cssi/SciSciGPT-SciSciNet huggingface dataset:
Nucleus Accumbens Shell and mPFC but Not Insula Orexin-1 Receptors Promote Excessive Alcohol Drinking.

Addiction to alcohol remains a major social and economic problem, in part because of the high motivation for alcohol that humans exhibit and the hazardous binge intake this promotes. Orexin-1-type receptors (OX1Rs) promote reward intake under conditions of strong drives for reward, including excessive alcohol intake. While systemic modulation of OX1Rs can alter alcohol drinking, the brain regions that mediate this OX1R enhancement of excessive drinking remain unknown. Given the importance of the nucleus accumbens (NAc) and anterior insular cortex (aINS) in driving many addictive behaviors, including OX1Rs within these regions, we examined the importance of OX1Rs in these regions on excessive alcohol drinking in C57BL/6 mice during limited-access alcohol drinking in the dark cycle. Inhibition of OX1Rs with the widely used SB-334867 within the medial NAc Shell (mNAsh) significantly reduced drinking of alcohol, with no effect on saccharin intake, and no effect on alcohol consumption when infused above the mNAsh. In contrast, intra-mNAsh infusion of the orexin-2 receptor TCS-OX2-29 had no impact on alcohol drinking. In addition, OX1R inhibition within the aINS had no effect on excessive drinking, which was surprising given the importance of aINS-NAc circuits in promoting alcohol consumption and the role for aINS OX1Rs in driving nicotine intake. However, OX1R inhibition within the mPFC did reduce alcohol drinking, indicating cortical OXR involvement in promoting intake. Also, in support of the critical role for mNAsh OX1Rs, SB within the mNAsh also significantly reduced operant alcohol self-administration in rats. Finally, orexin ex vivo enhanced firing in mNAsh neurons from alcohol-drinking mice, with no effect on evoked EPSCs or input resistance; a similar orexin increase in firing without a change in input resistance was observed in alcohol-naive mice. Taken together, our results strongly suggest that OX1Rs within the mNAsh, but not the aINS, play a central role in driving excessive alcohol drinking.
Integrating the Constructs of Anosognosia and Metacognition: a Review of Recent Findings in Dementia.

The current review integrates recent findings regarding the construct of self-awareness in dementia from both clinical and cognitive perspectives. We present the predominant theoretical models of awareness and summarize both traditional and emerging approaches to assessing awareness from clinical and meta-cognitive perspectives. In this review, we focus primarily on findings from recent studies in anosognosia and meta-cognition in the context of neurodegenerative disease with special emphasis on Alzheimer’s disease and frontotemporal dementia. Emerging trends in the study of awareness, including examination of the longitudinal course of anosognosia, and investigation of the neural substrates underlying meta-cognitive abilities are addressed. Finally, the practical importance of studying and assessing awareness from both theoretical and clinical angles is emphasized.
Hepatocyte ABCA1 Deletion Impairs Liver Insulin Signaling and Lipogenesis

Plasma membrane (PM) free cholesterol (FC) is emerging as an important modulator of signal transduction. Here, we show that hepatocyte-specific knockout (HSKO) of the cellular FC exporter, ATP-binding cassette transporter A1 (ABCA1), leads to decreased PM FC content and defective trafficking of lysosomal FC to the PM. Compared with controls, chow-fed HSKO mice had reduced hepatic (1) insulin-stimulated Akt phosphorylation, (2) activation of the lipogenic transcription factor Sterol Regulatory Element Binding Protein (SREBP)-1c, and (3) lipogenic gene expression. Consequently, Western-type diet-fed HSKO mice were protected from steatosis. Surprisingly, HSKO mice had intact glucose metabolism; they showed normal gluconeogenic gene suppression in response to re-feeding and normal glucose and insulin tolerance. We conclude that: (1) ABCA1 maintains optimal hepatocyte PM FC, through intracellular FC trafficking, for efficient insulin signaling; and (2) hepatocyte ABCA1 deletion produces a form of selective insulin resistance so that lipogenesis is suppressed but glucose metabolism remains normal.
Alternative approaches for econometric modeling of panel data using mixture distributions

The economic researcher is sometimes confronted with panel datasets that come from a population made of a finite number of subpopulations. Within each subpopulation the individuals may also be heterogenous according to some unobserved characteristics. A good understanding of the behavior of the observed individuals may then require the ability to identify the groups to which they belong and to study their behavior across groups and within groups. This may not be a complicated exercise when a group indicator variable is available in the dataset. However, such a variable may not be included in the dataset; and as a result, the econometrician is forced to work with the marginal distribution of the observed response variable, which takes the form of a mixture distribution. One can model a given response variable with a variety of mixture distributions. In this paper, I present several related mixture models. The most flexible one is an extension of the model by Kim et al. (2008) to the panel data setting. I have reviewed the estimation of some of these models by the Expectation-Maximization (EM) algorithm. The intent is to exploit the nice convergence properties of this algorithm when it is difficult to find good starting values for a Newton-type algorithm. I have also discussed how to compare these models and ultimately identify the one that provides the best fit to the data set under investigation. As an application I examine the investment behavior of U.S. manufacturing firms.
Floating-point input

The introduction to the last chapter briefly described format specifiers in C, Fortran, and Pascal. When used with the input facilities of those languages, they allow decimal data to be read easily, but binary, hexadecimal, and octal formats are unlikely to be widely supported.
Persistent mobile aerial surveillance platform using intelligent battery health management and drone swapping

Unmanned systems continue to be at the forefront of development for many industries, including homeland security and military. Unmanned systems operate with increasingly more advanced autonomy. According to the Defense Science Board report of 2012, the key aspect of enhancing autonomy is providing persistency. However, onboard fuel, in general, and battery capacity, for the electrically-powered systems in particular, limit the operational time of many systems characterized as persistent. That is why these days researchers explore a variety of solutions that have their advantages and disadvantages depending on the mission. These include using tethered systems, ground pads with contact and wireless (inductive) battery charging, solar-powered ground stations, power-line recharging stations, hydrogen fuel cells, solar-powered drones, laser-beam inflight recharging, etc. This paper focuses on the development and evaluation of simpler and seemingly more cost-efficient approach for a multi-rotor aerial persistent system enabling longer-duration missions using vehicle swapping and intelligent battery management. The developed prototype consists of three commercially available quadcopters, a wireless network router, and a laptop to execute Python code. System operation assumes autonomous operation swapping vehicles to maintain an airborne platform in the loiter area based on battery health. Based on analysis and assessment of the field test results, this paper proves the feasibility of the developed concept. For example, utilizing just four vehicle swaps the aerial surveillance platform was continuously available in the loiter area (on target) for about an hour, which is more than five times the air time of a single vehicle. While the field testing was conducted with a limited number of batteries, having nine batteries and chargers (for the particular commercial-off-the shelf system) would allow the developed system to operate for much longer durations, pretty much indefinitely.
Antioxidant is a Key Factor in Mussel Protein Adhesion

The underwater adhesion of marine mussels relies on mussel foot proteins (Mfps) rich in the catecholic amino acid 3,4-dihydroxyphenylalanine (Dopa). As a side chain, dopa is capable of strong bidentate interactions with a variety of surfaces, but its susceptibility to oxidation often renders it unreliable for adhesion. Mussels limit Dopa oxidation by imposing an acidic, reducing regime in the confined space of Mfp deposition. Using the surface forces apparatus (SFA) technique, I demonstrate that the adhesion of Mfp-3 to mica is closely coupled with Dopa redox and pH. Raising the pH from 3 to 7.5 decreases the adhesion energy of Mfp-3 on mica 20-fold and appears to be driven by the pH-dependent oxidation of Dopa. Addition of thiol-rich Mfp-6 restores Mfp-3 adhesion by coupling the oxidation of thiols to the reduction of Dopaquinones. How mussels preserve adhesive Dopa-containing proteins from oxidation has considerable biological and technological value.
Faith, Power and Family: Christianity and Social Change in French Cameroon

Between the two World Wars, the radical innovations of African Catholic and Protestant evangelists repurposed Christianity to challenge local and foreign governments operating in the French-administered League of Nations Mandate of Cameroon. Walker-Said explores how African believers transformed foreign missionary societies into profoundly local religious institutions with indigenous ecclesiastical hierarchies and devotional social and charitable networks, devising novel authority structures to control resources and govern cultural and social life. She analyses how African Christian religious leaders transformed social and labour relations, contesting forced labour and authoritarian decentralized governance as threats to family stability and community integrity. Inspired by Catholic and Protestant doctrines on conjugal complementarity and social equilibrium, as well as by local spiritual and charismatic movements, African Christians re-evaluated and renovated family and community authority structures to address the devastating changes colonialism wrought in the private sphere. The history of these reform-minded believers reveals how family intimacies and kinship ties constituted the force of community resistance to oppression and also demonstrates the relevance of faith in the midst of a tumultuous series of forces arising out of the colonial situation peculiar to Cameroon.Charlotte Walker-Said is Assistant Professor, Department of Africana Studies, John Jay College, City University of New York (CUNY).
The nature of the platyceratid–crinoid association as revealed by cross-sectional data from the Carboniferous of Alabama (USA)

The association of Paleozoic crinoids and platyceratid gastropods has drawn the attention of paleontologists for nearly 200 years. It has been variably interpreted as predatory, commensalistic, mutualistic or parasitic. Previous cross-sectional analyses of large populations of crinoids and platyceratids have favored the parasitic explanation for the interaction because of data suggesting that the average size of infested crinoids is less than that of their uninfested conspecifics. In this study, we examine a population of Dizygocrinus from the Carboniferous (Early Visean) Monteagle Limestone of Madison County, Alabama, USA. Of the 198 specimens examined from a single lens, 37 showed evidence of infestation by way of attached gastropods or drillholes at the base of their anal tubes—slender, cylindrical extensions of the tegmen with the periproct at the distal end. In contrast to the results of previous studies, the average size of the infested Dizygocrinus in this study was greater than that of the uninfested subset. Using conceptual and numerical models, we demonstrate that despite the slightly larger average size of the infested crinoids, the gastropods diminished the growth rates of their hosts. Thus, parasitism is the best explanation for this biotic interaction. The presence of an anal tube among the Monteagle Limestone Dizygocrinus may have diminished the negative impact of their parasites by increasing the length of the hindgut, and as a consequence, increased crinoids’ ability to absorb nutrients.
Broadening the tools for studying sand fly breeding habitats: A novel molecular approach for the detection of phlebotomine larval DNA in soil substrates.

Abstract Phlebotomine sand flies constitute a group of haematophagous insects of great medical and veterinary importance. Despite the significant knowledge on the biology and behavior of adult sand flies in the wild, there is little information available on the ecology of their larval stages due to difficulties of detecting them in the soil. So far, investigations on sand fly breeding sites have been based on methods to catch emerging adults or on microscopic examination of the soil for the presence of immatures, neither of which is very precise or efficient for studying immatures in the field. Thus, there is a need for a better method to detect, identify and quantify immatures in soil samples. To address this issue we developed a novel molecular genetic approach for the detection of sand fly larval DNA within soil samples. Different numbers of live larvae of Phlebotomus papatasi and P. tobbi (alone or in combination), were mixed with soil and analyzed to identify and quantify the sand flies. By modifying already existing soil DNA extraction protocols in combination with a real-time PCR using species-specific primers, we successfully detected as little as one larva/40 ml of soil. We could also distinguish the two species of sand flies. This method should be very useful for increasing our knowledge of sand fly larval ecology in the field, and thus help develop more efficient, targeted control strategies against Phlebotomus sand flies.
Unusual case of traumatic cervical internal carotid artery dissection presenting as pseudofenestration.

A 58-year-old man with no significant neurological history presented to the emergency department after being struck on the head and the back of the neck several times during an altercation 2 days earlier. At presentation, he had worsening headaches, blurry vision, nausea, vomiting and right-sided
Next generation sequencing data for use in risk assessment

Abstract Next-generation sequencing (NGS) represents several powerful platforms that have revolutionized RNA and DNA analysis. The parallel sequencing of millions of DNA molecules can provide mechanistic insights into toxicology and provide new avenues for biomarker discovery with growing relevance for risk assessment. The evolution of NGS technologies has improved over the last decade with increased sensitivity and accuracy to foster new biomarker assays from tissue, blood, and other biofluids. NGS technologies can identify transcriptional changes and genomic targets with base pair precision in response to chemical exposure. Furthermore, there are several exciting movements within the toxicology community that incorporate NGS platforms into new strategies for more rapid toxicological characterizations. These include the Tox21 in vitro high-throughput transcriptomic screening program, development of organotypic spheroids, alternative animal models, mining archival tissues, liquid biopsy, and epigenomics. This review will describe NGS-based technologies, demonstrate how they can be used as tools for target discovery in tissue and blood, and suggest how they might be applied for risk assessment.
STRUCTURE, FUNCTION, AND REGULATION OF RNA POLYMERASES IN ANIMAL CELLS

ABSTRACT. The mouse plasmacytoma class I, II, and III RNA polymerases have been purified and shown to have distinct structures and functions. The two large molecular weight subunits and some low molecular weight subunits differ between the class I, II, and III enzymes. However, some small subunits appear common to two or to three enzyme classes. α-Amanitin was used to distinguish the endogenous RNA polymerase activities of the class I, II, and III RNA polymerases in isolated nuclei and to show their functions, respectively, in transcription of the genes for the rRNAs, the HnRNAs, and the transfer and 5S RNAs. The cellular activity levels of solubilized RNA polymerases I and III vary with the physiological state of the cell in different mouse tissues, suggesting that the activities of the genes which they transcribe are regulated in part by specific enzyme levels in adult cell types. The increased RNA polymerase I levels in malignant mouse plasmacytoma cells reflect primarily increased enzyme concentrations. The levels of RNA polymerase II in mouse tissues show much less variability suggesting similar rates of HnRNA synthesis in these cell types or cellular excesses of this enzyme. During very early embryonic development in X. laevis all RNA polymerases are present in vast cellular excess and changes in specific gene function are not accompanied by changes in total enzyme levels, suggesting that factors other than enzyme levels are involved in regulating the transcription of all genes during this developmental period.
Children's Critical Reflections on Gender and Beauty through Responsive Play in the Classroom Context.

This qualitative, 8-month study analyzed first-grade children’s playful responses to literature in the classroom context. The broad purpose of this research was to investigate the ways that children construct meaning as they respond to literature through play as a form of reader response. The findings presented in this paper highlight the ways the children interpreted and reflected upon body image and ideals of beauty and the ways in which they enacted/performed gender and gender roles as they responded to literature through play. These findings suggest that, as critical readers of texts, children demonstrate great depth in their explorations and analyses of gender and beauty through their responsive play, that the potential for play as a form of reader response is immense, and that the intersection of responsive play and young children’s critical literacies requires further investigation, in and out of the classroom setting.
Introduction to this special section: Near-surface imaging and modeling

Abstract This special section on near-surface imaging and modeling was intended originally to focus on improving deeper imaging for exploration purposes through more accurate representations of the...
Computer Vision-Based Demersal Fish Length Measurement Technology

This study employed underwater cameras and simple spatial mechanism design to capture real-time demersal fish (e.g., Epinephelus lanceolatus or the so-called giant grouper) image stream. Computer vision-based algorithm processes and analyzes the captured image to locate a fish inside a bounding box. Sophisticated shape analysis and machine learning technique were then applied to the bounding box region of image to identify and extract the shape contour of the fishes on the image. Next, this contour was used to obtain the location and length of the fishes in image coordinates. Then, by using the spatial information provided to the system earlier (calibration), the scaling information (mm/pixel) can be used to transform the image length to physical scale. Beside, the fish activity also can be calculated based on the difference between current and previous image frame. The application of the research results can provide information for understanding the growing trend of fishes for fish farmers. In addition, the conversion of fish length and weight and detection of fish activity performed during feeding can serve as critical references for precise feeding management to mitigate feed waste and impede water quality deterioration.
Improving CT-Derived Fractional Flow Reserve Analysis: A Quality Improvement Initiative.

Objectives The aim of this study was to identify factors and quality improvement strategies to improve coronary computed tomography angiography (CCTA) studies referred for fractional flow reserve derived from CT angiography (FFRCT) analysis. Methods Thirty randomly selected CCTAs were analyzed for quality control. A uniform CCTA protocol was implemented by an in-house steering committee, emphasizing the importance of adequate heart rate control and nitroglycerine usage. Sixty additional randomly selected CCTAs were evaluated for quality at multiple time points during intervention, and FFRCT acceptance rate was analyzed at the conclusion. Results Prior to the implementation of this quality improvement program, our overall institution-specific percent acceptance rate was 76.1% for FFRCT compared to the national average of >95%. Post-intervention, this was improved to an average acceptance rate of 90% for FFRCT analysis. Conclusions Establishment and strict adherence to CCTA imaging protocols with appropriate training and adequate buy-in of CT technologists and nurses is a viable way of improving the quality of imaging and subsequent patient care.
Leptin receptor, a surface marker for a subset of highly engrafting long-term functional hematopoietic stem cells

The hematopoietic system is sustained by a rare population of hematopoietic stem cells (HSCs), which emerge during early embryonic development and then reside in the hypoxic niche of the adult bone marrow microenvironment. Although leptin receptor (Lepr)-expressing stromal cells are well-studied as critical regulators of murine hematopoiesis, the biological implications of Lepr expression on HSCs remain largely unexplored. We hypothesized that Lepr+HSCs are functionally different from other HSCs. Using in vitro and in vivo experimental approaches, we demonstrated that Lepr further differentiates SLAM HSCs into two distinct populations; Lepr+HSCs engrafted better than Lepr-HSCs in primary transplant. Compared to Lepr-LSK cells, Lepr+LSK cells were highly enriched for extensively repopulating and self-renewing HSCs. Molecularly, Lepr+HSCs were characterized by a pro-inflammatory transcriptomic profile enriched for Type-I Interferon and Interferon-gamma (IFN-γ) response pathways, which are known to be critical for the emergence of HSCs in the embryo. We conclude that although Lepr+HSCs represent a minor subset of HSCs, they are highly engrafting cells that possess embryonic-like transcriptomic characteristics, and that Lepr can serve as a reliable marker for functional long-term HSCs, which may have potential clinical applicability.
Software Defined Ambit of Data Integrity for the Internet of Things

On the Internet of Things (IoT), devices do not have the required computational power and storage capacity; and as a result, a variety of IoT devices may be required to outsource sensed or generated data to multiple heterogeneous cloud servers. We posit that it is the Data Owner’s responsibility to verify whether the stored data remain unchanged when the owner or some trusted third party further requires accessing this data. However, the "level" of this verification may be different under different contexts based on the application need. We propose four methods of integrity verification (which we call the ambit of data integrity – ADI) that considers the "toll" in terms of time, storage and communication by enlisting typically disparate integrity approaches under a single orbit. We adapt the notion of contextual integrity, previously used for assessing privacy grants, to extract important parameters required to decide on a suitable data integrity verification process. We propose a secure architecture using an integration of software defined perimeter (SDP) and software defined network (SDN) to perform authentication and gather each partition’s context information for an SDN application to decide the proper integrity verification method that addresses the context requirements. To the best of our knowledge, this is the first time that the scope of integrity (or the data context) is used to determine the required layer of integrity verification in IoT.
Timolol treatment prevents or delays glaucomatous visual field loss in individuals with ocular hypertension: a five-year, randomized, double-masked, clinical trial

A 5-year, randomized, double-masked, clinical trial was conducted to determine whether treatment with topical timolol maleate was effective in preventing or delaying the onset of glaucomatous visual field loss in subjects with ocular hypertension. Sixty-five individuals considered to be at moderate risk for developing open-angle glaucoma were recruited for the study. In each patient, one eye was chosen randomly to receive timolol twice-daily while the fellow eye received diluent (placebo). Timolol administration reduced IOP from baseline in the treated eyes over the course of the study by a mean +/- SD of 4.9 +/- 3.4 mm Hg. Timolol administration also produced a mean +/- SD contralateral reduction of IOP from baseline in the untreated fellow eyes of 2.9 +/- 3.1 mm Hg. The mean +/- SD difference in IOP between the treated and untreated eyes during the study was 2.3 +/- 2.6 mm Hg. Over the course of the study reproducible visual field loss developed in 4 timolol treated eyes and 10 placebo treated eyes (P = .039, McNemar test). Clinical progressive optic disc cupping was noted in four treated and eight untreated eyes (P = .11, McNemar test). In the 42 subjects who completed a minimum 4-year follow-up, baseline and final optic disc photographs were analyzed using a computer image analysis system to determine changes in the area of disc pallor. The mean +/- SD increase in optic disc pallor was 0.86% +/- 2.4% in the timolol treated eyes and 1.80% +/- 3.6% in the placebo treated eyes. This difference was statistically significant (P = .04, paired t-test). This study provides evidence that medical treatment prevents or delays the onset of glaucomatous visual field loss and optic disc damage in individuals with ocular hypertension. The magnitude of the protective effect of timolol was partially obscured by the contralateral reduction of IOP in the placebo treated fellow eyes.
Pyrin-Only Protein 2 Modulates NF-κB and Disrupts ASC:CLR Interactions

NF-κB is pivotal for transactivation of cell-cycle regulatory, cytokine, and adhesion molecule genes and is dysregulated in many cancers, neurodegenerative disorders, and inflammatory diseases. Proteins with pyrin and/or caspase recruitment domains have roles in apoptosis, innate immunity, and inflammation. Many pyrin domain (PYD) proteins modulate NF-κB activity as well as participate in assembling both the perinuclear “apoptotic speck” and the pro-IL1β/IL-18-converting inflammasome complex. “Pyrin-only” proteins (POP) are attractive as negative regulators of PYD-mediated functions and one such protein, POP1, has been reported. We report the identification and initial characterization of a second POP. POP2 is a 294 nt single exon gene located on human chromosome 3 encoding a 97-aa protein with sequence and predicted structural similarity to other PYDs. Highly similar to PYDs in CATERPILLER (CLR, NLR, NALP) family proteins, POP2 is less like the prototypic pyrin and ASC PYDs. POP2 is expressed principally in peripheral blood leukocytes and displays both cytoplasmic and nuclear expression patterns in transfected cells. TNF-α-stimulated and p65 (RelA)-induced NF-κB-dependent gene transcription is inhibited by POP2 in vitro by a mechanism involving changes in NF-κB nuclear import or distribution. While colocalizing with ASC in perinuclear specks, POP2 also inhibits the formation of specks by the CLR protein CIAS1/NALP3. Together, these observations demonstrate that POP2 is a negative regulator of NF-κB activity that may influence the assembly of PYD-dependent complexes.
α1-Adrenergic Receptor Subtypes and Signal Transduction

Abstract Two pharmacologically distinct α 1 -adrenergic receptors (α 1A and α 1B ) have been described in animal and human tissues using selective antagonists and site-directed alkylating agents, whereas three different α 1 -adrenergic receptor subtypes have been cloned (α 1b, α 1c, and α 1a/d ), all of which are members of the G protein linked receptor superfamily. The relationship between native and cloned subtypes was a source of much confusion. However, recently a consensus was reached that the α 1c clone encodes the pharmacological α 1A subtype, and that both the α 1b and α 1a/d clones encode receptors with α 1B -like pharmacology. It is now agreed that the cloned and native receptors should be called α 1a /α 1A , α 1b /α 1B , and α 1d /α 1D , and the α 1c designation has been dropped. Initial studies in isolated smooth muscle tissue suggested that the pharmacologically defined α 1A subtype preferentially activates voltage-gated Ca 2+ influx while the α 1B subtype stimulates formation of inositol (1,4,5) trisphosphate (IP 3 *) and mobilizes intracellular Ca 2+ stores. Although these two signalling pathways are generally associated with different receptor subtypes, further work with both native and recombinant subtypes has provided exceptions to this rule. For example, α 1A -adrenergic receptors are linked to inositol phosphate (InsP) formation and mobilization of intracellular Ca 2+ in human SK-N-MC neuroblastoma cells, and α 1b - and α 1d -adrenergic receptors are linked to voltage-gated Ca 2+ influx in rat medullary thyroid carcinoma (rMTC 6-23) cells. The exact mechanisms by which α 1 -adrenergic receptor subtypes initiate these signals in native cells and tissues are still unclear. When expressed in mammalian cells, all three cloned subtypes can stimulate InsP formation and release intracellular Ca 2+ , however the efficiency with which each subtype couples to this signalling system appears to vary (α 1a > α 1b > α 1d ). No model system is currently suitable for similar studies examining α 1 -adrenergic receptor modulation of voltagegated Ca 2+ influx in response to transfection of the cloned subtypes. These subtypes also activate other second messenger systems following transfection, including phospholipase A 2 (PLA 2 ) and adenylate cyclase. Use of inducible vectors to titrate the density of each cloned subtype in transfected cell lines allows direct determination of the efficacy of each subtype in activating second messenger responses.
Effect of structural modifications on 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione-induced hepatotoxicity in Fischer 344 rats

Glitazones, used for type II diabetes, have been associated with liver damage in humans. A structural feature known as a 2,4-thiazolidinedione (TZD) ring may contribute to this toxicity. TZD rings are of interest since continued human exposure via the glitazones and various prototype drugs is possible. Previously, we found that 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT) was hepatotoxic in rats. To evaluate the importance of structure on DCPT toxicity, we therefore studied two series of analogs. The TZD ring was replaced with: a mercaptoacetic acid group {[[[(3,5-dichlorophenyl)amino]carbonyl]thio]acetic acid, DCTA}; a methylated TZD ring [3-(3,5-dichlorophenyl)-5-methyl-2,4-thiazolidinedione, DPMT]; and isomeric thiazolidinone rings [3-(3,5-dichlorophenyl)-2- and 3-(3,5-dichlorophenyl)-4-thiazolidinone, 2-DCTD and 4-DCTD, respectively]. The following phenyl ring-modified analogs were also tested: 3-phenyl-, 3-(4-chlorophenyl)-, 3-(3,5-dimethylphenyl)- and 3-[3,5-bis(trifluoromethyl)phenyl]-2,4-thiazolidinedione (PTZD, CPTD, DMPT and DFMPT, respectively). Toxicity was assessed in male Fischer 344 rats 24 h after administration of the compounds. In the TZD series only DPMT produced liver damage, as evidenced by elevated serum alanine aminotransferase (ALT) activities at 0.6 and 1.0 mmol kg(-1) (298.6 ± 176.1 and 327.3 ± 102.9 Sigma-Frankel units ml(-1) , respectively) vs corn oil controls (36.0 ± 11.3) and morphological changes in liver sections. Among the phenyl analogs, hepatotoxicity was observed in rats administered PTZD, CPTD and DMPT; with ALT values of 1196.2 ± 133.6, 1622.5 ± 218.5 and 2071.9 ± 217.8, respectively (1.0 mmol kg(-1) doses). Morphological examination revealed severe hepatic necrosis in these animals. Our results suggest that hepatotoxicity of these compounds is critically dependent on the presence of a TZD ring and also the phenyl substituents.
Does Job Coaching Work?: Evidence from South Carolina

Providing employment-related services, including supported employment through job coaches, to individuals with developmental disabilities has been a priority in federal policy for the past twenty years starting with the Developmental Disabilities Assistance and Bill of Rights Act in 1984. We take advantage of a unique panel data set of all clients served by the SC Department of Disabilities and Special Needs between 1999 and 2005 to investigate whether job coaching leads to stable employment in community settings. The data contain information on individual characteristics, such as IQ and the presence of emotional and behavioral problems, that are likely to affect both employment propensity and likelihood of receiving job coaching. We control for unobserved heterogeneity and endogeneity using fixed effects and instrumental variable models. Our results show that unobserved individual characteristics and endogeneity strongly bias naive estimates of the effects of job coaching. However, even after controlling for these, an economically and statistically significant effect remains.
The viability of the cast-off menstrual endometrium.

Abstract The histogenesis of endometriosis is still under discussion, although Sampson's implantation theory has been widely accepted in this country. Some experimental work has been advanced to support Sampson's hypothesis but evidently no one has shown definitely that the endometrium exfoliated at menstruation is capable of survival and growth. The purpose of this communication is to show that under some conditions cast-off menstrual endometrium is viable in tissue culture preparations. A contraceptive diaphragm was inserted in the vagina on the second day of menstrual bleeding and left in place from eight to twelve hours. After removal the diaphragm was placed in a sterile Petri dish and the collected fluid was immediately examined for bits of tissue. In two out of seven instances sufficient material was obtained for tissue culture explantation.
On Packing Splittable Items with Cardinality Constraints

This paper continues the study of the the allocation of memory to processors in a pipeline problem. This problem can be modeled as a variation of bin packing where each item corresponds to a different type and the normalized weight of each item can be greater than 1, which is the size of a bin. Furthermore, in this problem, items may be split arbitrarily, but each bin may contain at most k types of items, for any fixed integer k ≥ 2. The case of k = 2 was first introduced by Chung el al. who gave a 3/2-approximation asymptotically. In this paper, we generalize the result of Chung et al. to higher k. We show that NEXT FIT gives a \(\left(1+\frac 1 k\right)\)-approximation asymptotically, for k ≥ 2. Also, as a minor contribution, we rewrite the strong NP-hardness proof of Epstein and van Stee for this problem for k ≥ 3.
Apyrase Activity of the Mammary Gland

Summary An enzymatic hydrolysis of ATP by preparations of lactating rat mammary gland has been observed. The action was a linear function of time and protein concentration. Added magnesium ions depressed apyrase activity of homogenates made with phosphate buffer. In contrast, the addition of magnesium to water homogenates produced a stimulation. Fluoride inhibited the apyrase action of either preparation. About 45% of the apyrase was extracted with water. The enzymatic activity of this extract was stimulated with either calcium or magnesium ions. The remaining apyrase was associated with cellular debris of the mammary tissue. Variation in the stimulation with ions suggested the presence of multiple enzymes. The enzymes in both fractions removed at least two phosphates from ATP.
Changes in Cerebral Oxygen Tension and Red Cell Content on Sensory Stimulation

According to current studies, the cerebral cortical circulation shows well developed “oxygen autoregulation” to the extent that local increases in oxygen consumption in the sensory cortex produced by peripheral stimulation are accompanied by increases in blood flow so finely adjusted that no local changes in Po2 can be detected (Leniger-Follert and Hossmann, 1979). If indeed there is no local fall in Po2, then hypoxia cannot be the signal for increased blood flow, and it is necessary to postulate some other mechanism similar to the old “axon reflex” to account for this type of autoregulation. However, if the signal involves a change in Po2 in a very small volume, perhaps a single neurone and occurring for a period of less than one second, then Polarographic electrodes might not have sufficient temporal and spatial resolution to measure this. With our T. V. system we can measure changes in oxygen tension and microregional red cell mass in cylinders of tissue of 10 um diameter and approximately 150 urn deep with a time resolution of 33 msecs.
Laboratory Diagnostics Market in East Africa: A Survey of Test Types, Test Availability, and Test Prices in Kampala, Uganda

Background Diagnostic laboratory tests are routinely defined in terms of their sensitivity, specificity, and ease of use. But the actual clinical impact of a diagnostic test also depends on its availability and price. This is especially true in resource-limited settings such as sub-Saharan Africa. We present a first-of-its-kind report of diagnostic test types, availability, and prices in Kampala, Uganda. Methods Test types (identity) and availability were based on menus and volumes obtained from clinical laboratories in late 2011 in Kampala using a standard questionnaire. As a measure of test availability, we used the Availability Index (AI). AI is the combined daily testing volumes of laboratories offering a given test, divided by the combined daily testing volumes of all laboratories in Kampala. Test prices were based on a sampling of prices collected in person and via telephone surveys in 2015. Findings Test volumes and menus were obtained for 95% (907/954) of laboratories in Kampala city. These 907 laboratories offered 100 different test types. The ten most commonly offered tests in decreasing order were Malaria, HCG, HIV serology, Syphilis, Typhoid, Urinalysis, Brucellosis, Stool Analysis, Glucose, and ABO/Rh. In terms of AI, the 100 tests clustered into three groups: high (12 tests), moderate (33 tests), and minimal (55 tests) availability. 50% and 36% of overall availability was provided through private and public laboratories, respectively. Point-of-care laboratories contributed 35% to the AI of high availability tests, but only 6% to the AI of the other tests. The mean price of the most commonly offered test types was $2.62 (range $1.83–$3.46). Interpretation One hundred different laboratory test types were in use in Kampala in late 2011. Both public and private laboratories were critical to test availability. The tests offered in point-of-care laboratories tended to be the most available tests. Prices of the most common tests ranged from $1.83-$3.46.
Apoptotic Triggers Initiate Translocations within the MLL Gene Involving the Nonhomologous End Joining Repair System

Translocations involving the MLL gene at 11q23 are a frequent finding in therapy-related leukemia and are concentrated within a short, 8.3-kb tract of DNA, the breakpoint cluster region. In addition, a specific site adjacent to exon 12 within this region of MLL is cleaved in cells undergoing apoptosis. We show here, using human TK6 lymphoblastoid cells, that irradiation and the apoptotic trigger anti-CD95 antibody are each able to initiate translocations at the MLL exon 12 cleavage site. The translocation junctions produced contain regions of microhomology consistent with operation of the nonhomologous end joining (NHEJ) repair process. Participation of the NHEJ process is supported by the identification of the NHEJ component DNA-PKcs at the site of apoptotic cleavage. Suppression of DNA-PKcs function by the phosphatidylinositol 3-kinase inhibitor wortmannin compromises DNA end joining, increases site-specific cleavage within MLL, and eliminates MLL-restricted translocations. We propose that activation of apoptotic effector nucleases alone is sufficient to generate proleukemogenic translocations and raises the possibility that some of these may persist in cells that evade apoptotic execution and survive.
Random element method for numerical modeling of diffusional processes

The random element method is a generalization of the random vortex method that was developed for the numerical modeling of momentum transport processes as expressed in terms of the Navier-Stokes equations. The method is based on the concept that random walk, as exemplified by Brownian motion, is the stochastic manifestation of diffusional processes. The algorithm based on this method is grid-free and does not require the diffusion equation to be discritized over a mesh, it is thus devoid of numerical diffusion associated with finite difference methods. Moreover, the algrithm is self-adaptive in space and explicit in time, resulting in an improved numerical resolution of gradients as well as a simple and efficient computational procedure.
Structural study by solid-state 71Ga NMR of thin film transistor precursors

Solid-state 71Ga NMR was used to investigate the structures of several heterometallic Group 13 hydroxo-aquo clusters, [Ga13−xInx (μ3-OH)6(μ2-OH)18(H2O)24](NO3)15 which are envisioned for thin film transistors. The characterization of these clusters in the solid state provides additional information in understanding the synthesis, structure and speciation of these precursors for high-quality, ultrasmooth thin films. Yet important structural information regarding these clusters – including the exact composition, isomeric structure, and coordination environments – were unknown prior to this precise NMR spectroscopy study. These molecular species, termed “Ga13−xInx”, contain three types of six-coordinate metal sites, with bridging OH− groups and H2O as capping ligands, and we report results on Ga7In6, Ga8In5, Ga10In3, Ga11In2, Ga12In1, and Ga13. Utilizing two magnetic fields (13.9 T and 21.1 T), the solid-state NMR spectra were interpreted in conjunction with computational modeling (using CASTEP) and simulation of spectral lineshapes (using Dmfit). The metal sites are best represented as distorted octahedra, and they exhibit a range of quadrupolar couplings and asymmetry parameters, which can be addressed using longitudinal strain analysis. Until now, there has been speculation about the sites for transmetallation within the synthetic cluster community. Here, we show that Ga NMR is a powerful technique to monitor the transmetallation of In for Ga in the Ga13−xInx clusters, specifically substituting in the “outer ring” sites, and not the “core” or “middle ring”.
The small intestinal basic electrical rhythm (slow wave) frequency gradient in normal men and in patients with a variety of diseases

Summary We used an intraluminal salt-bridge electrode to record the small intestinal slow wave or basic electrical rhythm (BER) at many levels of the intestine. We found a descending BER frequency gradient in 12 normal subjects and in 13 patients with a variety of diseases. The descending gradient was stepwise in some normal subjects but linear in others. The data from normal subjects have bfeen pooled to establish a range of normal values. The mean frequency at the ligament of Treitz was 11.80 cycles per min (sd 0.32); at 225 to 239 cm below the incisor teeth it was 9.39 cycles per min (sd 0.18). Abnormal gradients were found in patients with hyperthyroidism and hypothyroidism, and in a patient with hyperparathyroidism, gastric hypersecretion, and diarrhea. The form and magnitude of this gradient may be important determinants of small intestinal motor function.
The Cranial Nerves

There are 12 pairs of cranial nerves, and they originate from the brain and upper spinal cord and innervate the special sense organs in the head (eye, ear, nose, and taste buds), the skin over the face and neck, and muscles that permit us to speak, eat, turn our head, and produce facial expressions. These cranial nerves also provide parasympathetic innervation to the eye (III) and glands in the head and neck (VII, IX and X) and the X cranial nerve, the vagus innervates the skeletal muscles in the larynx that produce speech, and also innervate the organs of the cardiovascular system, pulmonary system, GI system, and urogenital systems.
Liver Regeneration: An Introduction

Liver is known for its remarkable ability to regenerate upon injury, either induced by surgical resection or chemical exposure or ischemia/reperfusion. The investigations in the mechanisms of liver regeneration have been at the center of liver biology for the last eight decades. Whereas we now know a great deal about the mechanisms that initiate liver regeneration and relatively less about the mechanisms of termination of regeneration, many more questions remain. Liver regeneration is an ever-evolving enigma for a liver researcher. This book is an effort to bring together the state-of-the art information on liver regeneration to the readers, and this chapter will provide an overview of liver regeneration research.
The effects of feedback on task group behavior: A review of the experimental research

Abstract Experimental research on the cueing and motivational effects of feedback on behavior in task groups is reviewed. The impact of feedback is seen as contingent on several factors including the nature of the feedback information (including level of aggregation, task/process focus, and evaluative content), the process of using feedback, individual differences among group members, and group task structure. Feedback is seen as contingently leading to affective and cognitive outcomes, including level of attraction to the group, pride in the group, motivation, defensive feelings, and acceptance of group problems. Feedback is also seen as potentially leading to behavioral outcomes such as task performance, membership behavior, and coping behavior. A preliminary model of the impact of feedback is constructed.
Minority Organ Donation: The Power of an Educated Community

Background In 1978 in Washington, DC, we became aware of the scarcity of minority donors, especially African Americans. Study Design From then until now, 4 decades later, we have been involved in a grass roots effort emphasizing community education and empowerment combined with the use of mass media, which has increased minority donation rates exponentially. This program was initiated with a $500 grant from Howard University and was subsequently funded by National Institutes of Health grants and other funding totaling more than $10 million between 1993 and 2008. Results Between 1990 and 2008, minority donations percentages have doubled (15% to 30%). African-American organ donors per million (ODM) have quadrupled from 8 ODM to 53 ODM between 1982 and 2008. Conclusions The investment of $10 million may seem substantial when we look at the cost-to-benefit ratio associated with the cost savings of $135,000 per donor. But it is small when compared with the more than $200 million saved by kidney donors alone, which is associated with the expected increase in the percentage of minority donors to 35% by 2010, or the equivalent of 1,750 minority donors.
The Forum: Intrusive Group Advising for the Probationary Student

“The Forum” is a group advising effort initiated to provide a more intrusive advising format for freshmen and sophomores who were on probation and reluctant to meet with their advisors. The Forum helped probationary students better understand the skills needed to maintain academic excellence. The results of the group activity suggest that it has been a significant retention tool.