cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification of Anisotropic Material Parameters in Elastic Tissue Using Magnetic Resonance Imaging of Shear Waves

This paper describes the application of a material parameter identification method based on elastic shear wave propagation to simulated and experimental data from magnetic resonance elastography (MRE). In MRE, the displacements of traveling transverse and longitudinal waves in elastic, biological tissue are captured as complex 3D images. Typically, the magnitude of these waves is small, and the equations of waves in linear elastic media can be used to estimate the material properties of tissue, such as internal organs, muscle, and the brain. Of particular interest are fibrous tissues which have anisotropic properties. In this paper, an anisotropic material model with three material parameters (shear modulus, shear anisotropy, and tensile anisotropy) is the basis for parameter identification. This model relates shear wave speed, propagation direction, and polarization to the material properties. A directional filtering approach is applied to isolate the speed and polarization of shear waves propagating in multiple directions. The material properties are then estimated from the material model and isolated shear waves using weighted least squares.Copyright © 2015 by ASME
A Cumulative Spore Killing Approach: Synergistic Sporicidal Activity of Dilute Peracetic Acid and Ethanol at Low pH Against Clostridium difficile and Bacillus subtilis Spores.

Background. Alcohol-based hand sanitizers are the primary method of hand hygiene in healthcare settings, but they lack activity against bacterial spores produced by pathogens such as Clostridium difficile and Bacillus anthracis. We previously demonstrated that acidification of ethanol induced rapid sporicidal activity, resulting in ethanol formulations with pH 1.5-2 that were as effective as soap and water washing in reducing levels of C difficile spores on hands. We hypothesized that the addition of dilute peracetic acid (PAA) to acidified ethanol would enhance sporicidal activity while allowing elevation of the pH to a level likely to be well tolerated on skin (ie, >3). Methods. We tested the efficacy of acidified ethanol solutions alone or in combination with PAA against C difficile and Bacillus subtilis spores in vitro and against nontoxigenic C difficile spores on hands of volunteers. Results. Acidification of ethanol induced rapid sporicidal activity against C difficile and to a lesser extent B subtilis. The addition of dilute PAA to acidified ethanol resulted in synergistic enhancement of sporicidal activity in a dose-dependent fashion in vitro. On hands, the addition of 1200-2000 ppm PAA enhanced the effectiveness of acidified ethanol formulations, resulting in formulations with pH >3 that were as effective as soap and water washing. Conclusions. Acidification and the addition of dilute PAA induced rapid sporicidal activity in ethanol. Our findings suggest that it may be feasible to develop effective sporicidal ethanol formulations that are safe and tolerable on skin.
Gut bacteria differentially affect egg production in the anautogenous mosquito Aedes aegypti and facultatively autogenous mosquito Aedes atropalpus (Diptera: Culicidae)

Aedes aegypti and A. atropalpus are related mosquitoes that differ reproductively. Aedes aegypti must blood-feed to produce eggs (anautogenous) while A. atropalpus always produces a first clutch of eggs without blood-feeding (facultatively autogenous). We recently characterized the gut microbiota of A. aegypti and A. atropalpus that were reared identically in the laboratory. Here, we assessed the effects of specific members of the gut microbiota in A. aegypti and A. atropalpus on female fitness including egg production. Gnotobiotic A. aegypti and A. atropalpus larvae were colonized by specific members of the gut microbiota. Survival, development time, size and egg production for each treatment was then compared to axenic and conventionally reared larvae. Most species of bacteria we tested supported normal development and egg production by A. aegypti but only one betaproteobacterium, a Comamonas, supported development and egg production by A. atropalpus to equivalent levels as conventionally reared females. Aedes atropalpus females colonized by Comamonas contained similar stores of glycogen and protein as conventionally reared females, whereas females colonized by Aquitalea did not. Small differences in bacterial loads were detected between gnotobiotic and conventionally reared A. aegypti and A. atropalpus, but this variation did not correlate with the beneficial effects of Comamonas in A. atropalpus. Specific members of the gut microbiota more strongly affected survival, size and egg production by A. atropalpus than A. aegypti.
Primary mediastinal nonseminomatous germ cell tumors: Results of a multimodality approach

Before cisplatin-based chemotherapy, long-term survival after resection of primary mediastinal nonseminomatous germ cell tumors was unusual. We reviewed the case histories of 48 patients who underwent multimodality treatment for mediastinal nonseminomatous germ cell tumor between 1976 and 1988. Twenty-eight patients received initial therapy at Indiana University and 20 were referred after having had unsuccessful initial therapy elsewhere. In 44 patients (92%) the levels of either one or both serum tumor markers were elevated at the time of diagnosis. Five patients had choriocarcinoma, three embryonal carcinoma, 12 yolk sac carcinoma, four teratocarcinoma, 22 mixed cell type, and two had an unclassified type. Twenty-two of the 28 patients in our initial therapy group had a complete response to treatment, as defined by normal serum tumor markers and absence of residual tumor. In this group, 16 patients had resection of residual disease after chemotherapy, four had total or near total resection before chemotherapy, and only two had chemotherapy alone. Seventeen patients are surviving after this treatment with a median survival of 64 months and a 57% 5-year Kaplan-Meier survival rate. Only two of the 20 patients who were referred for salvage chemotherapy had a complete response. Both required resection of residual disease after salvage chemotherapy. Only one patient survived after this treatment. There was no significant treatment morbidity or mortality. A multimodality approach to primary mediastinal nonseminomatous germ cell tumor with intensive cisplatin-based chemotherapy, emphasis on normalizing serum tumor markers, and aggressive resection of residual disease now offers survival to a significant number of patients.
Neonatal Rhabdomolysis and Dystrophy

A boy, aged 2 years, presenting at birth as a case of rhabdomyolysis and later shown to have an X-linked recessive dystrophy, is reported from the Section of Child Neurology, St. Christopher’s Hospital for Children, Philadelphia, PA, and the Child Neurology A.I. Dupont Institute, Wilmington, DE.
Homeostatic Role of the Krüppel-Like Factor 4 (KLF4) in Proliferation and Differentiation of Primitive Hematopoietic Progenitor Cells.

Abstract 1497 Poster Board I-520 KLF4 is a tumor suppressor in the gastrointestinal tract known to induce cell cycle arrest in a cell context dependent manner. We recently reported that KLF4 maintains quiescence of T lymphocytes downstream of T-cell receptor signaling (Yamada et al., Nature Immunology, 2009). The role of KLF4 in reprogramming adult somatic cells into pluripotent stem cells along with Oct3/4, c-Myc and Sox2 suggests that KLF4 restricts proliferation of undifferentiated cells. In spite of a redundant role of KLF4 in fetal liver hematopoietic stem cells (HSC), its role in the maintenance of adult bone marrow HSCs has not been studied yet. To study the role of KLF4 in the hematopoietic system we used gain- and loss-of-function mouse models. Retroviral transfer of KLF4 into wild type bone marrow (BM) cells led to significant reduction of colony forming units (CFU) in methylcellulose cultures due to increased apoptosis and lower proliferation. Then, Mx1-Cre was used to induce deletion of Klf4-floxed mice by polyI:C administration. Analysis of peripheral blood cells up to 6-9 months post polyI:C administration showed significant reduction of monocytes, as previously reported, and expansion of CD8+CD44+ T cells due to their increased proliferative potential. BM cells from Klf4-deficient mice exhibited increased number of myeloid progenitor cells measured by flow cytometry (Lin-Sca-1-c-kit+FcRII/III+CD34+ cells), CFU and CFU-S8. Cytoablation with 5-fluorouracil (5-FU) showed lower nadir of peripheral white blood cells in Klf4-deficient mice compared to control mice. In spite of normal multilineage reconstitution in BM transplants experiments, competitive reconstitution with Klf4-deficient and normal BM cells resulted in reduced contribution of Klf4-deficient cells to peripheral blood, likely due to homing and proliferative differences. Collectively, our data shows that KLF4 has an important role in function of hematopoietic stem and progenitor cells. Disclosures: No relevant conflicts of interest to declare.
High extinction ratio terahertz wire-grid polarizers with connecting bridges on quartz substrates.

A terahertz (THz) wire-grid polarizer with metallic bridges on a quartz substrate was simulated, fabricated, and tested. The device functions as a wide-band polarizer to incident THz radiation. In addition, the metallic bridges permit the device to function as a transparent electrode when a DC bias is applied to it. Three design variations of the polarizer with bridges and a polarizer without bridges were studied. Results show the devices with bridges have average s-polarization transmittance of less than −3 dB and average extinction ratios of approximately 40 dB across a frequency range of 220–990 GHz and thus are comparable to a polarizer without bridges.
Testing the Efficacy of a Kindergarten Mathematics Intervention by Small Group Size.

This study used a randomized controlled trial design to investigate the ROOTS curriculum, a 50-lesson kindergarten mathematics intervention. Ten ROOTS-eligible students per classroom (n = 60) were ...
Abstract WP11: Comparative Safety and Efficacy of the Trevo, Penumbra and Solitaire Devices in Treatment of Acute Ischemic Stroke

Background and Purpose: We performed a systematic review and meta-analysis comparing rates of recanalization, good neurological outcome, and mortality between patients treated with three modern devices used for endovascular treatment of acute ischemic stroke. Materials and Methods: We performed a comprehensive literature search on studies reporting outcomes of endovascular treatment of acute ischemic stroke. We selected studies including≥30 patients treated with either the Trevo stent-retriever, Penumbra aspiration system or the Solitaire stent-retriever. Outcomes studied included mrs≤2, 90-day mortality, symptomatic and intracranial hemorrhage (sICH), recanalization. Outcomes were pooled across studies using a random-effects meta-analysis. Results: 27 articles with 2666 patients were included (1514 Solitaire, 260 Trevo and 892 Penumbra). Rates of good neurological outcome (mRS≤2) were higher in the Solitaire group (54.0%, 95%CI=49.0-58.0%) than the Penumbra group (39.0%, 95%CI=31.0%-47.0%) (P Conclusions: Meta-analysis of incidence rates in noncomparative series reporting on over 2500 patients suggests that the Solitaire device maybe associated with superior neurological outcomes and lower rates of 90-day mortality. Comparative studies are needed to confirm these observations.
Simulated Soil Organic Carbon Response to Tillage, Yield, and Climate Change in the Southeastern Coastal Plains

Intensive tillage, low-residue crops, and a warm, humid climate have contributed to soil organic carbon (SOC) loss in the southeastern Coastal Plains region. Conservation (CnT) tillage and winter cover cropping are current management practices to rebuild SOC; however, there is sparse long-term field data showing how these management practices perform under variable climate conditions. The objectives of this study were to use CQESTR, a process-based C model, to simulate SOC in the top 15 cm of a loamy sand soil (fine-loamy, kaolinitic, thermic Typic Kandiudult) under conventional (CvT) or CnT tillage to elucidate the impact of projected climate change and crop yields on SOC relative to management and recommend the best agriculture management to increase SOC. Conservation tillage was predicted to increase SOC by 0.10 to 0.64 Mg C ha for six of eight crop rotations compared with CvT by 2033. The addition of a winter crop [rye ( L.) or winter wheat ( L.)] to a corn ( L.)-cotton ( L.) or corn-soybean [ (L.) Merr.] rotation increased SOC by 1.47 to 2.55 Mg C ha. A continued increase in crop yields following historical trends could increase SOC by 0.28 Mg C ha, whereas climate change is unlikely to have a significant impact on SOC except in the corn-cotton or corn-soybean rotations where SOC decreased up to 0.15 Mg C ha by 2033. The adoption of CnT and cover crop management with high-residue-producing corn will likely increase SOC accretion in loamy sand soils. Simulation results indicate that soil C saturation may be reached in high-residue rotations, and increasing SOC deeper in the soil profile will be required for long-term SOC accretion beyond 2030.
Differential Associations of Distinct Forms of Childhood Adversity With Neurobehavioral Measures of Reward Processing: A Developmental Pathway to Depression.

Childhood adversity is associated with altered reward processing, but little is known about whether this varies across distinct types of adversity. In a sample of 94 children (6-19 years), we investigated whether experiences of material deprivation, emotional deprivation, and trauma have differential associations with reward-related behavior and white matter microstructure in tracts involved in reward processing. Material deprivation (food insecurity), but not emotional deprivation or trauma, was associated with poor reward performance. Adversity-related influences on the integrity of white matter microstructure in frontostriatal tracts varied across childhood adversity types, and reductions in frontostriatal white matter integrity mediated the association of food insecurity with depressive symptoms. These findings document distinct behavioral and neurodevelopmental consequences of specific forms of adversity that have implications for psychopathology risk. [ABSTRACT FROM AUTHOR]
A Review of Three Commonly Used Fish Anesthetics

ABSTRACTAnesthesia plays a critical role in prevention of mechanical injuries and manipulation stress in fish. Commercially reared fish are subjected to confinement and handling including netting, ...
Asymptotic normality of interpoint distances for high-dimensional data with applications to the two-sample problem

SummaryInterpoint distances have applications in many areas of probability and statistics. Thanks to their simplicity of computation, interpoint distance-based procedures are particularly appealing for analysing small samples of high-dimensional data. In this paper, we first study the asymptotic distribution of interpoint distances in the high-dimension, low-sample-size setting and show that it is normal under regularity conditions. We then construct a powerful test for the two-sample problem, which is consistent for detecting location and scale differences. Simulations show that the test compares favourably with existing distance-based tests.
Agents of value

Agents, be they human or technological, act on behalf of others in the world. Autonomous software agents may also act as representations (as in simulations) of human concerns. To do so both effectively and ethically, these agents must in some meaningful way understand and account for what those for whom they act consider important in life. At stake is no less than the risk of designing technologies that undermine important human values. Yet, with our limited view, it is not at all obvious how to design agent technologies so that they are more likely to support the actions, relationships, institutions, and experiences that human beings care deeply about.In this invited speech I will explore the question of how to design agent technology to be sensitive to human values and concerns. I will draw from over two decades of design work and theory development in Value Sensitive Design. Along the way, I will touch on how agent technologies instantiate human values, the locus of value tensions in multi-agent systems, and key value tensions. From there, I will turn to methods from value sensitive design - direct and indirect stakeholder analyses, value scenarios, Envisioning Cards - which can be used to improve sensitivity to human values in agent technology research and design work. I will end with a few research challenges for which cutting edge agent technology design has provocative implications for human futures. Throughout, I will take an interactional stance: that agent technologies shape human experience and our very being; and through our experiences and being, we continually re-imagine those very technologies
Transforming growth factor-alpha increases alveolar liquid clearance in anesthetized ventilated rats.

The effect of transforming growth factor-alpha (TGF-alpha) on alveolar liquid clearance was examined in ventilated, anesthetized rats. An isosmolar Ringer lactate solution with 10, 50, or 200 ng/ml...
Building shalom: Integrating social work, peacebuilding and Catholic Social Teaching for transformational change

This article argues for greater integration between peacebuilding and social work, based on shared values, complementary practices, and congruence among key underlying theories in both fields. The ...
The orphan child: humanities in modern medical education

Use of humanities content in American medical education has been debated for well over 60 years. While many respected scholars and medical educators have purported the value of humanities content in medical training, its inclusion remains unstandardized, and the undergraduate medical curriculum continues to be focused on scientific and technical content. Cited barriers to the integration of humanities include time and space in an already overburdened curriculum, and a lack of consensus on the exact content, pedagogy and instruction. Edmund Pellegrino, physician and scholar of the latter twentieth century, spent much of his professional life promoting the value and importance of the humanities in medical education, seeking the best way to incorporate and teach this content in clinically relevant ways. His efforts included the founding of multiple enterprises starting in the 1960s and 1970s to promote human values in medical education, including the Society for Health and Human Values and its Institute on Human Values in Medicine. Regardless of his efforts and those of many others into the current century, the medical humanities remains a curricular orphan, unable to find a lasting home in medical education and training.
Design, Implementation, and Evaluation of a Diversity Program for Radiology.

Abstract Rationale and Objectives Diagnostic radiology training programs are less diverse than graduating US medical school classes and the patient populations they serve. Inclusion of physicians who are underrepresented minorities in medicine (URMM) can strengthen the profession and help to meet the needs of an increasingly diverse population. Our Department of Radiology developed and implemented a plan to increase the number of URMMs in our residency applicant pool and residency training program. Materials and Methods We designed a recruitment strategy to diversify the radiology residency applicant pool. This included website development, advertising, early exposure opportunities, travel to predominantly minority institutions and national meetings, and mentoring URMM medical students. We implemented parallel activities to increase the number of URMMs in our residency program. These included holistic screening tools for residency application review, a diverse residency recruitment committee, a welcome environment for visiting candidates, and “Second Look Weekend” visits for talented candidates. Primary outcomes measured include change in percentages of URMM applicants in our applicant pool and URMM residents in our residency program. Results The percentage of URMM radiology residency applicants increased from 7.5% (42 of 556) of the total applicant pool in the 2012 to 2013 recruitment year to 12.6% (98 of 777) in the 2017 to 2018 recruitment year (P = .001). URMM radiology residency representation increased from 0% (0 of 32) in the 2013 to 2014 academic year to 20% (6 of 30) in the 2018 to 2019 academic year (P = .01). Conclusion An intentional, strategic diversity program can diversify an institution’s residency applicant pool and increase representation of URMMs in a diagnostic radiology residency program.
The financial impact of physician practice patterns: An analysis of as-needed filgrastim versus prophylactic pegfilgrastim in patients with prostate cancer receiving docetaxel.

6506Background: Docetaxel improves survival in metastatic prostate cancer. Patients receiving docetaxel are at an intermediate risk of febrile neutropenia (FN). Granulocyte-colony stimulating facto...
Adaptive activation functions accelerate convergence in deep and physics-informed neural networks

Abstract We employ adaptive activation functions for regression in deep and physics-informed neural networks (PINNs) to approximate smooth and discontinuous functions as well as solutions of linear and nonlinear partial differential equations. In particular, we solve the nonlinear Klein-Gordon equation, which has smooth solutions, the nonlinear Burgers equation, which can admit high gradient solutions, and the Helmholtz equation. We introduce a scalable hyper-parameter in the activation function, which can be optimized to achieve best performance of the network as it changes dynamically the topology of the loss function involved in the optimization process. The adaptive activation function has better learning capabilities than the traditional one (fixed activation) as it improves greatly the convergence rate, especially at early training, as well as the solution accuracy. To better understand the learning process, we plot the neural network solution in the frequency domain to examine how the network captures successively different frequency bands present in the solution. We consider both forward problems, where the approximate solutions are obtained, as well as inverse problems, where parameters involved in the governing equation are identified. Our simulation results show that the proposed method is a very simple and effective approach to increase the efficiency, robustness and accuracy of the neural network approximation of nonlinear functions as well as solutions of partial differential equations, especially for forward problems. We theoretically prove that in the proposed method, gradient descent algorithms are not attracted to suboptimal critical points or local minima. Furthermore, the proposed adaptive activation functions are shown to accelerate the minimization process of the loss values in standard deep learning benchmarks using CIFAR-10, CIFAR-100, SVHN, MNIST, KMNIST, Fashion-MNIST, and Semeion datasets with and without data augmentation.
Use of tumor lines with selectable markers in assessing the effect on experimental metastases of combination chemotherapy with alkylating agents.

High-dose chemotherapy with a 3-day regimen of cyclophosphamide, cisplatin, and carmustine was used to treat mice bearing experimental lung metastases of mammary tumor cell lines with selectable markers (lines 66cl4 and 4TO7). Cloning of lung cells at various times after treatment revealed a rapid 3 to 4 log loss of clonogenic tumor cells, down to undetectable levels. However, after several weeks, clonogenic tumor cells reappeared in the lungs; few cures were obtained even when mice had a relatively low tumor burden when treated with chemotherapy. Splenocyte numbers and response to Concanavalin A indicated a transient immunosuppression. In one experiment, mice were treated with a second round of chemotherapy 3 weeks after the first. The number of clonogenic cells per lung again dropped, but regrowth of cells was rapid, and no cures were obtained. Inoculation of tumor-bearing mice s.c. after chemotherapy with lethally irradiated cells of the highly immunogenic tumor cell line 4TO7-IL-2 had little effect on the rate of reappearance of line 4TO7 in lungs, but subsequent growth of tumor cells in lungs was slowed. This model system can be used to test the efficacy of additional immunotherapy and chemotherapy regimens on minimal residual metastatic disease after high-dose chemotherapy, when remaining metastatic cells are apparently dormant. © Rapid Science Ltd.
Systematic Review of the Proposed Associations between Physical Exercise and Creative Thinking

The objective of this study was to evaluate the association between physical exercise and creative thinking. A systematic review approach was employed by searching PubMed, Google Scholar and PsychInfo databases. Among the evaluated 13 studies, 92% indicated a beneficial relationship. However, 77% were vulnerable to moderate-high risk for methodological bias, suggesting adherence to standardized and controlled research initiatives should be promoted. There appears to be weak to modest support for acute, moderate-intensity exercise to benefit creativity. Exercise timing relative to creativity assessment protocols should be addressed and further detailed. Creativity scoring procedures must be refined, and an increased focus on the motivational components of exercise may help guide researchers in measuring creative thoughts and behavior. Broader concluding claims that creativity, in general, is improved or impaired by exercise, is as problematic as sweeping statements that exercise improves or impairs a measure as dynamic as intelligence. Scientific inquiries must specify precisely which outcome characteristics are changing in line with research interventions. This review identifies several fallible linkages between physical activity and creativity. Too few studies were conducted on strong methodological foundations, perpetuating the risk for undermining or inaccurately inflating the potential association between exercise and creative thinking behavior.
Abstract 15092: The Yin-yang of Bmpr2 and Ces1 in the Pulmonary Endothelium Aad Its Role in Pulmonary Arterial Hypertension

Background/Hypothesis: Pulmonary Arterial Hypertension (PAH) is a life-threatening disease characterized by loss of pulmonary microvessels and vascular remodeling. Loss of function BMPR2 mutations ...
Sexual Decision Making Among Men Who Identify as Bears: a Grounded Theory Study

Gay and bisexual men who have sex with men (GBM) carry a disproportionate HIV infection burden, approximating 66% of all new HIV infections in 2017. GBM’s social networks may influence health and health risk perceptions, including HIV risk. One such social network is the bear subculture, which accounts for approximately 14–22% of the gay community. Previous research on GBM who identify as bears indicated that these men are more likely to engage in sexual practices such as condomless anal sex (CAS). The purpose of this study was to describe the sexual decision-making process among GBM who identify as bears. Utilizing a grounded theory approach, 25 in-depth semi-structured interviews were conducted with men who identify as bears, ranging in age from 22 to 77 years. Participants were recruited using purposive and snowball sampling. A theory grounded in the data entitled The Theory of Making Sexual Decisions Among Men Who Identify as Bears emerged that described how these men may make sexual decisions. The theory is constructed of one core category, “Making Sexual Decisions,” and four categories with subcategories: “Interacting with the Bear Subculture,” “Searching for Sexual Partners,” “Engaging in Sexual Activities,” and “Reflecting on Consequences.” Clinicians caring for this population should be aware of the complex nature of sexual decisions, potentially allowing for HIV risk reduction strategies for GBM who identify as bears. As HIV infection continues to disproportionately impact GBM, health policy campaigns may develop initiatives that include men who identify as bears.
Tailoring a dissonance-based body image intervention for adult women in a proof of concept trial: The Women's Body Initiative.

Abstract Although historically conceptualized as problems of youth, recent research indicates that women of all ages experience body dissatisfaction and eating disorder (ED) pathology. Despite this, existing body image interventions predominantly target youth. The Body Project (BP) has extensive support for reducing ED risk factors in younger women and girls. The current proof-of-concept study investigated the feasibility, acceptability, and estimates of intervention effect sizes of a modified BP for adult women, the Women’s Body Initiative (WBI). Conducted in the Southwestern United States, adult women (N = 13) aged 29–70 (M = 49.1) participated in 4, 1-h weekly sessions, completing measures at baseline, post-intervention, and 3-month follow-up. Participants rated the program as highly feasible and acceptable. Within-subjects effects sizes were medium to large for primary outcomes (body dissatisfaction, ED pathology) and secondary outcomes (psychosocial impairment, negative affect, quality of life, nutritious food consumption, and sleep) through 3-months. Results suggest preliminary feasibility and acceptability of WBI for adult women, and support proceeding with a larger trial to investigate intervention efficacy.
Vitamin D levels do not cause vitamin-drug interactions with dexamethasone or dasatinib in mice

Vitamin D3 (VD3) induces intestinal CYP3A that metabolizes orally administered anti-leukemic chemotherapeutic substrates dexamethasone (DEX) and dasatinib potentially causing a vitamin-drug interaction. To determine the impact of VD3 status on systemic exposure and efficacy of these chemotherapeutic agents, we used VD3 sufficient and deficient mice and performed pharmacokinetic and anti-leukemic efficacy studies. Female C57BL/6J and hCYP3A4 transgenic VD3 deficient mice had significantly lower duodenal (but not hepatic) mouse Cyp3a11 and hCYP3A4 expression compared to VD3 sufficient mice, while duodenal expression of Mdr1a, Bcrp and Mrp4 were significantly higher in deficient mice. When the effect of VD3 status on DEX systemic exposure was compared following a discontinuous oral DEX regimen, similar to that used to treat pediatric acute lymphoblastic leukemia patients, male VD3 deficient mice had significantly higher mean plasma DEX levels (31.7 nM) compared to sufficient mice (12.43 nM) at days 3.5 but not at any later timepoints. Following a single oral gavage of DEX, there was a statistically, but not practically, significant decrease in DEX systemic exposure in VD3 deficient vs. sufficient mice. While VD3 status had no effect on oral dasatinib’s area under the plasma drug concentration-time curve, VD3 deficient male mice had significantly higher dasatinib plasma levels at t = 0.25 hr. Dexamethasone was unable to reverse the poorer survival of VD3 sufficient vs. deficient mice to BCR-ABL leukemia. In conclusion, although VD3 levels significantly altered intestinal mouse Cyp3a in female mice, DEX plasma exposure was only transiently different for orally administered DEX and dasatinib in male mice. Likewise, the small effect size of VD3 deficiency on single oral dose DEX clearance suggests that the clinical significance of VD3 levels on DEX systemic exposure are likely to be limited.
Substrate Inhibition with Glucose Oxidase

The currently accepted mechanism for the action of glucose oxidase does not allow for substrate inhibition; on the other hand, a very similar flavin enzyme, l-amino acid oxidase, does show pronounced substrate inhibition. Experiments reported here done at very low oxygen levels show that glucose also inhibits the glucose oxidase reaction, and the probability is that, rather than each being unique, these two flavin enzymes operate by way of the same basic mechanism, the differences being in the relative values of the rate constants for the reactions associated with the mechanism.
The Livingston Survey: Still Useful After All These Years

The decisions of households, firms, and government agencies depend on forecasts of the overall economy. Large firms and the federal government often have the resources to hire their own economists to provide forecasts. But households, small firms, and local governments often depend on surveys of forecasters to get their information. In this article, Dean Croushore spotlights the Livingston Survey, which, even after 50 years, still provides useful forecasts of the economy.
Enforcement Cooperation in Combating Illegal and Unauthorized Fishing: An Assessment of Contemporary Practice

The emergence of the exclusive economic zone (EEZ) in the 1970s placed potentially vast areas under national jurisdiction. From relatively modest territorial seas close to the coast as the only basis of fisheries jurisdiction for States, suddenly the international community embraced a new form of jurisdiction over resources that extended to fisheries up to 200 nautical miles from land. This extension brought over one third of the world’s oceans under national jurisdiction, or more importantly, approximately ninety percent of the world’s wild fish catch. While the possibility of bringing the resources of these areas under national control was of tremendous value to many developing States, the difficulties of enforcement over such areas were not so readily considered. Some States, notably the States of the South Pacific, but by no means restricted to them, simply lacked the capacity to police their waters and protect their resources from the depredation of others. A vast area subject to national jurisdiction would potentially require substantial assets at sea and in the air in order to effectively patrol, police, and enforce the new jurisdiction vested in States. For oil and gas exploitation, deployment of few if any coast guard or naval assets in the EEZ was not a huge difficulty, as exploitation of the seabed is a slow and expensive business. For fisheries, which can be far more cheaply exploited, and in a more transitory fashion, a lack of enforcement capacity represented a potentially serious impediment.
Spatial Analysis for Environmental Studies

The cartoon shown below appeared in a local newspaper on the day I gave my talk at UMN. It is meant, here, to catch your attention and focus it on the importance of using available data in the best possible way to define the current state of the system under study, in order to update the model — whatever model we have in the works.
Sentinel lymphadenectomy accurately predicts nodal status in T2 breast cancer.

Abstract Background: Sentinel lymph node biopsy (SLNB) has emerged as a reliable, accurate method of staging the axilla for early breast cancer. Although widely accepted for T1 lesions, its use in larger tumors remains controversial. This study was undertaken to define the role of SLNB for T2 breast cancer. Study Design: From a prospective breast sentinel lymph node database of 1,627 patients accrued between September 1996 and November 1999, we identified 223 patients with clinical T1-2N0 breast cancer who underwent 224 lymphatic mapping procedures and SLNB followed by a standard axillary lymph node dissection (ALND). Preoperative lymphatic mapping was performed by injection of unfiltered technetium 99 sulfur colloid and isosulfan blue dye. Data about patient and tumor characteristics and the status of the sentinel lymph nodes and the axillary nodes were analyzed. Statistics were performed using Fisher's exact test. Results: Two hundred four of 224 sentinel lymph node mapping procedures (91%) were successful. Median tumor size was 2.0 cm (range 0.2 to 4.8 cm). One hundred forty-five of the 204 patients had T1 lesions and 59 patients had T2 lesions. There were 92 pathologically positive axillae, 5 (5%) of which were not evident either by SLNB or by intraoperative clinical examination. The false-negative rate and accuracy were not significantly different between the two groups, but axillary node metastases were observed more frequently with T2 than with T1 tumors (p = 0.005); other factors, including patient age, prior surgical biopsy, upper-outer quadrant tumor location, and tumor lymphovascular invasion were not associated with a higher incidence of false-negative SLNB in either T1 or T2 tumors. Conclusions: SLNB is as accurate for T2 tumors as it is for T1 tumors. Because no tumor or patient characteristics predict a high false-negative rate, all patients with T1-2N0 breast cancer should be considered candidates for the procedure. Complete clinical examination of the axilla should be undertaken to avoid missing palpable axillary nodal metastases.
A study of convergence in decentralized design processes

The decomposition and coordination of decisions in the design of complex engineering systems is a great challenge. Companies who design these systems routinely allocate design responsibility of the various subsystems and components to different people, teams or even suppliers. The mechanisms behind this network of decentralized design decisions create difficult management and coordination issues. However, developing efficient design processes is paramount, especially with market pressures and customer expectations. Standard techniques to modeling and solving decentralized design problems typically fail to understand the underlying dynamics of the decentralized processes and therefore result in suboptimal solutions. This paper aims to model and understand the mechanisms and dynamics behind a decentralized set of decisions within a complex design process. By using concepts from the fields of mathematics and economics, including Game Theory and the Cobweb model, we model a simple decentralized design problem and provide efficient solutions. This new approach uses matrix series and linear algebra as tools to determine conditions for convergence of such decentralized design problems. The goal of this paper is to establish the first steps towards understanding the mechanisms of decentralized decision processes. This includes two major steps: studying the convergence characteristics and finding the final equilibrium solution of a decentralized problem. Illustrations of the developments are provided in the form of two decentralized design problems with different underlying behavior.
Gö 6983: A Fast Acting Protein Kinase C Inhibitor that Attenuates Myocardial Ischemia/Reperfusion Injury

Reperfusion injury is characterized by a decrease in endothelial release of nitric oxide within 5 min after reperfusion, increased leukocyte-endothelium interaction, and transmigration of leukocytes into the myocardium, producing cardiac contractile dysfunction. Go 6983 is a fast acting, lipid soluble, broad spectrum protein kinase C inhibitor. When administered at the beginning of reperfusion, it can restore cardiac function within 5 min and attenuate the deleterious effects associated with acute ischemia/reperfusion. Go 6983 may offer greater cardioprotection than other broad-spectrum PKC inhibitors in postischemic reperfusion injury because it inhibits PKC(zeta) as well as four other isoforms. The cardioprotection is associated with decreased leukocyte superoxide release and increased endothelial derived nitric oxide from vascular tissue. In vitro studies of human tissue showed that Go 6983 significantly inhibited antigen-induced superoxide release from leukocytes of patients previously sensitized to tree pollen. In human vascular tissue, Go 6983 inhibited intracellular Ca(2+) accumulation, suggesting a mechanism for its vasodilator properties. These studies suggest that Go 6983 would be an effective compound to use in a clinical ischemia/reperfusion setting of organ transplantation and/or cerebral ischemia where inhibiting superoxide release and vasoconstriction in postischemic tissues would allow for better restoration of organ function during reperfusion. However, given the broad-spectrum action of Go 6983, careful titration of the dose regimen would be recommended to ensure a successful outcome in the setting of organ transplantation and/or cerebral ischemia.
The organisation of water resource development in the People's Republic of China☆

The People's Republic of China, faced nearly everywhere with serious hydraulic problems of one sort or another, has engaged in extensive water resource development, combining centralised, modern works with local, more traditional ones. This article focuses on the organisation, economics, and technology of water conservancy in the PRC. Particular attention is given to the role of the rural collective system in mobilising large amounts of labour (so much so that the PRC is faced with a shortage of rural labour), and to the impact of the state-collective dichotomy on the choice of technology. The operation of irrigation management, separate from the regular administrative apparatus which does the building, is also noted. A number of specific examples are cited from projects visited in 1974 by the US Water Resources Delegation, comprising nine hydraulic engineers, one geographer, and one economist.
Transport properties of anisotropic superconductors: Influence of arbitrary electron-impurity phase shifts.

We investigate electron-impurity scattering in a number of unconventional superconducting states with a low impurity concentration, making no assumption about the phase shift in the normal state. The scattering amplitude in the superconducting states is found not to exhibit particle-hole symmetry, and not to be invariant under time reversal. As a consequence, we find that there can be large thermoelectric effects, and that some tensor components of transport coefficients that vanish in the normal state can be finite in the superconducting state. Detailed calculations of the quasiparticle relaxation time, thermoelectric coefficients, viscosities and thermal conductivity are performed for the axial and polar p-wave states and an axial d-wave state.
Mutations in the nucleotide binding domain of the alpha subunits of the F1-ATPase from thermophilic Bacillus PS3 that affect cross-talk between nucleotide binding sites.

Inactivation of MF1 (bovine mitochondrial F1-ATPase) with 5'-p-fluorosulfonylbenzoylethenoadenosine is caused by labeling alpha Y244 [Verburg, J. G., and Allison, W. S. (1990) J. Biol. Chem. 265, 8065-8074]. In the crystal structure [Abrahams, J.P., Leslie, A. G. W., Lutter, R., and Walker, J. E. (1994) Nature 370, 621-628], alpha Y244 is hydrogen bonded to alpha R304 which is also hydrogen bonded to alpha Y300. The catalytic properties of mutant alpha 3 beta 3 gamma subcomplexes of the TF1-ATPase from the thermophilic Bacillus PS3 containing the alpha F244C, alpha R304C, and alpha Y300C substitutions have been examined. Each has unique features for hydrolyzing ATP and forming inhibitory ADP-fluoroaluminate complexes in catalytic sites. Unlike wild-type, the (alpha R304C)3 beta 3 gamma and (alpha Y300C)3 beta 3 gamma subcomplexes entrap inhibitory MgADP in a catalytic site during turnover which fails to dissociate when ATP binds to noncatalytic sites. Although the hydrolytic properties of the (alpha F244C)3 beta 3 gamma subcomplex and wild-type are similar, the mutant forms ADP-fluoroaluminate complexes 7 times faster than wild-type when Al3+ and F- are added to it in the presence of excess ADP and Mg2+. It also resists inhibition by high Mg2+ concentrations in the assay medium. At least one noncatalytic site of the (alpha F244C)3 beta 3 gamma subcomplex has increased affinity for ADP, indicating that the enhanced rate of formation of the ADP-fluoroaluminate complex reflects augmented cooperativity between noncatalytic and catalytic sites. The rate of formation of the ADP-fluoroaluminate complex in (alpha Y300C)3 beta 3 gamma increases only 40% when MgADP in bound to two catalytic sites rather than one, compared to a 9-fold increase exhibited by wild type. When Al3+ and F- are added to the (alpha Y300C)3 beta 3 gamma subcomplex after incubation with excess ADP and Mg2+, ADP-fluoroaluminate complexes are formed in three catalytic sites rather than two observed with the other subcomplexes. Reconciliation of the catalytic properties of the mutant subcomplexes in terms of the crystal structure suggests that alpha F244, alpha R304, and alpha Y300 of TF1 are part of a pathway that propagates conformational signals from one catalytic site to another.
Thermomicrobium carboxidum sp. nov., and Thermorudis peleae gen. nov., sp. nov., carbon monoxide-oxidizing bacteria isolated from geothermally heated biofilms.

Two thermophilic, Gram-stain-positive, rod-shaped, non-spore-forming bacteria (strains KI3T and KI4T) were isolated from geothermally heated biofilms growing on a tumulus in the Kilauea Iki pit crater on the flank of Kilauea Volcano (Hawai‘i, USA). Strain KI3T grew over an examined temperature range of 50–70 °C (no growth at 80 °C) and a pH range of 6.0–9.0, with optimum growth at 70 °C and pH 7.0. Strain KI4T grew at temperatures of 55–70 °C and a pH range of 5.8–8.0, with optimum growth at 65 °C and pH 6.7–7.1. The DNA G+C contents of strains KI3T and KI4T were 66.0 and 60.7 mol%, respectively. The major fatty acid for both strains was 12-methyl C18 : 0. Polar lipids in strain KI3T were dominated by glycolipids and phosphatidylinositol, while phosphatidylinositol and phosphoglycolipids dominated in strain KI4T. Strain KI3T oxidized carbon monoxide [6.7±0.8 nmol CO h−1 (mg protein)−1], but strain KI4T did not. 16S rRNA gene sequence analyses determined that the strains belong to the class Thermomicrobia , and that strains KI3T and KI4T are related most closely to Thermomicrobium roseum DSM 5159T (96.5 and 91.1 % similarity, respectively). 16S rRNA gene sequence similarity between strain KI3T and strain KI4T was 91.4 %. Phenotypic features and phylogenetic analyses supported the affiliation of strain KI3T to the genus Thermomicrobium , while results of chemotaxonomic, physiological and biochemical assays differentiated strains KI3T and KI4T from Thermomicrobium roseum . Strain KI3T ( = DSM 27067T = ATCC BAA-2535T) is thus considered to be the type strain of a novel species, for which the name Thermomicrobium carboxidum sp. nov. is proposed. Additionally, the characterization and phylogenetic position of strain KI4T showed that it represents a novel species of a new genus, for which the name Thermorudis peleae gen. nov., sp. nov. is proposed. The type strain of Thermorudis peleae is KI4T ( = DSM 27169T = ATCC BAA-2536T).
Atomic and molecular adsorption on Pd(111)

The adsorption properties of a variety of atoms (H, O, N, S, and C), molecules (N2, HCN, CO, NO, and NH3) and molecular fragments (CN, NH2, NH, CH3, CH2, CH, HNO, NOH, and OH) are calculated on the (0001) facet of ruthenium using periodic, self-consistent, density functional theory calculations (DFT-GGA) at 1/4 ML coverage. For each species, we determine the optimal binding geometry and corresponding binding energy. The vibrational frequencies of these adsorbed species are calculated and are found to be in good agreement with experimental values that have been reported in the literature. From the binding energies, we calculate potential energy surfaces for the decomposition of NO, CO, N2, NH3, and CH4 on Ru(0001), showing that the decomposition of all of these molecules is thermochemically preferred to their desorption.