cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract A134: Therapeutic targeting of Hdm2/HdmX E3 ligase with bioactive cyclotides

Reactivation of tumor-suppressor p53 for targeted cancer therapy is an attractive strategy for cancers bearing wild-type (WT) p53. Targeting the Hdm2-p53 interface or HdmX-p53 interface or both has been a focus in the field. However, targeting the E3 ligase activity of Hdm2–HdmX which is mediated by RING–RING interaction has recently appeared as a promising novel anticancer approach. Targeting the E3 ligase of Hdm2-HdmX should overcome HdmX-driven resistance, which is found in many cancers overexpressing HdmX, to p53-Hdm2 antagonists such a nutlins. Cyclotides are a novel class of micro-proteins (≈30-40 residues long) with a unique topology containing a head-to-tail cyclized backbone structure further stabilized by three disulfide bonds that form a cystine knot. This unique molecular framework makes them exceptionally stable to physical, chemical, and biological degradation compared to linear peptides of similar size. The cyclotides are also highly tolerant to sequence variability, aside from the conserved residues forming the cystine knot, orally bioavailable and able to cross cellular membranes to modulate intracellular protein-protein interactions (PPIs) both in vitro and in vivo. These unique properties make them ideal scaffolds for many biotechnological applications, including drug discovery. We report the discovery of a novel cyclotide, MCo-52-2, able to antagonize efficiently the interaction between the RING domains of Hdm2 and HdmX and show p53-specific anticancer activity in several cancer cell lines both in vitro and in vivo. We will also present different strategies to improve the cellular uptake and pharmacokinetic profiles of bioactive cyclotides. Citation Format: Julio A Camarero. Therapeutic targeting of Hdm2/HdmX E3 ligase with bioactive cyclotides [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A134. doi:10.1158/1535-7163.TARG-19-A134
Quantifying the utility of a multidisciplinary neuro-oncology tumor board.

Objective There has been limited research on the efficacy of multidisciplinary tumor boards (MDTBs) in improving the treatment of patients with tumors affecting the nervous system. The objective of the present study was to quantify the utility of MDTBs in providing alternative diagnostic interpretations and treatment plans for this patient population. Methods The authors performed a prospective study of patients in 4 hospitals whose cases were discussed at MDTBs between July and November 2019. Patient demographic data, diagnoses, treatment plans, and eligibility for clinical trials were recorded, among other variables. Results A total of 176 cases met eligibility criteria for study inclusion. The majority (53%) of patients were male, and the mean patient age was 52 years. The most frequent diagnosis was glioblastoma (32.4%). Among the evaluable cases, MDTBs led to 38 (21.6%) changes in image interpretation and 103 (58.2%) changes in patient management. Additionally, patients whose cases were discussed at MDTBs had significantly shorter referral times than patients whose cases were not discussed (p = 0.024). Conclusions MDTB discussions led to significant numbers of diagnostic and treatment plan changes as well as shortened referral times, highlighting the potential clinical impact of multidisciplinary care for patients with nervous system tumors.
Technical Note—On Revenue Management with Strategic Customers Choosing When and What to Buy

In practice, when thinking about their purchasing decisions, customers usually strategize along two dimensions: (1) when to buy and (2) what to buy. That is, they might delay a purchase in anticipa...
Relationships Between Dietary Intake and Weight-Related Experiential Avoidance Following Behavioral Weight-Loss Treatment

Interventions targeting weight-related experiential avoidance (EA) and disinhibited eating (DE) may also improve diet quality. Participants with overweight/obesity and DE who recently completed a behavioral weight-loss program were randomized to receive acceptance and commitment therapy or continued behavioral weight-loss treatment. In this secondary analysis, we explored (1) change in diet quality from baseline to 6-month follow-up (FU) and (2) whether weight-related EA at baseline and (3) change in weight-related EA during treatment were related to change in diet quality from baseline to FU. Veterans (N = 68) completed food frequency questionnaires at baseline and FU, which were used to generate diet quality scores on the healthy eating index-15 (HEI-15). Weight-related EA was assessed using the Acceptance and Action Questionnaire for Weight-Related Difficulties-Revised (AAQW-R) at baseline, post-treatment, and FU. Aims were examined with mixed ANOVA analyses. Across both treatment groups, HEI-15 scores declined from baseline to FU. Women’s HEI-15 decreased by about 5 times that of men. Baseline AAWQ-R was negatively associated with change in HEI-15. Neither AAWQ-R at post-treatment nor change in AAQW-R from baseline to post-treatment was significantly associated with change in HEI-15 at FU. Greater weight-related EA at baseline was associated with lower diet quality at FU, but change in weight-related EA during treatment did not predict change in diet quality at FU. Interventions targeting DE and weight-loss may require specific components to improve and sustain healthy dietary intake in Veterans with obesity and DE.
A Comparison of Young Adults With and Without Cancer in Concurrent Hospice Care: Implications for Transitioning to Adult Health Care.

Purpose: Concurrent hospice care provides important end-of-life care for youth under 21 years. Those nearing 21 years must decide whether to shift to adult hospice or leave hospice for life-prolong...
Effects of historical co-infection on host shift abilities of exploitative and competitive viruses.

Rapid evolution contributes to frequent emergence of RNA viral pathogens on novel hosts. However, accurately predicting which viral genotypes will emerge has been elusive. Prior work with lytic RNA bacteriophage ɸ6 (family Cystoviridae) suggested that evolution under low multiplicity of infection (MOI; proportion of viruses to susceptible cells) selected for greater host exploitation, while evolution under high MOI selected for better intracellular competition against co-infecting viruses. We predicted that phage genotypes that had experienced 300 generations of low MOI ecological history would be relatively advantaged in initial growth on two novel hosts. We inferred viral growth through changes in host population density, specifically by analyzing five attributes of growth curves of infected bacteria. Despite equivalent growth of evolved viruses on the original host, low MOI evolved clones were generally advantaged relative to high MOI clones in exploiting novel hosts. However, the specific attributes of growth curves that supported their advantage differed by host, indicating interactions between both viral and host genotype. Although there will be host specificity in viral growth, we suggest based on infectivity differences of viruses from high versus low MOI histories that prior MOI selection can later affect emergence potential. This article is protected by copyright. All rights reserved.
Improving the efficacy of exome sequencing at a quaternary care referral centre: novel mutations, clinical presentations and diagnostic challenges in rare neurogenetic diseases

Background We used a multimodal approach including detailed phenotyping, whole exome sequencing (WES) and candidate gene filters to diagnose rare neurological diseases in individuals referred by tertiary neurology centres. Methods WES was performed on 66 individuals with neurogenetic diseases using candidate gene filters and stringent algorithms for assessing sequence variants. Pathogenic or likely pathogenic missense variants were interpreted using in silico prediction tools, family segregation analysis, previous publications of disease association and relevant biological assays. Results Molecular diagnosis was achieved in 39% (n=26) including 59% of childhood-onset cases and 27% of late-onset cases. Overall, 37% (10/27) of myopathy, 41% (9/22) of neuropathy, 22% (2/9) of MND and 63% (5/8) of complex phenotypes were given genetic diagnosis. Twenty-seven disease-associated variants were identified including ten novel variants in FBXO38, LAMA2, MFN2, MYH7, PNPLA6, SH3TC2 and SPTLC1. Single-nucleotide variants (n=10) affected conserved residues within functional domains and previously identified mutation hot-spots. Established pathogenic variants (n=16) presented with atypical features, such as optic neuropathy in adult polyglucosan body disease, facial dysmorphism and skeletal anomalies in cerebrotendinous xanthomatosis, steroid-responsive weakness in congenital myasthenia syndrome 10. Potentially treatable rare diseases were diagnosed, improving the quality of life in some patients. Conclusions Integrating deep phenotyping, gene filter algorithms and biological assays increased diagnostic yield of exome sequencing, identified novel pathogenic variants and extended phenotypes of difficult to diagnose rare neurogenetic disorders in an outpatient clinic setting.
Effects of 9/11-related injury on retirement patterns among World Trade Center Health Registry enrollees

BACKGROUND Many survivors of the 9/11/2001 terrorist attacks in New York City sustained injuries. The aim of this study was to understand how 9/11-related injuries affected retirement patterns of World Trade Center Health Registry enrollees. METHODS The study included enrollees who participated in the 2017 Health & Quality of Life Survey, focused on 9/11-related injuries and quality of life, and the 2017-2018 Health & Employment Survey, focused on retirement and employment (N = 3535). Using Cox proportional hazards and logistic regression modeling, we calculated the risk of retiring at earlier ages and the odds of retirees working again, controlling for relevant covariates. RESULTS Results showed that 9/11-related injuries did affect retirement patterns. Injured enrollees were at greater risk of retiring at younger age compared to non-injured enrollees. Compared to more severely injured retirees, non-injured and less severely injured retirees were significantly more likely to work again postretirement. Our results suggested that being injured on 9/11 was associated with retirement, meaning that if the injury had not occurred, the individual may have continued working longer. CONCLUSIONS The need to retire earlier than planned could be addressed with employer and societal changes. Employers should consider making accommodations for those impacted by 9/11 a priority, as it is imperative for those who were injured on 9/11 to have the ability to work to support their physical, mental, and financial well-being.
Vertical coordinate and resolution dependence of the second moment turbulent closure models and their limitations

Abstract Coordinate and resolution dependence of three second moment turbulent closure models are studied using one-dimensional Navy Coastal Ocean Model (NCOM) experiments and large eddy simulations at Ocean Station Papa. Our results suggest that finer resolution near the base of the mixed layer is critical for better model performance. A mixed layer enhanced vertical grid is proposed that outperforms both the uniform and the stretched grids with significantly fewer vertical layers used. For the new grid, the model accuracy is strongly dependent on the resolution near the base of the mixed layer, and not affected much by the total number of vertical layers used. However, given the success of the new grid, the lack of representation for the near inertial gravity waves below the mixed layer has hampered the ability of second moment turbulent closure models on accurate representation of turbulent mixing in the water column. While both the Langmuir circulation and the variation of surface heat fluxes are shown to be able to significantly change the strength of the near inertial waves, they have negligible effect on the eddy viscosity in the transition layer.
Environmental PCBs in Guánica Bay, Puerto Rico: implications for community health

Guanica Bay, located in southwestern Puerto Rico, has suffered oil spills and other pollution discharges since the 1960s. Previous research showed elevated concentrations of polychlorinated biphenyls (PCBs) in coral reef and sediment. This research examined PCB concentrations in sediment and fish. Sediment and fish sampling in the bay was facilitated by community members. This study identified the second highest reported PCB level (129,300 ng/g) in sediment in the USA. Fish samples also showed elevated concentrations (1623 to 3768 ng/g), which were higher than the thresholds of safe levels of PCBs in fish for human consumption. The alarmingly high concentration of PCBs calls for proactive community engagement to bring awareness about contamination of the bay and more extensive sampling to test for the concentration of PCBs in seafood and the people of Guanica. This study also underscores the value of the involvement of local communities during sampling design aimed at identifying hot spots of contaminants.
Mechanism of Action of Pyruvate Kinase ROLE OF SULFHYDRYL GROUPS IN CATALYTIC ACTIVITY AS DETERMINED BY DISULFIDE INTERCHANGE

Evidence is presented that four sulfhydryl residues play a critical role in the activity of pyruvate kinase. Modification of the four most reactive sulfhydryl groups by 5,5′-dithiobis-(2-nitrobenzoate) leads to a disulfide interchange reaction in which a chemically modified but catalytically active enzyme is produced. This form, which contains 5-thio-2-nitrobenzoate in disulfide linkage to cysteine residues, is stable at low pH or in the presence of phosphoenolpyruvate and metal ions. At neutral pH and in the absence of these compounds, the thionitrobenzoate-enzyme undergoes an intramolecular disulfide interchange involving four additional but essential sulfhydryl residues to liberate thionitrobenzoate with the formation of cystine residues. The resulting form of pyruvate kinase is catalytically inactive.
Women and HIV/AIDS: Toward a Jurisprudence of Social and Economic Rights

This article argues that traditional HIV/AIDS prevention efforts focused on addressing individual risk factors are not sufficient to end the spread of the disease among women. Rather, systemic factors rooted in economic and gender inequality are the primary drivers of the HIV epidemic among women. As a result, the U.S. response to HIV/AIDS must address these factors, namely poverty and violence. The article then argues for a commitment to a social and economic rights framework as a key part of efforts to end the HIV epidemic. The social and economic rights critical to ending the HIV epidemic are those that would lift women and their families out of poverty, help them secure stable housing, give them the economic means to leave violent relationships, and give them access to health care. These rights include a right to a minimum level of economic support, a right to housing, and a right to health. The article finally articulates how a positive rights framework would offer descriptive, practical, and aspirational benefits necessary to eradicate the HIV epidemic among U.S. women.
A probabilistic analysis of in vitro selection of independent DNA words for computation

An important problem in DNA computing is cross-hybridization which, if it occurs between words, affects the reliability and efficiency of the computation. An in vitro selection protocol has been developed that selects maximally mismatched DNA sequences. The protocol is analyzed, and a probabilistic model of the protocol is developed. The analysis shows that the selection probability should obey a Poisson distribution for a large number of trials. The analysis shows the protocol's ability to produce maximally mismatched words.
Review of Richard Parker's John Kenneth Galbraith: His Life, His Politics, His Economics

The author reviews Richard Parker's book, John Kenneth Galbraith: His Life, His Politics, His Economics.
Prevalence of elder self-neglect in a Chicago Chinese population: The role of cognitive physical and mental health.

Aim The present study examined the cognitive, physical and psychological characteristics associated with elder self-neglect in a USA Chinese older population. Methods The Population Study of Chinese Elderly in Chicago is a population-based epidemiological study of Chinese older adults in the greater Chicago area. In total, 3159 Chinese older adults aged 60 years and older were interviewed from 2011 to 2013. Personal and home environment was rated on hoarding, personal hygiene, house in need of repair, unsanitary conditions and inadequate utility. Results The prevalence of elder self-neglect of all severities was higher among older adults who were with worsening health status, lower cognitive function, lower physical function and more depressive symptoms. Poorer health status (mild self-neglect OR 1.20, 95% CI 1.06–1.35; moderate/severe self-neglect: OR 1.52, 95% CI 1.30–1.77), lower physical function (activities of daily living moderate/severe self-neglect OR 1.09, 95% CI 1.05–1.13; instrumental activities of daily living mild OR 1.04, 95% CI 1.03–1.06; instrumental activities of dailiy living moderate/severe OR 1.06, 95% CI 1.04–1.07), lower cognitive function (mild self-neglect OR 1.05, 95% CI 1.03–1.07; moderate/severe self-neglect OR 1.07, 95% CI 1.04–1.09) and more depressive symptoms (mild self-neglect OR 1.05, 95% CI 1.02–1.07; moderate/severe self-neglect OR 1.08, 95% CI 1.06–1.11) were significantly associated with increased risk for elder self-neglect of all severities. Conclusion Older adults with lower levels of cognitive, physical, and psychological health were more likely to report elder self-neglect and its phenotypes. Future research is required to examine risk/protective factors associated with elder self-neglect. Geriatr Gerontol Int 2015; ●●: ●●–●●.
Discrete-element model for the interaction between ocean waves and sea ice.

We present a discrete-element method (DEM) model to simulate the mechanical behavior of sea ice in response to ocean waves. The interaction of ocean waves and sea ice potentially can lead to the fracture and fragmentation of sea ice depending on the wave amplitude and period. The fracture behavior of sea ice explicitly is modeled by a DEM method where sea ice is modeled by densely packed spherical particles with finite sizes. These particles are bonded together at their contact points through mechanical bonds that can sustain both tensile and compressive forces and moments. Fracturing naturally can be represented by the sequential breaking of mechanical bonds. For a given amplitude and period of incident ocean waves, the model provides information for the spatial distribution and time evolution of stress and microfractures and the fragment size distribution. We demonstrate that the fraction of broken bonds $\ensuremath{\alpha}$ increases with increasing wave amplitude. In contrast, the ice fragment size $l$ decreases with increasing amplitude. This information is important for the understanding of the breakup of individual ice floes and floe fragment size.
The phytofluors: a new class of fluorescent protein probes

Abstract Background: Biologically compatible fluorescent protein probes, particularly the self-assembling green fluorescent protein (GFP) from the jellyfish Aequorea victoria , have revolutionized research in cell, molecular and developmental biology because they allow visualization of biochemical events in living cells. Additional fluorescent proteins that could be reconstituted in vivo while extending the useful wavelength range towards the orange and red regions of the light spectrum would increase the range of applications currently available with fluorescent protein probes. Results: Intensely orange fluorescent adducts, which we designate phytofluors, are spontaneously formed upon incubation of recombinant plant phytochrome apoproteins with phycoerythrobilin, the linear tetrapyrrole precursor of the phycoerythrin chromophore. Phytofluors have large molar absorption coefficients, fluorescence quantum yields greater than 0.7, excellent photostability, stability over a wide range of pH, and can be reconstituted in living plant cells. Conclusions: The phytofluors constitute a new class of fluorophore that can potentially be produced upon bilin uptake by any living cell expressing an apophytochrome cDNA. Mutagenesis of the phytochrome apoprotein and/or alteration of the linear tetrapyrrole precursor by chemical synthesis are expected to afford new phytofluors with fluorescence excitation and emission spectra spanning the visible to near-infrared light spectrum.
Thermal Gelation of Myofibrils from Pork, Beef, Fish, Chicken and Turkey

Myofibril gels with 5, 7, or 10% protein and 2% NaCl were prepared from pork, beef, fish, chicken and turkey muscles using a heating rate of 0.7°C/min and pH 6.0 to compare the thermal gelation properties of myofibrillar protein from different species. The force required to rupture gel (Pf), force required to move plunger through gel (Fp), viscosity index (Ni), and elasticity (Ea) increased and cooking loss decreased with increasing protein contents. Myofibrils of chicken breast and thigh had lower and fish and turkey thigh had higher cooking loss at protein contents of 7% or 10%.
On systems of finite sets with constraints on their unions and intersections

Abstract Let F be a family of subsets of an n -element set. F is said to be of type ( n , r , s ) if A ∈ F , B ∈ F implies that | A ∪ B | ⩽ n − r , and | A ∩ B | ⩾ s . Let f ( n , r , s ) = max {| F | : F is of type ( n , r , s )}. We prove that f ( n , r , s ) ⩽ f ( n − 1, r − 1, s ) + f ( n − 1, r + 1, s ) if r > 0, n > s . And this result is used to give simple and unified proofs of Katona's and Frankl's results on f ( n , r , s ) when s = 0 and s = 1.
Impaired renal function exaggerates hyperbilirubinemia in bile duct-ligated dogs

When obstructive jaundice was produced in dogs by ligating the common bile duct, plasma bilirubin concentrations rose to a stable plateau when glomerular filtration rate remained stable. In bile duct-ligated dogs in which glomerular filtration rate was approximately halved by unilateral ureteral ligation, a further increase in plasma bilirubin concentration occurred. Urinary excretion of conjugated bilirubin assumes major importance when bilirubin cannot be excreted in the bile. In that circumstance, decreased renal function can heighten the severity of conjugated hyperbilirubinemia.
Identif ication of Enterohepatic Helicobacter Species by Restriction Fragment-Length Polymorphism Analysis of the 16S rRNA Gene

Background. Restriction fragment-length polymorphism (RFLP) analysis of a 1,200-bp polymerase chain reaction–amplified DNA fragment of gene coding for 16S rRNA was used to generate restriction profiles of 11 enterohepatic Helicobacter spp. isolated from various animals and humans. Methods. The amplicon from each Helicobacter sp. was digested with four restriction endonucleases: Alu I, Hinf I, Hha I, and Dde I. Alu I digestion produced five patterns that were useful for initial differentiation. Results. Most Helicobacter spp. isolated from rodents had the same RFLP profiles by Alu I digestion (except H. rodentium and H. cholecystus), but they had different RFLP profiles by Hha I digestion. Only H. bilis and “H. rappini” mouse isolates could not be readily distinguished by the polymerase chain reaction-RFLP method. However, these two species can be distinguished using H. bilis specific primers. Some of the Helicobacter spp. have an intervening sequence in their 16S rRNA gene, which changes the RFLP patterns; in these cases, sequencing is the preferred method to make an appropriate diagnosis. Conclusions. The RFLP method used in this study was straightforward and rapid and should prove useful as an adjunct for identification and classification of multiple enterohepatic Helicobacter spp.
Utility and accuracy of smell-driven performance analysis for end-user programmers

This paper proposes a technique, called smell-driven performance analysis (SDPA), which automatically provides situated explanations within a visual dataflow language IDE to help end-user programmers to overcome performance problems without leaving the visual dataflow paradigm. An experiment showed SDPA increased end-user programmers' success rates at finding performance problems and decreased the time required for finding solutions. Another study, based on using SDPA to analyze a corpus of example end-user programs, revealed that it is usually accurate at identifying performance problems. Based on these results, we conclude that SDPA provides a reliable basis for helping end-user programmers to troubleshoot performance problems, as well as a potential foundation for future work aimed at training users and at aiding code reuse. Smell-driven performance analysis (SDPA) finds dataflow performance problems.SDPA provides situated explanations within the visual dataflow language.We present an extended form of the technique that incorporates runtime profiling.In a user study, participants could more easily diagnose performance problems.A second study confirmed that profiling improves accuracy.
Endometrial leukocyte subpopulations associated with Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis genital tract infection

Objective The objective of the study was to characterize endometrial inflammation associated with common genital tract pathogens. Study Design The design of the study was the immunohistochemical characterization of the endometrial leukocyte subpopulations from 37 controls and 45 women infected with Chlamydia trachomatis , Neisseria gonorrhoeae , or Trichomonas vaginalis . Results Compared with uninfected women, endocervical infection with C trachomatis , N gonorrhoeae , or T vaginalis was associated with significant increases in endometrial T cells, B cells, plasma cells, and polymorphonuclear leukocytes. Even more substantial increases in T cell, B cell, and plasma cell numbers were detected among women infected endocervically and endometrially with C trachomatis . Conclusion Because lower genital tract C trachomatis , N gonorrhoeae , or T vaginalis infections were associated with comparable increases in the same endometrial leukocyte subpopulations, our results suggest the underappreciated involvement of T vaginalis in upper genital tract inflammatory processes. The more robust inflammatory infiltrate associated with C trachomatis endometrial ascension may offer insight into host inflammatory responses associated with pelvic inflammatory disease development.
Haplotypes of the HRES-1 endogenous retrovirus are associated with development and disease manifestations of systemic lupus erythematosus.

Objective Endogenous retroviral sequences represent a link between viral and genetic factors that may influence the development of systemic lupus erythematosus (SLE). The HRES-1 human endogenous retroviral sequence is centrally located at the 1q42 chromosomal region relative to microsatellites previously associated with SLE. We therefore undertook the present study to determine the haplotypes of the HRES-1 locus and their linkage to SLE. Methods One hundred six patients with SLE, 82 unrelated healthy Caucasian individuals, and 70 healthy members of 34 lupus families were examined. HRES-1 was amplified by polymerase chain reaction (PCR) and analyzed by sequencing and restriction enzyme mapping. Microsatellites were analyzed by PCR. Haplotype construction and transmission disequilibrium testing (TDT) were performed in lupus families. Results Based on 4 single-nucleotide polymorphisms (SNPs) within a 935-base interval, we detected 6 HRES-1 haplotypes that were differentially segregated in unrelated Caucasian patients and control subjects (χ2 = 16.86, P = 0.0048) and were in linkage disequilibrium (LD) with the D1S225 microsatellite (P = 0.0002). The microsatellites D1S225, D1S235, and D1S2785 (but not D1S229) were linked to SLE by TDT. Interestingly, LD between HRES-1 SNPs at bases 653 and 1259 was reduced in patients with SLE (P = 0.048). The HRES-1 653C/1259C–harboring alleles were associated with the presence of renal disease (P = 0.0021) and with the absence of lung disease (P = 0.0323), while the 956A allele was associated with the antiphospholipid syndrome in patients with SLE (P = 0.0036). Conclusion The HRES-1 locus represents a recombination hot spot at the 1q42 chromosomal region that influences the development and disease manifestations of SLE.
Stockpiling Antiviral Drugs for the Next Influenza Pandemic

The threat of an influenza pandemic has been at the forefront of public health preparedness for more than 5 years. The national planning effort has included stockpiling antiviral drugs in the Centers for Disease Control and Prevention's Strategic National Stockpile (SNS). This article highlights the composition of the SNS before the 2009 H1N1 pandemic and includes considerations for future antiviral stockpile purchases, focusing on emergence of oseltamivir resistance and the need for additional pediatric supplies.
Arrest of cell cycle progression during first interphase in murine zygotes microinjected with anti-PCM-1 antibodies

To investigate the function of the centrosome protein PCM-1, antibodies against PCM-1 were microinjected into either germinal vesicle stage meiotic oocytes or fertilized mouse eggs, and cell cycle progression events (i.e., microtubule assembly, chromosome and centrosome organization, meiotic maturation) were assayed. These studies determined that microinjected PCM-1 antibodies arrested cell cycle progression, with anti-PCM-1 arresting fertilized eggs at the pronucleate stage when injected during G1. Analysis of the injected eggs determined that centrosome disruption and microtubule cytaster disorganization accompanied the cell cycle arrest. Anti-PCM-1 blocked neither pronuclear centration, completion of mitosis when microinjected into zygotes at G2, nor meiotic maturation when microinjected into immature oocytes. These results identify a novel role for PCM- 1 in cell cycle regulation, and indicate that PCM-1 must fulfill an essential function for cells to complete interphase. Cell Motil. Cytoskeleton 52:183–192, 2002. © 2002 Wiley-Liss, Inc.
Graph-order dithering

This paper presents a generalization of dispersed-dot dithering. While existing methods such as Bayer's assume that color dots are arranged in a square matrix, this method works with arbitrarily-placed color points. To create a good dither pattern for arbitrarily-placed points, they must be ordered so that consecutive pairs are maximally separated. In this paper, the ordering is obtained by hierarchically coloring the vertices of the points' adjacency graph. Each level in the coloring hierarchy adds a color digit to each graph vertex's label, and sorting the resulting multi-digit labels produces the desired consecutive-point separation. The method can reproduce Bayer's dispersed-dot dither matrices, but can also produce many similar matrices. Multiple matrices can be used to minimize repetitive artifacts that plague Bayer dither, while retaining its parallelizability. The method can also be applied to artistic dithering: given a repeatable motif image, its pixels can be grouped into subsets, one for each gray level, and each subset ordered. Concatenating the subsets yields a dither matrix that reproduces a motif while displaying an overall image. Unlike in previous artistic dither methods, the motif image can be arbitrary, and need not be specially constructed.
Future biologic targets for IBD: potentials and pitfalls.

IBD treatment has evolved towards biologic therapy, which seeks to target specific immune and biochemical abnormalities at the molecular and cellular level. Improved understanding of the pathogenesis of IBD has suggested future drug biologic targets, which are currently being investigated. This Review article discusses the potentials and pitfalls of biologic therapy for IBD as this field advances at a rapid pace.
Abstract A72: Epigenetic loss of SLIT2 leads to an autocrine-to-paracrine switch of the SLIT2/ ROBO1 signaling network in pancreatic cancer.

University of Arizona Student Showcase 2012 President’s Award, University of Arizona Student Showcase 2012 1st Place Biological Sciences, AACR Special Meeting Pancreatic Cancer: Progress and Challenges Scholar-in-Training Award
The ‘sick’ woman: Pregnancy discrimination in employment

Abstract In legal terms, attempts to bring about equality between men and women in the workplace have failed, mainly because the view of what is equality is based on a false premise: attempts at equality have reinforced the traditional stereotype of ‘men's’ work and ‘women's’ work and have failed to address the structural inequalities that traditionally discriminate against women. A recent decision by the European Court of Justice in a case concerning the sacking of a woman because she was pregnant, reveals what could be a new approach by that Court. This case looks at the unique position of women and attempts to give special rights to women which are not dependent upon them meeting a male norm. It is too early yet to say whether this will presage a genuine equality.
Univentricular heart: an angiographic study.

Abstract Axial angiograms of 54 patients with a univentricular heart were reviewed to determine the anatomic details demonstrated by this technique. The main ventricular chamber was of left ventricular morphology in 36, right ventricular morphology in 13 and indeterminate in 5 patients. Forty-three patients had a rudimentary ventricular chamber that was supporting a great artery in 35 patients. Eighteen patients had separate atrioventricular (A-V) valves. In four of them, one A-V valve was overriding the trabecular septum, but predominantly committed to the main ventricular chamber. Eleven patients had a single right and 13 a single left A-V valve; a common A-V valve was present in 12. The techniques used provided good demonstration of the morphology of the ventricular mass, particularly the position and orientation of a septum when present. They also delineated the morphology of the A-V valve or valves and their precise ventricular connection. Ventriculoarterial connections and relations were readily determined. It is concluded that these methods are superior to isolated frontal and lateral views and provide thorough demonstration of the intracardiac anatomy of patients with a univentricular heart.
EPR spectroscopic analysis of TAR RNA-metal ion interactions.

Metal ion-induced changes in HIV-1 TAR RNA internal dynamics were determined by the changes in EPR spectral width for TAR RNAs containing spin-labeled nucleotides (U23, U25, U38, and U40). This gave a dynamic signature for each of 10 metal ions studied, which fell into one of three distinct groups. While Li þ and K þ had little effect on TAR RNA internal dynamics, Na þ unexpectedly had a dynamic signature that was similar to Ca 2þ and Sr 2þ , with a decrease in mobility at U23 and U38, little or no change at U25, and an increase in mobility at U40. Mg 2þ ,C o 2þ ,N i 2þ ,Z n 2þ , and Ba 2þ had similar effects on U23, U38, and U40, but the mobility of U25 was markedly increased. Our results show that RNA dynamics change upon metal binding to the TAR RNA bulge, indicating that RNA structure adapts to accommodate metal ions of different size and coordination properties. 2003 Elsevier Science (USA). All rights reserved.
The Protection Of Steel Piles By Selected Coatings In A Natural Sea Water Environment

Six types of coatings are evaluated on their ability to protect steel piles in offshore conditions. These coatings, made up of a single system metal pigmented paint and 5 two system nonmetallic coatings on metal filled primers, are described in detail. These protection coatings have displayed good to excellent resistance to deterioration in a sea water environment. A brief discussion of the corrosion of bare steel piles serving as controls is included. The electrochemical techniques used to evaluate the coating deterioration in situ, and the physical measurements made on the piles after removal are briefly described. The results found on these systems in the first six years of a fifteen year program are presented.
Small RNA sequencing for profiling microRNAs in long-term preserved formalin-fixed and paraffin-embedded non-small cell lung cancer tumor specimens.

Background The preservation of microRNAs in formalin-fixed and paraffin-embedded (FFPE) tissue makes them particularly useful for biomarker studies. The utility of small RNA sequencing for microRNA expression profiling of FFPE samples has yet to be determined.
Visualizing the Dynamics of SRC Homology 2 (SH2) Domain containing Proteins on the Live Cell Membrane

Epidermal growth factor (EGF) stimulation triggers downstream signaling cascades through binding of Src homology domain 2 (SH2) containing proteins to the phosphorylated tyrosine (p-Tyr) sites of the EGF receptor (EGFR). This tyrosine signaling plays an essential role in cell proliferation, metastasis, survival, tumorigenesis, etc. However in vivo kinetics and dynamics of this process are not well quantified. Here we use total internal reflection (TIR) microscopy and single molecule imaging to visualize interactions between individual SH2 modules and p-Tyr sites near the cell membrane which provides us with the statistical kinetics and dynamics parameters, dissociation and diffusion rate. We found that surprisingly a constant apparent dissociation rate (Δ) of SH2 modules within the TIR illumination field and it is significantly longer than predictions based on chemical dissociation rate constants, suggesting that SH2 modules quickly rebind to p-Tyr site in the vicinity of the previous binding site after dissociation. We also found that the effective diffusion coefficient, (Deff), is positively correlated with the Δ value for different SH2 modules and Δ is negatively correlated with the local density of receptor tyrosine kinase (RTK) phosphorylation. These results are theoretically well explained with diffusion-controlled rebinding model, describing the SH2 molecule competes in the diffusion and re-association event after dissociation. The studies suggest a mechanism whereby signal output can be regulated through the spatial organization of multiple binding sites, which will prompt reevaluation of many aspects of RTK signaling, such as signaling specificity, mechanisms of spatial control, and noise suppression.
The Archaeology of the West Coast of South Africa

The Archaeology of the West Coast of South Africa. Edited by Antonieta Jerardino, Antonia Malan, and David Braun. Cambridge Monographs in African Archaeology 84, BAR International Series 2526. Arch...
End-point thermodynamics of an atomic Fermi gas subject to a Feshbach resonance

The entropy and kinetic, potential, and interaction energies of an atomic Fermi gas in a trap are studied under the assumption of thermal equilibrium for finite temperature. A Feshbach resonance can cause the fermions to pair into diatomic molecules. The entropy and energies of mixtures of such molecules with unpaired atoms are calculated, in relation to recent experiments on molecular Bose-Einstein condensates produced in this manner. It is shown that, starting with a Fermi gas of temperature $T=0.1{T}_{F}^{0}$, where ${T}_{F}^{0}$ is the noninteracting Fermi temperature, an extremely cold degenerate Fermi gas of temperature $T\ensuremath{\lesssim}0.01{T}_{F}^{0}$ may be produced without further evaporative cooling. This requires adiabatic passage of the resonance, subsequent sudden removal of unpaired atoms, and adiabatic return. We also calculate the ratio of the interaction energy to the kinetic energy, a straightforward experimental signal which may be used to determine the temperature of the atoms and indicate condensation of the molecules.
Ge Photodetectors Integrated with Waveguides for Electronic-Photonic Integrated Circuits on CMOS Platform

Ge p-i-n photodetectors monolithically integrated with silicon oxynitride and silicon nitride waveguides on Si CMOS platform are presented. The devices demonstrated high efficiency (~1.08 A/W) and high-speed (>14 Gbit/s) performances at low bias.
A New Mechanism for Benzopyrone Formation in Aromatic Polyketide Biosynthesis

Aromatic polyketides are all biosynthesized from highly reactive poly-β-ketone intermediates. Keys to introducing the vast chemical diversity seen in these natural products are the enzymatic and non-enzymatic tailoring chemistries that occur after biosynthesis of the poly-β-keto backbone. In this work, we expand the scope of non-enzyme-catalyzed modifications and show that primary amides can act in vivo as an electrophilic center and be attacked by an intramolecular phenol to generate dibenzopyrones. Synthetic reaction sequences were developed to confirm that the displacement can take place under neutral, low temperature aqueous conditions. We demonstrate this tailoring reaction can be rationally introduced into an engineered biosynthetic pathway to produce new compounds. This mechanism is of particular note since it demonstrates the use of a “protecting group” in polyketide biosynthesis and may be the route by which pyrones are formed in other aromatic polyketide natural products.
The C-Terminal Heptapeptide of Bombesin Reduces the Deleterious Effect of Total Parenteral Nutrition (TPN) on Gut-Associated Lymphoid Tissue (GALT) Mass but Not Intestinal Immunoglobulin A In Vivo

Background: Bombesin, the amphibian analog of mammalian gastrin-releasing peptide, reverses total parenteral nutrition (TPN)–induced atrophy of gut-associated lymphoid tissue and increases intestinal and respiratory immunoglobulin A (IgA) levels. Structure-activity studies suggested that the biologically active portion of bombesin is a C-terminal heptapeptide (7AA). This study investigates the effect of 7AA on lymphocytes counts of the Peyer's patches (PP), the lamina propria (LP) and the intraepithelial layer (IE). Methods: Forty-eight male mice were randomized to receive chow (n = 13), TPN only (n = 9), TPN + 15 μg 7AA 3 times per day (n = 13) or TPN + 150 μg 7AA 3 times per day (n = 13). After 5 days of feeding, PP, LP, and IE lymphocytes were determined. Intestinal IgA levels were measured with ELISA. Groups were compared with ANOVA. Results: All TPN-fed mice lost more weight than mice fed chow (p < .04). Lymphocyte counts in PP, LP, and IE were significantly lower in the TPN group than in the 3 other...
Insecticides affecting acetylcholine receptor interactions.

Abstract : Nearly all insecticides act on the insect central nervous system, many inhibiting ACh-esterase (e.g., organophosphates and carbamates), while nicotine, cartap and possibly isothiocyanate as well as monocrotophos and dicrotophos interact with nicotinic ACh-receptors. DDT and pyrethroids have potent effects on axonal ionic channels; but only the latter also has a high affinity for the channel sites of the nicotinic ACH-receptor found in vertebrate muscle endplates. Cyclodienes and lindane may act presynaptically, causing excessive release of ACh and possibly other neurotransmitters. On the other hand, chlordimeform has diverse targets, amongst which are Ca(2+) and/or K(+) channels and possibly octopaminergic receptors. A major difference between insect and vertebrate neurotransmitter receptors is in the skeletal neuromuscular ones, because they are nicotinic ACh-receptors in vertebrates, but are excitatory glutamate receptors and inhibitory gamma-aminobutyric acid (GABA) receptors in insects. Thus, this is an ideal system to explore and search for differences that can be utilized to synthesize selective insecticides. There are indications of other differences, such as the strong potency of kainic acid as an excitant of vertebrate central glutamate receptors.
Lawyer Advertising and the First Amendment

A current Supreme Court case concerning lawyer advertising, In re R.M.J., is analyzed in the context of a discussion of the diverse state regulations governing lawyer advertising and solicitation. The article considers the regulations in terms of their constitutionality, their tendency to impede effective advertising, and the effect they have on the legal profession's provision of information to potential clients about the nature, availability, and cost of legal services. Analysis of the major commercial speech cases, from Virginia State Board of Pharmacy to Central Hudson, indicates that many state rules infringe on attorneys' First Amendment rights.
Distributed Computing Software Building-Blocks for Ubiquitous Computing Societies

The steady approach of advanced nations toward realization of ubiquitous computing societies has given birth to rapidly growing demands for new-generation distributed computing (DC) applications. Consequently, economic and reliable construction of new-generation DC applications is currently a major issue faced by the software technology research community. What is needed is a new-generation DC software engineering technology which is at least multiple times more effective in constructing new-generation DC applications than the currently practiced technologies are. In particular, this author believes that a new-generation building-block (BB), which is much more advanced than the current-generation DC object that is a small extension of the object model embedded in languages C++, Java, and C#, is needed. Such a BB should enable systematic and economic construction of DC applications that are capable of taking critical actions with 100-microsecond-level or even 10-microsecond-level timing accuracy, fault tolerance, and security enforcement while being easily expandable and taking advantage of all sorts of network connectivity. Some directions considered worth pursuing for finding such BBs are discussed.
Aligned Carbon Nanotubes/Amorphous Porous Carbon Nanocomposite: A Molecular Simulation Study

A nanocasting method in molecular dynamics (MD) simulation was developed to mimetically synthesize nanocomposites that contain aligned carbon nanotubes (CNTs) as fillers in an amorphous porous carbon (a-PC) matrix. Structural features of aligned CNTs/a-PC nanocomposites such as the crystallinity of the CNT and the matrix as well as the interfacial bond density between these two components can be controlled by the synthesis parameters, for instance, (i) the interaction strength between a template and carbon atoms, and (ii) the quench rate used in the mimetic nanocasting process. Our study shows that properties such as the Young’s modulus and buckling resistance of aligned CNTs/a-PC nanocomposites can be tuned via the mimetic synthesis process. These mimetic models allow us to quantify the relationship between the structure and properties of aligned CNTs/a-PC nanocomposites, and to identify the optimal synthesis parameters for desired structure and properties.
Characterization and Simulation of a 915MHz Wireless Receiver

A versatile test bench and CAE environment are employed to characterize and simulate a 915MHz receiver subsystem. The subsystem, which down-converts to a 70MHz IF frequency, is constructed with coaxial components and characterized at several different levels. The 3GHz test bench used includes a vector network analyzer, a spectrum analyzer, and a synthesized signal source. Measurements are compared to system simulations enabled by HP EEsof's Series IV: Communications Design Suite? (CDS). Simulation accuracy is improved through the use of measured component level characterization data. This receiver case study provides powerful insight into the capabilities of modern measurement and simulation tools for assessment of system-level linear and non-linear performance. The revealing case study, developed for a new undergraduate course in Wireless Circuits and Systems, would be easily duplicated for in-house company training, short course seminars, as well as RF/microwave courses at other universities.