cssi/SciSciGPT-SciSciNet huggingface dataset:
Evolutionary clues to eukaryotic DNA clamp-loading mechanisms: analysis of the functional constraints imposed on replication factor C AAA+ ATPases

Ring-shaped sliding clamps encircle DNA and bind to DNA polymerase, thereby preventing it from falling off during DNA replication. In eukaryotes, sliding clamps are loaded onto DNA by the replication factor C (RFC) complex, which consists of five distinct subunits (A-E), each of which contains an AAA+ module composed of a RecA-like alpha/beta ATPase domain followed by a helical domain. AAA+ ATPases mediate chaperone-like protein remodeling. Despite remarkable progress in our understanding of clamp loaders, it is still unclear how recognition of primed DNA by RFC triggers ATP hydrolysis and how hydrolysis leads to conformational changes that can load the clamp onto DNA. While these questions can, of course, only be resolved experimentally, the design of such experiments is itself non-trivial and requires that one first formulate the right hypotheses based on preliminary observations. The functional constraints imposed on protein sequences during evolution are potential sources of information in this regard, inasmuch as these presumably are due to and thus reflect underlying mechanisms. Here, rigorous statistical procedures are used to measure and compare the constraints imposed on various RFC clamp-loader subunits, each of which performs a related but somewhat different, specialized function. Visualization of these constraints, within the context of the RFC structure, provides clues regarding clamp-loader mechanisms--suggesting, for example, that RFC-A possesses a triggering component for DNA-dependent ATP hydrolysis. It also suggests that, starting with RFC-A, four RFC subunits (A-D) are sequentially activated through a propagated switching mechanism in which a conserved arginine swings away from a position that disrupts the catalytic Walker B region and into contact with DNA thread through the center of the RFC/clamp complex. Strong constraints near regions of interaction between subunits and with the clamp likewise provide clues regarding possible coupling of hydrolysis-driven conformational changes to the clamp's release and loading onto DNA.
Real-time, in vivo investigation of mechanical stimulus on cells with remotely activated, vibrational magnetoelastic layers

A system was developed for real-time, in vivo investigation of the relationship between local cell-level nano-mechanical perturbation and cell response to chemical-physical biomaterial surface properties. The system consisted of a magnetoelastic (ME) layer that could be remotely set to vibrate, at submicron levels, at a predetermined amplitude and profile. Experiments result indicated that submicron localized vibrations coupled with tailored biomaterial surface properties could selectively control cellular adhesion and possibly guide phenotypic gene expression. Practical application of this system includes modulation and monitoring of the surface of implantable biomaterials. The ME based vibrational system is the first of its kind for use in vitro for culture based mechanical testing, which could be readily deployed in situ as an in vivo system to apply local mechanical loads. It could be applied to specific implant surface sites and then subsequently sealed prior to long-term implantation. The potential advantage of this system over other similar approaches is that the system is translatable — the functional layer can serve as a “cellular workbench” material but could also be adapted and applied to the surface of implantable biomaterials and devices.
Mucolipidosis II (I-cell disease): studies of muscle biopsy and muscle cultures.

Summary: Muscle cultures from a patient with I-cell disease showed the characteristic morphologic and biochemical abnormalities previously observed in cultured fibroblasts. At early stages of myoblast growth, there were numerous inclusions. Biochemically, the intra-cellular activities of β-galactosidase, β-hexosaminidase, and α-mannosidase were reduced to 1,14, and 5%, respectively, of control values, and this was accompanied by elevated levels of β-hexosaminidase and α-mannosidase in the culture medium. Cultures from the patient did not fuse as well as controls; however, when well-developed myotubes possessing distinct cross-striations were present, these no longer had inclusions. In the muscle biopsy from this patient, only β-galactosidase was decreased to approximately 50% of the mean control value whereas β;-hexosaminidase and α-mannosidase activities were increased as compared to controls. These data suggest that the I-cell mutation is expressed during early myogenesis but not in well-differentiated myotubes or mature muscle fibers. Speculation: The expression of the I-cell mutation in cultured fibroblasts as compared to immature versus mature muscle suggests that the intracellular localization of acid hydrolases into lysosomes may occur via different pathways in different tissues and may also differ at various stages in development.
The role of chorionic gonadotropin (CG) in blastocyst implantation

Implantation is a complex spatio-temporal interaction between the genotypically different embryo and the mother. Success of this event requires the synchronization of development and effective biochemical communications from both sides. Chorionic gonadotropin (CG), which is a major embryonic signal in the primate, is a glycoprotein hormone synthesized and secreted by the trophoblast. Various isoforms exist in plasma, urine, and blastocyst culture medium, a result of posttranslational modifications. The exponential secretion of CG and its long circulatory half-life extends the life span of corpus luteum to maintain the supply of progesterone during the first 6-8 weeks of pregnancy. To study the direct effects of CG in the uterus, we used the baboon (Papio anubis) as a non-human primate model. In vivo stimulation with CG during the window of uterine receptivity results in further morphologic and biochemical modifications of the receptive endometrium. These are characterized by the plaque reaction in the luminal epithelium, an increase in glycodelin expression and secretion by the glandular epithelium, and the differentiation of subepithelial stromal fibroblasts characterized by expression of the alpha smooth muscle actin (alpha SMA). Pretreatment with progesterone receptor antagonist (PRa) completely or partially inhibits these effects. The signal transduction pathway activated by CG in primate endometrial epithelial cells involves the protein kinase A (PKA)-independent phosphorylation of extracellular signal regulated kinase (ERK 1/2). This alternate signal transduction pathway may prevent CG Receptor (R) downregulation at the implantation site and enhance epithelial cell proliferation and differentiation. Thus, our results suggest that CG plays an important role in implantation in addition to its luteotrophic role.
An intramolecular aza-[3+3] annulation approach to azaphenalene alkaloids. Total synthesis of myrrhine.

A detailed account on the stereoselective total syntheses of azaphenalene alkaloids via an intramolecular aza-[3 + 3] annulation strategy is described here. All five members of the Coccinellidae family of defensive alkaloids were prepared from the same common intermediate, which was derived from a stereoselective aza-[3 + 3] annulation reaction.
Effects of morphological complexity on phonological output deficits in fluent and nonfluent aphasia.

Abstract This study examined the effects of morphological complexity on aphasic speakers with lexical–phonological output deficits. Subjects were two fluent and two nonfluent aphasic speakers who repeated morphologically simple words at the same level of accuracy and whose errors were virtually all phonological in nature. They were asked to repeat a variety of morphologically complex (i.e., affixed) words. Results were interpreted within our two-stage model of lexical–phonological production (Kohn & Smith, 1994, 1995), which we expand to include a distinction between derivational and inflectional morphology. When comparing overall performance levels between morphologically simple and complex words, only three subjects exhibited more difficulty repeating the morphologically complex targets. Nevertheless, when comparing repetition accuracy between different types of morphologically complex words (e.g., derived vs. inflected), all four subjects displayed similar patterns. These findings suggested that while morphological complexity has different effects on the two stages within the lexical–phonological output system, the relative effects of different morphological structures are constant. At the level of error analysis, patterns of affix errors distinguished the nonfluent from the fluent subjects in ways that are reminiscent of the affix errors associated with agrammatic and paragrammatic speech. This finding raised questions concerning the relationship between morphosyntactic and morphophonological deficits.
Fragility and glass transition temperature of polymer confined under isobaric and isochoric conditions

It is now well established that the glass transition temperature (Tg) of polymers can deviate substantially from the bulk with nanoscale confinement. Understanding the impact of confinement on the Tg of polymers is important but it does not provide information about the temperature dependence of the cooperative segmental dynamics near the Tg, a phenomenon commonly referred to as the dynamic fragility. Here, we measure the dynamic fragility index (m) as well as the Tg of confined poly(4-methylstyrene) (P4MS) under isobaric and isochoric conditions. We accomplish this via variable cooling rate differential scanning calorimetry (DSC) studies on aqueous-suspended and silica-capped P4MS nanoparticles. We observe that both the isobaric (mp) and isochoric (mv) fragilities decrease with confinement. However, Tg decreases and remains constant with isobaric and isochoric confinement, respectively. The importance of interfaces in the observed trends as well as comparisons to prior studies is discussed.
The EGF Repeat-Specific O-GlcNAc-Transferase Eogt Interacts with Notch Signaling and Pyrimidine Metabolism Pathways in Drosophila

The O-GlcNAc transferase Eogt modifies EGF repeats in proteins that transit the secretory pathway, including Dumpy and Notch. In this paper, we show that the Notch ligands Delta and Serrate are also substrates of Eogt, that mutation of a putative UDP-GlcNAc binding DXD motif greatly reduces enzyme activity, and that Eogt and the cytoplasmic O-GlcNAc transferase Ogt have distinct substrates in Drosophila larvae. Loss of Eogt is larval lethal and disrupts Dumpy functions, but does not obviously perturb Notch signaling. To identify novel genetic interactions with eogt, we investigated dominant modification of wing blister formation caused by knock-down of eogt. Unexpectedly, heterozygosity for several members of the canonical Notch signaling pathway suppressed wing blister formation. And importantly, extensive genetic interactions with mutants in pyrimidine metabolism were identified. Removal of pyrimidine synthesis alleles suppressed wing blister formation, while removal of uracil catabolism alleles was synthetic lethal with eogt knock-down. Therefore, Eogt may regulate protein functions by O-GlcNAc modification of their EGF repeats, and cellular metabolism by affecting pyrimidine synthesis and catabolism. We propose that eogt knock-down in the wing leads to metabolic and signaling perturbations that increase cytosolic uracil levels, thereby causing wing blister formation.
A simplified approach on the elastic-plastic analysis of threaded connectors

The design of threaded connectors based on an elastic analysis appears overly conservative. This, in turn, will result in unnecessary material and manufacturing costs. To improve cost effectiveness, the design of connectors from the elastic-plastic viewpoint is warranted. This paper presents a simplified approach on the elastic-plastic finite element analysis of connectors. This approach would save tremendous computer costs which may be incurred in conducting a regular elastic-plastic analysis of threaded connectors.
Impact of recipient body mass index on organ allocation and mortality in orthotopic heart transplantation.

Background It is unknown whether obesity affects organ allocation in orthotopic heart transplantation (OHT). The United Network for Organ Sharing (UNOS) database provides an opportunity to examine this issue. Methods We reviewed UNOS data to identify 27,002 OHT candidates placed on the heart transplantation wait list (1998 to 2007). Patients were stratified by body mass index (BMI) at listing. Multivariate Cox proportional hazards model estimated the chance of receiving OHT, adjusting for factors that might affect allocation. Mortality on the wait list and post-OHT mortality were estimated using the Kaplan–Meier method. Results Of 27,002 patients listed, the distribution of BMI was as follows: BMI 18.5 to 24.9, n = 9,734 (36.0%); BMI 25 to 29.9, n = 10,063 (37.2%); BMI 30 to 34.9, 5,500 (20.4%); and BMI ≥35, 1,705 (6.3%). BMI was strongly associated with a decrease in the likelihood of receiving OHT once on the wait list (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.95 to 0.96, p p Conclusions Obese individuals wait longer and have a lower likelihood of receiving a donor heart after listing, despite similar short-term survival. The results of this study point to a potential provider bias for obese individuals in OHT.
Uncertain Tax Positions: Reconciling the Existing Guidance

ABSTRACT: Multiple revisions in recent years to IRC §6694, IRC §6662, U.S. Generally Accepted Accounting Principles (GAAP), and International Financial Reporting Standards (IFRS) have created conflicting recognition and disclosure requirements for uncertain tax positions. This paper reviews the existing recognition thresholds under these various standards—“reasonable basis,” “substantial authority,” and “more‐likely‐than‐not”—and discusses scenarios in which the standards may cause reporting conflicts between tax and financial reporting. This paper also reviews the extant disclosure guidance for uncertain tax positions included in tax and financial reporting, with a particular emphasis on the newly issued proposed IRS regulations regarding general and specific‐item disclosures for tax return preparers.
Alternative Smoothing and Scaling Strategies for Weighted Composite Scores

In this study, smoothing and scaling approaches are compared for estimating subscore-to-composite scaling results involving composites computed as rounded and weighted combinations of subscores. The considered smoothing and scaling approaches included those based on raw data, on smoothing the bivariate distribution of the subscores, on smoothing the bivariate distribution of the subscore and weighted composite, and two weighted averages of the raw and smoothed marginal distributions. Results from simulations showed that the approaches differed in terms of their estimation accuracy for scaling situations with smaller and larger sample sizes, and on weighted composite distributions of varied complexity.
Use of the Nonionic Superbase P(MeNCH2CH2)3N in the Selective Monoalkylation of Active-Methylene Compounds

The symmetric active-methylene compounds CH2(CO2Et)2 and CH2[C(O)Me]2 are selectively monoalkylated in the presence of 1.1 equiv of a variety of alkyl halides and 1 equiv of the nonionic superbase P(MeNCH2CH2)3N in 85−98% yields in 30 min at room temperature. The unsymmetrical active-methylene compound EtO2CCH2C(O)Me is selectively monoalkylated under the same conditions, except for the temperature, which is 0 °C, in 59−88% yields. The observation of selective C- rather than O-alkylation is rationalized in terms of the formation of an enolate whose negatively charged oxygen is sterically protected by a nearby HP(MeNCH2CH2)3N+ counterion in a tight ion pair.
I-V curve signatures of nonequilibrium-driven band gap collapse in magnetically ordered zigzag graphene nanoribbon two-terminal devices

Motivated by the very recent fabrication of sub-10-nm-wide semiconducting graphene nanoribbons [X. Li et al., Science 319, 1229 (2008)], where some of their band gaps extracted from transport measurements were closely fitted to density-functional theory predictions for magnetic ordering along zigzag edges that is responsible for the insulating ground state, we compute current-voltage $(I\text{\ensuremath{-}}V)$ characteristics of finite-length zigzag graphene nanoribbons (ZGNRs) attached to metallic contacts. The transport properties of such devices, at source-drain bias voltages beyond the linear-response regime, are obtained using the nonequilibrium Green's function formalism combined with the mean-field version of the Hubbard model fitted to reproduce the local spin-density approximation description of magnetic ordering. Our results indicate that magnetic ordering and the corresponding band gap in ZGNR can be completely eliminated by passing large enough direct current through it. The threshold voltage for the onset of band gap collapse depends on the ZGNR length and the contact transparency. If the contact resistance is adjusted to experimentally measured value of $\ensuremath{\simeq}60\text{ }\text{k}\ensuremath{\Omega}$, the threshold voltage for sub-10-nm-wide ZGNR with intercontact distance of $\ensuremath{\simeq}7\text{ }\text{nm}$ is $\ensuremath{\approx}0.4\text{ }\text{V}$. For some device setups, including $60\text{ }\text{k}\ensuremath{\Omega}$ contacts, the room-temperature $I\text{\ensuremath{-}}V$ curves demonstrate steplike current increase by one order of magnitude at the threshold voltage and can exhibit a hysteresis as well. On the other hand, poorly transmitting contacts can almost completely eliminate abrupt jump in the $I\text{\ensuremath{-}}V$ characteristics. The threshold voltage increases with the ZGNR length (e.g., reaching $\ensuremath{\approx}0.8\text{ }\text{V}$ for $\ensuremath{\simeq}13\text{-nm}$-long ZGNR) which provides possible explanation of why the recent experiments [Wang et al., Phys. Rev. Lett. 100, 206803 (2008)] on $\ensuremath{\sim}100\text{-nm}$-long GNR field-effect transistors with bias voltage $l1\text{ }\text{V}$ did not detect the $I\text{\ensuremath{-}}V$ curve signatures of the band gap collapse. Thus, observation of predicted abrupt jump in the $I\text{\ensuremath{-}}V$ curve of two-terminal devices with short ZGNR channel and transparent metallic contacts will confirm its zigzag edge magnetic ordering via all-electrical measurements, as well as a current-flow-driven magnetic-insulator--nonmagnetic-metal nonequilibrium phase transition.
A Calcium Wave Mediated by Gap Junctions Coordinates a Rhythmic Behavior in C. elegans

Summary Intercellular calcium waves can be observed in adult tissues, but whether they are instructive, permissive, or even required for behavior is predominantly unknown. In the nematode Caenorhabditis elegans , a periodic calcium spike in a pacemaker cell initiates a calcium wave in the intestine [1, 2]. The calcium wave is followed by three muscle contractions that comprise the defecation motor program [1]. Normal wave propagation requires the pannexin gap-junction subunit INX-16 at the interfaces of the intestinal cells. In the absence of this gap-junction subunit, calcium waves are frequently absent. The remaining waves are slow, initiate at abnormal locations, or travel in the opposite direction. Abnormal waves are associated with parallel effects in the first step of the motor program: The contractions of the overlying muscles fail to propagate beyond the pacemaker cell, are slow, initiate in abnormal locations, or are reversed. Moreover, the last two motor steps are predominantly absent. Finally, the absence of this gap-junction subunit also affects the reliability of the pacemaker cell; cycle timing is often irregular. These data demonstrate that pannexin gap junctions propagate calcium waves in the C. elegans intestine. The calcium waves instruct the motor steps and regulate the pacemaker cell's authority and reliability.
Structure and Moisture Permeability of Film-Forming Polymers

The study concluded that film-forming polymers having low moisture permeabilities should have the following structural characteristics: 1. Saturated or nearly saturated carbon chain, unless the chain has symmetry permitting high crystallinity; 2. Minimum of chain branching; 3. High degree of lateral symmetry; 4. Very high proportion of relatively small, nonhydrophilic substituents; 5. Fair degree of longitudinal order of symmetry. Extensive table of permeabilities given. 45 ref.
Competitive bioreactor hens on the horizon

The hen has long held promise as a low-cost, high-yield bioreactor for the production of human biopharmaceuticals in egg whites using genetic engineering. Two separate reports have recently appeared indicating the production of substantial levels of human monoclonal and single chain antibodies (>3mg and >150mg, respectively) in eggs of transgenic hens. These promising findings indicate that the hen is close to becoming a competitive manufacturing platform for the production of human biopharmaceuticals.
Friedel oscillations of density of states in a one-dimensional Mott insulator and incommensurate charge-density wave or superconductor

Oscillations of local density of states generated by a single scalar impurity potential are calculated for one-dimensional systems with dynamically generated charge or spin gap. At zero temperature, the oscillations develop at finite wave vector ($\ensuremath{\pi}$ for the Mott insulator and $2{k}_{F}$ for incommensurate charge-density wave or superconductor) and at frequencies larger than the soliton spectral gap $m$. Their amplitude has a broad maximum at $\ensuremath{\omega}\ensuremath{\approx}3m$, where $m$ is the gap magnitude.
Metabolic perturbations in the diabetic heart: Mechanisms and molecular targets

Diabetes is associated with altered myocardial substrate utilization, specifically increased fatty acid (FA) utilization and decreased glucose utilization. This switch in substrate utilization is associated with decreased cardiac efficiency and decreased energetic reserves, and can increase the risk of heart failure. Potential mechanisms include increased delivery of FAs to the heart, upregulation of FA utilization pathways via activation of transcription factors such as PPAR-α, myocardial insulin resistance and mitochondrial dysfunction. This review will summarize our current understanding of the pathophysiology of metabolic disturbances in the diabetic heart and will discuss potential therapeutic targets.
Changes in intracranial pressure, coagulation, and neurologic outcome after resuscitation from experimental traumatic brain injury with hetastarch

Background. In a model of traumatic brain injury (TBI), 2 protocols compared changes in intracranial pressure (ICP), coagulation, and neurologic outcome after intravenous fluid (IVF) resuscitation with either Hextend (HEX, 6% hetastarch in lactated electrolyte injection) or standard of care, crystalloid plus mannitol (MAN). Methods. In the nonsurvivor protocol, swine (n = 28) received a fluid percussion TBI and hemorrhage (27 ± 3 mL/kg). At 30 minutes, resuscitation began with lactated Ringer’s (LR) or HEX. After 60 minutes, MAN (1 g/kg) or placebo was given plus supplemental IVF to maintain cerebral perfusion pressure (CPP) $70 mm Hg for 240 minutes. Swine in the survivor group (n = 15) also underwent TBI and hemorrhage, and resuscitation with HEX was compared to that of normal saline (NS)+MAN. Neurologic outcome and coagulation were evaluated for 72 hours. Results. In the nonsurvivor protocol, HEX, LR+MAN, and HEX+MAN attenuated the time-related rise of ICP and prevented ICP >20 mm Hg versus LR alone (P < .05). HEX alone maintained CPP (relative to baseline) and decreased total IVF by 50% versus LR ± MAN (P < .05). MAN had no additive effect with HEX. Coagulation, measured by thromboelastograph reaction time (R), was 11 ± 1 and 9 ± 1 minutes at baseline and after TBI (before randomization). At 240 minutes after HEX or LR+MAN, R was 6 ± 1o r 7± 2 minutes, which indicates a hypercoagulable state, but there was no difference between treatments. In the survivor protocol, ICP and CPP were similar with NS+MAN versus HEX, but IVF requirement was 161 ± 20 versus 28 ± 3 mL/kg (P < .05). Motor scores were higher on days 2 and 3 with HEX (P < .05). At 72 hours, R was 28 ± 14 versus 26 ± 6 minutes with NS+MAN versus HEX, which indicates a hypocoagulable state, but there was no difference between treatments. Conclusions. Hextend as the sole resuscitation fluid after severe TBI reduces fluid requirement, obviates the need for mannitol, improves neurologic outcome, and has no adverse effect on the coagulation profile relative to the crystalloid plus mannitol standard of care. (Surgery 2004;136:355-63.)
Accuracy of the rapid fetal fibronectin TLi system in predicting preterm delivery.

Numerous studies have demonstrated that fetal fibronectin (fFN) is an excellent marker of preterm delivery with a negative predictive value (NPV) >99% for predicting delivery within 7 or 14 days in symptomatic women (1)(2)(3). Interestingly, these studies have been performed by sending the sample to Adeza Biomedical for testing using an ELISA microtiter plate or by a rapid colloidal gold test marketed only outside the US. In the US, however, the only method available for rapid fFN analysis is the TLi™ system (Adeza Biomedical). Our objective was to assess the utility of the TLi rapid fFN system to predict delivery in symptomatic patients within 7, 14, or 21 days. We used 501 cervicovaginal samples consecutively received in the Barnes-Jewish Hospital Laboratory for physician-ordered fFN analysis during an 18-month period for the study (February 2001–August 2002). From this cohort, charts for 243 patients were available for review. This constitutes the group of patients who delivered at Barnes-Jewish Hospital. Study inclusion criteria included the following: signs …
Surface Flashover of Water Repellant Insulators under Moist Conditions

A study was conducted to determine how surface moisture can lower the flashover strength of insulation, with particular reference to out-door high voltage insulation. Since water repellant greases are used to prevent flashover under moist, contaminated conditions, and since new insulator materials will have improved water repellancy, the study concentrated on surface wetting effects. Studies were made of droplet growth during fog for several surfaces. Flashover studies showed that near threshold, flashover occurred by means of droplet deformation in the electric field. Rough agreement was obtained with a simple theory. The study provided further support for the development of hydrophobic coatings for outdoor insulation.
Soil microbial responses to elevated phosphorus and pH in acidic temperate deciduous forests

Although northern temperate forests are generally not considered phosphorus (P) limited, ecosystem P limitation may occur on highly weathered or strongly acidic soils where bioavailable inorganic P is low. In such environments, soil organisms may compensate by increasing the utilization of organic P via the production of extracellular enzymes to prevent limitation. In this study, we experimentally increased available P and/or pH in several acidic eastern deciduous forests underlain by glaciated and unglaciated soils in eastern Ohio, USA. We hypothesized that where inorganic P is low; soil microbes are able to access organic P by increasing production of phosphatase enzymes, thereby overcoming biogeochemical P limitations. We measured surface soil for: available P pools, N mineralization and nitrification rates, total C and N, enzymes responsible for C, N, and P hydrolysis, and microbial community composition (PLFA). Increasing surface soil pH a whole unit had little effect on microbial community composition, but increased N cycling rates in unglaciated soils. Phosphorus additions suppressed phosphatase activities over 60% in the unglaciated soils but were unchanged in the glaciated soils. All treatments had minimal influence on microbial biomass, but available pools of P strongly correlated with microbial composition. Microbes may be dependent on sources of organic P in some forest ecosystems and from a microbial perspective soil pH might be less important overall than P availability. Although our sampling was conducted less than 1 year after treatment initiation, microbial community composition was strongly influenced by available P pools and these effects may be greater than short-term increases in soil pH.
Dendroaspis natriuretic peptide relaxes isolated human arteries and veins.

Background: Dendroaspis natriuretic peptide (DNP) is the newest member of the natriuretic peptide family and is a circulating peptide in humans. The effects of DNP on the human vasculature are unknown. Since other natriuretic peptides are known to cause vasorelaxation, we determined the response to DNP on human blood vessels in vitro. We also investigated the mechanism of DNP mediated vasorelaxation. Methods: Rings of human internal mammary artery and saphenous vein were suspended in an organ bath. The response to cumulative concentrations of DNP was obtained. Inhibiting agents were used to determine the mechanism of this vasorelaxation. Results: DNP caused dose-dependent relaxation, with a greater effect on the internal mammary arteries (relaxation from 10−7 mol/l DNP: 80.6±4.1%) than the saphenous veins (33.4±4.1%). At 10−7 mol/l, DNP resulted in less arterial relaxation compared with atrial and C-type natriuretic peptides and similar relaxation to brain natriuretic peptide. In veins, DNP caused the greatest relaxation of the natriuretic peptides. DNP increased tissue cyclic guanosine monophosphate (cGMP) determined by radioimmunoassay by over 7-fold. Barium chloride and indomethacin attenuated DNP mediated vasorelaxation. However, glibenclamide, charydotoxin, apamin, tetraethyl-ammonium chloride and diisothiocyanato-stilbene-2,2′-disulfonic acid did not. DNP mediated vasorelaxation was mildly attenuated with removal of the endothelium. DNP immunoreactivity was identified in both arteries and veins. Conclusions: The current study demonstrates that DNP is an endogenous human natriuretic peptide that relaxes human arteries more than veins. Furthermore, DNP mediated vasorelaxation involves the inward rectifying potassium channels, prostaglandins, and cGMP. This newest member of the natriuretic peptide family may have an important physiologic role in the human vasculature.
Preventive antibiotic usage in traumatic thoracic injuries requiring closed tube thoracostomy.

Objective To evaluate the safety and effectiveness of antibiotics in reducing the infectious complications following closed tube thoracostomy for isolated chest trauma. Design Double-blind, randomized clinical trial. Setting: Medical school affiliated large urban teaching hospital and trauma center. Patients One hundred nineteen of 159 patients over 18 years old presenting to the emergency department requiring closed tube thoracostomy for isolated chest injuries (113 penetrating, 6 blunt). Intervention Patients received either placebo or 1 g cefonicid daily intravenously started at chest tube insertion and stopped within 24 h of removal. Measurements and results: The development of wound infections, pneumonia (CDC criteria), or empyema; the incidence of adverse events; length of hospitalization. One nonspecific infection was seen in the cefonicid group (1.6 percent) and six respiratory tract infections (10.7 percent) in the placebo group (three empyema, one empyema with pneumonia, two pneumonia) (p=0.0505; p=0.0094 [excluding nonspecific infection]). No significant differences with antibiotic use were seen in the duration of chest tube use (p=0.766), peak WBC counts (p=0.108), lower peak temperatures (p=0.063), or length of hospitalization (p=0.165). Patients who developed infectious complications averaged approximately 8 days longer hospitalization than those without (p
Glia: Regulating Synaptogenesis from Multiple Directions

Glia cells are uniquely positioned at synapses, contacting pre- and post-synaptic terminals. At the Drosophila neuromuscular junction, a novel glia-derived TGF-β ligand has been found that modulates a retrograde synaptogenic signal.
Inactivation of human lipase by proteases

To determine if human lipase is inactivated by trypsin and chymotrypsin, we intubated 22 human subjects with an oroduodenal tube and stimulated pancreatic secretion with cholecystokinin octapeptide. The duodenal aspirate from each subject was divided into a control and a test sample and incubated in a 37 degrees C water bath for 2 h. An inhibitor of trypsin or chymotrypsin or more of one of these enzymes was added to the test sample. We found that the loss of lipase activity was partly prevented by inhibiting trypsin with aprotinin (910 KU/ml; P = 0.03) and was accelerated by adding bovine trypsin (2.5 mg/ml; P = 0.01). Inhibiting chymotrypsin with turkey egg white (2.5 mg/ml) totally abolished the loss of lipase activity (P = 0.01), and addition of bovine chymotrypsin (5 mg/ml) accelerated the loss of lipase activity more than adding trypsin (P = 0.01). After inhibiting chymotrypsin (to maintain lipase activity), increasing trypsin activity by adding a single or repeated doses of trypsin did not decrease lipase activity. Conversely, the addition of a single dose of chymotrypsin after inhibiting trypsin activity markedly decreased lipase activity (P less than 0.004). In conclusion, chymotrypsin is a more potent inactivator of human lipase than trypsin; chymotrypsin inactivates lipase in the absence of trypsin, but trypsin inactivation of lipase requires chymotrypsin.
Solving dilemmas by computer or counselor.

Results of studies in which either a human counselor or a computer was used to solve personal dilemmas are compared. Subjects were 415 undergraduate students. To increase stability of comparisons t...
Fretting behavior of Ti-6Al-4V under combined high cycle and low cycle fatigue loading

Abstract The fretting-fatigue behavior of titanium alloy Ti-6Al-4V under variable-amplitude (V-A) loading was investigated. This involved a two-level block of low-frequency (1 Hz) large-amplitude cycles and high-frequency (200 Hz) low-amplitude cycles, which represented the low- and high-cycle components of the turbine engine mission loading. The measured fretting-fatigue lives were compared with the predicted lives obtained from the Palmgren–Miner linear damage rule as well as from a nonlinear damage rule. These comparisons showed that there is a reasonable agreement between the predicted life from linear rule and the experimental data under variable loading conditions when conventional fatigue life relationships on the semi-logarithmic scales are employed and when the ratio of HCF and LCF cycles is large. However, the Palmgren–Miner linear prediction differs significantly from experimental data when these were compared based on the damage fraction induced by LCF and HCF components of combined cycling, and thus a non-linear method of damage accumulation is more appropriate for estimating the fretting-fatigue life under the V-A loading.
Volume Growth and General Rate Quantization on Grassmann Manifolds

The Grassmann manifold Gn,p (L) is the set of all p-dimensional planes (through the origin) in the n-dimensional Euclidean space Ln, where L is either R or C. This paper considers an unequal dimensional quantization in which a source in Gn,q (L) is quantized through a code in Gn,p (L), where p and q are not necessarily the same. The analysis for unequal dimensional quantization is based on the volume of a metric ball in Gn,q (L) whose center is in Gn,p (L). Our chief result is to show that as n, p, q and the square radius approach infinity with constant ratios, the volume of a metric ball "grows" as exp (-n2V (1 + o (1))) for a computable constant V ges 0. This result is stronger than our previous volume formula which is only valid when the radius is at most one. The tools behind the present result include large deviation techniques and equilibrium measure ideas from potential theory. Based on the volume growth formula, the rate distortion tradeoff is precisely quantified in our asymptotic region. Finally, we prove that random codes are asymptotically optimal in probability.
A quantitative model of cellular senescence influence on cancer and longevity

Contrary to the paradigm that cancer incidence increases indefinitely with age, significant data now suggest cancer incidence may markedly reduce beyond age 80 years for humans and beyond 800 days for mice, and is not inevitable. We show that increasing cellular senescence with age is a possible cause of this reduction, since senescent cells are removed from the pool of cells that retain proliferative ability necessary for cancer. We further show that animal interventions appearing to alter senescence, p53 mutation and melatonin dosing, support the prediction that increasing senescence rate reduces cancer while reducing lifespan, and vice versa. Studies of environmental agents associated with increased cancer might be re-examined to find if there is an association with longevity increases, which may markedly alter our view of such agents. We also show that if an agent functions by slowing both senescence and carcinogenesis, longevity is increased while reducing cancer. Dietary restriction is the only known intervention that accomplishes this, but there may be others.
The creation of interdisciplinary biomedical informatics education in an information technology curriculum

Unprecedented growth in the interdisciplinary domain of biomedical informatics reflects the recent advancements in genomic sequence availability, high-content biotechnology screening systems, as well as the expectations of computational biology to command a leading role in drug discovery and disease characterization. These forces have moved much of life sciences research almost completely into the computational domain. Importantly, educational training in biomedical informatics has been limited to students enrolled in the life sciences curricula, yet much of the skills needed to succeed in biomedical informatics involve or augment training in information technology curricula. This manuscript describes the methods and rationale for training students enrolled in information technology curricula in the field of biomedical informatics, which augments the existing information technology curriculum and provides training on specific subjects in Biomedical Informatics not emphasized in bioinformatics courses offered in life science programs, and does not require prerequisite courses in the life sciences.
Explaining Cross‐National Variation in the Effect of Higher Education on Religiosity

While sociologists have long argued that higher education has a secularizing influence, recent research emphasizes the moderating role of social contexts in the relationship between social class and religion. I extend this line of research by examining sources of cross-national variation in the association between higher education and religiosity using survey data from more than 46,000 respondents in 39 nations. Multilevel models of a religiosity scale show (1) in the aggregate, higher education has a moderate, negative effect on the religiosity scale, (2) this effect varies considerably across nations, and (3) the negative effect of higher education on religiosity is most robust in relatively religious nations. These results demonstrate the importance of national contexts in moderating the effect of education on religiosity. The results also support a cultural diffusion argument that suggests that the highly educated are innovators and early adopters of secular behaviors but that low levels of religiosity then diffuse to less-educated segments of a population as secularity becomes more common.
Prodrug based optimal drug delivery via membrane transporter/receptor

The carrier-mediated absorption of drugs and prodrugs across epithelial and endothelial barriers is emerging as a novel trend in biotherapeutics. This review examines the important advances in this field in the past decade. The feasibility of drug absorption of the parent drug or the appropriately modified prodrug via these transporters is discussed in detail. Several successful examples of synthesis of prodrugs recognised by the targeted transporters are described. The applicability of this approach in translocating drugs across the almost impenetrable blood-brain barrier (BBB) has also been examined.
Modeling Housing Appreciation Dynamics in Disadvantaged Neighborhoods

There is long-standing interest in predicting if and when less advantaged urban neighborhoods will experience upsurges in their housing prices, yet little research has investigated year-to-year neighborhood price dynamics. The authors advance knowledge in this realm by employing anually updated, readily available indicators created from the Home Mortgage Disclosure Act and assessor’s data from Washington, D.C., census tracts for 1995 to 2005 to estimate a hazard model of the year when consistent, substantial, and sustained housing price appreciation starts in disadvantaged neighborhoods, based on predictors measured one and two years in advance. The results suggest that proximity to stronger neighborhoods, a robust metropolitan housing market, and inflows of higher-status home buyers are key predictors of appreciation onset in disadvantaged neighborhoods, but replications and refinements are needed before firm generalizations about this process can be made.
Smarter Blogroll: An Exploration of Social Topic Extraction for Manageable Blogrolls

The already huge number of blogs in existence is increasing rapidly, and many users are struggling to find a way to keep up with the expansion. A number of existing tools aim to capture the general topics of all currently popular topics among the entire blogosphere, while others allow individuals to read a fixed list of blogs. However, few personalized tools exist to help the individual get an overview of the specific blogs he or she reads. This paper presents the concept of social topic extraction via the Smarter Blogroll, which displays current topics for a selection of blogs. While there was little difference in users' ability to identify topics using the smarter blogroll, the results of our user study point to design recommendations for improving the use of metadata within blogroll entries, thereby facilitating blog reading. The paper concludes with implications for the design of tools to aid in blog navigation and reading, as well as recommended directions for future research.
Inheritance Studies Implicate a Genetic Mechanism for Apparent Sex Reversal in Chinook Salmon

Abstract The apparent increase in altered sexual differentiation in Pacific salmon Oncorhynchus spp. is a growing concern. Previous studies suggest that incongruence between genetic and phenotypic sex in Chinook salmon O. tshawytscha may be a result of altered sexual differentiation through exposure to endocrine-disrupting chemicals (EDCs). Artificial crosses between genotypically normal Chinook salmon, or between genotypically normal males and apparent sex-reversed males (XY females), were performed to test the validity of OtY1 and growth hormone pseudogene (GHΨ) genetic markers as indicators of phenotypic sex in fall-run Chinook salmon. The offspring produced were genotyped with the Y-chromosome-specific markers and were dissected to observe gonad morphology. The results of the breeding experiments indicate that approximately half of the phenotypic female offspring of XY females have a male genotype according to both Y-chromosome markers. These results refute an earlier hypothesis that phenotypic female...
Characteristics of Wetland Soils Impacted by Acid Mine Drainage

Abstract A proposed section of Appalachian Corridor H, an interstate highway that begins at I-79 near Weston, WV, and will continue east to I-81 at Strasburg, VA, will pass through an area of the Beaver Creek watershed that was previously mined for the acid-producing Upper Freeport coal. Beaver Creek flows into the Blackwater River after flowing out of Canaan Valley. Partially reclaimed spoils from past mining activities are generating acid mine drainage. Wetlands adjacent to the spoils support plant communities that appear to be naturally treating the drainage. To better understand the chemical and physical functions within the wetlands and to assist the West Virginia Division of Highways in constructing wetlands for mitigating environmental damage, we described the soils of the mine-drainage-impacted wetlands (Narrow Wetland, Iron Pond, and Railroad Grade) and took samples for subsequent laboratory analyses. For comparison, we also described and sampled unimpacted soils in Elder Swamp, which is an adjac...
Two Birds With One Myth-Debunking Campaign Engaging Students to Target Psychological Misconceptions

Misconceptions of psychological phenomena are widespread and often not easily eliminated—even among students completing college-level psychology courses. As part of a research methods psychology co...
The Impact of Downward Auditor Changes on Information Risk for Non-Accelerated Filers

In this study, we examine the impact of changes in auditor quality on financial reporting information risk, particularly for smaller public companies (non-accelerated filers). Non-accelerated filers represent a large share of public reporting companies (over 60% in 2009), and given opportunity to grow, can create new jobs, providing incentives for recent efforts to exempt or scale back costly regulations. The regulatory easing has created lower disclosure and audit requirements for smaller public companies (non-accelerated filers) compared to larger public companies (accelerated filers). The demise of Arthur Andersen and increased attestation requirements for larger public companies has caused a dramatic decrease in Big 4 audits of smaller public companies. A downward auditor change (from a Big 4 to lower tier auditor) provides the setting to examine the extent to which auditor quality (proxied by auditor size) attenuates or mitigates non-accelerated filer information risk, as measured by stock return synchronicity. Contrary to our expectations, we find that non-accelerated filers have lower information risk in the period following downward auditor changes from Big 4 auditors compared to a matched sample of non-accelerated filers that continue to retain Big 4 auditors. This result also applies when the comparison group is a sample of accelerated filers that change from Big 4 auditors. The results are particularly salient for downward changes to Tier 2 auditors. Our study adds to the literature on audit quality and should be of interest to investors, researchers, and regulators.
Self-Employment/Employment Taxes and the Entity Choice Decision for Owners of Closely Held Firms

Organizing closely held firms as partnerships or S corporations determines whether self-employment taxes or employment taxes are paid on owners' distributed earnings. If tax rates and income subject to taxation are identical for both entities, then the entity choice decision is irrelevant for purposes of minimizing self-employment/employment taxes. In this paper, we review Internal Revenue Code provisions, court cases, and revenue rulings to isolate situations that appear to favor one organizational form over the other for minimizing self-employment/employment taxes. Particularly relevant are rulings related to the tax treatment of dividends for S corporations and the regulatory requirement to aggregate self-employment earnings from all businesses. In some cases, such as real estate investments, the entity choice decision appears to be irrelevant. For inactive S corporation stockholders and limited partners the entity choice decision also appears to be inconsequential. Active owners can minimize self-employment/employment taxes the most from initial entity choice or change to/from one entity to the other, but the timing of earnings distributions is critical.