a trend towards increased contrast enhancement following regadenoson administration in patients with presumably normal brains. Transient disruption of the BBB to facilitate drug entry using an FDA approved agent could be of significant importance to the field of neuro-oncology.
Rape and Mental Health Outcomes Among Women Examining the Moderating Effects of “Healthy” Fear Levels

This study examined the mediating and moderating impact of fear of victimization on the relationships between forcible and vicarious rape on depression and post-traumatic stress disorder (PTSD) among college women. Forcible and vicarious rape positively affected PTSD and depression symptomology, but fear did not mediate these relationships. Fear moderated the impact of forcible rape on PTSD, but was not a moderator for depression. Findings suggest that there may be "healthy" levels of fear in the aftermath of victimization where having too little fear may leave women unnecessarily vulnerable to victimization, while having too much fear may lead to social isolation and withdrawal.
Effect of a Surfactant on the Electric-Field Assembly of Oil-Water Emulsions for Making Foam Targets

The electric-field–assembly technique proposed for making fusion targets uses the electrical force from dielectrophoresis and electrowetting-on-dielectric phenomena to form droplets of oil and wate...
Comparison of equilibrium ohmic and nonequilibrium swarm models for monitoring conduction electron evolution in high-altitude EMP calculations

Here, atmospheric electromagnetic pulse (EMP) events are important physical phenomena that occur through both man-made and natural processes. Radiation-induced currents and voltages in EMP can couple with electrical systems, such as those found in satellites, and cause significant damage. Due to the disruptive nature of EMP, it is important to accurately predict EMP evolution and propagation with computational models. CHAP-LA (Compton High Altitude Pulse-Los Alamos) is a state-of-the-art EMP code that solves Maxwell inline images equations for gamma source-induced electromagnetic fields in the atmosphere. In EMP, low-energy, conduction electrons constitute a conduction current that limits the EMP by opposing the Compton current. CHAP-LA calculates the conduction current using an equilibrium ohmic model. The equilibrium model works well at low altitudes, where the electron energy equilibration time is short compared to the rise time or duration of the EMP. At high altitudes, the equilibration time increases beyond the EMP rise time and the predicted equilibrium ionization rate becomes very large. The ohmic model predicts an unphysically large production of conduction electrons which prematurely and abruptly shorts the EMP in the simulation code. An electron swarm model, which implicitly accounts for the time evolution of the conduction electron energy distribution, can bemore » used to overcome the limitations exhibited by the equilibrium ohmic model. We have developed and validated an electron swarm model previously in Pusateri et al. (2015). Here we demonstrate EMP damping behavior caused by the ohmic model at high altitudes and show improvements on high-altitude, upward EMP modeling obtained by integrating a swarm model into CHAP-LA.« less
Gender- and ethnic-specific associations with obesity: individual and neighborhood-level factors.

Objective Gender- and ethnicity-specific groups face different risks for obesity, but little is understood about the factors that predict group-specific risks. We evaluated individual and neighborhood factors in relation to obesity. Design Cross-sectional surveys of adults (ages 18-100 years) from southeastern Pennsylvania were analyzed. Individual- and neighborhood-level factors were included in fully-adjusted regression models to estimate relationships with obesity for specific gender-ethnic groups. The study included 679 Asian women, 655 Asian men, 4190 African-American women, 1568 African-American men, 1248 Hispanic women, 586 Hispanic men, 11791 European American women, and 6547 European American men. Results There were significant differences in the predictors of obesity by gender-ethnic groups. Obesity was differentially associated with age (p Conclusions We observed that individual- and neighborhood-level variables are associated with obesity. Several individual-level effects differ by gender-ethnic group. Publication Index PubMed
Successful Use of Bivalirudin in the Treatment of Patients Suspected, or at Risk of, Heparin-Induced Thrombocytopenia.

Abstract Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy. As thrombosis occurs in 50% of untreated patients, prompt treatment with a direct thrombin inhibitor (DTI) is recommended. Lepirudin and argatroban are currently approved for the treatment of HIT. However, their use is complicated by antibody formation with potential for anaphylactic shock (lepirudin), effects on the PT/INR that complicate transition to coumadin (argatroban), and significant dose adjustments in patients with renal (lepirudin) or liver (argatroban) impairment. The effectiveness of bivalirudin, another DTI, as a replacement for heparin has been well documented in percutaneous coronary intervention, but there are little published data on its use in treating HIT. We now report our experience with bivalirudin in 52 patients with clinical suspicion of HIT, or at increased risk of this complication. HIT was suspected on the basis of a falling platelet count and/or thrombosis in the setting of current or recent heparin therapy (n=49). Patients were considered at increased risk of HIT if they required ongoing intravenous anticoagulation in a setting associated with a high incidence of heparin-platelet factor 4 (HPF4) antibodies (n=3). Data were collected by retrospective chart review, and patients classified according to whether HIT was very likely (n=13), likely (n=17), unlikely (n=11) or very unlikely (n=11). Bivalirudin was given by intravenous infusion, typically at an initial dose of 0.15 - 0.20 mg/kg/h and adjusted to achieve an APTT of approximately 1.5–2.5 x baseline. Twenty-one patients had moderate or severe renal impairment. The infusion rate was significantly lower for patients with severe renal insufficiency, but was not different in those with mild renal dysfunction. ELISA-detectable HPF4 antibodies were present in 43/52 cases. Twenty-seven patients were significantly thrombocytopenic (
Abstract 1386: KLF5 inhibits angiogenesis in PTEN-deficient prostate cancer by attenuating AKT activation and subsequent HIF1α accumulation

Background: KLF5 is a basic transcriptional factor that regulates multiple physiopathological processes. Our recent study showed that deletion of Klf5 in mouse prostates promotes tumorigenesis initiated by the deletion of Pten. While molecular characterization of Klf5-null tumors suggested that angiogenesis was partially responsible for tumor promotion, the precise function and mechanism of KLF5 deletion in prostate tumor angiogenesis remain unclear. Results: Using histological staining of Pten-null mouse prostates, we observed that deletion of Klf5 significantly increased the number of microvessels, which was accompanied by the upregulation of multiple angiogenesis-related genes based on microarray analysis with MetaCore software. In human umbilical vein endothelial cells (HuVECs), tube formation and migration, both of which are indicators of angiogenic activities, were decreased by conditioned media from PC-3 and DU 145 human prostate cancer cells with KLF5 overexpression, but increased by media from cells with KLF5 knockdown. HIF1α, a key angiogenesis inducer, was upregulated by KLF5 loss at the protein but not the mRNA level in both mouse tissues and human cell lines, as examined by immunohistochemical staining, real-time RT-PCR and Western blotting. Consistently, KLF5 loss also upregulated VEGF and PDGF, two pro-angiogenic mediators of HIF1α function, as analyzed by immunohistochemical staining in mouse tissues and ELISA in conditioned media. Mechanistically, AKT activity, which caused the accumulation of HIF1α, was increased by KLF5 knockout or knockdown but decreased by KLF5 overexpression. Consistently, PI3K/AKT inhibitors abolished the effects of KLF5 knockdown on angiogenic activity, HIF1α accumulation, and VEGF and PDGF expression. Conclusion: KLF5 loss enhances tumor angiogenesis by attenuating PI3K/AKT signaling and subsequent accumulation of HIF1α in PTEN deficient prostate tumors. Citation Format: Xinpei Ci, Changsheng Xing, Baotong Zhang, Zhiqian Zhang, Jenny Jianping Ni, Wei Zhou, Jin-Tang Dong. KLF5 inhibits angiogenesis in PTEN-deficient prostate cancer by attenuating AKT activation and subsequent HIF1α accumulation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1386. doi:10.1158/1538-7445.AM2015-1386
Cancer's Big Data Problem

The US Department of Energy (DOE) has partnered with the National Cancer Institute (NCI) to use DOE supercomputers to aid in the fight against cancer by building sophisticated models based on data available at the population, patient, and molecular levels. Through a three-year pilot project called the Joint Design of Advanced Computing Solutions for Cancer (JDACSC), four participating national laboratories--Argonne, Lawrence Livermore, Los Alamos, and Oak Ridge--will focus on three problems singled out by the NCI as the biggest bottlenecks to advancing cancer research.