cssi/SciSciGPT-SciSciNet huggingface dataset:
The anatomy of the ferret paratracheal parasympathetic nerve-ganglion plexus

Silver-impregnated preparations of the ferret paratracheal nerve-ganglion plexus were studied for description and quantitation of the general morphology of ganglia and nerve bundles and trunks. Most ganglia were found in one or two chains, separated by interganglionic nerve trunks, running the length of the trachea in close apposition to the trachealis muscle. Ganglia were flat, one cell deep, and characterized by irregular spacing and small and variable numbers of perikarya. Perifascicular, infrafascicular, and mixed types of ganglia were seen. The mean perikaryon density was 127 ± 20/cm2 of trachealis muscle. In addition to connections to the interganglionic nerve trunk, more than 70% of ganglia were also apparently “connected” to nerve bundles running to the periphery and/or the center of the preparation, and the plexus seemed considerably more complex than originally described. There was no significant change in density, size or type, or connections of ganglia with nerve bundles in the cervical or tho...
The effect of colchicine on guinea pig intestinal enzyme activity.

The intestinal mucosal reaction to colchicine in guinea pigs as measured by sucrase, maltase, and gamma glutamyl transpeptidase activity is described. There is a significant fall in disaccharidase activity without alteration in the peptidase activity after colchicine administration. This suggests a specific response of the disaccharidase system rather than a generalized toxic mucosal effect of colchicine.
Residues in Conserved Loops of Intramembrane Metalloprotease SpoIVFB Interact with Residues near the Cleavage Site in Pro-σK

Intramembrane metalloproteases (IMMPs) control critical biological processes by cleaving membrane-associated proteins within a transmembrane segment or at a site near the membrane surface. Phylogenetic analysis divides IMMPs into four groups. SpoIVFB is a group III IMMP that regulates Bacillus subtilis endospore formation by cleaving Pro-σK and releasing the active sigma factor from a membrane. To elucidate the enzyme-substrate interaction, single-cysteine versions of catalytically inactive SpoIVFB and C-terminally truncated Pro-σK(1-126) (which can be cleaved by active SpoIVFB) were coexpressed in Escherichia coli, and proximity was tested by disulfide cross-linking in vivo. As expected, the results provided evidence that catalytic residue Glu-44 of SpoIVFB is near the cleavage site in the substrate. Also near the cleavage site were two residues of SpoIVFB in predicted conserved loops; Pro-135 in a short loop and Val-70 in a longer loop. Pro-135 corresponds to Pro-399 of RseP, a group I IMMP, and Pro-399 was reported previously to interact with substrate near the cleavage site, suggesting a conserved interaction across IMMP subfamilies. Val-70 follows a newly recognized conserved motif, PXGG (X is a large hydrophobic residue), which is in a hydrophobic region predicted to be a membrane reentrant loop. Following the hydrophobic region is a negatively charged region that is conserved in IMMPs of groups I and III. At least two residues with a negatively charged side chain are required in this region for activity of SpoIVFB. The region exhibits other features in IMMPs of groups II and IV. Its possible roles, as well as that of the short loop, are discussed. New insights into IMMP-substrate interaction build toward understanding how IMMPs function and may facilitate manipulation of their activity.
Incremental Method for Structural Analysis of Joined-Wing Aircraft

Joined-wing aircraft are characterized by statically indeterminate structures, i.e., structures with multiple load paths. A newway of analyzing these configurations is introduced. This new formulation is based on the fully intrinsic equations, which introduce neither singularities nor infinite-degree nonlinearities caused by finite rotation. The formulation makes use of an incremental form of the kinematical equations, which allows preservation of the main advantageous features of the fully intrinsic equations. Themethod is applied and verified for a joined-wing structure.
Communication theoretic analysis of underwater ad-hoc networks in the presence of interference

We consider the performance of underwater acoustic ad-hoc networks in the presence of interference. We assume a uniform distribution of nodes over a finite area. The node-to-node channel is modeled using frequency dependent path loss and Ricean fading. We adopt a communication theoretic approach and study the interdependence of the sustainable number of hops through the network, end-to-end frame error probability, power and bandwidth allocation. The network operation is highly dependent on the node density with two distinct regions of limited performance: the coverage-limited region, where the number of nodes in the network is small, and the interference-limited region, where the number of nodes is large. We show that a desired level of connectivity can be achieved through a judicious selection of the operating frequency, power and bandwidth. Numerical examples are presented that illustrate the results of the analysis.
Upper Ordovician (Mohawkian) carbon isotope (δ13C) stratigraphy in eastern and central North America: Regional expression of a perturbation of the global carbon cycle

Abstract The Guttenberg carbon isotope excursion (GICE) documented from eastern North America demonstrates the effects that regional, geochemically distinct water masses, upwelling, and ocean circulation have on the carbon isotope record from carbonate platforms. Late Turinian–Chatfieldian carbonates from Oklahoma, Kentucky, Virginia, and West Virginia record a positive carbon isotope excursion (≥ + 3.0‰), the GICE excursion. The GICE excursion has relations to established biostratigraphy (beginning in the North American Midcontinent Phragmodus undatus Conodont Zone and continuing through the Plectodina tenuis Zone), sequence, and event stratigraphy. Previously established models for positive carbon isotope shifts on carbonate platforms have been tested during the GICE excursion, where geochemically distinct water masses are defined for the Upper Ordovician. A major eustatic sea-level rise before the GICE promoted a greater exchange of open ocean waters onto the carbonate platform of Laurentia; however, restricted or sluggish circulation and exchange between water masses within the epeiric seas and the adjacent Iapetus Ocean were still apparent. Local variations documented in the GICE excursion are directly related to upwelling of nutrient rich isotopically light waters, increased primary productivity, and the subsequent organic carbon production and burial.
The seed concepts constraint in code switching

: The ‘seed concepts’ hypothesis states that there exists in the human mind a set of most fundamental concepts that crystallize during the earliest period of ‘concept formation’ in the mind of the infant, a period which is broadly concomitant with the incipient ‘single-word’ stage (around 18–24 months) in the child's language acquisition process. These concepts seem to stem from the child's need to distinguish his ‘self from the ‘nonself through the instrumentality, primarily, of sensorimotor activity. This notion of ‘seed concepts’, in turn, gives rise to the ‘seed concepts constraint’, on all-encompassing, universal principle. This principle holds that in the intra-sententially code-switched speech of the bilingual the ‘seed concepts’ get heavily marked for realization in the phonetics of the first language (the ‘seed language’) in contradistinction to the second language (the ‘feed language’). It is claimed that, although subject to parameterization to a limited extent, the ‘seed concepts constraint’ suffices to replace the various particularistic grammatical claims concerning intrasentential code switching hitherto proposed in the literature.
Design methodology to trade off power, output quality and error resiliency: application to color interpolation filtering

Power dissipation and tolerance to process variations pose conflicting design requirements. Scaling of voltage is associated with larger variations, while Vdd up-scaling or transistor up-sizing for process tolerance can be detrimental for power dissipation. However, for certain signal processing systems such as those used in color image processing, we noted that effective trade-offs can be achieved between Vdd scaling, process tolerance and "output quality". In this paper we demonstrate how these tradeoffs can be effectively utilized in the development of novel low-power variation tolerant architectures for color interpolation. The proposed architecture supports a graceful degradation in the PSNR (peak signal to noise ratio) under aggressive voltage scaling as well as extreme process variations in sub-70 nm technologies. This is achieved by exploiting the fact that some computations are more important and contribute more to the PSNR improvement compared to the others. The computations are mapped to the hardware in such a way that only the less important computations are effected by Vdd-scaling and process variations. Simulation results show that even at a scaled voltage of 60% of nominal Vdd value, our design provides reasonable image PSNR with 69% power savings.
Low edge safety factor operation and passive disruption avoidance in current carrying plasmas by the addition of stellarator rotational transform

Low edge safety factor operation at a value less than two ( q(a)=1/ιtot(a)<2) is routine on the Compact Toroidal Hybrid device with the addition of sufficient external rotational transform. Presently, the operational space of this current carrying stellarator extends down to q(a)=1.2 without significant n = 1 kink mode activity after the initial plasma current rise phase of the discharge. The disruption dynamics of these low edge safety factor plasmas depend upon the fraction of helical field rotational transform from external stellarator coils to that generated by the plasma current. We observe that with approximately 10% of the total rotational transform supplied by the stellarator coils, low edge q disruptions are passively suppressed and avoided even though q(a) < 2. When the plasma does disrupt, the instability precursors measured and implicated as the cause are internal tearing modes with poloidal, m, and toroidal, n, helical mode numbers of m/n=3/2 and 4/3 observed on external magnetic sensors and...
The Role of Protestant Missionaires in Mexico ' s Indigenous Awakening

Protestantism has grown rapidly among Latin America’s indigenous population since the 1980s. Despite Protestantism’s attractiveness to indigenous people, the literature has historically regarded it as incompatible with indigenous culture. Recent scholarship has moved beyond this assertion, focusing instead on the complexities of conversion and the paradoxes associated with it. Most scholars now argue that Protestantism can be compatible with indigenous culture. It is unclear, however, how Protestant institutions came to have a compatible relationship with indigenous culture. Indeed, Protestant churches/clergy continue to eschew many of the practices associated with indigenous culture. In this paper I address this question by examining the work of Protestant missionaries. I choose missionaries as my point of analysis because they were crucial in establishing Protestantism in the region, and thus the base point from which it is defined, practiced, and altered. As a case study I examine mission work in Oaxaca, Mexico. I argue that missionaries have changed both their conversion strategies and tactics for dealing with indigenous traditions. These changes make it easier for indigenous people to convert to Protestantism without rejecting key parts of their culture, and in a few cases by even embracing it. I examine two conversion strategies—group targeting and church planting. I also analyze three tactics missionaries use to negotiate indigenous customs considered ‘pagan.’ I choose tequio, village fiestas, and language politics because they have historically been sources of conflict between converts and their Catholic neighbours.
Course, Prognosis, and Management of Psychosis in Parkinson's Disease: Are Current Treatments Really Effective?

It is essential to recognize and treat psychosis in Parkinson's disease for several reasons. Studies have shown that psychosis in Parkinson's disease patients is a strong risk factor for nursing home placement. Psychosis may be the greatest source of stress for caretakers of Parkinson's patients; it is often persistent, and its presence markedly increases mortality. Treatment of psychotic symptoms should occur only after potential medical and environmental causes of delirium have been eliminated or addressed. Initial pharmacologic changes should include limiting the patient's antiparkinsonian medications to those that are necessary to preserve motor function. Should that fail, an atypical antipsychotic is presently the treatment of choice. An emerging treatment option is acetylcholinesterase inhibitors. This article reviews what is currently known about the course, prognosis, and treatment strategies in Parkinson's disease psychosis.
Identification of Cyclic AMP-Regulated Genes in Mycobacterium tuberculosis Complex Bacteria under Low-Oxygen Conditions

Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), which kills approximately 2 million people a year despite current treatment options. A greater understanding of the biology of this bacterium is needed to better combat TB disease. The M. tuberculosis genome encodes as many as 15 adenylate cyclases, suggesting that cyclic AMP (cAMP) has an important, yet overlooked, role in mycobacteria. This study examined the effect of exogenous cAMP on protein expression in Mycobacterium bovis BCG grown under hypoxic versus ambient conditions. Both shaking and shallow standing cultures were examined for each atmospheric condition. Different cAMP-dependent changes in protein expression were observed in each condition by two-dimensional gel electrophoresis. Shaking low-oxygen cultures produced the most changes (12), while standing ambient conditions showed the fewest (2). Five upregulated proteins, Rv1265, Rv2971, GroEL2, PE_PGRS6a, and malate dehydrogenase, were identified from BCG by mass spectrometry and were shown to also be regulated by cAMP at the mRNA level in both M. tuberculosis H37Rv and BCG. To our knowledge, these data provide the first direct evidence for cAMP-mediated gene regulation in TB complex mycobacteria.
Engineered silica nanoparticles act as adjuvants to enhance allergic airway disease in mice

With the increase in production and use of engineered nanoparticles (NP; ≤ 100 nm), safety concerns have risen about the potential health effects of occupational or environmental NP exposure. Results of animal toxicology studies suggest that inhalation of NP may cause pulmonary injury with subsequent acute or chronic inflammation. People with chronic respiratory diseases like asthma or allergic rhinitis may be even more susceptible to toxic effects of inhaled NP. Few studies, however, have investigated adverse effects of inhaled NP that may enhance the development of allergic airway disease. We investigated the potential of polyethylene glycol coated amorphous silica NP (SNP; 90 nm diameter) to promote allergic airway disease when co-exposed during sensitization with an allergen. BALB/c mice were sensitized by intranasal instillation with 0.02% ovalbumin (OVA; allergen) or saline (control), and co-exposed to 0, 10, 100, or 400 μg of SNP. OVA-sensitized mice were then challenged intranasally with 0.5% OVA 14 and 15 days after sensitization, and all animals were sacrificed a day after the last OVA challenge. Blood and bronchoalveolar lavage fluid (BALF) were collected, and pulmonary tissue was processed for histopathology and biochemical and molecular analyses. Co-exposure to SNP during OVA sensitization caused a dose-dependent enhancement of allergic airway disease upon challenge with OVA alone. This adjuvant-like effect was manifested by significantly greater OVA-specific serum IgE, airway eosinophil infiltration, mucous cell metaplasia, and Th2 and Th17 cytokine gene and protein expression, as compared to mice that were sensitized to OVA without SNP. In saline controls, SNP exposure did cause a moderate increase in airway neutrophils at the highest doses. These results suggest that airway exposure to engineered SNP could enhance allergen sensitization and foster greater manifestation of allergic airway disease upon secondary allergen exposures. Whereas SNP caused innate immune responses at high doses in non-allergic mice, the adjuvant effects of SNP were found at lower doses in allergic mice and were Th2/Th17 related. In conclusion, these findings in mice suggest that individuals exposed to SNP might be more prone to manifest allergic airway disease, due to adjuvant-like properties of SNP.
ASYSTOLE ASSOCIATED WITH IOHEXOL MYELOGRAPHY IN A DOG

This is a report of a 10-year-old female neutered Doberman Pinscher with a clinical diagnosis of myelopathy. The dog was anesthetized using oxymorphone, thiopental, and halothane in oxygen for a cerebrospinal tap and a myelogram. Iohexal injection into the subarachnoid space by lumbar puncture was uneventful. Additional iohexal was given into the cerebeliomedullary cistern. Immediately following iohexal administration into the cerebellomedullary cistern, several electrocardiographic changes occurred. Two extended periods of asystole responded to intravenous glycopyrrolate administration. A slow multiform ventricular escape rhythm was established after the second dose of glycopyrrolate. Ultimately, atrial activity with apparent AV dissociation resumed, atrial fibrillation developed, and the rhythm converted to normal sinus rhythm. The dog had a normal cardiac examination the following day. Two days later, the dog was anesthetized using a similar anesthetic regimen with maintenance on isoflurane in oxygen for a hemilaminectomy. The dog recovered uneventfully from surgery and was discharged 2 days later.
Density of Lipschitz mappings in the class of Sobolev mappings between metric spaces

We prove that Lipschitz mappings are dense in the Newtonian–Sobolev classes N 1,p (X, Y) of mappings from spaces X supporting p-Poincare inequalities into a finite Lipschitz polyhedron Y if and only if Y is [p]-connected, π 1(Y) = π 2(Y) = · · · = π [p](Y) = 0, where [p] is the largest integer less than or equal to p.
Effectiveness of machine checks for error diagnostics

Machine Check Architecture (MCA) is a processor internal architecture subsystem that detects and logs correctable and uncorrectable errors in the data or control paths in each CPU core and the Northbridge. These errors include parity errors associated with caches, TLBs, ECC errors associated with caches and DRAM, and system bus errors. This paper reports on an experimental study on: (i) monitoring a computing cluster for machine checks and using this data to identify patterns that can be employed for error diagnostics and (ii) introducing faults into the machine to understand the resulting machine checks and correlate this data with relevant performance metrics.
Physical aging in particulate-filled composites with an amorphous glassy matrix

Physical aging was studied on particulate -filled glassy network polymers by means of mechanical -dilatational, differential scanning calorimetry (DSC) and density measurements on specimens that were aged at room temperature. The composites aged for 0.5 day fractured in a brittle manner at a constant ultimate stress, which is close to the tensile strength of the unfilled material, regardless of the filler content and the presence of a coupling agent. This type of mechanical behavior is caused by the compressive residual stresses that are present due to curing and differential thermal shrinkage. As aging takes place, the compressive residual stresses are relieved; as a result the ultimate tensile strengths of the composites decrease. The 120 -day -old untreated glass bead containing composites exhibited dilatation and yield in mechanical -dilatational testing. This type of behavior is described as “having no adhesion” between the filler and the matrix. The 120 -day -old composites with coupling agent -treated glass beads fractured at a tensile stress which is equal to 1/1.6 the tensile strength of the unfilled material. These materials did not exhibit dilatation and yield in mechanical -dilatational testing. Density and DSC data indicate densification and enthalpy relaxation upon again and support the hypothesis presented for the observed change in the mechanical -dilatational behavior.
Optimum and suboptimum receivers for M-ary CPM signals based upon the Laurent representation

This paper involves a method for reduced complexity demodulation of continuous phase modulated (CPM) signals, which is based upon the extended Laurent representation of the nonlinear CPM modulation as a sum of time-offset pulse amplitude modulations. For signaling schemes with a long memory we derive a reduced complexity maximum-likelihood (ML) detector by approximating the CPM signal with a set of optimized pulses. The implementation is done for the non-binary case and for partial response CPM systems. It is demonstrated that, in the context of sequence detection, a remarkable receiver complexity reduction is possible using this method. The performance criteria used in the paper is symbol error probability and comparisons are made with other algorithms.
Towards Combining Ontologies and Model Weaving for the Evolution of Requirements Models

Software change resulting from new requirements, environmental modifications, and error detection creates numerous challenges for the maintenance of software products. While many software evolution strategies focus on code-to-modeling language analysis, few address software evolution at higher abstraction levels. Most lack the flexibility to incorporate multiple modeling languages. Not many consider the integration and reuse of domain knowledge with design knowledge. We address these challenges by combining ontologies and model weaving to assist in software evolution of abstract artifacts. Our goals are to: recover high-level artifacts such as requirements and design models defined using a variety of software modeling languages; simplify modification of those models; reuse software design and domain knowledge contained within models; and integrate those models with enhancements via a novel combination of ontological and model weaving concepts. Additional benefits to design recovery and software evolution include detecting high-level dependencies and identifying differences between evolved software and initial specifications.
An evaluation of the fecal recovery method for determining intestinal absorption of cobalt60-labeled vitamin B12.

T HREE methods are available t,o mt’asure intestinal ahsorption ol’ vitamill B 12) with use of. radioactive ( robalt”“-lal)elec~) vitamin B,,. The ti rst reported by Heinle and associates,’ in 1952, invoh-en c~ollcc+ion of stools aftev oral administration of a test dose. The difference betwcIen radioactivity recovered in t,he feces and t,he amount adntinisterrtf rqresclnts the aInoun1 absorbed. In the second method, devised by Schilling” in 1953, a test ciosc~ is given followed by parenteral injection of 1,000 mcg. ot’ nonradioactive .B,,,. This results in “flushing out” of some of the absorbed radioactivity into the urine where it can be counted. A third mctthotl, reported by Glass and coworkerq3 consists of surface scintillation eount.ing over l-he liver sovcra.1 days after administration of a test dose of radioactive I>,,,. If absorption has occurred, radioactivity will be detected over the? liver where most OP the H,, is concentrated. The urinary excretion test is simpler to (tarry out than the f~a1 recovr?r\ test. Furthermore, it does not involve work with stools, which may be objectionable to laboratory and ward personnel. Therefore it has been used tnore extensively.4-6 However, in respect to quantitative det,crmination of ahsorption it would appear that the most direct means would be to subtrset radioactivity eliminated in the feces from the amount administered by maul h. Four hundred and eighty-six fecal excretion tests have been performeti in this laboratory. The first 146 tests were carried out by t,ransferring each stool to a porcelain crucible and then drying it, ashing in a muffle furnace, and counting the ashed residue rnade up to 25 ml. Because of the cumhcrsome features of this method, a simpler technique was devised which does not. involve drying and ashing or transfer of feccls from one c~ontainer to another’. Three hundred and forty t&s havr bt~c~n carric>d ollt I)!this Iati(lla dir.cd -c~orlnting method. Results of the test in pernicious anemia ant1 total gastrtdomy and the effect ot’ intrinsic factor in these two conditions, as well as in normal individuals, have been previously reported.i-” The t:tYtJc?t elf antibiotics OII. aI>sorption in a variety of conditions has also heen rtXpr)rtrcl.“‘, ”
Life History Traits and Niche Instability Impact Accuracy and Temporal Transferability for Historically Calibrated Distribution Models of North American Birds.

A primary assumption of environmental niche models (ENMs) is that models are both accurate and transferable across geography or time; however, recent work has shown that models may be accurate but not highly transferable. While some of this is due to modeling technique, individual species ecologies may also underlie this phenomenon. Life history traits certainly influence the accuracy of predictive ENMs, but their impact on model transferability is less understood. This study investigated how life history traits influence the predictive accuracy and transferability of ENMs using historically calibrated models for birds. In this study I used historical occurrence and climate data (1950-1990s) to build models for a sample of birds, and then projected them forward to the ‘future’ (1960-1990s). The models were then validated against models generated from occurrence data at that ‘future’ time. Internal and external validation metrics, as well as metrics assessing transferability, and Generalized Linear Models were used to identify life history traits that were significant predictors of accuracy and transferability. This study found that the predictive ability of ENMs differs with regard to life history characteristics such as range, migration, and habitat, and that the rarity versus commonness of a species affects the predicted stability and overlap and hence the transferability of projected models. Projected ENMs with both high accuracy and transferability scores, still sometimes suffered from over- or under- predicted species ranges. Life history traits certainly influenced the accuracy of predictive ENMs for birds, but while aspects of geographic range impact model transferability, the mechanisms underlying this are less understood.
The effect of chromosome 9p21 variants on cardiovascular disease may be modified by dietary intake.

Several genome-wide association studies have identified the chromosome 9p21 region as the most robust genetic association for cardiovascular disease (CVD) and myocardial infarction (MI). The authors state that observed variation in the effect of genetic factors in different populations may be partly attributed to varying levels of environmental exposures (eg, physical activity, smoking, and diet) and that gene-environment interaction studies may contribute to explaining some of the phenotypic variance that is not accounted for by common variants.1 They further state that the interaction of the 9p21 locus with environmental factors has not been extensively explored and that prior studies have been plagued by small sample sizes and limited to single environmentally homogenous populations of European origin. Therefore, they hypothesized that testing the effects of 9p21 and environmental factors related to MI in individuals of different ethnicities may increase the ability to discover gene-environment interactions. ### How Was the Hypothesis Tested? The authors conducted a large-scale multiethnic study of variants in the 9p21 region and acute MI in 8114 individuals (3820 cases and 4294 control subjects) from 5 ethnicities—European, South Asian, Chinese, Latin American, and Arab—who participated in the INTERHEART study, a global retrospective case-control study of risk factors for acute nonfatal MI. Standardized dietary phenotypes were measured by a short qualitative food frequency questionnaire of 19 food items, which identified 3 dietary patterns subjectively labeled as Oriental (soy sauce, tofu, pickled foods, green leafy vegetables, eggs, and low sugar), Western (eggs, meats, fried and salty foods, sugar, nuts, and desserts), and prudent (raw vegetables, fruits, green leafy vegetables, nuts, desserts, and dairy products). They also generated a dietary risk score using a point system from the food items that included a tabulation of food items that were considered to be protective of CVD (fruits and green, leafy vegetables, other cooked vegetables, and other raw vegetables) …
Campylobacter-associated enterocolitis in childhood. Report of a fatal case

The full clinical range of Campylobacter fetus enterocolitis has become apparent only recently. This case study describes the clinical and pathologic findings in a chronically ill child who developed signs of inflammatory bowel disease. Following a negative bacteriologic culture, Crohn's disease was diagnosed by roentgenographic criteria. A trial of immunosuppressive therapy failed, and a repeat of microbiologic examination identified a heavy growth of Campylobacter fetus ss. jejuni. Various complications developed and the patient died with a coagulopathy and a widespread enterocolitis. The role of the Campylobacter in this clinical setting of inflammatory bowel disease is discussed in light of current understanding.
Curved Lipid Bilayer Membranes : Protein Motions and Hydrodynamic Transport

We present theory and results for protein diffusion and active transport within curved lipid bilayer membranes. Our theory takes into account the hydrodynamics within bilayer leaflets, intermonolayer slip between leaflets, and coupling with the bulk solvent fluid. Saffman and Delbruck's 1975 paper introduced a hydrodynamic model for a homogeneous flat membrane sheet and a now widely used theory for the diffusivity of membrane proteins. When membrane sheets are curved, we show how geometric and topological effects can significantly augment the protein diffusivity. We present results showing how these effects contribute to the individual and collective motions of protein inclusions in diffusive transport and self-assembly within curved lipid bilayer membranes.
Effects of Functional Bias on Supervised Learning of a Gene Network Model

Gene networks have proven to be an effective approach for modeling cellular systems that are capable of capturing some of the extreme complexity of cells in a formal theoretical framework. Not surprisingly, this complexity, combined with our still-limited amount of experimental data measuring the genes and their interactions, makes the reconstruction of gene networks difficult. One powerful strategy has been to analyze functional genomics data using supervised learning of network relationships based upon reference examples from our current knowledge. However, this reliance on the set of reference examples for the supervised learning can introduce major pitfalls, with misleading reference sets resulting in suboptimal learning. There are three requirements for an effective reference set: comprehensiveness, reliability, and freedom from bias. Perhaps not too surprisingly, our current knowledge about gene function is highly biased toward several specific biological functions, such as protein synthesis. This functional bias in the reference set, especially combined with the corresponding functional bias in data sets, induces biased learning that can, in turn, lead to false positive biological discoveries, as we show here for the yeast Saccharomyces cerevisiae. This suggests that careful use of current knowledge and genomics data is required for successful gene network modeling using the supervised learning approach. We provide guidance for better use of these data in learning gene networks.
Instructional Learning Objects in the Digital Classroom: Effectively Measuring Impact on Student Success

ABSTRACTDemonstrating library impact on student success is critical for all academic libraries today. This article discusses how the library of a large online university serving non-traditional students evaluated how customized point-of-need learning objects (LOs) embedded in the learning management system impacted student learning. Using a comprehensive mixed-methods approach utilizing Google analytics, reference statistics, and citation analysis via rubrics, the author investigated the extent to which LOs contributed to students' ability to conduct research independently and ability to create quality bibliographies. Results indicated high usage of LOs, that student research independence increased in all courses analyzed, and bibliographies improved for students in an anthropology course after LO integration. This initiative provided substantial evidence that the LOs positively affected student learning and allowed the library to communicate this impact to key stakeholders.
BitCube: A Three-Dimensional Bitmap Indexing for XML Documents

XML is a new standard for exchanging and representing information on the Internet. Documents can be hierarchically represented by XML-elements. In this paper, we propose that an XML document collection be represented and indexed using a bitmap indexing technique. We define the similarity and popularity operations suitable for bitmap indexes. We also define statistical measurements in the BitCube: center, and radius. Based on these measurements, we describe a new bitmap indexing based technique to cluster XML documents. The techniques for clustering are motivated by the fact that the bitmap indexes are expected to be very sparse. Furthermore, a 2-dimensional bitmap index is extended to a 3-dimensional bitmap index, called the BitCube. Sophisticated querying of XML document collections can be performed using primitive operations such as slice, project, and dice. Experiments show that the BitCube can be created efficiently and the primitive operations can be performed more efficiently with the BitCube than with other alternatives.
Spike and Wave EEG Abnormalities in ADHD

Investigators at Istanbul University, Turkey, studied sleep EEGs in 134 patients with ADHD.
Elevation of Plasma Von Willebrand Factor and Tumor Necrosis Factor-α in Obese Subjects and Their Reduction by Low Molecular Weight Heparin.

Background: Increased plasma-soluble von Willebrand factor (vWF) level, a marker of vascular endothelial cell dysfunction, is a predictor of atherosclerotic cardiovascular disease in the general population. We compared associations between vWF level and markers of inflammation as well as the effects of low molecular weight heparin (LMWH) in obese as compared to healthy human subjects. Methods: Plasma samples were obtained from healthy volunteers (n = 32) and obese subjects (n = 12) before and after administration of a single subcutaneous (SC) dose of tinzaparin, given at a deep vein thrombosis (DVT) prophylaxis dose of 75 IU/kg once a day. These samples were analyzed for vWF and tumor necrosis factor-α (TNF-α) by ELISA. Also examined was the effect of different LMWH on the release of vWF from human umbilical vein endothelial cells (HUVEC) in response to various stimuli, such as oxidized low density lipoprotein (LDL) or endotoxin. Results: Obese subjects showed higher plasma levels of TNF-α compared with normal-weight subjects. Regression analysis showed plasma vWF levels to be directly associated with the presence of higher plasma levels of TNF-α in these obese subjects. Tinzaparin, given at a prophylaxis dose for DVT (75 IU/kg, SC, QD), significantly reduced elevated plasma levels of endothelial dysfunction marker vWF associated with higher inflammatory TNF-α levels ( P Conclusion: Plasma values of vWF and TNF-α are higher in obese than in normal-weight individuals. Treatment with tinzaparin lowers plasma levels of TNF-α in both obese and normal-weight subjects. The levels of vWF were higher in obese subjects than in normal-weight ones because of the higher levels of circulating TNF-α. Tinzaparin reduced vWF levels in these obese subjects. Table 1. Effect of Tinzaparin (75 IU/kg, SC, QD) on Plasma vWF in Obese and Normal-Weight Subjects Table 2. Effect of Tinzaparin (75 IU/kg, SC) on Plasma TNF-α in Obese and Normal-Weight Subjects
The Role of Nitric Oxide in γ-Globin Induction by Hydroxyurea.

Abstract Hydroxyurea (HU) has been shown to induce fetal hemoglobin (HbF) synthesis through activation of the soluble guanosine cyclase/cyclic guanosine monophosphate signaling pathway. The release of NO from HU by heme iron is thought to be involved in this mechanism of HbF induction. Studies completed in sickle cell patients confirmed increased serum NO levels after oral HU therapy but NO generation in red blood cells and the effect on γ-gene transcription have not been extensively investigated. Therefore, we performed studies to quantify NO generated by HU in K562 cells and normal erythroid progenitors as a mechanism for γ-globin activation. NO levels were measured after drug treatments using the Nitric Oxide Assay Kit (Calbiochem) and γ-globin mRNA was measured using quantitative PCR. HU (100μM) increased NO 1.4 to 1.8-fold at 24–72 hrs in K562 cells compared to a 2.0 to 2.5-fold increase in NO produced by the known NO donor, deta-nonoate (DE; 400μM). NO levels were also measured in erythroid progenitors grown in liquid cultures; a 1.6-fold increase in NO was produced by 30μM HU after 48 hrs with comparable increases produced by 200μM DE. To understand the effects of HU on normal NO synthesis from L-arginine through the action of NO synthase (NOS), we performed studies with the NOS inhibitor, NG-Monomethyl-L-arginine (L-NMMA). Interestingly, HU increased NO levels 2.5-fold at 24 hrs when combined L-NMMA compared a 1.4-fold increase produced by HU alone; this pattern persisted up to 72 hrs. Parallel with these findings γ-globin activation by HU was augmented approximately 25% by L-NMMA; DE combined with L-NMMA did not produce the same effect. These data suggest a novel mechanism for NOS regulation by HU compared to DE. Subsequent studies were completed to determine if HbF synthesis could be augmented by combining NO donors since they have different mechanisms of action. HbF levels in K562 cells were measured by ELISA (Bethyl Laboratories) and normalized by total hemoglobin and protein. Treatment with HU or DE increased HbF 3.6-fold and 4.6-fold respectively; when HU was combined with DE an additive 7.6-fold increase in HbF was produced. These data confirm that HU treatment lead to NO generation in K562 cells and normal erythroid progenitors which plays a role in its mechanism of γ-globin activation. HU combined with DE had an additive effect on HbF synthesis. These findings are relevant to current research efforts to develop novel HbF inducers for therapy in sickle cell patients.
Characterization of positive cloud-to-ground Lightning Discharges

We examined 52 positive cloud-to-ground flashes containing 63 return strokes recorded in Gainesville, Florida, in 2007-2008. The U.S. National Lightning Detection Network located 51 (96%) of the positive return strokes at distances of 7.8 to 157 km from the field measuring station and correctly identified 48 (91%) of them as cloud-to-ground discharges. The average number of strokes per flash (multiplicity) is 1.2. In three (38%) of eight two-stroke flashes, the second stroke likely followed the channel of the first stroke and in five (62%) flashes it likely created a new termination on ground . The characteristics of positive return-stroke electric field and field derivative waveforms are analyzed. The GM values of initial electric field peak normalized to 100 km for 48 positive return strokes and corresponding NLDN-reported peak current are 18.1 V/m and 74.6 kA, respectively.
Reversible Lifting of Surface Supported Lipid Bilayers with a Membrane-Spanning Nonionic Triblock Copolymer

Neutron reflectometry was used to monitor structural variations in surface-supported dimyristoylphosphatidycholine (DMPC) bilayers induced by the addition of Triton X-100, a surfactant commonly used to aid solubilization of membrane proteins, and the coaddition of a membrane spanning nonionic amphiphilic triblock copolymer, (PEO117–PPO47–PEO117, Pluronic F98). Surfactant addition causes slight compression of the bilayer thickness and the creation of a distinct EO layer that increases the hydrophilic layer proximal to the supporting substrate (i.e., a water and EO gap between the lipid bilayer and quartz) to 6.8 ± 0.4 A. Addition of the triblock copolymer into the DMPC:Triton X-100 bilayer increases the complexity of (broadens) the lipid phase transition, further compresses the bilayer, and continues to expand the proximal hydrophilic layer thickness. The observed structural changes are temperature dependent with transmembrane polymer insertion achieved at 37 °C, leading to a compressed membrane thickness ...
Genetically Encoded Tools for Compartment-Specific Manipulation of NAD+/NADH or NADP+/NADPH Ratios

Background The pool sizes and ratios of the pyridine nucleotides NAD(P)+ and NAD(P)H play a fundamental role in cellular metabolism and have emerged as key factors in numerous pathologies, including mitochondrial disorders, neurodegenerative diseases, cancer and aging. However, evaluating the impact of changes in concentrations of particular pyridine nucleotides in these conditions has not been possible due to lack of tools with which to directly perturb the NAD(P)+/NAD(P)H ratios. The aim of our study was to develop such tools, which are based on heterologous expression of naturally occurring or engineered water-forming NAD(P)H oxidases (NOXes). NOXes catalyze a four-electron reduction of oxygen to water using reducing equivalents of NAD(P)H, and their natural function is to detoxify O2 in several facultative or strictly anaerobic bacteria and parasitic protozoa. Methods Naturally occurring eukaryotic and bacterial NOXes were screened in human cells with or without a mitochondrial targeting sequence and assessed for their ability to consume oxygen and to change NAD(P)+/NAD(P)H ratios. The best candidates were overproduced in E.coli, purified and biochemically characterized for their substrate specificity and activity. Structural enzymology and rational mutagenesis were employed to engineer NAD(P)H specific variants. Results Our kinetic and structural studies revealed that bacterial NOX from Lactobacillus brevis (LbNOX) is strictly specific for NADH over NADPH, produces negligible H2O2, and has high catalytic activity compared to other candidate NOXes. Expression of LbNOX in mitochondria or cytoplasm of human cells is well tolerated and leads to a compartment-specific increase in the NAD+/NADH ratio. We used LbNOX to demonstrate the dependence of key metabolic fluxes and signaling on the cytosolic or mitochondrial NAD+/NADH ratios. In addition, LbNOX can fully complement electron transport chain function to support mammalian cell proliferation by re-oxidizing NADH to NAD+. Conclusions Taken together, the genetically encoded tools which we are developing provide a toolkit for compartment-specific manipulation of the NAD+/NADH and NADP+/NADPH ratios in living cells.
Glucagon, Insulin and their Hepatic Receptors: An Endocrine Pattern Characterizing Hepatoproliferative Transitions in the Rat

Hyperglucagonemia and hypoinsulinemia (absolute or relative) characterize at least four “different” hepatoproliferative states which include: 1. Regeneration after 70% hepatectomy; 2. Developmental transitions; 3. Lipotrope-deficiency induced proliferation; and 4. Combined hormonal infusion During regeneration, glucagon receptor sites “disappear” from the liver, as revealed by labelled hormone binding studies and Scatchard analyses of the data. However, this is not detected during the early prereplipcative phase of regeneration when numerous glucagon-dependent changes (particularly those involving altered hepatic VLDL metabolism) are known to occur. By contrast, isolated liver “membranes” from regenerating liver early in the prereplicative phase show an enhanced ability to bind labelled insulin. A common endocrine pattern, related to the physiology of pancreatic hormones and interactions with their receptors, may participate in controlling normal hepatocyte proliferation.
Assessing climate change impacts on extreme weather events: the case for an alternative (Bayesian) approach

The conventional approach to detecting and attributing climate change impacts on extreme weather events is generally based on frequentist statistical inference wherein a null hypothesis of no influence is assumed, and the alternative hypothesis of an influence is accepted only when the null hypothesis can be rejected at a sufficiently high (e.g., 95% or “p = 0.05”) level of confidence. Using a simple conceptual model for the occurrence of extreme weather events, we show that if the objective is to minimize forecast error, an alternative approach wherein likelihoods of impact are continually updated as data become available is preferable. Using a simple “proof-of-concept,” we show that such an approach will, under rather general assumptions, yield more accurate forecasts. We also argue that such an approach will better serve society, in providing a more effective means to alert decision-makers to potential and unfolding harms and avoid opportunity costs. In short, a Bayesian approach is preferable, both empirically and ethically.
Deconstructing the Confinement Effect upon the Organization and Dynamics of Water in Hydrophobic Nanoporous Materials: Lessons Learned from Zeolites

The properties of confined water are relevant to many chemical, geological, and biological phenomena, where they underpin essential changes to molecular scale reactivity–perturbing both the energetic and configurational landscape. Though much prior literature has focused on hydrophilic confinement, the hydrophobic confinement of water is less well understood. Here, we use molecular dynamics simulations to investigate the structures and dynamics of water in hydrophobic all-silica zeolites that have sequentially smaller pore dimensions. Of special interest is the role that pure geometric restriction imparts, relative to the rugged potential energy landscape for water interacting with the atomistic pore surface. These two effects were studied via the hydrogen bond dynamics, specifically the rates and mechanisms of hydrogen bond breakage and formation. Measuring the dynamic features as a function of scaling the water:zeolite interaction energy revealed that geometric restriction is responsible for 67%–86% of ...
Effectively reducing amylase testing using computer order entry in the emergency department: quality improvement without eliminating physician choice.

Background Amylase and lipase, pancreatic biomarkers, are measured in acute pancreatitis diagnosis. Since amylase testing does not add diagnostic value, lipase testing alone is recommended. Despite new recommendations, many physicians and staff continue to test both amylase and lipase. Objective To reduce unnecessary diagnostic testing in acute pancreatitis. Methods The pre-checked amylase test within the Emergency Department’s Computerised Provider Order Entry (CPOE) abdominal pain order set was changed to an un-checked state but kept as an option to order with a single click. Amylase testing, lipase testing and cost were measured for one year pre- and post-intervention. Results Simple de-selection intervention reduced redundant amylase testing from 71% to 9%, resulting in a percent of decrease of 87% and an annualised saving of approximately $719,000 in charges. Conclusion CPOE de-selection is an effective tool to reduce non-value added activity and reduce cost while maintaining quality patient care and physician choice.