cssi/SciSciGPT-SciSciNet huggingface dataset:
Outcomes in Obese and Overweight Acute Myeloid Leukemia (AML) Patients Receiving Chemotherapy Dosed According to Actual Body Weight

Abstract Abstract 1496 Background: Cytotoxic chemotherapy (CT) dosages are traditionally calculated according to body surface area (BSA). There are no recommendations for the dosing of CT in obese (OB) and overweight (OV) patients (pts) with AML. In solid tumor malignancies, use of actual body weight to calculate CT dosages in OB pts did not result in increased toxicities. Due to the lack of data in leukemia pts, we investigated efficacy and safety outcomes between underweight and normal weight (NW), OV, and OB pts when CT was dosed according to BSA based on actual body weight. Methods: We identified AML pts treated with anthracycline and cytarabine-based remission induction CT dosed according to actual body weight from 2002 to 2009 at Cleveland Clinic. Pts were divided into three groups according to body mass index (BMI): NW (BMI 30.0). Cytogenetics were categorized according to CALGB. Complete remission (CR) rates, overall survival (OS), and safety outcomes were compared between groups. Means, percentages, and median survival time were compared among groups using ANOVA, chi-square tests, survival analysis with log-rank tests and Cox regressions, as appropriate. Results: Of the 247 AML pts included, 81 were NW, 81 were OV, and 85 were OB. Baseline characteristics were not different between groups; within the entire study population, the mean age was 55.6 years (SD 14.3), 49.0% were female, and 69.2% had de novo AML. Favorable, intermediate, and unfavorable cytogenetics were not significantly different in NW (6.2%, 55.6%, and 30.9%), OV (18.5%, 38.3%, and 29.5%), and OB pts (15.3%, 42.4%, and 27.1%; p=0.107), respectively. Among NW, OV, and OB pts, CR rates were similar (69.1%, 79.0%, and 76.5%, respectively; p=0.321), as was median OS (10.7, 16.7, and 14.2 months, respectively, p=0.352) and early mortality within 30 days of induction CT (3.7%, 2.5%, and 7.1%, respectively, p=0.331). There was no difference in days to neutrophil recovery (34.4, 31.9, and 32.7, respectively, p=0.134) or days to platelet recovery (34.2, 31.7, and 31.2, respectively, p=0.490). Days spent in the hospital during initial induction CT (p=0.095) and incidence of documented bacteremia (p=0.288) also did not differ among groups. Post-therapy left ventricular ejection fraction Conclusions: CR rates and CT-associated adverse events were not significantly different among NW, OV, and OB AML pts when standard induction CT was dosed according to actual body weight. This demonstrates that standard induction CT can be safely dosed using actual body weight in these pts. Although not significant, NW patients had the lowest CR rate and shortest median OS. Low BMI could be a marker of worse performance status. Disclosures: No relevant conflicts of interest to declare.
Variation in subsurface thermal characteristics of microrefuges used by range core and peripheral populations of the American pika (Ochotona princeps).

Microrefuges provide microclimates decoupled from inhospitable regional climate regimes that enable range-peripheral populations to persist and are important to cold-adapted species in an era of accelerated climate change. However, identifying and describing the thermal characteristics of microrefuge habitats is challenging, particularly for mobile organisms in cryptic, patchy habitats. We examined variation in subsurface thermal conditions of microrefuge habitats among different rock substrate types used by the American pika (Ochotona princeps), a climate-sensitive, rock-dwelling Lagomorph. We compared subsurface temperatures in talus and lava substrates in pika survey sites in two US national park units; one park study area on the range periphery and the other in the range core. We deployed paired sensors to examine within-site temperature variation. We hypothesized that subsurface temperatures within occupied sites and structurally complex substrates would be cooler in summer and warmer in winter than unoccupied and less complex sites. Although within-site variability was high, with correlations between paired sensors as low as 47%, we found compelling evidence that pikas occupy microrefuge habitats where subsurface conditions provide more thermal stability than in unoccupied microhabitats. The percentage of days in which microhabitat temperatures were between -2.5 and 25.5°C was significantly higher in occupied sites. Interestingly, thermal conditions were substantially more stable (p < .05) in the lava substrate type identified to be preferentially used by pikas (pahoehoe vs. a'a) in a previous study. Our study and others suggest that thermal stability appears to be the defining characteristic of subsurface microrefuges used by American pikas and is a likely explanation for enigmatic population persistence at the range periphery. Our study exemplifies an integrated approach for studying complex microhabitat conditions, paired with site use surveys and contextualized with information about gene flow provided by complementary studies.
Human Performance Under Sequences of Fixed-Ratio Schedules: Effects of Ratio Size and Magnitude of Reinforcement

In a discrete-trials procedure, adult humans chose between two sequential fixed-ratio (FR) schedules. Points, later exchangeable for money, were given for the completion of each FR. When each sequence produced two points for an equal number of responses overall, the value of the first FR in a sequence did not affect choice. When the values of the first FR in each sequence were equal, subjects preferred the alternative with the smaller second FR. Once a preference was established for the alternative with the smaller overall response requirement, two points were given for completing the second FR of the nonpreferred sequence. This sequence then provided three total points. Preference immediately shifted to the alternative requiring more responses overall (and per point) but offering more points.
A comparison of outcomes between open, laparoscopic and robotic pancreaticoduodenectomy.

Abstract Background The advantages and comparison of minimally invasive techniques for pancreaticoduodenectomies have not been fully explored using large national multicenter data. Study design A retrospective review of NSQIP targeted data from 2014 to 2015 was performed. Demographics and outcomes were compared between open (OPD), laparoscopic (LPD) and robotic pancreaticoduodenectomies (RPD). Results Of 6827 pancreaticoduodenectomies, 6336 (92.8%) were OPD, 280 (4.1%) were LPD, and 211 (3.1%) were RPD. Compared to OPD, LPD required more post-operative drainage procedures (18.4% vs 13.2%, p = 0.013), had less SSI (3.2% vs 9%, p = 0.001), and had fewer discharges to a new facility (8.1% vs 13%, p = 0.018). Compared to OPD, RPD had less perioperative transfusions (14.2% vs 20.5%, p = 0.026) and more readmissions (23.2% vs 16.7%, p = 0.013). After controlling for differences, LPD was independently associated with decreased 30-day morbidity compared to OPD (OR 0.75, 95% CI 0.56–0.99). There was no difference in 30-day mortality. Conclusions This is the first study to compare the outcomes of laparoscopic and robotic pancreaticoduodenectomies to open using the NSQIP database. After controlling for differences between groups, LPD is independently associated with less morbidity. In experienced hands, it appears safe and valuable to pursue refinement of minimally invasive techniques for pancreaticoduodenectomies.
Sequential Neighborhood Effects: The Effect of Long-Term Exposure to Concentrated Disadvantage on Children’s Reading and Math Test Scores

Prior research has suggested that children living in a disadvantaged neighborhood have lower achievement test scores, but these studies typically have not estimated causal effects that account for neighborhood choice. Recent studies used propensity score methods to account for the endogeneity of neighborhood exposures, comparing disadvantaged and nondisadvantaged neighborhoods. We develop an alternative propensity function approach in which cumulative neighborhood effects are modeled as a continuous treatment variable. This approach offers several advantages. We use our approach to examine the cumulative effects of neighborhood disadvantage on reading and math test scores in Los Angeles. Our substantive results indicate that recency of exposure to disadvantaged neighborhoods may be more important than average exposure for children's test scores. We conclude that studies of child development should consider both average cumulative neighborhood exposure and the timing of this exposure.
Partnering Medical Students With Barbers to Cut Hypertension in Black Men

The article discusses a partnership between the Student National Medical Association at the University of Pennsylvania's Perelman School of Medicine and barbershops in West Philadelphia, Pennsylvania to improve the health of Black men in the community. Topics include health education, health counseling, and medical screening offered to Black men from the community at the barbershops, the high prevalence of hypertension among Black men in the U.S., and medical students' efforts to reduce health disparities.
Evolution of MG AZ31 twin activation with strain: A machine learning study

Abstract Complex relationships between microstructure and twin formation in AZ31 magnesium are investigated as a function of increasing strain using supervised machine learning. In one approach, strain is incorporated as an implicit attribute in a single predictive model, in a second method, separate decision trees are formed for each strain level. A comparison of the methods shows that the second better uncovers the underlying physics. The correlations revealed are found to exhibit similarities with parameters used in conventional modeling techniques, leading to the conclusion that machine learning has potential to assist in future microstructural modeling.
Patterns of Population Growth and Dispersal

Bacteria in our gut, insects in a field, trees in a forest, and plants borne by air and water around the world are among the many examples of spatial distributions of organisms that are important and interesting to study. Mechanisms of pattern formation and dispersal operate on a wide range of spatial scales from microscopic random movements to long-distance transport by air or water. On the other hand, organisms can also reflect uneven distributions of nutrients or toxins in their growth patterns. These are important, for example, in palenology, where the distributions of microbial fossils are used to find oil, and they provide places to look for new species of microbes, such as petroleum-digesting bacteria that are now used to clean oil tanks.
Peyronie’s-Like Plaque after Penile Injection of Prostaglandin E1

AbstractIntracavernous Injection of vasoactive medication may cause fibrosis of the tunica albuginea or corpus cavernosum. These adverse effects have been clearly linked to papaverine and phentolamine but to our knowledge the development of fibrosis or a Peyronie’s-like plaque after the injection of prostaglandin E1 has not been previously described. We report a case of intracavernous hematoma, penile curvature deformity and Peyronie’s-like plaque that developed after initiating intracorporeal self-injection of prostaglandin E1 for erectile dysfunction.
Grandma or Mommy: Familial Labels as Constructs of Identity in Grandfamilies

ABSTRACTOne challenge that grandfamilies, families in which grandparents act as caregivers to grandchildren, must navigate is assignment of labels – whether to go by traditional grandparent labels ...
BCL6 Interacts with Cullin-3 Ubiquitin Ligase Complex In B Cells

Abstract Abstract 3129 The proto-oncogene BCL6 encodes for a BTB/POZ-zinc finger transcriptional repressor which plays an essential role in germinal center (GC) formation and is implicated in the pathogenesis of B-cell lymphoma. BCL6 is shown to be a critical regulator modulating many important functions in B cells, including activation, differentiation, cell cycle arrest and apoptosis. Tight regulation of BCL6 is, therefore, critical for the control of GC reaction as well as for the phenotype of GC-derived lymphomas. In response to B cell receptor activation or DNA damage induction, BCL6 protein is phosphorylated and subsequently degraded through distinct mechanisms that involve ubiquitination process. Here we report that BCL6 interacts with Cullin-3 (Cul3), major component of a multimeric E3 ubiquitin ligase complex. Consistent with previous reports indicating that BTB/POZ domain proteins interact with Cul3, the BCL6-POZ domain is sufficient for BCL6 interaction with Cul3. Importantly, BCL6 and Cul3 interaction is also readily detected in native B cells. Interestingly, this interaction does not affect BCL6 transcriptional repression activity nor does it affect basal level of BCL6 stability. The pathophysiological consequence of this interaction is investigated, including a possibility that BCL6 functions as a specific substrate adaptor for the Cullin-3 ubiquitin complex. Disclosures: No relevant conflicts of interest to declare.
The great agrarian conquest: the colonial reshaping of a rural world: by Neeladri Bhattacharya, Bangalore, Orient BlackSwan, 2018, 522 pp., US$40.83 (hardback)

Neeladri Bhattacharya narrates the “great agrarian conquest”, the colonial transformation of variegated rural spaces into the homogenous “agrarian” space of bounded villages, settled peasants and d...
Microtwist elasticity: A continuum approach to zero modes and topological polarization in Kagome lattices

Abstract The topologically polarized isostatic lattices discovered by Kane and Lubensky (2014, Nat. Phys. 10, 39–45) challenged the standard effective medium theories used in the modeling of many truss-based materials and metamaterials. As a matter of fact, these exhibit Parity (P) asymmetric distributions of zero modes that induce a P-asymmetric elastic behavior, both of which cannot be reproduced within Cauchy elasticity. Here, we propose a new effective medium theory baptized “microtwist elasticity” capable of rendering polarization effects on a macroscopic scale. The theory is valid for trusses on the brink of a polarized-unpolarized phase transition in which case they necessarily exhibit more periodic zero modes than they have dimensions. By mapping each periodic zero mode to a macroscopic degree of freedom, the microtwist theory ends up being a kinematically enriched theory. Microtwist elasticity is constructed thanks to leading order two-scale asymptotics and its constitutive and balance equations are derived for a fairly generic isostatic truss: the Kagome lattice. Various numerical and analytical calculations, of the shape and distribution of zero modes, of dispersion diagrams and of polarization effects, systematically show the quality of the proposed effective medium theory.
Calibration of Probabilistic Model Output: Introduction and Online Tool

: Many machine learning algorithms provide probabilistic predictions as their outputs. Analysis techniques familiar to physicians (e.g., calculation of sensitivity and specificity and construction of receiver operating characteristics curves) do not allow for the assessment of model calibration and prevent proper evaluation of these models. We reviewed statistical and graphical (shown in Figure 1) methods for calibration analysis and presented a framework for the implementation of these techniques using open-source codes and an online tool.
A new phenomenological model to describe root-soil interactions based on percolation theory

Abstract In his paper on net primary productivity of terrestrial communities predicted from climatological data, Rosenzweig (1968) argued that variability in productivity is well accounted for by (evapo)-transpiration, and that water from transpiration is, on global scales, the most variable component in the photosynthesis reaction. The goal of this paper is to investigate whether variability in plant growth on local scales and within species is primarily related to transpiration under several scenarios including different terrain curvature, slope aspect, soil characteristics, and climate ranges. We test the hypothesis that this relationship exists because root growth into the surface soil layers (0–2 m) tends to follow paths with minima in resistance, which in turn maximizes water flow and nutrient delivery rates that regulate growth. The set of all connected paths with individual pore-to-pore flow resistances less than a critical, percolating, value forms a cluster with mass fractal dimensionality, df. We propose that roots follow paths through the 2D percolation cluster, defining the set of all optimal flow paths, making the 2D value of df from percolation relevant to root fractal dimensionality. The tortuosity of such optimal paths as defined in percolation theory should then relate root length to root radial extent, linking the parameters of root tortuosity and plant productivity. Our analysis of large data sets across species implies that root radial extent and tree height are both proportional to cumulative transpiration until trees approached maximum height, and their growth rates are proportional to the transpiration rate, not to the moisture content. Local variations in tree height as functions of the variables investigated appear generally consistent with deduced variations in transpiration. Here this correlation is investigated more closely in the context of studies addressing individual tree species.
Pill-Swallowing Training in Very Young Children With Cancer: A Case Series and Developmental Considerations

Pill-swallowing training (PST) is a promising behavioral intervention. However, previous studies of PST have largely reported outcomes only in children aged 6 years and older. In the pediatric oncology setting, younger children may benefit from learning to swallow pills, with motivators such as avoiding bad-tasting liquid medications, simplifying oral medication routines, and accessing trials for patients with poor prognoses. Here, we briefly describe the standard PST intervention protocol and report success with very young patients experiencing a variety of medical, emotional, behavioral, and developmental complications. The current case series illustrates the utility of traditional behavioral PST interventions with novel supplements, such as intervention to increase general compliance or decrease anxiety, in four young children with cancer. These cases highlight the effectiveness of PST and describe the positive impact reported by each family. Developmental considerations for using PST with young children with cancer are offered.
Vector Potential Dyadic Green’s Function and Normal Modes in Cavity of Arbitrary Shape

A semi-analytical approach for rapid calculation of the vector potential normal modes and dyadic Green's function inside the cavity of irregular shape over a broad range of frequency is presented. The method is based on the extraction of the Green's function at an imaginary wave number from itself to obtain a rapidly convergent hybrid spatial-spectral expansion of the Green's function. The extracted term encompasses the singularity of the Green's function and is computed using surface integral equation. The method is applied to a V-grooved cavity to obtain the vector potential Green's function inside the cavity.
Autonomous and Financial Mortgage Prepayment

Using individual data from Freddie Mac’s portfolio of conventional mortgages, this paper estimates prepayment probabilities as a function of characteristics pertaining to the borrower, the loan, regional, and economic variables. Distinction is made between induced and autonomous prepayments. Based on the curvature of the underlying termination pattern, nonparametric methods are derived to estimate the prepayment probabilities and to predict a mortgage life under various scenarios. The findings point to a response asymmetry with respect to the level and trend of interest rates. Non-interest effects reveal the significance of the borrower’s characteristics, property age and regional mobility rates on mortgage termination.
Determination and representation of the stress coefficient terms by path-independent integrals in anisotropic cracked solids

Because the elastic T-stress and other coefficients of the higher-order terms play an important role in fracture mechanics such as the stability of crack kinking, crack path, and two-parameter characterization of elastic-plastic crack tip fields, determination of all the coefficients in the crack tip field expansion in an anisotropic linear elastic solid is presented in this paper. Utilizing conservation laws of elasticity and Betti's reciprocal theorem, together with selected auxiliary fields, T-stress and third-order stress coefficients near the crack tip are evaluated first from path-independent line integrals. To determine the T-stress terms using the J-integral and Betti's reciprocal work theorem, auxiliary fields under a concentrated force and moment acting at the crack tip are used respectively. Through the use of Stroh formalism in anisotropic elasticity, analytical expressions for all the coefficients including the stress intensity factors are derived in a compact form that has surprisingly simple structure in terms of one of the Barnett-Lothe tensors, L. The solution forms for degenerated materials, monoclinic, orthotropic, and isotropic materials are also presented.
Development of 18 GHz GaAs static frequency dividers and their evaluation by electrooptic sampling

This paper describes high-speed GaAs static divider circuits operating up to 18.05 GHz at room temperature, and the use of electrooptic testing for the evaluation of their performance. The dividers were implemented in both buffered FET logic (BFL) and capacitively enhanced logic (CEL.), and were fabricated with 0.2-μm gatelength MESFETs, molecular beam epitaxy (MBE)-grown active channels, and airbridge interconnects.
Balloon aortic valvuloplasty for aortic stenosis using a novel percutaneous dilation catheter and power injector.

Calcific aortic stenosis is the most common valvular heart disease in the Western world. Although definitive treatment is valve replacement, many patients are not replacement candidates due to high surgical risk from older age and comorbid illness or lack of desire for a surgical or replacement procedure. Percutaneous balloon aortic valvuloplasty (BAV) is an option for palliative treatment in nonsurgical patients, although this procedure is complicated during the immediate postprocedure period by bleeding requiring transfusion for about 1 in 5 patients and subsequent restenosis. This report describes BAV using a smaller profile balloon designed to withstand higher pressures, rapidly inflated with a power injector. Twenty consecutive high-risk patients with severe aortic stenosis were treated. In all cases, New York Heart Association (NYHA) class improved from IV before BAV to I or II at 30 days follow-up. Six-month posttreatment follow-up data were available for 19 of 20 patients: 15 patients were either NYHA class I or II, 1 patient was class III, and 3 deaths occurred unrelated to aortic stenosis. One patient was lost to follow-up. Average systolic gradient peak-to-peak pressure decreased by 40.0% (range 18.0–70.0%) and mean gradient decreased by 30.0% (range 13.7–70.8%). Aortic valve area increased from 0.59 ± 0.16 cm2 to 0.92 ± 0.23 cm2, representing a mean increase of 30.0% (range 7.8%–58.2%). There were no significant bleeding complications. The only procedural complication was a single case of pericardial tamponade. There were no other complications during the first 24 hours post-BAV. These data support that the reported BAV technique may offer an effective alternative for patients with severe aortic stenosis who are not surgical candidates or prefer to avoid aortic valve replacement. (J Interven Cardiol 2011;24:92–98)
Identification of nucleoside transport binding sites in the human myocardium

The role of nucleoside transport in ischemia-reperfusion injury and arrhythmias has been well documented in various animal models using selective blockers. However, clinical application of nucleoside transport inhibitors remains to be demonstrated in humans. It is not known whether human heart has nucleoside transport similar to that of animals. The aim of this study is to pharmacologically identify the presence of nucleoside transport binding sites in the human myocardium compared to animals.
The Force of Action: Legitimizing the Coup in Bamako, Mali:

The coup d’etat that occurred in Bamako in March 2012 brought a previously unknown army captain named Amadou Sanogo to power. This paper analyses Malian media reports to explore how Sanogo and his associates sought to legitimize their takeover with reference to local conceptions of heroism, power and destiny, and how Sanogo’s public image resonated with time-honoured narratives about heroic figures in Malian culture. This case demonstrates that understanding religious worldviews is essential for understanding the workings of political power.
The Rhodanese Reaction MECHANISM OF SULFUR-SULFUR BOND CLEAVAGE

Abstract Kinetic studies comparing methanethiosulfonate and thiosulfate as rhodanese substrates have shown that the cleavage of the thiosulfate sulfur-sulfur bond limits the over-all maximum velocity of the thiosulfate-cyanide sulfur transfer reaction. A kinetically significant enzyme-thiosulfate complex has thus been shown. The same studies have indicated that the Michaelis constant for thiosulfate is a true dissociation constant for this complex. Infrared spectral studies and experiments involving the reaction between thiosulfonates and cyanide in nonenzymic systems have shown that the reactivity of the planetary sulfur atom toward cyanide is enhanced by a shift of electrons away from the sulfur-sulfur bond. Studies of the enzyme-catalyzed reaction between the thiosulfonates and cyanide have suggested that one aspect of enzymic catalysis in the thiosulfate reaction is such a shift of electrons away from the sulfur-sulfur bond. A basis for the anomalous behavior of aromatic substrates has been discussed.
Splitting the Unsplittable: Toward a Formulary Approach to Allocating Residuals Under Profit Split

It has been recognized at least since the publication of the US Treasury White Paper in 1988 that the key problem in applying the Arm’s Length Standard (ALS) to multinational enterprises (MNEs) is what to do in the absence of comparables. The White Paper proposed to apply a functional analysis to the various components of the MNE, and to allocate profits based on the comparables that can be found for each function. This led to the development of the profit split method, which was incorporated in the US regulations in 1994 and into the OECD Guidelines soon thereafter. The OECD paper on intangibles has recently recognized that profit split is the most likely candidate of the five ALS compliant methods to be applied to modern MNEs that derive the bulk of their profit from intangibles.But the problem with the profit split method is that it frequently results in a residual that cannot be allocated under the functional analysis because it results from cost savings that inhere in the relationship of the group members to each other. The OECD Transfer Pricing Guidelines do not say what should be done with residuals under the profit split method. The OECDs preferred method of applying the profit split method is to analyze the functions, assets and risk of each member of the affiliated group. However, in the context of residuals this method also proves to be illusory. A functional analysis can only be applied to those functions that can be assigned to the group members, such as production or distribution, but it does not help with residuals that result from the relationship among the group members. Assets can include intangibles, which are usually the most valuable assets of a modern MNE, but intangibles also get their value from the relationship among the group members,and they cannot be allocated to either where they were developed or where they are exploited. Risk is the most tricky concept of all. Recent case studies by the US Joint Committee on Taxation reveal a model in which the entrepreneurial risk for a product is assigned to an affiliate in a low tax jurisdiction and the manufacturing and distribution of the product in high tax jurisdictions are done on a contract manufacturing and commissionaire basis. But it is not clear what the allocation of entrepreneurial risk means among related parties. If a product fails because of technological change or defects in manufacturing or environmental hazards, the risk is effectively borne by the entire MNE.I would therefore propose that the OECD accept the use of formulas to allocate the residual in the profit split method. Specifically, I would suggest using a formula based entirely on the destination to which the goods and services that the MNE provides are sold.
Strand breaks without DNA rearrangement in V (D)J recombination.

Abstract Somatic gene rearrangement of immunoglobulin and T-cell receptor genes [V(D)J recombination] is mediated by pairs of specific DNA sequence motifs termed signal sequences. In experiments described here, retroviral vectors containing V(D)J rearrangement cassettes in which the signal sequences had been altered were introduced into wild-type and scid (severe combined immune deficiency) pre-B cells and used to define intermediates in the V(D)J recombination pathway. The scid mutation has previously been shown to deleteriously affect the V(D)J recombination process. Cassettes containing a point mutation in one of the two signal sequences inhibited rearrangement in wild-type cells. In contrast, scid cells continued to rearrange these cassettes with the characteristic scid deletional phenotype. Using these mutated templates, we identified junctional modifications at the wild-type signal sequences that had arisen from strand breaks which were not associated with overall V(D)J rearrangements. Neither cell type was able to rearrange constructs which contained only a single, nonmutated, signal sequence. In addition, scid and wild-type cell lines harboring cassettes with mutations in both signal sequences did not undergo rearrangement, suggesting that at least one functional signal sequence was required for all types of V(D)J recombination events. Analysis of these signal sequence mutations has provided insights into intermediates in the V(D)J rearrangement pathway in wild-type and scid pre-B cells.
Biologic Properties of Hepatitis B Viral Genomes with Mutations in the Precore Promoter and Precore Open Reading Frame

It is now well recognized that mutations in the hepatitis B virus (HBV) genome occur during the natural course of chronic viral infection. Regions of the viral genome that are frequently affected by such mutations, rearrangements, and/or deletions generally involve the precore promoter, precore, and core as well as the preS gene regions. However, little is known regarding the biologic consequences of these mutations on the functional properties of the variant viral strains with respect to effects on viral replication. In this study, we investigated the functional significance of precore promoter and precore gene mutations that reduce or abolish the synthesis of hepatitis B e antigen (HBeAg). We found that precore promoter mutations diminished the expression of HBeAg but did not affect the synthesis of pregenomic RNA. However, these precore mutations were associated with a modest increase in HBV replication. In contrast, a naturally occurring mutant that carries a termination codon in position 28 of the precore open reading frame demonstrated increased encapsidation of pregenomic mRNA into nucleocapsid particles. Consequently, this variant viral strain demonstrated a substantial increase in the level of viral replication compared to "wild-type" HBV and other precore promoter mutant viral strains. These studies suggest that substitutions in the precore promoter and precore gene not only alter the synthesis of HBeAg but also affect the level of viral replication.
High acceleration board level reliability drop test using Dual Mass Shock Amplifier

The advance of mobile electronics applications has been demanding higher drop/shock reliability performance under more severe drop/shock impacts. This in turn is requiring the board level reliability (BLR) drop test to be able to reach higher peak acceleration, particularly higher than 5000 G. One method to reach this high acceleration is to use an apparatus called Dual Mass Shock Amplifier (DMSA) attached onto a conventional drop tester. The conventional drop tester typically generates a primary impact in the range of 1000 ~ 2000 G, and the DMSA, which hangs above the drop table of the drop tester and continues to fall down immediately following the primary impact, is capable to generate a secondary impact with the drop table with magnitude 2~5x of the primary impact in terms of peak acceleration. In this study, the mechanics of drop test and DMSA was introduced and modeled with Newton physics. Two DMSAs with various different features were custom-designed, fabricated, assembled, and tested. Various aspects of the DMSA, including materials, layout, weight, gap height, holding mechanism, were evaluated and addressed. The effects of drop height, weight of DMSA, and gap height on the change of velocity and peak acceleration of secondary impact were studied. The strain on BLR drop test board under high acceleration impact was measured and discussed. Consistency of the shock amplification characterized by C pk was studied and method to improve the consistency was discussed. It is demonstrated through this study that using DMSA can be a simple, economical, and consistent method to achieve high acceleration for BLR drop test.
Recent Evidence on the Determinants of Concert Attendance for Mid-Size Symphonies

This study provides some recent evidence regarding the determinants of aggregate annual attendance at the concert performances of mid-size symphonies. In data from the 2003, 2004, and 2005 seasons from fifty-two mid-size symphonies, attendance is found to be positively affected by quality of the symphony, number of concert performances, and possibly the proportion of the population with some college level education or better. Attendance is negatively affected by ticket price, proportion of the population with very high income levels, the number of competing symphonies in the region, and the square of the number of concert performances. The effect on attendance from age depends on the age cohort.
On generalized Stackelberg strategies

The concept of Stackelberg strategy for a nonzero-sum two-person game is extended to allow for a nonunique “rational” response of the follower. This leads to the notion of a generalized Stackelberg strategy for the leader, which guarantees him a cost value that cannot be exceeded, no matter what the “rational” response of the follower. Then, a generalized Stackelberg strategy pair is defined. A simple example is given. The idea of a generalized Stackelberg strategy and strategy pair is then applied to the situation of one leader and many “rational” followers.
Evidence for SV40 specific RNA containing virus and host specific sequences.

AFTER infection of monkey kidney cells with simian virus 40 (SV40), several species of SV40 specific RNA are synthesized1. Most SV40 RNA have a molecular weight of about 6×105 and 8×105 as measured by polyacrylamide gel electrophoresis1. In addition to these classes of RNA, a large heterogeneous SV40 specific RNA species of up to three times the length of the monomeric SV40 DNA molecule has been observed1–4. Nothing is known about the structure of this large heterogeneous virus specific RNA.
Statistical mechanics of a classical one-component coulomb gas using collective coordinates

Abstract We develop a new expansion for the logarithm of the canonical partition function ln Q for the classical one-component Coulomb gas, using collective coordinates. Our initial use of collective coordinates is similar to that of Iuknovskii 1958, and our expansion resembles that of Abe (1959) . Our result for the lowest-order correction to the Debye-Huckel theory is the same as these earlier results, while our next order correction is different. From our expansion for ln Q we obtain an expansion for the grand function Ω = F − μN = −pV . The ultimate purpose of this work is to develop a new mathematical technique for obtaining thermodynamic properties of an ionized gas from quantum statistical mechanics.
Selected configuration tradeoffs of contour optical instruments

Abstract The Comet Nucleus Tour (CONTOUR) is a low-cost NASA Discovery mission designed to conduct three close flybys of comet nuclei. Selected configuration tradeoffs conducted to balance science requirements with low mission cost are reviewed. The tradeoffs discussed focus on the optical instruments and related spacecraft considerations. Two instruments are under development. The CONTOUR Forward Imager (CFI) is designed to perform optical navigation, moderate resolution nucleus/jet imaging, and imaging of faint molecular emission bands in the coma. The CONTOUR Remote Imager and Spectrometer (CRISP) is designed to obtain high-resolution multispectral images of the nucleus, conduct spectral mapping of the nucleus surface, and provide a backup optical navigation capability. Tradeoffs discussed are: (1) the impact on the optical instruments of not using reaction wheels on the spacecraft, (2) the improved performance and simplification gained by implementing a dedicated star tracker instead of including this function in CFI, (3) the improved flexibility and robustness of switching to a low frame rate tracker for CRISP, (4) the improved performance and simplification of replacing a visible imaging spectrometer by enhanced multispectral imaging in CRISP, and (5) the impact on spacecraft resources of these and other tradeoffs.
Role of individual N-linked glycosylation sites in the function and intracellular transport of the human alpha folate receptor.

Glycosylation is a structural feature of all three isoforms of the human folate receptor. We have used site-directed mutagenesis to study the role of individual glycosylation sites in the assembly and function of the a isoform of the human folate receptor (alpha(h)FR). Three potential N-linked glycosylation sites in the alpha(h)FR sequence were disrupted by conservative mutation of the S or T residues in the consensus sequence (N-X-S/T) to A or V, respectively. Constructs with the single mutations S(71)-->A (alpha(h)FR(-1)), T(163)-->V (alpha(h)FR(-2)), and S(203)-->A (alpha(h)FR(-3)); the double mutation S(71)--> A/S(203)-->A (alpha(h)FR(-1-3)); and the triple mutation S(71)--> A/S(203)--> A/T(163)--> V (alpha(h)FR(-1-2-3)) were stably transfected into Chinese hamster ovary (CHO) cells. The proteins produced in CHO cells by the mutated cDNAs have apparent molecular weights that are reduced relative to the wild type and are consistent with the loss of carbohydrate residues. The triple mutant, which lacks all three consensus glycosylation sites, yields protein that comigrates with the enzymatically deglycosylated native protein. Determinations of the K(D) for folic acid by Scatchard analyses of the glycosylation mutants indicate that folic acid binding affinity is not significantly affected in the single mutants alpha(h)FR(-1) and alpha(h)FR(-2). However, in the single mutant, alpha(h)FR(-3), and the double mutant, alpha(h)FR(-1-3), folic acid binding affinity is respectively 2.7- and 3.5-fold lower than that in wild type. Deglycosylation by mutation of all three consensus sites (alpha(h)FR(-1-2-3) eliminates both folic acid binding and cell surface expression. In contrast, enzymatic deglycosylation of purified wild-type alpha(h)FR with endoglycosidase F does not significantly affect folate binding affinity. Thus, while carbohydrate residues are not essential for the folate binding activity of the mature folate receptor, at least one of the three core glycosylated residues is necessary for the synthesis of alpha(h)FR in its active conformation.
Optical chromatographic sample separation of hydrodynamically focused mixtures

Optical chromatography involves loosely focusing a laser beam into a fluid flowing opposite to the direction of laser propagation. When microscopic particles in the flow path encounter this beam they are optically trapped along the beam and are pushed upstream by the radiation pressure from the laser focal point to rest at a position where the optical and fluid drag forces on the particle balance. Because optical and fluid forces are sensitive to differences in the physical and chemical properties of a particle, fine separations are possible. A laser beam which completely fills a fluid channel has been operated as an optically tunable filter for the separation of polymeric/colloidal and biological samples. We demonstrate here how this technique coupled with an advanced microfluidic platform can be used as both a coarse and fine method to fractionate particles in an injected sample. The microfluidic network allows for a monodisperse mixed particle sample of polystyrene and poly(methyl methacrylate) to be injected, hydrodynamically focused and completely separated. To test the limit of separation, a mixed polystyrene sample containing two particles varying in size by less than 0.2% was run in the system. The analysis of the resulting separation sets the framework for continued work to perform ultra-fine separations.
Learning Set: Comparison of Macaca Mulatta and M. Speciosa

M. mulatta and M. speciosa performed similarly on 800 six-trial visual discrimination problems.
Tyrosine hydroxylase: Allosteric activation induced by stimulation of central noradrenergic neurons

Electrical stimulation of the rat locus coeruleus causes about a 300% increase in the activity of the tyrosine hydroxylase prepared from the hippocampus on the stimulated side and assayed in the presence of subsaturating concentrations of tyrosine and pteridine cofactor. Addition of calcium or cAMP to soluble preparations of tyrosine hydroxylase isolated from the hippocampus produces a similar activation of tyrosine hydroxylase. The activation of tyrosine hydroxylase produced by calcium is reversed by addition of the calcium chelator, EGTA, while the activation produced by cAMP addition or by electrical stimulation of the locus coeruleus is unaffected by addition of EGTA to the assay medium. The activation of tyrosine hydroxylase produced by electrical stimulation or by addition of calcium or cAMP to the assay medium appears to be mediated in part by alterations in the kinetic properties of the enzyme. All treatment causes the enzyme to have an increased affinity for substrate and pteridine cofactor and a decreased affinity for the endproduct inhibitor, norepinephrine. These results are suggestive that the activation of tyrosine hydroxylase which occurs during periods of increased impulse flow in noradrenergic neurons may be initiated by alterations in calcium fluxes or by changes in the steady state levels of cAMP which accompany neuronal depolarization.
Anomalous inelastic He-atom scattering intensities for the vibrational modes of alkali metals on graphite

Abstract Low-energy (2.3–4.4 meV) vibrational modes have been observed from K, Rb, and Cs chemisorbed on the basal plane of graphite using inelastic He-atom scattering. These modes are interpreted as phonons propagating in the sagittal plane and polarized parallel to the surface plane. Modes having perpendicular polarization were undetectable. This anomalous result may be due to the coupling of the He atoms to the conduction electrons in the surface.
Energy efficient proactive thermal management in memory subsystem

Energy management of memory subsystem is challenging due to performance and thermal constraints. Big energy gains can be obtained by clustering memory accesses, however this also leads to a higher need for cooling due to larger temperatures in active areas of memory. Our solution to memory thermal management problem is based on proactive thermal management that intelligently allocates workload pages to few memory units and powers down rest of the memory. Our experimental results show that this approach improves energy savings by 43% and reduces performance overhead by 85% with respect to the state of the art polices.
Activation of skin tyrosinase.

L'activite de tyrosinase integumentale est augmente par un sejour de 10–18 jours a 0–4°C sous oxygene ou en plein air mais pas nitrogene. Les 3 especes vertebres qui montrent cette reaction sontMyxine glutinosa, Lepisosteus osseus etNeoceratodus fosteri.
The scandal of ecstasy: communication, Sufi rites, and social reform in 1930s Morocco

Modern Islamic reformists in Morocco condemned ecstatic Sufi trance rites as heterodox spectacles. But if the heterodoxy of these rites remains self-evident, the still common reformist critique of spectacle begs historical explanation. This article proposes that a main theme of post-1930 nationalist reformism in Morocco was communication and its containment. In this period, new reformists – “Young Moroccans” and “New Salafis” – fixated upon the power of ecstatic rites to connect and coalesce the urban underclasses and to elicit recognition from the colonial state and an emergent global audience. Just as new reformists sought to use technologies of mass communication, including the newspaper and camera, to speak to and for “the People,” they chafed at the global renown these same media lent to public Sufi spectacles. Examining Moroccan print media in 1930s Fez, I show that anti-Sufi critiques were primarily neither doctrinal nor anti-colonial; new reformists aimed, rather, to domesticate the popular connective force of ritual as well as the enhanced power of these picturesque rites to speak for the nation.
Rapid gas-liquid chromatographic method for plasma verapamil level determination.

Verapamil is a newly marketed antiarrhythmic drug. It has a significant presystemic elimination when administered orally and, therefore, intravenous therapy is often recommended. Optimum therapeutic effect is obtained when verapamil plasma concentrations are between 100 and 400 ng/ml. Several chromatographic procedures for the determination of verapamil in biological fluids have been described in the literature [l-11]. Some of the procedures have also quantitated verapamil metabolites [l, 6, 7 1. The highperformance liquid chromatographic (HPLC), as well as the gas-liquid chromatographic (GLC) procedures are sensitive but require lengthy and tedious multiple extraction steps especially when the metabolites are quantitated. This report describes a rapid, sensitive and accurate GLC procedure with thermionic specific detection for the determination of verapamil in dog plasma. This procedure also has a potential use in controlled clinical pharmacokinetic studies of this antiarrhythmic agent in humans.
Stress distribution in helium-ion implantations

Abstract The stress introduced into a material in a monoenergetic helium-ion implantation is calculated for a ion beam with a gaussian intensity distribution. An effective beam spot of the order of several millimeters was chosen as typical of blistering experiments. The sample is assumed to be semi-infinite and isotropic. The ion distribution is cylindrically symmetric with a gaussian depth profile. The parameters defining the distribution are consistent with incident ion energies of ~40 and ~400 keV in both nickel and niobium. The volume expansion caused by the implanted ions is assumed to be proportional to the local helium concentration; the validity of this assumption is discussed. The maximum shear stress is calculated as a function of depth, and the volume expansion per helium atom required to produce plastic deformation at the experimentally observed critical doses in niobium is found to be of the order of half an atomic volume.