cssi/SciSciGPT-SciSciNet huggingface dataset:
Understanding Vicious Cycles in Server Clusters

In this paper, we present an automated on-line service for troubleshooting performance problems in server clusters caused by unintended vicious cycles. The tool complements a large volume of prior performance troubleshooting and diagnostic literature for server farms that identifies problems arising due to resource bottlenecks or failed components. We show that unintended interactions between components in large-scale systems can cause performance problems even in the absence of bottlenecks or failures. Our tool leverages discriminative sequence mining to identify anomalous sequences of events that are candidates for blame for the performance problem. The tool looks for patterns consistent with "vicious cycles" or unstable behavior, as such patterns, when present, are most likely to be problematic. It highlights candidates that are semantically conflicting, such as those arising when different performance management mechanisms make adjustments in conflicting directions. Our approach offers two key advantages in performance troubleshooting. First, it does not require detailed prior knowledge of the underlying system to diagnose the problem. Second, contrary to simple statistical techniques, such as correlation analysis, that work well for continuous variables, our scheme can also identify chains of events (labels) that may explain the root cause of a problem. Our service is deployed on a web server testbed of 17 machines. To make the comparison of our scheme to prior work more concrete, we first reproduce two real-life problem scenarios reported in earlier literature, then explore a third, new case study. In all cases, our tool reports the patterns that explain the cause of the problem without requiring detailed a priori knowledge.
Creative Computer Science Teaching Techniques

Computer science classrooms can be thriving environments that cultivate creative students and utilize the power of nontraditional students to prepare students for the “real world.” Team assignments and modification exercises simulate real‐world situations. The need for good documentation and the development of test data are emphatically emphasized by nontraditional students. Writing letters and discussing journal articles improve both written and oral communication skills. Visualization of recursion in a concrete fashion aids students in understanding mathematical induction. All these activities help students enter the real world with skills desired by employers. And creative classrooms provide benefits for all: teachers, students, and employers, too.
Assessment of Resident Physicians' Knowledge of Physical Therapy

Half of all US medical schools offer courses in rehabilitation medicine; however, 46 states require physician referrals for physical therapy services. The purpose of this study was to identify areas of deficit in resident physicians' knowledge of selected physical therapy modalities and evaluative procedures and to determine if resident physicians perceived themselves to have adequate background to refer patients to physical therapy effectively. We mailed a questionnaire to 345 resident physicians chosen from area hospitals and obtained a response rate of 32 percent. The demographic portion of the questionnaire was analyzed by the use of descriptive and chi-square statistics. We tested knowledge of modalities and evaluative procedures through matching of treatment referrals with specific patient diagnoses and analyzed the data in terms of chi-square, frequencies, and correlated statistics. The results indicated that the majority of respondents refer patients to physical therapy (98%) and feel adequately informed to do so (54%). Test results, however, ranged from 1 to 73 percent correct, with only one score above 70 percent correct. This finding indicated a deficit in resident physicians' knowledge of physical therapy. We also identified a need for physical therapists to educate physicians about treatment modalities and evaluative procedures through continuing education programs.
Antagonists of Myosin Light Chain Kinase and of Myosin II Inhibit Specific Events of Egg Activation in Fertilized Mouse Eggs

Although recent studies have demonstrated the importance of calcium/calmodulin (Ca 2þ /CAM) signaling in mammalian fertilization, many targets of Ca 2þ /CAM have not been investigated and represent potentially important regulatory pathways to transduce the Ca 2þ signal that is responsible for most events of egg activation. A well-established Ca 2þ /CAM-dependent enzyme is myosin light chain kinase (MYLK2), the downstream target of which is myosin II, an isoform of myosin known to be important in cytokinesis. In fertilized mouse eggs, established inhibitors of MYLK2 and myosin II were investigated for their effects on events of egg activation. The MYLK2 antagonist, ML-7, did not decrease the activity of Ca 2 þ /CAM protein kinase II or the elevation of intracellular Ca 2 þ , and it did not delay the onset of Ca 2 þ oscillations. In contrast, ML-7 inhibited second polar body (PB) formation in a dose-dependent manner and reduced cortical granule (CG) exocytosis by a mean of approximately 50%. The myosin II isoform-specific inhibitor, blebbistatin, had similar inhibitory effects. Although both antagonists had no effect on anaphase onset, they inhibited second PB formation by preventing spindle rotation before telophase II and normal contractile ring constriction. To our knowledge, this is the first report that MYLK2 and myosin II are involved in regulating the position of the meiotic spindle, formation of the second PB, and CG exocytosis. The present results suggest that MYLK2 is one of a family of CAM-dependent proteins that act as multifunctional regulators and transduce the Ca 2þ signal at fertilization.
An investigation of waveform sampling for improved signal processing in TOF PET

The development of fast photodetectors and of fast, high light output scintillation crystals has placed an increased emphasis on the need for fast readout electronics used for Time-Of-Flight (TOF) PET detectors. These improvements have paralleled developments in analog sampling technology that makes fast waveform digitizing of photodetector signals an attractive alternative to custom PCB and IC designs. Waveform digitization offers a flexible means for evaluating and implementing more complex signal processing algorithms. We used a commercial 1GHz 2Gs/s waveform digitizing system to acquire coincident pulses from LYSO and LaBr 3 (5%Ce) scintillator crystals coupled to a fast PMT. By measuring the time pickoff based on a linear fit to the rising edge of the pulse, we show an improvement in coincident timing resolution from ∼200ps to ∼80ps FWHM for LaBr 3 (5%Ce) coupled to Photonis XP20D0 PMTs, and from ∼160ps to ∼80ps Full Width at Half Maximum (FWHM) for LaBr 3 (5%Ce) coupled to Hamamatsu H4998 PMTs. Our results show a consistent improvement in timing resolution as well as reduced sensitivity to signal risetime as compared to leading edge (LE) pickoff techniques. Measurements with partial detector modules indicate that system timing resolution of ≪200ps is attainable with LaBr 3 (5%Ce) pixelated detectors designed for TOF PET.
Measuring hydrogen-deuterium exchange in protein monolayers

A Fourier transform infrared (FTIR) spectroscopy assay to measure hydrogen–deuterium exchange (HDX) in surface-adsorbed protein monolayers is developed to provide information on protein tertiary structure, because the typical secondary structural analysis of our surface and solution protein samples proved to be very similar. Adsorbed protein HDX is quantified by exposing the protein to a 50% deuterated NaPO4 buffer solution and then measuring the normalized intensity change of the amide II band in the FTIR reflection spectrum. When collected as a function of exchange time, this intensity follows the kinetics of the exposure of the protein amides to solvent. HDX kinetics have been obtained for bovine serum albumin (BSA) in solution and adsorbed to gold surfaces. Using experiments designed to allow comparisons between protein in solution and on surfaces, the extent of HDX was found to increase over that observed for BSA in solution, consistent with an increase in the exposure of albumin amide groups and protein unfolding upon adsorption. We also show that BSA adsorbs to the surface of gold in multilayers and that the increase in amide exposure is present only in the first adsorbed monolayer. Published in 2009 by John Wiley & Sons, Ltd.
Efficiency of digestion in germ-free and conventional rabbits.

1. Germ-free (GF) and conventional (CV) rabbits wearing collars to prevent coprophagy were fed an autoclaved diet with added cellulose. Their faecal excretion was analysed to determine nutrient digestibility.2. Clearly distinguishable hard faeces were excreted by the GF rabbit only if the diet contained at least 15% cellulose. Unlike CV rabbits, the GF rabbits did not consume their soft faeces even when permitted to do so. Soft faeces made up a larger proportion of the total output of GF than of CV rabbits. Food intake and total dry-matter excretion per kg body-weight were similar in both groups.3. Although digestibility of dry matter was similar in the two groups, in the GF rabbits there was a higher digestibility of crude fat and true protein and a lower digestibility of crude fibre and nitrogen-free extract. GF rabbits excreted a higher percentage of ingested calcium and phosphorus in the urine than did CV rabbits.4. The results suggest that intestinal microbes, even without the enhancing effect of coprophagy, aid in the digestion of carbohydrate by rabbits. The greater faecal excretion of crude fat and true protein by CV rabbits could result from poorer digestion and absorption, but could also represent nutrients synthesized by microbes from simpler materials. The reingestion of faecal crude fat and true protein might therefore improve the quality of the total nutrient intake. The results suggest ways of assuring an adequate dietary intake by GF rabbits in the absence of contributions from an intestinal microflora.
Implicit Theories of Creativity Across Cultures: Novelty and Appropriateness in Two Product Domains

One potential problem for creativity theory is whether both novelty and appropriateness are equally valid dimensions across cultures. Taking an implicit theory approach, the authors surveyed more than 400 students from Japan, China, and the United States. Using repeated measures scenarios of cooking and textbook products, novelty was found to be important across the three countries for evaluations of creativity. However, the Chinese were more swayed than were the Americans by the novelty manipulation in terms of how much they desired the products. Appropriateness was more important for Americans and Japanese for evaluations of creativity and desire for products. Both novelty and appropriateness had large effects. Rather than relying on assumed country variations, the authors argue that cross-cultural research be used to understand the nature of creativity.
The Succession Experience of the Next Generation

Literature indicates that succession is critical to the future of a family firm. However, little is known about how the next generation actually experiences the process of succession. An in-depth biographical study of thirty-two next-generation family members indicates specific factors critical to succession. The findings are delineated in a framework that portrays these influences, their relationships, and the effect they have on the succession experience of next-generation family members.
Design and performance of a capacitor sensor and impedance analyzer for nondestructive moisture content determination

In this work, the design and performance of a low-cost impedance analyzer, called the CI Meter, that was assembled and calibrated to measure impedance and phase angles at 1, 5 and 9 MHz is given. A cylindrical sample holder with a single set of parallel-plate electrodes embedded inside along its length that can hold samples (100–150 g) of peanut pods (in-shell peanuts) was built and used with this instrument. The measured values of impedance and phase angle with this experimental setup were used in an empirical equation to obtain the average moisture content values of peanut samples with moisture contents in the range of 6–23%. The moisture content values determined by this system and a commercial impedance meter were compared with those obtained by a standard method. For over 90% of the samples tested in the moisture range between 6 and 23% the moisture content values were found to be within 1% of the standard values for both systems. Ability to determine the average moisture content of in-shell peanuts without shelling and cleaning them, with a low-cost instrument, will be of considerable use in the peanut industry. This method could be extended to other types of in-shell nuts.
Pulmonary Hypertension Associated with Bronchiolitis Obliterans after Stem Cell Transplant

Mean age (years) at SCT (Range) 7.1 (0.9-28.7) 4.6 (0.3-29.8) 5.4 (0.9-32.8) 9.2 (2.2-27.5) Median days from SCT to BSI (IQR) 7 (4-55) 59 (8-137) 70 (48-118) 149 (58-313) Diagnosis Immune Deficiency (n1⁄432) Malignancy (n1⁄417) Marrow Failure (n1⁄48) Benign Hematology (n1⁄45) Genetic/Metabolic (n1⁄42) 8 (44%) 13 (65%) 4 (31%) 7 (54%) 6 (33%) 5 (25%) 3 (23%) 3 (23%) 2 (11%) 0 3 (23%) 3 (23%) 1 (6%) 1 (5%) 3 (23%) 0 1(6%) 1 (5%) 0 0 Myeloablative conditioning (n1⁄428) 8 (44%) 12 (60%) 5 (38%) 3 (23%) GVHD (Grade II-IV) at 100 days (n1⁄419) 4 (22%) 5 (25%) 6 (46%) 4 (31%) Sepsis/shock (n1⁄431) 4 (22%) 10 (50%) 3 (23%) 14 (36%) ICU care within 7 days of BSI (n1⁄415) 4 (22%) 4 (20%) 3 (23%) 4 (10%) Died (n1⁄427) 8 (44%) 8 (40%) 3 (23%) 8 (62%) Non relapsed mortality (n1⁄420) 6 (33%) 6 (30%) 3 (23%) 5 (38%) Median days from BSI to death (IQR) 90 (51-152) 119 (50-206) 44 (34-63) In patients with > 1 BSI, median days from last BSI to death (IQR) 156 (113-302) Abstracts / Biol Blood Marrow Transplant 21 (2015) S206eS239 S217
Winner takes all: competing viruses or ideas on fair-play networks

Given two competing products (or memes, or viruses etc.) spreading over a given network, can we predict what will happen at the end, that is, which product will 'win', in terms of highest market share? One may naively expect that the better product (stronger virus) will just have a larger footprint, proportional to the quality ratio of the products (or strength ratio of the viruses). However, we prove the surprising result that, under realistic conditions, for any graph topology, the stronger virus completely wipes-out the weaker one, thus not merely 'winning' but 'taking it all'. In addition to the proofs, we also demonstrate our result with simulations over diverse, real graph topologies, including the social-contact graph of the city of Portland OR (about 31 million edges and 1 million nodes) and internet AS router graphs. Finally, we also provide real data about competing products from Google-Insights, like Facebook-Myspace, and we show again that they agree with our analysis.
Lived and Imaginary Narratives and Their Place in Taking Oneself up as a Gendered Being

: The relation between the way in which children understand feminist stories and their understanding of everyday life are examined in a feminist poststrucluralist framework. Sex-role socialisation theory is rejected as inadequate for the purposes of explaining either the sense children make of the stories they hear or how and why children take up their genderedness in the way that they do. Through preschool children's responses to feminist stories and through observations of preschool children's play, an alternative explanatory framework is elaborated. At the same time the relation between lived and imaginary narratives is explored.
High incidence of spontaneous cataracts in aging laboratory rabbits of an inbred strain

Objective To investigate the occurrence of spontaneous cataracts in a breeding colony of the inbred EIII/JC strain of New Zealand White rabbits (Oryctolagus cuniculi) and the congenic strain of EIII/JC-HLA-A2.1transgenic rabbits. Procedure A retrospective study was conducted by collecting and analyzing data from clinical records for individual rabbits filed between January 2011 and October 2013. Results Thirteen cases (eight females and five males) of cataract were identified in a group of 51 EIII/JC inbred rabbits with a morbidity of 25.5%. The median age of the rabbits identified with unilateral or bilateral cataracts was 43 months in contrast to the median age of 23 months of the entire group of 51 rabbits. Additionally, seven cases (five females and two males) of cataracts were identified in a group of 21 EIII/JC-HLA-A2.1 transgenic rabbits. The EIII/JC-HLA-A2.1 transgenic rabbits showed similar morbidity (33.3%) and median age (41 months) for the development of cataracts as the EIII/JC rabbits. In both groups, none of the rabbits younger than 37 months developed cataracts while 13 (93%) of 14 EIII/JC rabbits aged 37–49 months and seven (63.6%) of 11 EIII/JC-HLA-A2.1 transgenic rabbits aged 37–43 months developed cataracts. In contrast, none of 78 outbred rabbits with a median age of 26 months (10–67 months) developed cataracts. Conclusion Results of this study indicate that the occurrence and high incidence of spontaneous cataracts in this inbred strain (EIII/JC) of rabbits were strictly age related and consistently transmitted through inbreeding.
Impact of medical academic genealogy on publication patterns: An analysis of the literature for surgical resection in brain tumor patients

"Academic genealogy" refers to the linking of scientists and scholars based on their dissertation supervisors. We propose that this concept can be applied to medical training and that this "medical academic genealogy" may influence the landscape of the peer-reviewed literature. We performed a comprehensive PubMed search to identify US authors who have contributed peer-reviewed articles on a neurosurgery topic that remains controversial: the value of maximal resection for high-grade gliomas (HGGs). Training information for each key author (defined as the first or last author of an article) was collected (eg, author's medical school, residency, and fellowship training). Authors were recursively linked to faculty mentors to form genealogies. Correlations between genealogy and publication result were examined. Our search identified 108 articles with 160 unique key authors. Authors who were members of 2 genealogies (14% of key authors) contributed to 38% of all articles. If an article contained an authorship contribution from the first genealogy, its results were more likely to support maximal resection (log odds ratio = 2.74, p < 0.028) relative to articles without such contribution. In contrast, if an article contained an authorship contribution from the second genealogy, it was less likely to support maximal resection (log odds ratio = -1.74, p < 0.026). We conclude that the literature on surgical resection for HGGs is influenced by medical academic genealogies, and that articles contributed by authors of select genealogies share common results. These findings have important implications for the interpretation of scientific literature, design of medical training, and health care policy.
Accidental death rates and suicide.

Two hypotheses were considered for the association between accidental death rates and suicide rates: (1) that suicidal deaths may be misclassified occasionally as accidental deaths, and (2) that accidental death rates provide an index of the availability of methods for suicide. Correlations over time produced results supporting the second hypothesis. Language: en
Self-ordering dual-layered honeycomb nanotubular titania: a study in formation mechanisms

A new method for creating a honeycomb morphology of TiO2 nanotubular arrays has been proposed using a two-step anodization process. The first anodization step utilizes fluoride containing ethylene glycol as an electrolyte (EG-solution). The anodic oxide formed during the first anodization step was removed to expose hemispherical nanoindentations created on the substrate. These nanoimprints acted as templates for honeycomb morphology during the second step of anodization that was carried out in fluoride containing phosphoric acid solution (PA-solution). Several small diameter nanotubes were grown in each honeycomb cell during the second anodization step. The formation of such honeycomb morphology required a threshold concentration of Ti4+ in the anodization electrolyte. Below the threshold Ti4+ concentration (4 × 10−3 M in this investigation), a good honeycomb morphology was not observed. The formation mechanism proposed is based on weakly linear surface perturbation theory aided by compressive growth stresses and a decrease in surface energy due to the presence of [TiF6]2− species.
LOCALIZATION OF DIPSOGENIC RECEPTORS FOR ANGIOTENSIN II

Publisher Summary This chapter presents evidence that supports the proposition that the subfornical organ (SFO) contains dipsogenic receptors for angiotensin II. Studies performed with a variety of techniques support this hypothesis. Angiotensin II (AII) exerts several effects which are mediated by the central nervous system. Among these effects are the elevation of blood pressure via sympathetic outflow—an effect upon the secretion of antidiuretic hormone—and the elicitation of water ingestion. The elicitation of drinking following extracellular dehydration is mediated in part by an elevated renal secretion of rennin. This effect of the renin–angiotensin system is apparently mediated by angiotensin II. The chapter demonstrates that angiotensin-elicited drinking in water-replete animals follows systemic or direct intracranial applications of the hormone. The fact that angiotensin crosses neither the blood–brain barrier nor the blood-cerebrospinal fluid barrier may limit the loci, which might be considered as candidates to contain dipsogenic receptors for circulating angiotensin.
Periodic fluctuations in resistance of a myeloma tumor (MOPC-315-el) to cytotoxic T lymphocytes.

We have previously reported that MOPC-315-EL, a myeloma subline of MOPC-315, periodically becomes reversibly altered in its reactivity with both syngeneic and allogenic cytotoxic T lymphocytes (CTLs). In this report we demonstrate that the change from the reactive to the unreactive phenotype can take place in BALB/c nude mice and in culture with essentially the same kinetics and to the same degree as that which occurs in conventional BALB/c mice. The reactive and unreactive MOPC-315-EL cells obtained from nude mice or grown in culture express identical amounts of the serologically defined H-2d antigens, as determined by quantitative adsorptions of anti-H-2d antibodies, suggesting that non-H-2 components determine the unreactive phenotype. The change in reactivity with T cells does not require that MOPC-315-EL cells undergo division, but it does appear to be dependent upon certain growth factors.
Fusarium Crown-Rot Development in Alfalfa Stressed by Threecornered Alfalfa Hopper (Homoptera: Membracidae) Feeding

Alfalfa, Medicago sativa L., plants were inoculated with Fusarium oxysporum Schlecht and infested with Spissistilus festinus (Say) nymphal populations for six harvest periods under greenhouse conditions. Significant interactions between insect populations and F. oxysporum were found for number of harvestable stems and percent acid detergent fiber. The main effect of inoculation did not significantly affect any of the plant parameters examined. Insect populations, however, reduced plant height, root carbohydrate concentration, forage yield, and forage quality. S. festinus nymphs also were found to cause a significant increase in Fusarium crown-rot severity after six harvest periods.
The fitness landscape of a tRNA gene

Fitness landscapes describe the genotype-fitness relationship and represent major determinants of evolutionary trajectories. However, the vast genotype space, coupled with the difficulty of measuring fitness, has hindered the empirical determination of fitness landscapes. Combining precise gene replacement and next-generation sequencing, we quantified Darwinian fitness under a high-temperature challenge for more than 65,000 yeast strains, each carrying a unique variant of the single-copy tRNA(CCU)(Arg) gene at its native genomic location. Approximately 1% of single point mutations in the gene were beneficial and 42% were deleterious. Almost half of all mutation pairs exhibited statistically significant epistasis, which had a strong negative bias, except when the mutations occurred at Watson-Crick paired sites. Fitness was broadly correlated with the predicted fraction of correctly folded transfer RNA (tRNA) molecules, thereby revealing a biophysical basis of the fitness landscape.
Advances in the clinical assessment of dissociation: the SCID-D-R

A comprehensive assessment of dissociative symptoms is recommended for effective treatment of trauma survivors. The author reviews the systematic detection of dissociative symptoms and disorders using the Structured Clinical Interview for DSM-IV Dissociative Disorders--Revised (SCID-D-R) in adolescents and adults (Steinberg, 1994b). Numerous investigations have reported good-to-excellent reliability and validity of the SCID-D-R, both in the United States and abroad. Clinical applications, including the SCID-D-R's utility for psychological and forensic evaluations, treatment planning, differential diagnosis, and evaluation of malingering, are reviewed.
Bootstrapping a lunar civilization

In this chapter we introduce and discuss the two financial aspects of the creation of a lunar settlement. The first is: How do we fund the return to the Moon? And the second aspect is: How do we make it self-sustaining once we are there? One of the great challenges that faced our space pioneers was how to finance the settlement of the Moon. Initially, only rockets were available to carry mass into orbit from the Earth to the Moon. Near the turn of the 20th century, historical documents1 tell us that Atlas and Delta rockets accounted for about 90% of U.S. commercial launches, each bringing about 8,000–10,000 lb into geosynchronous orbit. An Atlas launch cost about $80 million and the Delta about $60 million.
Elder Care in the United States

The aging of American society, particularly the emergence of an aging Baby Boomer population has prompted questions regarding how to provide care for this ever expanding group. In 2012 there were more than 43.1 million people aged 65 and older in the United States. Of the 43.1 million people aged 65 and older, 5.1 million, or about 13 percent, were aged 85 and older. As the increases in longevity and life expectancy of elderly persons expand, so too will their presenting chronic health conditions, which will also impact the need for elder care in the years ahead. Keywords: aging; caregiver; activities of daily living (ADL); instrumental activities of daily living (IADL); caregiving; elder care
Adaptation and resilience

Lessons learned, opportunities, and barriers to scaling up health adaptation were identified from evaluation reports and other materials from three multinational health adaptation projects covering 14 low- and middle-income countries and from qualitative data collected through a focus group consultation and interviews with key informants purposively selected for their expertise and role in health adaptation. The national projects aimed to increase resilience to climate-sensitive health outcomes by focusing on incremental improvements in policies and programs to address climate variability and by beginning to establish enabling environments for further adaptation. At this early stage in implementing health adaptation, projects have made limited plans for scaling up specific health adaptation activities outside of normal ministry approaches. Scaling up is needed to prepare for the challenges ahead, including by improving integrated surveillance and other programs to manage the health risks of a changing climate.
Absence Of The E3 Ubiquitin Ligase SKP2 Attenuates Notch-Induced T-Cell Leukemogenesis

Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in childhood, accounting for almost 30% of pediatric cancers. In pediatric T-cell acute lymphoblastic leukemia (T-ALL), around 30% of the children still undergo disease relapse, which is associated with poor prognosis. Hence, novel therapeutic strategies for the treatment of T-ALL are necessary, since conventional therapies still fail to cure a significant number of patients. Notch signaling contributes to the regulation of normal T-cells homeostasis, whereas oncogenic, activated form of Notch is present in the majority of the T-ALL cases. Previous studies in our laboratory demonstrated that Notch1 signaling induces transcriptional activation of SKP2, the F-box protein of the SCF E3-ubiquitin ligase complex. SKP2 targets the major cell cycle inhibitors, the CKIs p21Cip1, p27Kip1, p57Kip2 and p130, for proteasome-mediated degradation. Increased Skp2 expression accelerates cell cycle progression in hematopoietic cells, and its overexpression is frequently found in cancers, in particular lymphomas and leukemias, in which is associated with poor prognosis. We found that Skp2 expression is dynamically regulated during T-cell differentiation coinciding with the Notch expression pattern. Moreover, primary thymocytes cultured in vitro responded to Notch stimulation by the Delta1 ligand increasing their Skp2 expression and their cell cycle activity. As anticipated, we found that Skp2 expression is increased in T-ALL patient samples. Our hypothesis is that Notch activation promotes T-cell leukemogenesis by altering the cell cycle control through upregulation of SKP2. To better define the role of SKP2 in T-ALL, we analyzed the Skp2 expression in a murine model of Notch-induced T-cell leukemia. Mice transplanted with stem/progenitor cells transduced with the constitutive active form of Notch (ICN), developed T-ALL and died by week 12 after transplant. Analysis of T-ALL cells revealed a 5 fold upregulation of Skp2 expression compared to controls. Next, we tested whether SKP2 was required for T-ALL development. To this end, we evaluated leukemia development in mice transplanted with SKP2 deficient cells overexpressing ICN. Stem/progenitor cells derived from Skp2 +/+ , Skp2 +/- or Skp2 -/- mice were transduced with ICN and then transplanted into WT recipients. Loss of SKP2 significantly delayed the development of T-cell leukemia in transplanted mice and increased their survival by 60% at 12 weeks. Taken together, these results demonstrate a previously unrecognized role for SKP2 in the initiation and progression of T-ALL and its potential role as a therapeutic target. Disclosures: No relevant conflicts of interest to declare.
18 F-FDG-PET/CT for systemic staging of patients with newly diagnosed ER-positive and HER2-positive breast cancer.

This study assesses 18F–FDG-PET/CT for patients with newly diagnosed estrogen receptor-positive/human epidermal growth factor receptor-negative (ER+/HER2-) and human epidermal growth factor receptor-positive (HER2+) breast cancer. In this Institutional Review Board-approved retrospective study, our Healthcare Information System was screened for patients with ER+/HER2- and HER2+ breast cancer who underwent 18F–FDG-PET/CT prior to systemic or radiation therapy. The initial stage was determined from mammography, ultrasound, magnetic resonance imaging, and/or surgery.18F–FDG-PET/CT was evaluated to identify unsuspected extra-axillary regional nodal and distant metastases. The proportion of patients upstaged overall and stratified by stage and receptor phenotypes was calculated along with confidence intervals (CI). A total of 238 patients with ER+/HER2- and 245 patients with HER2+ who met inclusion criteria were evaluated. For patients with ER+/HER2-breast cancer, 18F–FDG-PET/CT revealed unsuspected distant metastases in 3/71 (4%) initial stage IIA, 13/95 (14%) stage IIB, and 15/57 (26%) stage III. For patients with HER2+ breast cancer, 18F–FDG-PET/CT revealed unsuspected distant metastases in 3/72 (4%) initial stage IIA, 13/93 (14%) stage IIB, and 13/59 (22%) stage III. The overall upstaging rate for IIB was 14% (95% confidence interval (CI): 9–20%). 18F–FDG-PET/CT revealed distant metastases in 14% (95% CI: 9–20%) of patients with stage IIB ER+/HER2- and HER2+ breast cancer, which is similar to upstaging rates previously seen in patients with stage IIB triple-negative breast cancer (15%, 95% CI: 9–24%). The detection of unsuspected distant metastases in these patients alters treatment and prognosis. NCCN guidelines should consider adding patients with stage IIB breast cancer for consideration of systemic staging with 18F–FDG-PET/CT at the time of initial diagnosis.
Applications of a Cognitively Informed Framework for the Design of Interactive Spatio-temporal Representations

Publisher Summary This chapter describes strategies that help cartographers design geovisualization interfaces and environments. It presents a framework, informed by cognitive science, for designing and developing modes of interaction for use in geovisualization environments. It also reviews some applications of that framework in the context of representing the temporal component of geographic data. The factors that guided in applications may assist both geovisualization users in understanding the limitations and opportunities presented by the tools they are using and geovisualization developers in the creation of tools. Because geovisualization tools are meant to be used in conjunction with one another, designing tools through testing them in isolation is often impractical. Therefore, designing tools is most successfully and efficiently accomplished by using a sound theoretical framework, informed by cognitive science and usability engineering. The design of effective geovisualization systems is based on the encouragement of creative and multiple perspectives on the data represented. This can be achieved by recognizing that users can be prompted to such perspectives with tools that conform to, but also alter, their internal representations of space, time, and the represented data.
Glioblastoma multiforme-derived extracellular vesicles drive normal astrocytes towards a tumour-enhancing phenotype.

Glioblastoma multiforme (GBM) is a devastating tumour with abysmal prognoses. We desperately need novel approaches to understand GBM biology and therapeutic vulnerabilities. Extracellular vesicles (EVs) are membrane-enclosed nanospheres released locally and systemically by all cells, including tumours, with tremendous potential for intercellular communication. Tumour EVs manipulate their local environments as well as distal targets; EVs may be a mechanism for tumourigenesis in the recurrent GBM setting. We hypothesized that GBM EVs drive molecular changes in normal human astrocytes (NHAs), yielding phenotypically tumour-promoting, or even tumourigenic, entities. We incubated NHAs with GBM EVs and examined the astrocytes for changes in cell migration, cytokine release and tumour cell growth promotion via the conditioned media. We measured alterations in intracellular signalling and transformation capacity (astrocyte growth in soft agar). GBM EV-treated NHAs displayed increased migratory capacity, along with enhanced cytokine production which promoted tumour cell growth. GBM EV-treated NHAs developed tumour-like signalling patterns and exhibited colony formation in soft agar, reminiscent of tumour cells themselves. GBM EVs modify the local environment to benefit the tumour itself, co-opting neighbouring astrocytes to promote tumour growth, and perhaps even driving astrocytes to a tumourigenic phenotype. Such biological activities could have profound impacts in the recurrent GBM setting. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Heads up: evolution of exaggerated head length in the minute litter bug genus Nannocoris Reuter (Hemiptera: Schizopteridae)

Evolutionary biologists have long been intrigued by exaggerated morphologies tied to sexual or natural selection. In insects, relatively few studies have investigated the evolution of such traits at the genus level and above and have used comparative phylogenetic methods to do so. We here investigate the interspecific evolution of head length in the minute litter bug genus Nannocoris Reuter based on the first phylogenetic hypothesis of the group (25 ingroup species, five gene regions, 3409 bp) and ancestral state reconstruction. Head lengths in this speciose genus range from approximately one sixth of the total body length to more than a quarter of the body length, while the head and mouthpart (rostrum) lengths are correlated. Different species therefore possess a markedly different reach of the rostrum when extended. The analyses show that head length evolution in Nannocoris is plastic, with head length elongations and reductions occurring in several clades, derived from ancestors with moderately elongated heads. Evidence is provided that exaggerated head lengths evolved through elongation of either the genal (pricei group) or the tip (arimensis group) region of the head. The biology of species in the genus Nannocoris is unknown, but given the lack of sexual dimorphism of head lengths, we speculate that head evolution in this genus may be driven by natural selection, potentially in the context of prey capture.
Analyzing occupational challenges through the lens of body and biography

ABSTRACTIntroduction: Occupational scientists are tasked with the responsibility of examining the relationship between occupational engagement and health, yet as occupations are explored in situ, these concepts only become more complex. For example, lifestyle trade-offs occur when individuals make conscious decisions between two competing sets of actions: actions taken in promotion of physical health versus actions in agreement with an identity-driven biography. In this study, these dilemmas are viewed as parts of an ongoing occupational challenge to balance physical health with subjective well-being in everyday life.Methods: Anselm Strauss’s concepts of body state and biographical moment are conceptualized as analytic tools to study dimensions within which occupation is performed. A descriptive, single-case analysis of a young adult diagnosed with diabetes is presented as an exemplar of how Strauss’s tools may be utilized.Results: Four themes emerged within the presented narrative: (1) by the book versus...
Baseline Psychosocial Characteristics Predict Frequency of Continuous Glucose Monitoring in Youth with Type 1 Diabetes.

Abstract Background: Consistent use of continuous glucose monitoring (CGM) has been associated with improved glycemic control in youth with type 1 diabetes (T1D). There are many barriers to device ...
Empirical Research of the Relevance among Analysts Coverage, Institutional Environment and Earnings Management

The paper uses discretionary accruals as the main substitute variable for earnings management, and analyzes the relationship between earnings management and analyst coverage and also concerns how the institutional environment impacts this relationship by 2,514 listed companies in Shanghai and Shenzhen Stoke Exchange in China during the Period of year 2004–2005. We find that a higher level of analysts coverage is related to less earnings management. We also find that analysts coverage is more negatively associated with earnings management for companies in weak institutional environment regions than for companies in strong institutional environment regions. The result suggests that analysts coverage has a substitute role to investor protection. Analysts coverage can play effective external governance role.
Chemo-Mechanical Consolidation of Clays: Analytical Solutions for a Linearized One-Dimensional Problem

Consolidation (and swelling) of clayey soils caused by change in chemistry of pore fluid is addressed. Such phenomena are caused by changes in the concentration of various species in the solution and result primarily from a stress-independent deformation of individual clusters, and from a mechanical weakening or strengthening of the clay solid matrix in the presence of stress. Second, transport of chemicals that involves concentration gradients induces additional driving forces of osmotic consolidation due to semipermeable membrane nature of clay. In this paper an extension of Terzaghi's model of the mechanical consolidation to incorporate chemical loading of soil is proposed. A linearized model is used to solve analytically two one-dimensional problems of consolidation of a homogeneous layer simulating a landfill liner with drained or undrained boundaries. The numerical results show a strong dependence of distribution of pore pressure on the chemical load and chemically induced settlements of soil to be comparable to the mechanical ones.
Mitral regurgitation surgery in heart failure due to ischemic cardiomyopathy: a 24-year experience.

BACKGROUND AND AIM OF THE STUDY: The long-term benefits of mitral regurgitation (MR) surgery in ischemic cardiomyopathy (ICM) are controversial. Herein are reported the results and trends of this surgical approach over the past 24-year period. METHODS: Patients were identified in refractory heart failure due to ICM with NYHA functional class III/IV symptoms, left ventricular ejection fraction < or =35% and MR who underwent mitral surgery between 1979 and 2002. The early and late outcomes were analyzed and compared for the different surgical eras classified as early (1979 to 1986), middle (1987 to 1994), and late (1995 to 2002). RESULTS: Mitral repair (70%) and replacement (30%) were performed with coronary artery bypass grafting (CABG) (85%) and tricuspid valve repair (7%) in 179 patients (mean age 68 +/- 9 years). The overall one- and five-year survival rates were 84% and 51%, respectively, and the corresponding freedom from recurrent MR after repair 86% and 55%. An increasing number of patients underwent surgery from the early to the late era. Whereas patients more frequently presented with cardiomegaly and renal failure during the early era, they were older, more often had prior CABG, concurrent tricuspid regurgitation and underwent mitral repair during the late era. A progressive improvement was observed in operative mortality from the early to late eras (24%, 11% and 5%, respectively; p = 0.009), and also for the one-and five-year survivals (68%, 85% and 89%; 46%, 43% and 57%, respectively; p = 0.06). Preoperative renal failure and concomitant tricuspid valve repair were predictors of late mortality. CONCLUSION: During the past 24 years, operative results for the surgical correction of MR in patients with heart failure due to ICM have steadily improved. Currently, while the early and mid-term survival are satisfactory the long-term survival is limited, especially when heart failure is complicated by renal failure and severe tricuspid regurgitation.
Views on the nature of the gene, the structure and function of the chromosome, and heterochromatic heredity.

Goldschmidt’s early acceptance of the classical definition of genes, as discrete, hereditary units, linearly arranged on chromosomes (derived from the Mendelian genetic analyses of the Morgan school) changed eventually to outright rejection1,2 when he considered the facts regarding position effects discovered by Sturtevant in 19253 in which physical rearrangements among the chromosomes lead to different activities of the same gene. He proposed an alternative model in 1938 (see below) in which the chromosome was the basic functional unit of heredity and any breakage or rearrangement within the chromosome would result in a change in the genetic functioning of the chain-like molecule as a whole.
Cellular Regulation in Hematopoiesis

The hematopoietic system, which includes the reticuloendothelial system and the immune system, maintains blood cells in circulatory and recirculatory phases and supports large-scale cell migration to specific, diverse, and distant tissues where rapid cell turnover, cell differentiation, and cell functions occur (Metcalf and Moore, 1971). Regulation in this system is intricate, extensive, and efficient, effected through the actions of hormones and other systemic factors, local humoral factors, and cell surface molecules on blood cells, stromal cells, and the vasculature, which respond in tight sequences.
Arthrography of the hand and wrist.

SUMMARY Arthrography of the wrist and hand is easy to perform, but accurate diagnosis requires meticulous technique and thorough knowledge of anatomy, pathology, and imaging principles. Wrist arthrography is usually performed to assess pain or instability after trauma; a complete examination usually requires injection of the RC, midcarpal, and distal radioulnar joints. Abnormalities that can be detected include interosseous ligament tears, capsular tears, triangular fibrocartilage perforations and separations, cartilaginous defects, loose bodies, and synovial abnormalities including adhesive capsulitis. Arthrography can also be useful in the evaluation of masses and scaphoid nonunion. Finger arthrography can demonstrate capsular injury, ligament tears, tendon derangement, volar plate disruption, cartilage abnormalities, fibrous ankylosis, synovial abnormalities, and ganglia. Tenography is seldom performed; this technique can delineate synovial abnormalities and can be used to evaluate tendon subluxation.
Sleep in Aging

The ability to maintain restful sleep decreases with age but is likely independent of age itself. Medical and psychiatric disorders, medication, circadian rhythm changes, and primary sleep disorders (such as sleep-disordered breathing, restless leg syndrome/periodic limb movement in sleep, and REM behavior disorder) all contribute to older adults’ decreased ability to maintain a full night’s sleep. Each of these disorders is treatable, and treatment should never be withheld because of age or because of assumed noncompliance.