cssi/SciSciGPT-SciSciNet huggingface dataset:
Loss of insulin‐like growth factor‐1 signaling in astrocytes disrupts glutamate handling

Insulin-like Growth Factor-1 (IGF-1) has been studied extensively for its ability to promote neuronal growth and excitability. Declining levels of IGF-1 have been correlated with impaired learning and memory as well as an increased risk of neurodegenerative diseases. While neuronal regulation by IGF-1 is well understood, the role of IGF-1 in influencing astrocyte function requires further exploration. Astrocytes regulate many aspects of the brain microenvironment, including controlling glutamate-glutamine cycling, which ultimately supports neuronal metabolism, neurotransmission, and protection from over stimulation. In this study, we examined whether IGF-1 acts through its cognate receptor, IGFR, to alter astrocytic glutamate handling. We utilized both small molecule IGFR inhibitors and Cre-driven genetic approaches to reduce IGFR in vivo and in cultured rodent astrocytes. When IGFR was knocked out of primary astrocytes derived from igfrf/f mice using AAV5-CMV-Cre, significant reductions in glutamate uptake were observed. Similarly, inhibition of IGFR with picropodophyllotoxin for 2 h, as well as 24 h, reduced glutamate uptake in vitro. Mechanistically, short-term inhibition of IGFR resulted in a significant decrease in glutamate transporter availability on the cell surface, as assessed by biotinylation. Long-term inhibition of IGFR led to significant reductions in mRNA expression of glutamate transport machinery, as assessed with qPCR. Reduced glutamate transporter mRNA was also observed in the brains of astrocyte-specific IGFR-deficient mice, three to four months after knock-out was induced with tamoxifen. Interestingly, long-term IGF-1 inhibition also resulted in an increase in adenosine triphosphate-stimulated glutamate release, though no change in adenosine triphosphate-stimulated calcium flux was observed nor were any changes in purinergic receptor protein expression. Together, these data suggest that reduced IGF-1 signaling will favor an accumulation of extrasynaptic glutamate, which may contribute to neurodegeneration in disease states where IGF-1 levels are low. Cover Image for this issue: doi: 10.1111/jnc.14534.
How the NIH Genetic Testing Registry and Medical Genetics Summaries can help oncologists adopt pharmacogenetics guidelines.

e14141Background: Oncology is one of the few medical specialties where pharmacogenetic dosing is becoming a routine part of patient management. In the US, oncology drugs account for one-third of al...
Synthesis of Repair Materials and Methods for Reinforced Concrete and Prestressed Bridge Girders

Bridge structures nationwide across the United States are aging and in need of repair or, in some cases, full replacement. Repair decisions are common among bridge owners because of the economic feasibility when compared to the higher cost of full replacement of damaged or deteriorated bridge components such as girders. Using a proper repair approach, as a long-term or just a short-term solution, can lead to benefits that could not be achieved otherwise such as considerable savings in both time and cost. Additionally, an appropriate repair approach can help avoid adverse environmental impacts, interruptions to service, overburdening of nearby infrastructure, and local opposition to construction. The main objective of this paper is to provide a synthesis of the repair methods and materials for reinforced concrete bridge girders proposed in research studies, i.e., state-of-the-art as well as state-of-the-practice established methods. Different steps in the general repair procedure are explained first. Next, a detailed description of three common bridge girder deficiencies, i.e., shear, flexural, and fire damage, is provided. For each damage type, the main causes and common solutions found in the literature are presented. The authors then provide specific recommendations to each repair procedure. This is intended to enable researchers, engineers, and decision makers to compare the available repair methods more conveniently to find the optimal repair approach for specific projects based on economic and environmental requirements as well as structural and construction conditions.
Enhancing Short Circuit Ruggedness of 1.7 kV IGBTs using a Gate-Source-Shorted Depletion-Mode MOSFET in Series with the Emitter

Commercial IGBTs optimized with low on-state voltage drop (V CE,SAT ) have poor short circuit ruggedness (t SC ). This paper demonstrates a new concept to enhance t SC for commercially available 1.7 kV IGBTs designed with low V CE,SAT using a gate-source-shorted (GSS) Si depletion-mode (DM) MOSFET in series. A five-fold improvement in t SC to over 25 μs was achieved at a DC bus voltage of 1100 V with only 15% increase in V CE,SAT and no change in total switching loss. The new concept also provides a sense voltage to monitor collector current during normal circuit operation and to detect SC events.
Comparison of Outcomes Following Coronary Artery Bypass Grafting With Arterial Versus Venous Conduits

Abstract This review assesses the comorbidities affecting the coronary artery disease (CAD) population to assess generalizability and applicability to individual conduit selection. We also examine the influence of procedural factors, including conduit dimensions, lesion severity, and target vessel location. By summarizing these topics, we hope to facilitate a better understanding of conduit choice for the cardiac anesthesiologist to support evidenced-based, patient-centered care.
Sexual Violation Without Law

This Essay, written for a conference held in honor of Stephen Schulhofer, considers #MeToo era evidence that the spectrum of sexual violation remains mostly untouched by criminal law. In addition to highlighting the endurance of pronounced gaps in legal protection, I argue that #MeToo stories should catalyze needed reform.
Ten-year follow-up of patient-centered comprehensive care using case completion curriculum

Introduction The purpose of this study was to evaluate the patient-based comprehensive model in the student teaching practice at Harvard School of Dental Medicine (HSDM) as a result of the case completion curriculum. The patient-centered assessment system was implemented in 2009 as a clinical reform in clinical education to redirect predoctoral clinical learning from a student requirement-driven assessment system to a patient-centered treatment delivery model. Methods The sample for the 10-year retrospective cohort study consisted of the graduating classes of 2010 through 2019 at HSDM and all data regarding case completion and student feedback were obtained from the Office of Dental Education. Results The average number of completed cases by the predoctoral graduating class has risen from 22.8 in 2010 to 33.26 in 2019, and as a result, the number of completed cases required for graduation has been adjusted twice, from 15 to 20 in 2012, and from 20 to 25 including two pediatric cases in 2018. Conclusion The redesigned clinical component of the curriculum can contribute to improved efforts in providing a patient-based comprehensive care environment and in helping broaden student learning experience in the predoctoral dental education program.
Wicksell, Myrdal and Swedish Intellectual Thought on Inequality

The ‘Swedish Model’ of the welfare state was born from a confluence of geographic, cultural, political, and economic factors in the immediate post-war period. Its intellectual history, however, lay in a much longer tradition that originated with the economist Knut Wicksell (1851 – 1926). A radical and progressive thinker on issues of inequality, social justice and the role of the state, Wicksell had a profound influence on Swedish economic thought. His concerns carried over to the next generation of Swedish economists, including Gunnar Myrdal (1898 – 1987) – Nobel Prize winning economist, public intellectual, architect of the Swedish welfare state, and technocrat of postwar international economic order. This paper takes Wicksell as its starting point, considering the intellectual history of Myrdal’s views on inequality and the welfare state as a ‘middle way’, a ‘system of social morals.’ Like Wicksell, Myrdal initially conceived of inequality as a national problem. However, Myrdal’s Beyond the Welfare State (1960) extended Swedish intellectual thought on domestic inequality to issues of international economic development. Myrdal argued that contemporary welfare programs were too narrow and irrationally nationalistic, concluding that what was needed was a welfare world, not a welfare state.
Do people have differing motivations for participating in a stated-preference study? Results from a latent-class analysis

Researchers and policy makers have long suspected that people have differing, and potentially nefarious, motivations for participating in stated-preference studies such as discrete-choice experiments (DCE). While anecdotes and theories exist on why people participate in surveys, there is a paucity of evidence exploring variation in preferences for participating in stated-preference studies. We used a DCE to estimate preferences for participating in preference research among an online survey panel sample. Preferences for the characteristics of a study to be conducted at a local hospital were assessed across five attributes (validity, relevance, bias, burden, time and payment) and described across three levels using a starring system. A D-efficient experimental design was used to construct three blocks of 12 choice tasks with two profiles each. Respondents were also asked about factors that motivated their choices. Mixed logistic regression was used to analyze the aggregate sample and latent class analysis identified segments of respondents. 629 respondents completed the experiment. In aggregate “study validity” was most important. Latent class results identified two segments based on underlying motivations: a quality-focused segment (76%) who focused most on validity, relevance, and bias and a convenience-focused segment (24%) who focused most on reimbursement and time. Quality-focused respondents spent more time completing the survey (p < 0.001) and were more likely to identify data quality (p < 0.01) and societal well-being (p < 0.01) as motivations to participate. This information can be used to better understand variability in motivations to participate in stated-preference surveys and the impact of motivations on response quality.
Spin splitting and spin Hall conductivity in buckled monolayers of group 14: First-principles calculations

Elemental monolayers of group 14 with a buckled honeycomb structure, namely, silicene, germanene, stanene, and plumbene, are known to demonstrate spin splitting as a result of an electric field parallel to their high-symmetry axis, which is capable of tuning their topological phase between a quantum spin Hall insulator and an ordinary band insulator. We perform first-principles calculations based on density functional theory to quantify the spin-dependent band gaps and the spin splitting as a function of the applied electric field and extract the main coefficients of the invariant Hamiltonian. Using linear response theory and the Wannier interpolation method, we calculate the spin Hall conductivity in the monolayers and study its sensitivity to an external electric field. Our results show that the spin Hall conductivity is not quantized and, in the case of silicene, germanene, and stanene, degrades significantly as the electric field inverts the band gap and brings the monolayer into the trivial phase. The electric-field-induced band gap does not close in the case of plumbene with a spin Hall conductivity that is robust to the external electric field.
GNSS-R Soil Moisture Retrieval with a Deep Learning Approach

GNSS reflection measurements can be calibrated with data from SMAP to yield estimates of soil moisture with enhanced spatiotemporal resolution useful to certain hydro-logical/meteorological studies. Current approaches use simple models of the relation between the DDM (delay-Doppler map) and soil moisture and can fail in certain regions of the planet. Complex information contained in the complete 2D DDM could help in these areas, and can be extracted through the application of deep learning based techniques. Our work explores the data-driven approach of convolutional neural networks to determine complex relationships between the reflection measurement and surface parameters. We developed a neural network trained using CYGNSS DDMs and ancillary datasets aligned with SMAP soil moisture values; the results of which are analyzed and compared to existing global soil moisture products.
Decreasing Length of Stay in Opioid Withdrawal.

INTRODUCTION In 2017, more than 1,200 opioid-related deaths were reported in Virginia, with slightly fewer in 2018, at 1,193 deaths. The current opioid crisis has placed a strain on an already limited number of mental health (MH) inpatient beds. The industry standard for assessment and treatment of opioid withdrawal symptoms, in the inpatient setting, is the Clinical Opiate Withdrawal Scale (COWS), and yet some units continue to utilize the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) for this population. AIM The purpose of this nurse-led performance improvement project was to implement COWS in the inpatient MH setting and improve length of stay (LOS) by 1 day. METHOD In 2018, in a large federal teaching facility in the mid-Atlantic region, the COWS was implemented to replace the CIWA-Ar for opioid withdrawal, with the focus on decreasing LOS. Prior to implementation of COWS, LOS on the inpatient MH unit for opioid withdrawal was 8.6 days, which was higher than the ~6- to 7-day LOS for surrounding private sector hospitals. Individual electronic medical records were reviewed for LOS and completion of COWS and pertinent details were discussed daily with nursing staff and monthly with the interdisciplinary team. Baseline data were collected from April 2017 to March 2018, with data collection continuing through the project implementation, April to September 2018. RESULTS Completion of COWS on 100% of patients admitted with opioid withdrawal and a decrease in LOS from 8.6 to 4.7 days was found, a 45% reduction. CONCLUSION The nurse-driven performance improvement project affected business acumen, through decreased LOS, as well as quality of care, through better symptom management.
Development of the small intestine in the hypophysectomized rat. I. Growth histology, and activity of alkaline phosphatase, maltase, and sucrase.

Abstract Rats hypophysectomized at 6 days of age continue to grow but at a subnormal rate. At 24 days, when maturation of the intestinal epithelium normally culminates, the intestine is disproportionately small. The crypts are shallow and the mitotic rate low. The villi are short, and they fail to achieve the broad, leaflike form found in controls. The absorptive cells acquire a deep subnuclear zone, and their surfaces apparently cease to carry on pinocytosis. Rough endoplasmic reticulum is however sparse, and the Golgi complexes are small and atypical in structure. Duodenal alkaline phosphatase remains at the low level characteristic of the neonatal intestine. Sucrase activity appears in the jejunum, and maltase activity increases slightly, but both activities are less than a third of those in intact animals at 24 days. If the pituitary is removed later than 6 days, enzyme activities are higher than after early ablation, but they remain deficient even when the operation is performed at 16 days.
Bretton Woods 1.0: An Essay in Constructive Retrieval

This Article, which brings together two series by the author on financial regulation and the global financial architecture, respectively, retrieves and updates J. M. Keynes’s original International Clearing Union plan for what ultimately became the International Monetary Fund (“IMF,” “Fund”). Its motives are not antiquarian. The Article argues that our current domestic and global financial and macroeconomic troubles are best viewed as products of our not having gone something more like that original Keynesian route with the Fund. Part I tells the tale of Keynes’s original Clearing Union plan. It emphasizes the plan’s basic structure and motivations, as decisively rooted in Keynes’s financially oriented re-conception of what subsequently came to be known as “macroeconomic” theory. It highlights in particular the Clearing Union’s projected role as an institutional lever through which trading nations could jointly prevent financial-stability-imperiling global imbalances in the form of persistent trade surpluses and deficits, hence ensure stable investment, sustained consumer demand, and thus full employment globally as Keynes’s earlier work had shown possible to manage domestically. Part II traces our and the wider world’s recent financial and macroeconomic troubles to our not having adopted something more like the Keynesian IMF. In particular, building on earlier papers, it models our recent spate of recession-inducing asset price bubbles and busts as collective action problems rooted in chronic, uncontrolled, and apparently uncontrollable tendencies toward excess credit-money in the American financial economy. That oversupply in turn stems in significant measure from an excess of global credit-money. And the latter is rooted in massive and still growing industrial overcapacity and consequent trade surpluses enjoyed by a small number of state actors that act “as if” playing by mercantilist monetary rules even when doing so for legitimate prudential reasons – reasons that a Keynesian IMF would preempt. Part III sketches an updated version of Keynes’s Clearing Union arrangement suitable for today’s international monetary and financial order. In effect, it serves as rough blueprint for a new IMF – a Fund more like the “old” one we never gave a go. It does so, moreover, in a manner that makes optimal, albeit modified, use of the principal pillars of the global financial architecture we already have. It also emphasizes that something like this new IMF will be prerequisite to global monetary and financial stability, hence to continued “globalization” itself. The Article concludes with a look ahead to next steps in the direction of fully instituting the revived Global Clearing Union plan that it proposes.
5.1.2 Entering a Brave New World: Applying Systems Engineering to American Infrastructure Projects

Systems Engineering is a well accepted engineering discipline in most industries, including information technology, defense, aerospace, automobile, and medicine, across the globe. When it comes to railroad infrastructure projects in the United States, however, these projects inevitably rely on the Plans, Specifications and Estimate (PS&E) process used in the construction industry. Large scale conventional rail projects are highly complex. Large scale high-speed rail systems are even more so. Systems Engineering inevitably has a fundamental impact on the traditional engineering approach of railroad infrastructure projects, perhaps not unlike what the introduction of electrification did during the steam locomotive era, as depicted in Figure 1. This technical paper presents a case study illustrating how Systems Engineering is being combined with the established Plans, Specifications and Estimate approach, and how the $65 billion California High Speed Train Project (full Phase 1 in 2010 dollars) is benefitting from the values of Systems Engineering [1]. This paper provides a brief overview of the California High-Speed Train Project, describes the Systems Engineering (SE) objectives, discusses how SE was planned and implemented, and demonstrates how Systems Engineering is benefitting the design of the California High-Speed Train Project (CHSTP).
Security and social implications of radio frequency identification

Radio Frequency Identification (RFID) is a technological advance that has caught the attention of many people. Hailed by some for its ability to overshadow the present day barcode as well as track objects, RFID technology is also ridiculed by many others for reasons that include very little security, minimal privacy, and ethical and legal issues. While RFID has the potential to change the way we interact with items on a day-to-day basis, without proper attention, regulation, and security, this technology could prove to be a key that opens Pandora’s box.
Epidermolysis bullosa simplex: a keratin 5 mutation is a fully dominant allele in epidermal cytoskeleton function.

Abstract To explore the relationship between abnormal keratin molecules, 10-nm intermediate filament (IF) organization, and epidermal fragility and blistering, we sought to determine the functional consequences of homozygosity for a dominant keratin defect. We describe a family with an autosomal dominant skin-blistering disorder, epidermolysis bullosa simplex, Koebner subtype (EBS-K), that has a novel point mutation, occurring in the keratin 5 gene (KRT5), that predicts the substitution of an evolutionarily conserved lysine by an asparagine residue (K173N). Unlike previous heterozygous mutations located within the initial segment of domain 1A of keratin molecules, K173N heterozygosity did not result in severe disease or clumping of keratin filaments. One family member was found to be homozygous for the K173N allele, having inherited it from each of her affected first-cousin parents. Despite a lack of normal keratin 5 molecules, and an effective doubling of abnormal molecules, available for heterodimerization with keratin 14 during IF formation, there were no significant differences in the clinical severity or the ultrastructural organization of the keratin IF cytoskeleton of the homozygous individual. These data demonstrate that the K173N mutation behaves as a fully dominant allele and indicate that a limited number of abnormal keratin molecules are sufficient to impair cytoskeletal function and elicit epidermal fragility and blistering.
Chew on this: amoebic trogocytosis and host cell killing by Entamoeba histolytica

Entamoeba histolytica was named 'histolytica' (from histo-, 'tissue'; lytic-, 'dissolving') for its ability to destroy host tissues. Direct killing of host cells by the amoebae is likely to be the driving factor that underlies tissue destruction, but the mechanism was unclear. We recently showed that, after attaching to host cells, amoebae bite off and ingest distinct host cell fragments, and that this contributes to cell killing. We review this process, termed 'amoebic trogocytosis' (trogo-, 'nibble'), and how this process interplays with phagocytosis, or whole cell ingestion, in this organism. 'Nibbling' processes have been described in other microbes and in multicellular organisms. The discovery of amoebic trogocytosis in E. histolytica may also shed light on an evolutionarily conserved process for intercellular exchange.
Reflections on Treating Addictive Disorders: A Psychodynamic Perspective

In this paper I would like to reflect and draw upon apsychodynamic perspective and four decades of work withdrug-dependent patients, to look at the struggles and suf-fering that make addictions so powerful and compelling.Drawing on that perspective and experience, I would thenliketooffersomethoughtsaboutessentialelementsofgoodtreatmentandhowclinicianscandevelopafocustoaddress,understand, and modify in psychotherapy the vulnerabili-ties that have caused drug-dependent individuals to sufferand behave in the ways that they do. The paper will soundfamiliar to many practitioners of my generation, and inthis respect it is intended as a recap and summation of mywork, but it is also my aim to introduce these ideas to anew generation of clinicians who are taking up the chal-lenge to provide a humanistic psychological approach tounderstanding and treating addictive disorders.Treating addictive disorders, as with other medical andpsychiatric conditions, rests on the principle that effectivetreatment best occurs when the underlying processes andmechanisms involved in the disorder are understood andtargeted. Over the past several decades considerable evi-dence has emerged, as recently reviewed by Shedler,
Conceptualizing and Measuring Collaborative Networks

Walter J.M. Kickert, Erik-Hans Klijn, and Joop F. M. Koppenjan, eds., Managing Complex Networks: Strategies for the Public Sector (London: Sage Publications, 1997). 206pp., $41.95 paper, ISBN: 0-7619-5548-8. Myrna P. Mandell, ed., Getting Results through Collaboration: Networks and Network Structures for Public Policy and Management (Westport, CT: Quorum Books, 2001). 275 pp., $89.95 hard, ISBN: 1-56720-455-4. Robert Agranoff, and Michael McGuire, Collaborative Public Management: New Strategies for Local Governments (Washington, DC: Georgetown University Press, 2003). 219 pp., $26.95 paper, ISBN: 1-58901-018-3.
Defective release of tissue plasminogen activator in patients with sickle cell anemia.

Recent studies suggest that intravascular coagulation occurs in sickle cell anemia. There is also some evidence that decreased fibrinolytic activity may be associated with the disorder. In the current study we measured tissue plasminogen activator levels (t-PA) in seven asymptomatic patients with sickle cell anemia. The mean level of releasable t-PA was only 0.01 IU/mL +/- 0.005 (SEM) as compared to 118 healthy volunteers with levels of 0.70 +/- 0.10 (SEM). Despite the small sample size, the difference between the two groups was statistically significant (P less than .001). These data suggest that defective release of t-PA may contribute to a hypercoagulable state in sickle cell anemia.
Synthesis and structure of trans-PtCl2(P(t-Bu)2CH2CHCH2CH2CH2)2, a platinum(II) complex containing the new ligand (DI-t-butyl)cyclobutylmethylphosphine

Abstract The synthesis and spectral properties of trans-dichlorobis((di-t-butyl)cyclobutylmethylphosphine)platinum(II), trans-PtCl2(P(t-Bu)2CH2 CHCH 2 CH 2 C H2)2, and of the new phosphine (di-t-butyl)cyclobutylmethylphosphine, P(t-Bu)2(CH2- CHCH 2 CH 2 C H2), are described. The crystal structure of the Pt complex has been determined. The material crystallizes in the monoclinic system, space group C52h-P21/c, with two formula units in a cell of dimensions a 8.521(2), b 12.774(1), c 14.374(2) A, β 107.71(2)°. A total of 5667 unique reflections were measured on a CAD4 diffractometer at 113 K. The final value of R(F) is 0.028 for those 4223 reflections having F2o > 3σ(F2). The crystal structure consists of the packing of discrete neutral molecules of trans-PtCl2(P(t-Bu)2CH2 CHCH 2 CH 2 C H2)2. A crystallographic center of symmetry is imposed on each molecule. Important intramolecular distances include PtP, 2.353(1) and PtCl, 2.306(1) A. The shortest non-bonding distance between the Cl atom and a carbon atom of a t-Bu group is Cl⋯C(4), 3.387(3) A. No interaction between the Pt atom and the cyclobutane ring is observed. The absence of extreme steric congestion in the complex may explain the lack of such an interaction.
Call blocking probabilities in a traffic-groomed tandem optical network

In this paper, we consider an optical network consisting of N nodes arranged in tandem. We assume traffic grooming, which permits multiple sub-rate traffic streams to be carried on the same wavelength. This optical network is modeled by a tandem queueing network of multi-rate Erlang loss nodes with simultaneous resource possession, with a view to calculating call blocking probabilities. The queueing network is analyzed by decomposition using a modified version of Courtois' algorithm. Numerical comparisons of the decomposition algorithm against simulation show that the algorithm has good accuracy. Also, it is shown that the proposed algorithm is an improvement over the well-known single-node decomposition algorithm based on the link-independence assumption.
Autologous hematopoietic stem cell transplantation may reverse renal failure in patients with multiple myeloma.

Approximately 20% of patients with multiple myeloma (MM) have renal failure at diagnosis, and about 5% are dialysis-dependent. Many of these patients are considered ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) because of a high risk of treatment-related toxicity. We evaluated the outcome of 46 patient with MM and renal failure, defined as serum creatinine >2 mg/dL sustained for >1 month before the start of preparative regimen. Patients received auto-HSCT at our institution between September 1997 and September 2006. Median serum creatinine and creatinine clearance (CrCl) at auto-HSCT were 2.9 mg/dL (range: 2.0-12.5) and 33 mL/min (range: 8.7-63), respectively. Ten patients (21%) were dialysis-dependent. Median follow-up in surviving patients was 34 months (range: 5-81). Complete (CR) and partial responses (PR) after auto-HSCT were seen in 9 (22%) and 22 (53%) of the 41 evaluable patients, with an overall response rate of 75%. Two patients (4%) died within 100 days of auto-HSCT. Grade 2-4 nonhematologic adverse events were seen in 18 patients (39%) and included cardiac arrythmias, pulmonary edema, and hyperbilirubinemia. Significant improvement in renal function, defined as an increase in flomerular filtration rate (GFR) by 25% above baseline, was seen in 15 patients (32%). Kaplan-Meier estimates of 3-year progression-free survival (PFS) and overall survival (OS) were 36% and 64%, respectively. In conclusion, auto HSCT can be offered to patients with MM and renal failure with acceptable toxicity and with a significant improvement in renal function in approximately one-third of the transplanted patients. In this analysis, a melphalan (Mel) dose of 200 mg/m2 was not associated with an increase in toxicity or nonrelapse (Mel) mortality (NRM).
Anthracycline-induced Tension in Permeabilized Cardiac Fibers: Evidence for the Activation of the Calcium Release Channel of Sarcoplasmic Reticulum

Anthracyclines, such as doxorubicin (DOX), are important cancer chemotherapeutic agents that are cardiotoxic. The mechanism for the cardiotoxicity is not well-defined. Recent studies have concluded that anthracyclines release calcium (Ca2+) from membrane fractions containing sarcoplasmic reticulum (SR). To determine whether anthracyclines release Ca2+ in situ from cardiac SR, the effects of DOX on Ca(2+)-activated contractions were analyzed in membrane-permeabilized and membrane-intact fibers from rabbit heart. DOX (10-120 microM) induced tension development in calcium-preloaded permeabilized fibers. DOX-induced tension required submicromolar Ca2+, and was blocked by ruthenium red (20 microM) and Triton X-100 treatment, characteristics shared by caffeine-induced tension referable to SR Ca(2+)-release. DOX (50 microM) did not alter the maximum Ca(2+)-activated tension or shift the Ca2+ concentration-tension relationship of permeabilized fibers, indicating no effect of DOX on the myofilaments. DOX (44-350 microM) depressed post-rest isometric contractility of membrane-intact fibers but did not inhibit steady-state contractility (at 1 Hz; 2.5 Mm Ca2+), similar to effects of caffeine and submicromolar ryanodine. The specific effects of DOX on post-rest contractility of membrane-intact fibers are consistent with DOX-induced Ca2+ release from the SR of membrane-permeabilized fibers. Thus, DOX alters SR Ca2+ release in situ which may contribute to the inotropic and lusitropic dysfunction observed with anthracyclines.
Amine Dendrimers as Templates for Amorphous Silicas

The generation 4.0 PAMAM dendrimer is used as a template for silica gels made from tetraethyl orthosilicate via the sol−gel method. X-ray diffraction and adsorption data show that quasi-spherical dendritic structures can be used as porogens. Used as templates, amine dendrimers are unique in that (I) they have the potential, depending upon dendrimer size, to produce mesopores and micropores with single molecules instead of micelles, and (II) spheroidal pores are the expected pore shape imprinted on inorganic solids.
Stacking fault stability in GaAs/Si hetero-epitaxial growth

Abstract Stacking faults are commonly observed with dislocations in the early stage of GaAs/Si hetero-epitaxial growth. However, it has not been clearly understood whether these come from mis-stacking of atoms or from the nucleation of partial dislocations. We suggest a simple model for stacking fault stability that depends on the thickness and surface smoothness of the GaAs epilayer. This model shows that the successive glides of edge partial dislocations play an important role in forming stacking faults in the GaAs epilayer. The morphology and distribution of stacking faults observed by cross-section transmission electron microscope (TEM) coincides with this analysis.
The use of isoimmune sera for identification of hemopoietic cells from blood-injected radiation chimeras.

Use has been made of the antigenic differences among mice with respect to both erythrocytes and nucleated cells to identify hemopoietic cells of radiation chimeras. By employing isoimmune sera in agglutination and cytotoxic techniques, it has been shown that long-term leukemoid blood chimeras contain lymphocytes, erythrocytes, and nucleated bone marrow cells of the blood-donor type; blood from normal mice can repopulate lymphoid tissues of radiationbone marrow chimeras, and the blood-derived cells might take part in graft-versus-host immune reactions; and normal peripheral leukocytes from F/sub 1/ hybrid donors can reestablish lymphopoiesis, granulopoiesis, and erythropoiesis when injected into lethally irradiated parent strain mice. Cytotoxic typing of the nucleated hemopoietic cells shows that they are of donor origin. (auth)
Interactive image matting for multiple layers

Image matting deals with finding the probability that each pixel in an image belongs to a user specified dasiaobjectpsila or to the remaining dasiabackgroundpsila. Most existing methods estimate the mattes for two groups only. Moreover, most of these methods estimate the mattes with a particular bias towards the object and hence the resulting mattes do not sum up to 1 across the different groups. In this work, we propose a general framework to estimate the alpha mattes for multiple image layers. The mattes are estimated as the solution to the Dirichlet problem on a combinatorial graph with boundary conditions. We consider the constrained optimization problem that enforces the alpha mattes to take values in [0; 1] and sum up to 1 at each pixel. We also analyze the properties of the solution obtained by relaxing either of the two constraints. Experiments demonstrate that our proposed method can be used to extract accurate mattes of multiple objects with little user interaction.
Nonsense-mediated mRNA decay (NMD) in animal embryogenesis: to die or not to die, that is the question

Nonsense-mediated mRNA decay (NMD) is a well-studied cellular quality-control pathway. It decreases the half-lives of eukaryotic mRNAs that aberrantly contain premature termination codons and additionally regulates an estimated 10–20% of normal transcripts. NMD factors play crucial roles during embryogenesis in many animals. Here, we review data indicating that NMD factors are required for proper embryogenesis by discussing the abnormal developmental phenotypes that result when the abundance of individual NMD factors is either downregulated or completely eliminated. We conclude that while NMD per se affects the embryogenesis of all animals, it is required to avoid embryonic lethality in only some animals. The critical roles of many NMD factors in other metabolic pathways undoubtedly also contribute to embryonic development if not viability.
Effects of nerve graft on nitric oxide synthase, NAD(P)H oxidase, and antioxidant enzymes in chronic spinal cord injury.

Abstract Oxidative stress and nitrosative stress play important roles in the pathogenesis of secondary spinal cord injury. Recently, we demonstrated that peripheral nerve grafts (PNG) with acidic fibroblast growth factor (aFGF) partially restore hind limb locomotion in adult rats with completely transected spinal cords. This study investigated the protein abundances of the superoxide (O2 )-generating enzyme nicotinamide adenine dinucleotide (phosphate) oxidase (NAD(P)H oxidase; gp91phox subunit), nitric oxide synthases (NOS), antioxidant enzymes, superoxide dismutases (Cu Zn SOD, Mn SOD), catalase, and glutathione peroxidase (GPX) as well as nitrotyrosine in the spinal cord tissue 4 months after spinal cord transection in rats with and without PNG and aFGF. The protein abundances of the gp91phox subunit of NAD(P)H oxidase, Mn SOD, catalase, GPX, eNOS, and nitrotyrosine were significantly upregulated, whereas Cu Zn SOD and nNOS were unchanged in the injury group compared to the sham controls. The nerve graft with aFGF treated group showed significantly better hind limb locomotion recovery than the injury group. Although the protein abundances of gp91phox, nitrotyrosine, and Cu Zn SOD were similar in the treated group (nerve graft with aFGF) compared to the injury group, Mn SOD, GPX, catalase, and eNOS protein abundances were significantly higher, whereas nNOS was markedly lower in the treated group. We conclude that the combination of nerve graft and aFGF enhances the local antioxidant defense system after spinal cord transection in rats.
Social identity in later life: a situational approach to understanding old age stigma

Social identity it a product of emergent definitional processes occurring in socially defined situations. This article presents a situational approach to understanding an aspect of social identity in later life—the social stigma of old age. Social stigma is conceptualized as an attribute which is perceived to be discrediting, incongruent with expectations, and non-pivotal in regard to the cluster of attributes associated with a specific social category. A typology of situations, based on their potential for producing the stigmatization of old age, is presented. Additionally, stigmatization in these situations is influenced by the following: commitment and legitimation, generational contacts, performance norms, and gender. Implications of a situational approach to the investigation of old age are discussed.
Quantifying variability in phase portraits: application to gait ontogeny.

Abstract We describe new Fourier- and shape-based methods for quantifying variation in phase-portraits, and re-analyze previously-published ontogenetic and adult data [Clark, J. E., & Phillips, S. J. (1993). A longitudinal study of intralimb coordination in the first year of independent walking: A dynamical systems approach. Child Development, 64, 1143–1157]. Results show considerable variation between individuals and through development, but after 6 months of walking some gait patterns stabilize.
Multi‐Slice MRI of Rat Brain Perfusion During Amphetamine Stimulation Using Arterial Spin Labeling

When a single coil is used to measure perfusion by arterial spin labeling, saturation of macromolecular protons occurs during the labeling period. Induced magnetization transfer contrast (MTC) effects decrease tissue water signal intensity, reducing the sensitivity of the technique. In addition, MTC effects must be properly accounted for in acquiring a control image. This forces the image to a single slice centered between the labeling plane and the control plane. In this work, a two-coil system is presented as a way to avoid saturation of macromolecular spins during arterial spin labeling. The system consists of one small surface coil for labeling the arterial water spins, and a head coil for MRI, actively decoupled from the labeling coil by using PIN diodes. It is shown that no signal loss occurs due to MTC effects when the two-coil system is used for MRI of rat brain perfusion, enabling three-dimensional perfusion imaging. Using the two-coil system, a multi-slice MRI sequence was used to study the regional effects of amphetamine on brain perfusion. Amphetamine causes significant increases in perfusion in many areas of the brain including the cortex, cingulate, and caudate putamen, in agreement with previous results using deoxyglucose uptake to monitor brain activation.
Shape space object recognition

In this paper, we describe a shape space based approach for invariant object representation and recognition. In this approach, an object and all its similarity transformed versions are identified with a single point in a high-dimensional manifold called the shape space. Object recognition is achieved by measuring the geodesic distance between an observed object and a model in the shape space. This approach produced promising results in 2D object recognition experiments: it is invariant to similarity transformations and is relatively insensitive to noise and occlusion. Potentially, it can also be used for 3D object recognition.
The concept of a continuum of residence: Comparing activities of daily living among the elderly

The inadequacies and limitations of dichotomous residential comparisons (e.g. rural/urban or metropolitan/non-metropolitan), coupled with a greater awareness of the diversity that exists among small towns and rural communities, has precipitated a number of attempts to transform the concept of a continuum of residence into an operationalized set of discrete points. If characteristics and conditions of the aged are thought to be systematically associated with the underlying continuum, then it is often assumed that such factors will vary in an unbroken progression as one moves incrementally along the continuum. Using data from the National Health Interview Survey [NCHS, Kovar, M.G. (1986) Advance Data from Vital and Health Statistics, no. 115; NCHS, Kovar, M.G. and Poe, G.S. (1985) Vital and Health Statistics, series 1, no. 18], the distribution of ADL scores along a continuum of residence is explored. Zero-order and multivariate analyses did identify residential differences and patterns in the data; but, there was no support for the conjecture that ADLs would align themselves in conformity to a simple rural-urban residential continuum. The implications for future gerontological research of these results, and of multivariate approaches to determining the effects of residence on the lives of elders, are discussed.
Differences in NOy speciation predicted by three photochemical mechanisms

Abstract We describe the production and speciation of NOy in current chemical mechanisms using model simulations with three different chemical mechanisms run under three different chemical scenarios representative of a low-emission rural, a high-emission rural, and a heavily polluted urban scenario. In this study we examine predictions from the Carbon Bond 4 mechanism, the Regional Acid Deposition Model 2 mechanism, and an explicit mechanism used in global modeling. Several reactions are identified which influence the concentrations of important NOy species. The most important reaction under rural conditions is the oxidation of isoprene, which influences the production of PAN and organic nitrate. Differences among mechanisms cause large differences in the NOy concentrations, which propagate throughout the entire mechanism, affecting the chemistry of all species. The largest differences in NOy species among the mechanisms occur in the rural simulations, while predictions are the most similar under urban conditions, for which photochemical mechanisms have been studied and evaluated. The differences in NOy speciation cause uncertainties in the use of these mechanisms for predicting oxidant chemistry over long distances and multi-day episodes under non-urban conditions. Predictions from all mechanisms should be regarded with caution under rural conditions.
Dietary variation and stress among prehistoric Jomon foragers from Japan.

Current archaeological evidence indicates that greater dietary reliance on marine resources is recorded among the eastern Jomon, while plant dependence prevailed in western/inland Japan. The hypothesis that the dietary choices of the western/inland Jomon will be associated with greater systemic stress is tested by comparing carious tooth and enamel hypoplasia frequencies between the eastern and western/inland Jomon. Demographic collapse coincides with climate change during the Middle to Late Jomon period, suggesting dwindling resource availability. It is hypothesized that this change was associated with greater systemic stress and/or dietary change among the Middle to Late Jomon. This hypothesis is tested by comparing enamel hypoplasia and carious tooth frequencies between Middle to Late and Late to Final Jomon foragers. Enamel hypoplasia was significantly more prevalent among the western/inland Jomon. Such findings are consistent with archaeological studies that argue for greater plant consumption and stresses associated with seasonal resource depletion among the western/inland Jomon. Approximately equivalent enamel hypoplasia frequencies between Middle to Late and Late to Final Jomon foragers argues against a demographic collapse in association with diminished nutritional returns. Significant differences in carious tooth frequencies are, however, observed between Middle to Late and Late to Final Jomon foragers. These results suggest a subsistence shift during the Middle to Late Jomon period, perhaps in response to a changed climate. The overall patterns of stress documented by this study indicate wide-spread environmentally directed biological variation among the prehistoric Jomon. Am J Phys Anthropol, 2007. © 2007 Wiley-Liss, Inc.
Metabolism of Carbon Tetrachloride to Trichloromethyl Radical: An ESR and HPLC-EC Study

Extensive ESR spin-trapping studies with α-phenyl-N-tert-butylnitrone (PBN) have shown that carbon tetrachloride (CCl4) is metabolized to trichloromethyl radical (•CCl3). However, the ESR analysis of α-phenyl-N-tert-butylnitrone (PBN)-spin trapped •CCl3 in biological systems appears to be complicated. It has been reported that after in vivo administration of PBN and CCl4 to rats, most of the PBN−CCl3 adduct collected in the bile was ESR silent, suggesting reduction of the nitroxide to its hydroxylamine form. The PBN−CCl3 nitroxide was also shown to undergo a NADPH-dependent reduction in the presence of liver microsomes. Thus, it appears that the variability (or the absence) of the ESR signal of PBN−CCl3 nitroxide in biological systems reflects, at least in part, the fluctuations in the equilibrium between the nitroxide and hydroxylamine forms of this adduct. To test this possibility, ESR and HPLC experiments with electrochemical detection (EC) were conducted for analysis of the major redox form of the PBN...
Blunt Facial Trauma From a Bungee Jump

A 28-year-old man was brought to the emergency department for severe facial swelling the morning after a bungee jumping accident. The patient had been making jumps nearly every weekend for the past 3 years without injury. This time, he had performed a nighttime jump from a railroad trestle over the gorge of a small river. The height of the bridge at the center of the gorge was about 200 ft, and the river was about 12 ft deep. When the patient jumped, he hit the water face first, plunging under the surface to his waist. The cause of the accident was thought to be a miscalculation of the bridge height.
Episodic central neurogenic hyperventilation in an awake child with systemic histiocytosis.

A 3 year old boy with systemic histiocytosis, diabetes insipidus and a lytic parietal bone lesion experienced episodes of central neurogenic hyperventilation 3 weeks after radiation to the head but was conscious and alert at presentation. At admission, the P aO2 was 133 mmHg, P aCO2 was 8 mmHg and pH 7.65. Magnetic resonance imaging revealed a pontomedullary lesion that resolved during the ensuing year. Central neurogenic hyperventilation has not been described previously as a complication of systemic histiocytosis
Viscosity, first and second normal-stress coefficients, and molecular stretching in concentrated solutions and melts

Abstract A numerical method to solve the diffusion equation for the encapsulated FENE-dumbbell model is presented. Viscosity, first and second normal-stress coefficients, and molecular stretching for steady state shear flow are calculated. From the graphs of these quantities one can see the effect of anisotropy of Stokes' resistance and the Brownian force on rheological properties. The accuracy of the approximate method used by Bird and DeAguiar is assessed.