cssi/SciSciGPT-SciSciNet huggingface dataset:
Tissue‐specific reactions to positional discontinuities in the regenerating axolotl limb

We investigated cellular contributions to intercalary regenerates and 180° supernumerary limbs during axolotl limb regeneration using the cell autonomous GFP marker and exchanged blastemas between white and GFP animals. After distal blastemas were grafted to proximal levels tissues of the intercalary regenerate behaved independently with regard to the law of distal transformation; graft epidermis was replaced by stump epidermis, muscle-derived cells, blood vessels and Schwann cells of the distal blastema moved proximally to the stylopodium and cartilage and dermal cells conformed to the law. After 180° rotation, blastemas showed contributions from stump tissues which failed to alter patterning of the blastema. Supernumerary limbs were composed of stump and graft tissues and extensive contributions of stump tissues generated inversions or duplications of polarity to produce limbs of mixed handedness. Tail skeletal muscle and cardiac muscle broke the law with cells derived from these tissues exhibiting an apparent anteroposterior polarity as they migrated to the anterior side of the blastema. We attribute this behavior to the possible presence of a chemotactic factor from the wound epidermis.
INVESTIGATION ON THE POTENTIAL, ROLE OF THE AH RECEPTOR NUCLEAR TRANSLOCATOR PROTEIN IN VITAMIN D RECEPTOR ACTION

The Ah receptor nuclear translocator protein (ARNT) is required for binding of the Ah (dioxin) receptor to the xenobiotic responsive element (XRE), and is a structural component of the XRE-binding form of the Ah receptor. The vitamin D receptor requires an accessory protein for binding to the vitamin D responsive element (VDRE) in the osteocalcin gene. Since the vitamin D receptor has similarities to the Ah receptor, we investigated whether ARNT is also required for vitamin D receptor activity. Two lines of evidence demonstrate that ARNT is not required for vitamin D receptor activity, and therefore does not correspond to the vitamin D receptor accessory protein: i) Antibodies to ARNT have no effect on binding of the vitamin D receptor to the VDRE. ii) c4, a mutant of Hepa-1 cells that is defective in ARNT activity, and in which binding of the Ah receptor to the XRE does not occur, possesses a vitamin D receptor with full activity for binding the VDRE.
Differential gene expression analysis using coexpression and RNA-Seq data

RNA-Seq is increasingly being used for differential gene expression analysis which was dominated by the microarray technology in the past decade. However, inferring differential gene expression based on the observed difference of RNA-Seq read counts has unique challenges that were not present in microarray-based analysis. The differential expression estimation may be biased against low read count values such that the differential expression of genes with high read counts is more easily detected. The estimation bias may further propagate in downstream analyses at the systems biology level if it is not corrected. To obtain a better inference of differential gene expression, we propose a new efficient algorithm based on a markov random field (MRF) model, called MRFSeq, that uses additional gene coexpression data to enhance the prediction power. Our main technical contribution is the careful selection of the clique potential functions in the MRF so its maximum a posteriori (MAP) estimation can be reduced to the well-known maximum flow problem and thus solved in polynomial time. Our extensive experiments on simulated and real RNA-Seq datasets demonstrate that MRFSeq is more accurate and less biased against genes with low read counts than the existing methods based on RNA-Seq data alone. For example, on the well-studied MAQC dataset, MRFSeq improved the sensitivity from 11.6% to 38.8% for genes with low read counts. MRFSeq is implemented in C++ and available at http://www.cs.ucr.edu/~yyang027/mrfseq.htm.
High Spontaneous Rate of Gene Duplication in Caenorhabditis elegans

Summary Gene and genome duplications are the primary source of new genes and novel functions and have played a pivotal role in the evolution of genomic and organismal complexity [1, 2]. The spontaneous rate of gene duplication is a critical parameter for understanding the evolutionary dynamics of gene duplicates; yet few direct empirical estimates exist and differ widely. The presence of a large population of recently derived gene duplicates in sequenced genomes suggests a high rate of spontaneous origin, also evidenced by population genomic studies reporting rampant copynumber polymorphism at the intraspecific level [3‐6]. An analysis of long-term mutation accumulation lines of Caenorhabditis elegans for gene copy-number changes with array comparative genomic hybridization yields thefirst direct estimate of the genome-wide rate of gene duplication in a multicellular eukaryote. The gene duplication rate in C. elegans is quite high, on the order of 10 27 duplications/ gene/generation. This rate is two orders of magnitude greater than the spontaneous rate of point mutation per nucleotide site in this species and also greatly exceeds an earlier estimate derived from the frequency distribution of extant gene duplicates in the sequenced C. elegansgenome.
Confidence as Higher-Order Uncertainty

With conflicting evidence, a reasoning system derives uncertain conclusions. If the system is open to new evidence, it faces additionally a higher-order uncertainty, because the first-order uncertainty evaluations are uncertain themselves — they can be changed by future evidence. A new measurement, confidence, is introduced for this higher-order uncertainty. It is defined in terms of the amount of available evidence, and interpreted and processed as the relative stability of the first-order uncertainty evaluation. Its relation with other approaches of “reasoning with uncertainty” is also discussed.
Femicide in New York City 1990 to 1999

This article reports resultsof an ongoing studyof femicide in New York City. Using medical examiner records, femicides occurring between 1990 and 1999 were categorized according to whether an intimate partner perpetrated the homicide. Descriptive analyses results revealed that most femicide victims were young, Black, and killed in poor neighborhoods. Among cases with a known perpetrator, 40% were intimate partner femicides. Whereas the rate of nonintimate partner femicide decreased between 1990 and 1999, the rate of intimate partner femicide remained relatively stable. Multivariate analyses revealed that the strongest predictors of femicide by an intimate partner included having children under 18, living in a private residence, and being foreign born. Homicide followed by the suicide of the offender was also strongly associated with intimate partner femicide. Intimate partner femicide exhibits a unique epidemiology, and this knowledge should be used to plan and guide prevention activities.
Acute sporadic non-A, non-B, non-C, non-D, non-E hepatitis

Patients presenting with clinical and laboratory features consistent with a diagnosis of acute non-A, non-B hepatitis were evaluated for evidence of hepatitis C or hepatitis E infection and for evidence of severe or prolonged disease. Antibody to hepatitis C virus (anti-HCV) was detected in 75 of 108 (69%) patients, antibody to hepatitis E virus (anti-HEV) in three patients (3%), and neither antibody in 31 (29%) patients. One patient had both anti-HCV and anti-HEV. HCV RNA was not detected in sera from any of 20 patients with seronegative (non-ABCDE) hepatitis, but in all 10 patients with anti-HCV who were tested by polymerase chain reaction (PCR). Compared with patients with acute hepatitis C, those with non-ABCDE hepatitis had a lower incidence of parenteral risk factors (6% vs. 70%; P 15 mg/dL; P 5 weeks after onset; P 3 second prolongation; P < .001), more severe hypoalbuminemia (39% vs. 9% with albumin <3 g/dL; P < .01), and more frequent major clinical complications (13% vs. 0% with encephalopathy; P < .01; 10% vs. 0% with death or transplant; P = .024). Patients with acute non-ABCDE hepatitis were less likely to develop chronic hepatitis than those with acute hepatitis C (23% vs. 68%; P < .05). Thus, patients with acute non-ABCDE hepatitis are epidemiologically distinct from those with acute hepatitis C and have a significantly more severe acute illness.
Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity of amyloid beta

Amyloid protein aggregates are associated with dozens of devastating diseases including Alzheimer's, Parkinson's, ALS, and diabetes type 2. While structure-based discovery of compounds has been effective in combating numerous infectious and metabolic diseases, ignorance of amyloid structure has hindered similar approaches to amyloid disease. Here we show that knowledge of the atomic structure of one of the adhesive, steric-zipper segments of the amyloid-beta (Aβ) protein of Alzheimer's disease, when coupled with computational methods, identifies eight diverse but mainly flat compounds and three compound derivatives that reduce Aβ cytotoxicity against mammalian cells by up to 90%. Although these compounds bind to Aβ fibers, they do not reduce fiber formation of Aβ. Structure-activity relationship studies of the fiber-binding compounds and their derivatives suggest that compound binding increases fiber stability and decreases fiber toxicity, perhaps by shifting the equilibrium of Aβ from oligomers to fibers. DOI:http://dx.doi.org/10.7554/eLife.00857.001.
Heat transfer and melting in subglacial basaltic volcanic eruptions: implications for volcanic deposit morphology and meltwater volumes

Subglacial volcanic eruptions can generate large volumes of meltwater that is stored and transported beneath glaciers and released catastrophically in jokulhlaups. At typical basaltic dyke propagation speeds, the high strain rate at a dyke tip causes ice to behave as a brittle solid; dykes can overshoot a rock-ice interface to intrude through 20-30% of the thickness of the overlying ice. The very large surface area of the dyke sides causes rapid melting of ice and subsequent collapse of the dyke to form a basal rubble pile. Magma can also be intruded at the substrate-ice interface as a sill, spreading sideways more efficiently than a subaerial flow, and also producing efficient and widespread heat transfer. Both intrusion mechanisms may lead to the early abundance of meltwater sometimes observed in Icelandic subglacial eruptions. If meltwater is retained above a sill, continuous melting of adjacent and overlying ice by hot convecting meltwater occurs. At typical sill pressures under more than 300 m ice thickness, magmatic CO 2 gas bubbles form c. 25 vol% of the pressurized magma. If water drains and contact with the atmosphere is established, the pressure decreases dramatically unless the overlying ice subsides rapidly into the vacated space. If it does not, further CO 2 exsolution plus the onset of H 2O exsolution has the potential to cause explosive fragmentation, i.e. a fire-fountain that forms at the dyke-sill connection, enhancing melting and creating another candidate pulse of meltwater. The now effectively subaerial magma body becomes thicker, narrower, and flows faster so that marginal meltwater drainage channels become available. If the ice overburden thickness is much less than c. 300 m the entire sill injection process may involve explosive magma fragmentation. Thus, there should be major differences between subglacial eruptions under local or alpine glaciers compared with those under continental-scale glaciers.
Parallel best—first search of state-space graphs: a summary of results

This paper presents many different parallel formulations of the A*/Branch-and-Bound search algorithm. The parallel formulations primarily differ in the data structures used. Some formulations are suited only for shared-memory architectures, whereas others are suited for distributed-memory architectures as well. These parallel formulations have been implemented to solve the vertex cover problem and the TSP problem on the BBN Butterfly parallel processor. Using appropriate data structures, we are able to obtain fairly linear speedups for as many as 100 processors. We also discovered problem characteristics that make certain formulations more (or less) suitable for some search problems. Since the best-first search paradigm of A*/Branch-and-Bound is very commonly used, we expect these parallel formulations to be effective for a variety of problems. Concurrent and distributed priority queues used in these parallel formulations can be used in many parallel algorithms other than parallel A*/branch-and-bound.
Aerobic Growth on Nitroglycerin as the Sole Carbon, Nitrogen, and Energy Source by a Mixed Bacterial Culture

Nitroglycerin (glycerol trinitrate [GTN]), an explosive and vasodilatory compound, was metabolized by mixed microbial cultures from aeration tank sludge previously exposed to GTN. Aerobic enrichment cultures removed GTN rapidly in the absence of a supplemental carbon source. Complete denitration of GTN, provided as the sole C and N source, was observed in aerobic batch cultures and proceeded stepwise via the dinitrate and mononitrate isomers, with successive steps occurring at lower rates. The denitration of all glycerol nitrate esters was found to be concomitant, and 1, 2-glycerol dinitrate (1,2-GDN) and 2-glycerol mononitrate (2-GMN) were the primary GDN and GMN isomers observed. Denitration of GTN resulted in release of primarily nitrite-N, indicating a reductive denitration mechanism. Biomass growth at the expense of GTN was verified by optical density and plate count measurements. The kinetics of GTN biotransformation were 10-fold faster than reported for complete GTN denitration under anaerobic conditions. A maximum specific growth rate of 0.048 +/- 0.005 h-1 (mean +/- standard deviation) was estimated for the mixed culture at 25 degreesC. Evidence of GTN toxicity was observed at GTN concentrations above 0. 3 mM. To our knowledge, this is the first report of complete denitration of GTN used as a primary growth substrate by a bacterial culture under aerobic conditions.
Dynamic coupling of quasi-electrostatic thundercloud fields to the mesosphere and lower ionosphere: sprites and jets

Red Sprites and Blue Jets are two different types of recently discovered optical flashes ob- served above large thunderstorm systems. Sprites are luminous glows occurring at altitudes typically ranging from approximately 50 to 90 km. In video they exhibit a red color at their top which gradually changes to blue at lower altitudes. Sprites may occur singly or in clusters of two or more. The lateral extent of "unit" sprites is typically 5-10 km and they endure for several milliseconds. Jets are upward moving (approximately 100 km/s) highly collimated beams of luminosity, emanating from the tops of thunderclouds, extending up to approximately 50 km altitude and exhibiting a primarily blue color. We propose that sprites result from large electric field transients capable of causing electron heating, breakdown ionization and excitation of optical emissions at mesospheric altitudes following the removal of thundercloud charge by a cloud-to-ground discharge. Depending on the history of charge accumulation and removal, and the distribution of ambient atmospheric conductivity, the breakdown region may have the shape of vertically oriented ionization column(s). Results of a two-dimensional and self consistent quasi-electrostatic (QE) model indicate that most of the observed features of sprites can be explained in terms of the formation and self-driven propagation of streamer type channels of breakdown ionization. Comparison of the optical emission intensities of the 1st and 2nd positive bands of N2, Meinel and 1st negative bands of N2(+) and the 1st negative band of O2(+) demonstrates that the 1st positive band of N2 is the dominant optical emission in the altitude range approximately 50-90 km, which accounts for the observed red color of sprites. Optical emissions of the 1st and 2nd positive bands of N2 occur in carrot-like vertical structures with typical transverse dimension approximately 5-10 km which can span an altitude range from approximately 80 km to well below approximately 50 km. The appearance of optical emissions associated with sprites can be delayed in time (approximately 1-20 ms) with respect to the causative cloud to ground discharge. Theoretical model results are found to be in good agreement with recent video, photometric and spectral measurements of sprites.
Investing in size and book-to-market portfolios using information about the macroeconomy: some new trading rules

We propose new trading strategies that invest in size and book-to-market (B/M) decile portfolios. These trading strategies are based on a forecast model that uses mainly business cycle-related variables as predictors. Extensive out-of-sample experiments show profitable predictability in the returns of the decile portfolios. In particular, the proposed strategies outperform passive investments in the same deciles, as well as SMB- and HML-type of strategies. A key characteristic of the proposed strategies is that the long and short positions can be invested in different decile portfolios across time. This is in contrast to the traditional SMB- and HML-type of strategies that always go long and short on the same portfolios. Active strategies that involve the market portfolio, SMB and HML are also examined. A significant level of predictability is identified for SMB. Our results suggest that time variation in SMB and HML is linked to variations in aggregate, macroeconomic, nodiversifiable risk. Thus, our results most closely support a risk-based explanation for SMB and HML.
Where Are the Healthcare Leaders? The Need for Investment in Leadership Development

Is there a crisis in healthcare leadership? In order to understand this question we must first look at what is meant by the term leadership. We prize and admire leadership skills, yet we have little understanding of how and why some persons are more effective leaders than others. This paper describes the changing concept of leadership in the context of both corporate and healthcare settings. The approaches taken in corporate leadership development programs are contrasted with the way in which leaders have been developed in healthcare. The authors assert that there are unique characteristics of health systems and organizations that warrant a tailored approach. A new model of developing healthcare leaders is proposed, one that could transform the educational process and improve outcomes. The authors call for a "back to basics" about how adults learn and outline an approach to leadership development in healthcare that includes principles of competency-based development, interdisciplinary and team learning and continuous assessment. Their conclusion is that leadership development is not done solely to improve the leadership skills of one individual but is an essential component of the development of the organization as a whole. Progressive health systems that invest in leadership development for the entire senior management team will have the more significant return on investment in terms of organizational effectiveness.
Evolution of wireless and personal communications. Road towards FPLMTS

FPLMTS (future public land mobile telecommunications system) will be the first wireless network, which applies the same basic radio technology for different environments, and which will provide global mobility to the users. The justification of FPLMTS is to open network operators and service providers to new and more powerful services and applications which can be tailored to the specific needs of a given user. These personalized services must be accessible through any network, at any time, in a uniformed way using a unique personal identity. This requires a flexible and powerful network infrastructure. One of the main challenges is how to ensure an orderly transition from current wireless and wireline systems to FPLMTS. The realization of FPLMTS requires not only an architecture that supports the vision of personal communication but also to strike a balance between reuse of investments already made and the introduction of new technologies so that the impact on existing networks can be minimized. FPLMTS must integrate technologies used in PSTN, PLMN, (B)ISDN and private networks to maximize utilization of existing infrastructure and achieve low-cost transport.
Addressing link-level design tradeoffs for integrated photonic interconnects

Integrated photonic interconnects have emerged recently as a potential solution for relieving on-chip and chip-to-chip bandwidth bottlenecks for next-generation many-core processors. To help bridge the gap between device and circuit/system designers, and aid in understanding of inherent photonic link tradeoffs, we present a set of link component models for performing interconnect design-space exploration connected to the underlying device and circuit technology. To compensate for process and thermal-induced ring resonator mismatches, we take advantage of device and circuit characteristics to propose an efficient ring tuning solution. Finally, we perform optimization of a wavelength-division-multiplexed link, demonstrating the link-level interactions between components in achieving the optimal degree of parallelism and energy-efficiency.
Estrogen and Androgen Receptor Activities of Hydraulic Fracturing Chemicals and Surface and Ground Water in a Drilling-Dense Region

The rapid rise in natural gas extraction using hydraulic fracturing increases the potential for contamination of surface and ground water from chemicals used throughout the process. Hundreds of products containing more than 750 chemicals and components are potentially used throughout the extraction process, including more than 100 known or suspected endocrine-disrupting chemicals. We hypothesizedthataselectedsubsetofchemicalsusedinnaturalgasdrillingoperationsandalsosurface and ground water samples collected in a drilling-dense region of Garfield County, Colorado, would exhibit estrogen and androgen receptor activities. Water samples were collected, solid-phase extracted, and measured for estrogen and androgen receptor activities using reporter gene assays in human cell lines. Of the 39 unique water samples, 89%, 41%, 12%, and 46% exhibited estrogenic, antiestrogenic, androgenic, and antiandrogenic activities, respectively. Testing of a subset of natural gas drilling chemicals revealed novel antiestrogenic, novel antiandrogenic, and limited estrogenic activities. The Colorado River, the drainage basin for this region, exhibited moderate levels of estrogenic, antiestrogenic, and antiandrogenic activities, suggesting that higher localized activity at sites with known natural gas–related spills surrounding the river might be contributing to the multiple receptor activities observed in this water source. The majority of water samples collected from sites in a drilling-dense region of Colorado exhibited more estrogenic, antiestrogenic, or antiandrogenic activities than reference sites with limited nearby drilling operations. Our data suggest that natural gas drillingoperationsmayresultinelevatedendocrine-disruptingchemicalactivityinsurfaceandground water. (Endocrinology 155: 897–907, 2014)
Vibrotactile temporal summation: probability summation or neural integration?

Temporal summation, a decrease in the detection threshold that occurs when either the duration of a stimulus or the number of stimuli in a sequence is increased, has been attributed to the operations of either the mechanism of neural integration or of probability summation. Our experiments indicate that under certain conditions, both mechanisms may operate, but that the process of neural integration is an exclusive characteristic of the Pacinian (P) channel. The P channel was isolated by applying 250 Hz stimuli through a 1.5 cm2 contactor to the thenar eminence of the hand and the NPII channel was isolated by applying the stimuli through a 0.01 cm2 contactor. The finding that the slopes of the psychometric functions were the same within both channels indicated that probability summation could not account for temporal summation for stimulus durations less than 1 s. The finding that the threshold for the detection of multiple-pulse stimuli increased as the interpulse interval increased indicated that, for t...
Intelligence and Diversity: A Western and Eastern View from a Global Paradigm

Intelligence, whether hereditary or acquired, has been the subject of discussion since the beginning of time. Multiple intelligences have been in existence for thousands of years and the use of these various capabilities can greatly impact a person’s thinking, feelings, and habits. Based upon previous studies and experiences on multiple intelligences, this paper attempts to shed light on the topic from a global perspective to clarify the stereotypes regarding intelligence which are attached to people of different countries, cultures, and genders. Research has identified a relationship between the domains of multiple intelligences such as interpersonal, intrapersonal, linguistic intelligences, leadership, and demographic characteristics such as, age, gender and ethnicity among various populations and professions. Using literature and secondary sources, the authors provide a view of multiple intelligences from a global perspective along with a theoretical framework. Studies seem to indicate that despite the existing stereotypes people of all backgrounds and cultures have similar levels of intelligences. The paper concludes by offering a discussion on the skills of social intelligence as well as suggestions on respecting and understanding each other’s differences. The literature and content can be useful for clarifying stereotypes, management selection, as well as training and development in today’s global corporations that are competing in a highly complex world.
The Optimal Capital Structure of Banks under Deposit Insurance and Capital Requirements

Capital structure is an important topic in corporate finance, both for practitioners and academic researchers. This paper examines the impact of deposit insurance and capital requirements on the optimal capital structure of banks. The contingent claims model of capital structure is extended to incorporate deposit insurance and capital requirements. Unlike previous studies on the capital structure of banks, our model suggests that there exists an interior optimal capital ratio in the presence of deposit insurance, taxes and a minimum fixed capital ratio. Moreover, a significant financial burden associated with violating capital requirements is needed in order to obtain the interior capital ratio.
Implementation of Multi-Year Product Innovation Projects

A methodology and case study detailing the implementation of multi-year product innovation projects is presented. A product called the Waterboy, an inexpensive water purification system designed for under developed countries, was developed by three different groups of students over a span of two years. The initial concept was first developed by a six member entrepreneurial team composed of senior level business and engineering students enrolled in a one semester Product Innovation and Development course. This team was responsible assessing the market need, determining product requirements and developing a limited functionality prototype capable of demonstrating the intended product function. A second team consisting of two Mechanical Engineering students continued the project as their one semester Senior Capstone Design project and was charged with the task of developing a fully functional prototype capable of purifying contaminated water. A third student completed the project as a one semester senior level Design Projects course and was charged with the task of modifying the previous design to minimize cost, facilitate ease manufacture and reduced assembly and distribution costs.In the Fall of 2010, the entrepreneurial team conducted interviews with health professionals and performed research involving a number of world health and philanthropic organizations. They identified the need for an improved water purification device which could purify enough water for a family of four in a reasonable amount of time and at a cost which would make it accessible to people in underdeveloped countries who are at risk of dying from the consumption of contaminated drinking water. They developed a bicycle driven system which used an ultraviolet germicidal bulb to purify water. The team developed a prototype which demonstrated the basic function of the device which was estimated to cost about $80. The project was continued in the Fall of 2011 by the second team of Mechanical Engineering seniors who refined the purification system and function of the device while simplifying the design, resulting in an estimated cost of $49 per unit. The team built and tested a fully functional prototype which confirmed it was capable of reducing water borne bacteria by a factor of 1000. The project was then completed in the Fall of 2012 by a Senior Mechanical Engineering Student who further reduced the cost of the design and improved its portability in order to reduce distribution costs. A partnership with Goodwill Industries was formed to utilize their recycled materials and inexpensive labor force, which reduced the product cost about $24.Copyright © 2014 by ASME
Winifred Van Hagen 1881–1968

(1969). Winifred Van Hagen 1881–1968. Journal of Health, Physical Education, Recreation: Vol. 40, No. 5, pp. 89-90.
Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease

Recurrence of malignant brain tumors results in a poor prognosis with limited treatment options. High-dose chemotherapy with autologous hematopoietic cell rescue (AHCR) has been used in patients with recurrent malignant brain tumors and has shown improved outcomes compared with standard chemotherapy. Temozolomide is standard therapy for glioblastoma and has also shown activity in patients with medulloblastoma/primitive neuro-ectodermal tumor (PNET), particularly those with recurrent disease. Temozolomide was administered twice daily on days -10 to -6, followed by thiotepa 300 mg/m(2) per day and carboplatin dosed using the Calvert formula or body surface area on days -5 to -3, with AHCR day 0. Twenty-seven patients aged 3-46 years were enrolled. Diagnoses included high-grade glioma (n=12); medulloblastoma/PNET (n=9); central nervous system (CNS) germ cell tumor (n=4); ependymoma (n=1) and spinal cord PNET (n=1). Temozolomide doses ranged from 100 mg/m(2) per day to 400 mg/m(2) per day. There were no toxic deaths. Prolonged survival was noted in several patients including those with recurrent high-grade glioma, medulloblastoma and CNS germ cell tumor. Increased doses of temozolomide are feasible with AHCR. A phase II study using temozolomide, carboplatin and thiotepa with AHCR for children with recurrent malignant brain tumors is being conducted through the Pediatric Blood and Marrow Transplant Consortium.
USE OF DISCREPANCY SENSITIVITY IN UNCERTAINTY QUANTIFICATION AND OPTIMIZATION

Approximately uniform distributions of sample points are useful in certain problems in engineering and mathematics, notably optimization and uncertainty. For example, weight-controlled Monte Carlo simulation (MCS), a technique to improve estimates of low-probability events, would ideally have samples approximately uniformly distributed throughout the sample space with weights estimating probability. Response surface methodologies likewise benefit from an even distribution of sample points, not only over the input space but also over the output space, particularly in regions where steep gradients occur. The notion of uniformity can be quantified by the concept of discrepancy, which is a measure of the difference between a sample distribution and an ideal distribution -- in this case, a uniform distribution. This paper advances the discrepancy sensitivity, a linear approximation for the change in discrepancy when adding or removing a particular sample point, as a numerical measure of a sample point’s contribution to uniformity. Essentially, this quantifies the level of “new” information provided by a sample point. Several examples are given of its use in choosing sample points for response surface characterization. The example problems, while of trivial computational complexity, exhibit some of the “difficult” behaviors — such as multimodality, sharp corners, and so forth — that are typical of many real world applications. It is demonstrated that using the discrepancy sensitivity, sample points can be effectively spread throughout the “interesting” regions of these functions. Some indications of the current work-inprogress and future directions are given. †
Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis.

Bacille Calmette–Guerin (BCG) is currently the only approved vaccine against tuberculosis (TB) and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0–80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM) found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium), a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naive BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. This has implications in TB-burdened countries where drug resistance is on the rise and health care options are limited due to economic considerations. A successful vaccine against TB is necessary in these areas as it is both effective and economical.
Biochemical consequences of resistance to a recently discovered IMP dehydrogenase inhibitor, benzamide riboside, in human myelogenous leukemia K562 cells

Benzamide riboside (BR) exhibits potent antitumor activity in a variety of cultured human tumor cells. The drug is metabolized to benzamide adenine dinucleotide (BAD), which in turn functions as a selective inhibitor of IMP dehydrogenase (IMPDH) activity with a Ki of 0.118 microM. In vitro, BR is a more potent antitumor inhibitor of IMPDH than tiazofurin, another IMPDH inhibitor which has shown significant oncolytic activity in adult patients with end-stage leukemia. To elucidate the mechanism of resistance, a variant of human myelogenous leukemia K562 cells was developed by subculturing sensitive cells in sublethal concentrations of BR over 60 generations. The BR resistant line that emerged exhibited an IC50 (a concentration producing 50% reduction in cell proliferation) of 148 microM, compared to the sensitive line which had an IC50 of 1.6 microM. The activity of the target enzyme, IMPDH, was increased 3-fold in the resistant variant. Studies on BR metabolism revealed that resistant cells formed only 18% of the active metabolite, BAD, compared to sensitive cells. This finding, in turn, correlated with the specific activity of NAD pyrophosphorylase (the enzyme responsible for the synthesis of BAD) which was reduced to undetectable levels in the resistant variant. The basal levels of NAD and guanylates were also significantly decreased to 41% and 48%, respectively, in the resistant line compared to the parent line. Additionally, after treatment with BR a decrease in guanylate level was observed only in the sensitive cells. Sensitive and resistant cells exhibit comparable cytotoxicity to agents outside the tiazofurin family, suggesting that a multidrug resistance was unlikely to explain the resistance to BR. Moreover, BR resistant cells exhibit collatoral sensitivity to 6-aminopurine, cytarabine and 5-fluorouracil, which have different mechanisms of action. In conclusion, these studies establish that the primary mechanism of resistance to BR involves an increase in IMPDH (target enzyme) activity with a concurrent decrease in NAD pyrophosphorylase (BAD synthetic enzyme) activity.
A feedback linearization control scheme for maximum power generation in wind energy systems

As the penetration of wind turbines into the power grid increases, greater emphasis is placed on designing advanced control approaches for optimum power generation. This paper proposes a novel control scheme for a DFIG-driven variable speed wind energy system. The approach aims at reaching optimum performance in terms of power generation at the point of common coupling. The control scheme is derived based on the feedback linearization technique, allowing both decoupling and linearization of the nonlinear multivariable system. The proposed approach is based on the theory of feedback linearization and is aimed at achieving optimum power generation at any wind speed within the operating range. Application of the proposed approach to a DFIG-based variable speed wind turbine has led to optimum operations at various speed ranges. Simplicity and ease of implementation of the overall scheme along with its fast dynamic response in addition to the optimum power production are the main positive features of the proposed approach.
Physicochemical concepts in drug design.

A successful drug candidate has the right attributes to reach and bind its molecular target and has the desired duration of action. Binding to the target can be optimised by designing the proper three-dimensional arrangement of functional groups. Each chemical entity also has, through its structure, physicochemical and biopharmaceutical properties. These are generally related to processes such as dissolution, oral absorption, uptake into the brain, plasma protein binding, distribution, and metabolism. Therefore fine-tuning of the physicochemical properties has an important place in lead optimization.
The Top Quark in the Context of the Standard Model

The analyses presented in this thesis deal with measurements of the production of top quark pairs at the Large Hadron Collider, as predicted in the framework of the Standard Model of Particle Physics. The first part of this chapter will focus on the theoretical framework in general, while the second part will describe the production and properties of top quarks in more detail and give an overview of the current experimental knowledge of top quark production.
The Bis(triethylammonium) Salt of 3,5,12- Trinitrotricyclo[5.3.1.1 2,6 ]dodecan-8,10,11-trione-3,8-(NO 2 ,O)-dianion

Reaction of phloroglucinol with s-trinitrobenzene and triethylamine results in formation of the deep red bis-triethylammonium salt of 3,5,12-trinitrotricyclo[5.3.1.12,6]dodecan-8,10,11-trione-3,8-(NO2,O) dianion, [(C6H15NH)+]2 (C12H7N9)2−. Crystals are monoclinic, and at 150(2) K a = 6.8612(7), b = 35.284(3), c = 11.0118(15) A, β = 94.601(10)°, and V = 2657.3(5) A3 with Z = 4. Both enolate and nitropropenenitronate groups are delocalized with lengthened C–O and N–O distances and shortened intervening C–C distances. The neutral nitro group at C12 has been determined to be endo to the nitroproprene nitronate. Triethylammonium ions form N+–H··O Hydrogen-bonds with the enolate oxygens and weaker methylene C–H··O contacts with the nitronates. Phloroglucinol, s-trinitrobenzene and trimethylamine react to form a tricyclic dodecane dianion, which has been isolated as its bis(triethylammonium) salt.
Children’s Activity Levels and Lesson Context During Summer Swim Instruction

Summer swim programs provide a unique opportunity to engage children in PA as well as an important life-saving skill. Offering summer swim programs is critical, especially for minority populations who tend to have higher rates of drowning, specifically in youth populations. The purpose of this study was to determine the lesson context and children’s participation levels during a summer swimming program taught by two experienced PE teachers. The participants in this study were two experienced PE teachers and 45 children who were enrolled in the summer swim program. Data were collected using the System for Observing Fitness Instruction Time (SOFIT) and analyzed using MANOVA and ANOVA statistical tests. Results indicated that the students overall MVPA levels during the swim program were very high (58.96 %). Results also indicated that a majority of the lesson context was spent in skill practice (47.31%), and management (20.23%) was the lowest. These findings provide additional indications that swim instruction is a viable option to provide children with ample MVPA. It would be beneficial moving forward for schools to include swim instruction in the curriculum not only to improve water safety, but also to provide high levels of PA.
CYANIDE-INSENSITIVE RESPIRATORY SYSTEMS IN NEUROSPORA

ABSTRACT The respiration of some mutant strains of Neurospora crassa and of wild-type cells treated with chloramphenicol is composed of three distinct pathways. These can be distinguished by the use of inhibitors. Pathways are present that are inhibited by cyanide, substituted hydroxamic acids, and by azide in the presence of both cyanide and hydroxamic acid. A series of nuclear mutants has been isolated that cannot produce the hydroxamate-sensitive pathway under conditions where it is induced in wild-type cells. Mutants of this type which also lack the azide-sensitive pathway cannot grow in the presence of antimycin A. Mutants of mixed phenotype which lack the hydroxamate-sensitive pathway but have the azide-sensitive pathway do grow in the presence of antimycin A. An extranuclear mutant, cni-3, has been isolated which has the hydroxamate-sensitive pathway present at all times during the growth cycle. Mitochondria from cni-3 have normal cytochrome content, ATP and pyridine nucleotide levels and normal oxidative phosphorylation. Titration of cni-3. with cyanide and salicyl hydroxamic acid indicates that the hydroxamate-sensitive pathway in these cells is not utilized in vivo.
Revisiting Ethnic Niches: A Comparative Analysis of the Labor Market Experiences of Asian and Latino Undocumented Young Adults

Drawing on thirty in-depth interviews with Korean- and Mexican-origin undocumented young adults in California, this comparative analysis explores how the intersection of immigration status and ethnoracial background affects social and economic incorporation. Respective locations of principal ethnic niches, and access to these labor market structures, lead to divergent pathways of employment when no legal recourse exists. Despite similar levels of academic achievement, Korean respondents were more likely to enter into a greater diversity of occupations relative to Mexican respondents. However, the experiences of Mexican respondents varied depending on their connection to pan-ethnic Latino nonprofit organizations. Illegality, therefore, is conditioned by opportunity structures that vary strongly by membership in different ethnoracial communities, leading to structured heterogeneity in experiences with undocumented status.
Purification, Characterization, and Molecular Cloning of the Chicken Gizzard Smooth Muscle Ecto-ATPase

The ecto-ATPase from chicken smooth muscle was solubilized, purified, and characterized. Mono- and polyclonal antibodies were raised and the tissue distribution based on Western analysis was determined. N-terminal and internal protein sequences were determined and used to design degenerate oligonucleotide probes to screen a chicken muscle cDNA library. Two overlapping partial clones encoding most of the ecto-ATPase were isolated and sequenced. A unified theory as to the mechanism by which many varied types of molecules modulate ecto-ATPase activity was developed, and the theory was supported by cross-linking data.
Practical Approaches for Assessment of Daily and Post-discharge Room Disinfection in Healthcare Facilities

Cleaning and disinfection in healthcare facilities is essential to ensure patient safety. This review examines practical strategies used to assess and improve the effectiveness of daily and post-discharge manual cleaning in healthcare facilities. Effective implementation of cleaning interventions requires objective monitoring of staff performance with regular feedback on performance. Use of fluorescent markers to assess thoroughness of cleaning and measurement of residual ATP can provide rapid and objective feedback to personnel and have been associated with improved cleaning. Direct observation of cleaning and interviews with front-line staff are useful to identify variations and deficiencies in practice that may not be detected by other methods. Although not recommended for routine monitoring, cultures can be helpful for outbreak investigations. Monitoring and feedback can be effective in improving cleaning and disinfection in healthcare facilities. Ongoing commitment within institutions is needed to sustain successful cleaning and disinfection programs.
Comparing Behavior of Unbiased and Standard Versions of Popular Indices

In the previous chapter I outlined the rationale for unbiased versions of indices of uneven distribution. Additionally, I presented results from analysis of expected group residential distributions under a binomial probability model to establish that the unbiased versions of popular indices have expected values of zero when residential distributions are random. In this chapter I report analyses of the behavior of standard and unbiased versions of indices of uneven distribution to document two things: the potential undesirable impact of bias on the scores of standard versions of indices and the attractive behavior of the scores of unbiased versions of the same indices.
Permeability prediction from a pore-scale network model constrained by low-pressure nitrogen sorption isotherms

Abstract The matrix permeability of shale is controlled by the microstructure of shale pore network. Therefore, a thorough understanding of shale pore structure is fundamental to the prediction of shale permeability. We constructed a physically representative pore network model for two Barnett Shale samples. We predicted a Darcy permeability of 7.19 nanodarcies (nd) and apparent permeability of 57.34 nd for these samples. We explored the pore structure of shale matrix with low-pressure nitrogen adsorption/desorption isotherms. The pore size distribution, the network connectivity, as well as pore spatial arrangement are determined for the organic matter and the whole matrix. We separated pores in the network model into two groups: the affiliated pores and the dominant pores. For these samples, the affiliated pores are pores with diameters smaller than 8 nm and the dominant pores are with diameters larger than 8 nm. The affiliated pores develop on the walls of the dominant pores. The cutoff value between affiliated pores and dominant pores may differ for different samples. The pore spatial arrangement is validated against previous literature resultsand a diagenetic explanation for development of shale pore system. The network model can be used to predict shale permeability and other petrophysical properties.