cssi/SciSciGPT-SciSciNet huggingface dataset:
TU-A-BRC-03: A Novel Technique to Use CT Images for in Vivo Detection and Quantification of the Spatial Distribution of Radiation-Induced Damage to the Esophagus

Purpose: Current dose‐response studies use symptom endpoints (e.g. grade 2 esophagitis) as substitutes for data about actual tissue damage. CTimaging could provide objective spatial data on radiation‐induced damage to the esophagus in lungcancer patients. Methods: Deformable image registration techniques were used to register weekly CTimages taken during radiotherapytreatment with the original planning CTimage. The esophagus contours were automatically mapped. The impact of day‐to‐day variations in the degree of collapse of the esophagus was reduced by using thresholding to remove air from the esophagus. The cross‐sectional area of the esophagus was then calculated for each CT slice. The results from surrounding slices were averaged to reduce apparent abrupt steps in cross‐ sectional area between adjacent CT slices caused by varying undulations/folds in the esophagus. Finally, the relative expansion of the esophagus was calculated as the ratio of the cross‐sectional area of the esophagus in the weekly CT (minus air) to that on the corresponding CT slice in the planning image. This technique was applied to weekly CTimages of 5 lungcancer patients (35 CTs), with acute esophageal toxicity grade 0 to 3. For these patients we examined (1) The correlation between the relative expansion of the esophagus and the clinical toxicity grade, and (2) the correlation between the spatial dose distribution and the spatial variation in esophageal expansion. Results: The average maximum esophageal expansions for toxicity grades 0, 2, and 3 were 1.2, 1.7 and 1.9, respectively. The difference between grade 2 and 0 was statistically significant (p=0.008). The location and degree of variation of the changes in esophagus cross‐section were found to be related to the high dose given at the same location. Conclusion: Radiation‐induced injury to the esophagus can be detected in CTimages. This has potential for use in dose‐response studies.
Cost-reducing protein production and delivery for sexually transmitted disease prevention

Discusses producing vaccines and antibody proteins from plants with "green vaccines". In passive immunization, antibodies are produced outside the body and manufactured to be active against a specific pathogen (such as herpes virus). With active immunization, one of the major obstacles to cost-reduction is the identification of inexpensive but effective methods for converting the plant cells or tissues into an orally active formulation.
Financial Regionalism in East Asia: Regional Surveillance Cooperation and Enforcement Problem*

Since the Asian financial crisis in 1997, many financial cooperative arrangements among the ASEAN+3 countries have been formed to facilitate policy coordination and to prevent another crisis from adversely affecting East Asia. This paper focuses on regional surveillance cooperation, which has been regarded as a pre-requisite for deeper financial cooperation including bilateral swap arrangements under Chiang Mai Initiatives. Although East Asian states have acknowledged the significance of the regional surveillance mechanism in the midst of the crisis, which could facilitate information sharing and frank discussion of potential risks in the region, it showed little progress until very recently. What explains this unsuccessful regional surveillance cooperation given the initial enthusiasm and widely-acknowledged need for it? This article takes seriously domestic implementation capacities and enforcement problems on a regional level. It argues that member states are discouraged from exchanging frank views on other states' financial conditions because they expect that even non-intrusive policies would not necessarily be successfully implemented in those countries where sufficient domestic regulatory and supervisory capacities are lacking. Moreover, regional surveillance cooperation had troubles in enforcement: the norm of non-interventionism, lack of independent regional agencies and staff that could monitor and enforce compliance, and lack of transparency. In these circumstances, current surveillance mechanisms are likely to become a stumbling block for deeper financial integration in East Asia until serious efforts are made to tackle problems with enforcement.
Screening for Therapeutic Targets of Vorinostat by SILAC-based Proteomic Analysis in Human Breast Cancer Cells

Histone deacetylases (HDACs) play critical roles in silencing tumor suppressor genes. HDAC inhibitors reactivate tumor suppressor genes and inhibit tumor cell growth in vitro and in vivo, and several HDAC inhibitors are currently being evaluated in clinical trials for cancer therapy. A comprehensive analysis of proteins regulated by HDAC inhibitors would enhance our ability to define and characterize their essential therapeutic targets. Here, we employed stable isotope labeling with amino acids in cell culture-based quantitative proteomics to identify acetylated proteins in human breast cancer cells. Treatment with the clinically relevant HDAC inhibitor, suberoylanilide hydroxamic acid (vorinostat), induces lysine acetylation of 61 proteins in MDA-MB-231 human breast cancer cells. Suberoylanilide hydroxamic acid not only induces lysine acetylation in chromatin-associated proteins, but also acetylates previously unrecognized nonhistone proteins, including transcriptional factors and regulators, chaperones, cell structure proteins, and glycolytic enzymes in a time-dependent manner. Knowledge of the full repertoire of acetylated proteins will provide a foundation for further defining the functions of HDACs in cancer cells.
Monitoring, Analysis and Diagnosis of Distributed Processes with Agent-Based Systems*

Multiagent systems provide a powerful framework for developing real-time process supervision and control systems for distributed and networked processes by automating adaptability and situation-dependent rearrangement of confidence to specific monitoring and diagnosis techniques. An agent-based framework for monitoring, analysis, diagnosis, and control with agent-based systems (MADCABS) is developed and tested by using detailed models of chemical reactor networks. MADCABS is composed of three main hierarchical layers, the physical communication layer, the supervision layer and the agent management layer. The supervision layer consists of agents and methods for data preprocessing, process monitoring, fault diagnosis, and control. The agent management layer conducts the assessment of agent performances to assign the priorities for selecting the most useful methods of process supervision for specific types of situations. The paper illustrates the operation of MADCABS for monitoring and fault detection.
Statistical Nonrecursive Spatial Filter For Processing Of Infrared Mosaic Sensor Images

Statistical nonrecursive spatial filters are used to process noisy infrared mosaic sensor images for background clutter suppression and target detection. It is assumed that the clutter can be modeled as an additive, spatially correlated noise and described by its auto-correlation function. The filter is designed to estimate the targets and also to suppress the clutter based on "a priori" knowledge of the statistical property of the noise. Square shaped spatial filters are studied. Signals of all pixels in the filter are linearly weighted and summed to estimate the signal at the center of the filter. The weighting coefficients are designed by a minimization of mean squared error procedure. Target detection is accomplished by thresholding after the spatial filtering. Furthermore, this filter can also be designed to accomplish discrimination of point and line targets simultaneously with the enhancement of target to clutter ratio. Filter results based on computer simulation are shown.© (1978) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Elevation of internal auditory canal pressure by vestibular schwannomas.

Objective The exact mechanism of hearing loss, the most common presenting symptom in patients with vestibular schwannomas, remains unclear. To test whether increased pressure in the internal auditory canal from tumor growth is responsible for this clinical finding, the intracanalicular pressure in patients harboring these tumors was measured. Study design Prospective study. Setting Tertiary referral hospital. Patients Fifteen consecutive patients undergoing a retrosigmoid approach for resection of vestibular schwannomas were included in the study. Intervention The intracanalicular pressure in every patient was measured by introducing a pressure microsensor into the internal auditory canal. The pressure readings, which were performed before tumor resection, were then correlated with tumor size and respective preoperative hearing status. Results Placement of the pressure monitor into the internal auditory canal revealed a biphasic waveform in every patient. Whereas the mean intracanalicular pressure was 20 mm Hg, there was significant variability among patients (range, 1-45 mm Hg). The intracanalicular pressure directly correlated with the amount of tumor in the internal auditory canal (r > 0.63, p 0.075). Furthermore, eight patients with class A preoperative hearing (American Academy of Otolaryngology-Head and Neck Surgery classification) had lower intracanalicular pressures than did five patients with class B hearing (16 +/- 5 vs. 28 +/- 4). Although this observation suggested an inverse correlation between the intracanalicular pressure and hearing function, the difference between the two groups was not statistically significant (p = 0.14). Conclusion Pressure on the cochlear nerve as a result of tumor growth in the internal auditory canal may be responsible for hearing loss in patients with vestibular schwannomas. Modification of surgical techniques to address the elevated intracanalicular pressure may be beneficial in improving hearing preservation in these patients.
Estimation of inhibitory effects of hemicellulosic wood hydrolysate inhibitors on PHA production by Burkholderia cepacia ATCC 17759 using response surface methodology

Sugar maple hemicellulosic hydrolysate was utilized as a renewable feedstock for polyhydroxyalkanoates production by Burkholderia cepacia ATCC 17759. To estimate inhibitory effects of the hydrolysate, response surface methodology was utilized to analyze cell growth and PHA accumulation in the presence of multiple inhibitors. Mixture design was employed to study the correlation between the proportion of phenolics and total inhibition. The resultant models (R(2) as 92.42% and 93.14% for cell growth and PHA production, respectively) indicated syringic acid was the most inhibitory among three phenolics and synergistic inhibition was observed for the combinations of vanillin/syringic acid and vanillic acid/syringic acid. When furfural, levulinic acid, and acetate were also present during the fermentation, central composite design was employed. The regression model using 48 h cell growth as the response surface (R(2)=87.82%) showed acetate was the most inhibitory. Additionally, strong synergistic effects were observed for the combinations of acetate/phenolics and levulinic acid/furfural.
Progress on the development of multiwavelength imaging pyrometer

Experimental Multi-wavelength Imaging Pyrometer (M-WIP) is presented for remote sensing of temperature profiles of targets with unknown spectrally varying emissivity. A software package was developed for calibration and real-time M-WIP measurements. An experimental 7-filter line-sensing M- WIP system was implemented with a 320 X 122-element PtSi IR-CCD imager and an assembly of narrow-band striped IR filters in the spectral range from 1797 nm through 4512 nm. The M-WIP system was calibrated against a commercial blackbody source over temperature range from 450 degree(s)C to 950 degree(s)C. The signal processing included background subtraction, compensation for variation of dark current with detected signal and correction for non-linearities of IR imager response. Initial M-WIP measurements demonstrated real-time temperature resolution (Delta) T of +/- 1 degree(s)C for blackbody target over temperature range from 600 degree(s)C to 900 degree(s)C. Temperature resolution of +/- 4 degree(s)C was demonstrated for the blackbody source viewed through the double polished silicon wafer with unknown spectral transmissivity in the temperature range from 500 degree(s)C to 950 degree(s)C.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Segregation of two spectrin forms in the chicken optic system: A mechanism for establishing restricted membrane-cytoskeletal domains in neurons

Abstract The chicken optic system contains a brain-specific form of spectrin (αγ-spectrin or fodrin) as a major membrane-associated, axonally transported cytoskeletal protein. We show here that the chicken optic system also contains an erythrocyte-specific form of spectrin (αβ′β-spectrin), which has a more restricted distribution; it is confined to the plasma membrane of dendrites and cell bodies of retinal ganglion cells, is absent from the optic nerve fibers, and is not axonally transported from the retina into the optic nerve. During development of the optic system, the expression of αγ-spectrin is constitutive in all cell types. On the other hand, the accumulation of αβ′β-spectrin is detected in only the ganglion cells, and at a time in development which coincides with the phase of synaptogenesis. These results indicate the existence of a developmentally regulated mechanism that topologically segregates the erythroid and brain forms of spectrin from each other, and the former from axonal transport, and suggest that erythroid spectrin may be involved in establishing restricted membrane-cytoskeletal domains in neurons during synaptogenesis, and maintaining them in the adult cell.
Density correction for a boiling liquid hydrogen target

Abstract A method to determine the density correction of a boiling liquid target is presented. The correction is determined from the time required to empty the target and from the bubble velocity. The case of a cylindrical liquid hydrogen target is evaluated.
Effect of Prolactin and 5-Bromo-2-thienyl-ethyl Ketone Thiospmicarbazone on Ovarian Progestin Levels in the Rat

The effect of prolactin and of 5- bromo-2-thienyl-ethyl ketone thiosemicarbazone (70026) on the ovarian progestin levels and ovarian, uterine and body weights of rats was studied to determine the mode of action of 70026 in inhibiting the deciduomal reaction and pregnancy. Hypophysectomized and hypophysectomized- prolactin-treated rats that were injected with 70026 for 5 days, beginning on the day of estrus, served as the experimental subjects for this study. The study indicated that 70026 siglificantly reduced the mean uterine weight and total ovarian content and concentration of both 20α-hydroxypregn-4-en-3-one (20α-OH-P) and progesterone. It had no significant effect, however,however, on relative uterine weight (uterine weight/ final body weight), relative ovarian weight ovarian weight/final body weight), mean ovarian weight or change in body weight. Prolactin significantly increased the relative and mean uterine weights and the total ovarian content and concentration of 20α-OH-P and progesterone. Prola...
Pulling the strings: Effects of friend and parent opinions on dating choices

The current study examined how dating choices are affected when individuals are faced with social network opinions that are in agreement or disagreement about the quality of potential dates. In a virtual dating game paradigm, participants spoke to 2 potential romantic partners online and received positive and/or negative feedback ostensibly from their friend and parent about 1 of the partners. The study employed a 2 (parent opinion: approve, disapprove) × 2 (friend opinion: approve, disapprove) × 2 (interaction partner: evaluated target, control target—within subjects) mixed factorial design. Friend opinion influenced who the participants liked, whereas parental opinion was influential when participants relied on their parent for more resources than their friend. In the end, though, only friend opinion predicted dating choice.
Timing of mitotic chromosome loss caused by the ncd mutation of Drosophila melanogaster.

We studied the timing of mitotic loss of maternally and paternally derived chromosomes among the progeny of Drosophila melanogaster females homozygous for an amorphic mutation in ncd, a gene encoding a kinesin-like protein. In order to determine the division at which chromosome loss occurs, we estimated the fraction of XO nuclei resulting from X chromosome loss by scoring the phenotype of 47 adult cuticular landmarks in 160 XX–XO mosaics (gynandromorphs) derived from maternal X chromosome loss, and 33 gynandromorphs derived from paternal X chromosome loss. The results show that while most of the mitotic loss of maternally derived chromosomes occurs at the first cleavage division, the mitotic loss of paternally derived chromosomes occurs only at the second and later divisions. This means that paternally derived chromosomes are immune from the effects of ncd prior to karyogamy, which occurs after the first cleavage division. We discuss the implications of these results for the function of the ncd gene product and for other kinesin-like proteins in Drosophila. © 1992 Wiley-Liss, Inc.
Comparison between structural properties of bulk GaN grown in liquid Ga under high N pressure and GaN grown by other methods

In this paper defects formed in GaN grown by different methods are reviewed. Formation of particular defects are often related to the crystallographic direction in which the crystals grow. For bulk crystals the highest growth rates are observed for directions perpendicular to the c-axis. Threading dislocations and nanopipes along the c-axis are not formed in these crystals, but polarity of the growth direction plays a role concerning defects that are formed and surface roughness. For growth of homoepitaxial layers, where growth is forced to take place in the c-direction threading dislocations are formed and their density is related to the purity of constituents used for growth and to substrate surface inhomogeneities. In heteroepitaxial layers two other factors: lattice mismatch and thermal expansion mismatch are related to the formation of dislocations. Doping of crystals can also lead to the formation of defects characteristic for a specific dopant. This type of defects tends to be growth method independent but can depend on growth polarity.
Survey of materials for high-temperature bearing and sliding applications

A review of materials which have properties likely to be useful in sliding-contact applications is presented. Wear and friction data for these materials are included along with discussion, conclusions, and a bibliography of 118 references. (J.R.D.)
Effects of intertrial interval and exteroceptive feedback duration on discriminative avoidance acquisition in the gerbil

A series of studies of shuttlebox-avoidance learning in the gerbil evaluated the efficacy of an exteroceptive feedback stimulus (FS). Experiment 1 assessed the relative effectiveness of a FS at 30- and 90-sec intertriai intervals (ITIs), and found that the FS and warning signal termination contingencies were additive sources of avoidance reinforcement; i.e., they produced “supernormal acquisition” at the short ITI, but not at the 90-sec ITI. The effectiveness of a FS at the 30-sec ITI was further explored in Experiments 2 and 3, in which FS duration was varied in delayed and trace avoidance conditioning, respectively. In both studies, a FS facilitated acquisition but FS duration was not a critical determinant of performance. These results were interpreted in terms of an expectancy account of the informational value of a FS, and the problem of experimentally distinguishing between cognitive and inhibition-of-fear accounts of avoidance learning was discussed.
Processor interconnection networks from Cayley graphs

Abstract Cayley graphs of groups are presently being considered by the computer science community as models of architectures for large scale parallel processor computers. In the first section of this paper we discuss Cayley graphs and show how they may be used as a tool for the design and analysis of network architectures for these types of computers. Observing that routing on a Cayley graph is equivalent to a certain factoring problem in the associated group, we have been able to use a known powerful factoring technique in computational group theory to produce a fast efficient routing algorithm on the associated Cayley graph. In the second section of this paper we present this work. This research can be regarded as a first attempt to find general purpose routing algorithms for interconnection networks. Believing that average diameter of a network for a large scale MIMD machine is the predominant factor in determining network performance, we designed Cayley graphs to be used in a special study performed at the Supercomputing Research Center (SRC). The importance of the average diameter in determining network performance was supported by the fact that the graphs found by us had the smallest average diameter and outperformed all other graphs evaluated in the study. In fact, before being driven into saturation, one of our graphs sustained 9.4% more network traffic than the next best candidate, a butterfly architecture, and 74.3% better than the bench mark 2-d mesh. The last section of our paper is devoted to this work. This paper is divided into three sections. In the first section we discuss Cayley graphs and show how they may be used as a tool for the design and analysis of network architectures for parallel computers. In the second section we present our research on the routing problem. This research can be regarded as a first attempt to find general purpose routing algorithms for interconnection networks. In the last section we present some evidence that average diameter of a network for a large scale MIMD machine is the predominant factor in determining network performance.
The French Horror Film Martyrs and the Destruction, Defilement, and Neutering of the Female Form

Abstract Pascal Laugier's Martyrs, because of both its controversy and the power of its narrative, is deserving of critical attention. This article approaches the film from a two-pronged analysis, one that looks both at the external ramifications of the film on its audience and then at the symbolism of the story itself.
Detour learning in the chick: effect of reserpine administered during embryonic development.

Chicks hatched from eggs injected with reserpine prior to incubation showed impaired performance in detour learning between 7 and 17 days of age, although locomotor activity and brainstem catecholamine levels were not significantly different from controls at 18 days. Day-old chicks injected with the same amount of drug showed no significant depletion of brainstem catecholamines 7 days later, supporting the possibility that behavioral effects were due to exposure to the drug during embryogenesis.
In vivo selectivity of a selective cyclooxygenase 2 inhibitor in the oral surgery model

Objective Prostanoids formed by cyclooxygenase play an important role in pain and the induction of inflammation. It is generally believed that COX-1 is constitutively expressed, whereas COX-2 is primarily inducible during inflammation. This study examined the in vivo selectivity of celecoxib, a COX-2 inhibitor, and evaluated whether estimates of selectivity that are based on in vitro and ex vivo analyses are reliable indicators ofin vivo selectivity. Methods Subjects (103 outpatients undergoing surgical removal of two impacted mandibular third molars) received either 200 mg celecoxib, 600 mg ibuprofen, or placebo 8hours before surgery and a second dose 1 hour before surgery. After surgery, microdialysis probes were placed in the surgical sites for collection of inflammatory transudate. Samples were collected every 20 minutes and pain intensity was estimated concurrently with avisual analog scale and a categorical rating scale for up to 4 hours after surgery. Results A significant analgesic effect (P < .01, compared with placebo) was shown for both drugs, with the efficacy of celecoxib being intermediate betweenibuprofen and placebo. A similar relationship was observed for the suppression of prostaglandin E2 (a product of both isoforms) at time points consistent with COX-2 expression (P < .001). Ibuprofen consistently suppressed thromboxane B2 (a product of COX-1) levels at all time points (P < .05), whereas the effect of celecoxib did not differ from that of placebo. Conclusions The suppression of products of COX-2 coincident with pain suppression and the absence of COX-1 inhibition suggest that celecoxib is a relatively selective COX-2 inhibitor in vivo. Clinical Pharmacology & Therapeutics (2002) 72, 44–49; doi: 10.1067/mcp.2002.125560
Effects of fertility on biomass, phytotoxicity, and allelochemical content of cereal rye

Studies were conducted to evaluate biomass production, tissue phytotoxicity, and allelochemical content of rye (Secale cereale L.) shoots grown in three fertility regimes (low, medium or high) in the greenhouse. Wheeler rye or a polyculture of rye and hairy vetch (Vicia villosa Roth) grown with high fertility produced the greatest biomass (78.7 and 82.7 g), with the lowest root-to-shoot ratio (0.22 and 0.43) produced in the high-fertility treatments. The polyculture treatment grown with low fertility had a greater proportion of hairy vetch (18%) than when grown with high fertility (6%). Rye shoot residue phototoxicity was affected by fertility regime. Radicle elongation of cress (Lepidium sativum L.) and barnyardgrass [Enchinochloa crus-galli (L.) Beauv. I was inhibited by rye shoot residues in a modified Parker bioassay. Rye shoot residue grown with low fertility was less inhibitory to cress radicle elongation than rye residue from the medium- or high-fertility regimes. Extracts of dried rye shoots grown with high fertility were less inhibitory than extracts from other fertility regimes. The concentrations of ether extracts of rye causing 50% inhibition (I50) of cress radicle elongation were between 125 and 276 µg/ml for greenhouse-grown and 60 and 138 µg/ml for the field-grown rye shoots. The major phytotoxic compounds in the rye shoot extracts were identified as DIBOA and BOA. The concentration of DIBOA in the greenhouse-grown rye shoots ranged between 128 and 423 µg/g while BOA concentration ranged between 2.5 and 31 µg/g. DIBOA and BOA levels were lowest in rye shoots grown with high fertility. Correlations between rye shoot biomass, DIBOA and BOA concentration, and cress barnyardgrass radicle length were significant.
Salience and relativity in classification

In response to arguments that the most basic or salient level of classification for any given domain is largely a reflection of objective reality and, therefore, consistent across human populations, this paper argues that the salience of categories within a given semantic domain is primarily a function of man's attention to or indifference toward the membership of the domain concerned. As the salience of a domain decreases, the most salient category distinctions become increasingly more inclusive.
Revealing Student Teachers’ Thinking through Dilemma Analysis

We explore the potential of dilemma analysis as an assessment tool to reveal student teachers’ thinking and concerns about their practice. For this purpose we analyze the dilemma analyses completed by 22 student teachers enrolled in our science teacher preparation program over a period of four semesters. Student teachers’ dilemmas fall into two main groups: dilemmas about student performance and dilemmas associated with instructional decisions. These dilemmas reveal a variety of concerns that student teachers have about their work. In particular, concerns about lack of student motivation and its consequences on performance and instruction play a central role in student teachers’ thinking. The recognition of common patterns of thought in our student teacher thinking has made us reflect on and re-evaluate important components of the curriculum in our science teacher preparation program.
Abstract 2374: Mir-29/Hsp47 regulate breast cancer progression by modulating the ECM transcription network

The extracellular matrix (ECM), an essential component of tumor microenvironment, play crucial roles in cancer development and progression. Using gene co-expression network analysis, we have identified an ECM transcription network from hundreds of human breast cancer. In this report, we show how the molecular chaperone protein Hsp47 functions as a nodal hub in regulating an ECM gene transcription network. We found that Hsp47 expression was activated during breast cancer development and progression. Hsp47 silencing reprogrammed human breast cancer cells to form growth-arrested and/or non-invasive structures in 3D cultures, and to limit tumor growth in xenograft assays by reducing deposition of collagen and fibronectin. Co-expression network analysis also showed that levels of microRNA-29b and 29c were inversely correlated with expression of Hsp47 and ECM network genes in human breast cancer tissues. We found that miR-29 repressed expression of Hsp47 along with multiple ECM network genes. Ectopic expression of miR-29b suppressed malignant phenotypes of breast cancer cells in 3D culture. Clinically, increased expression of Hsp47 and reduced levels of miR-29b and 29c were associated with poor survival outcomes in breast cancer patients. Our results show that Hsp47 is regulated by miR-29 during breast cancer development and progression, and that increased Hsp47 expression promotes cancer progression in part by enhancing deposition of ECM proteins. Citation Format: Jieqing Zhu, Gaofeng Xiong, Ren Xu. Mir-29/Hsp47 regulate breast cancer progression by modulating the ECM transcription network. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2374. doi:10.1158/1538-7445.AM2015-2374
Diabetes susceptibility genes Pdx1 and Clec16a function in a pathway regulating mitophagy in β-cells

Mitophagy is a critical regulator of mitochondrial quality control and is necessary for elimination of dysfunctional mitochondria to maintain cellular respiration. Here, we report that the homeodomain transcription factor Pdx1, a gene associated with both type 2 diabetes and monogenic diabetes of the young, regulates mitophagy in pancreatic β-cells. Loss of Pdx1 leads to abnormal mitochondrial morphology and function as well as impaired mitochondrial turnover. High-throughput expression microarray and chromatin occupancy analyses reveal that Pdx1 regulates the expression of Clec16a, a type 1 diabetes gene and itself a key mediator of mitophagy through regulation of the E3 ubiquitin ligase Nrdp1. Indeed, expression of Clec16a and Nrdp1 are both reduced in Pdx1 haploinsufficient islets, and reduction of Pdx1 impairs fusion of autophagosomes containing mitochondria to lysosomes during mitophagy. Importantly, restoration of Clec16a expression after Pdx1 loss of function restores mitochondrial trafficking during mitophagy and improves mitochondrial respiration and glucose-stimulated insulin release. Thus, Pdx1 orchestrates nuclear control of mitochondrial function in part by controlling mitophagy through Clec16a. The novel Pdx1-Clec16a-Nrdp1 pathway we describe provides a genetic basis for the pathogenesis of mitochondrial dysfunction in multiple forms of diabetes that could be targeted for future therapies to improve β-cell function.
ATDRS payload technology R&D

Four technology development tasks which were chosen to reduce the technology risks associated with proposed approaches to the Advanced Tracking and Data Relay satellite (ATDRS) are described. The four tasks relate to a triband antenna feed system, a digital beamforming system for the S-band multiple-access system (SMA), an SMA phased-array antenna, and a configuration thermal/mechanical analysis task. The objective, approach, and status of each task and spacecraft configuration studies are discussed. >
RESPONSE OF UNREINFORCED MASONRY BUILDINGS

A summary of dynamic measurements are presented that illustrate relations between linear seismic demand and true nonlinear response of unreinforced masonry buildings with flexible diaphragms and rocking piers subjected to a series of simulated earthquake motions.
How does doxorubicin work

A new mechanism involving cleavage of a transcription factor called CREB3L1 has been proposed to explain the anti-tumour effects of doxorubicin.
Compatibility of the Abbott IMx homocysteine assay with citrate-anticoagulated plasma and stability of homocysteine in citrated whole blood.

Hyperhomocysteinemia is widely regarded as a risk factor for arterial thrombosis (1)(2), and it is also implicated as a risk factor for venous thrombosis (3)(4)(5)(6). Therefore, homocysteine (Hcy) often is included in hypercoagulability evaluations (7). The Abbott IMx Hcy fluorescence polarization immunoassay instructions recommend EDTA- or lithium heparin-anticoagulated plasma or serum, whereas other coagulation tests are generally performed on citrate-anticoagulated specimens. To simplify specimen collection and avoid unnecessary phlebotomy, we investigated the compatibility of the Abbott IMx Hcy assay with citrate-anticoagulated plasma. Previous reports have suggested that acidic citrate stabilizes the Hcy concentration in whole-blood specimens for at least 6 h at room temperature (8)(9). Therefore, we also studied the stability of Hcy in whole-blood specimens collected in sodium citrate. To evaluate the correlation between citrate and EDTA Hcy values, 114 sets of paired specimens were concurrently obtained from 96 nonfasting individuals (87 healthy volunteer platelet donors and 9 patients undergoing hypercoagulability evaluation) in Becton Dickinson Vacutainer lavender-top [tripotassium EDTA (K3EDTA)] and blue-top (3.2% sodium citrate) tubes. For each patient, the citrate tube was drawn immediately before the EDTA tube, in accordance with the NCCLS guidelines. The conditions and timing for specimen collection, processing, storage, and assay performance were identical for the two anticoagulants. The specimen pairs were separated from the cells within 30 min of phlebotomy unless specimen transportation would be longer than 30 min, in which case specimen pairs were placed immediately on ice and separated from cells within 4 h. Plasma samples were then kept frozen at −20 °C or lower until blinded analysis using a standard Abbott IMx analyzer and a single lot of Abbott Hcy reagents (kindly donated by Dr. Jessie Shih, Abbott …
Supersaturation For Ramsey-Turán Problems

For an l-graph $${\user1{\mathcal{G}}}$$, the Turan number $${\text{ex}}{\left( {n,{\user1{\mathcal{G}}}} \right)}$$ is the maximum number of edges in an n-vertex l-graph $${\user1{\mathcal{H}}}$$ containing no copy of $${\user1{\mathcal{G}}}$$. The limit $$\pi {\left( {\user1{\mathcal{G}}} \right)} = \lim _{{n \to \infty }} {\text{ex}}{\left( {n,{\user1{\mathcal{G}}}} \right)}/{\left( {^{n}_{l} } \right)}$$ is known to exist [8]. The Ramsey–Turan density $$p{\left( {\user1{\mathcal{G}}} \right)}$$ is defined similarly to $$\pi {\left( {\user1{\mathcal{G}}} \right)}$$ except that we restrict to only those $${\user1{\mathcal{H}}}$$ with independence number o(n). A result of Erdős and Sos [3] states that $$\pi {\left( {\user1{\mathcal{G}}} \right)} = p{\left( {\user1{\mathcal{G}}} \right)}$$ as long as for every edge E of $${\user1{\mathcal{G}}}$$ there is another edge E′of $${\user1{\mathcal{G}}}$$ for which |E∩E′|≥2. Therefore a natural question is whether there exists $${\user1{\mathcal{G}}}$$ for which $$p{\left( {\user1{\mathcal{G}}} \right)} 2.We prove the existence of a phenomenon similar to supersaturation for Turan problems for hypergraphs. As a consequence, we construct, for each l≥3, infinitely many l-graphs $${\user1{\mathcal{G}}}$$ for which $$0 < \ifmmode\expandafter\tilde\else\expandafter\~\fi{p}{\left( {\user1{\mathcal{G}}} \right)} < \pi {\left( {\user1{\mathcal{G}}} \right)}$$.We also prove that the 3-graph $${\user1{\mathcal{G}}}$$ with triples 12a, 12b, 12c, 13a, 13b, 13c, 23a, 23b, 23c, abc, satisfies $$0 < p{\left( {\user1{\mathcal{G}}} \right)} < \pi {\left( {\user1{\mathcal{G}}} \right)}$$. The existence of a hypergraph $${\user1{\mathcal{H}}}$$ satisfying $$0 < p{\left( {\user1{\mathcal{H}}} \right)} < \pi {\left( {\user1{\mathcal{H}}} \right)}$$ was conjectured by Erdős and Sos [3], proved by Frankl and Rodl [6], and later by Sidorenko [14]. Our short proof is based on different ideas and is simpler than these earlier proofs.
Primary Prevention of Ischemic Stroke

To the Editor: In the American Heart Association’s Scientific Statement on the Primary Prevention of Ischemic Stroke,1 the committee …
On marching cubes

A characterization and classification of the isosurfaces of trilinear functions is presented. Based upon these results, a new algorithm for computing a triangular mesh approximation to isosurfaces for data given on a 3D rectilinear grid is presented. The original marching cubes algorithm is based upon linear interpolation along edges of the voxels. The asymptotic decider method is based upon bilinear interpolation on faces of the voxels. The algorithm of this paper carries this theme forward to using trilinear interpolation on the interior of voxels. The algorithm described here will produce a triangular mesh surface approximation to an isosurface which preserves the same connectivity/separation of vertices as given by the isosurface of trilinear interpolation.
Win the match and vote for me : the politicisation of Ghana's Accra Hearts of Oak and Kumasi Asante Kotoko football clubs*

There is a common perception in Ghana that Accra Hearts of Oak is the soccer club of the National Democratic Congress, and Kumasi Asante Kotoko that of the New Patriotic Party. In this paper we explore the roots of these perceptions by examining the social history of these two clubs specifically, and the Ghanaian soccer league system in general, with an eye for the actors, practices and events that injected political airs into purportedly ‘apolitical ’ athletic competitions. With this social history clearly defining the popularly perceived ‘ us ’ versus ‘them ’ of the Hearts/Kotoko rivalry, we analyse on the basis of a modest survey some of the assumptions these widely held stereotypes rely upon. We find that ethnicity and location matter both in terms of predicting one’s affinity for a given soccer
Working Conditions and Parents’ Ability to Care for Children’s Preventive Health Needs

Objective: To determine whether workplace flexibility policies influence parents’ ability to meet their children’s preventive primary health care needs. Patients and Methods: Study sample included ...
Inlining as staged computation

Inlining and specialization appear in various forms throughout the implementation of modern programming languages. From mere compiler optimizations to sophisticated techniques in partial evaluation, they are omnipresent, yet each application is treated differently. This paper is an attempt at uncovering the relations between inlining (as done in production compilers) and staged computation (as done in partial evaluators) in the hope of bringing together the research advances in both fields. Using a two-level lambda calculus as the intermediate language, we show how to model inlining as a staged computation while avoiding unnecessary code duplication. The new framework allows us to define inlining annotations formally and to reason about their interactions with module code. In fact, we present a cross-module inlining algorithm that inlines all functions marked inlinable, even in the presence of ML-style parameterized modules.
Shape model segmentation of long-axis contrast enhanced echocardiography

We segment long-axis, four-chamber contrast enhanced echocardiography imagery using active shape models. The active shape model algorithm uses principal component analysis to model the shape variability found in a database of training shapes. Accurate segmentation from this model is accomplished by applying a specialized gradient vector flow field to guide the contours to the myocardial borders. The success of the proposed algorithm was verified by application to 65 patient myocardial contrast echocardiography (MCE) studies and through comparison with manually drawn contours. This approach improved accuracy over previously reported data, providing an average accuracy of 0.98, sensitivity of 0.84, specificity of 0.99, and RMSE of 3.3 pixels, when compared to ground truth. Error and variability from automatic segmentation were found to be less than those among multiple human observers. The approach also compares favorably against a standard active contour solution.
Monochloramine Cometabolism by Nitrosomonas europaea under Drinking Water Conditions

Abstract Chloramine is widely used in United States drinking water systems as a secondary disinfectant, which may promote the growth of nitrifying bacteria because ammonia is present. At the onset of nitrification, both nitrifying bacteria and their products exert a monochloramine demand, decreasing the residual disinfectant concentration in water distribution systems. This work investigated another potentially significant mechanism for residual disinfectant loss: monochloramine cometabolism by ammonia-oxidizing bacteria (AOB). Monochloramine cometabolism was studied with the pure culture AOB Nitrosomonas europaea (ATCC 19718) in batch kinetic experiments under drinking water conditions. Three batch reactors were used in each experiment: a positive control to estimate the ammonia kinetic parameters, a negative control to account for abiotic reactions, and a cometabolism reactor to estimate the cometabolism kinetic constants. Kinetic parameters were estimated in AQUASIM with a simultaneous fit to all experimental data. The cometabolism reactors showed a more rapid monochloramine decay than in the negative controls, demonstrating that cometabolism occurs. Cometabolism kinetics were best described by a pseudo first order model with a reductant term to account for ammonia availability. Monochloramine cometabolism kinetics were similar to those of ammonia metabolism, and monochloramine cometabolism was a significant loss mechanism (30–60% of the observed monochloramine decay). These results suggest that monochloramine cometabolism should occur in practice and may be a significant contribution to monochloramine decay during nitrification episodes in drinking water distribution systems.
Comparisons of the effects of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin on chemically impacted and nonimpacted subpopulations of Fundulus heteroclitus: I. TCDD toxicity

A subpopulation of Fundulus heteroclitus inhabiting the chemically impacted estuary of Newark Bay, New Jersey, was found to be resistant to the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as compared to a chemically non-impacted subpopulation of F. heteroclitus in Tuckerton, New Jersey. The Newark/Raritan Bay estuary is a major site of TCDD contamination. The Newark F. heteroclitus embryos, when exposed to 12 to 100 parts per trillion (pptr) [{sup 3}H]TCDD/acetone (nominal water concentrations) did not exhibit TCDD-dependent lesions or death. In contrast, the Tuckerton embryos exhibited both TCDD concentration-related lesions and death that was associated with the lesions. The Newark embryonic resistance to TCDD toxicity could not be attributed to a lesser absorption of [{sup 3}H]TCDD as compared to the Tuckerton embryos. The Newark F. heteroclitus adult fish, when dermally treated with 0.30 to 60 ng/g [{sup 3}H]TCDD/DMSO, did not exhibit TCDD treatment-related increases in death, lesions, or liver-to-body-weight ratios, whereas the Tuckerton adult fish did. The Newark fish did exhibit greater parasitic infestations of the liver, greater hepatic neoplasias, and greater liver-to-body-weight ratios, all of which were independent of laboratory TCDD treatment, as compared to the Tuckerton fish. These hepatic effects in the Newark fish may be indicative of the chronicmore » chemical exposure of this F. heteroclitus subpopulation.« less
Gastric Parietal Cell Atrophy and Depletion after Administration of a Sphingosine-1-Phosphate 1 Inhibitor

Sphingosine-1-phosphate (S1P) is a major bioactive phospholipid, which binds to and activates a family of five G-protein-coupled receptors designated as S1P 1 (S1P1) through S1P5. The S1P1 receptor subtype, expressed primarily on lymphocytes, is known to play a critical role in the regulation of lymphocyte trafficking. S1P1 inhibitors result in the inhibition of lymphoid cell trafficking and are of interest to treat various inflammatory conditions. In this study, we describe a gastric finding associated with oral gavage administration of a small molecule S1P1 inhibitor to Sprague-Dawley rats. Rats were administered an S1P1 inhibitor once daily for 4 weeks and necropsies were conducted at the end of the dosing phase, and clinical pathology and histopathologic examination were performed. Lymphopenia and changes in lymphoid tissues were noted and were consistent with the pharmacodynamic effects for S1P1 inhibitory action. Histopathologic examination of the stomach revealed atrophy and depletion of gastric parietal cells in the glandular portion of the stomach. There are no literature data to suggest that this gastric effect is related to S1P1 pharmacology. Therefore, the mechanism of the observed gastric lesion is likely chemotype mediated.
Sex differences in oxytocin and vasopressin: Implications for autism spectrum disorders?

Autism spectrum disorders (ASD) are male-biased and characterized by deficits in social behavior and social communication, excessive anxiety or hyperreactivity to stressful experiences, and a tendency toward repetitiveness. The purpose of this review is to consider evidence for a role for two sexually dimorphic neuropeptides, oxytocin (OT) and arginine vasopressin (VP), in these features of ASD. Both VP and OT play a role in normal development. VP is androgen-dependent and of particular importance to male behavior. Excess VP or disruptions in the VP system could contribute to the male vulnerability to ASD. Alternatively, protective processes mediated via OT or the OT receptor might help to explain the relatively rare occurrence of ASD in females. Disruptions in either OT or VP or their receptors could result from genetic variation or epigenetic modifications of gene expression, especially during early development. Deficits in other developmental growth factors, such as reelin, which may in turn regulate or be regulated by OT or VP, are additional candidates for a role in ASD.