cssi/SciSciGPT-SciSciNet huggingface dataset:
Extensive alternative splicing of cytochrome P4502D6 (CYP2D6) mRNA: explanation for variability among subjects with identical genotypes?

The cause of variability of CYP2D6 activity within subjects with identical genotypes remains an enigma. To date only one SNP (-1584C>G) modulating transcription levels has been described. Alternatively, splice events may contribute to the observed variability by giving rise to variable ratios of functional to aberrantly spliced mRNA. Recently, we described information theory as a quantitative measure of the relative strength of CYP2D6 splice acceptor and donor sites (Rogan et al, PG 13, 207, 2003). Relatively low information for exons 6 and 7 (Ri values<1.6 bits) and exons 2 and 3 (Ri=2 to 3.6 bits) suggested that these regions may be susceptible to alternative splicing. To test this hypothesis, liver RNA (n=5) was reverse transcribed and exons 1-9 and 3–9 amplified. Multiple products were observed after PCR in each sample. Cloning and sequencing revealed splice variants with a loss of exon 3 or 6, partial intron1 retention and intron 5 or 6 retention; 51 amino acids are lost with exon 3, while all other variants contain a premature stop-codon. Other clones that may contain additional variants are being characterized. In conclusion, CYP2D6 mRNA undergoes extensive alternative splicing, and the relative abundance of properly to aberrantly spliced mRNA appears to be an additional source of interindividual variability in CYP2D6 activity in vivo and in vitro. Furthermore, it may also explain the relatively poor correlation between in vitro activity and “mRNA” levels. Clinical Pharmacology & Therapeutics (2004) 75, P52–P52; doi: 10.1016/j.clpt.2003.11.195
An Essential Role for Nuclear Factor κB in Promoting Double Positive Thymocyte Apoptosis

To examine the role of nuclear factor (NF)-kappaB in T cell development and activation in vivo, we produced transgenic mice that express a superinhibitory mutant form of inhibitor kappaB-alpha (IkappaB-alphaA32/36) under the control of the T cell-specific CD2 promoter and enhancer (mutant [m]IkappaB-alpha mice). Thymocyte development proceeded normally in the mIkappaB-alpha mice. However, the numbers of peripheral CD8(+) T cells were significantly reduced in these animals. The mIkappaB-alpha thymocytes displayed a marked proliferative defect and significant reductions in interleukin (IL)-2, IL-3, and granulocyte/macrophage colony-stimulating factor production after cross-linking of the T cell antigen receptor. Perhaps more unexpectedly, double positive (CD4(+)CD8(+); DP) thymocytes from the mIkappaB-alpha mice were resistant to alpha-CD3-mediated apoptosis in vivo. In contrast, they remained sensitive to apoptosis induced by gamma-irradiation. Apoptosis of wild-type DP thymocytes after in vivo administration of alpha-CD3 mAb was preceded by a significant reduction in the level of expression of the antiapoptotic gene, bcl-xL. In contrast, the DP mIkappaB-alpha thymocytes maintained high level expression of bcl-xL after alpha-CD3 treatment. Taken together, these results demonstrated important roles for NF-kappaB in both inducible cytokine expression and T cell proliferation after TCR engagement. In addition, NF-kappaB is required for the alpha-CD3-mediated apoptosis of DP thymocytes through a pathway that involves the regulation of the antiapoptotic gene, bcl-xL.
Large-Signal Analysis of Terahertz Generation in Submicrometer GaN Diodes

The conditions for microwave power generation in a submicrometer GaN diode, with a relatively lightly doped active channel, coupled to an external resonant circuit are investigated. Applying a high-field electron transport model based on the local quasi-static approximation, we show that oscillations in group III-nitride diodes can be supported in the terahertz-frequency range near the limited space-charge accumulation regime. The shape of the diode voltage and electronic current waveforms are examined in terms of the circuit parameters and operating frequencies over the bandwidth of active generation. Based on a Fourier series analysis of the diode voltage and current, the generated power and dc-to-RF conversion efficiency at the fundamental and the second or higher order harmonic frequencies are estimated. The calculation results clearly indicate that submicrometer GaN diodes (channel doping of 1 × 1017 cm-3) can achieve large output powers (> 1 W) in the absence of Gunn domain formation, over a wide range of frequencies, near 0.5 THz.
Shared Conceptualizations and Divergent Experiences of Counseling Among African American and White Older Adults

Research findings suggest that older adults prefer counseling for depression treatment; however, few older adults use counseling services. In this article we present the results of our analysis of semistructured interviews with 102 older adults to explore conceptualizations of counseling and impediments to use among African American and White older adults. We found that older adults believe counseling is beneficial; however, use was hindered in multiple ways. Older adults were skeptical about establishing a caring relationship with a professional. African American older adults did not mention social relationships to facilitate depression care, whereas White older adults described using personal relationships to navigate counseling services. African American older men were least familiar with counseling. Our findings suggest that African American and White older adults share a strong cultural model of counseling as beneficial; however, significant impediments exist and affect older adults differentially based on ethnicity.
Mass spectra of sulfur compounds: Alkyl phenoxythioacetates

The mass spectra of some alkyl phenoxythioacetates have been examined. An unusual rearrangement ion [M C6H5O CO]+ was observed. The structure is confirmed by high resolution mass measurement and isotopic labeling studies.
A prospective, multi-institutional comparative effectiveness study of lumbar spine surgery in morbidly obese patients: does minimally invasive transforaminal lumbar interbody fusion result in superior outcomes?

Background Obese and morbidly obese patients undergoing lumbar spinal fusion surgery are a challenge to the operating surgeon. Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open-TLIF have been performed for many years with good results; however, functional outcomes after lumbar spine surgery in this subgroup of patients remain poorly understood. Furthermore, whether index MIS-TLIF or open-TLIF for the treatment of degenerative disc disease or spondylolisthesis in morbidly obese results in superior postoperative functional outcomes remains unknown. Methods A total of 148 (MIS-TLIF: n = 40, open-TLIF: n = 108) obese and morbidly obese patients undergoing index lumbar arthrodesis for low back pain and/or radiculopathy between January 2003 and December 2010 were selected from a multi-institutional prospective data registry. We collected and analyzed data on patient demographics, postoperative complications, back pain, leg pain, and functional disability over 2 years. Patients completed the Oswestry Disability Index (ODI), Medical Outcomes Study Short-Form 36 (SF-36), and back and leg pain numerical rating scores before surgery and then at 12 and 24 months after surgery. Clinical outcomes and complication rates were compared between both patient cohorts. Results Compared with preoperative status, Visual Analog Scale (VAS) back and leg pain, ODI, and SF-36 physical component score/mental component score were improved in both groups. Both MIS-TLIF and open-TLIF patients showed similar 2-year improvement in VAS for back pain (MIS-TLIF: 2.42 ± 3.81 vs. open-TLIF: 2.33 ± 3.67, P = 0.89), VAS for leg pain (MIS-TLIF: 3.77 ± 4.53 vs. open-TLIF: 2.67 ± 4.10, P = 0.18), ODI (MIS-TLIF: 11.61 ± 25.52 vs. open-TLIF: 14.88 ± 22.07, P = 0.47), and SF-36 physical component score (MIS-TLIF: 8.61 ± 17.72 vs. open-TLIF: 7.61 ± 15.55, P = 0.93), and SF-36 mental component score (MIS-TLIF: 4.35 ± 22.71 vs. open-TLIF: 5.96 ± 21.09, P = 0.69). Postoperative complications rates between both cohorts were also not significantly divergent between (12.50% vs. 11.11%, P = 0.51). Conclusion MIS-TLIF is a safe and viable option for lumbar fusion in morbidly obese patients and, compared with open-TLIF, resulted in similar improvement in pain and functional disability. Postoperative complications rates between both cohorts were also not significantly divergent.
Stepwise Dissection of the Hin-catalyzed Recombination Reaction from Synapsis to Resolution

The Hin DNA invertase promotes a site-specific DNA recombination reaction in the Salmonella chromosome. The native Hin reaction exhibits overwhelming selectivity for promoting inversions between appropriately oriented recombination sites and requires the Fis regulatory protein, a recombinational enhancer, and a supercoiled DNA substrate. Here, we report a robust recombination reaction employing oligonucleotide substrates and a hyperactive mutant form of Hin. Synaptic complex intermediates purified by gel electrophoresis were found to contain four Hin protomers bound to two recombination sites. Each Hin protomer is associated covalently with a cleaved DNA end. The cleaved complexes can be ligated into both parental and recombinant orientations at equivalent frequencies, provided the core residues can base-pair, and are readily disassembled into separated DNA fragments bound by Hin dimers. Kinetic analyses reveal that synapsis occurs rapidly, followed by comparatively slow Hin-catalyzed DNA cleavage. Subsequent steps of the reaction, including DNA exchange and ligation, are fast. Thus, post-synaptic step(s) required for DNA cleavage limit the overall rate of the recombination reaction.
Origin of probabilities and their application to the multiverse

We argue using simple models that all successful practical uses of probabilities originate in quantum fluctuations in the microscopic physical world around us, often propagated to macroscopic scales. Thus we claim there is no physically verified fully classical theory of probability. We comment on the general implications of this view, and specifically question the application of purely classical probabilities to cosmology in cases where key questions are known to have no quantum answer. We argue that the ideas developed here may offer a way out of the notorious measure problems of eternal inflation.
Learning laws for neural-network implementation of fuzzy control systems

A method of designing adaptive fuzzy control systems using structured neural networks is discussed. The basic idea is to implement a rule-based fuzzy control system with a neural network consisting of two subnetworks of pattern recognition, and fuzzy reasoning and control synthesis. The neural network is arranged such that the structure and operations of the original fuzzy control system can be fully retrieved from its network implementation. Equipped with the learning capability of neural networks, this implementation provides a mechanism to refine the existing rules and generate new rules for fuzzy control. It also opens a way for fuzzy control systems to exploit neural networks for carrying out their inherent parallel computation and suppressing the memory space required by their knowledge bases and inference programs. >
Algorithmic design of self-assembling structures

We study inverse statistical mechanics: how can one design a potential function so as to produce a specified ground state? In this article, we show that unexpectedly simple potential functions suffice for certain symmetrical configurations, and we apply techniques from coding and information theory to provide mathematical proof that the ground state has been achieved. These potential functions are required to be decreasing and convex, which rules out the use of potential wells. Furthermore, we give an algorithm for constructing a potential function with a desired ground state.
Necrotizing Tracheobronchitis (NTB) Following High Frequency Ventilation: Role of an Angiotensin Converting Enzyme Inhibitor

The purpose of this investigation was to study the effect of an angiotensin converting enzyme inhibitor (enalaprilat) on the morphologic manifestations of experimentally induced necrotizing tracheobronchitis (NTB). Twenty piglets were anesthetized before saline lung lavage. High frequency flow interrupter (HFFI) ventilation was used with a strategy known to produce NTB. Animals were randomly assigned to receive IV enalaprilat 0.1 mg/kg (ENP-Hi), enalaprilat 0.01 mg/kg (ENP-Lo), or saline (C). After 8 hours of ventilation, the piglets were sacrificed. Total airway injury scores (mean +/- S.D.) were 1.2 +/- 0.7 for ENP-Hi, 0.2 +/- 0.2 for ENP-Lo, and 21.3 +/- 16 for group C. Enalaprilat minimizes NTB lesions in neonatal piglets exposed to high frequency oscillatory ventilation. Although the origin of NTB is multifactorial, airway mucosa ischemia may play an important role. Enalaprilat may compensate for the reduction of mucosal blood flow by limiting formation of angiotensin II and/or preventing degradation of bradykinin.
Localization of obturator and pectineal motoneurons in the dog

The motoneuron columns of the obturator and pectineal nerves were localized within the lumbar spinal cords of dogs by observing retrograde chromatolysis following resection of the respective nerves. The obturator column was located in segments L4 through L6 while the pectineal column was located in segments L4 and L5. The dorsal-to-ventral and medial-to-lateral boundaries were determined for each column and the pectineal column was located within the boundaries determined for the obturator column in segments L4 and L5. Antidromic stimulation of the pectineal nerve localized the origin of motor fibers from lumbar spinal nerves L4 and L5. The results provide an anatomical basis for studies of motoneurons innervating the pectineus muscles of dogs affected with a developmental myopathy of this muscle.
Hydrochory in the Florida Everglades: Temporal and Spatial Variation in Seed Dispersal Phenology, Hydrology, and Restoration of Wetland Structure

Hydrochory may move species into areas appropriate for establishment, increasing the probability that species can take advantage of restored habitat. This research examined the influence of Everglades ridge and slough degradation on hydrochory, the interaction of hydrochory, hydrology, and ecosystem structure, and the role of hydrochory in ecosystem restoration. We identified 41 seed species from 2343 and 2849 seeds trapped in the intact and degraded sites, respectively. Month and the interaction of month and site type had significant effects within subjects in repeated measures ANOVA for seed density/trap, species richness, water depth, and water velocity. Percent cover of standing vegetation and periphyton, and Sorenson’s Similarity Index comparing standing vegetation and the dispersing seed pool differed significantly between sites in both the wet and dry seasons. Regression analyses indicated that seed species richness and seed density/trap were significantly positively related to water depth and velocity. The timing of increasing water depths and velocity coincided with the dispersal phenology strategy in intact sloughs in late spring/early summer, which may assist the dispersal of slough species through the system into physically restored deeper water areas once they are restored. Ridge species in degraded sloughs, such as swamp sawgrass ( Cladium jamaicense ) and common buttonbush ( Cephalanthus occidentalis ), timed their seed release with peak water depths immediately before drawdown, and during substantially reduced water velocities. This strategy may increase the probability of these species being deposited on elevated peat locations.
Enabling access to timeseries, geospatial data for on-demand visualization

Data volumes in the geosciences have been increasing substantially over the past decade. This data naturally includes both spatial and chronological information. Fast access to specific portions of large collections of such datasets is a precursor to efficiently visualizing them. Here, we provide an overview of how a geospatial storage system, GALILEO, provides storage of such timeseries data while providing access to specific portions of the dataset.
Inventing Selves: Images and Image‐Making in a Japanese Popular Music Genre

Cet article propose une etude des images et de leur fabrication dans la chanson populaire japonaise la plus traditionnelle appartenant au genre musical enka. Ce type de chanson est connu pour l'expression des emotions sinceres et sa popularite aupres des milieux sociaux modestes. La construction de la sincerite est une representation de l'image de soi. L'A. repond a trois questions : 1) Quelles sont les images produites par le genre enka et ses chanteurs? ; 2) Comment ces images sont cultivees et transmises? ; 3) Quel est le reflet offert par ces images a la societe japonaise des annees 1990 ? Ces images renforcent les stereotypes des genres sexuels, font l'apologie d'un discours de la nostalgie du passe rural et modifient le sens de l'identite culturelle japonaise du passe.
Long-Term Effects of Parenting Practices During Adolescence on Well-Being Outcomes in Young Adulthood

This research investigated the consequences of parent-child relationships during adolescence for young adults' well-being and substance use. Analysis of longitudinal data from the National Survey of Families and Households provided support for the hypothesis that parent-adolescent relationships have long-term consequences for young adult well-being and behavior. The findings are consistent with individuation theory and show that coercive parental control in adolescence is associated with lower well-being and more substance use in young adulthood. The long-term effects of parenting were mediated in part by the effects of parenting on adolescent adjustment, which influenced well-being in young adulthood.
The Science of Quality-of-Life-Directed Care!

Aspirations have no limit, barring reality. The obstacles imposed by reality to temper aspirations can be divided into 3 categories. First are those obstacles that are not negotiable (eg, 24 hours in a day, we all must die). Second are those that are negotiable, easily or with difficulty, but come at an acceptable opportunity cost. Such obstacles often are the foundation of aspirations and inspirations alike; examples of achievements in medicine and elsewhere overcoming them are too numerous to illustrate. Third are those that are negotiable but come only at a high opportunity cost. Here, the devil really does lie in the details, because the definition of opportunity cost is not absolute; hence, the debate. Let us examine the article by Allen et al1 in the current issue of Circulation: Cardiovascular Quality and Outcomes in this framework. Article see p 389 The primary concern of healthcare providers is to deliver the best treatment to all patients, with an aim to extend longevity and improve quality of life. This concern is even more important for patients with chronic diseases. During the past 2 decades, several drugs and devices have been shown to improve mortality risk from heart failure with depressed ejection fraction.2–4 Allen and colleagues1 very nobly contend that mortality should not be the only outcome that we focus on, and that improving quality of life should be an important aim. How can one disagree with this assertion? To help to achieve this goal, the authors assessed the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan) trial database5 to identify factors related to 6-month mortality or unfavorable quality of life (defined as Kansas City Cardiomyopathy Questionnaire scores <45) after discharge for decompensated heart failure. As might be expected from a large …
Postoperative gastric atony after vagotomy for obstructing peptic ulcer

Abstract From 1979 through 1984, truncal vagotomy and drainage were performed in 71 patients with symptomatic obstructing peptic ulcers, whereas proximal gastric vagotomy with or without drainage was performed in 30 patients. Seven patients (7 percent) developed prolonged early postoperative gastric atony. Six of the 71 patients (8 percent) who had truncal vagotomy had atony, whereas only 1 of the 30 patients (3 percent) with proximal gastric vagotomy had atony (p = 0.08). The atony resolved with medical management in all patients after a median of 23 days. At follow-up (median 3 years), 74 percent of patients with truncal vagotomy had an excellent or good result compared with 86 percent of those with proximal gastric vagotomy (p > 0.1). The conclusion was that prolonged early postoperative gastric atony occurs uncommonly after vagotomy for obstructing peptic ulcer. Preservation of antropyloric innervation by using proximal gastric vagotomy instead of truncal vagotomy may be helpful, but does not completely prevent the atony.
A statistical, coarse-sampled data filter

A digital filter design may be implemented with only one analog summing device, two shift registers with respective lengths equal to the orders of numerator and denominator, a generator of uniformly distributed analog noise, and either a simple low-pass RC filter or a counter. The principle of operation is based on polarity correlation. It has an economic advantage due to lack of storage and digital multipliers, but is applicable only when the data sampling rate is fairly low.
SPATIAL AND TEMPORAL WATER QUALITY VARIABILITY IN AQUATIC HABITATS OF A CULTIVATED FLOODPLAIN

The floodplains of lowland rivers contain diverse aquatic habitats that provide valuable ecosystem services but are perturbed when intensively cultivated. Hydrologic, water chemistry and biological (fish) conditions in five aquatic habitats along the Coldwater River, Mississippi, were measured for more than 4years: the river, two severed meanders that functioned as backwaters, a managed wetland and an ephemeral channel draining cultivated fields. Off-channel habitats were connected to downstream regions 0.10% to 32% of the dry season and 24% to 67% of the wet season. The median temperatures for the five monitored sites ranged from 18 Ct o 23C, the median total solids concentration for all sites was 135mg L 1 , the median total phosphorus was 0.29mg L 1 and the median total nitrogen was 1.56mg L 1 . Chemical and physical water quality displayed strong seasonal differences between the wet winter/spring and the dry summer/fall periods so that temporal variation consisted of gradual seasonal trends superimposed on strong diurnal variations. All off-channel habitats exhibited periods of hypoxia and temperatures >30C during the dry season. Between-site gradients of water and habitat quality were strongly coupled to water depth and runoff loading. The rehabilitation of one backwater by increasing water depth and diverting agricultural runoff was associated with improved water quality and fish species richness relative to an adjacent untreated backwater. The diversion of polluted runoff and the use of water control structures to maintain greater water depth were observed to be effective management tools, but the former reduces the water supply to habitats that tend to dry up and the latter reduces connectivity. Published in 2011 by John Wiley & Sons, Ltd.
Multiview social behavior analysis in work environments

In this paper, we propose an approach that fuses information from a network of visual sensors for the analysis of human social behavior. A discriminative interaction classifier is trained based on the relative head orientation and distance between a pair of people. Specifically, we explore human interaction detection at different levels of feature fusion and decision fusion. While feature fusion mitigates local errors and improves feature accuracy, decision fusion at higher levels significantly reduces the amount of information to be shared among cameras. Experiment results show that our proposed method achieves promising performance on a challenging dataset. By distributing the computation over multiple smart cameras, our approach is not only robust but also scalable.
R&D and the overseas earnings of Indian firms

Abstract This article examines the impact of undertaking R&D, a measure of the enhancement of dynamic capabilities, on firms' overseas earnings patterns, for a panel of several thousand Indian firms, for the period from 1991–92 to 2005–06. The results show that undertaking R&D spending is associated with a significant rise in firms' average overseas earnings levels. These results point to the need for materially enhancing the very low levels of R&D undertaken by firms in India.
Interdependency of Stored Food and Changes in Body Temperature During Hibernation of the Eastern Chipmunk, Tamias Striatus

Duration of torpor by eastern chipmunks, Tamias striatus, kept at 5°C progressively increased at the beginning of hibernation (autumn phase), remained long and relatively constant (winter phase), and then decreased (spring phase) in a fashion similar to that observed in hibernators that store energy as body fat. Duration of bouts of torpor in winter and spring and amount of time animals hibernated before starting the energetically demanding spring phase were related inversely to amount of food provided at the beginning of the experiment. In addition, chipmunks given the least amount of food (400 g) continued to hibernate until they consumed all seeds; those provided with abundant food (5,000 g) terminated hibernation spontaneously early in the spring phase and remained euthermic thereafter. Animals given an intermediate ration (1,000 g) hibernated until food was gone (42%) or spontaneously terminated hibernation with abundant food uneaten (58%). Thermoregulatory responses of chipmunks appear more flexible than those of species that store energy as body fat, but the match between use and availability of energy during dormancy is imprecise.
mAD and Conditional Quantile Estimators

All krigings are linked to the variance characteristic for spread of errors. The mean absolute deviation (mAD) characteristic leads to median and other quantile-type estimators. The relationships among these criteria and their impact on the corresponding estimators is discussed.
Detection of low-signature targets in rough surface terrain for forward-looking ground penetrating radar imaging

We develop an image-domain target detector for forward-looking ground penetrating radar (FLGPR) applications. An FLGPR offers the advantage of standoff sensing for detecting ground targets, but the target responses are more vulnerable to interference scattering arising from interface roughness and subsurface clutter. The proposed detection scheme draws all inferences regarding target and clutter statistics from the data measurements. More specifically, it iteratively adapts to the target and clutter statistics of the FLGPR images. Both single- and multi-aperture radar configurations are considered and the detection performance of each configuration is evaluated using electromagnetic modeling data.
Rapid reversal of adaptive increases in muscle GLUT-4 and glucose transport capacity after training cessation

Previous studies have shown that when exercise is stopped there is a rapid reversal of the training-induced adaptive increase in muscle glucose transport capacity. Endurance exercise training bring...
Family-Based Interventions Targeting Childhood Obesity: A Meta-Analysis.

Abstract Background: With the rising prevalence of childhood obesity over the last several decades, and the call for more family-based intervention research to combat childhood obesity, it is important to examine the extant research on family-based interventions in order to make recommendations and improve future research. Objective: To conduct a meta-analysis of family-based interventions targeting childhood obesity in the last decade in order to inform the research in the next decade. Methods: A literature review was conducted between December 2009-April 2010. Studies published between the years 2000–2009 that used family-based interventions to treat childhood obesity were included. A total of 20 studies met inclusionary criteria. Results: Although results varied by study design, the majority of studies had a moderate to large effect size for change in the target child's BMI (BMI percentile, zBMI, percent overweight) after participating in a family-based intervention. Long-term change varied by study, b...
The metadata legal conundrum from a public records act perspective

The Freedom of Information Act (FOIA) allows the release of public records inclusive of metadata. The agencies fulfilling FOIA and Public Records Act (PRA) requests are having challenges appropriately interpreting metadata because of the technological complexities involved. The Washington courts appear to be deliberating inconsistently when addressing metadata related cases. The purpose of this paper is to analyze the metadata interpretation on a set of court cases; and propose a framework that can be leveraged to achieve consistency across public records requests that include a metadata component whether explicitly or implicitly.
The Association Between Urine Output, Creatinine Elevation, and Death.

Background Acute kidney injury can be defined by a fall in urine output, and urine output criteria may be more sensitive in identifying acute kidney injury than traditional serum creatinine criteria. However, as pointed out in the Kidney Disease Improving Global Outcome guidelines, the association of urine output with subsequent creatinine elevations and death is poorly characterized. The purpose of this study was to determine what degrees of reduced urine output are associated with subsequent creatinine elevation and death. Methods This was a retrospective cohort study of adult patients (age ≥18 years) cared for in a cardiovascular intensive care unit after undergoing cardiac operations in a tertiary care university medical center. All adult patients who underwent cardiac operations and were not receiving dialysis preoperatively were studied. The development of acute kidney injury was defined as an increase in creatinine of more than 0.3 mg/dL or by more than 50% above baseline by postoperative day 3. Results Acute kidney injury developed in 1,061 of 4,195 patients (25%). Urine output had moderate discrimination in predicting subsequent acute kidney injury (C statistic = .637 ± .054). Lower urine output and longer duration of low urine output were associated with greater odds of developing acute kidney injury and death. Conclusions We found that there is similar accuracy in using urine output corrected for actual, ideal, or adjusted weight to discriminate future acute kidney injury by creatinine elevation and recommend using actual weight for its simplicity. We also found that low urine output is associated with subsequent acute kidney injury and that the association is greater for lower urine output and for low urine output of longer durations. Low urine output ( –1 · h –1 ), even in the absence of acute kidney injury by creatinine elevation, is independently associated with mortality.
Normal and tangential impact in micro electromechanical structures

Micro-electromechanical structures made of polycrystalline silicon (poly-Si) have been fabricated, analyzed, and tested for repetitive impact at frequencies of up to 14 kHz and for durations of 46 continuous hours in order to characterize both normal and tangential impact on the microscale. Nonlinear dynamic models of the impact bumper and target impact wall have been formulated using coefficients of restitution for both normal and tangential impact. It was estimated that the coefficient of restitution can be very small (0-0.25), which indicates that the impact of poly-Si microstructures can, under certain circumstances, dissipate substantial kinetic energy. An analytic model assuming Coulomb friction and no sliding during oblique impact has been formulated, and it is believed that slipping indeed exists, requiring a more complicated model. A wear test has been carried out with a design of a microstructure to generate large surface contact stress (approximately 2 GPa) resulting from impact. After 12 hours of testing, a surface defect in the impacting surface is observable. >
MR Safe Robot, FDA Clearance, Safety and Feasibility of Prostate Biopsy Clinical Trial

Compatibility of mechatronic devices with the MR environment has been a very challenging engineering task. After over a decade of developments, we report the successful translation to clinical trials of our MR safe robot technology. MrBot is a six degree of freedom, pneumatically actuated robot for transperineal prostate percutaneous access, built exclusively of electrically nonconductive and nonmagnetic materials. Its extensive preclinical tests have been previously reported. Here, we present the latest technology developments, an overview of the regulatory protocols, and technically related results of the clinical trial. The Food and Drug Administration (FDA) has approved the MrBot for the biopsy trial, which was successfully performed in five patients. With no trajectory corrections and no unsuccessful attempts to target a site, the robot achieved an MRI-based needle targeting accuracy of 2.55 mm. To the best of our knowledge, this is the first robot approved by the FDA for the MR environment. The results confirm that it is possible to perform safe and accurate robotic manipulation in the MRI scanner, and the development of MR safe robots is no longer a daunting technical challenge.
The impact of working in a green certified building on cognitive function and health

Thirty years of public health research have demonstrated that improved indoor environmental quality is associated with better health outcomes. Recent research has demonstrated an impact of the indoor environment on cognitive function. We recruited 109 participants from 10 high-performing buildings (i.e. buildings surpassing the ASHRAE Standard 62.1-2010 ventilation requirement and with low total volatile organic compound concentrations) in five U.S. cities. In each city, buildings were matched by week of assessment, tenant, type of worker and work functions. A key distinction between the matched buildings was whether they had achieved green certification. Workers were administered a cognitive function test of higher order decision-making performance twice during the same week while indoor environmental quality parameters were monitored. Workers in green certified buildings scored 26.4% (95% CI: [12.8%, 39.7%]) higher on cognitive function tests, controlling for annual earnings, job category and level of schooling, and had 30% fewer sick building symptoms than those in non-certified buildings. These outcomes may be partially explained by IEQ factors, including thermal conditions and lighting, but the findings suggest that the benefits of green certification standards go beyond measureable IEQ factors. We describe a holistic "buildingomics" approach for examining the complexity of factors in a building that influence human health.
Shelf-Life Extension of Vacuum Packaged Frankfurters Made from Beef Inoculated with Streptococcus lactis.

Fresh beef, containing .5% dextrose, was inoculated with Streptococcus lactis, incubated for 3, 5 and 7 d at 7±1°C, and then used to manufacture frankfurters. The frankfurters were vacuum-packaged and stored for 1, 2, 4 and 6 weeks at 3±1°C. Microbial quality was evaluated by examining frankfurters for aerobic and psychrotrophic counts at the end of each storage period. The level of nisin, an antibiotic substance produced by this strain of S. lactis, was also monitored in fresh meat and processed products. During the incubation period, no appreciable reduction in pH occurred in fresh meat. Growth of psychrotrophs was slower in treated than untreated fresh meat, but whether this was due to presence of nisin or competition resulting from the heavy inoculation with S. lactis is unclear. Before and after processing, nisin levels in the 5- and 7-d incubation-treated groups were higher than in the 3-d group, and all treated groups had higher nisin levels than untreated groups. Little difference in aerobic and p...
Essential Role of the Transcription Factor ZBP-89 in Lymphopoiesis

Abstract 277 We previously identified the Kruppel-type zinc finger transcription factor ZBP-89 (also called zfp148) as a novel GATA1 associated protein in erythroid and megakaryocytic cells. ZBP-89 also associates with other GATA family members such as GATA2 and GATA3, Friend of GATA (FOG) cofactors, and RUNX1. It is ubiquitously expressed, but has high-level expression in a subset of tissues including thymus, spleen, bone marrow, lung and brain. Our prior studies using morpholino knockdown in zebrafish, in vitro differentiation and chimeric mouse analysis of ZBP-89 genetrap embryonic stem cells, and lentiviral shRNA knock down in primary human CD34+ cells demonstrated a functional role for ZBP-89 in erythroid and megakaryocyte maturation. In this study, we generated conditional knock out mice to further examine the requirements for ZBP-89 in vivo. On a mixed strain background, full ZBP-89 knock out mice were born at close to Mendelian ratios. However, the ZBP-89−/− mice were severely runted and had increased mortality over the first 30 days of life. Surviving pups had significant growth failure, but eventually matched their wild type and heterozygous littermates by about 6 weeks of age. Analysis of erythroid maturation in bone marrow and spleen using flow cytometry for CD71 and Ter119 demonstrated impaired erythroid maturation in a ZBP-89 allele-dose dependent manner. On a pure C57BL/6 genetic background, nearly 100% of the ZBP-89−/− mice died within the first 10 days of life from unclear causes. ZBP-89fl/fl, Mx1-Cre mice developed lymphopenia and platelet abnormalities following activation of Cre by polyI-polyC injection. The lymphopenia was due to reduction in both B and T cells. Further delineation of the T-cell defect using ZBP-89fl/fl, Lck-Cre mice demonstrated impaired maturation of double negative (CD4−CD8−) T cells at the DN3 (CD25+ CD44−) to DN4 (CD25−CD44−) stages in thymi from 5–6 week old mice. These findings indicate that ZBP-89 plays functional roles in multiple hematopoietic lineages. Moreover, they identify ZBP-89 as a novel transcriptional regulator of lymphocyte development. We speculate that this latter role involves its known interactions with GATA3, FOG-1, and/or RUNX1, which are all similarly involved in lymphopoiesis. We also show that the ZBP-89 family member ZBP-99 is highly expressed in thymus and other hematopoietic tissues, and may therefore play partially overlapping roles with ZBP-89. Disclosures: No relevant conflicts of interest to declare.
Partitioning of γ-Secretase and its Substrates in Lipid Microdomains

γ-Secretase is a multiprotein complex that catalyzes intramembranous cleavage of mutiple transmembrane I proteins. The sequential proteolysis of the amyloid precursor protein (APP) by γ-Secretase generates amyloid beta peptides that form plaques, one of the main pathological hallmarks of Alzheimer's disease. γ-Secretase also cleaves Notch the abnormal signaling of which can lead to cancer. The lipid environment regulates the location and activity of many transmembrane proteins and defines membrane micro or nanodomains, which serve as spatio-temporal platforms for proteins to function properly, and therefore have a modulatory impact on the intramembrane proteolysis. Mechanistically, the lipids may affect substrate recognition by binding to γ-secretase and substrates and by excluding or enriching both partners within a microdomain. Despite substantial advances in elucidating how this enzyme complex functions, the effect of the local membrane lipid microenvironment on γ-secretase cleavage of substrates is still poorly understood. Here, we characterize the partitioning of APP and Notch1 substrate and γ-secretase using solid supported membranes to determine whether the function and activity of γ-Secretase and its substrates r is influenced by the membrane lateral organization. As a membrane model we chose a canonical raft mixture containing phosphatidylcholine, sphingomyelin and cholesterol. Atomic force microscopy (AFM) data revealed membrane heterogeneities, ordered (lo) and disordered (ld) domains, and the selective localization and clustering of membrane proteins. Notch substrate is uniformly distributed in the ld phase while APP substrate clusters prefer the boundary between ld and lo domains in agreement with fluorescence microscopy measurements carried out on proteolipobeads, suggesting that proteolysis and specificity of these substrates are modulated by membrane microenvironement. In addition, AFM time-course measurements suggests that γ-secretase recruits specific membrane components and thus creates a favorable lipidic environment for its assembly and activity.
The Effect of Salpingectomy on Ovarian Function.

Tubal surgery is performed for a variety of indications in gynecology. Salpingectomy is the most aggressive form of tubal surgery and may be performed for potential risk reduction for epithelial ovarian cancer, sterilization, and ectopic pregnancy and as a method to enhance fertility in the setting of hydrosalpinx. Depending on the indication, alternatives include conservative therapy alone, tubal occlusion, and salpingostomy. However, aggressive tubal surgery may impact fertility and ovarian reserve because of its effects on adjacent ovarian tissue. Ovarian damage may manifest as alterations in serum and sonographic markers of ovarian function as well as in vitro fertilization (IVF) response and, ultimately, impair outcomes in assisted reproductive and spontaneous conception cycles. We performed a review of articles from PubMed, Cochrane, and MEDLINE from 1946 to 2016 and included 48 relevant publications. For most indications for salpingectomy, ovarian reserve is not impacted. Although there are several conflicting studies suggesting a slight impairment of the parameters of ovarian reserve, these studies were mostly in patients who underwent salpingectomy for an ectopic pregnancy. For patients attempting to conceive naturally, salpingectomy overall does not confer a substantial decrease in conception. Conservative options may increase their risk for persistent trophoblastic disease. In patients planning on IVF, salpingectomy does not appear to significantly affect ovarian stimulation parameters or clinical pregnancy rates. Furthermore, salpingectomy is recommended in cases of hydrosalpinx. Overall, salpingectomy has no significant effects on ovarian reserve. However, the impact on IVF success and spontaneous pregnancy rates must be weighed by the indication for possible salpingectomy. A review of these risks and benefits should aid in choosing between salpingectomy and less aggressive alternatives.
Discrepancy In Diagnosis of Myelodysplastic Syndrome (MDS) Between Referral and Tertiary Care Centers: Experience at MD Anderson Cancer Center (MDACC)

Abstract Abstract 1870 Background: Patients (pts) referred to tertiary care centers occasionally have a final diagnosis that may differ from that made at the initial referring center. Previous studies have shown a discordance of 18% in the diagnoses of leukemia patients (AMJ. 1998;104:246-251). The aim of this study was to analyze the rate and implications of diagnostic discordance in pts with MDS referred to MDACC. Methods: A total of 915 pts presented to MDACC between September 2005 and December 2009 with an outside diagnoses of MDS. We reviewed the medical record of each patient for the pathology report on the diagnostic outside bone marrow slide sent for review. We also reviewed the outside hematopathology report sent with it. Diagnoses were coded according to WHO and the FAB MDS classification systems depending on time period. Information on pt characteristics including age, gender, IPSS, cytogenetics, complete blood count, % bone marrow blasts and transformation to acute myeloid leukemia (AML) were also recorded. Finally median survival was calculated using Kaplan-Meier method. Results: Out of the 915 charts reviewed, discordance in diagnosis was documented in 150 pts (16%). Sixty pts (40%) had an outside diagnoses of RA/RARS/RCMD/RCMD-RS (marrow blast 20%) at MDACC. Similarly, 15 (26%) pts diagnosed with RAEB on the outside, were diagnosed with RA/RARS/RCMD/RCMD-RS at MDACC whereas 40 (70%) pts diagnosed with RAEB were diagnosed with RAEB-T. Only 2 pts diagnosed with RAEB-T on the outside were diagnosed with RAEB at MDACC. Moreover, 3 pts were diagnosed with chronic myelomonocytic leukemia (CMML), 3 with MDS unclassified, 2 with MDS/MPD had a different diagnoses at MDACC. The characteristics of pts with discordance were compared with the 765 pts without discordance. Essentially no difference was noted in the age, gender, cytogenetics, hemoglobin or platelet count between the two groups. A difference was noted with pts in the discordant group having a higher percent of RAEB-T (37% vs. 10%, p 6 months. Nine pts of these showed a higher marrow blast percentage than outside, indicating progression of disease. Conclusion: Discordance in the diagnosis of MDS pts is important as it can affect the treatment plan and overall prognosis of these patients. In our study, pts in the discordant group were observed to have a higher risk disease. However, no significant difference in survival was noted between the two groups. These results demonstrate the complexity of the morphological diagnosis of MDS and indicate that morphological classifications have a limited role in the prognosis of these pts. Analysis of implications of therapy based on diagnostic discordance is ongoing. Disclosures: No relevant conflicts of interest to declare.
Oxidants and Mitogenesis as Causes of Mutation and Cancer: The Influence of Diet

A very high level oxidative damage to DNA occurs during normal metabolism. In each rat cell, the steady-state level of this damage is estimated to be about 10 6 oxidative adducts, and about 10 5 new adducts are formed daily. This endogenous DNA damage appears to be a major contributor to cancer and aging. The oxidative damage rate in mammalian species with a high metabolic rate, short life span, and high age-specific cancer rate such as in rats is much higher than the rate in humans, long-lived mammals with a lower metabolic rate, and a lower age-specific cancer rate. It is argued that deficiency of micronutrients, that protect against oxidative DNA damage, is a major contributor to human cancer.