cssi/SciSciGPT-SciSciNet huggingface dataset:
Distribution of monocarboxylate transporters MCT1 and MCT2 in rat retina.

Transport of lactic acid and other monocarboxylates such as pyruvate and the ketone bodies through cellular membranes is facilitated by specific transport proteins. We used chicken polyclonal antibodies to the monocarboxylate transporters-1 and -2 to determine their cellular and subcellular distributions in rat retina, and we compared these distributions to those of the glucose transporters-1 and -3. Monocarboxylate transporter-1 was most highly expressed by the apical processes of retinal pigment epithelium that surround the outer segments of the photoreceptor cells. In contrast to glucose transporter-1, monocarboxylate transporter-1 was not detected on the basal membranes of pigment epithelium. The luminal and abluminal endothelial plasma membranes in retina also exhibited heavy labeling by antibody to monocarboxylate transporter-1. In addition, this transporter was associated with the Muller cell microvilli, the plasma membranes of the rod inner segments, and all retinal layers between the inner and external limiting membranes. Monocarboxylate transporter-2 was found to be abundantly expressed on the inner (basal) plasma membrane of Muller cells and by glial cell processes surrounding retinal microvessels. This transporter was also present in the plexiform and nuclear layers but was not detected beyond the external limiting membrane. Recent studies have shown that lactic acid transport is of particular importance at endothelial and epithelial barriers where membranes of adjoining cells are linked by tight junctions. Our results suggest that monocarboxylate transporter-1 functions to transport lactate between the retina and the blood, both at the retinal endothelium and the pigment epithelium. The location of monocarboxylate transporter-2 on glial foot processes surrounding retinal vessels suggests that this transporter is also important in blood-retinal lactate exchange. In addition, the abundance of these transporters in Muller cells and synaptic (plexiform) layers suggests that they function in lactate exchange between neurons and glia, supporting the notion that lactate plays a key role in neural metabolism.
The social origins of black American doctorates in the sciences

Most sociological studies of U.S. scientists tend to disregard black Americans. This paper seeks to provide some necessary demographic data on black U.S. scientists on which future studies may build. A sample of 557 black scientists responded to a questionnaire designed to provide demographic data. The results show that the typical black U.S. scientist is a male who grew up in a predominantly black neighborhood in a lower middle‐class family with both parents present and usually another sibling or two. After graduating in the top quartile of a predominantly black public high school, he enrolled in a predominantly black college where his academic achievement was above average. When the decision was made to pursue the Ph.D. degree, the preference was a university located in the Midwest. After completing the doctorate the pattern was to return to the South to pursue a career in a predominantly black college.
Prevention of Early Childhood Caries—Results of a Fluoride Toothpaste Demonstration Trial on Chinese Preschool Children after Three Years

OBJECTIVES: This field demonstration trial evaluates the long-term effects of introducing daily toothbrushing with fluoride toothpaste in a Chinese kindergarten (test group) compared to caries development in children who had no organized preventive program (control group). METHODS: In the test group teacher-supervised toothbrushing was initiated with 1,000 ppm MFP toothpaste in addition to oral health education activities. Test and control children were examined at baseline (n = 289, aged 3 years) and annually thereafter. RESULTS: After three years, 251 children (87%) were still in the trial. Caries development (dmfs) calculation included only those children who were present at both baseline and subsequent annual examinations. At baseline the mean dmfs was 4.8 in the test group and 6.5 in the control group (NS). After three years the caries increment was 6.2 and 8.4 in the test group and the control group, respectively (P < .05). Adjusting for reversals, the net caries increment was 3.6 and 6.3, respectively (P < .01). Additionally, multiple linear regression analysis indicated that both baseline dmfs, the program and plaque level had a significant effect on the net caries increment. The use of hierarchical caries severity zones was useful for the identification of those children most at risk for further caries development. CONCLUSIONS: We conclude that a daily toothbrushing with limited involvement of professional staff was feasible in a Chinese kindergarten and that caries development was significantly slowed in the test children. Caries severity zones may possibly assist in determining levels of intervention.
Cell type- and differentiation-dependent expression from the mouse acetylcholine receptor ϵ-subunit promoter

The nicotinic acetylcholine receptor (AChR) in adult skeletal muscle is composed of alpha-, beta-, epsilon-, and delta-subunits and is localized at the neuromuscular junction; in contrast, the more diffusely distributed fetal form is composed of alpha-, beta-, gamma-, and delta-subunits. To define sequences necessary for the transcriptional regulation of the mouse epsilon-subunit gene, we sequenced and analyzed 1036 bp upstream of the transcription start site. Using deletion analysis of the 5'-flanking region linked to the bacterial chloramphenicol acetyltransferase (CAT) gene and transfection of the resulting constructs into established cell lines, we demonstrate that a 151 bp fragment exhibits cell type- and differentiation-specific promoter activity. This activity was independent of a myogenic factor putative binding site (E-box). However, transactivation experiments with recombinant myoD, myogenin, or MRF4 showed that the E-box was functional and that MRF4 preferentially transactivates the epsilon-promoter. Thus, like other AChR promoters, the proximal region of the epsilon-promoter contains information for cell type-specific and developmental regulation of CAT and can be transactivated by myogenic factors in cultured cell lines. Unlike the other AChR promoters characterized to date, epsilon-promoter function can be partially independent of myogenic factors of the helix-loop-helix class.
Noxious heat induces fMRI activation in two anatomically distinct clusters within the nucleus accumbens.

Abstract Using functional magnetic resonance imaging (fMRI) we found that a noxious thermal stimulus (46 °C) to the hand activates the nucleus accumbens (NAc) in humans, while a non-noxious warm stimulus (41 °C) does not. Following the noxious stimulus, two distinct foci of decreased activation were observed showing distinct time course profiles. One focus was anterior, superior, and lateral and the second that was more posterior, inferior, and medial. The anatomical segregation may correlate with the functional components of the NAc, i.e., shell and core. The results support heterogeneity of function within the NAc and have implications for the understanding the contribution of NAc function to processing of pain and analgesia.
The role mining problem: finding a minimal descriptive set of roles

Devising a complete and correct set of roles has been recognized as one of the most important and challenging tasks in implementing role based access control. A key problem related to this is the notion of goodness/interestingness -- when is a role good/interesting? In this paper, we define the role mining problem (RMP) as the problem of discovering an optimal set of roles from existing user permissions. The main contribution of this paper is to formally define RMP, and analyze its theoretical bounds. In addition to the above basic RMP, we introduce two different variations of the RMP, called the δ-approx RMP and the Minimal Noise RMP that have pragmatic implications. We reduce the known "set basis problem" to RMP to show that RMP is an NP-complete problem. An important contribution of this paper is also to show the relation of the role mining problem to several problems already identified in the data mining and data analysis literature. By showing that the RMP is in essence reducible to these known problems, we can directly borrow the existing implementation solutions and guide further research in this direction.
Cell division, guillotining of dimer chromosomes and SOS induction in resolution mutants (dif, xerC and xerD) of Escherichia coli

We have studied the growth and division of xerC, xerD and dif mutants of Escherichia coli, which are unable to resolve dimer chromosomes. These mutants express the Dif phenotype, which includes reduced viability, SOS induction and filamentation, and abnormal nucleoid morphology. Growth was studied in synchronous cultures and in microcolonies derived from single cells. SOS induction and filamentation commenced after an apparently normal cell division, which sheared unresolved dimer chromosomes. This has been called guillotining. Microcolony analysis demonstrated that cell division in the two daughter cells was inhibited after guillotining, and microcolonies formed that consisted of two filaments lying side by side. Growth of these filaments was severely reduced in hipA+ strains. We propose that guillotining at dif destroys the expression of the adjacent hipBA genes and, in the absence of continued formation of HipB, HipA inhibits growth. The length of the filaments was also affected by SfiA: sfiA dif hipA mutants initially formed filaments, but cell division at the ends of the filaments ultimately produced a number of DNA-negative cells. If SOS induction was blocked by lexA3 (Ind-), filaments did not form, and cell division was not inhibited. However, pedigree analysis of cells in microcolonies demonstrated that lethal sectoring occurred as a result of limited growth and division of dead cells produced by guillotining.
Severe Occlusive Carotid Artery Disease: Hemodynamic Assessment by MR Perfusion Imaging in Symptomatic Patients

BACKGROUND AND PURPOSE: Cerebral hemodynamic status has been reported to influence the occurrence and outcome of acute stroke. The purpose of this study was to assess hemodynamic compromise in symptomatic patients with severe occlusive disease of the carotid artery by the use of echo-planar perfusion imaging. METHODS: Spin-echo echo-planar perfusion imaging was performed in 11 patients (two had bilateral disease) with severe stenosis or occlusion of the carotid artery who had experienced either a recent transient ischemic attack or minor stroke. Relative cerebral blood volume (rCBV) maps and relative mean transit time (rMTT) maps were generated from the time-concentration curve. Findings on T2-weighted images, angiograms, rCBV maps, and rMTT maps were compared and assessed qualitatively and quantitatively. RESULTS: Although the abnormalities on T2-weighted images were absent, minimal, and/or unrelated to the degree of stenosis or collateral circulation, rMTT maps showed much larger and more distinct perfusion abnormalities along the vascular distribution of the affected vessels in all 13 vascular territories of the 11 patients. Despite obvious abnormalities on rMTT maps, none of the patients had evidence of decreased rCBV in the affected brain tissue (increased in three, normal in eight). A statistically significant difference in rMTT values was found between the affected and unaffected brain tissue, whereas no significant difference was seen in rCBV values. CONCLUSION: Echo-planar perfusion imaging is a noninvasive and rapid method for evaluating the hemodynamics in severe occlusive carotid artery disease and the compensatory vascular changes, and it may be useful in patient management.
Genetic screen of African Americans with Fuchs endothelial corneal dystrophy

Purpose: Fuchs endothelial corneal dystrophy (FECD) is a genetically heterogeneous disorder that has been primarily studied in patients of European or Asian ancestry. Given the sparse literature on African Americans with FECD, we sought to characterize the genetic variation in three known FECD candidate genes in African American patients with FECD. Methods: Over an 8-year period, we enrolled 47 African American probands with FECD. All participants were clinically examined with slit-lamp biomicroscopy, and when corneal tissue specimens were available, histopathologic confirmation of the clinical diagnosis was obtained. The coding regions of known FECD susceptibility genes collagen, type VIII, alpha 2 (COL8A2); solute carrier family 4, sodium borate transporter, member 11 (SLC4A11); and zinc finger E-box binding homeobox 1 (ZEB1 [also known as TCF8]) were Sanger sequenced in the 47 probands using DNA isolated from blood samples. Results: Twenty-two coding variants were detected across the COL8A2, SLC4A11, and ZEB1 genes; six were nonsynonymous variants. Three novel coding variants were detected: a synonymous variant each in COL8A2 and SLC4A11 and one nonsynonymous variant in ZEB1 (p.P559S), which is predicted to be benign and tolerated, thus making its physiologic consequence uncertain. Conclusions: Variation in the COL8A2, SLC4A11, and ZEB1 genes is present in only a small fraction of our African American cases and as such does not appear to significantly contribute to the genetic risk of FECD in African Ameri cans. This observation is on par with findings from previous sequencing studies involving European or Asian ancestry patients with FECD.
Credit Scores and College Investment

The private market of student loans has become an important source of college financing in the U.S. Unlike government student loans, eligibility conditions on private student are based on the credit history of the student and the parents. Also, interest rates on private loans vary significantly with credit scores. We quantify the effects of credit scores on college investment in a heterogeneous life-cycle economy that exhibits a government and private market for student loans. We find that students with better credit scores invest in more college education. The importance of credit scores varies across alternative credit market arrangements. JEL Codes: E24; I22
The site of origin of the 1918 influenza pandemic and its public health implications.

The 1918-1919 influenza pandemic killed more people than any other outbreak of disease in human history. The lowest estimate of the death toll is 21 million, while recent scholarship estimates from 50 to 100 million dead. World population was then only 28% what it is today, and most deaths occurred in a sixteen week period, from late September 1918 to early January 1919. The site of origin has never been clearly established. A new review of contemporary medical and lay literature has found previously-overlooked epidemiological evidence that suggests that the pandemic began in a sparsely populated region of southwestern Kansas. The fact that a new influenza virus could cross from animals to man in such a region demonstrates the need for WHO to get the political and diplomatic support and the resources necessary to expand its influenza surveillance system, currently limited to only about half the countries in the world.
Association between Lung Function and Mental Health Problems among Adults in the United States: Findings from the First National Health and Nutrition Examination Survey

The objective of this study was to determine the association between lung function and mental health problems among adults in the United States. Data were drawn from the First National Health and Nutrition Examination Survey (1971-1975), with available information on a representative sample of US adults aged 25-74 years. Lung function was assessed by spirometry, and provisional diagnoses of restrictive and obstructive airway disease were assigned based on percentage of expected forced expiratory volume. Mental health problems were assessed with the General Well-Being scales. Restrictive lung function and obstructive lung function, compared with normal lung function, were each associated with a significantly increased likelihood of mental health problems. After adjustment for differences in demographic characteristics, obstructive lung function was associated with significantly lower overall well-being (p = 0.025), and restrictive lung function was associated with significantly lower overall well-being (p < 0.001), general health (p < 0.0001), vitality (p < 0.0001), and self-control (p = 0.001) and with higher depression (p = 0.002) subscale scores compared with no lung function problems. Consistent with previous findings from clinical and community-based studies, these results extend available data by providing evidence of a link between objectively measured lung function and self-reported mental health problems in a representative sample of community adults. Future studies are needed to determine the mechanisms of these associations.
An evaluation of blocking probability for three-fold SDMA

Space division multiple access (SDMA) uses the advantage of the smart antenna technology to form a directional antenna pattern in a cellular. By exploiting the directional antenna pattern for users, SDMA can achieve spatial orthogonality among users and channel reuse within a cell. Several studies (Fuhl 1997; Buracchini et al. 1996) have shown the performance improvement of SDMA in a mobile communication environment. This paper extends the two-folding SDMA blocking probability derivation from Galvan-Tejada and Gardiner (1999) and approximately two-folding SDMA approaches from Huang and Doherty (2001). An approximate model is proposed for three-folding SDMA and the corresponding blocking probability is derived. Analytical and simulation results show that three-fold SDMA increases capacity over the traditional cellular system, which demonstrates the effectiveness of SDMA for resource management.
Variability in Interpretive Performance at Screening Mammography and Radiologists’ Characteristics Associated with Accuracy

Fellowship training in breast imaging was the only radiologists’ characteristic significantly associated with greater sensitivity and higher overall accuracy; however, fellowship-trained radiologists also had significantly higher false-positive rates.
Group Size Effects in Public Goods Provision: The Voluntary Contributions Mechanism

This paper examines the relationship between variations in group size and "free-riding" behavior in the voluntary provision of public goods. We examine experimentally two pertinent concepts: the marginal return to an individual from contributions to the public good, and the actual number of members in the group. Our results strongly support a hypothesis that increasing group size leads to a reduction in allocative efficiency when accompanied by a decrease in marginal return from the public good (as from crowding or an association of large groups with imperceptibility of marginal benefits). Our results do not support a pure numbers-in-the-group effect.
Nonparetic arm force does not overinhibit the paretic arm in chronic poststroke hemiparesis.

Abstract Objective To determine whether nonparetic arm force overinhibits the paretic arm in patients with chronic unilateral poststroke hemiparesis. Design Case-control neurophysiological and behavioral study of patients with chronic stroke. Setting Research institution. Participants Eighty-six referred patients were screened to enroll 9 participants (N=9) with a >6 month history of 1 unilateral ischemic infarct that resulted in arm hemiparesis with residual ability to produce 1Nm of wrist flexion torque and without contraindication to transcranial magnetic stimulation. Eight age- and handedness-matched healthy volunteers without neurologic diagnosis were studied for comparison. Interventions Not applicable. Main Outcome Measure Change in interhemispheric inhibition targeting the ipsilesional primary motor cortex (M1) during nonparetic arm force. We hypothesized that interhemispheric inhibition would increase more in healthy controls than in patients with hemiparesis. Results Healthy age-matched controls had significantly greater increases in inhibition from their active to resting M1 than patients with stroke from their active contralesional to resting ipsilesional M1 in the same scenario (20%±7% vs −1%±4%, F 1,12 =6.61, P =.025). Patients with greater increases in contralesional to ipsilesional inhibition were better performers on the 9-hole peg test of paretic arm function. Conclusions Our findings reveal that producing force with the nonparetic arm does not necessarily overinhibit the paretic arm. Though our study is limited in generalizability by the small sample size, we found that greater active contralesional to resting ipsilesional M1 inhibition was related with better recovery in this subset of patients with chronic poststroke.
Reducing maltreated children's reluctance to answer hypothetical oath-taking competency questions.

Before allowing child witnesses to testify, courts routinely require children to describe what would happen to them if they lied. However, young children often refuse to reason hypothetically if they view the premises as implausible or undesirable, and might be more willing to discuss the consequences of lying if they are asked about another child rather than themselves. On the other hand, children might view themselves as invulnerable to punishment, and therefore believe that whereas other children will be punished for lying, they will not be. In this study, 64 maltreated 5- and 6-year-old children were asked to describe the consequences of lying to three professionals (a judge, a social worker, and a doctor). Participants in the “self” condition were asked what would happen to them if they lied, whereas participants in the “other” condition were asked to describe what would happen to a story child if he or she lied. Asking children about “other” children increased responsiveness, and did not reveal perceptions of invulnerability. The results suggest that young children's understanding that they will be punished for lying may make them reluctant to discuss the consequences of lying, leading to underestimation of their oath-taking competency.
Radiofrequency Thermotherapy vs Bone-Anchored Suspension for Treatment of Lateral Nasal Wall Insufficiency: A Randomized Clinical Trial

ImportanceLateral nasal wall insufficiency is a common problem with little consensus on optimal treatment. ObjectiveTo assess the efficacy of radiofrequency (RF) thermotherapy for the treatment of ...
Release of Neptunium, Plutonium, Uranium and Technetium from the Metallic Waste form from the Electrometallurgical Treatment Process

This waste form is an alloy consisting of stainless steel with 15 wt% zirconium and acts as a host for the immobilization of radioelements that remain with the spent fuel cladding hulls following their treatment using an electrometallurgical treatment process. The results presented here are from 14, 34 and 90-day immersion tests conducted at 90 °C. These tests show that the release of uranium is considerably higher than that of all other major elements present (Fe, Cr, Ni, Zr), but that release of all constituents is comparable to or lower than that for borosilicate glass.
Evaluation of pediatric oncology patients with previous multiple central catheters for vascular access: is Doppler ultrasound needed?

Background/Purpose Pediatric oncology patients who have undergone placement of multiple central venous catheters may have thrombosis or stenosis in the upper venous system. The purpose of this study was to identify factors that predict venous thrombosis or stenosis and to evaluate the role of Doppler ultrasonography in assessing the upper venous system of pediatric patients requiring multiple central vascular catheters. Methods The medical records of eligible patients were reviewed with regard to demographics, primary disease, type of catheter, duration of previous central venous access, association with infection, operative notes, and Doppler ultrasonographic findings. Results Our evaluation criteria were met in 50 cases (47 patients). In 10 cases, Doppler ultrasonography revealed abnormality in the upper venous system. Patient demographics, primary disease, type of catheter, duration of previous central venous access, or association with infection were not found to significantly predict the abnormality in the upper venous system. Placement of central venous access device was performed without difficulty when the site of placement was chosen on the basis of ultrasonographic findings. Conclusion Doppler ultrasonography is useful in diagnosing thrombosis or stenosis in asymptomatic pediatric patients requiring placement of multiple central venous catheters. Pediatr Blood Cancer 2007;48:527–531. © 2006 Wiley-Liss, Inc.
Coarse-Grained Brownian Dynamics Simulations of the 10-23 DNAzyme

Deoxyribozymes (DNAzymes) are single-stranded DNA that catalyze nucleic acid biochemistry. Although a number of DNAzymes have been discovered by in vitro selection, the relationship between their tertiary structure and function remains unknown. We focus here on the well-studied 10-23 DNAzyme, which cleaves mRNA with a catalytic efficiency approaching that of RNase A. Using coarse-grained Brownian dynamics simulations, we find that the DNAzyme bends its substrate away from the cleavage point, exposing the reactive site and buckling the DNAzyme catalytic core. This hypothesized transition state provides microscopic insights into experimental observations concerning the size of the DNAzyme/substrate complex, the impact of the recognition arm length, and the sensitivity of the enzymatic activity to point mutations of the catalytic core. Upon cleaving the pertinent backbone bond in the substrate, we find that the catalytic core of the DNAzyme unwinds and the overall complex rapidly extends, in agreement with experiments on the related 8-17 DNAzyme. The results presented here provide a starting point for interpreting experimental data on DNAzyme kinetics, as well as developing more detailed simulation models. The results also demonstrate the limitations of using a simple physical model to understand the role of point mutations.
Indiana Bats in the Midwest: The Importance of Hydric Habitats

The endangered Indiana bat (Myotis sodalis) requires very specific habitats to provide necessary day-roosting and foraging resources during the spring and summer months throughout its distribution in the eastern United States. Maternity colonies of Indiana bats are almost always found under the exfoliating bark of dead or dying trees. Furthermore, they switch frequently among multiple roosts within large but still somewhat local areas. Therefore, habitats with large numbers of snags or decadent trees are needed to support Indiana bat maternity colonies. These habitats arise naturally and anthropogenically in a variety of ways. However, these conditions often are rare relative to other forest conditions. In the Midwest, such as southern and central Illinois, USA, maternity colonies are more commonly associated with bottomland, riparian, wetland, or other hydric forest types. It is unclear if this occurs because areas with large numbers of snags are more common in these habitats, if maternity colonies prefer these habitats for their foraging resources, or if decades of intensive agriculture have restricted colonies to these habitats. Because many large maternity colonies have been observed in hydric habitats of the Midwest, I hypothesize that these are preferred maternity habitats. Moreover, very few large maternity colonies have been located using upland forest habitats within the region. Elsewhere, such as in the central and southern Appalachians, maternity colonies have been located in upland areas where bottomland habitats are less extensive. However, these colonies are usually characterized by small numbers of bats and ephemeral persistence. Future conservation efforts for the Indiana bat should focus on protecting and regenerating bottomland habitats along the major river systems of the midwestern United States. It is within these bottomland and riparian habitats that future large and long-term maternity colonies will be established.
Circulating Prostate Cancer Cells Detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR): What Do They Mean?

BackgroundMolecular techniques have been developed recently to assess for circulating tumor cells. This “molecular staging” of prostate cancer uses the reverse transcription-polymerase chain reacti...
Volition and alcohol-risk reduction: the role of action orientation in the reduction of alcohol-related harm among college student drinkers.

The present study examined the role of action orientation in health behavior change. Eighty-six binge drinking college students completed measures of alcohol use, alcohol-related consequences (e.g., driving drunk), motivation to change drinking, and action orientation. Alcohol use and consequences were reassessed 1 month later. Results showed that, although there was no significant change in alcohol quantity per occasion, students reported a significant decline in alcohol-related problems over time. Hierarchical regression analyses were conducted to examine whether action orientation was associated with changes in alcohol involvement. Controlling for alcohol problems and motivation to change at Time 1, those with higher dispositional action orientation showed fewer alcohol-related consequences at Time 2. These results suggest that those who are low in action orientation may have more difficulty enacting intentions to modify harmful health behaviors. The findings underscore the importance of volitional skills in interventions to promote change in health behavior.
A satellite formation flying approach providing both positioning and tracking

Abstract A magnetic field approach is presented whereby a large number of closely located satellites can be positioned and oriented relative to each other, but can also be tracked in six degrees of freedom. This is accomplished by using frequency-multiplexed magnetic fields where coils are placed on each satellite to allow them to generate magnetic fields, to interact with the magnetic fields from other satellites, and to sample the surrounding magnetic fields. By doing this, a satellite can choose which alternating field to push or pull against, to provide torque about, or to sample in order to determine its location and orientation relative to the other satellites. Theory is provided demonstrating the capability of this approach along with its advantages and limitations. An experimental system allowing 3 degrees-of-freedom was constructed and used to demonstrate a feedback and control system where a satellite is told to move to a location and it does this by interacting with the surrounding satellites to both generate forces and torques and to track its position and orientation.
Clinical pharmacology research strategy for dissolvable tobacco products.

INTRODUCTION Dissolvable tobacco products (DTPs) are relatively new to the market. Some researchers and manufacturers describe them as finely ground tobacco that has been compressed into sticks, strips, and orbs that dissolve or disintegrate in the mouth and do not require spitting. While the pharmacokinetic profiles of nicotine and other tobacco-associated compounds and pharmacological effects of these products are complex, their clinical pharmacology has not been systematically evaluated. We reviewed the scientific literature regarding the known pharmacokinetic (PK) characteristics and pharmacodynamic (PD) effects of DTPs with the purpose of identifying research gaps and informing future studies. OBJECTIVES To evaluate current knowledge of the pharmacological properties of DTPs; to assess their similarities and differences with other tobacco products, especially smokeless tobacco products, and Food and Drug Administration-approved nicotine replacement therapies; to identify gaps in existing information; and to propose a strategy for future clinical pharmacology studies of DTPs. METHODS We reviewed the peer-reviewed literature and generated research questions for future clinical pharmacology studies. RESULTS AND CONCLUSIONS Data on the PK and PD of DTPs are sparse and inconsistent. The results of existing studies are limited and inconclusive, and their interpretation is complicated by methodological and/or study design issues. This review identifies a need for larger, comprehensive, and prospectively designed studies that include PK/PD measurements and data analyses. We propose a research agenda for future DTP studies related to the clinical pharmacology of nicotine, its metabolites, tobacco-specific nitrosamines, and other toxic compounds.
Functional MR imaging in human visual system

Blood oxygenation-level dependent functional MRI (BOLD-fMRI) realizes the functional organization of the visual system in humans. There are many important fruits in the field. The paper will talk about parallel processing and hierarchial organization in the visual information processing in detail. Also,we will summarize the development about functional MRI in the localization of the visual cortex,colour identification and motion perception in humans.
Bayesian Cue Interaction in Human Spatial Navigation

We examined the manner in which people integrated visual cues and self-motion cues during spatial navigation when the two cues varied in reliability independently. Results showed that when responses were pooled across reliability levels of the manipulated cue, people integrated cues optimally or nearly optimally in a Bayesian manner. However, when responses were analyzed within reliability levels, navigation behavior often deviated from Bayesian optimal integration. These results suggest that when experiencing spatial cues changing in reliability, navigators combine cues in a way consistent with Bayesian integration theory overall, but at the cost of being non-optimal at the individual reliability levels.
Simulation-based performance assessment: an innovative approach to exploring understanding of physical science concepts

ABSTRACTThis paper illustrates the use of simulation-based performance assessment (PA) methodology in a recent study of eighth-grade students’ understanding of physical science concepts. A set of four simulation-based PA tasks were iteratively developed to assess student understanding of an array of physical science concepts, including net force, acceleration, velocity, and inertia. Illustrative examples drawn from the administration of these simulation-based PA tasks to a sample of eighth-grade students (n = 74) highlight the potential of simulation-based tasks for revealing conceptual understanding of science concepts and for informing curriculum development within the context of design-based implementation research. The paper also describes a variety of challenges encountered over the course of the development, administration, and analysis of the PA data that may be informative for researchers and educators as they consider implementing simulation-based PAs.
Adipocyte Differentiation of SOD2−/− Mouse Bone Marrow Stromal Cells Is Associated with Decreased Antioxidant Reserves and Is Reversed by the Antioxidant WR2721 (Amifostine).

Cell lines from homozygous deletion recombinant negative manganese superoxide dismutase (SOD2 −/− ) mice have intrinsic ionizing radiation sensitivity that is reversed by expression of the transgene for human SOD2 (Radiation Research154:365, 2000). This study tests whether redox status influences adipocyte differentiation potential of bone marrow stromal cells by comparing the differentiation potential of SOD2 −/− and SOD2 +/+ bone marrow stromal cell lines. Cells were cultured in basal medium (Dulbecco’s Modified Eagle’s Medium, 1% fetal bovine serum (FBS), 100 U/ml penicillin and 100 μg/mL streptomycin +/ − adipocytogenic supplements (10 μg/ml insulin, 1 μM dexamethasone, 100 mM indomethacin)). Adipocytogenesis was assessed by spectrophotometric content of oil red-O dye and by RT-PCR for peroxisome proliferator-activated receptor-gamma (PPARγ) and lipoprotein lipase (LPL). Glutathione peroxidase (GPX) activity or glutathione (GSH) levels were measured by a Glutathione Peroxidase, Cellular Assay Kit or Glutathione Assay Kit, respectively, by Calbiochem, Inc. SOD2 +/+ cells developed adipocytes only when treated with adipocytogenic supplements and expressed PPARγ and LPL at day 5. SOD2 −/− cells cultured in basal conditions demonstrated constitutive adipocytogenesis. The level of GPX activity in SOD2 −/− cells (43.2 ± 3.5 mU/ml) was 52.7% (p +/+ cells (82.0 ± 2.3). The level of GSH in SOD2 −/− cells (173 ± 2 μM) was 78.6% (p=0.0089) of that in SOD2 +/+ cells (220 ± 4 μM). Three day treatment of SOD2 −/− with 4 mM WR2721 resulted in 22% reduction in oil red-O content. In addition, in SOD2 −/− cells cultured in adipocytogenic medium, 3-day treatment in 4 mM WR2721 resulted in 46% reduction in oil red-O content and undetectable expression of PPARγ and LPL. In conclusion, WR2721 limits constitutive adipocytogenesis and inhibits induced adipocytogenesis in SOD2 −/− cells. These data provide evidence for the involvement of the cellular redox pathway in adipocyte differentiation of bone marrow stromal cells.
Abnormal sleep duration associated with hastened depressive recurrence in bipolar disorder

Abstract Background Abnormal sleep duration (ASD, Methods Outpatients referred to the Stanford BD Clinic during 2000–2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation at baseline, and with the Clinical Monitoring Form at monthly follow-ups for up to two years of naturalistic treatment. Prevalence and clinical correlates of ASD in 93 recovered (euthymic ≥8 weeks) and 153 depressed BD patients were assessed. Kaplan-Meier analyses (Log-Rank tests) assessed relationships between baseline ASD and longitudinal depressive severity, with Cox Proportional Hazard analyses assessing potential mediators. Results ASD was only half as common among recovered versus depressed BD outpatients, but was significantly associated with hastened depressive recurrence (Log-Rank p=0.007), mediated by lifetime anxiety disorder and attenuated by lifetime history of psychosis, and had only a non-significant tendency towards association with delayed depressive recovery (Log-Rank p=0.07). In both recovered and depressed BD outpatients, baseline ASD did not have significant association with any baseline BD illness characteristic. Limitations Self-reported sleep duration. Limited generalizability beyond our predominately white, female, educated, insured American BD specialty clinic sample. Conclusions Baseline ASD among recovered BD patients may be a risk marker for hastened depressive recurrence, suggesting it could be an important therapeutic target between mood episodes.
Behavior Problems of Behaviorally Disordered and Normal Adolescents.

Adolescent boys and girls aged 14 to 18 years, identified as either behaviorally disordered or normal, were rated by their teachers on the Behavior Problem Checklist. Analysis of these ratings reve...
Quality of life after coronary artery bypass graft surgery versus percutaneous coronary intervention: what do the trials tell us?

Purpose of review With an ever-aging population, the treatment of multi-vessel coronary artery disease (CAD) has increasingly become focused not only on mortality, but on symptom relief and improving quality of life (QOL). The purpose of this review is to present a summary on the subject of QOL after percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG), highlighting the latest comparative trials in the field. Recent findings About 1 month after revascularization, patients recovering from either PCI or CABG report improvements in angina frequency. However, at 6 months and in the years that follow, angina relief is significantly better after CABG compared with PCI. Correspondingly, the use of antiangina medication is significantly higher following PCI, even in recent years with the use of drug-eluting stents. Regarding general health status, at the 1-month time point, PCI patients have recovered faster than those who have had surgery, reporting fewer physical limitations, less bodily pain, and greater QOL and treatment satisfaction. Nevertheless, these differences disappear by 6 months, and in the years thereafter, CABG patients report fewer physical limitations compared with those who have undergone PCI. About 5 years after revascularization, significant benefits remain favoring CABG in term of physical, emotional, and mental health. Summary Patients with multivessel coronary artery disease attain important QOL benefits following revascularization with either PCI or CABG. Percutaneous treatments lead to a more rapid recovery and improved short-term health status compared with CABG at 1 month. However, surgery results in greater angina relief and improved QOL compared with PCI 6 months after revascularization and beyond.
Abstract 10808: Clusterin Up-regulation and Akt Pathway Activation Are Key to GATA-4 Mediated Cytoprotection of Mesenchymal Stem Cells Against Ischemia Injury

Clusterin (Clu) is a stress-responding protein with multiple biological functions, including the inhibition of apoptosis and inflammation. Our preliminary microarray studies show that clusterin was prominently upregulated in mesenchymal stem cells (MSCs) overexpressing GATA-4 (MSC GATA-4 ). Here, we directly investigate whether the upregulation of clusterin is involved in GATA-4 mediated cytoprotection. Methods: MSCs harvested from bone marrow of SD rats were transduced with GATA-4. The expression of clusterin in MSCs was documented by real-time PCR and western blotting. Simulation of ischemia was achieved by MSCs exposure to a hypoxic environment. Lactate dehydrogenase (LDH) released from MSCs was served as a biomarker of cell injury and MTT uptake was used to estimate cell viability. Mitochondrial function was assessed using mitochondrial membrane potential (ΔΨm) and caspase 3/7 activity. Results: (1) Clusterin expression was up-regulated in MSC GATA-4 compared to control MSCs which transfected with empty-vector (MSC Null ) ( Fig. A1 - A2 ). MSC GATA-4 were tolerant to 72 h hypoxia exposure; expressed as less LDH release and higher MTT uptake ( Fig. A3 ). This protection was abrogated by transfecting with Clu-siRNA ( Fig. A4 - A5 ). (2) Exogenous clusterin significantly decreased LDH release and increased MSC survival in hypoxic environment. Moreover, ΔΨm was maintained and caspase 3/7 activity was reduced by exogenous clusterin in a concentration-dependent manner (Fig. B ). (3) p-Akt expression in MSCs was upregulated following pre-treated with clusterin, although there was no significant change in total Akt ( Fig. C1 - C2 ). Moreover, cytoprotection mediated by clusterin (2μM/ml) was partially abrogated by Akt inhibitor LY294002 (5μMml) ( Fig. C3 ). Conclusions: Up-regulation of clusterin and activation of Akt signaling pathway is involved in GATA-4 mediated cytoprotection consequent to hypoxia stress.
Infective endocarditis: Refer for expert team care as soon as possible.

Infectious endocarditis needs multidisciplinary care. if surgery is indicated, it is best done sooner.
Probabilistic Bias Analysis

To this point we have considered situations in which the bias parameters for a bias analysis are known with certainty or modeled as if they are known with certainty (i.e., simple bias analysis, see Chaps. 4– 6). We have also considered models of the impact of combinations of bias parameters on an observed estimate of association (i.e., multidimensional bias analysis, see Chap. 7). Simple bias analysis is an improvement over conventional analyses, which implicitly assume that all the bias parameters are fixed at values that confer no bias. However, the usefulness of simple bias analysis is limited by its assumption that the bias parameters are known without error, a situation that is rarely, if ever, a reality. Multidimensional bias analysis improves on simple bias analysis by examining the impact of more than one set of bias parameters, but even this approach only examines the bias conferred by a limited set of bias parameters. For any analysis, many other possible combinations of bias parameters are plausible, and a multidimensional analysis will not describe the impact of these possibilities. More important, multidimensional analysis gives no sense of which corrected estimate of association is the most likely under the assumed bias model, which can make interpretation of the results challenging.
SPECIFICITY OF MEMORY DEFICITS IN ALCOHOLISM

Inferences of specific impairments in memory from prolonged abuse of alcohol have come from initial studies reporting that visuospatial memory and problem solving were impaired but verbal memory and learning were not. The apparent specificity, however, is demonstrated to be an artifact of the more difficult visual tests. With task complexity increased, impairments are shown also in both learning and recall of words, story, or designs. A common condition for deficits to be detected is the demand for effort in encoding and retrieving of to-be-remembered information. In general, deficits are mild and diffuse and do not seem to be clearly specific to material or modality. Furthermore, deficits are more pronounced in old alcoholics, although these tend to have longer drinking careers. Age and length of abstinence are more significant predictors of impairment than length or rate of alcohol drinking; however, concomitant disease and familial history of alcoholism are recognized to contribute to wide differences in effort-requiring memory processing.
Oral Cancer Overview: The Significance of Metastasis and Surgical Management of the Neck

Squamous cell carcinoma of the oral cavity has the propensity to metastasize to the cervical lymph nodes even in the early stages. The presence of lymph node metastasis is the most significant independent variable in determining survival of patients with cancer of the head and neck. Therefore, the diagnosis and management of cervical lymph node metastasis is one of the most important responsibilities of the head and neck oncologist.
Micropipet Aspiration of the Human Neutrophil

Micropipet aspiration has been widely employed to study the mechanical behavior of passive neutrophils. The observed dynamics have been rationalized in terms of mechanical models that describe these cell as “slippery droplets” of viscous fluid enclosed by a surface or cortical tension. Here, a low Reynolds number hydrodynamics code based on the finite element method was utilized to analyze several such fluid models (e.g., Newtonian and shear thinning). We investigated the behavior of these models as a function of surface tension, droplet radius, viscosity, aspiration pressure, and pipet radius. In addition, for the simplest case of a Newtonian fluid droplet, we tabulated a dimensionless factor, M, which was utilized to approximate the apparent viscosity of the neutrophil. This analysis resulted in a useful method by which rheological parameters could be determined and subsequent models tested. Overall, of the models tested, the mechanical behavior of the passive neutrophil during micropipet aspiration can be best represented by a fluid droplet consisting of a shear thinning bulk viscosity, a shear thinning dilatational surface viscosity, and an area-dependent surface tension.
A note on the sensitivity of the histochemical plasmal reaction.

Comparison of the results from both histochemical and biochemical determinations of the plasmalogen concentration in several tissues and organs shows that the two methods are in general agreement. A comparison of the two methods also indicates that the lowest concentration of plasmalogen detectable with the histochemical procedure is about 0.7 μ moles per gram when 10 μ sections are employed.