cssi/SciSciGPT-SciSciNet huggingface dataset:
Octreotide-Targeted Lcn2 siRNA PEGylated Liposomes as a Treatment for Metastatic Breast Cancer.

Lcn2 overexpression in metastatic breast cancer (MBC) can lead to cancer progression by inducing the epithelial-to-mesenchymal transition and enhancing tumor angiogenesis. In this study, we engineered a PEGylated liposomal system encapsulating lipocalin 2 (Lcn2) small interfering RNA (Lcn2 siRNA) for selective targeting MBC cell line MCF-7 and triple-negative breast cancer cell line MDA-MB-231. The PEGylated liposomes were decorated with octreotide (OCT) peptide. OCT is an octapeptide analog of somatostatin growth hormone, having affinity for somatostatin receptors, overexpressed on breast cancer cells. Optimized OCT-targeted Lcn2 siRNA encapsulated PEGylated liposomes (OCT-Lcn2-Lipo) had a mean size of 152.00 nm, PDI, 0.13, zeta potential 4.10 mV and entrapment and loading efficiencies of 69.5% and 7.8%, respectively. In vitro uptake and intracellular distribution of OCT-Lcn2-Lipo in MCF-7 and MDA-MB-231 and MCF-12A cells demonstrated higher uptake for the OCT-targeted liposomes at 6 h by flow cytometry and confocal microscopy. OCT-Lcn2-lipo could achieve approximately 55−60% silencing of Lcn2 mRNA in MCF-7 and MDA-MB-231 cells. OCT-Lcn2-Lipo also demonstrated in vitro anti-angiogenic effects in MCF-7 and MDA-MB-231 cells by reducing VEGF-A and reducing the endothelial cells (HUVEC) migration levels. This approach may be useful in inhibiting angiogenesis in MBC.
Post-traumatic Neuroinflammation: Relevance to Pediatrics

Both detrimental and beneficial effects of post-traumatic neuroinflammation have become a major research focus as they offer the potential for immediate as well as delayed targeted reparative therapies. Understanding the complex interactions of central and peripheral immunocompetent cells as well as their mediators on brain injury and recovery is complicated by the temporal, regional, and developmental differences in their response to injuries. Microglia, the brain-resident macrophages, have become central in these investigations as they serve a major surveillance function, have the ability to react swiftly to injury, recruit various cellular and chemical mediators, and monitor the reparative/degenerative processes. In this review we describe selected aspects of this burgeoning literature, describing the critical role of cytokines and chemokines, microglia, advances in neuroimaging, genetics and fractal morphology analysis, our research efforts in this area, and selected aspects of pediatric post-traumatic neuroinflammation.
Performance Metrics Calculation for Assembly Systems with Exponential Reliability Machines

Assembly systems are commonly seen in production practice, where multiple components are joined in a manufacturing process to make a final product. In this paper, a decomposition/aggregation-based method is presented to evaluate the performance metrics of assembly systems with machines following the exponential reliability model (either synchronous or asynchronous). In particular, we consider the assembly system with multiple merge operations, each connected to a single external component line. The idea of the proposed method is to decompose the assembly system into a set of virtual serial lines based on the overlapping decomposition technique, evaluate of the starvation and blockage of the merge operations, and recursively update of the virtual machines’ parameters in the thus-obtained serial lines. Then, the performance metrics of the original assembly system can be approximated based on the corresponding machines and buffers in the virtual serial lines. Numerical experiments are carried out to justify the convergence and computational efficiency of the method, as well as to evaluate the approximation accuracy of the proposed algorithm.
The neural mechanisms of manual dexterity.

The hand endows us with unparalleled precision and versatility in our interactions with objects, from mundane activities such as grasping to extraordinary ones such as virtuoso pianism. The complex anatomy of the human hand combined with expansive and specialized neuronal control circuits allows a wide range of precise manual behaviours. To support these behaviours, an exquisite sensory apparatus, spanning the modalities of touch and proprioception, conveys detailed and timely information about our interactions with objects and about the objects themselves. The study of manual dexterity provides a unique lens into the sensorimotor mechanisms that endow the nervous system with the ability to flexibly generate complex behaviour. Hands enable us to interact with objects in precise and versatile ways. In this Review, Sobinov and Bensmaia discuss aspects of mundane and expert manual behaviours, the anatomical complexity of the human hand and neural mechanisms that underlie manual dexterity.
Interaction of m-dinitrobenzene (DNB) with calcium and potassium saturated reference smectites in aqueous suspensions

Smectites are the most commonly found clay mineral in many temperate region soils. It exhibits variability in shrink – swell behavior and sorption of organic molecules. Previous research has established the relationship between extent of swelling and sorption of organic compounds by smectites. The effect of the interlayer cation on sorption of organic compounds and the inter-relationship between cation exchange selectivity and extent of swelling has also been demonstrated. We investigated the effect of sorption of an organic compound on cation exchange selectivity and the interaction between organic sorption, cation exchange, and clay swelling. Our hypothesis was that adsorption of organic molecules in the interlayers of smectite influences the affinity of the clay for inorganic cations in aqueous systems. Caand Ksaturated SPV (bentonite) and SAz-1 were equilibrated with mixed salt solutions containing 0.01 M KCl and 0.005 M CaCl2 in the presence or absence of 200 ppm m-dinitrobenzene (DNB). Concentrations of Ca and K in solution and on the clay and concentrations of m-DNB were measured. The clay suspensions, both with and without the m-DNB, were also analyzed on the x-ray diffractometer to study the clay structure and the d-spacing. In general, SPV that was initially saturated with Ca sorbed more m-DNB than the SPV that was initially saturated with K. In general, the SPV sorbed more m-DNB than the SAz-1. Sorption of m-DNB on SPV increased preference for K relative to Ca for samples initially saturated with Ca, but it had little effect on exchange selectivity for samples that
The Boundary Condition Problem

We have not discussed one problem that must be faced in using the stochastic Lagrangian models of turbulent diffusion that we studied in the preceding chapters: How should we treat the trajectories of “marked particles” near the boundaries of the turbulent atmospheric boundary layer? The following discussion is in the context of two-dimensional simulations with vertical (z) and longitudinal (x) coordinates. We are concerned with the boundaries at the bottom and the top. The lower boundary is the bottom of the computational domain that generally corresponds to the land or water surface. This boundary can act as a perfect reflector, a sink (deposition), or a source (evaporation, resuspension, etc.). There can be two upper boundaries: that of the computational domain and, at a lower level, that of the turbulent atmospheric boundary layer. In the latter case, there can be entrainment into or out of the boundary layer.
Nonvanishing of the central L-values with large weight

Abstract In this paper we establish an optimal nonvanishing result for the central L -values of holomorphic cuspidal Hecke eigenforms with large individual weight.
Expected Utility Calibration for Continuous Distributions

Recently, Rabin criticized the use of diminishing marginal utility in explaining risk aversion in small gambles with a mathematical theorem, which compares revealed risk averting behavior in small gambles to the risk behavior implied by expected utility theory in somewhat larger gambles, using discrete payoff distributions. To examine whether his criticism holds in more realistic risky situations, we generalize his theorem to the cases of continuous distributions and of continuous choice. The results suggest that the absolute size of the risk may not be as important as the relative size of the possible risk reduction, and that expected utility is likely a poor explanation for any short term risk response. We discuss some rules of thumb for judging the appropriateness of expected utility in practice.
A Review of Multiscale Analysis: Examples from Systems Biology, Materials Engineering, and Other Fluid–Surface Interacting Systems

Abstract Multiscale simulation is an emerging scientific field that spans many disciplines, including physics, chemistry, mathematics, statistics, chemical engineering, mechanical engineering, and materials science. This review paper first defines this new scientific field and outlines its objectives. An overview of deterministic, continuum models and discrete, particle models is then given. Among discrete, particle models, emphasis is placed on Monte Carlo stochastic simulation methods in well-mixed and spatially distributed systems. Next, a classification of multiscale methods is carried out based on separation of length and time scales and the computational and mathematical approach taken. Broadly speaking, hybrid simulation and coarse graining or mesoscopic modeling are identified as two general and complementary approaches of multiscale modeling. The former is further classified into onion- and multigrid-type simulation depending on length scales and the presence or not of gradients. Several approaches, such as the net event, the probability weighted, the Poisson and binomial τ -leap, and the hybrid, are discussed for acceleration of stochastic simulation. In order to demonstrate the unifying principles of multiscale simulation, examples from different areas are discussed, including systems biology, materials growth and other reacting systems, fluids, and statistical mechanics. While the classification is general and examples from other scales and tools are touched upon, in this review emphasis is placed on stochastic models, their coarse graining, and their integration with continuum deterministic models, i.e., on the coupling of mesoscopic and macroscopic scales. The concept of hierarchical multiscale modeling is discussed in some length. Finally, the importance of systems-level tools such as sensitivity analysis, parameter estimation, optimization, control, model reduction, and bifurcation in multiscale analysis is underscored.
Endogenous Hierarchies Under Representational Concerns

This paper examines the following question: how do representational concerns affect a firm's hierarchical structure? Employers, facing a population of agents who can be distinguished by their productivity and identity, seek to assign them to positions in the organizations hierarchy that differ their sensitivity of output to productivity. It is observed that historically under-privileged workers feature predominantly in the lower ranks and earn systematically less in aggregate wages. It is shown that affirmative action like policies that are intended to reduce wage inequality, induce employers to adopt assignment policies that are more group egalitarian and choose an organizational hierarchy that is "flatter" than under Laissez-faire.
SPECIAL ARTICLE: SUCKING IN INFANCY

Seventy healthy, apparently happy babies were studied in an attempt to evaluate the common occurrence of extranutritional sucking and its importance. Sixty-one manifested an appreciable amount of extra sucking which seemed to be gratifying in itself to the infant and which did not necessarily represent fatigue, hunger or discomfort. The onset of this varied from birth to 3 months of age. Its intensity increased until 7 months then began to decrease spontaneously, coincident with other motor accomplishments. By 12 months all but 4 of these babies had ceased to suck their hands except under stress. Only 2 have continued beyond the age of 2 years. The importance of extranutritional sucking as a source of gratification in infancy is pointed out. Its occurrence is normal and its disappearance is spontaneous in most infants when not inhibited
Vesicle fiesta at the synapse

Communication between nerve cells is what makes our brains work. Several new studies offer us a close-up view of the chemical signals controlling these cellular conversations.
Health care burden of cervical spine fractures in the United States: Analysis of a nationwide database over a 10-year period: Presented at the 2009 Joint AANS/CNS Spine Section Meeting - Clinical article

Object The objective of this work was to search a national health care database of patients diagnosed with cervical spine fractures in the US to analyze discharge, demographic, and hospital charge trends over a 10-year period. Methods Clinical data were derived from the Nationwide Inpatient Sample (NIS) for the years 1997 through 2006. The NIS is maintained by the Agency for Healthcare Research and Quality and represents a 20% random stratified sample of all discharges from nonfederal hospitals within the US. Patients with cervical spine fractures with and without spinal cord injury (SCI) were identified using the appropriate ICD-9-CM codes. The volume of discharges, length of stay (LOS), hospital charges, total national charges, discharge pattern, age, and sex were analyzed. National estimates were calculated using the HCUPnet tool. Results Approximately 200,000 hospitalizations were identified. In the non-SCI group, there was a 74% increase in hospitalizations and charges between 1997 and 2006, but LOS ...
Surgical management of chronic pancreatitis: current utilization in the United States

Abstract Background Surgical intervention is uncommon in chronic pancreatitis. Literature largely describes single institution or international experiences. This study describes US‐based chronic pancreatitis surgical management. Methods Retrospective analysis of chronic pancreatitis patients in the Healthcare Cost and Utilization Project Florida State Inpatient Database 2007–2011. Patients with malignancy or congenital abnormalities were excluded. Univariate analysis using the chi‐square test. The number of readmissions, inpatient length of stay and cost using Wilcoxon's signed‐rank test. Multivariate analysis of surgery by logistic regression. Results Twenty‐one thousand four hundred and forty‐five patients with chronic pancreatitis. 10.8% (2 307) underwent surgery including 1652 cholecystectomies, 564 drainage procedures and 498 pancreatectomies. Procedures decreased from 12.1% to 8.3% over time ( P P = 0.017). 15.3% (3 278) had pancreatic cysts/pseudocysts and 43.4% (9 312) had diabetes. The median numbers of admissions were 2 [interquartile range (IQR) 1,5] and 3 (IQR 2,7) among non‐surgical and surgical patients, respectively ( P Conclusion Chronic pancreatitis leads to numerous inpatient readmissions, but surgical intervention only occurs in a minority of cases. Complicated patients are more likely to undergo surgery. The complexities of chronic pancreatitis management warrant early multidisciplinary evaluation and ongoing consideration of surgical and non‐surgical options.
Nonuniform deformations in polycrystals and aspects of the validity of the Taylor model

Abstract F ull solutions to mixed rate boundary value problems over polycrystalline domains are performed via the finite element method. In order to make these finite element calculations feasible, an idealized two-dimensional crystal structure is studied. These boundary value problems rigorously satisfy the averaging theorems of Hill (Proc. R. Soc.A326, 131, 1972) so that well defined Taylor model analogue problems may be identified and solved. Comparisons between the finite element solutions and their corresponding Taylor model analogues yield a quantitative assessment of the Taylor model's validity with respect to its predictions of texture development and global stress-strain response. The finite element calculations also provide physical insight into the mechanisms contributing to the development of nonuniform and localized deformations in polycrystals.
Subsurface and deeper ocean remote sensing from satellites: An overview and new results

Satellite remote sensors cannot see far beneath the surface layers of the ocean. Yet many important ocean processes and features are located well below the surface and at considerable depths. Examples include Mediterranean Eddies (meddies), mixed layer depth, internal waves, and bottom topography. Deeper ocean remote sensing is becoming even more important because recent data seem to indicate that the deeper ocean is responding to climate variability and change. Many of these subsurface phenomena have surface manifestations which can be interpreted with the help of models to derive key parameters of deeper ocean processes. The objective of this paper is to provide an overview of satellite remote sensing and modeling techniques which enable scientists to characterize subsurface and deeper ocean processes and features and to present some new results.
Effects of Varying Dietary Undegradable Protein on Dry Matter Intake, Growth, and Carcass Composition of Holstein Calves

Abstract The objective was to study the effect of feeding diets varying in rumen undegradable protein on DMI, growth, feed efficiency, and carcass composition in Holstein calves from birth to 25 wk of age. Sixty Holstein calves were assigned in a randomized complete block design to one of three dietary treatment groups that differed in rumen undegradable protein as a percentage of total protein. Protein undegradabilities of the TMR fed for ad libitum intake for period 1 (wk 1 to 12 of age) were 33,37, and 46% and for period 2 (wk 14 to 25 of age) were 30, 34, and 38%. Intake was not different among diets during period 1. During period 2, animals fed the highest and lowest levels of undegradable protein diet consumed less DM, and those animals on the highest undegradable diet had the least amount of crude protein intake. Feed efficiency was increased with increasing rumen undegradable protein for period 2. Carcass composition was not affected by dietary treatment for either 9-10-11 rib section or the half carcass. Prediction equations for carcass protein and fat were calculated for 25-wk Holstein calves using urea space and live weight. These results indicate that the amount of undegradable intake protein currently recommended for growing dairy replacements may not be justified when intake is ad libitum. In the present study, urea space was not found to be beneficial over live weight for predicting carcass protein and fat in intact male or female Holstein calves.
A functional analysis of congressional television spots, 1986–2000

Despite the hundreds of millions of dollars spent on television advertising in congressional campaigns, relatively little research has examined the content purchased by those advertising dollars. This study applied the Functional Theory of Political Campaign Discourse to a purposive sample of television spots from U.S. House and Senate races from 1986 to 2000. Acclaims (self‐praise: 64%) outnumbered both attacks (criticisms: 35.5%) and defenses (refutation of attacks: 0.5%). Policy utterances comprised the bulk of the discussions in the ads (70%), while character utterances appeared less frequently (30%). Past deeds of candidates were the overwhelming focus of policy discussions (81%), while personal qualities dominated the discourse on character utterances (86%). Incumbents had a strong proclivity to acclaim (79%) more than challengers (51%) whereas challengers had a tendency to attack (49%) more than incumbents (21%). Incumbents were more likely to use past deeds to acclaim, whereas challengers used pas...
Cyclin-dependent Kinases Phosphorylate Human Cdt1 and Induce Its Degradation

Eukaryotic cells tightly control DNA replication so that replication origins fire only once during S phase within the same cell cycle. Cell cycle-regulated degradation of the replication licensing factor Cdt1 plays important roles in preventing more than one round of DNA replication per cell cycle. We have previously shown that the SCFSkp2-mediated ubiquitination pathway plays an important role in Cdt1 degradation. In this study, we demonstrate that human Cdt1 is a substrate of Cdk2 and Cdk4 both in vivo and in vitro. Overexpression of cyclin-dependent kinase inhibitors such as p21 and p27 dramatically suppresses the phosphorylation of Cdt1, disrupts the interaction of Cdt1 with the F-box protein Skp2, and blocks the degradation of Cdt1. Further analysis reveals that Cdt1 interacts with cyclin/cyclin-dependent kinase (Cdk) complexes through a cyclin/Cdk binding consensus site, located at the N terminus of Cdt1. A Cdt1 mutant carrying four amino acid substitutions at the Cdk binding site dramatically reduces associations with cyclin/Cdk complexes. This mutant is not phosphorylated, fails to bind Skp2 and is more stable than wild-type Cdt1. These data suggest that cyclin/Cdk-mediated Cdt1 phosphorylation is required for the association of Cdt1 with the SCFSkp2 ubiquitin ligase and thus is important for the cell cycle dependent degradation of Cdt1 in mammalian cells.
Radical prostatectomy in patients infected with human immunodeficiency virus

OBJECTIVE To present the complications and early outcomes in a small series of men infected with human immunodeficiency virus (HIV) and treated with radical prostatectomy (RP) for prostate cancer, and to review reports on surgery in HIV-positive patients. PATIENTS AND METHODS During 2002–2005, seven men infected with HIV underwent RP at our institution. For the five patients whose HIV status was known before surgery, we retrospectively examined preoperative variables, including HIV-specific data (clinical category, CD4+ lymphocyte count, viral load, duration of HIV diagnosis, and opportunistic infections), and the complications and early outcomes after RP. RESULTS Before RP all the patients were in the Center for Disease Control clinical category A (asymptomatic HIV infection). The CD4+ counts before RP ranged from 269–870 cells/µL and viral loads ranged from <50–18 700 copies/mL. Three patients were on highly active anti-retroviral therapy (HAART) at the time of surgery. After RP, two patients had incisional wound infections, including one requiring re-hospitalization for intravenous antibiotics. During the follow-up (median 26 months) none of the patients progressed to acquired immunodeficiency syndrome or developed biochemical recurrence of prostate cancer. One healthcare worker was exposed to contaminated urine and placed on prophylactic therapy, but has not sero-converted. CONCLUSION The risk of peri-operative complications in HIV-positive patients can be minimized by carefully selecting the patient and procedure, and by measuring routine and HIV-specific preoperative variables. The two infectious complications in this series were in patients with less favourable preoperative factors, i.e. the lowest CD4+ count and the highest viral load. Further experience is needed to determine whether the risk of surgical infections is higher in this cohort. However, our results are consistent with reports from other surgical specialities that surgery in asymptomatic HIV-positive patients is safe and effective.
Computer-Based Image Analysis of Liver Steatosis with Large-Scale Microscopy Imagery and Correlation with Magnetic Resonance Imaging Lipid Analysis

Most pathology analyses and measurements are prevalently carried out by trained reviewers in both clinical and research settings. Therefore, the resulting outputs are inexorably biased by interpreters and degraded with poor reproducibility. In this paper, we propose a computerized image analysis paradigm enabling quantitative characterizations of steatosis areas in microscopy images of pediatric liver biopsies. With the same set of patients, we also acquired the lipid measurements from magnetic resonance imaging data analysis for correlation investigation. Our preliminary results suggest a high correlation between the steatosis areas quantized with microscopy images and the lipid percentages calculated from radiology imaging data. Additionally, we compared the performance of the proposed analysis method with those of three certified pathologists and a popular commercial algorithm. The results suggest the superiority of our method to both human reviewers and the commercial method in terms of the steatosis-lipid correlation strength. This demonstrates that the developed method is promising for generating quantitative and reliable analysis results to better support further liver disease study.
Effect of fish oil on bone mineral density in aging C57BL/6 female mice

Life expectancy has increased considerably over the last century in the United States. It is expected that this longevity will be accompanied by an increase in the prevalence of osteoporosis and accompanying complications in the elderly population. Age-related loss of bone mass and bone fragility are major risk factors for osteoporosis, leading to an increased risk of fractures. Therefore, nutritional strategies and lifestyle changes that prevent age-related osteoporosis and improve the quality of life for the elderly population are urgently needed. Hence, the present study compared the effects of corn oil (CO; n-6 fatty acids; commonly present in Western diets) and fish oil (FO; n-3 fatty acids) on bone mineral density (BMD) in aging C57BL/6 female mice. After 6 months of dietary treatment, we found that 18-month-old FO-fed mice maintained higher BMD in different bone regions compared to CO-fed mice. These findings were accompanied by a decreased activity of pro-inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6 in stimulated splenocytes; a nonsignificant but greater increase in bone formation markers alkaline phosphatase and osteocalcin in the serum; and lower osteoclast generation in bone marrow cell cultures in FO-fed mice. In conclusion, these findings suggest that providing n-3 fatty acids may have a beneficial effect on bone mass during aging by modulating bone formation and bone resorption factors.
Solar concentrator advanced development project

The Solar Concentrator Advanced Development Project has successfully designed, fabricated, and tested a full scale prototypical solar dynamic concentrator for space station applications. A Truss Hexagonal Panel reflector was selected as a viable solar concentrator concept to be used for space station applications. This concentrator utilizes a modular design approach and is flexible in attainable flux profiles and assembly techniques. The detailed design of the concentrator, which included structural, thermal and optical analysis, identified the feasibility of the design and specific technologies that were required to fabricate it. The needed surface accuracy of the reflectors surface was found to be very tight, within 5 mrad RMS slope error, and results in very close tolerances for fabrication. To meet the design requirements, a modular structure composed of hexagonal panels was used. The panels, made up of graphite epoxy box beams provided the strength, stiffness and dimensional stability needed. All initial project requirements were met or exceeded by hardware demonstration. Initial testing of structural repeatability of a seven panel portion of the concentrator was followed by assembly and testing of the full nineteen panel structure. The testing, which consisted of theodolite and optical measurements over an assembly-disassembly-reassembly cycle, demonstrated that the concentrator maintained the as-built contour and optical characteristics. The facet development effort within the project, which included developing the vapor deposited reflective facet, produced a viable design with demonstrated optical characteristics that are within the project goals.
Debris swarms seen by SMEI

Abstract The large 3° × 60° fields-of-view of the Solar Mass Ejection Imager (SMEI) instruments are oriented on the stabilized Coriolis satellite to image most of the sky each Sun-synchronous orbit. Besides observing coronal mass ejections, the SMEI mission objective, SMEI also has detected a plethora of Earth-orbiting satellites (resident space objects or RSOs) brighter than ∼8th magnitude at a rate of about 1 per minute. Occasionally, SMEI sees an RSO swarm: a sudden onset of a large number of RSOs, many more than the nominal rate, upto dozens detected in a 4-s frame. These swarms usually last for a few minutes. A sample of six such RSO ensembles is analyzed in this paper in which the distance and the direction of the velocity vector for individual objects are estimated. We present the observational evidence indicating that the swarms must be near-field objects traveling in orbits near that of Coriolis, and that the relatively speeds between the objects and Coriolis are low. Further, analyses indicate that the RSOs are quite close (
89 HEREDITARY RED BLOOD CELL ADENOSINE DEAMINASE OVERPRODUCTION: ASSOCIATION WITH INCREASED LEVELS OF STRUCTURALLY NORMAL ADA mRNA

A marked tissue-specific increase in erythrocyte adenosine deaminase activity is associated with an autosomal dominantly inherited hemolytic anemia. Preliminary studies suggested that the defect lay at the level of ADA mRNA translation in red blood cells. We have directly analyzed reticulocyte ADA mRNA from affected individuals. Sequencing of seven proband reticulocyte ADA cDNA clones did not reveal any base changes in coding or non-coding regions. RNase mapping demonstrated that the 5′- and 3′-untranslated regions of reticulocyte and B lymphoblast ADA mRNAs from affected individuals were identical to those of normal B lymphoblasts. However, RNase mapping failed to detect any comparable bands in RNA from control reticulocytes. Northern blot analysis performed under stringent hybridization and washing conditions confirmed a markedly increased amount of reticulocyte ADA mRNA in affected individuals compared to controls. These findings were obscured in the previous study by non-specific hybridization of the ADA cDNA probe to 18s ribosomal RNA. We conclude that the red cell-specific overexpression of ADA probably occurs at the level of transcription in erythroid precursors.
Dysfunction of ouabain-induced cardiac contractility in mice with heart-specific ablation of Na,K-ATPase β1-subunit

Abstract Na,K-ATPase is composed of two essential α- and β-subunits, both of which have multiple isoforms. Evidence indicates that the Na,K-ATPase enzymatic activity as well as its α1, α3 and β1 isoforms are reduced in the failing human heart. The catalytic α-subunit is the receptor for cardiac glycosides such as digitalis, used for the treatment of congestive heart failure. The role of the Na,K-ATPase β1-subunit (Na,K-β1) in cardiac function is not known. We used Cre/loxP technology to inactivate the Na,K-β1 gene exclusively in the ventricular cardiomyocytes. Animals with homozygous Na,K-β1 gene excision were born at the expected Mendelian ratio, grew into adulthood, and appeared to be healthy until 10 months of age. At 13–14 months, these mice had 13% higher heart/body weight ratios, and reduced contractility as revealed by echocardiography compared to their wild-type (WT) littermates. Pressure overload by transverse aortic constriction (TAC) in younger mice, resulted in compensated hypertrophy in WT mice, but decompensation in the Na,K-β1 KO mice. The young KO survivors of TAC exhibited decreased contractile function and mimicked the effects of the Na,K-β1 KO in older mice. Further, we show that intact hearts of Na,K-β1 KO anesthetized mice as well as isolated cardiomyocytes were insensitive to ouabain-induced positive inotropy. This insensitivity was associated with a reduction in NCX1, one of the proteins involved in regulating cardiac contractility. In conclusion, our results demonstrate that Na,K-β1 plays an essential role in regulating cardiac contractility and that its loss is associated with significant pathophysiology of the heart.
Quantitative re-evaluation of descending serotonergic and non-serotonergic projections from the medulla of the rodent: evidence for extensive co-existence of serotonin and peptides in the same spinally projecting neurons, but not from the nucleus raphe magnus.

A quantitative analysis of serotonin (5-HT) and spinally-projecting neurons was re-evaluated in the rodent. The findings indicate that most (nearly 90%) of the medullary 5-HT neurons projected to the lumbar spinal cord, and most (up to 85%) of the spinally projecting neurons within the distribution of the serotonergic neurons contained 5-HT immunoreactivity. However, in nucleus raphe magnus (NRM) only about two-thirds of the projection cells were 5-HT immunoreactive. These data support two general conclusions: (1) the raphe-spinal system consists primarily of an extensive 5-HT pathway with neuronal subsets containing the co-localized peptides. Only the NRM contains a major non-5-HT projection. (2) As most of the medullary 5-HT neurons project to the caudal spinal segments of the rodent, collateralization of individual 5-HT neurons is extensive and widespread, existing to different spinal cord levels, as well as to other medullary nuclei, e.g., cranial nerve and inferior olivary nuclei. These findings argue that although differences are present within the 5-HT distributions, the raphe-spinal system as a whole should be considered to be a relatively homogeneous pathway containing 5-HT as the common element rather than as separate populations containing major projections of 5-HT alone, 5-HT co-localized with peptides and peptides without 5-HT.
Metastatic carcinoma of prostate masquerading as abdominal aortic aneurysm

A case is reported in which the patient had classic findings of an abdominal aortic aneurysm, including a pulsatile abdominal mass, curvilinear aortic calcification, and anterolateral deviation of the left ureter. These findings were subsequently demonstrated at surgery to be due to metastatic nodes from prostatic carcinoma. Data presented indicate that further diagnostic studies may be in order in unusual cases in which patients are suspected of having abdominal aortic aneurysm. This is especially true if the patient is known to have another condition such as carcinoma which may mimic aneurysm with metastatic periaortic lymph nodes. Aortography and/or lymphangiography occasionally have their place in selected patients, and this is discussed.
The Nurr1 activator 1,1-bis(3′-indolyl)-1-(p-chlorophenyl) methane blocks inflammatory gene expression in BV-2 microglial cells by inhibiting nuclear factor κB

NR4A family orphan nuclear receptors are an important class of transcription factors for development and homeostasis of dopaminergic neurons that also inhibit expression of inflammatory genes in glial cells. The identification of NR4A2 (Nurr1) as a suppressor of nuclear factor κB (NF-κB)–related neuroinflammatory genes in microglia and astrocytes suggests that this receptor could be a target for pharmacologic intervention in neurologic disease, but compounds that promote this activity are lacking. Selected diindolylmethane compounds (C-DIMs) have been shown to activate or inactivate nuclear receptors, including Nurr1, in cancer cells and also suppress astrocyte inflammatory signaling in vitro. Based upon these data, we postulated that C-DIM12 [1,1-bis(3′-indolyl)-1-(p-chlorophenyl) methane] would suppress inflammatory signaling in microglia by a Nurr1-dependent mechanism. C-DIM12 inhibited lipopolysaccharide (LPS)–induced expression of NF-κB–regulated genes in BV-2 microglia including nitric oxide synthase (NOS2), interleukin-6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2), and the effects were attenuated by Nurr1-RNA interference. Additionally, C-DIM12 decreased NF-κB activation in NF-κB–GFP (green fluorescent protein) reporter cells and enhanced nuclear translocation of Nurr1 primary microglia. Chromatin immunoprecipitation assays indicated that C-DIM12 decreased lipopolysaccharide-induced p65 binding to the NOS2 promoter and concurrently enhanced binding of Nurr1 to the p65-binding site. Consistent with these findings, C-DIM12 also stabilized binding of the Corepressor for Repressor Element 1 Silencing Transcription Factor (CoREST) and the Nuclear Receptor Corepressor 2 (NCOR2). Collectively, these data identify C-DIM12 as a modulator of Nurr1 activity that results in inhibition of NF-κB–dependent gene expression in glial cells by stabilizing nuclear corepressor proteins, which reduces binding of p65 to inflammatory gene promoters.
Passive microwave‐derived snow melt regions on the Greenland Ice Sheet

By comparing data from the Special Sensor Microwave Imager (SSM/I) to field data, a melt threshold of the cross-polarized gradient ratio (XPGR), which is a normalized difference between the 19 GHz horizontally-polarized and 37 GHz vertically polarized brightness temperatures, is determined. This threshold, XPGR = -0.025, is used to classify dry and wet snow. The annual areal extent of melt is mapped for the years 1988 through 1991, and inter-annual variations of melt extent are examined. The results show that the melt extent varied from a low of 38.3% of the ice sheet (1990) to a high of 41.7% (1991) during the years 1988-1991.
Workplace Self-Expansion: Implications for Job Satisfaction, Commitment, Self-Concept Clarity, and Self-Esteem Among the Employed and Unemployed

Similar to how individuals in close relationships incorporate aspects of their partner into their self-concept, we suggest that jobs promote self-expansion when they lead people to develop skills and assume new identities. In Study 1, we sampled currently employed individuals, and results show that self-expansion predicts job satisfaction and commitment, even when controlling for salary, tenure, and demographic variables. In Study 2, we examined the impact of losing a self-expanding job by sampling currently unemployed individuals, and results show that losing a self-expanding job results in lower amounts of self-concept clarity and self-esteem.
Recommenders for the enterprise: event, contact, and group

This extended abstract provides a summary of MITRE's Recommender demonstrations for ACM RecSys 2012. We have three demonstrations: Event Recommender, Contact Recommender, and Group Recommender. MITRE is a technology company with thousands of staff and varied government customers. Help from recommenders is becoming a necessity to find the right resources to bring to bear on large, multidisciplinary problems. We have developed and deployed these recommenders to explore their effectiveness, implementation challenges for an enterprise, and their use models.
Effectiveness of the Derived Alcohol Use Disorders Identification Test (AUDIT‐C) in Screening for Alcohol Use Disorders and Risk Drinking in the US General Population

Background: The three consumption questions from the Alcohol Use Disorders Identification Test (AUDIT-C) are increasingly used as a screener for alcohol use disorders (AUDs) and risk drinking. Methods: In a representative sample of US adults 18 years of age and older, AUDIT-C scores (derived from consumption questions embedded in a large national survey) were used to estimate sensitivity, specificity, and areas under receiver operator characteristic curves (AUROCs) for alcohol dependence, any AUD, and risk drinking. AUDs were defined according to DSM-IV criteria. For men, risk drinking was defined as consuming >14 drinks per week or >4 drinks in a single day at least once a month; for women, the weekly and daily limits were >7 drinks and >3 drinks, respectively. The derived AUDIT-C was evaluated among past-year drinkers (n= 26,946), within the total population (n= 43,093), in groups defined by age, sex, and race/ethnicity, and among pregnant women, persons attending an emergency room, and college students. Results: For past-year drinkers, the AUROCs for the derived AUDIT-C were 0.887 for alcohol dependence, 0.860 for any AUD, and 0.966 for risk drinking. Scores were higher in the total population, 0.931, 0.917, and 0.981, respectively. The derived AUDIT-C performed slightly better in screening for dependence among women than men. Screening for risk drinking was better among men, probably because the third AUDIT-C question directly mirrors one of the definitions of risk drinking for men but not for women. Performance in pregnant women, past-year emergency room patients, and college students was on a par with performance in the general population. Conclusions: The derived AUDIT-C performs well in screening for AUDs and risk drinking. The use of variable cut points for men and women improves its sensitivity and specificity. Validation in a realistic screening situation, in which the AUDIT-C questions are asked as stand-alone and not embedded items, is a critical future step.
Disjoint identifying-codes for arbitrary graphs

Identifying codes have been used in a variety of applications, including sensor-based wireless location detection in harsh environments. In such applications, a user determines his location through a unique signature (i.e. a codeword in an identifying code) based on sensor transmissions that he can hear. Adding sensors to such a system can increase its robustness at the expense of added signal interference and, consequently, decreased reliability. In this work we propose and develop an alternate approach to maintaining robustness and reliability through the use of "disjoint identifying codes", which reduces inter-sensor interference by dividing a system into physically separate and independent location determining sub-systems. We provide information-theoretic upper and lower bounds on the number of such sub-systems for a given connectivity graph, and we show that these bounds are asymptotically tight for a modification of Hadamard matrices
TECHNIQUES FOR MEASURING VESSEL LENGTHS AND DIAMETERS IN STEMS OF WOODY PLANTS

Results were compared between the latex paint and compressed air methods for determining total vessel lengths, and between the sectioning and maceration methods for determining vessel diameters. The minimum, mean, median, and maximum vessel diameters were less with the sectioning method than with the maceration technique. Vessel diameter distributions were always nonnormal and had roughly similar patterns with the two techniques, but were statistically different from one another. In all six species where the paint and air methods for determining vessel length were compared, both methods showed a similar skewed vessel length distribution, with many short vessels and few long ones. Although there was no consistent pattern to the difference in results with these two methods, the vessel length frequency distributions were statistically different from one another. With the paint method, many vessels, especially many of the narrowest ones, were not paint-filled at the paint infusion port. The air method utilized the paint method, in part, and, in addition, is based upon the incorrect assumption that all vessels in the stem are the same diameter. Both techniques tended to exclude vessel lengths of the narrowest vessels. However, the narrow vessels, although numerous, contributed an insignificant amount to the total theoretical hydraulic conductance in stems.
Time-resolved photoelectron angular distributions as a map of rotational motion

Abstract We discuss the application of photoelectron angular distributions as a probe of time-evolving rovibrational wavepackets. A physical picture is drawn of the mechanism through which rotation–vibration coupling mechanisms are reflected in the time-dependent photoionisation asymmetry parameters. The effects of complicating features that may obscure the interpretation of time-resolved photoelectron spectroscopies, including the field intensity and the inherent complexity of ionisation processes are examined.
The Softening of Secondary X-Rays

DR. A. H. COMPTON in a letter on this subject in NATURE of November 17, p. 366, described an experiment in which he reflected the Kα rays from a molybdenum Coolidge tube on to a slab of paraffin, and measured the absorption coefficient of the secondary scattered rays at different angles with respect to the direction of the primary beam. The absorption coefficient of the secondary rays was found to be 29 per cent. greater than that of the primary Kα beam at θ = 90°, and 6 per cent. greater at θ=20°. This softening of the rays on being scattered was still more pronounced when the K lines of tungsten were used.
Unexpected Upper Airway Obstruction Due to Disseminated Human Papilloma Virus Infection Involving the Pharynx in a Parturient

Human papilloma virus has been implicated as the cause of juvenile-onset recurrent respiratory papillomatosis in first-born children. Thus, cesarean section is strongly recommended by obstetricians to avoid direct contact with papilloma in an infected birth canal. We report a parturient with silent hypopharyngeal papilloma, which was associated with severe clinical problems at the induction of general anesthesia. The anesthesiologist considered general anesthesia for this case because of disseminated skin warts and secondary pus across the patient's body. Although the patient's breathing was smooth before starting general anesthesia, it was difficult to maintain positive pressure ventilation despite administration of a muscle relaxant. High air-way resistance without chest wall motion was noted, despite the insertion of an oral airway. Therefore, direct laryngoscopy was immediately performed and an obstructing mass was found. This mass acted as a check valve during positive ventilation. Our report should remind clinicians that human papilloma virus infection, although benign, can be disastrous in certain circumstances, as in our case where it resulted in airway obstruction and distal spread during cesarean section. Its presence necessitated preoperative laryngoscopic evaluation and aggressive treatment.
Isolated eyelid-opening apraxia: Report of a new levodopa-responsive syndrome

Eyelid-opening apraxia (or involuntary levator inhibition) has been described chiefly in the context of basal ganglia disease. We present two novel cases in which apraxia of eyelid opening developed in the absence of any other CNS signs, and which resolved following treatment with levodopa. We suggest that when inability to open the eyes occurs without associated motor impairment, "apraxia" is the correct descriptive term, and a trial of levodopa should be considered.
Absolute Lymphocyte Count on Day 30 Is a Surrogate for Robust Hematopoietic Recovery and Strongly Predicts Outcome after T Cell-Depleted Allogeneic Stem Cell Transplantation

Several studies have shown that a higher lymphocyte count 3-4 weeks after allogeneic stem cell transplantation (SCT) is associated with better transplant outcome. However, the factors determining early lymphocyte recovery are not defined. To further explore the relationship between lymphocyte recovery and outcome we analyzed lymphocyte counts and other engraftment parameters in 157 patients with leukemia (48 acute myelogenous leukemia, 80 chronic myelogenous leukemia, and 29 acute lymphoblastic leukemia [ALL]) receiving T cell-depleted myeloablative SCT from an HLA-identical sibling. In multivariate analysis the day 30 absolute lymphocyte count (LC30) above the median of 450/muL was associated with improved survival (71% +/- 5% versus 38% +/- 6%, P < .0001), less relapse (21% +/- 5% versus 44% +/- 7%, P = .009), less nonrelapse mortality (NRM; 9 +/- 3 versus 36% +/- 6%, P < .0001) and less acute graft-versus-host disease (aGVHD) (34% +/- 5% versus 51% +/- 6%, P = .025). The beneficial effect of a higher LC30 influenced outcome in patients with both standard and high-risk disease but did not affect survival and relapse in ALL. We found that a higher LC30 correlated with higher lymphocyte counts at all time points between 30 and 90 days post-SCT and also with more rapid neutrophil and platelet engraftment. These results indicate that LC30 is a surrogate for robust engraftment and identifies an "at-risk" population of patients after T cell-depleted SCT.