cssi/SciSciGPT-SciSciNet huggingface dataset:
Serial passage of HIV-2F: a pigtail macaque model for HIV emergence

The AIDS pandemic affects over 35 million people worldwide. Human immunodeficiency types 1 and 2 (HIV-1 and HIV-2), the etiologic agents of AIDS, originated from simian immunodeficiency viruses of chimpanzees (SIVcpz) in Cameroon and SIVsm from sooty mangabeys in West Africa. While the simian origin of HIV is well established, how the virus adapted to humans is poorly understood. The bulk of HIV-2 morbidity and mortality is caused by a few strains; however, new pathogenic subtypes of HIV-2 continue to emerge (HIV-2F, 2008 and HIV-2H, 2004) underscoring the need for deeper understanding of the mechanisms behind the adaption of these viruses to humans. This study aims to test the serial passage theory of HIV emergence and elucidate adaptive mechanisms to a new host using the newly emerged, pathogenic HIV-2F virus in an in vivo pigtail macaque (PTM) model. We inoculated one pigtail macaque with HIV-2F isolated from the patient followed by serial passage into 2 PTMs. Blood, lymph node; endoscopy and vaginal wash were collected. An HIV-2F specific quantitative PCR (qPCR) assay was developed (LOQ=1.9 log VC/mL) for this experiment. All three PTMs were infected; reaching peak PVLs between 6.0 and 7.2 log viral copies/milliliter. PTM KF25, passage one, cleared the virus by day 42 post inoculation (PI) and remains qPCR negative at day 344 PI. KF26 and KF24, passages two and three, cleared the virus following acute infection by days 42 and 60 respectively. Importantly, virus rebounded in the 2nd and 3rd passage animals at day 150 and 120, respectively, and remains between 5.6 and 3.2 log VC/mL. Following one passage in PTMs, HIV-2 F escaped host control and sustained replication, showing that the virus adapted to the new host via serial passage. Sequence analysis comparing peak and re-emergent virus is ongoing and will be completed for presentation. Flow cytometry analysis to correlate changes in VL with cytokine markers of pathogenesis is in process. Clinical monitoring is ongoing to assess pathogenesis of passaged HIV-2F.
Bounded dilation maps of hypercubes into Cayley graphs on the symmetric group

LetG andH be graphs with ¦V(G)≤ ¦V(H)¦. Iff:V(G) →V(H) is a one-to-one map, we letdilation(f) be the maximum of distH(fx),f(y)) over all edgesxy inG where distH denotes distance inH. The construction of maps fromG toH of small dilation is motivated by the problem of designing small slowdown simulations onH of algorithms that were originally designed for the networkG.
Discriminative vs motivational interpretations of avoidance extinction: Extensions to learned helplessness

Resistance to extinction of discriminated barpress avoidance in rats was assessed through the use of three procedures, each of which served to break the response-reinforcement contingency, classical extinction (CE), operant extinction (OE), and a variable-ratio shock schedule (VR). Greatest resistance to extinction was found for the VR group, followed by OE and then by CE Ss. thus supporting a discriminative rather than a motivational analysis. Reacquisition rates following extinction suggested evidence of “learned helplessness” in some Ss exposed to noncontingent CS-US presentations.
Information flow analysis of scientific workflows

Recently, scientific workflows have emerged as a platform for automating and accelerating data processing and data sharing in scientific communities. Many scientific workflows have been developed for collaborative research projects that involve a number of geographically distributed organizations. Sharing of data and computation across organizations in different administrative domains is essential in such a collaborative environment. Because of the competitive nature of scientific research, it is important to ensure that sensitive information in scientific workflows can be accessed by and propagated to only authorized parties. To address this problem, we present techniques for analyzing how information propagates in scientific workflows. We also present algorithms for incrementally analyzing how information propagates upon every change to an existing scientific workflow.
Continuum limits of interacting particle systems

Abstract We study the continuum limits of discrete particle systems with short range repulsive forces. We establish the existence of a class of short range interparticle force laws with the property that the asymptotic trajectories of two sufficiently energetic particles of equal mass entering and leaving the region of a binary interaction are the same as the asymptotic trajectories of particles which undergo a simple point-mass elastic collision. Using such force laws, we consider the evolution of an N particle gas, each particle having mass 1 N , for initial data which are guaranteed to generate only binary collisions. We show that such problems are exactly solvable and we characterize the continuum limit (N→∞) of such solutions. These limit flows are independent of the details of the repulsive forces and are the same as obtained if one replaces the interparticle force law by the elastic collision rule which simply interchanges particle velocities during a collision.
Analysis of particle-to-particle elastic interactions in syntactic foams

Abstract This work analyzes the elastic interaction between a pair of hollow particles embedded in a dissimilar medium subjected to remote uniaxial tensile loading. The Boussinesq–Papkovich stress function approach is combined with a multi-pole series expansion to derive a semi-analytical solution of the Navier–Cauchy equation and determine stress and displacement fields in the inclusions and the surrounding medium. Stress profiles, stress intensification factors, circumferential stress resultants in the particles, and strain energy storage are presented for a broad range of particle wall thicknesses, sizes, and relative inter-particle distances. Results specialized to glass–vinyl ester systems demonstrate that particle wall thicknesses and size distributions can be used to modulate the effects of particle-to-particle interaction on the overall mechanical behavior of syntactic foams.
Abstract 2639: RanGAP1·SUMO1 hyperphosphorylation (RGSH) and mitotic arrest by ON 01910.Na, okadaic acid or tubulin agents

INTRODUCTION: RanGAP1·SUMO1 is phosphorylated before nuclear envelope breakdown when cells enter mitosis. Previous work from our laboratory showed that a new anticancer antimitotic agent, ON 01910.Na (abbreviated 1910), a benzyl styryl sulfone analog, induced RGSH in all four human tumor cell lines tested. RGSH was not observed in the presence of 1911, inactive analog of 1910. However, RGSH was observed in the presence of tubulin depolymerizing agent nocodazole. Tubulin polymerization assay revealed that, unlike nocodazole, neither 1910 nor 1911 had effects on tubulin polymerization in vitro. In this study, we examined whether other tubulin agents induce RGSH and whether known mitotic phosphatases are involved. METHODS and RESULTS: We used two cell lines, MOLT-3 ALL and DU145 prostate cancer cell lines. We examined RGSH in the presence of known tubulin toxins including paclitaxel, vinblastine, vincristine, colchicine and nocodazole at a concentration of 1 µM in 4 h and 24 h. Doxorubicin and camptothecin served as negative controls. Following treatment with drugs, cells were analyzed by Western blotting. Drug concentrations that inhibited cell growth by 50% (IC50) or 90% (IC90) were determined in 3-day drug exposure experiments. All tubulin agents in the study were capable of inducing RGSH after 4h and 24 h exposure in both cell lines. The drug-induced RGSH was inhibited by caffeine, an ATM and ATR kinase inhibitor, and roscovitine, a Cdk kinase inhibitor. Okadaic acid (OA), known primarily as PP1 and PP2A phosphatase inhibitor, was also found to be capable of RGSH, therefore making it plausible by analogy that 1910 is RanGAP1·SUMO1 phosphatase inhibitor. The concentrations of 1910, OA or tubulin agents sufficient to elicit RGSH in 24 h, also caused 50 to 90% growth inhibition, respectively. 1910, as well as all tubulin agents in the study, induced phosphorylation of the phosphatase Cdc25C (aka “mitotic” Cdc25C) and down-regulation of interphase form of Cdc25C. CONCLUSION: 1910 and selected tubulin agents caused RGSH at IC50 – IC90 concentrations. Similar to tubulin agents, 1910 produced Cdc25C phosphorylation and down-regulation of its interphase form. OA inhibition of PP1 phosphatase and activation of RGSH suggest that 1910 could also serve as a phosphatase inhibitor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2639. doi:10.1158/1538-7445.AM2011-2639
The Relationship Between the Supplemental Security Income and the Old-Age, Survivors, and Disability Insurance Programs During the 1990s

Abstract The purpose of this paper is to discuss the relationships between the Supplemental Security Income (SSI) program and the Old-Age, Survivors, and Disability Insurance (OASDI) programs during the 1990s. The focus is on the persons concurrently receiving benefits from both programs, but analyzed from the alternative perspectives of the SSI and OASDI programs separately. Longitudinal sample data drawn from Social Security Administration administrative records are used to perform the analysis. Fourteen tables and eight figures present the data stratified in various ways by gender, age, and program involvement. An analysis of observed trends is presented, along with some suggestions for needed future research.
Physiological responses to simulated firefighter exercise protocols in varying environments

For decades, research to quantify the effects of firefighting activities and personal protective equipment on physiology and biomechanics has been conducted in a variety of testing environments. It is unknown if these different environments provide similar information and comparable responses. A novel Firefighting Activities Station, which simulates four common fireground tasks, is presented for use with an environmental chamber in a controlled laboratory setting. Nineteen firefighters completed three different exercise protocols following common research practices. Simulated firefighting activities conducted in an environmental chamber or live-fire structures elicited similar physiological responses (max heart rate: 190.1 vs 188.0 bpm, core temperature response: 0.047°C/min vs 0.043°C/min) and accelerometry counts. However, the response to a treadmill protocol commonly used in laboratory settings resulted in significantly lower heart rate (178.4 vs 188.0 bpm), core temperature response (0.037°C/min vs 0.043°C/min) and physical activity counts compared with firefighting activities in the burn building. Practitioner Summary: We introduce a new approach for simulating realistic firefighting activities in a controlled laboratory environment for ergonomics assessment of fire service equipment and personnel. Physiological responses to this proposed protocol more closely replicate those from live-fire activities than a traditional treadmill protocol and are simple to replicate and standardise.
The dynamic growth of a single void in a viscoplastic material under transient hydrostatic loading

We have examined the problem of the dynamic growth of a single spherical void in an elastic-viscoplastic medium, with a view towards addressing a number of problems that arise during the dynamic failure of metals. Particular attention is paid to inertial, thermal and rate-dependent effects, which have not previously been thoroughly studied in a combined setting. It is shown that the critical stress for unstable growth of the void in the quasistatic case is strongly affected by the thermal softening of the material (in adiabatic calculations). Thermal softening has the effect of lowering the critical stress, and has a stronger influence at high strain hardening exponents. It is shown that the thermally diffusive case for quasistatic void growth in rate-dependent materials is strongly affected by the initial void size, because of the length scale introduced by the thermal diffusion. The effects of inertia are quantified, and it is demonstrated that inertial effects are small in the early stages of void growth and are strongly dependent on the initial size of the void and the rate of loading. Under supercritical loading for the inertial problem, voids of all sizes achieve a constant absolute void growth rate in the long term. Inertia first impedes, but finally promotes dynamic void growth under a subcritical loading. For dynamic void growth, the effect of rate-hardening is to reduce the rate of void growth in comparison to the rate-independent case, and to reduce the final relative void growth achieved.
A NORMATIVE RESOURCE TRANSFER MODEL

In this paper, the author suggests a methodology for facilitating interactive decision making in a decentralized organization by providing information which may result in the transfer of divisional resources. The resource-transfer information is generated at the beginning of the planning period so that the organization's production control and evaluation systems may be formalized.
Fuzzy and random sets

The two distinct concepts of fuzzy and random sets coexist to form the basics for modeling perception-based information gathering processes in artificial intelligence. These processes, viewed as coarsening schemes, provide also justifications for various types of uncertainty measures such as belief functions and possibility measures.
Certifying and constructing minimally rigid graphs in the plane

We study minimally rigid graphs in the plane or plane isostatic graphs. These graphs (also called Laman graphs) admit characterizations based on decomposition into trees (Crapo's theorem and Recski's theorem). Tree partitions can be viewed as certificates of plane isostatic graphs. Unfortunately, they require Ω(n2) time to verify their validity where n is the number of vertices in the graph. We present a new construction (which can be viewed as a hierarchical decomposition of the graph) called red-black hierarchy that (i) is a certificate for plane isostatic graphs, and (ii) can be verified in linear time. We also show that it can be computed in O(n2) time.A classical result in Rigidity Theory by Henneberg [9] states that the plane isostatic graphs can be constructed incrementally by special vertex insertions. We study the following computational problem: given a Laman graph G, compute a sequence of Henneberg insertions that yields G. We show that the red-bl ack hierarchy can be used to compute a Henneberg construction in O(n2) time. Applied to planar graphs our algorithm can speed up a recent algorithm by Haas et al. [8] for embedding a planar Laman graph as a pointed pseudo-triangulation by a factor of O(n).
Optical correlator performance of binary phase-only filters using Fourier and Hartley transforms

Theoretical studies of the performance capabilities of binary phase-only filters (BPOFs), constructed using both Fourier and Hartley transforms, are presented. A thorough analysis of the Fourier BPOF is given. We show that, although BPOFs constructed using Fourier transforms perform well in optical correlator systems, they are also subject to additional noise sources and have the possibility of generating large false correlation signals. We then present an analysis of BPOFs constructed using the Hartley transform. We show that BPOFs made using the Hartley transform provide superior false correlation rejection and more uniformly sized correlation signals for heavily multiplexed BPOFs, compared with those made using the Fourier transform. We also present a technique for constructing Hartley BPOFs. Therefore, although it is well known that the quality of the correlation signal depends on the object, this work demonstrates that the quality of the correlation signal can also depend on the technique used in the synthesis of the BPOF.
RODENT MODELS OF SLEEP APNEA

Rodent models of sleep apnea have long been used to provide novel insight into the generation and predisposition to apneas as well as to characterize the impact of sleep apnea on cardiovascular, metabolic, and psychological health in humans. Given the significant body of work utilizing rodent models in the field of sleep apnea, the aims of this review are three-fold: first, to review the use of rodents as natural models of sleep apnea; second, to provide an overview of the experimental interventions employed in rodents to simulate sleep apnea; third, to discuss the refinement of rodent models to further our understanding of breathing abnormalities that occur during sleep. Given mounting evidence that sleep apnea impairs cognitive function, reduces quality of life, and exacerbates the course of multiple chronic diseases, rodent models will remain a high priority as a tool to interrogate both the pathophysiology and sequelae of breathing related abnormalities during sleep and to improve approaches to diagnosis and therapy.
Analyses of multi-level and multi-component compressed bitmap indexes

Bitmap indexes are known as the most effective indexing methods for range queries on append-only data, and many different bitmap indexes have been proposed in the research literature. However, only two of the simplest ones are used in commercial products. To better understand the benefits offered by the more sophisticated variations, we conduct an analytical comparison of well-known bitmap indexes, most of which are in the class of multi-component bitmap indexes. Our analysis is the first to fully incorporate the effects of compression on their performance. We produce closed-form formulas for both the index sizes and the query processing costs for the worst cases. One surprising finding is that the two simple indexes are in fact the best among multi-component indexes. Additionally, we investigate a number of novel variations in a class of multi-level indexes, and find that they answer queries faster than the best of multi-component indexes. More specifically, some two-level indexes are predicted by analyses and verified with experiments to be 5 to 10 times faster than well-known indexes. Furthermore, these two-level indexes have the optimal computational complexity for answering queries.
Selective toxicity of the polyene antibiotics and their methyl ester derivatives

Abstract The methyl ester hydrochlorides of amphotericin B and nystatin are less effective than the parent compounds in causing K + release from human erythrocytes. The parent compounds and the derivatives are of comparable activity toward Candida albicans . The enhanced selective toxicity of polyene methyl ester salts for C. albicans may mean that these antibiotics will be more effective therapeutic agents for systemic fungal infections.
Characterization of the Rac-GAP (Rac-GTPase-activating protein) activity of β2-chimaerin, a 'non-protein kinase C' phorbol ester receptor

The regulation and function of beta2-chimaerin, a novel receptor for the phorbol ester tumour promoters and the second messenger DAG (diacylglycerol), is largely unknown. As with PKC (protein kinase C) isoenzymes, phorbol esters bind to beta2-chimaerin with high affinity and promote its subcellular distribution. beta2-Chimaerin has GAP (GTPase-activating protein) activity for the small GTP-binding protein Rac1, but for not Cdc42 or RhoA. We show that acidic phospholipids enhanced its catalytic activity markedly in vitro, but the phorbol ester PMA had no effect. beta2-Chimaerin and other chimaerin isoforms decreased cellular levels of Rac-GTP markedly in COS-1 cells and impaired GTP loading on to Rac upon EGF (epidermal growth factor) receptor stimulation. Deletional and mutagenesis analysis determined that the beta2-chimaerin GAP domain is essential for this effect. Interestingly, PMA has a dual effect on Rac-GTP levels in COS-1 cells. PMA increased Rac-GTP levels in the absence of a PKC inhibitor, whereas under conditions in which PKC activity is inhibited, PMA markedly decreased Rac-GTP levels and potentiated the effect of beta2-chimaerin. Chimaerin isoforms co-localize at the plasma membrane with active Rac, and these results were substantiated by co-immunoprecipitation assays. In summary, the novel phorbol ester receptor beta2-chimaerin regulates the activity of the Rac GTPase through its GAP domain, leading to Rac inactivation. These results strongly emphasize the high complexity of DAG signalling due to the activation of PKC-independent pathways, and cast doubts regarding the selectivity of phorbol esters and DAG analogues as selective PKC activators.
Mouse vision as a gateway for understanding how experience shapes neural circuits

Genetic programs controlling ontogeny drive many of the essential connectivity patterns within the brain. Yet it is activity, derived from the experience of interacting with the world, that sculpts the precise circuitry of the central nervous system. Such experience-dependent plasticity has been observed throughout the brain but has been most extensively studied in the neocortex. A prime example of this refinement of neural circuitry is found in primary visual cortex (V1), where functional connectivity changes have been observed both during development and in adulthood. The mouse visual system has become a predominant model for investigating the principles that underlie experience-dependent plasticity, given the general conservation of visual neural circuitry across mammals as well as the powerful tools and techniques recently developed for use in rodent. The genetic tractability of mice has permitted the identification of signaling pathways that translate experience-driven activity patterns into changes in circuitry. Further, the accessibility of visual cortex has allowed neural activity to be manipulated with optogenetics and observed with genetically-encoded calcium sensors. Consequently, mouse visual cortex has become one of the dominant platforms to study experience-dependent plasticity.
Immunofocusing: antigen engineering to promote the induction of HIV-neutralizing antibodies

Understanding how neutralizing antibodies recognize HIV could aid the design of antigens that induce protective antibodies upon immunization. There have been several advances in this area of AIDS vaccine research, including structural elucidation of the core of two gp120 envelope glycoproteins and, more recently, determination of the structures of the broadly HIV-1-neutralizing antibodies b12, 2G12 and 2F5. The structures have enabled features governing the molecular interaction of each antibody with its epitope to be explored. For the antibody b12, this has resulted in the design of novel, tailored antigens aimed at inducing similar antibodies with equivalent neutralizing properties. This template-based approach to immunogen design shows promise as a means to engineer innovative AIDS vaccine candidates.
Evaluation of the Cobas 4800 HPV Test for Detecting High-Risk Human Papilloma-Virus in Cervical Cytology Specimens

As new platforms for high-risk strains of human papillomavirus (HR HPV) testing are introduced into the clinical laboratory, it is important to verify their performance and agreement. In this validation study, post-aliquot cervical cytopathology specimens (n = 226) were used to analyze agreement between the Invader HPV ASR assay (Hologic) and the recently FDA-approved Cobas 4800 high-risk HPV assay (Roche). Residual sample from 92 Invader positive and 134 Invader negative samples were analyzed with the Cobas 4800 test. Discordant results were further analyzed by Linear Array HPV genotype testing (Roche). To assess intra- and inter-run precision, 31 Invader positive samples were run in duplicate on the Cobas 4800 by different operators over multiple days and purchased HR HPV DNA control was run in ten replicates. Cross-contamination during cytology processing was evaluated by spiking 6 Invader negative samples with different volumes of Acrometrix HPV High Risk Positive Control and analyzed on the Cobas with 4 negative samples in between. There was significant discordance between the assays (p < 0.001; exact McNemar X2 test), with overall agreement of 82%. Of the 92 Invader positive samples, 58 (63%) were positive with the Cobas assay, while 34 (37%) were negative. Of the 134 Invader negative samples, 6 (4%) were positive with the Cobas while 128 (96%) were negative. The observed discordance may be attributed to the previously described false positive rate of the Invader ASR assay. The Cobas 4800 high-risk HPV assay is a viable new tool for use in the clinical setting to identify high-risk HPV.
The Influence of Practice Management on Primary Cesarean Birth

As the cesarean delivery rate has increased to once unimaginable levels, obstetricians should question the loss of our credibility. Older mothers, obesity, larger birth weights, too many twins, and no more breech vaginal deliveries have all been cited as contributing factors to the increase in primary cesarean birth, but one cannot neglect the influence of physician practice style. Attempts to curtail or reverse the escalating incidence of primary abdominal deliveries should focus on caution with inductions of labor, patience with the management of arrest disorders, more accurate assessment of fetal compromise, patient education and informed decision making about the benefits/risks of operative delivery, and improvement in the medicolegal environment.
Tocotrienol and fatty acid composition of barley oil and their effects on lipid metabolism.

Barley oil was extracted with hexane from the grain of a high oil waxy hull-les barley. Twelve male broiler chicks were fed corn-based diets with either 10% barley oil, 10% corn oil or 10% margarinead libitum for ten days. Total plasma cholesterol concentration of the chicks fed barley oil was 34% lower (p<0.05) than that of the chicks fed margarine. Plasma low density lipoprotein cholesterol concentration of chicks fed barley oil was 53% and 59% lower (p<0.05) than those of chicks fed corn oil and margarine, respectively. Plasma high density lipoprotein cholesterol and triglyceride concentration of the barley oil group were similar to those of the margarine but higher (p<0.05) than those of the corn oil group. Chicks fed the barley oil gained more (p<0.05) body weight than those fed the corn oil and margarine. Barley oil had an effect in suppression of TC and LDLC in chicks compared to margarine. Barley oil supressed LDLC but not HDLC in chicks compared to corn oil. A greater weight gain of the chicks fed barley oil suggested that these chicks had normally functioning digestion and absorption. α-Tocotrienol and γ-tocotrienol content of the barley oil were 24 and 17 times greater, respectively, than those observed in the corn oil, while the same fractions were not detectable in the margarine. Polyunsaturated fatty acid content of the barley oil was more than threefold that of margarine. These data suggest that α-tocotrienol and polyunsaturated fatty acids are hypocholesterolemic components in barley oil.
Single-machine scheduling to minimize absolute deviation of completion times from a common due date

The article considers a single-machine n-job scheduling problem to minimize the sum of absolute lateness given a common due date. Two models are defined depending on whether the start time t0 of schedules is arbitrary or fixed. Conditions are provided when those two models coincide. The developed branch-and-bound procedure is tested on nine known examples from the literature (6 ⩽ n ⩽ 14) and 90 medium-size random problems (15 ⩽ n ⩽ 25) with a fixed t0.
Experimental Studies on Blood Sulfanilamide Levels Attained After Powdered Drug Administration by Inhalation.

Summary and conclusionsThe intratracheal insufflation of sulfanilamide powder in dogs will produce high blood levels of the drug (up to 33.2 mg/100 cc) associated with high urinary levels (up to 1660 mg/100 cc) and accompanied by general symptoms of depression and intoxication. A local accumulation of the powder persists during at least the first 6 hours and is followed by cough and signs of irritation of the lining of the trachea and bronchi which may last for several days.
Age 40 years and under does not confer superior prognosis in patients with multiple myeloma undergoing upfront autologous stem cell transmplant.

Multiple myeloma (MM) rarely occurs in patients 40 years of age and younger. This young age has been reported to correlate with improved survival in patients with MM. The objective of this study is to describe presenting features and outcomes of patients ≤40 years of age with MM who undergo autologous stem cell transplantation (ASCT) as first-line treatment, and compare overall survival (OS) and progression free survival (PFS) to patients aged 41-65 years. We performed a retrospective institutional review of all patients ≤40 years of age and 41-65 years of age at the time of diagnosis of MM who had undergone upfront ASCT from January 1, 1990, to July 31, 2007. Thirty-eight patients ≤40 years of age and 608 patients aged 41-65 were identified. There was a high rate of plasma cell leukemia (PCL) in young patients at 11% compared to the reported rate of 2%-4%. At diagnosis, there was an increased rate of renal failure in the young cohort compared to patients aged 41-65 years at 25% versus 16% and Bence Jones proteinuria at 81% versus 51%. The rate of complete or partial response was similar between the groups at 79% and 83% in the young and older cohorts, respectively. Median PFS post-ASCT was 22.0 months (95% confidence interval [CI]: 16.1, 28.0), versus 26.9 months (95% CI: 24.0, 29.8) for patients aged 41-65 years (P = .66). Median OS from date of ASCT was also similar to those over 40 years: 68.1 months (95% CI: 39.0, 97.2) versus 80.7 months (95% CI: 68.1, 93.4); P = .90. Treatment-related mortality (TRM) was low at 2.6% and 2.3% in the young and older cohorts, respectively. Despite previous reports that young age is a positive prognostic marker, our study found OS post-ASCT is equivalent to those aged 41-65 years. This study emphasizes the importance of developing strategies to better the outcomes of young patients with MM.
God in America: Why Theology Is Not Simply the Concern of Philosophers

As citizens of the most technologically advanced and economically developed country in the world, nearly all Americans stalwartly maintain their faith in God, much more so than residents of other postindustrial countries (Norris and Ingelhart 2004). But what is the content and meaning of this belief? Perhaps belief in God has become so pervasive in contemporary American culture that it reflects little about believers' deeper religious thoughts, identities, and actions. We find the opposite to be true. Outside the confines of seminaries, competing beliefs about who God is and what God wants have a clear and important connection to everyday religious life in the United States. Subtle distinctions in American images of God powerfully predict religious diversity as measured by belief in the truth of a single religious faith, religious devotion, and attitudes about the compatibility of secular and religious spheres. More specifically, we discern that American religious conservatism, in all its forms, can be aptly characterized by the belief that God is highly engaged in the world and particularly judgmental of human behavior.
Porcine Submaxillary Mucin Forms Disulfide-bonded Dimers between Its Carboxyl-terminal Domains

COS-7 cells transfected with three different expression vectors encoding the 240-amino acid residue, disulfide-rich domain at the carboxyl terminus of porcine submaxillary mucin have been used to determine the possible function of the domain in forming higher oligomers of the mucin polypeptide chain. The domain is expressed as a disulfide-bonded dimer, as shown by SDS-gel electrophoretic analysis of the immunoprecipitated domain in the presence and absence of reducing agent and the cross-linking agent bis(sulfosuccinimidyl) suberate. Molecular weight determination by gel filtration on agarose columns in 6 M guanidine HCl confirmed dimer formation. However, the domain expressed is heterogeneous as the result of different extents of glycosylation. Pulse-chase studies with the 35S-labeled domain show that dimer formation and secretion from cells occur very rapidly. Moreover, dimer formation is not dependent on the N-linked oligosaccharides on the domain. Evidence is presented that dimer formation most likely occurs in the endoplasmic reticulum before complex-type oligosaccharide synthesis is completed. Neither brefeldin A nor tunicamycin interferes with the rate of dimer formation. These studies suggest that the disulfide-rich domain acts to form dimers of the polypeptide chain of mucin. This role of the domain is consistent with its amino acid sequence similarity to the disulfide-rich domain of human prepro-von Willebrand factor, which also serves to form dimers of this blood coagulation factor.
Analysis and elimination of hysteresis and noisy precursors in power amplifiers

Power amplifiers (PAs) often exhibit instabilities leading to frequency division by two or oscillations at incommensurate frequencies. This undesired behavior can be detected through a large-signal stability analysis of the solution. However, other commonly observed phenomena are still difficult to predict and eliminate. In this paper, the anomalous behavior observed in a Class-E PA is analyzed in detail. It involves hysteresis in the power-transfer curve, oscillation, and noisy precursors. The precursors are pronounced bumps in the power spectrum due to noise amplification under a small stability margin. The correction of the amplifier performance has required the development of a new technique for the elimination of the hysteresis. Instead of a trial-and-error procedure, this technique, of general application to circuit design, makes use of bifurcation concepts to suppress the hysteresis phenomenon through a single simulation on harmonic-balance software. Another objective has been the investigation of the circuit characteristics that make the noisy precursors observable in practical circuits and a technique has been derived for their elimination from the amplifier output spectrum. All the different techniques have been experimentally validated.
Beam-ion confinement for different injection geometries

The DIII-D tokamak is equipped with neutral beam sources that inject in four different directions; in addition, the plasma can be moved up or down to compare off-axis with on-axis injection. Fast-ion data for eight different conditions have been obtained: co/counter, near-tangential/near-perpendicular and on-axis/off-axis. Neutron measurements during short beam pulses assess prompt and delayed losses under low-power conditions. As expected, co-injection has fewer losses than counter, tangential fewer than perpendicular and on-axis fewer than off-axis; the differences are greater at low current than at higher current. The helicity of the magnetic field has a weak effect on the overall confinement. Fast-ion Dα (FIDA) and neutron measurements diagnose the confinement at higher power. The basic trends are the same as in low-power plasmas but, even in plasmas without long wavelength Alfven modes or other MHD, discrepancies with theory are observed, especially in higher temperature plasmas. At modest temperature, two-dimensional images of the FIDA light are in good agreement with the simulations for both on-axis and off-axis injection. Discrepancies with theory are more pronounced at low fast-ion energy and at high plasma temperature, suggesting that fast-ion transport by microturbulence is responsible for the anomalies.
Optimization of Influenza Vaccine Selection

The World Health Organization (WHO) recommends which strains of influenza to include in each year's vaccine to countries around the globe. The current WHO strategy attempts to match the vaccine strains with the expected upcoming epidemic strains, a strategy we refer to as thefollow policy. The recently proposed antigenic distance hypothesis suggests that vaccine efficacy can be enhanced by taking into account the antigenic histories of vaccinees. To assess the potential benefit of history-based vaccination, we formulate the annual vaccine-strains selection problem as a stochastic dynamic program using the theory of shape space, which maps each vaccine and epidemic strain into a point in multidimensional space. Computational results show that a near-optimal policy can be derived by approximating the entire antigenic history by a single reduced historical strain, and then solving the multiperiod problem myopically, as a series of single-period problems. The modest suboptimality of the follow policy, together with our current inability to quantitatively link the model's objective function (a measure of cross-reactivity) with actual vaccine efficacy, leads us to recommend the continued use of the follow policy.
Influence of Soybean Products on the Bone Ash of Chicks Fed Certain Phosphorus-Deficient Purified Diets

Abstract IT has been recognized for some time that biological availability of a given phosphate may be influenced by the composition of the diet in which it is fed. Scott et al. (1956, 1962) reported that soybean meal would increase the bone ash of turkey poults fed certain diets containing inadequate levels of CaHPO4, a phosphate which is poorly available to the poult. Jensen and Mraz (1966) demonstrated the same phenomenon in chicks fed purified diets based on isolated soybean protein. Carlson et al. (1964a,b) suggested that isolated soybean protein contained a rachitogenic factor and that heated soybean meal contained an anti-rachitic factor which overcame it when soybean meal was added to an isolated soybean protein diet. Griffith et al. (1966) and Jensen and Mraz (1966) reported the “anti-rachitic” or “phosphorus availability” factor of soybean to be associated with the water isoluble portion of soybean meal. Griffith et al. (1966) also . . .
Interview with Rohina Rubicz, Winner of the 2010 Gabriel W.Lasker Prize

An international jury composed of Guido Barbujani (Italy), David Caramelli (Italy), Roberto Macchiarelli (France), John Relethford (U.S.A.), and Alan Goodman (U.S.A.) selected the article entitled Genetic Architecture of a Small, Recently Aggregated Aleut Population: Bering Island, Russia by Rohina Rubicz, Mark Zlojutro, Guangyun Sun, Victor Spitsyn, Ranjan Deka, Kristin Young, and Michael Crawford as the best contribution to the 82 volume of Human Biology (2010). This research paper appeared in a special double issue, entitled Origins of the Populations of the Aleutian Islands guest edited byMichael Crawford, DixieWest (both at theUniversity of Kansas, Manhattan, Kansas), and Dennis O’Rourke (University of Utah, Salt Lake City, Utah). Rohina Rubicz is a postdoctoral researcher at the Texas Biomedical Research Institute (formerly the Southwest Foundation for Biomedical Research), San Antonio, Texas. She received her Ph.D. in biological anthropology (population genetics) in 2007 from the University of Kansas. As a graduate student she used molecular genetic markers (mitochondrial, Y chromosome, and autosomal DNA) to investigate questions concerning the peopling of the Americas, the co-evolution of genes and languages (Rubicz et al. 2002), and the origins of Aleuts and their relationship to other North American and Siberian populations (Rubicz et al. 2003; Zlojutro et al. 2006). Rohina’s current research applies statistical genetic methods to the study of complex phenotypes, including the role of host genetics in susceptibility to infectious disease, and the relationship between infection and risk factors for chronic diseases of aging (i.e., cardiovascular disease and diabetes) in Mexican Americans. She also continues her work in population genetics, with a recent publication on genetic substructure among the peoples of Beringia (Rubicz et al. 2010).
The Base Substitution and Frameshift Fidelity of Escherichia coli DNA Polymerase III Holoenzyme in Vitro

Abstract We have investigated the in vitrofidelity of Escherichia coli DNA polymerase III holoenzyme from a wild-type and a proofreading-impaired mutD5 strain. Exonuclease assays showed the mutD5 holoenzyme to have a 30–50-fold reduced 3′→5′-exonuclease activity. Fidelity was assayed during gap-filling synthesis across the lacI dforward mutational target. The error rate for both enzymes was lowest at low dNTP concentrations (10–50 μM) and highest at high dNTP concentration (1000 μM). The mutD5 proofreading defect increased the error rate by only 3–5-fold. Both enzymes produced a high level of (−1)-frameshift mutations in addition to base substitutions. The base substitutions were mainly C→T, G→T, and G→C, but dNTP pool imbalances suggested that these may reflect misincorporations opposite damaged template bases and that, instead, T→C, G→A, and C→T transitions represent the normal polymerase III-mediated base·base mispairs. The frequent (−1)-frameshift mutations do not result from direct slippage but may be generated via a mechanism involving “misincorporation plus slippage.” Measurements of the fidelity of wild-type and mutD5 holoenzyme during M13 in vivo replication revealed significant differences between the in vivo and in vitro fidelity with regard to both the frequency of frameshift errors and the extent of proofreading.
Development of an image-guided robot for small animal research.

We developed a robot system that can be used for image-guided experimental procedures on small animals, where the goal is to perform physical actions at specific positions identified on a preoperative image. The animal is first placed in a fixture that is compatible with all imaging systems of interest, including PET, SPECT, CT and MRI. After imaging, the fixture is attached and registered to the robot system, where the image-guided intervention is performed. This system has been applied to perform pO2 measurements with physical probes based on tumor hypoxia images obtained in an animal PET scanner. This paper focuses on the design and validation of the robot system. The validation is performed using a phantom and includes a new method for estimating the Fiducial Localization Error (FLE) that is based on the measured Fiducial Distance Error (FDE). The results indicate that the robot system can position the measurement probe at a defined target with a mean error that is less than 0.4 mm.
Leveraging speech production knowledge for improved speech recognition

This study presents a novel phonological methodology for speech recognition based on phonological features (PFs) which leverages the relationship between speech phonology and phonetics. In particular, the proposed scheme estimates the likelihood of observing speech phonology given an associative lexicon. In this manner, the scheme is capable of choosing the most likely hypothesis (word candidate) among a group of competing alternative hypotheses. The framework employs the Maximum Entropy (ME) model to learn the relationship between phonetics and phonology. Subsequently, we extend the ME model to a ME-HMM (maximum entropy-hidden Markov model) which captures the speech production and linguistic relationship between phonology and words. The proposed ME-HMM model is applied to the task of re-processing N-best lists where an absolute WRA (word recognition rate) increase of 1.7%, 1.9% and 1% are reported for TIMIT, NTIMIT, and the SPINE (speech in noise) corpora (15.5% and 22.5% relative reduction in word error rate for TIMIT and NTIMIT).
Fiber grating sensors

We review the recent developments in the area of optical fiber grating sensors, including quasi-distributed strain sensing using Bragg gratings, systems based on chirped gratings, intragrating sensing concepts, long period-based grating sensors, fiber grating laser-based systems, and interferometric sensor systems based on grating reflectors.
Partial Rescue of Taste Responses of α-Gustducin Null Mice by Transgenic Expression of α-Transducin

The transduction of responses to bitter and sweet compounds utilizes guanine nucleotide binding proteins (G proteins) and their coupled receptors. Alpha-gustducin, a transducin-like G protein alpha-subunit, and rod alpha-transducin are expressed in taste receptor cells. Alpha-gustducin knockout mice have profoundly diminished behavioral and electrophysiological responses to many bitter and sweet compounds, although these mice retain residual responses to these compounds. Alpha-gustducin and rod alpha-transducin are biochemically indistinguishable in their in vitro interactions with retinal phosphodiesterase, rhodopsin and G protein betagamma-subunits. To determine if alpha-transducin can function in taste receptor cells and to compare the function of alpha-gustducin versus alpha-transducin in taste transduction in vivo, we generated transgenic mice that express alpha-transducin under the control of the alpha-gustducin promoter in the alpha-gustducin null background. Immunohistochemistry showed that the alpha-transducin transgene was expressed in about two-thirds of the alpha-gustducin lineage of taste receptor cells. Two-bottle preference tests showed that transgenic expression of rod alpha-transducin partly rescued responses to denatonium benzoate, sucrose and the artificial sweetener SC45647, but not to quinine sulfate. Gustatory nerve recordings showed a partial rescue by the transgene of the response to sucrose, SC45647 and quinine, but not to denatonium. These results demonstrate that alpha-transducin can function in taste receptor cells and transduce some taste cell responses. Our results also suggest that alpha-transducin and alpha-gustducin may differ, at least in part, in their function in these cells, although this conclusion must be qualified because of the limited fidelity of the transgene expression.
Genomes on the shrink

Because genetic events do not fossilize, we are forced to deduce the evolution of bacterial genomes by comparing the features of contemporary organisms. This comparative approach has exposed many of the alterations endured by bacterial genomes (bouts of expansion and contraction or changes in base compositions), but such reconstructions are often imprecise, and sometimes incorrect, because they are limited by the spectrum and relationships of the sequenced genomes that are available. Determining whether changes in gene repertoires and genome size were gradual or episodic is not feasible when the genomes being considered diverged several hundred million years ago. Fortunately, the results reported by Nilsson et al. (1) in this issue of PNAS indicate how such transformations proceed and help to explain one of the most interesting and pervasive trends in the evolution of bacterial genomes. When analyzed in a molecular phylogenetic perspective, every clade of bacteria with genome sizes of <2 Mb was derived from ancestors with substantially larger genomes (Fig. 1). This pattern dispels the long-held notion that bacteria evolved by the successive doubling of small-genomed progenitors (2, 3) and raises numerous questions about an evolutionary process that seems to affect all bacterial lineages. Among the groups best suited for investigating the progression toward reduced genomes are the γ-proteobacteria, due principally to the large number of fully sequenced constituents (53 at last count). Within this phylum, which includes the workhorses of bacterial genetics and pathogenesis, Escherichia coli and Salmonella typhimurium , the sizes of already-sequenced genomes vary over an order …