cssi/SciSciGPT-SciSciNet huggingface dataset:
Dendritic Cell Activation Prevents MHC Class II Ubiquitination and Promotes MHC Class II Survival Regardless of the Activation Stimulus

The expression of MHC class II (MHC-II) on the surface of antigen-presenting cells, such as dendritic cells (DCs), is tightly regulated during cellular activation. Many cells, including DCs, are activated following stimulation of innate Toll-like receptors (TLRs) by products of microorganisms. In the resting (immature) state, MHC-II is ubiquitinated in immature DCs and is rapidly degraded; however, after activation of these cells with MyD88-dependent TLR ligands, MHC-II ubiquitination is blocked, and MHC-II survival is prolonged. We now show that DC activation using MyD88-dependent TLR ligands, MyD88-independent TLR ligands, and even infection with the intracellular parasite Toxoplasma gondii leads to identical changes in MHC-II expression, ubiquitination, and surface stability, revealing a conserved role for enhanced MHC-II stability after DC activation by different stimuli.
Relationship between hypnotic susceptibility, fear of failure and need for achievement.

Summary.-21 men were administered a modified version of Murray's (1938) Thematic Apperception Test (TAT) to measure fear of failure and need for achievement. Hypnotic susceptibility was then tested using the Harvard Group Scale, Form A. The prediction that those subjects high in fear of failure would be less susceptible than those in low fear of failure was supported. No relationship was found between need for achievement and hypnotic susceptibility, supporting previous findings. The results were discussed in terms of the dimensions of fear of failure which would lead to low susceptibility. The interest in hypnotic susceptibility has led to an abundance of literature attempting to outline the structure of the hypnotically susceptible person. Hull (1933) concluded that attempts to uncover the personality of the susceptible person were inconclusive. More recent investigations utilizing personality inventories have yielded few direct relationships (Tellegen & Atkinson, 1974), supporting Hull's conclusions of more than 40 years before. Meaningful insights into the composition of the hypnotically susceptible person were uncovered by Hilgard ( 1962), who found that individuals susceptible to hypnosis had a developed sense of responsible participation. By responsible participation, it was meant that the individual had the ability to cooperate with others while sharing in the duties of accomplishing a task. Hilgard (1962) also observed that the hypnotically susceptible person was one who was able to conform in daily life without hostile defiance. Likewise, it was further posited that the susceptible person was one who was able to take responsibilities as a leader. The susceptible person then, according to Hilgard (1962) was one who could be a responsible leader or follower and one who could work with those under him and those over him without hostility. Based upon the Thematic Apperception Test (TAT) as developed by Murray ( 1938), McClelland, Atkinson, Clark, and Lowell ( 1953 ) devised a measure for need for achievement (nAch). McClelland and his associates spoke of the necessity to distinguish between individuals showing hope of
Targeted Nucleotide Exchange in the Alkaline Phosphatase Gene of HuH-7 Cells Mediated by a Chimeric RNA/DNA Oligonucleotide

Although a variety of methods has been devised for modification of hepatic genes, none has been effective for long-term correction of genetic disorders. In this study, we employed a recently described novel experimental strategy for site-directed nucleotide exchange in genomic DNA of HuH-7 human hepatoma cells. A chimeric 2′-O-methylated-RNA/DNA oligonucleotide containing sequences complementary to 25 bases of the alkaline phosphatase gene was constructed as a duplex containing a G to A substitution at nucleotide 935. Cells were transfected with oligonucleotides for 48 hours, then harvested for DNA isolation and polymerase chain reaction (PCR) amplification of exon 6 of the alkaline phosphatase gene. Colony lifts were hybridized to 17 mer 32P-labeled oligonucleotide probes specific to the 935-G and 935-A sequences. Hybridizing colonies were grown, plasmid DNA isolated, and sequenced. Transfection efficiency was determined at 24 hours by nuclear uptake of fluorescein-12-dUTP-labeled chimeric oligonucleotides. Colonies hybridizing with the 935-A probe were identified only from cells transfected with the specific chimeric oligonucleotide; and there was no evidence of cross-hybridization. Conversion of G to A at nucleotide 935 occurred at an overall frequency of up to 11.9% and when corrected for transfection efficiency approached 43%. No other alterations were detected in the sequence of exon 6 with the targeted nucleotide exchange. These results show that a single base pair alteration in the alkaline phosphatase gene of HuH-7 cells can be introduced at a relatively high frequency following transfection with chimeric RNA/DNA oligonucleotides. This technique offers a novel and potentially powerful strategy for site-directed hepatic gene alteration without the use of viral-based vectors.
The Book of Job and the Cure of Souls

Though his example is warmly commended in the Epistle of James (5.11), Christian piety has never been altogether comfortable with the Job whose sterling patience in adversity is set forth in the book's first two chapters. The man who is there shown suffering bravely the loss of property and family and the onset of disease of a kind that in these distant days had the sentence of death written over it, yet steadfastly refuses to blame God for such disasters, is certainly admired. But his dauntless sentiments of 1.21, The Lord gave, and the Lord has taken away; blessed be the name of the Lord, and of 2.10, What? Shall we receive good at the hand of God, and shall we not receive evil? — the latter in response to his wife who, unable to put up with his agonies any longer, calls on him to curse God and be done with it all — are just too hard to take. A hymn made out of a similarly passive sounding Old Testament text like My times are in thy hand (Ps. 31.15) is one thing. But Job's insistence on implicating God directly in the tragedies that may befall a good man is quite another thing. I doubt, therefore, whether these texts from Job chapters 1 and 2 figure much in the pastoral care of the sick and the bereaved in the modern Church, though in sturdier ages it seems that they did.
The Modernity of Witchcraft: Politics and the Occult in Postcolonial Africa

The Modernity of Witchcraft: Politics and the Occult in Postcolonial Africa. PETER GESCHIERE. Charlottesville: University Press of Virginia, 1997. xiv. 311 pp., index, bibliography, notes, map.
ESR linewidth studies on naphthalene ion in low bulk dielectric constant media

Abstract The potassium naphthalenide system has been studied in various mixtures of 1, 2-dimethoxyethane and hydrocarbon solvent (benzene, cyclohexane and n -hexane). The observed increase in linewidth with increasing mole fraction hydrocarbon has been attributed to an increasing unresolved potassium splitting.
Effect of Genetic Variation in a Drosophila Model of Diabetes-Associated Misfolded Human Proinsulin

The identification and validation of gene–gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression of the mutant preproinsulin (hINSC96Y) in the eye imaginal disc mimics the human disease: it activates conserved stress-response pathways and leads to cell death (reduction in eye area). Dominant-acting variants in wild-derived inbred lines from the Drosophila Genetics Reference Panel produce a continuous, highly heritable distribution of eye-degeneration phenotypes in a hINSC96Y background. A genome-wide association study (GWAS) in 154 sequenced lines identified a sharp peak on chromosome 3L, which mapped to a 400-bp linkage block within an intron of the gene sulfateless (sfl). RNAi knockdown of sfl enhanced the eye-degeneration phenotype in a mutant-hINS-dependent manner. RNAi against two additional genes in the heparan sulfate (HS) biosynthetic pathway (ttv and botv), in which sfl acts, also modified the eye phenotype in a hINSC96Y-dependent manner, strongly suggesting a novel link between HS-modified proteins and cellular responses to misfolded proteins. Finally, we evaluated allele-specific expression difference between the two major sfl-intronic haplotypes in heterozygtes. The results showed significant heterogeneity in marker-associated gene expression, thereby leaving the causal mutation(s) and its mechanism unidentified. In conclusion, the ability to create a model of human genetic disease, map a QTL by GWAS to a specific gene, and validate its contribution to disease with available genetic resources and the potential to experimentally link the variant to a molecular mechanism demonstrate the many advantages Drosophila holds in determining the genetic underpinnings of human disease.
An artificial visual cortex drives behavioral evolution in co-evolved predator and prey robots

Using a rule-based system for growing artificial neural networks [1], we have evolved controllers for physically simulated 18-degree-of-freedom robotic "spiders". These robots previously evolved "galloping" gaits and tracked a compass heading. Here, we introduce an artificial "visual cortex" that permits distinct predator and prey species to "see" one another. It has been claimed [2] that the "Cambrian explosion" of evolutionary diversity was due the emergence of animal eyes, which created a new dynamic in the interaction between predators and prey. The survival of both was for the first time determined by interactions between animals some distance apart. Here, we find that the introduction of vision does indeed generate complex interactions both between and within the two species, as they species evolve complex hunting or avoidance behavior, modulating their galloping gaits with dynamic input from their visual systems.
Electron correlation effects in the ab initio study on tautomerism of guanine

Abstract The molecular structures of three quanine tautomers are examined using ab initio method at the MP2/6–31G ** //HF/6–31G level. The study predicts amino—oxo Gua N(7)H tautomer ( 1 ) to be the global minimum. The second amino—oxo Gua N(9)H ( 2 ) and amino—hydroxy Gua * N(9)H ( 3 ) tautomers have relative energies of 0.5 and 4.6 kJ mol −1 (MP2/6–31G ** +ZPE), respectively. These results explain well recent experimental IR matrix-isolation and UV photoelectron studies on guanine. The shift of tautomeric equilibria towards 2 on going from the isolated molecules towards polar solvents is predicted. The influence of the basis set and electron correlation contributions on the relative energies of tautomers is discussed.
Corporate voting: Evidence from charter amendment proposals

Abstract Some argue that managers effectively control corporate voting: hence the process is meaningless. Others contend that shareholder voting motivates managers to maximize firm value. We provide evidence on this debate by analyzing the results from a large sample of management-sponsored anti-takeover amendments. Our results do not support the extreme form of either hypothesis. The evidence suggests that shareholder voting is important and indicates the circumstances where voting is most likely to constrain managers. Our results also have implications for the use of voting in political and other non-corporate contexts.
Experimental results from parallel backward-chained expert systems

There are many applications which may be done by an expert system in real time, if the system is capable of real time response. the first Lisp- and Prolog-based expert systems have typically been too slow for real time response. This has lead to an effort to use other languages, the development of fast pattern matching techniques, and other methods of improving the speed of expert systems. Another approach to developing faster expert systems is to make use of the emerging parallel processing computer technology. A further use for parallelism is to allow reasonable response time for large knowledge bases. the size of knowledge bases may become as large as 20,000 chunks of knowledge (and more) in the near future in medical and space applications. This article describes the use of parallel processing in the EMYCIN backward chained rule-based model. Performance on two examples of shared memory multiprocessors is presented and contrasted with earlier simulations.
Energy-efficient instruction cache using page-based placement

Energy consumption is a crucial factor in designing battery-operated embedded and mobile systems. The memory system is a major contributor to the system energy in such environments. In order to optimize energy and energy-delay in the memory system, we investigate ways of splitting the instruction cache into several smaller units, each of which is a cache by itself (called subcache). The subcache architecture employs a page-based placement strategy, a dynamic cache line remapping policy and a predictive precharging policy in order to improve the memory system energy behavior. Using applications from the SPECjvm98 and SPECint2000 benchmarks, the proposed subcache architecture is shown to be effective in improving both the energy and energy-delay metrics.
Surface Damage After Multiple Dislocations of a 38-mm-Diameter, Metal-on-Metal Hip Prosthesis

Abstract We present, for the first time, a detailed damage assessment of a large-diameter metal-on-metal (L-MOM) hip prosthesis to show the extent of surface damage that can occur in a patient after multiple dislocations. The patient was a man (51 years old) who dislocated 8 times and was finally revised at 27 months. Radiographically, the cup was malpositioned with 65° lateral opening and 15° retroversion. The retrieved cup was a 1-piece, 38-mm Co-Cr-Mo (M2a; Biomet, Warsaw, Ind) with a titanium-alloy backing. The retrieved components demonstrated all known modes of wear, including a polished wear scar, multidirectional scratching, “stripe” wear, surface contamination of titanium-alloy, front face wear, and backside wear. The clinical significance is that cup positioning remains critical regardless of whether a large diameter head is used or not.
An ionic liquid-coordinated palladium complex: a highly efficient and recyclable catalyst for the Heck reaction.

The monoquaternary product of 2,2‘-biimidazole with iodobutane is an ionic liquid that acts as both the solvent and ligand for catalytic reactions. A new palladium complex was prepared by adding PdCl2 to this ionic liquid to form a catalytic solution that is effective for Heck reactions with good recyclability.
An analysis of subunit exchange in the dimeric DNA-binding and DNA-bending protein, TF1

Abstract TF1 is the Bacillus subtilis bacteriophage-encoded dimeric type II DNA-binding protein. This relative of the eubacterial HU proteins and of the Escherichia coli integration host factor binds preferentially to 5-(hydroxymethyluracil)-containing DNA. We have examined the dynamics of exchange of monomer subunits between molecules of dimeric TF1. The analysis takes advantage of the fact that replacement of phenylalanine with arginine at amino acid 61 in the β-loop ‘arm’ of TF1 alters DNA-bending and -binding properties, generating DNA complexes with distinctively different mobilities in gel electrophoresis. New species of DNA-protein complexes were formed by mixtures of wild type and mutant TF1, reflecting the formation of heterodimeric TF1, and making the dynamics of monomer exchange between TF1 dimers accessible to a simple gel retardation analysis. Exchange was rapid at high protein concentrations, even at 0°C, and is proposed to be capable of proceeding through an interaction of molecules of TF1 dimer rather than exclusively through dissociation into monomer subunits. Evidence suggesting that DNA-bound TF1 dimers do not exchange subunits readily is also presented.
On Cooperative Relaying Schemes for Wireless Physical Layer Security

We consider a cooperative wireless network in the presence of one or more eavesdroppers, and exploit node cooperation for achieving physical (PHY) layer based security. Two different cooperation schemes are considered. In the first scheme, cooperating nodes retransmit a weighted version of the source signal in a decode-and-forward (DF) fashion. In the second scheme, referred to as cooperative jamming (CJ), while the source is transmitting, cooperating nodes transmit weighted noise to confound the eavesdropper. We investigate two objectives: i) maximization of the achievable secrecy rate subject to a total power constraint and ii) minimization of the total power transmit power under a secrecy rate constraint. For the first design objective, we obtain the exact solution for the DF scheme for the case of a single or multiple eavasdroppers, while for the CJ scheme with a single eavesdropper we reduce the multivariate problem to a problem of one variable. For the second design objective, existing work introduces additional constraints in order to reduce the degree of difficulty, thus resulting in suboptimal solutions. Our work raises those constraints, and obtains either an analytical solution for the DF scheme with a single eavesdropper, or reduces the multivariate problem to a problem of one variable for the CJ scheme with a single eavesdropper. Numerical results are presented to illustrate the proposed results and compare them to existing work.
Dehydrogenation of cyclohexane on a hydrogen-porous membrane

Abstract In the presence of hydrogen at 125 °C, cyclohexane is thermodynamically stable with respect to cyclohexene. However, by forcing nonequilibrium conditions on a hydrogen-porous palladium-silver alloy membrane, cyclohexane vapor at about 0.1 atm is readily dehydrogenated to cyclohexene. The dehydrogenation occurs when hydrogen is pumped out of the reactor by diffusion through the membrane. For any fixed hydrogen pressure in the reactor and any steady rate of diffusion of hydrogen through the membrane, a corresponding steady ratio of cyclohexane to cyclohexene results, attained within a few minutes after experimental conditions are changed. According to a proposed mechanism, sorbed hydrogen atoms are required for the dehydrogenation, but their concentration on the catalytic surface is maintained far below the normal equilibrium concentration (for the external hydrogen pressure) by pumping them through the membrane.
Quasiparticle Theory of Transport Coefficients for Hadronic Matter at Finite Temperature and Baryon Density

We develop a flexible quasiparticle theory of transport coefficients of hot hadronic matter at finite baryon density. We begin with a hadronic quasiparticle model which includes a scalar and a vector mean field. Quasiparticle energies and the mean fields depend on temperature and baryon chemical potential. Starting with the quasiparticle dispersion relation, we derive the Boltzmann equation and use the Chapman-Enskog expansion to derive formulas for the shear and bulk viscosities and thermal conductivity. We obtain both relaxation-time approximation formulas and more general integral equations. Throughout the work, we explicitly enforce the Landau-Lifshitz conditions of fit and ensure the theory is thermodynamically self-consistent. The derived formulas should be useful for predicting the transport coefficients of the hadronic phase of matter produced in heavy-ion collisions at the Relativistic Heavy Ion Collider and at other accelerators.
Manual Application of Impulses while Tractionless

The percentage of 20 naive subjects who, while tractionless in a horizontal plane and anchored by one handhold, push in or pull out a plunger in one motion against various frictional forces and travel distances, decreases directly as the force and distance required. With large-force impulses, the impulse is linear and the situation can be described by the impulse = momentum theorem) t0Fdt= mv1-mv0. The shape of the impulse is saw-toothed, and its area approximated by taking three-fourths of the area of a rectangle whose base is the duration, and height, the force of the impulse. For this experiment, the maximum duration of an effective impulse for a required force of 40 lb is 0.5 sec for a push-in, and 0.3 sec for a pull-out impulse.
Leaf physiology does not predict leaf habit; examples from tropical dry forest

Leaf structure and physiology are thought to be closely linked to leaf longevity and leaf habit. Here we compare the seasonal variation in leaf hydraulic conductance (kleaf) and water potential of two evergreen tree species with contrasting leaf life spans, and two species with similar leaf longevity but contrasting leaf habit, one being deciduous and the other evergreen. One of the evergreen species, Simarouba glauca, produced relatively short-lived leaves that maintained high hydraulic conductance year round by periodic flushing. The other evergreen species, Quercus oleoides, produced longer-lived leaves with lower kleaf and as a result minimum leaf water potential was much lower than in S. glauca (−2.8 MPa vs −1.6 MPa). Associated with exposure to lower water potentials, Q. oleoides leaves were harder, had a higher modulus of elasticity, and were less vulnerable to cavitation than S. glauca leaves. Both species operate at water potentials capable of inducing 20 (S. glauca) to 50% (Q. oleoides) loss of kleaf during the dry season although no evidence of cumulative losses in kleaf were observed in either species suggesting regular repair of embolisms. Leaf longevity in the deciduous species Rhedera trinervis is similar to that of S. glauca, although maximum kleaf was lower. Furthermore, a decline in leaf water potential at the onset of the dry season led to cumulative losses in kleaf in R. trinervis that culminated in leaf shedding.
Perovskite solar cells: Continuing to soar

The dream of printing highly efficient solar cells is closer than ever to being realized. Solvent engineering has enabled the deposition of uniform perovskite semiconductor films that yield greater than 15% power-conversion efficiency.
EarthVision 2000: Examining Students' Representations of Complex Data Sets.

Graphic representations are powerful tools used by scientists and other professionals to help them understand multifaceted natural phenomena. They can also serve teachers and students as they attempt to understand complex data sets. This study examines pencil-and-paper graphs produced by students at the beginning of a 1-week summer teacher/student institute, as well as computer-based graphs produced by the same students at the end of the institute. Initial problems with managing the data set and producing meaningful graphs disappeared quickly as students used a process of “building up” to handle the complexity of web-based data on water quality. This process is examined, as are findings from the institute related to (a) barriers to accessing web-based data, (b) students' problem-solving processes, and (c) the promise of this approach for learning about environmental science issues.
IGF-1 Overexpression Rescues the Failing Heart

Congestive heart failure (CHF) is a syndrome affecting nearly 5 million Americans with 550 000 new cases diagnosed annually. Despite recent advances in pharmacological therapy, the enormity of the clinical problem has stimulated cardiovascular scientists to test a variety of new and provocative hypotheses that may ultimately prove useful in CHF prevention and treatment. One such novel approach is addressed by Welch et al1 in this issue of Circulation Research . They tested the hypothesis that insulin-like growth factor-1 (IGF-1), a peptide growth factor involved in cardiomyocyte proliferation, differentiation, and cell survival, can positively affect CHF progression in a transgenic mouse model of dilated cardiomyopathy. The study provides new and important information about the cellular mechanisms leading to ventricular remodeling and also adds to the current controversy regarding the roles of cardiomyocyte apoptosis and regeneration in the pathogenesis of CHF. Welch et al1 make use of two previously characterized transgenic mouse lines in a selective crossbreeding experiment. Dilated cardiomyopathy was modeled by overexpression of the cytoskeletal protein tropomodulin, to produce homozygous animals (tropomodulin-overexpressing transgenic [TOT] mice) with many of the features of human idiopathic dilated cardiomyopathy.2 Tropomodulin is an actin-binding protein that associates with the pointed ends of actin filaments. This occurs late in the process of myofibrillogenesis and is thought to be responsible for maintaining the final length of thin filaments in mature, striated myofibrils.3 Sussman and coworkers have previously shown that tropomodulin overexpression in cultured cardiomyocytes produced shortened actin filaments and myofibrillar degeneration, whereas antisense downregulation of tropomodulin produced abnormally long actin filaments at the cell periphery.4 Thus, it might seem surprising that TOT cardiomyocytes are elongated, with a markedly increased length-to-diameter ratio. Cardiomyocyte elongation is a feature common to many other forms of …
Functional inputs to passive correlation detectors for oscillatory transient signals

This research investigates whether passive detection of transient signals can be improved by replacing received signals with functionals of the received signals in correlation detectors. Specifically, this paper assesses the impact of using energy spectrum and autocorrelation functional inputs to the cross-correlation (energy), bicorrelation, and tricorrelation detectors. Test signals with differing autocorrelation and energy spectrum properties are used in computer simulations with independent Gaussian noise to evaluate detector performance. Detection results are presented for the case when only two channels of input data are available to form the correlations, as well as the case when three and four channels of input data are available to form the higher order correlations. In the former case, it is shown that detection performance can be improved for the narrow-band signals by using the energy spectrum and autocorrelation functional inputs rather than the original received signal. In the latter case, it is shown that detection performance can be improved by using the autocorrelation input for the broadband signal and the energy spectrum input for the narrow-band signals, and that the tricorrelation detector performs best for the signals tested.
The Role of Goal-Focused Leadership in Enabling the Expression of Conscientiousness

The authors tested the hypothesis that goal-focused leadership enables conscientious workers to perform effectively by helping them to accurately understand organizational goal priorities. Data collected from 162 workers in a private sector document processing organization supported the hypotheses that goal-focused leadership moderates the relationship between conscientiousness and job performance and that person-organization goal congruence mediates this moderated relationship. Specifically, conscientiousness was more strongly positively related to performance among workers who perceived that their supervisors effectively set goals and defined roles, responsibilities, and priorities than among workers who did not perceive this type of goal-focused leadership.
An all-optical long-distance multi-Gbytes/s bit-parallel WDM single-fiber link

An all-optical long-distance (>30 km) bit-parallel wavelength division multiplexed (WDM) single-fiber link with 12 bit-parallel channels having 1 Gbyte/s capacity has been designed. That system functionally resembles an optical fiber ribbon cable, except that all the bits pass on one fiber-optic waveguide. This single-fiber bit parallel wavelength link can be used to extend the (speed x distance) product of emerging cluster computer networks, such as, the MyriNet, SCI, Hippi-6400, ShuffleNet, etc. Here, the detailed design of this link using the commercially available Corning DS (dispersion-shifted) fiber is given. To demonstrate the viability of this link, two WDM channels at wavelengths 1530 and 1545 nm carrying 1 ns pulses on each channel were sent through a single 25.2-km long Corning DS fiber. The walkoff was 200 ps, well within the allowable setup and hold time for the standard ECL logic which is 350 ps for a bit period of 1 ns. This result implies that 30 bit-parallel beams spaced 1 nm apart between 1530-1560 nm, each carrying 1 Gbits/s signal, can be sent through a 25.2-km Corning DS fiber carrying information at a 30 Gb/s rate.
Investigation of the Roles of Toxin-Coregulated Pili and Mannose-Sensitive Hemagglutinin Pili in the Pathogenesis of Vibrio cholerae O139 Infection

In this study, adult volunteers were fed tcpA and mshA deletion mutants of V. cholerae O139 strain CVD 112 to determine the role of toxin-coregulated pili (TCP) and mannose-sensitive hemagglutinin (MSHA) in intestinal colonization. Eight of 10 volunteers who received CVD 112 or CVD 112 ΔmshA shed the vaccine strains in their stools; the geometric mean peak excretion for both groups was 1.4 × 105 CFU/g of stool. In contrast, only one of nine recipients of CVD 112 ΔtcpA shed vibrios in his stool (P < 0.01); during the first 24 h after inoculation, 3 × 102 CFU/g was recovered from this volunteer. All recipients of CVD 112 and 8 (80%) of the recipients of CVD 112 ΔmshA developed at least a fourfold rise in vibriocidal titer after immunization. In contrast, only one (11%) of the nine recipients of CVD 112 ΔtcpA developed a fourfold rise in vibriocidal titer (P < 0.01). We conclude that TCP are an important colonization factor of V. cholerae O139 and probably of El Tor V. cholerae O1. In contrast, MSHA does not appear to promote intestinal colonization in humans.
Pregabalin is more effective than placebo for restless legs syndrome with mild adverse effects of daytime somnolence, headache and unsteadiness

Commentary on: D Garcia-Borreguero, O Larrosa, AM Williams, et al.. Treatment of restless legs syndrome with pregabalin: a double-blind, placebo-controlled study.Neurology2010;74:1897–904.
General epistatic models of the risk of complex diseases.

The range of possible gene interactions in a multilocus model of a complex inherited disease is studied by exploring genotype-specific risks subject to the constraint that the allele frequencies and marginal risks are known. We quantify the effect of gene interactions by defining the interaction ratio, , where KR is the recurrence risk to relatives with relationship R for the true model and is the recurrence risk to relatives for a multiplicative model with the same marginal risks. We use a Markov chain Monte Carlo (MCMC) procedure to sample from the space of possible models. We find that the average of CR increases with the number of loci for both low frequency (p = 0.03) and higher frequency (p = 0.25) causative alleles. Furthermore, the probability that CR > 1 is nearly 1. Similar results are obtained when more weight is given to risk models that are closer to the comparable multiplicative model. These results imply that, in general, gene interactions will result in greater heritability of a complex inherited disease than is expected on the basis of a multiplicative model of interactions and hence may provide a partial explanation for the problem of missing heritability of complex diseases.
Translocation and Unwinding Mechanisms of RNA and DNA Helicases

Helicases and remodeling enzymes are ATP-dependent motor proteins that play a critical role in every aspect of RNA and DNA metabolism. Most RNA-remodeling enzymes are members of helicase superfamily 2 (SF2), which includes many DNA helicase enzymes that display similar structural and mechanistic features. Although SF2 enzymes are typically called helicases, many of them display other types of functions, including single-strand translocation, strand annealing, and protein displacement. There are two mechanisms by which RNA helicase enzymes unwind RNA: The nonprocessive DEAD group catalyzes local unwinding of short duplexes adjacent to their binding sites. Members of the processive DExH group often translocate along single-stranded RNA and displace paired strands (or proteins) in their path. In the latter case, unwinding is likely to occur by an active mechanism that involves Brownian motor function and stepwise translocation along RNA. Through structural and single-molecule investigations, researchers are developing coherent models to explain the functions and dynamic motions of helicase enzymes.
Challenges in Large-Scale Molecular Simulations of Intracellular Environments

Owing to advances in structural biology, proteomics and computational modeling it is now possible to consider constructing working simulation models of certain intracellular environments. Using bacterial systems for illustrative purposes, this talk will first briefly describe some promising results obtained with Brownian dynamics simulations methods - such as the ability to capture aspects of protein diffusion and thermodynamic stability in the bacterial cytoplasm. The talk will then discuss recent developments and ongoing projects before attempting to highlight a number of significant challenges likely to be faced by simulation models intended to more realistically describe events in vivoView Large Image | View Hi-Res Image | Download PowerPoint Slide.
AIDS And The Funeral Industry In Southeastern Africa

This paper examines the impact of AIDS on the Funeral Industry in Southeastern Africa. It first presents an overview of AIDS in Southeastern Africa and then it delves into an examination of family funeral customs in select countries and how they have been affected by the AIDS epidemic. These countries include: Zimbabwe, Malawi, Zambia, South Africa, Botswana, and Uganda. Next, this paper takes a look at the impact of AIDS on hospital mortuaries in Zimbabwe. This is followed by an examination of the rise in the number of orphans along with the effect of AIDS on the classroom setting. Finally, four suggestions for fighting the disease are presented.
Metallothionein overexpression does not protect against inflammatory bowel disease in a murine colitis model

BACKGROUND: We evaluated whether modulation of metallothionein (MT, and subsequent oxidative stress) would influence the development and progression of colitis. MATERIAL/METHODS: MT-transgenic (MT-TG), MT-knockout (MT-KO), and wild-type (WT) mice were treated with Dextran Sodium Sulfate (DSS) to induce colitis compared to controls (no DSS). RESULTS: The DSS treated MT-TG and MT-KO mice responded in a manner similar to that of DSS treated WT mice, with all groups developing severe colitis. The colonic MT content in DSS treated animals increased drastically when compared to controls. The colonic and blood levels of the antioxidant, glutathione (GSH), were significantly reduced in DSS treated MT-TG and MT-KO mice. Howevei there was no significant difference in the cysteine levels in these mice. The subeellular level of MT was highest in intestinal crypts loci of MT-TG mice and was not observed in MT-KO mice as well as in the inflammatory lesions. CONCLUSIONS: We conclude that MT does not appear to influence the development or progression of intestinal pathology in the DSS animal model of IBD.
Brain radiation injury leads to a dose- and time-dependent recruitment of peripheral myeloid cells that depends on CCR2 signaling

Cranial radiotherapy is used to treat tumors of the central nervous system (CNS), as well as non-neoplastic conditions such as arterio-venous malformations; however, its use is limited by the tolerance of adjacent normal CNS tissue, which can lead to devastating long-term sequelae for patients. Despite decades of research, the underlying mechanisms by which radiation induces CNS tissue injury remain unclear. Neuroinflammation and immune cell infiltration are a recognized component of the CNS radiation response; however, the extent and mechanisms by which bone marrow-derived (BMD) immune cells participate in late radiation injury is unknown. Thus, we set out to better characterize the response and tested the hypothesis that C-C chemokine receptor type 2 (CCR2) signaling was required for myeloid cell recruitment following brain irradiation. We used young adult C57BL/6 male bone marrow chimeric mice created with donor mice that constitutively express enhanced green fluorescent protein (eGFP). The head was shielded to avoid brain radiation exposure during chimera construction. Radiation dose and time response studies were conducted in wild-type chimeras, and additional experiments were performed with chimeras created using donor marrow from CCR2 deficient, eGFP-expressing mice. Infiltrating eGFP+ cells were identified and quantified using immunofluorescent microscopy. Brain irradiation resulted in a dose- and time-dependent infiltration of BMD immune cells (predominately myeloid) that began at 1 month and persisted until 6 months following ≥15 Gy brain irradiation. Infiltration was limited to areas that were directly exposed to radiation. CCR2 signaling loss resulted in decreased numbers of infiltrating cells at 6 months that appeared to be restricted to cells also expressing major histocompatibility complex class II molecules. The potential roles played by infiltrating immune cells are of current importance due to increasing interest in immunotherapeutic approaches for cancer treatment and a growing clinical interest in survivorship and quality of life issues. Our findings demonstrate that injury from brain radiation facilitates a dose- and time-dependent recruitment of BMD cells that persists for at least 6 months and, in the case of myeloid cells, is dependent on CCR2 signaling.
The Roles of Surface Adsorption and Mobility in Geologic Systems and Materials

Surface adsorption and diffusion play an important role in a number of geologic processes. The rate of crystal nucleation and growth from a molten liquid, in addition to the general morphology of the crystals are controlled to a great extent by surface mobility. Hydrologic processes such as concentration depletion during aquifer migration are extremely adsorption dependent. There are also a great number of practical applications involving the use of surface active agents to enhance natural processes. These applications include; enhanced petroleum recovery, mineral separation and a variety of others which will be discussed later in more detail.
Spatiotemporal Changes in Comfortable Weather Duration in the Continental United States and Implications for Human Wellness

We examined the spatial distribution of monthly, seasonal, and annual changes in comfortable weather hours (CWHs) between 1950 and 2011 and explored the relationship between human wellness and the amount and timing of CWHs. Using a thermohygrometric index based on air temperature and dewpoint temperature recorded every three hours from thirty-five U.S. cities, we determined whether changes in human thermal comfort were coincident with warming and more humid atmospheric conditions. We tested for significant trends in CWHs for every season for each city for nighttime, daytime, and total (i.e., night and day) periods. Although approximately 75 percent of the cities did not experience significant changes in CWHs on an annual basis, total changes in CWHs were marked by increases during spring and decreases in summer conditions, with the largest positive changes in CWHs found during spring nights, spring days, and autumn nights and the largest negative changes during summer nights and days. Spatially, increases...
THE CONSERVATIVE COMPENSATION-DEROTATION TREATMENT OF SCOLIOSIS

1 . Compensation of the scoliosis is a necessary prerequisite for maintenance of correction and posture. 2. The combined compensation-derotation method is adequate to obtain compensation in suitable cases and leads to definite maintenance of posture. 3. The rotary deformity of the thoracic spine cannot be corrected at present. Attempts to correct the thoracic deformity by rotation to the concave side are preposterous. The thorax is already rotated to the concave side in relation to the spinal column, and such attempts only make the situation worse. 4. Derotation is directed toward the lumbar and cervicothoracic section of the spine, and, by limbering up these sections, aids in the development of adequate counter curves. 5. If the compensation can be accomplished without forcible cast correction, and provided muscle development is adequate, the spine need not be fused. However, if the compensation must be forced by a cast, fusion will become necessary to hold the correction obtained. 6. Failure must be expected, with or without fusion, when compensation is lost or not obtained. Only a few cases at the end of the growth period hold the correction when decompensated. 7. Failure must also be expected in the absence of adequate muscle development, unless fusion is performed. 8. Compensation-derotation plus adequate muscle development promises success in the great majority of all non-paralytic cases. 9. Adequate compensation-derotation plus fusion in the presence of inadequate musculature, likewise, holds out promise of success in all paralytic and many congenital cases.
Impact of increasing heat waves on U.S. ozone episodes in the 2050s: Results from a multimodel analysis using extreme value theory

We develop a statistical model using extreme value theory to estimate the 2000–2050 changes in ozone episodes across the United States. We model the relationships between daily maximum temperature (Tmax) and maximum daily 8 h average (MDA8) ozone in May–September over 2003–2012 using a Point Process (PP) model. At ~20% of the sites, a marked decrease in the ozone-temperature slope occurs at high temperatures, defined as ozone suppression. The PP model sometimes fails to capture ozone-Tmax relationships, so we refit the ozone-Tmax slope using logistic regression and a generalized Pareto distribution model. We then apply the resulting hybrid-extreme value theory model to projections of Tmax from an ensemble of downscaled climate models. Assuming constant anthropogenic emissions at the present level, we find an average increase of 2.3 d a−1 in ozone episodes (>75 ppbv) across the United States by the 2050s, with a change of +3–9 d a−1 at many sites.
Using a Multiphase Flow Numerical Model to Simulate Geysers in Stormwater Systems

The temporary belowground storage of stormwater is useful in urban areas to prevent flooding. During intense rain events the conduits can fill rapidly and completely undergo a transition from open channel flow to pressurized flow. This transition can create large discrete pockets of trapped air as the interface advances into the free-surface portions of the system. These pockets pressurize in the horizontal reaches of the system and then are released through vertical vents, potentially creating a geyser condition. There have been some experimental and numerical investigations of the geyser effect, but the complex nature of the physics and geometry make this a challenging problem. Numerical studies have treated the geyser as a lumped mass or rigid column, with no consideration to the multiphase flow dynamics. This work presents a preliminary finding of a multiphase flow numerical model to capture both the liquid and gas dynamics, as well as the necessary interaction to create the geyser.
Hormones produced by tumours

There are 2 broad areas of tumour-related endocrinology: (1) Appropriate hormones secreted in inappropriate quantities by recognizable endocrine tumours, and (2) Inappropriate hormones secreted in any quantity by overtly non-endocrine tumours (the so-called ‘ectopic hormones’). In either case, the hormones secreted, and the clinical syndrome resulting from such secretion may serve as a tumour marker for early detection of the tumour and for follow-up reassessment of adequacy of treatment. Recognition of ectopic hormone production is limited only by the interests and intuition of the clinician and the technical facilities available to him for measuring hormones. Underdiagnosis is the rule, although at least 8 syndromes secondary to ectopic hormone production are fairly readily recognized: Cushing's Syndrome due to ectopic ACTH secretion; hyponatraemia due to ectopic antidiuretic hormone; hypercalcaemia due to ectopic parathormone; gynaecomastia in older men and precocious puberty in boys due to ectopic gonadotrophin; galactorrhoea due to ectopic prolactin; erythrocytosis due to ectopic erythropoietin; and hypoglycaemia possibly due to ectopic secretion of insulin-like activity. Ectopic thyrotrophin, calcitonin, growth hormone and human placental lactogen (HPL) rarely lead to clinical manifestations. Ectopic hormones are invariably polypeptides, never steroids. This fact underlies several explanations for the possible mechanism of ectopic hormone production. The concept of derepression within tumours of genetic material for polypeptide synthesis which is inherent in the genetic complement of all cells is now being questioned in favour of the theory that tumours secreting ectopic hormones either themselves arise from, or contain endocrinologically competent cells of neuroectodermal origin. Some go so far as to identify the oat cell carcinoma of lung as an endocrine tumour ‘per se’ This tumour is of particular interest because, like few others, it is capable of secreting multiple ectopic hormones. Taken from a different viewpoint, intensive study of hormone-secreting non-endocrine tumours may lead to an understanding of the mechanisms leading to neoplastic transformation.
Growth of mumps virus in organ cultures of rhesus testis.

An important complication of mumps infection in males is orchitis (Candel, 1951; Roseman, 1958), but very few reports of isolation of the virus from the testis have been published (Hook et al, 1949; Bolin and Leymaster, 1952). Attempts to produce orchitis in laboratory animals by inoculation have not yielded fruitful results. Johnson and Goodpasture (1934) did not obtain any evidence for testicular involvement in monkeys which were injected with mumps virus via Stensen' s duct. No evidence of in-
AT-48A PHASE 1 TRIAL OF CARBOXYAMIDOTRIAZOLE OROTATE (CTO) IN COMBINATION WITH BEVACIZUMAB FOR ADULT PATIENTS WITH RECURRENT MALIGNANT GLIOMA POST-BEVACIZUMAB FAILURE

CTO, an oral inhibitor of non-voltage-dependent calcium signaling, modulates several pathways, including EGFR, MEK, RAS, HDAC, HSP90, WNT/B-catenin, Akt, ERK, VEGF and Bcr-Abl. A recent Phase I safety study ({"type":"clinical-trial","attrs":{"text":"NCT01107522","term_id":"NCT01107522"}}NCT01107522) in advanced solid tumors, including glioblastoma, demonstrated a safe toxicity profile and responses to CTO. Primary objective is to assess the maximum tolerated dose, dose limiting toxicity (DLT) and activity of CTO when combined with Bevacizumab among patients with recurrent malignant glioma (WHO grade III or IV) post Bevacizumab failure. CTO dose escalation follows a classical 3 + 3 design at a dosage ranging from 225-642mg/m2/day. Bevacizumab is being administered intravenously at 10mg/kg every 2 weeks. Pharmacokinetic sampling is performed during cycle 1 at each dose level. MRI of the brain is evaluated at baseline and then every 8 weeks using RANO criteria. To date, 11 patients have been enrolled. Of the eight evaluable patients, seven have WHO grade IV and one has WHO grade III glioma. Median age at enrollment is 54 (32-66) years with the average KPS of 80% (60-90%) in five female and three male patients. Of the three patients treated at dose level 1 of CTO (225mg/m2/day), two have completed 4 cycles and demonstrated CAI (the active moiety of CTO in plasma) levels of 2317 and 361 ng/ml. Of the three patients treated at the dose level 2 (293mg/m2/day), one experienced DLT with Grade 3 fatigue and hypertension. Three additional patients are being enrolled at dose level 2. Two patients died due to progression of tumor within 30 days of coming off study. The most frequently recorded adverse events were constipation, fatigue, nausea, vomiting, hypertension, proteinuria, hypokalemia and dizziness. CTO at a dose of 225mg/m2/day given in combination with Bevacizumab is safe and tolerable. Dose escalation is ongoing.