cssi/SciSciGPT-SciSciNet huggingface dataset:
Acute treatment with the N-methyl-d-aspartate receptor antagonist MK-801: effect of concurrent administration of haloperidol or scopolamine on preproenkephalin mRNA levels of the striatum and nucleus accumbens of the rat brain

We injected rats three times at 3 h intervals (from 0900 h to 1500 h) with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 at 0.1 or 0.5 mg/kg of body weight. Three hours after the last injection, animals were sacrificed and the brains were processed for in situ hybridization histochemistry. Preproenkephalin (PPE) mRNA levels were significantly decreased throughout the caudate-putamen (CPu) and nucleus accumbens (NAc) at the lower dose. The higher dose produced significant decreases only in anterior CPu (aCPu) and NAc. Concurrent administration of the muscarinic cholinergic receptor antagonist scopolamine at 2 or 5 mg/kg neither potentiated nor prevented the effect of MK-801 on PPE mRNA levels in the neostriatum. In contrast, co-administration of haloperidol (dopamine receptor antagonist) with MK-801 blocked the effect of the latter in the NAc, and elevated PPE mRNA levels throughout the CPu. The data demonstrate that the acute effects of glutamate receptor activity on striatal and accumbal PPE mRNA expression via the NMDA receptor can be modulated by the dopaminergic system in the brain of the rat.
Optimised rate-responsive pacing does not improve either right ventricular haemodynamics or exercise capacity in adults with a systemic right ventricle.

BACKGROUND: Inappropriate heart rate response to exercise - chronotropic incompetence - and exercise intolerance are common in patients with a systemic right ventricle. We aimed to assess the relationship between heart rate increase, oxygen consumption, and timing of the right ventricular cardiac cycle in this cohort. METHODS: We prospectively studied nine patients with systemic right ventricles and pre-existing pacemakers using Doppler-echocardiography and treadmill exercise testing. Echocardiography was performed at increasing heart rates. Exercise tests were performed with baseline pacemaker settings and with optimised heart rate response in random order. In addition, eight age- and gender-matched controls underwent exercise testing using a similar exercise protocol. RESULTS: Patients with a systemic right ventricle had significantly lower peak oxygen consumption compared to controls - 12.6 plus or minus 6.8 versus 31.4 plus or minus 6.6 metres per kilogram per minute (p = 0.0006) - at baseline and active pacemaker reprogramming failed to increase peak oxygen consumption in this cohort - 12.6 plus or minus 6.8 versus 12.4 plus or minus 4.9 millilitres per kilogram per minute (p = NS) at baseline and with reprogramming, respectively. We found not only a marked increase in total isovolumic time but also a significant reduction in total filling time and the aortic velocity time integral, p-value is less than 0.001 for all, at higher heart rates compared to baseline conditions. CONCLUSION: This study suggests that despite chronotropic incompetence at baseline, rate-responsive pacing does not improve exercise capacity in patients with a systemic right ventricle. It further indicates that high heart rates may be detrimental in these patients by reducing diastolic filling and stroke volume. These findings may have clinical implications when considering implantation of a permanent pacemaker in this cohort.
Longitudinal methods for describing the relationship between pulmonary function, respiratory symptoms and smoking in elderly subjects: the Tucson Study

In this study recently developed longitudinal techniques are used to examine the relationship between respiratory symptoms, smoking and pulmonary function measures in elderly subjects. The subjects were participants in the Tucson Epidemiological Study of Airways Obstructive Disease, aged > or = 55 yrs at the first survey 1972-1973, who had received pulmonary function testing and completed questionnaires in at least one of the six selected surveys. There were 633 males and 891 females, with up to 14 yrs follow-up included in the analysis. Based on their questionnaire responses, subjects were classified according to their respiratory symptoms and smoking habits at each survey. The pulmonary function testing included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and their ratio (FEV1/FVC). The pulmonary function data were analysed gender specific, with and without stratifying on vital status. The results indicate that respiratory symptoms are generally associated with lower levels of lung function, and that the impairment associated with chronic cough was observed predominantly in male subjects. The negative association of smoking was apparent in most measures, but was largest and most progressive in the FEV1/FVC ratios. Ex-smokers, in all cases, had better lung function values than current smokers, but their mean curves were always significantly below the values of nonsmokers.
Ecology of the hagfish, Myxine glutinosa L. in the Gulf of Maine I. Metabolic rates and energetics

Abstract The hagfishes, as an extant group, represent the most primitive living craniates. Although of interest to evolutionary biologists, little is known about the physiological ecology of hagfish, despite the occurrence of large, commercially exploited populations around the world. In the Gulf of Maine, the Atlantic hagfish, Myxine glutinosa L., is a nuisance to the groundfishing industry, but may play an important role in the ecology of soft-bottom habitats. The recent exploitation of these hagfish populations for the “eelskin” fishery has resulted in renewed interest regarding their ecology and physiology. Direct measurement of oxygen consumption rates for M. glutinosa with versus without gill pouch perfusion indicate that the majority of oxygen uptake at rest occurs cutaneously. The measured rates of oxygen consumption imply extremely low energetic demands. Hagfish adaptations to hypoxic environments, which include cutaneous respiration, allow them to occupy burrows where oxygen concentrations are low. These adaptations would also permit long intervals between periods of opportunistic feeding. Although the energetic demands of individual hagfish is low, the impact of large populations of hagfish on commercially important species could be significant.
Geomorphic and land cover identification of dust sources in the eastern Great Basin of Utah, U.S.A.

Abstract This study identifies anthropogenically disturbed areas and barren playa surfaces as the two primary dust source types that repeatedly contribute to dust storm events in the eastern Great Basin of western Utah, U.S.A. This semi-arid desert region is an important contributor to dust production in North America, with this study being the first to specifically identify and characterize regional dust sources. From 2004 to 2010, a total of 51 dust event days (DEDs) affected the air quality in Salt Lake City, UT. MODIS satellite imagery during 16 of these DEDs was analyzed to identify dust plumes, and assess the characteristics of dust source areas. A total of 168 plumes were identified, and showed mobilization of dust from Quaternary deposits located within the Bonneville Basin. This analysis identifies 4 major and 5 secondary source areas for dust in this region, which produce dust primarily during the spring and fall months and during moderate or greater drought conditions, with a Palmer Drought Index (PDI) of − 2 or less. The largest number of observed dust plumes (~ 60% of all plumes) originated from playas (ephemeral lakes) and are classified as barren land cover with a silty clay soil sediment surface. Playa surfaces in this region undergo numerous recurrent anthropogenic disturbances, including military operations and anthropogenic water withdrawal. Anthropogenic disturbance is necessary to produce dust from the vegetated landscape in the eastern Great Basin, as evidenced by the new dust source active from 2008 to 2010 in the area burned by the 2007 Milford Flat Fire; this fire was the largest in Utah's history due to extensive cover of invasive cheatgrass ( Bromus tectorum ) along with drought conditions. However, dust mobilization from the Milford Flat Burned Area was limited to regions that had been significantly disturbed by post-fire land management techniques that consisted of seeding, followed by chaining or tilling of the soil. Dust storms in the eastern Great Basin negatively impact air quality and transportation in the populated regions of Utah; this study details an improved forecasting protocol for dust storm events that will benefit transportation planning and improve public health.
Employing a polyketide synthase module and thioesterase in the semipreparative biocatalysis of diverse triketide pyrones

To demonstrate the potential of polyketide synthase (PKS) modules as biocatalysts that can synthesize polyketides in vitro, the terminal module and thioesterase (TE) from the erythromycin PKS were employed in the multimilligram, chemoenzymatic syntheses of diverse triketide pyrones. Methylmalonyl-S-NAC extender units were generated by the promiscuous malonyl-CoA ligase Streptomyces coelicolor MatB. Initiating the reaction with β-ketoacyl-S-NAC diketides yielded the anticipated triketide pyrones through chain extension and cyclization. TE-mediated hydrolysis of the substrates prevented quantitative yields; however, a reaction with 200 mg of diketide substrate generated 20 mg of pyrone product. Trace quantities of a particular pyrone were observed in all reactions and was hypothesized to result from extender unit decarboxylation and subsequent “stuttering”. To harness this polymerase-like activity, reactions were initiated with diverse acyl-S-NACs to yield the anticipated triketide pyrones, one harboring a terminal alkyne chemical handle. This biocatalytic system enables more informative analysis of in vitro PKS reactions by HPLC, NMR, and crystallography and sets the stage for the preparative generation of polyketides such as chiral building blocks valuable in the synthesis of natural products and pharmaceuticals.
β-Blockade as an alternative to cardioplegic arrest during cardiopulmonary bypass

Abstract Background . As an alternative to cardioplegic arrest, cardiac surgical conditions have been produced using β-blocker–induced minimal myocardial contraction (MMC) during cardiopulmonary bypass. The technique of MMC involves the use of high-dose intravenous esmolol to suppress myocardial chronotropy and inotropy sufficiently to produce cardiac surgical conditions. The purpose of this study was to compare conventional crystalloid cardioplegic arrest with MMC in terms of ischemia avoidance, myocardial edema formation, and cardiac function. Methods . Twelve dogs were placed on cardiopulmonary bypass. Six dogs were subjected to crystalloid cardioplegic arrest for 2 hours. Surgical conditions were produced in the other 6 dogs for 2 hours using intravenous esmolol without aortic clamping or cardioplegia. Arterial and coronary sinus lactate concentrations were determined as a gauge of myocardial ischemia. Myocardial water content was determined using microgravimetry and preload recruitable stroke work was determined using sonomicrometry and micromanometry. Results . Significant lactate washout was demonstrated after cardioplegic arrest but not after MMC. Myocardial water content was significantly less during and after MMC compared with cardioplegic arrest ( p p Conclusions . In contrast to a previous study that involved 1 hour of MMC, in this study, ventricular function was decreased to the same extent as with cardioplegic arrest after 2 hours of MMC. This was attributed to the accumulation of ASL-8123, the primary metabolite of esmolol, which possesses β-antagonist properties. Although postbypass ventricular function is similar in both groups, MMC appears to be superior in terms of ischemia avoidance and myocardial edema formation.
Characterizing Transition Behaviors in Internet Attack Sequences

Cyber attacks from the Internet often span over multiple ports and multiple hosts. This work hypothesizes that there are distinct sequential patterns revealing hacking behavior. A feature called Attack Transition Action (ATA) is defined to represent the changes on attacked destinations and ports over time. The simplicity of the feature enables the development of a probabilistic model, revealing higher order transitions hidden within the attack sequences. The model trained with a real-world attack dataset uncovers several natural clusters of Internet attack behaviors. The discovered behavior patterns are explained with representative hacking strategies. Our systematic modeling and analysis provides an effective means to characterize classes of Internet attacks.
Quality and the curate's egg

A famous cartoon in the satirical magazine Punch from the 1890s shows a meek curate assuring his dinner host that his egg is not spoiled. “Parts of it are exceptional”, he suggests. We, the knowing reader, appreciate the humour. An egg cannot be good in parts. For those who think about quality, the question of whether care can be good in parts is a tricky one. That a hospital might deliver better care for one clinical service—top notch cardiac surgery, say, but below average stroke care—would not surprise anyone. But, the idea that quality itself, even within a given clinical domain, like cardiac surgery or stroke care, might be ‘good in parts’ has been recognised only recently. The US Institute of Medicine lays out six key dimensions of quality: effectiveness, safety, patient-centeredness, efficiency, timeliness and equity.1 In the UK, the National Health Service (NHS) highlights three domains of quality: clinical effectiveness, patient safety and the patient experience.2 As a result of this conceptual division, people have become interested in how these different parts relate to one another. Patient experience—traditionally the poor, subjective cousin in the quality family—sometimes struggles to defend its seat at the table. Some have argued that measuring patient experience is a distraction. Take the patient dissatisfied by his doctor when he is denied antibiotics for a cold. This is bad for experience, but good clinical practice, and good for society. Many clinicians accept this disconnect between what they regard as appropriate care and what will make patients happy, seeing it as no more significant than a medication that tastes terrible. In acute care settings, hospital emergency rooms, for instance, clinicians may regret that patients often wait on stretchers that are uncomfortable, pillows …
McTaggart and Modern Physics

This paper delves into McTaggart’s metaphysical account of reality without time, and compares and contrasts McTaggart’s account with the account of reality given by modern physics. This comparison is of interest, because there are suggestions from contemporary physics that there is no time at the fundamental level. Physicists and philosophers of physics recognize that we do not have a good understanding of how the world could be such that time is unreal. I argue that, from the perspective of one who is trying to understand modern physics, McTaggart’s metaphysical views do provide some insight into how reality can be timeless at the fundamental level, but the insight that they provide is limited.
Effects of Increasing Tibial Slope on the Biomechanics of the Knee

PurposeTo determine the effects of increasing anterior-posterior (A-P) tibial slope on knee kinematics and in situ forces in the cruciate ligaments.MethodsTen cadaveric knees were studied using a robotic testing system using three loading conditions: (1) 200 N axial compression; (2) 134 N A-P tibial load; and (3) combined 200 N axial and 134 N A-P loads. Resulting knee kinematics were determined before and after a 5-mm anterior opening wedge osteotomy. Resulting in situ forces in each cruciate ligament were determined.ResultsTibial slope was increased from 8.8 ± 1.8 ° to 13.2 ± 2.1 °, causing an anterior shift in the resting position of the tibia relative to the femur up to 3.6 ± 1.4 mm. Under axial compression, the osteotomy caused a significant anterior tibial translation up to 1.9 ± 2.5 mm (90 °). Under A-P and combined loads, no differences were detected in A-P translation or in situ forces in the cruciates (intact versus osteotomy).ConclusionsResults suggest that small increases in tibial slope do no...
Role of ibrutinib for the treatment of mantle cell lymphoma in the elderly

SUMMARY Mantle cell lymphoma (MCL) is an uncommon, incurable B-cell non-Hodgkin lymphoma that primarily occurs in the elderly. There is no standard management of MCL, with options varying from observation in asymptomatic patients to aggressive induction/consolidation regimens in younger patients with rapidly progressive disease. Ibrutinib is a first-in-class covalent inhibitor of Bruton’s tyrosine kinase and has shown clinical activity in several B-cell lymphomas including MCL. It is taken orally once daily and appears to be well tolerated. Based on promising results from a Phase II clinical trial in MCL, ibrutinib received breakthrough therapy designation and was approved by the US FDA for treatment of patients with MCL that have received at least one prior line of therapy. It is undergoing further testing in the front line and relapsed setting.
Relationship between tendon stiffness and failure: a metaanalysis

Tendon is a highly specialized, hierarchical tissue designed to transfer forces from muscle to bone; complex viscoelastic and anisotropic behaviors have been extensively characterized for specific ...
The construction and analogical transfer of symbolic visualizations.

Two studies explored whether adolescents can and will construct abstract visualizations to structure complex information. Experiment 1 showed that students can structure novel information with visualizations. Seventh-, 9th-, and 10th-grade students were directed to construct visualizations of complex transmission problems in biology (e.g., epidemiology). Two-thirds of the resulting visualizations at each grade level captured the structure of the problems. The 9th/10th graders primarily constructed path diagrams (i.e., directed graphs), and the 7th graders constructed more original visualizations. Experiment 2 showed that students will analogically transfer specific visualizations and will transfer the strategy of visualizing. On pre- and posttests 7th graders solved transmission problems without cues to visualize. During an intervention, students in two treatments constructed and learned visualizations for three problem types. In the Path treatment, one problem type involved path diagrams. In the No-Path treatment an alternate problem type was used as a filler visualization task. Overall, 50% more students used visualizations on the posttest compared to the pretest. Students in the Path treatment analogically transferred the path diagram to the posttest, whereas students in the No-Path treatment spontaneously constructed alternative visualizations. These findings suggest that instruction in visualizing may develop a strategy that students can and will use to understand the structure in complex and novel information.
Influence of Marinating on Weight Gain and Coating Characteristics of Broiler Drumsticks

The weight gain of broiler drumsticks at 4°C was compared to those at 23°C after marinating in distilled water with agitation for 30 and 60 min. At 23°C there was significantly greater absorption (P = 0.001), with an average of 3.81%. The effect of different additives were studied in relation to weight gain, coating pickup, cooking loss, crumb loss, and overall yield of coated broiler drumsticks. Skinless drumsticks marinated in 4% Kena solution (90% tripolyphosphate and 10% hexametaphosphate blend) had significantly greater coating pickup, and a cooking loss was significantly reduced by increased marinating time in 4% Kena. The mean overall yield was highest for drumsticks soaked in distilled water (86.67%), and lowest for ‘those treated with 0.5% ascorbic acid (80.01%) and 0.002% papain (78.30%).
Identification of nucleocapsid binding sites within coronavirus-defective genomes.

The coronavirus nucleocapsid (N) protein is a major structural component of virions that associates with the genomic RNA to form a helical nucleocapsid. N appears to be a multifunctional protein since data also suggest that the protein may be involved in viral RNA replication and translation. All of these functions presumably involve interactions between N and viral RNAs. As a step toward understanding how N interacts with viral RNAs, we mapped high-efficiency N-binding sites within BCV- and MHV-defective genomes. Both in vivo and in vitro assays were used to study binding of BCV and MHV N proteins to viral and nonviral RNAs. N-viral RNA complexes were detected in bovine coronavirus (BCV)-infected cells and in cells transiently expressing the N protein. Filter binding was used to map N-binding sites within Drep, a BCV-defective genome that is replicated and packaged in the presence of helper virus. One high-efficiency N-binding site was identified between nucleotides 1441 and 1875 at the 3' end of the N ORF within Drep. For comparative purposes N-binding sites were also mapped for the mouse hepatitis coronavirus (MHV)-defective interfering (DI) RNA MIDI-C. Binding efficiencies similar to those for Drep were measured for RNA transcripts of a region encompassing the MHV packaging signal (nts 3949-4524), as well as a region at the 3' end of the MHV N ORF (nts 4837-5197) within MIDI-C. Binding to the full-length MIDI-C transcript (approximately 5500 nts) and to an approximately 1-kb transcript from the gene 1a region (nts 935-1986) of MIDI-C that excluded the packaging signal were both significantly higher than that measured for the smaller transcripts. This is the first identification of N-binding sequences for BCV. It is also the first report to demonstrate that N interacts in vitro with sequences other than the packaging signal and leader within the MHV genome. The data clearly demonstrate that N binds coronavirus RNAs more efficiently than nonviral RNAs. The results have implications with regard to the multifunctional role of N.
Stable isotope (δ13C and δ15N) values of sediment organic matter in subtropical lakes of different trophic status

Lake sediments contain archives of past environmental conditions in and around water bodies and stable isotope analyses (δ13C and δ15N) of sediment cores have been used to infer past environmental changes in aquatic ecosystems. In this study, we analyzed organic matter (OM), carbon (C), nitrogen (N), phosphorus (P), and δ13C and δ15N values in sediment cores from three subtropical lakes that span a broad range of trophic state. Our principal objectives were to: (1) evaluate whether nutrient concentrations and stable isotope values in surface deposits reflect modern trophic state conditions in the lakes, and (2) assess whether stratigraphic changes in the measured variables yield information about shifts in trophic status through time, or alternatively, diagenetic changes in sediment OM. Three Florida (USA) lakes of very different trophic status were selected for this study. Results showed that both δ13C and δ15N values in surface sediments of the oligo-mesotrophic lake were relatively low compared to values in surface sediments of the other lakes, and were progressively lower with depth in the sediment core. Sediments of the eutrophic lake had δ13C values that declined upcore, whereas δ15N values increased toward the sediment surface. The eutrophic lake displayed δ13C values intermediate between those in the oligo-mesotrophic and hypereutrophic lakes. Sediments of the hypereutrophic lake had relatively higher δ13C and δ15N values. In general, we found greater δ13C and δ15N values with increasing lake trophic state.
Detonation wave structure of gases at elevated initial pressures

ABSTRACT The characteristic “structure” of gaseous detonation waves, defined here as the spatial variation of the pressure, temperature, density, species concentrations, and velocity within the detonation wave is examined theoretically at elevated initial pressures. The approach taken in this work is to extend the Zel'dovich-von Neumann-Doering (ZND) theory of gas-phase detonation to use real-gas equations of state, Chemkin Real Gas, a computer program capable of calculating real-gas thermodynamic properties and chemical kinetic reaction rates, is used to describe the P-V-T behaviour of the gaseous mixtures in this investigation. The mathematical model for a ZND detonation wave is presented in an equation of state independent form and integrated numerically for a hydrogen-oxygen system to determine the structure of the detonation wave. The ZND model is used to characterize the thermodynamic states and reaction zone length scales present in the detonation wave. The variation of the reaction zone length par...
Conformational specificity of the C4F6 SOD1 antibody; low frequency of reactivity in sporadic ALS cases.

Greater than 160 missense mutations in copper-zinc superoxide dismutase-1 (SOD1) can cause amyotrophic lateral sclerosis (ALS). These mutations produce conformational changes that reveal novel antibody binding epitopes. A monoclonal antibody, clone C4F6 - raised against the ALS variant G93A of SOD1, has been identified as specifically recognizing a conformation shared by many ALS mutants of SOD1. Attempts to determine whether non-mutant SOD1 adopts a C4F6-reactive conformation in spinal tissues of sporadic ALS (sALS) patients has produced inconsistent results. To define the epitope recognized by C4F6, we tested its binding to a panel of recombinant ALS-SOD1 proteins expressed in cultured cells, producing data to suggest that the C4F6 epitope minimally contains amino acids 90–93, which are normally folded into a tight hairpin loop. Multiple van der Waals interactions between the 90–93 loop and a loop formed by amino acids 37–42, particularly a leucine at position 38, form a stable structure termed the β-plug. Based on published modeling predictions, we suggest that the binding of C4F6 to multiple ALS mutants of SOD1 occurs when the local structure within the β-plug, including the loop at 90–93, is destabilized. In using the antibody to stain tissues from transgenic mice or humans, the specificity of the antibody for ALS mutant SOD1 was influenced by antigen retrieval protocols. Using conditions that showed the best discrimination between normal and misfolded mutant SOD1 in cell and mouse models, we could find no obvious difference in C4F6 reactivity to spinal motor neurons between sALS and controls tissues.
Modules for gigahertz digital testing of ECL

A family of high-speed, low-cost multiplexer and data capture circuits is introduced. These hybrid circuits are based on previously introduced principles and are used to extend the upper frequency limits of existing test systems. The modules are based on low-cost ECL technology yet support testing up to about 1 Gpbs. Multiplexers with typical edge rates of 500 ps are demonstrated. Subnanosecond-wide data bits are captured with either a multi-pass sampling circuit or a single-pass demultiplexer. The family of modules includes a variety of reusable circuits for pattern generation and data capture. Through 8:1 pin multiplexing, the paper demonstrates extension of a 200 MHz host system to beyond 1 GHz. These modules have been used in limited cases at frequencies about 1.5 GHz. >
Multidimensional MR spectroscopic imaging of prostate cancer in vivo

Prostate cancer (PCa) is the second most common type of cancer among men in the United States. A major limitation in the management of PCa is an inability to distinguish, early on, cancers that will progress and become life threatening. One-dimensional (1D) proton ((1)H) MRS of the prostate provides metabolic information such as levels of choline (Ch), creatine (Cr), citrate (Cit), and spermine (Spm) that can be used to detect and diagnose PCa. Ex vivo high-resolution magic angle spinning (HR-MAS) of PCa specimens has revealed detection of more metabolites such as myo-inositol (mI), glutamate (Glu), and glutamine (Gln). Due to the J-modulation and signal overlap, it is difficult to quantitate Spm and other resonances in the prostate clearly by single- and multivoxel-based 1D MR spectroscopy. This limitation can be minimized by adding at least one more spectral dimension by which resonances can be spread apart, thereby increasing the spectral dispersion. However, recording of multivoxel-based two-dimensional (2D) MRS such as J-resolved spectroscopy (JPRESS) and correlated spectroscopy (L-COSY) combined with 2D or three-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) using conventional phase-encoding can be prohibitively long to be included in a clinical protocol. To reduce the long acquisition time required for spatial encoding, the echo-planar spectroscopic imaging (EPSI) technique has been combined with correlated spectroscopy to give four-dimensional (4D) echo-planar correlated spectroscopic imaging (EP-COSI) as well as J-resolved spectroscopic imaging (EP-JRESI) and the multi-echo (ME) variants. Further acceleration can be achieved using non-uniform undersampling (NUS) and reconstruction using compressed sensing (CS). Earlier versions of 2D MRS, theory of 2D MRS, spectral apodization filters, newer developments and the potential role of multidimensional MRS in PCa detection and management will be reviewed here.
Huntingtin Interacting Protein 1 mutations lead to abnormal hematopoiesis, spinal defects and cataracts

Huntingtin Interacting Protein 1 (HIP1) binds clathrin and AP2, is overexpressed in multiple human tumors, and transforms fibroblasts. The function of HIP1 is unknown although it is thought to play a fundamental role in clathrin trafficking. Gene-targeted Hip1-/- mice develop premature testicular degeneration and severe spinal deformities. Yet, although HIP1 is expressed in many tissues including the spleen and bone marrow and was part of a leukemogenic translocation, its role in hematopoiesis has not been examined. In this study we report that three different mutations of murine Hip1 lead to hematopoietic abnormalities reflected by diminished early progenitor frequencies and resistance to 5-FU-induced bone marrow toxicity. Two of the Hip1 mutant lines also display the previously described spinal defects. These observations indicate that, in addition to being required for the survival/proliferation of cancer cells and germline progenitors, HIP1 is also required for the survival/proliferation of diverse types of somatic cells, including hematopoietic progenitors.
Entrainment of a dense layer by thermal plumes

The large mismatch between Earth's heat flux and that which would be produced in a uniform mantle with the composition of the mid-ocean ridge basalt source region, and several recent seismic models, suggest that the bottom part of the mantle may form a compositionally distinct layer. The long-term stability of such a dense but hot abyssal layer may hinge on the rate of entrainment of the dense material by upwelling thermal plumes that would originate from the thermal boundary layer at the compositional boundary. We have formulated high-resolution numerical models to examine the efficiency of such an entrainment. To isolate the physics of entrainment, thermal buoyancy forces that drive the flow and entrain the dense material are prescribed in both space and time in axisymmetric finite-element models with an isoviscous structure. Our models employ a marker chain method to track the evolution of the material interface. Thermal plumes entrain the dense material, forming a concentric annular structure, with a hot thermal plume surrounding an inner cylinder of dense material. The entrainment rate is controlled by two parameters: the radius of the thermal plume, r T , and the ratio of compositional to thermal buoyancy, Ra b t . The smaller r T is or the larger Ra b t , the smaller the entrainment rate will be, as expected. As Ra b t increases, the radius of the entrained compositional plume decreases, but the vertical velocity of the compositional plume also increases. We found that the entrainment rate scales as Ra - 2 . 4 8 btr 3 . 8 0 T, while the radius of the entrained compositional plume scales as Ra - 1 . 4 3 btr 1 . 2 4 T. For a mantle viscosity of 10 2 1 Pas, thermal plumes with r T ∼ 100 km and temperature 600 K hotter than the ambient mantle, and with horizontal spacings that are approximately the same as the mantle thickness, and for a denser layer with a thickness of 1000 km and net negative buoyancy of approximately 1 per cent, more than 90 per cent of the dense material can survive for 4.5 Gyr.
Use of human acellular dermal matrix during classic bladder exstrophy repair

Summary Introduction The extent of the abdominal wall defect in people with classic bladder exstrophy (CBE) varies, and can be extensive. In this study, human acellular dermis (HAD) was used to bridge the fascial gap, as an alternative to osteotomy, to support a fascial repair of the abdominal wall, and as a filler in selected cases of CBE. Objective To demonstrate the efficacy of the employed techniques of using HAD within the bladder exstrophy population. Materials and methods The medical records of six males, born with CBE, and who had abdominal wall defects were reviewed. Two children, aged 6 and 8 years old, were referred from overseas with unrepaired bladder exstrophy plates and large abdominal wall defects (8 cm and 12 cm wide). Both had their bladders reconstructed, placed within the pelvis, and HAD was used to replace the absent abdominal wall (bridged repair) without the use of pelvic osteotomy. In three other patients, HAD reinforced the native fascial repair (bolster repair). In three patients, HAD also served as a filler for the abdominal depression that was present following initial staged repair. Where HAD was used for bridged or bolster repair, the edges of the allograft were extended 2–3 cm circumferentially beyond the perimeter of the abdominal wall defect. Results All six patients healed well, without evidence of abdominal wall hernias at 1–3 years postoperatively. Functionally, each patient regained an appropriate level of abdominal wall strength. Two children successfully underwent a secondary procedure through the bridged allograft repair, as each required bladder neck reconstruction and bilateral ureteral reimplantation through the reconstructed abdominal wall. Continence was achieved in these two patients, with one child voiding at 2-hourly intervals and the second at 3-hourly intervals. One patient developed a urethral-cutaneous fistula, distant to location of the allograft. There were no associated wound complications. Conclusions In this series of patients born with classic bladder exstrophy, HAD acted as a biologic scaffold and allowed native cellular ingrowth and tissue remodeling. It served as an alternative to pelvic osteotomy in older patients with unrepaired CBE. The material reinforced a weak or potentially suboptimal fascial repair and filled a tissue gap, resulting in improved aesthetics. Given its ease of preparation and the lack of significant morbidity associated with its use, combined with the functional and esthetic results in the present series, HAD may be considered during delayed reconstruction of abdominopelvic tissues in people born with CBE. Download : Download high-res image (221KB) Download : Download full-size image Figure .
Regulation of cell migration by the integrin beta subunit ectodomain

CS-1 melanoma cells transfected with cDNAs encoding either the beta 3 or beta 5 integrin subunit protein express alpha v beta 3 or alpha v beta 5, respectively, enabling them to adhere to vitronectin yet only alpha v beta 3 promotes cell spreading and migration on this substrate. Following exposure to insulin or insulin-like growth factor, alpha v beta 5-expressing CS-1 cells gain the ability to migrate on vitronectin. To identify structural regions in beta 3 or beta 5 that account for these distinct biological properties, CS-1 cells were transfected with one of two chimeric beta subunit proteins, in which the ecto- and cytoplasmic domains of beta 3 and beta 5 were exchanged (termed alpha v beta 3/5 or alpha v beta 5/3). Surprisingly, alpha v beta 3/5 expressing cells spread and migrate on vitronectin while cells expressing alpha v beta 5/3 do not unless they are exposed to cytokine. These findings suggest that the distinct migratory properties mediated by integrins alpha v beta 3 and alpha v beta 5 and their response to cytokine activation is determined by a sequence(s) within the ectodomain of the integrin beta subunit.
Tracheal Aspirate Levels of the Matricellular Protein SPARC Predict Development of Bronchopulmonary Dysplasia.

Background Isolation of tracheal aspirate mesenchymal stromal cells (MSCs) from premature infants has been associated with increased risk of bronchopulmonary dysplasia (BPD). MSCs show high levels of mRNAs encoding matricellular proteins, non-structural extracellular proteins that regulate cell-matrix interactions and participate in tissue remodeling. We hypothesized that lung matricellular protein expression predicts BPD development. Methods We collected tracheal aspirates and MSCs from mechanically-ventilated premature infants during the first week of life. Tracheal aspirate and MSC-conditioned media were analyzed for seven matricellular proteins including SPARC (for Secreted Protein, Acidic, Rich in Cysteine, also called osteonectin) and normalized to secretory component of IgA. A multiple logistic regression model was used to determine whether tracheal aspirate matricellular protein levels were independent predictors of BPD or death, controlling for gestational age (GA) and birth weight (BW). Results We collected aspirates from 89 babies (38 developed BPD, 16 died before 36 wks post-conceptual age). MSC-conditioned media showed no differences in matricellular protein abundance between cells from patients developing BPD and cells from patients who did not. However, SPARC levels were higher in tracheal aspirates from babies with an outcome of BPD or death (p<0.01). Further, our logistic model showed that tracheal aspirate SPARC (p<0.02) was an independent predictor of BPD/death. SPARC deposition was increased in the lungs of patients with BPD. Conclusions In mechanically-ventilated premature infants, tracheal aspirate SPARC levels predicted development of BPD or death. Further study is needed to determine the value of SPARC as a biomarker or therapeutic target in BPD.
The Electric Age

In Chapter 6, we discussed the development of steam engines during the eighteenth and nineteenth centuries. These engines enabled industrialization by making available the vast stores of energy contained in coal, wood, and oil. By burning fuel, chemical energy is converted into heat energy, which in turn can be used to boil water to produce steam. By letting the steam expand against a piston or a turbine blade, heat energy can be converted to mechanical energy. In this way, a steam engine can power machinery.
Public transportation and the idiocy of urban life

This paper asserts urban transportation’s centrality to debates on ‘the public,’ the ‘right to the city’ and political mobilisation in cities. The paper begins with a re-reading of Marx and Engels’...
High Temperature Analog-to-Digital Converter Reliability Testing

Initial test results have been previously reported for a high-temperature (225°C) 12-bit analog-to-digital converter (HTADC12) fabricated using a production high-temperature silicon-on-insulator (SOI) CMOS process and assembled in hermetically sealed ceramic packages (ref. 1). Reliability test results for the HTADC12 are presented including parametric and functional test results from 1500 hours of dynamic life test at 250°C as well 1000 temperature cycles from −65°C to 200°C. Results of post-stress wirebond, and die bond testing are also provided.
Use of a card sort task to assess students' ability to coordinate three levels of representation in chemistry

There is much agreement among chemical education researchers that expertise in chemistry depends in part on the ability to coordinate understanding of phenomena on three levels: macroscopic (observable), sub-microscopic (atoms, molecules, and ions) and symbolic (chemical equations, graphs, etc.). We hypothesize this “level-coordination ability” is related to the formation and use of principle-based, vs. context-bound, internal representations or schemas. Here we describe the development, initial validation, and use of a card sort task to measure the level-coordinating ability of individuals with varying degrees of preparation in chemistry. We have also developed a novel method for generating two-dimensional sorting coordinates which were used to arrange participants along a hypothetical progression of level-coordination ability. Our findings suggest the card sort task shows promise as a tool to assess level-coordination ability. With the exception of graduate students, participant groups on average progressed from sorting by level of representation toward sorting by underlying principle. Graduate students unexpectedly sorted primarily by level of representation. We use these data to form initial hypotheses about a typical process for the development of level-coordination ability and schema formation. In doing so, we demonstrate the usefulness of our task paired with sorting coordinate analysis as a tool to explore the space between novice and expert behavior. Finally, we suggest potential uses for the task as a formative assessment tool at the classroom and program levels.
Spray Flames in an Air-heptane Swirling Combustor

Three-dimensional n-heptane spray flames in a model swirl combustor are investig ated by means of direct numerical simulation to provide insight into spray evaporation and combustion in realistic combustors. The variable-density, low-Mach number Navier-Stokes equations are solved using a fully conservative finite difference scheme in cylindrical coordinates. Dispersed droplets are tracked in the Lagrangian framework. The droplet evaporation process is described by an equilibrium model and the vapor combustion is modeled using an adaptive one-step reaction. The results show that the vortex and flame structures are quite complex. The effect of different parameters, including the equivalence ratio, co- or counter-swirling, and inflow conditions are analyzed and are found to influence the fluid dynamics and fl ame structures. It is also found that the spray combustion is characterized by lean premixed, rich premixed, and diffusion flames, and stabilized by different mechanisms in this geometry. Furthermore, premixed flam es are found to contribute more than diffusion flames to the total heat release rate, though their appearanc e seems to be less. An unsteady flamelet model is also proposed to account for the influence of evaporation on c ombustion.
PARTISANSHIP AND GROUP SUPPORT OVER TIME: A MULTIVARIATE ANALYSIS

parties by means of multivariate techniques that have become standard in other areas of political behavior. This approach yields improved insights into the marginal difference made by membership in each group and into the nature of a party's support coalition. As an example of this approach, we analyze the Democratic coalition since 1952. Our results differ from those of previous studies in a number of ways. Most significantly, differences with respect to the strength and timing of partisan changes lend support to Carmines and Stimson's conclusion that a realignment centering on race occurred in the mid-1960s. Our findings also indicate that the Democratic party is no longer so dependent on a few groups, as it was in the 1950s, but is now almost equally dependent on six groups.
A Numerical Exploration of Parameter Dependence in Power Optimal Flapping Flight

A computational framework for analyzing and designing efficient flapping flight vehicles is presented. Two computational tools are considered: a Betz Criterion code proposed by Hall et. al., and an accelerated, unsteady, potential flow solver. The parameters considered in this paper are: the flapping frequency, the flapping amplitude in both up-down and forward-aft directions, and the addition of a mid-wing hinge for articulated flapping flight. The flapping kinematics are represented using harmonics. Three numerical experiments are examined for the flapping flight analysis. The first experiment involves sweeping through a basic flapping flight parametric design space. The second experiment minimizes flight power at a given flight condition using a quasi-Newton optimization. The third experiment demonstrates the conversion of the problem from a wake only analysis to a 3-D flapping wing geometry.
A Theoretical Framework for Sociological Research in Community Organization

is represented by variation in time. This contention rests perhaps on outmoded evolutionary assumptions about communal change which require demonstration rather than postulation. So far as community analyses are concerned, these practices leave us with only a synchronic analysis of community functions and process. A second reason for the apparent ahistorical bias in community study is the argument that "community no longer is a meaningful unit of analysis in modern societies." Such an argument fairly begs the question of valid reasons for studying any phenomenon in social science, for it is assumed we seek not a science of the present but one which has validity through time. This ahistorical approach therefore ignores the question of change most flagrantly. If the postulate "there is no community now" is valid, then a study of community is necessary for an understanding of "why no community now" and for a prediction of "will there be communities in the future, and if so, under what conditions?" A corollary of this argument is the contention that the concept of community is useful to describe the rural community only as it once was. To be trite, perhaps the rural community never "was."9 In any event, the U. S. rural community "never was" in the sense in which social scientists idealize the small farm owner community as rural. The careful delineation of community phenomena should permit a description and comparative analysis of empirical cases of communities in history and under current conditions so that we may analyze community as a form of human activity. Whether "community" now "empirically exists" in the United States is only partially relevant to this more general consideration. A further corollary of the ahistorical argument is that what community is now, it must always be. Perhaps it is worthwhile simply to note that in science we may at least aspire to learn what may be possible.
Recent Developments in Derivatives Markets

This slide deck is intended to provide an up-to-date background on financial derivatives markets at the undergraduate level.
Depressive Symptoms and Perceptions of Child Difficulty Are Associated with Less Responsive Feeding Behaviors in an Observational Study of Low-Income Mothers

Abstract Background: Maternal depressive symptoms and perceptions of child difficulty are associated with negative effects on general development and cognitive functioning in children. The study examined associations between maternal depressive symptoms, perceptions of child difficulty, and maternal feeding behaviors in a population at elevated risk for childhood obesity. Methods: Participants were 138 low-income black and Hispanic mothers and their children (ages 3–5) participating in an observational study of mealtimes among Head Start families. Three dinnertime observations were conducted over 2 weeks on each family and audio/videotaped for coding. Coding included eating influence attempts and other food- and nonfood-related interactions exhibited by the mother during dinner. Mothers completed questionnaires on depressive symptoms and perceptions of child difficulty. Linear regressions were conducted, examining associations between maternal depressive symptoms, perceptions of child difficulty, and code...
Regional Brain Volume and Cognitive Outcome in Preterm Infants

Regional cortical volumes, measured by structural magnetic resonance imaging scans, were compared in 25 eight-year-old preterm children and 39 term control children, in a study performed at Yale and Brown University Medical Schools, and reported from the Yale Child Study Center, New Haven, CT.