cssi/SciSciGPT-SciSciNet huggingface dataset:
Ras Effector Pathways Differentially Support Proliferation and Survival of Acute Myeloid Leukemia

Mutations that lead to activation of Ras oncogenes and their effector pathways are common in acute myeloid leukemia (AML) making Ras signaling an attractive therapeutic target. To date, efforts to therapeutically target Ras directly have proven difficult and clinical outcomes have been disappointing. The rational development of strategies for targeting Ras effector pathways in AML have been hindered by a limited understanding of the how specific Ras pathways maintain AML proliferation and survival. To determine the roles of specific Ras effector pathways in AML we disrupted signaling through canonical Ras effector pathways (RAF-MEK-ERK, PI3K-AKT-mTOR, and RAL) in murine and human AML cells. Consistent with previously published data (Kim et al. Blood. 2009;113:1086), we found that suppression of NRAS(V12) expression in a tetracycline-repressible NRAS(V12) and Mll-AF9 -driven murine AML model (tNM AML) led to AML remission in leukemic mice in vivo and almost completely suppressed leukemic-colony formation in vitro (20-fold reduction, p NRAS oncogene led to apoptosis of AML cells, but had little effect on cell cycle progression. Surprisingly, pharmacologic inhibition of the major oncogenic Ras effector pathways, RAF-MEK-ERK and PI3K-AKT-mTOR, alone or in combination suppressed AML cell growth by inducing G0/G1 cell cycle arrest in both tNM AML cells and human AML cell lines, but did not promote apoptosis in either. Conversely, pharmacologic inhibition of RALB signaling in both mouse and human AML cells induced apoptosis, but had little effect on cell cycle progression. Notably, these effects were seen in both NRAS mutant (tNM and THP1) and NRAS wild-type (MOLM13) AML cells. In preclinical studies, the RALB inhibitor Dinaciclib and the dual PI3K/mTOR inhibitor BEZ235 synergized to suppress AML growth in vitro, and had a potent anti-leukemic activity against tNM AML in vivo. We are currently evaluating the effects of a dominant negative mutant of RALB , RALB(N28) , on AML growth and survival, and investigating whether RALB signaling supports AML survival through TBK1, NF-kB, and BCL2 family members as has been shown for KRAS -driven epithelial cancers (Barbie et al. Nature. 2009;462:108). By elucidating the distinct roles for RAS effector pathways in maintaining AML proliferation and survival, we have uncovered a critical role for RALB signaling in AML survival. This work suggests that combination therapy targeting both Ras effectors that promote proliferation (PI3K/mTOR) and survival (RALB) may provide a rational treatment approach for AML. Disclosures Largaespada: NeoClone Biotechnology: Consultancy, Equity Ownership; Discovery Genomics, Inc.: Consultancy, Equity Ownership.
Exome Sequencing Reveals The Genetic Landscape Of Rare Atypical e6a2 CML

Background Over 90% of Ph-positive chronic myelogenous leukemia (“typical CML”) patients have breakpoints in the M-bcr, which typically result in b2a2 (e13a2) and/or b3a2 (e14a2) fusion mRNAs, both of which are translated into the p210 BCR-ABL protein. CML patients with the p190 BCR-ABL (m-bcr) or p230 BCR-ABL (μ-bcr) fusion genes have been reported. Atypical BCR breakpoints outside these cluster regions are extremely rare. For instance, only 8 cases have been described of e6a2 fusion CML. Very little is known about the clinical or biological characteristics of this subtype of CML, including the role of collaborating gene mutations in the development of disease. In this study, we defined the gene mutations that occurred in a rare e6a2 CML case and compared the observed gene mutations to those in “typical” chronic phase (CP)-CML cases. To our knowledge, this is the first comparison of the genetic mutations occurring in typical CML and in this rare atypical form of CML. Methodology We identified the index e6a2 CML patient, and eight additional typical CML patients for whom we had bone marrow aspirate, peripheral blood and paired normal tissue. We performed whole-exome sequencing for all of these samples using the Agilent solution-based system of exon capture, which uses RNA baits to target all protein coding genes (CCDS database), as well as ∼700 human miRNAs from miRBase (v13). In all, we generated over 3 GB of sequencing data using high throughput sequencing on the Illumina platform. Results We identified 15 candidate cancer genes that were somatically mutated in our e6a2 CML patient. Commonly implicated biological processes comprising these genes included transcription (STAT5A, TET2, GTF2F1), cellular differentiation (TP73), and signal transduction (GPR116). Interestingly, the majority of these mutations also occurred in typical CML, albeit at lower frequency. Thus, genes mutated common to our atypical case and typical CMLs included STAT5A, TET2, GTF2F1, ABL1 and CYP2A6. Thus, while atypical e6a2 BCR-ABL fusion CML cases are extremely rare, they appear to share many aspects of the biology with typical CMLs. Conclusion This study represents an in-depth analysis of a rare e6a2 CML in combination with one of the first analyses of gene mutations that occur in typical CML. Our data provide a significant first step to identifying genes that play a role in the pathogenesis along with BCR-ABL that perhaps contribute to drug resistance, and ultimately impact overall survival. Disclosures: No relevant conflicts of interest to declare.
Visual complications in diabetes mellitus: beyond retinopathy

Diabetic retinopathy is the most common cause of vision loss in people with diabetes mellitus; however, other causes of visual impairment/loss include other retinal and non-retinal visual problems, including glaucoma, age-related macular degeneration, non-arteritic anterior ischaemic optic neuropathy and cataracts. Additionally, when a person with diabetes complains of visual disturbance despite a visual acuity of 6/6, abnormalities in refraction, contrast sensitivity, straylight and amplitude of accommodation should be considered. We review and highlight these visual problems for physicians who manage people with diabetes to ensure timely referral and treatment to limit visual disability, which can have a significant impact on daily living, especially for those participating in sports and driving.
Issues in Nutrition: Dietary Considerations in Select Chronic Conditions

Chronic diseases that affect the gastrointestinal tract also tend to affect nutrition. The incidence of chronic liver disease is increasing. As the prevalence of obesity rises, so do the incidences of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Patients with chronic liver disease usually have some degree of malnutrition. In the absence of encephalopathy, patients with chronic liver disease should consume more protein than that in the average diet. There is some controversy about whether diet plays a role in the development of inflammatory bowel disease. Patients with ulcerative colitis and Crohn disease frequently present with weight loss as a symptom, and require careful nutritional assessment. Exclusive enteral nutrition plays an important role in inducing remission in children with Crohn disease but the same is not true in adults. Celiac disease is a relatively common enteropathy characterized by an autoimmune response in the intestinal lining. Patients with celiac disease should avoid eating gluten, which is found in wheat, soy, and barley. There is no evidence that gluten avoidance results in improved health outcomes in patients who are not gluten intolerant.
An in Vitro and in Vivo Evidence That Human Rhabdomyosarcomas (RMS) Express Functional CXCR7 Receptor: Overlapping and Distinct Role of CXCR4-SDF-1 and CXCR7-SDF-1/ITAC Axes in Regulating Metastatic Behavior of RMS Cells

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of adolescents and children that frequently infiltrates the bone marrow (BM). We have demonstrated that the a-chemokine stromal-derived factor (SDF)-1-CXCR4 axis (Blood 2002;100:2597, Cancer Res. 2003;63:7926, Cancer Res.2007;67:2131) plays an important role in RMS metastases. With the recent description of CXCR7, a new receptor for SDF-1 that also binds the interferon-inducible T cell-alpha chemoattractant (ITAC) chemokine, we become interested in the role of the CXCR7-SDF-1/ITAC axis in RMS metastasis. To address this issue, we evaluated 7 highly metastatic alveolar RMS (ARMS) and 3 less metastatic embryonal RMS (ERMS) cell lines. We found that all RMS cell lines express CXCR7 in contrast to CXCR4, which was expressed by 7 of 10 RMS cell lines only. CXCR4 was expressed at a much higher level by highly metastatic ARMS lines while CXCR7 was expressed at a high level on the less metastatic ERMS lines. More importantly, CXCR7 receptor on RMS cell lines was functional after stimulation with ITAC and SDF-1 as evidenced by MAPKp42/44-, AKT-, and STAT-3 phosphorylation, chemotaxis, cell motility, and adhesion assays. We also noticed that CXCR7 undergoes rapid internalization after stimulation with SDF-1 and ITAC, is a lipid raft-associated receptor, and, surprisingly, has a downregulated expression in response to hypoxia. We also noticed that similarly to CXCR4, signaling from activated CXCR7 was not associated with increased RMS proliferation or cell survival. Thus, we conclude that both CXCR4 and CXCR7 are not affecting proliferation of RMS cells; however they play an important role in both SDF-1- and ITAC-directed metastasis. For the first time, we also identify ITAC as a new regulatory chemokine that is actively involved in this process. In conclusion, since CXCR7 is more important in adhesion and becomes down-regulated during hypoxia, this changes the balance in SDF-1 signaling through both receptors (CXCR7/CXCR4). As a result, SDF-1 activates more robust CXCR4 receptor, which promotes chemotactic responses of RMS cells. As a biological consequence, this switch in SDF-1 receptor signaling increases the metastatic potential of RMS by mobilizing tumor cells to egress from the tumor into the peripheral blood and lymph and migrate to new tissue locations. We also conclude that targeting of the CXCR-SDF-1 axis alone without simultaneous blockage of CXCR7 will be an inefficient strategy to inhibit metastasis of RMS cells. This is currently being tested in our laboratories in immunodeficient mice inoculated with human RMS cells.
Adherence to National Comprehensive Cancer Network Guidelines is Associated with Improved Survival for Patients with Stage 2A and Stages 2B and 3 Extremity and Superficial Trunk Soft Tissue Sarcoma

Background The National Comprehensive Cancer Network (NCCN) has instituted treatment guidelines for stage 2A and stages 2B and 3 extremity and superficial trunk soft tissue sarcomas (ETSTS). This study examined adherence to the NCCN guidelines and factors associated with nonadherent treatment and survival outcomes. Methods Patients with stage 2A and stages 2B and 3 ETSTS (n = 15,957) were categorized as undergoing adherent or nonadherent treatment based on the 2014 NCCN guidelines. Multivariate logistic regression models were used to determine factors associated with nonadherent treatment. Overall survival (OS) and disease-specific survival (DSS) were calculated, and Cox models were used to generate adjusted survival curves and hazard ratios (HRs). Results The findings showed that 87.2% of the patients with stage 2A disease and 58.3% of the patients with stage 2B or 3 disease received adherent treatment. Community treatment facilities and uninsured or unknown insurance status were associated with nonadherent treatment for both stage groups. Adherent treatment was associated with higher 5-year adjusted OS and DSS for stage 2A and stage 2B or 3 patients. In Cox models, nonadherent treatment was associated with worse survival for both stage 2A disease (HR, 2.31; 95% confidence interval [CI], 2.02-2.63) and stages 2B and 3 disease (HR, 1.63; 95% CI, 1.53-1.73). Increasing age and non-private insurance were associated with poorer outcomes. For stages 2B and 3 disease, treatment at a community center and African American race were associated with worse survival. Conclusions Adherence to NCCN guidelines is excellent for stage 2A and poor for stages 2B and 3 ETSTS. Adherent treatment was associated with improved survival outcomes, highlighting the importance of adherence to NCCN guidelines.
TNF-α Blocker-Induced Psoriasiform Dermatitis:

BackgroundThe anti-TNF-α agents adalimumab, infliximab and etanercept are indicated for a variety of autoimmune diseases such as rheumatoid arthritis (RA), Crohn's disease (CD), ankylosing spondyli...
Inflammatory Bowel Disease Telemedicine Clinical Trial: Impact of Educational Text Messages on Disease-Specific Knowledge Over 1 Year.

Background Effective treatments are available for patients with inflammatory bowel disease (IBD); however, suboptimal outcomes occur and are often linked to patients' limited disease knowledge. The aim of this analysis was to determine if delivery of educational messages through a telemedicine system improves IBD knowledge. Methods TELEmedicine for Patients with IBD (TELE-IBD) was a randomized controlled trial with visits at baseline, 6 months, and 12 months; patient knowledge was a secondary aim of the study. Patients were randomized to receive TELE-IBD every other week (EOW), weekly (TELE-IBD W), or standard of care. Knowledge was assessed at each visit with the Crohn's and Colitis Knowledge (CCKNOW) survey. The primary outcome was change in CCKNOW score over 1 year compared between the TELE-IBD and control groups. Results This analysis included 219 participants. Participants in the TELE-IBD arms had a greater improvement in CCKNOW score compared with standard care (TELE-IBD EOW +2.4 vs standard care +1.8, P = 0.03; TELE-IBD W +2.0 vs standard care +1.8, P = 0.35). Participants with lower baseline CCKNOW scores had a greater change in their score over time (P < 0.01). However, after adjusting for race, site, and baseline knowledge, there was no difference in CCKNOW score change between the control and telemedicine arms. Conclusions Telemedicine improves IBD-specific knowledge through text messaging, although the improvement is not additive with greater frequency of text messages. However, after adjustment for confounding variables, telemedicine is not superior to education given through standard visits at referral centers. Further research is needed to determine if revised systems with different modes of delivery and/or frequency of messages improve disease knowledge.
Protein Function Prediction in Proteomics Era

The increasing number of genome sequences has become an essential data for biology of this century and function annotation to genes in those genomes is basis of the all biological research. To overcome the limitation of conventional homology-based function annotation methods, here we introduce two types of approaches: A sequence-based approach and a protein surface tertiary shape based approach. The structure-based approach is aimed to predict function of proteins whose tertiary structure was solved. The need of predicting function of proteins from their tertiary structure has emerged by the structural genomics projects, which solve an increasing number of protein structures of unknown function.
State of Play: Changing Climate at Copenhagen

Behind the current drama of climate change politics, international and domestic law play a key role, both facilitating and inhibiting progress on the Bali Action Plan. This article (published just before the Copenhagen climate conference) describes some of the hurdles to be overcome in reaching a legally binding international climate change agreement and suggests possible solutions.
A Quality Improvement project to decrease overuse of vancomycin in an inpatient Hematology/Oncology service.

e18167Background:Vancomycin (vanc) is an important but frequently misused antibiotic. In hematology/oncology (hem/onc) population, aggressive dosing, with concurrent nephrotoxic medications and che...
The Aza-hexadehydro-Diels-Alder Reaction.

The generation of pyridynes from diyne nitriles is reported. These cyano-containing precursors are analogues of the triyne substrates typically used for the hexadehydro-Diels–Alder (HDDA) cycloisom...
Influence of Parental Physical Activity and Sedentary Behavior on Young Children: Considering Time Together.

Purpose: Parents are key role models for their young child’s physical activity (PA) and sedentary behavior. This study examined the relationship between parents and their young child’s PA and seden...
On the Prefix Granularity Problem in NDN Adaptive Forwarding

One unique architectural benefit of Named Data Networking (NDN) is adaptive forwarding, i.e., the forwarding plane is able to observe data retrieval performance of past Interests and use it to adjust forwarding decisions for future Interests. To be effective, adaptive forwarding assumes Interest Routing Locality, meaning that Interests sharing the same prefix are likely to follow a similar forwarding path within a short period of time. Therefore, past observations can provide insight into how forwarding will likely perform for the same prefix in the near future. Since Interests can have multiple common prefixes with different lengths, the real challenge is determining which prefix length should be used in adaptive forwarding to record path measurements - we refer to this as the Prefix Granularity Problem. The longer the common prefix is, the better Interest Routing Locality. However, finer grained-prefixes cover fewer Interests each and require a larger forwarding table. Existing adaptive forwarding designs use a static prefix length, which is known to encounter issues in the event of partial network failures. In this work, we propose to dynamically aggregate and de-aggregate name prefixes in the forwarding table in order to use the prefixes that are the most appropriate given current network situation. In addition, to reduce the overhead of adaptive forwarding, we propose mechanisms to minimize the use of longest prefix matching during the processing of Data packets. Simulations demonstrate that the proposed techniques can result in better forwarding decisions in the event of partial network failures with significantly reduced overhead.
Parenchymal field effect analysis for breast cancer risk assessment: evaluation of FFDM radiomic similarity

Histologically normal areas of the breast parenchyma have been shown to share molecular similarity with breast tumors, suggesting the presence of a field effect in breast cancer. To further understand a potential cancer field effect, we compared mammographic parenchymal texture features across four regions of the breast. The study included 103 FFDMs with at least one identified malignant tumor. All FFDM images (12-bit quantization and 70 micron pixels) were acquired with a Hologic Lorad Selenia system and retrospectively collected under an IRB-approved protocol. Regions of interest (ROI) of 128x128 and 256x256 pixels were selected from four regions across the craniocaudal projection: within the identified tumor, adjacent to the tumor, distant from the tumor, and behind the nipple in the contralateral breast. Radiographic texture analysis was used to extract 45 features in each region. Kolmogorov-Smirnov (KS) and Pearson correlation tests assessed similarity between features in each region. KS test results, with a 95% confidence interval on the KS test statistic bootstrapped with 2000 iterations indicated that 81.8% (128x128) and 88.4% (256x256) of feature distributions across all ROI regions showed equivalence with a threshold equal to the critical value at the p = 0.05 level. Pearson correlation results demonstrated a majority of structure-based feature comparisons which reached statistical significance, and less intensity-based feature comparisons which reached statistical significance. These results support our hypothesis of a potential cancer field effect across tumor and non-tumor regions and support the development of computerized analysis of mammographic parenchymal patterns to assess breast cancer risk.
Performance of overnight on-call radiology residents in interpreting unenhanced abdominopelvic magnetic resonance imaging studies performed for pediatric right lower quadrant abdominal pain

Abdominopelvic magnetic resonance imaging (MRI) is increasingly being used to evaluate children with abdominal pain suspected of having acute appendicitis. At our institution, these examinations are preliminarily interpreted by radiology residents, especially when performed after hours. To determine the accuracy of preliminary reports rendered by radiology residents in this setting. Three hundred seventy-seven pediatric abdominopelvic MRI examinations were included. The preliminary (resident) and final (attending) radiology reports were coded as diagnosing acute appendicitis or no acute appendicitis. The concordance between resident and attending radiologist interpretations was calculated. Additionally, both resident and attending reports were compared to available surgical pathology or clinical follow-up data. Overall concordance rate for the diagnosis of acute appendicitis was 97.1%. Concordance for verified cases of acute appendicitis was 93.4%. Concordance rates did not differ by residents’ postgraduate year levels. When compared against surgical pathology or clinical follow-up data, residents demonstrated 91.2% sensitivity and 97.6% specificity. There was no statistically significant difference in the sensitivity or specificity of resident or attending radiologist interpretations. Radiology residents demonstrate high concordance with attending pediatric radiologists in their interpretations of pediatric abdominopelvic MRI for acute appendicitis. The diagnostic performances of residents and attendings were comparable.
Impact of particle flocculation on the dissolution and bioavailability of injectable suspensions

Abstract Injectable suspensions occasionally exhibit variations in dissolution and bioavailability, which may impact the clinical outcome of the drug product. Here, variation in the injection method (i.e., applied shear) for triamcinolone acetonide (TA) injectable suspension (40 mg/mL) altered the flocculation state of the particles and subsequently their dissolution. Notably, TA suspensions contained primary particles of approximately 2 µm and secondary flocculates of tens of microns. The conversion between flocculated and deflocculated particles was rapid, reversible and highly shear dependent. As such, changing shear rates during laser diffraction (LD) measurement like stirring rate, sonication, and sample introduction method (micropipette vs 25-gauge needle) may result in variability in particle size distributions (PSD) that have the potential to alter drug dissolution. Furthermore, a non-sink, discriminatory in vitro release testing (IVRT) method was developed, which combined in-situ fiber optic UV with LD to simultaneously monitor the dissolution and changing PSD of the suspension. The simultaneously measured dissolution and PSD data showed that flocculated and deflocculated particles followed different dissolution pathways. Importantly, deflocculated particles dissolved up to six times faster than the flocculated particles. Similar shear-induced changes during injection could occur in a clinical setting and have implications for drug bioavailability.
Menstrual migraine

Migraine is a common disorder that is disproportionately prevalent in women, especially during the reproductive years. Hormonal changes may play a role in the etiology of migraine, as many women note that their migraine attacks occur in temporal relationship with their menses. The Headache Classification Subcommittee of the International Headache Society has recently defined menstrual and menstrually related migraine. We review the most relevant and recent literature on menstrual migraine, with a special focus on pathophysiology and therapy. Although the pathogenesis of menstrual and menstrually related migraine is not well understood, estrogen withdrawal seems to play an important role as a trigger for menstrual migraine attacks. The therapeutic approach also may differ from the treatment of nonmenstrual migraine. Some patients do not require prophylaxis when they can abort their attacks effectively, whereas others may benefit from perimenstrual prophylaxis or standard migraine prophylaxis.
Visualization of O‐GlcNAc Glycosylation Stoichiometry and Dynamics Using Resolvable Poly(ethylene glycol) Mass Tags

O-linked N-acetylglucosamine (O-GlcNAc) glycosylation is a dynamic protein posttranslational modification with roles in processes such as transcription, cell cycle regulation, and metabolism. Detailed mechanistic studies of O-GlcNAc have been hindered by a lack of methods for measuring O-GlcNAc stoichiometries and the interplay of glycosylation with other posttranslational modifications. We recently developed a method for labeling O-GlcNAc-modified proteins with resolvable poly(ethylene glycol) mass tags. This mass-tagging approach enables the direct measurement of glycosylation stoichiometries and the visualization of distinct O-GlcNAc-modified subpopulations. Here, we describe procedures for labeling O-GlcNAc glycoproteins in cell lysates with mass tags.
Physiological response of Neurospora conidia to freezing in the dehydrated, hydrated, or germinated state

This study concerned the response to freezing of Neurospora crassa conidia in four different states: air-dry, hydrated in water, hydrated in Vogel medium lacking only sucrose, or hydrated in complete Vogel medium. All hydrated conidia were incubated in one of the above media for various times before freezing and were then washed and frozen in distilled water. Viability was estimated by three techniques, and the agreement among them was good. Hydration of air-dry conidia was found to be very rapid and, once hydrated, the conidia were much more sensitive to rapid freezing than they were before hydration. Rapidly cooled conidia survived freezing to a much higher extent when the warming rate was rapid than when it was slow; slowly cooled conidia showed little or no dependence on the warming rate. This sensitivity to rapid cooling and slow warming was attributed to the effects of intracellular ice. The sensitivity to freezing could be reversed by dehydrating the conidia in vacuo before freezing; thus, it was concluded that the presence or absence of water is the determining factor in the initial sensitivity due to freezing. In water, the sensitivity remained constant from 2 min to 15 days after hydration. Although conidia hydrated in growth medium lacking sucrose remained metabolically inactive, their sensitivity to rapid freezing decreased as a function of time in the medium before freezing. The reason for this decreased sensitivity is not understood. Conidia hydrated in complete growth medium (i.e., containing sucrose) became metabolically active and, after the initial sensitivity associated with hydration, became increasingly more sensitive to freezing as a function of their time in the medium. Drying itself was deleterious to metabolically active conidia, and those that survived dehydration did not exhibit a large absolute increase in resistance to subsequent freezing. The increase in sensitivity to freezing and to drying seems associated with the presence of metabolic activity; however, the precise cause of the sensitization remains obscure.
Broadband Structural Control using Statistical Energy Analysis Concepts

An approach is described for designing broadband controllers for flexible structures with collocated sensors and actuators. The Statistical Energy Analysis assumptions of equipartition and incoherence, together with conservation of energy, are used to express the average value of a global H 2 performance metric in terms of the power dissipation of the compensator. This power dissipation can be represented using a dereverberated model; an experimentally determined local structural model that ignores the effect of the reverberant field. Minimizing the resulting cost yields controllers with good performance which are guaranteed to be stabilizing. The approach is demonstrated experimentally on the M.I.T. Space Engineering Research Center interferometer testbed. This approach achieved a performance reduction that was approximately 30% greater than the constant gain "rate feedback" approach.
First steps for a library publisher: Developing publishing services at UNC Charlotte J. Murrey Atkins library

Purpose – The purpose of this paper is to presents the very recent development of e-journal publishing services at the University of North Carolina (UNC) at Charlotte. In 2011, the J. Murrey Atkins Library at UNC Charlotte created a new unit in the library, the Digital Scholarship Lab (DSL), which partners with faculty and graduate students in the use of digital and networked research tools to create, disseminate and store new knowledge. E-journal publishing and hosting are among the suite of services offered by the DSL, and we currently publish three journals (https://journals.uncc.edu/). Design/methodology/approach – This report provides an overview of the context of our library’s decision to begin publishing journals, including a discussion of our university’s becoming more research-intensive, our university system mandating increased efficiencies and sharing research with the state citizens, and the library’s own goals of raising awareness of and supporting open access. Also outlined are the technical...
Evolution of Skin Pigmentation Differences in Humans

The distribution of human skin pigmentation variation is highly correlated with the intensity of ultraviolet radiation (UVR). Several hypotheses propose that this strong relationship between skin colour and UVR is best explained by natural selection. The identification of a large number of genes involved in the pigmentary system now enables researchers to test these hypotheses within an evolutionary genetics framework. Genetic data indicate that the light pigmentation that characterizes populations in Europe and East Asia has evolved independently through positive selection, and that functional variation in pigmentation genes in high UVR populations has likely been subject to purifying selection. Keywords: skin pigmentation; natural selection; human evolution
Dialysis continuous process for ammonium-lactate fermentation: improved mathematical model and use of deproteinized whey.

Separate terms for substrate limitation and product inhibition were incorporated into an equation describing the rate of cell growth for the steady-state fermentation of lactose to lactic acid with neutralization to a constant pH by ammonia. The equation was incorporated into a generalized mathematical model of a dialysis continuous process for the fermentation, developed previously, in which the substrate is fed into the fermentor and the fermentor contents are dialyzed through a membrane against water. The improved model was used to simulate the fermentation on a digital computer, and the results agreed with previous experimental tests using whole whey as the substrate. Further simulations were then made to guide experimental tests using deproteinized whey as the substrate. Dried cheese-whey ultrafiltrate was rehydrated with tap water to contain 242 mg of lactose per ml, supplemented with 8 mg of yeast extract per ml, charged into a 5-liter fermentor without sterilization, adjusted in pH (5.5) and temperature (44°C), and inoculated with an adapted culture of Lactobacillus bulgaricus. The fermentor and dialysate circuits were connected, and a series of steady-state conditions was managed nonaseptically for 71 days. The fermentation of deproteinized whey relative to whole whey, with both highly concentrated, resulted in similar extents of product accumulation but at a lesser rate.
Stochastic Choice and Consistency in Decision Making Under Risk: An Experimental Study

This paper reports the results of an experiment designed to uncover the stochastic structure of individual preferences over lotteries. Unlike previous experiments, which have presented subjects with pair-wise choices between lotteries, our design allowed subjects to choose between two lotteries or (virtually) any convex combination of the two lotteries. We interpret the mixtures of lotteries chosen by subjects as a measure of the stochastic structure of choice. We test between two alternative interpretations of stochastic choice: the random utility interpretation and the deterministic preferences interpretation. The main findings of the experiment are that the typical subject prefers mixtures of lotteries rather than the extremes of a linear lottery choice set. The distribution of choices does not change between a first and second asking of the same question. We argue that this provides support for the deterministic preferences interpretation over the random utility interpretation of stochastic choice. As a subsidiary result, we find a small proportion of subjects make choices that violate transitivity, but the level of intransitive choice falls significantly over time.
Analyzing Paradata to Investigate Measurement Error

This Article is brought to you for free and open access by the Sociology, Department of at DigitalCommons@University of Nebraska - Lincoln. It hasbeen accepted for inclusion in Sociology Department, Faculty Publications by an authorized administrator of DigitalCommons@University ofNebraska - Lincoln.
Snapshots of Laser‐Generated Wakefields

We report the first single‐shot holographic measurements of transverse and longitudinal structure of laser‐generated wakefields. Real‐time, non‐averaged measurements of resonant wakes reveal detailed temporal and spatial features that depend on pulse energy and electron density. Simulations with the PIC code WAKE show excellent agreement with the morphology of the wakefields.
Clinical and immunological assessment of 94 patients with primary humoral immunodeficiency: Common variable immunodeficiency, selective IgA deficiency and polysaccharide antibody deficiency syndrome

We present the clinical and B cell immunophenotypical characterization of 94 patients with Common Variable immunodeficiency (CVID), selective IgA deficiency (SIgAD) and polysaccharide antibody deficiency syndrome (SAD). Study design: We retrospectively investigated clinical findings and B cell compartment in 31 patients with CVID, 35 with SIgAD and 28 with SAD. Regardless of underlying disease, a delay was observed between age at diagnosis and onset of first symptoms. The predominant clinical findings were upper and lower respiratory tract infections. Allergic symptoms were more frequent in SAD and SIgAD patients, hematological and autoimmune manifestations in CVID and celiac disease in SIgAD. B-cell Immunophenotype abnormalities were observed in SAD and CVID patients: both had reduced memory B cells (CD19+ CD27+), and increased transitional B cells (CD24++ CD38++) was found in SAD. We did not find any statistically significant abnormalities in any of differentiation stages of B cells in SIgAD. Defects of the B cell compartment were associated with bronchiectasis, splenomegaly, autoimmunity and/or malignancy in CVID and SAD patients.We conclude that flow cytometric evaluation of the B cell compartment could be a useful tool for the diagnosis and follow up of these patients.
Variable microsatellite markers for a snapping shrimp (Alpheus armillatus) species complex

Snapping shrimp (Alpheus) are an important ecological component of tropical marine systems and are excellent models for studies of phylogeography and behavioural ecology. Here, I describe 10 variable microsatellite loci for the Alpheus armillatus species complex of snapping shrimp. The primers were tested on 60 individuals representing three evolutionary lineages within the complex, and yielded three to 21 alleles. These loci will be effective tools in future studies on population genetics and mating behaviour in this complex.
Experimental Simulation of Plagioclase Diagenesis at P-T Conditions of 3.5 km Burial Depth

Dissolution of plagioclase under the physical conditions at shallow to intermediate burial depths is a prime candidate for secondary porosity generation in feldspathic siliciclastic sediments. The diagenetic behavior of granular aggregates of plagioclase feldspar and quartz has been investigated by experimentation performed in a Bridgeman-type pressure vessel. The experiments, each of two weeks duration, simulated pressure-temperature conditions approximating 3.5 km burial depth. By using a double-acting pore-fluid reservoir, solutions of various chemistries were cycled through samples composed of oligoclase or labradorite feldspar and quartz (90:10 wt% respectively).
Distributed Localization of Modular Robot Ensembles

Internal localization, the problem of estimating relative pose for each module of a modular robot, is a prerequisite for many shape control, locomotion, and actuation algorithms. In this paper, we propose a robust hierarchical approach that uses normalized cut to identify dense sub-regions with small mutual localization error, then progressively merges those sub-regions to localize the entire ensemble. Our method works well in both two and three dimensions, and requires neither exact measurements nor rigid inter-module connectors. Most of the computations in our method can be distributed effectively. The result is a robust algorithm that scales to large ensembles. We evaluate our algorithm in two- and three-dimensional simulations of scenarios with up to 10,000 modules.
Conflict Resolution in Games and Sports

Structural elements which seem to limit and control conflicts in games and sports are examined. How these elements may be developed within sport environments is then discussed. Valuable lessons can be learned (a) from sports and games in non-Western societies where conflict is often controlled by ritual, (b) from the informal games of children, where the play element often is maintained, and (c) from the concept of subordinate goals, developed as a way of ensuring association. Finally, these three forms of conflict resolution are demonstrated in the game of rugby football.
Retinal Toxicity Associated With Occupational Exposure to the Fish Anesthetic MS-222

Purpose To report a case of retinopathy associated with chronic occupational exposure to ethyl-m-aminobenzoic acid methanesulfonate (MS-222), a retinotoxic fish anesthetic. Method Case report with electroretinograms to document changes in visual electrophysiology. Results An ichthyologist with a long history of skin exposure to MS-222 was initially examined for decreased vision, photophobia, and photopsia. His electroretinogram abnormalities were similar to those seen in animal models of acute MS-222 toxicity. After terminating MS-222 contact for 7 months, his vision returned to normal, and his electroretinogram improved. Conclusion Individuals with occupational exposure to MS-222 should exercise caution to avoid systemic absorption of this retinotoxic compound.
Synthesis, processing, and secretion of hepatic very low density lipoprotein

Very low density lipoprotein (VLDL) is the major vehicle in the plasma which carries triacylglycerol synthesized in the liver to peripheral tissues for utilization. Estrogen-induced chick parenchymal liver cells (hepatocytes) synthesize and secrete large amounts of VLDL. These cells, in a primary monolayer culture system developed in this laboratory, have been employed to study the operative and regulatory aspects of VLDL synthesis, assembly, and secretion. Some 10 min are required for the translation of the principle VLDL protein constituent, apolipoprotein B, and 30-35 min are required for the two newly translated chick VLDL apolipoproteins, apolipoprotein B and apolipoprotein II, to be secreted. Apolipoprotein B is synthesized on membrane-bound polysomes as a contiguous polypeptide chain of 350K molecular weight (MW) and is not assembled posttranslationally from smaller-peptide precursors. Translocation of puromycin-discharged apolipoprotein B nascent chains into the endoplasmic reticulum lumen and their subsequent secretion are independent of both ongoing protein synthesis and the attachment of the nascent peptides to ribosomes. Apolipoprotein B nascent chains discharged by puromycin assemble with glycerolipid (mainly triacylglycerol) and are secreted as immunoprecipitable VLDL. Core oligosaccharides are added to the apolipoprotein B nascent chain co-translationally in at least two stages, at molecular weights of approximately 120K and approximately 280K . Inhibition of N-linked glycosylation of apolipoprotein B with tunicamycin affects neither the assembly of glycerolipids into VLDL nor the secretion of the VLDL particle, indicating that aglyco -apolipoprotein B can serve as a functional component for VLDL assembly and secretion. Active synthesis of the VLDL apolipoproteins is required, however, for glycerolipid assembly into VLDL and secretion from the hepatocyte. The differential kinetics with which newly synthesized apolipoproteins and glycerolipids are secreted as VLDL and the timing of the effects of protein-synthesis inhibitors on their secretion indicate that VLDL constituents are assembled sequentially in the intact liver cell. The bulk of the VLDL triacylglycerol and some VLDL phosphoglyceride is introduced early in the secretory pathway proximal, yet subsequent to apopeptide synthesis, while a significant fraction of VLDL phosphoglyceride associates with the resulting triacylglycerol-rich lipid-protein complexes just prior to their secretion as mature VLDL. Within the context of current models for VLDL structure, the late assembly of phosphoglyceride into VLDL is taken to represent a surface maturation of the nascent VLDL particle.
Quality of Work Life and Employee Outcomes: A Survey of Employees in Hotel Business

In this paper, we discussed the relationship between Quality of Work Life and employee outcomes in China. We used organizational commitment and organizational citizenship behavior (OCB) to reflect employee outcomes. By employing several statistics techniques, such as factor analysis, reliability and validity analysis, the data of questionnaires has been analyzed. The results show that there is a significant positive relationship between QWL and all the indicators of employee outcomes (Organizational Commitment and OCB).
Evaporative Cutting of a Semitransparent Body With a Moving CW Laser

The formation of a groove by partial evaporation of a moving semi-infinite and semitransparent solid is considered. Evaporative removal of material is achieved by focusing a high-power, highly concentrated Gaussian laser beam of continuous wave (CW) onto the surface of the solid. Surface heat losses due to radiation and convection are assumed to be negligible, and conductive losses are treated in an approximate fashion using a simple integral method. The relevant nonlinear partial differential equations are solved numerically, and results for groove depth and shape are presented for a variety of laser and solid parameters.
Downhole seismometers in the deep ocean

The advances made using data from the sparse land-based digital seismic networks operating since the mid-1970s have been spectacular. There are now tomographic maps of the Earth's interior, reaching from the lithosphere to the inner core of the Earth. A clear potential has been demonstrated for the mapping of temperature anomalies and flow in the mantle by the determination of velocity anomalies and changes in azimuthal or polarization anisotropy. The first maps of the topography of the core mantle boundary were published last year. However, the resolution of these studies and the uniqueness of their results is limited by the lack of adequate spatial sampling of the seismic wave field over the entire globe.
Is there a competitive market for hospital services

This paper focuses on the price elasticity of hospital-specific demand curves. Each hospital is assumed to practice price discrimination with respect to Medicare, Medicaid, and other patients. Among the third group, patients covered by Blue Cross are analyzed separately from those who pay their own bills or are covered by commercial insurance or a health maintenance organization (HMO). We use two different methods to estimate the price elasticity of demand. First, a pricing rule is developed from which hospital-specific price elasticities may be inferred. Second, the distribution of each payer's admissions at specific hospitals is examined to determine if low-priced hospitals attract more patients. Data for the analysis are taken from 31 hospitals in the Minneapolis-St. Paul metropolitan area in 1981. Results of the first analytic method indicate that hospitals had monopoly power in their markets for Blue Cross and self pay/commercial insurance/HMO patients. These results are confirmed and extended to Medicare patients by the hospital demand analysis.
DID A VOLCANIC MEGA-ERUPTION CAUSE GLOBAL COOLING DURING THE LATE ORDOVICIAN?

The Late Ordovician Taconic orogeny was associated with volcanic eruptions along the subduction zones of the Iapetus Ocean. One of these eruptions, which led to the deposition of the Deicke K-bentonite Bed, is believed to have been larger than the largest recent and subrecent volcanic eruptions (e.g., Toba, Pinatubo). The Deicke eruption has been proposed to have led to a cooling event and associated faunal turnover during the Sandbian–Katian of Laurentia based in part on the observed lowering of global surface temperature after recent mega-eruptions. We tested for a geologically resolvable climatic perturbation associated with the Deicke eruption by estimating changes in ocean temperatures from the oxygen isotope ratios of single-species separates of conodont apatite from a section of the Carimona Member of the Platteville Formation in southeastern Minnesota, United States, that includes the Deicke K-bentonite. In contrast to predictions of models invoking more or less direct volcanic forcing for Ordovician climate trends, we found no obvious or consistent change in temperature at or above the bentonite, but did see evidence of cooling (∼4 °C) among presumed nekto-benthic taxa in the 0.7 meters of the section below the bentonite. Thus, at least for the study area, there is no evidence that the Deicke eruption induced a significant cooling event.
DISTRIBUTIONS OF REAL INCOME: WITHIN COUNTRIES AND BY WORLD INCOME CLASSES

Income and expenditure data from 14 countries (representing one-third of the world's population), mostly from the 1970s, are used to construct national income distributions and, after normalizing by purchasing power parities, to construct a “world” distribution of real income. The density of real-income equivalent groups (socio-economic classes) across countries is measured for the “affluent,” the “well-off,” and the “poor.” In comparison with earlier studies, most national distributions of income seem to have been improving, the numbers of those in poverty (based on real income) are lower, and, most important (and disturbing for some) is that the “affluent” class (and those above “middle class” income levels) has (prematurely) swelled in a number of developing countries.
Claudin-19 and the Barrier Properties of the Human Retinal Pigment Epithelium

Purpose. The retinal pigment epithelium (RPE) separates photoreceptors from choroidal capillaries, but in age-related macular degeneration (AMD) capillaries breach the RPE barrier. Little is known about human RPE tight junctions or the effects of serum on the retinal side of the RPE.
Reflection and Outlook for the Future of Addictions Treatment and Training: An Interview with William R. Miller

ABSTRACT The development of motivational interviewing (MI) has contributed to a significant change in the zeitgeist of substance abuse treatment. Dr. William Miller has been instrumental in the direction MI has taken. Dr. Miller helped develop MI, guide research and training initiatives, and as a result set a solid foundation for the future of MI. In this article, an interview with Dr. Miller is provided, in which he reflects on his career as he prepares for retirement and provides his perspective on the future of substance abuse treatment and training. Dr. Miller's recommendations for training therapists in MI are also highlighted.