cssi/SciSciGPT-SciSciNet huggingface dataset:
RNA Interference in the Pathogenic Fungus Cryptococcus neoformans

Cryptococcus neoformans is a pathogenic fungus responsible for serious disease in immunocompromised individuals. This organism has recently been developed as an experimental system, with initiation of a genome project among other molecular advances. However, investigations of Cryptococcus are hampered by the technical difficulty of specific gene replacements. RNA interference, a process in which the presence of double-stranded RNA homologous to a gene of interest results in specific degradation of the corresponding message, may help solve this problem. We have shown that expression of double-stranded RNA corresponding to portions of the cryptococcal CAP59 and ADE2 genes results in reduced mRNA levels for those genes, with phenotypic consequences similar to that of gene disruption. The two genes could also be subjected to simultaneous interference through expression of chimeric double-stranded RNA. Specific modulation of protein expression through introduction of double-stranded RNA thus operates in C. neoformans, which is the first demonstration of this technique in a fungal organism. Use of RNA interference in Cryptococcus should allow manipulation of mRNA levels for functional analysis of genes of interest and enable efficient exploration of genes discovered by genome sequencing.
Distinct dissolved organic matter sources induce rapid transcriptional responses in coexisting populations of Prochlorococcus, Pelagibacter and the OM60 clade

A considerable fraction of the Earth's organic carbon exists in dissolved form in seawater. To investigate the roles of planktonic marine microbes in the biogeochemical cycling of this dissolved organic matter (DOM), we performed controlled seawater incubation experiments and followed the responses of an oligotrophic surface water microbial assemblage to perturbations with DOM derived from an axenic culture of Prochlorococcus, or high-molecular weight DOM concentrated from nearby surface waters. The rapid transcriptional responses of both Prochlorococcus and Pelagibacter populations suggested the utilization of organic nitrogen compounds common to both DOM treatments. Along with these responses, both populations demonstrated decreases in gene transcripts associated with nitrogen stress, including those involved in ammonium acquisition. In contrast, responses from low abundance organisms of the NOR5/OM60 gammaproteobacteria were observed later in the experiment, and included elevated levels of gene transcripts associated with polysaccharide uptake and oxidation. In total, these results suggest that numerically dominant oligotrophic microbes rapidly acquire nitrogen from commonly available organic sources, and also point to an important role for carbohydrates found within the DOM pool for sustaining the less abundant microorganisms in these oligotrophic systems.
Karl Llewellyn and the Origins of Contract Theory

Karl Llewellyn was America's leading legal realist, academic law reformer, and Sales Law theorist. Though extensive anlyses exist of Llewellyn's performance in the first two of these roles exist, no studies use his original work to evaluate his performance in the third role. Citation analysis reveals that many of the ideas in these articles retain value today, but modern scholars commonly infer his views on contract theory from other sources. This essay is predicated on the notion that Llewellyn's theory is best recovered from the articles that originally set it out rather than from later partial references by Llewellyn or from UCC drafts that commonly reflected both the work of the author and what it was politically acceptable to say. (forthcoming, The Jurisprudential Foundations of Corporate and Commercial Law, eds., Krause and Walt, Cambridge). Contact the Law and Economics Program at Boalt Hall, UC Berkeley, Berkeley, CA 94720 for a copy of this paper.
Going Beyond the Limits of the Terminal Model

The terminal model still is the most widely used model for describing binary copolymerization processes. The Mayo—Lewis equation (1.9) is frequently applied at even high conversions. At least 90% of known copolymerization systems can be adequately represented by the terminal mode1.450
Multiplexed infrared photodetection using resonant radio-frequency circuits

We demonstrate a room-temperature semiconductor-based photodetector where readout is achieved using a resonant radio-frequency (RF) circuit consisting of a microstrip split-ring resonator coupled to a microstrip busline, fabricated on a semiconductor substrate. The RF resonant circuits are characterized at RF frequencies as function of resonator geometry, as well as for their response to incident IR radiation. The detectors are modeled analytically and using commercial simulation software, with good agreement to our experimental results. Though the detector sensitivity is weak, the detector architecture offers the potential for multiplexing arrays of detectors on a single read-out line, in addition to high speed response for either direct coupling of optical signals to RF circuitry, or alternatively, carrier dynamics characterization of semiconductor, or other, material systems.
Long-term management of differentiated thyroid cancer.

The goal of surveillance and management of patients with thyroid cancer who are at low risk for recurrence is to avoid unnecessary testing, radiation exposure, and cost, whereas the goal for high-risk patients is to treat aggressively for cure or maximal palliation. Thyroglobulin measurements, chest radiograph, and neck ultrasonography are useful in following patients with little risk for recurrence or metastases. In patients with more aggressive disease, iodine-131 total body scanning, computed tomography or magnetic resonance imaging, and occasionally bone scans also may be needed. Aggressive treatment of recurrences or metastases with surgery, radioiodine, external radiation therapy, or chemotherapy will prolong life expectancy.
Exploring the Design Space of an Energy-Efficient Accelerator for the SKA1-Low Central Signal Processor

The Square Kilometre Array (SKA) will be the biggest radio telescope ever built, with unprecedented sensitivity, angular resolution, and survey speed. Collectively, the SKA’s antennas are expected to gather exabytes of data per second and store one petabyte of data every day, requiring exa operations per second for the processing. This paper focuses on the SKA1-Low, the SKA’s aperture-array instrument consisting of 131,072 antennas that will be built in the first phase of the deployment of the project. In particular, our work explores the design of a custom architecture for the central signal processor (CSP) of the SKA1-Low. The CSP processes digitized samples sent by antennas receiving extra-terrestrial radio-frequency signals between 50 and 350 MHz. We describe the challenges in building the CSP, and present a quantitative study for the implementation of a custom hardware architecture for executing the main CSP algorithms. By taking advantage of emerging 3D-stacked-memory devices and by exploring the design space for a 14-nm implementation, we estimate a power consumption of 9.62 W for processing all channels of a sub-band and an energy efficiency at application level of up to 312 GFLOPS/W for our architecture.
Highly Aligned Block Copolymer Thin Films by Synergistic Coupling of Static Graphoepitaxy and Dynamic Thermal Annealing Fields

Directed self-assembly of cylinder forming block copolymer (c-BCP) thin films via a dynamic thermal field on multidimensional symmetric graphoepitaxy channels is reported. A synergy of dynamic thermal and static boundary fields induces highly aligned c-BCP cylinders inside the channels with a power law dependence of orientational order parameter f, on trench width, f ∼ d–0.3, analogous to dual-field alignment of semiconducting metals and liquid crystals on graphoepitaxy surfaces, f′ ∼ d–1. Static thermal annealing of identical films in a vacuum oven for several days fails to produce comparable results. Furthermore, we demonstrate global c-BCP cylinder alignment over mesas and trenches by tuning the synergy between the dynamic thermal field and asymmetry of the graphoepitaxy static field.
Bacteriologic study of middle ear infections

This investigation of acute and chronic otitis media was approached from a different standpoint than any previously reported. Although interested in the relative prevalence of the different organisms, the primary object was to determine, if possible, factors contributing to chronicity and impaired hearing. It seemed that by studying a certain number of individual cases over a long period of time, with a close correlation of the clinical and bacteriologic findings, there might be some indication of the factors involved. Furthermore, the source of the ear infection was another point under investigation.
Small gene, big number, many effects

In this issue of Blood , Eisfeld and colleagues present strong evidence that miR-3151 and the host gene BAALC (brain and acute leukemia, cytoplasmic) concomitantly affect the outcome of patients with cytogenetically normal acute myeloid leukemia (CN-AML) by influencing significant signaling pathways
Review: Mechanical and manual CPR do not differ for survival or neurologic outcome in out-of-hospital cardiac arrest

Source Citation Bonnes JL, Brouwer MA, Navarese EP, et al. Manual cardiopulmonary resuscitation versus CPR including a mechanical chest compression device in out-of-hospital cardiac arrest: a compr...
Hypothermia attenuates β1 integrin expression on extravasated neutrophils in an animal model of meningitis

Brain injury in meningitis occurs in part as a consequence of leukocyte migration and activation. Leukocyte integrins are pivotal in the inflammatory response by mediating adhesion to vascular endothelium and extracellular matrix proteins. We have demonstrated that moderate hypothermia early in the course of meningitis decreases leukocyte sequestration within the brain parenchyma. This study examines whether hypothermia alters neutrophil integrin expression in a rabbit model of bacterial meningitis. Prior to the induction of meningitis, peripheral blood samples were obtained and the neutrophils isolated. Sixteen hours after inducing group B streptococcal meningitis, animals were treated with antibiotics, IV fluids, and mechanically ventilated. Animals were randomized to hypothermia (32–33°C) or normothermia conditions. After 10 hours of hypothermia or normothermia, neutrophils were isolated from the blood and cerebral spinal fluid (CSF), stained for β1 and β2 integrins, and analyzed using flow cytometry. Cerebral spinal fluid neutrophil β1 integrin expression was significantly decreased in hypothermic animals. Beta-1 integrins can assume a higher affinity or "activated" state following inflammatory stimulation. Expression of "activated" β1 integrins was also significantly decreased in hypothermic animals. Beta2 CSF neutrophil integrin expression was decreased in hypothermic animals, but failed to reach significance. These data suggest hypothermia may attenuate extravasated leukocyte expression of both total and "activated" β1 integrins.
Soil compaction from human trampling, biking, and off-road motor vehicle activity in a blackbrush ( Coleogyne ramosissima ) shrubland

Soil compaction from human trampling, biking, and off-road motor vehicle traffic was quantitatively investigated in a blackbrush ( Coleogyne ramosissima ) shrubland in Kyle Canyon of the Spring Mountains in southern Nevada. A significant difference was detected in soil compaction, bulk density, and percent pore space at a particular frequency of visits in each of 4 disturbance types. On average a single vehicle pass was equivalent to 10 human footprints. Ten and 100 footprints were equivalent to 1 motorcycle pass and 10 vehicle passes, respectively. Soil compaction is a product of increased bulk density and decreased pore space. The degree of soil compaction is a function of disturbance type and visit frequency when examining these 2 factors independently. However, interactive effects of disturbance type and visit frequency on soil bulk density, compaction, and percent pore space were not significantly different. The greatest effects occurred during the first few passes, with changes per pass decreasing as the number of passes increased in all 4 trails. Results of this study suggest that the effects of hiking and biking slowly increase over time relative to the effects of motor vehicle traffic in the Coleogyne shrubland of Kyle Canyon in southern Nevada.
CT of severe inner ear anomalies, including aplasia, in a case of Wildervanck syndrome.

The authors describe some unusual features of a case of Wildervanck syndrome (male patient and facial nerve paralysis), and present and discuss CT images of inner ear aplasia
A clinic-based pilot intervention to enhance diabetes management for elderly Hispanic patients.

Background and objectives: Successful diabetes self-management requires behavioral and lifestyle changes. However, low-income patients may face challenges related to poverty that make it difficult to engage in lifestyle changes. We piloted an intervention designed to help older, low-income, Hispanic, patients with diabetes access free or low-cost community resources to enhance diabetes self-management. Results from this pilot intervention are reported. Design and Methods: Patients were recruited at baseline to complete surveys assessing diabetes self-care activities, diabetes self-efficacy, and general self-efficacy. Volunteers were trained by a clinic social worker to help patients identify needs and make referrals to local community resources (e.g., housing, transportation, food, clothing, dental and prescription services, employment, or family social services). Identical surveys were administered at 3-month follow-up. Results: 28 patients were recruited at baseline and 18 patients completed the follow-up assessment. No significant changes in diabetes care and self-efficacy were detected. All patients requested at least one referral to a community resource. The most common requests were for low-cost dental clinics, food assistance, and housing support. At follow-up, nine (50%) patients contacted their given referrals. Conclusions: The need for assistance with basic social services is high in this population. The rate of referral uptake (50%) is high for a relatively low intensity intervention. Since the completion of the pilot, the program has trained 21 volunteers and helped over 220 patients in a primary care clinic. Using a volunteer model and creating connections to existing community resources is a cost-conscious way to deliver needed services to patients.
Communication—Sol-Gel Synthesized Magnesium Vanadium Oxide, MgxV2O5 · nH2O: The Role of Structural Mg2+ on Battery Performance

Magnesium intercalated vanadium oxide xerogels, Mg0.1V2O5 · 2.35H2O and Mg0.2V2O5 · 2.46H2O were synthesized using an ion removal sol gel strategy. X-ray diffraction indicated lamellar ordering with turbostratic character. X-ray absorption spectroscopy indicated greater distortion of the vanadium-oxygen coordination environment in Mg0.2V2O5 · 2.46H2O. Elemental analysis after cycling in Li+ or Mg2+ based electrolytes revealed that the magnesium content was unchanged, indicating structural Mg2+ are retained. Furthermore, the Mg0.1V2O5 · 2.35H2O material displayed high voltage, energy density, and discharge/charge efficiency, indicating promise as a cathode material for future magnesium based batteries.
Medial tibial "spackling" to lessen chronic medial tibial soft tissue irritation.

Abstract We describe a unique, utilitarian reconstructive treatment option known as tibial "spackling" for chronic, localized medial joint line pain corresponding with progressive radiographic peripheral medial tibial bone loss beneath a well-fixed revision total knee arthroplasty tibial baseplate. It is believed that this localized pain is due to chronic irritation of the medial capsule and collateral ligament from the prominent medial edge of the tibial component. In the setting of failed nonoperative treatment, our experience with utilizing bone cement to reconstruct the medial tibial bone defect and create a smooth medial tibial surface has been successful in eliminating chronic medial soft tissue irritation.
The effects of optimism and gratitude on adherence, functioning and mental health following an acute coronary syndrome

Abstract Objective This study examined the effects of optimism and gratitude on self-reported health behavior adherence, physical functioning and emotional well-being after an acute coronary syndrome (ACS). Methods Among 156 patients, we examined associations between optimism and gratitude measured 2 weeks post-ACS and 6-month outcomes: adherence to medical recommendations, mental and physical health-related quality of life (HRQoL), physical functioning, depressive symptoms and anxiety. Multivariable linear regression models were used, controlling for increasing levels of adjustment. Results Optimism [ β =.11, standard error (S.E.)=.05, P =.038] and gratitude ( β =.10, S.E.=.05, P =.027) at 2 weeks were associated with subsequent self-reported adherence to medical recommendations (diet, exercise, medication adherence, stress reduction) at 6 months in fully adjusted models. Two-week optimism and gratitude were associated with improvements in mental HRQoL (optimism: β =.44, S.E.=.13, P =.001; gratitude: β =.33, S.E.=.12, P =.005) and reductions in symptoms of depression (optimism: β =−.11, S.E.=.05, P =.039; gratitude: β =−.10, S.E.=.05, P =.028) and anxiety (optimism: β =−.15, S.E.=.05, P =.004; gratitude: β =−.10, S.E.=.05, P =.034) at 6 months. Conclusion Optimism and gratitude at 2 weeks post-ACS were associated with higher self-reported adherence and improved emotional well-being 6 months later, independent of negative emotional states. Optimism and gratitude may help recovery from an ACS. Interventions promoting these positive constructs could help improve adherence and well-being.
Women’s agency and its relationship to current contraceptive use in lower- and middle-income countries: A systematic review of the literature

Research shows a positive relationship between women's empowerment and reproductive health. Yet we know little about the quantitative relationship between women's agency and contraceptive use. We conducted a systematic review of peer-reviewed literature assessing the link between women's decision-making and freedom of movement with their contraceptive use in lower- and middle-income countries. Of 102 articles that met the initial screening criteria, 12 met all inclusion and exclusion criteria. Of the 12 included studies, consistently positive associations with contraceptive use were found in those that measured decision-making and freedom of movement as separate constructs. Composite measures had a less clear relationship with contraceptive use. In conclusion, women's agency is associated with women's contraceptive use in lower- and middle-income countries. However, the relationship is sensitive to how agency and its components are measured. Our review suggests the need for consistent validation of scales for women's agency as well as more rigorous research using standardised and validated scales, when possible. Longitudinal and intervention studies in lower- and middle-income countries will be useful for understanding the causal impact of women's agency on contraceptive use, and will help to inform policies and programmes to increase contraceptive use in these settings.
Long-Term Mortality in Diabetic Patients with Tractional Retinal Detachments.

Purpose To determine the long-term, all-cause mortality rate of diabetic patients requiring vitrectomy surgery for tractional retinal detachment (TRD). Design Institutional review board–approved, retrospective, comparative study. Participants Four hundred eyes of 316 patients undergoing vitrectomy surgery from 2005 to 2015. Methods Long-term, all-cause mortality rates in the study population were compared with mortality in a historical control group of diabetic patients with minimal to no retinopathy. Subgroup analysis was done based on bilaterality of TRD and initial vision. Other concurrent associated diabetic comorbidities, use of insulin, and type 1 diabetes are also reported. Data were used to create Kaplan-Meier survival curves. Main Outcome Measure Long-term, all-cause mortality rate of diabetic patients undergoing vitrectomy surgery from 2005 to 2015. Results Mean survival after diagnosis of TRD requiring vitrectomy surgery was 2.7 years (median, 2 years; range, 0.17–9.00 years). Kaplan-Meier survival curve analysis revealed a 48.7% (154/316 patients) long-term, all-cause mortality rate for diabetics requiring vitrectomy surgery for TRDs at 10 years, compared with a mean 2% long-term, all-cause mortality rate in diabetics with minimal to no retinopathy. Subgroup analysis of those patients with bilateral TRDs requiring surgery revealed a 48.9% mortality rate with a mean survival after diagnosis of TRD of 2.6 years (median, 2 years; range, 0.25–9.00 years). Those patients with count fingers or worse vision in one or both eyes at diagnosis had a 52.0% mortality rate ( P Conclusions In our population, diabetic patients with TRDs requiring surgery have a 48.7% long-term, all-cause mortality rate, with those presenting with count fingers or worse vision having a higher mortality rate. Diabetic TRD requiring vitrectomy surgery is a marker of poor long-term survival.
History of Maltreatment in Childhood and Subsequent Parenting Stress in At-Risk, First-Time Mothers: Identifying Points of Intervention During Home Visiting

Home visiting is an effective preventive intervention that can improve parenting outcomes for at-risk, new mothers, thereby optimizing subsequent child development. A history of maltreatment in childhood is common in mothers participating in home visiting, yet the extent to which such a history is related to parenting outcomes during home visiting is unknown. The current study evaluated whether mothers with a history of maltreatment in childhood respond less favorably to home visiting by examining the direct and indirect pathways to subsequent parenting stress, a key parenting outcome affecting child development. First-time mothers (N = 220; age range = 16-42) participating in one of two home visiting programs, Healthy Families America or Nurse Family Partnership, were evaluated at enrollment and again at 9-and 18-month post-enrollment assessments. Researchers administered measures of maternal history of maltreatment in childhood, depressive symptoms, social support, and parenting stress. Maternal history of maltreatment in childhood predicted worsening parenting stress at the 18-month assessment. Mediation modeling identified two indirect pathways, one involving social support at enrollment and one involving persistent depressive symptoms during home visiting, that explained the relation between a history of maltreatment in childhood and parenting stress at the 18-month assessment. Ways to improve the preventive effects of home visiting for mothers with a history of maltreatment in childhood through the identification of relevant intervention targets and their ideal time of administration are discussed.
A 500 kHz, 3.3 kW boost PFC with low loss coupled auxiliary ZVT circuit

The paper presents a low-loss auxiliary circuit in a power factor correction (PFC) circuit to achieve zero voltage transition and hence improving the efficiency and operating frequency. The high dynamic energy generated in the switching node during turn-on is diverted by providing a parallel path through a coupled auxiliary inductor and a transistor placed across the main inductor. The auxiliary devices operate with soft-switching at both turn-on and turn-off instances and this addition has no effect on the control of the main PFC circuit. Using a coupled inductor reduces the losses in the auxiliary circuit in addition to the inherent loss savings in the main PFC switch. The paper discusses the theoretical analysis, operating principles and design of the proposed scheme in detail and validated with an hardware showing experimental results on a 3.3 kW/ 500 kHz PFC prototype.
Bisexual-Specific Minority Stressors, Psychological Distress, and Suicidality in Bisexual Individuals: the Mediating Role of Loneliness

Bisexual individuals are at higher risk for poor mental health outcomes compared to heterosexual as well as lesbian and gay individuals and experience minority stressors, such as discrimination, from both heterosexual and sexual minority communities. However, there is little research examining the negative effects of bisexual-specific minority stressors on bisexual individuals’ mental health as well as psychological factors that might help explain minority stressors’ deleterious effects. This research examined the effects of distal minority stressors (i.e., anti-bisexual experiences from both heterosexual as well as lesbian and gay people) and proximal stressors (i.e., internalized heterosexism and sexual orientation concealment) on psychological distress and suicidality among bisexual adults (N = 503). Building on the relational framing of the minority stress model, we also tested one relational factor (i.e., loneliness) as a mediator of the associations between distal and proximal minority stressors and poor mental health (i.e., psychological distress and suicidality). Structural equation modeling analyses were used to test the mediating effects of loneliness on the associations between minority stressors and psychological distress and suicidality. Although distal and proximal minority stressors were not associated with each other, loneliness mediated the effects of distal and proximal minority stressors on psychological distress and suicidality. The results of this study underscore the importance of targeting bisexual-specific minority stressors as well as loneliness in preventive interventions to improve the mental health of bisexual individuals.
China During an Era of Change

It was into violent conflicts between the Chinese and Japanese, and Nationalists and Communists, that McCarthy entered China. He arrived in Shanghai in 1943, undergoing internment under Japanese occupation. Charles McCarthy was among those Californians sent to Zikawei, where he joined French and Chinese Jesuits, taught as a faculty member in the Society’s schools, served as vice-rector of the theologate, and then as vice-superior of the California Jesuits in China. From 1948 to 1949 he was editor of Catholic Review, Assistant Director of the Hua Ming News Service, and directed radio work. After the establishment of the People’s Republic of China on October 1, 1949, the Communist party moved aggressively against the Church, inaugurating anti-Christian campaigns. Letters home included increasingly traumatic accounts.
Heart Failure: Impact of Genetics and Genomics

Abstract This chapter focuses on the impact of genetics and genomics on heart failure. Part one outlines how genetics provides insight to the underpinnings of heart failure. Part two highlights where genetics and genomics has impacted (or has the potential to impact) the management of patients with heart failure. Part two is divided into four main sections that include the impact of genetics and genomics on susceptibility, diagnosis, prognosis, and pharmacogenomics.
Quantized deep neural networks for energy efficient hardware-based inference

Deep Neural Networks (DNNs) have been adopted in many systems because of their higher classification accuracy, with custom hardware implementations great candidates for high-speed, accurate inference. While progress in achieving large scale, highly accurate DNNs has been made, significant energy and area are required due to massive memory accesses and computations. Such demands pose a challenge to any DNN implementation, yet it is more natural to handle in a custom hardware platform. To alleviate the increased demand in storage and energy, quantized DNNs constrain their weights (and activations) from floating-point numbers to only a few discrete levels. Therefore, storage is reduced, thereby leading to less memory accesses. In this paper, we provide an overview of different types of quantized DNNs, as well as the training approaches for them. Among the various quantized DNNs, our LightNN (Light Neural Network) approach can reduce both memory accesses and computation energy, by filling the gap between classic, full-precision and binarized DNNs. We provide a detailed comparison between LightNNs, conventional DNNs and Binarized Neural Networks (BNNs), with MNIST and CIFAR-10 datasets. In contrast to other quantized DNNs that trade-off significant amounts of accuracy for lower memory requirements, LightNNs can significantly reduce storage, energy and area while still maintaining a test error similar to a large DNN configuration. Thus, LightNNs provide more options for hardware designers to trade-off accuracy and energy.
A Modularity View of Alliance Portfolio Configuration and Organizational Ambidexterity

I develop a modularity view of alliance portfolio configuration and organizational ambidexterity, or the simultaneous pursuit of exploitative and exploratory innovation. Drawing from the conceptual...
Designing Library Components

This chapter presented various ways designs can be generated in Quartus II. At the same time we presented several utility hardware structures. The structures presented are put in a library to be accessible by designs of the following chapters. On the use of Quartus II, this chapter showed definition and usage of megafunctions, defining and using HDL blocks, using existing components in a design, and editing and customizing component symbols. On the organizational side, this chapter showed how a library of parts could be generated and tested. Finally, from digital design point of view, this chapter showed small, but useful, parts that many designs can use.
Mapping the Learning Engram in a “Model” System, the Mollusk Pleurobranchaea californica

In recent years, several laboratories have begun to employ relatively simple, invertebrate organisms for the study of the cellular basis of complex behavioral phenomena, in a paradigm that has become known as the “model systems” approach. The term is somewhat of a misnomer, since most experimental preparations, simple and complex, serve as models of fundamental biological principles that are presumed to apply more broadly. The term is nonetheless useful, in that it reflects two of the basic assumptions implicit in the model systems paradigm. The first of these assumptions is that evolution has been conservative in its solution to general biological problems, i.e., that “models” may in fact be useful tools toward a broader understanding. The second assumption is that complex behavioral phenomena are indeed accessible to reductionist analysis at the cellular level, i.e., that the formulation of feasible cellular models of behavior is possible.
Quantification of desmosine and isodesmosine using MALDI-ion trap tandem mass spectrometry

Desmosine (Des) and isodesmosine (Isodes), cross-linking amino acids in the biomolecule elastin, may be used as biomarkers for various pathological conditions associated with elastin degradation. The current study presents a novel approach to quantify Des and Isodes using matrix-assisted laser desorption ionization (MALDI)-tandem mass spectrometry (MS2) in a linear ion trap coupled to a vacuum MALDI source. MALDI-MS2 analyses of Des and Isodes are performed using stable-isotope-labeled desmosine d4 (labeled-Des) as an internal standard in different biological fluids, such as urine and serum. The method demonstrated linearity over two orders of magnitude with a detection limit of 0.02 ng/μL in both urine and serum without enrichment prior to mass spectrometry, and relative standard deviation of < 5%. The method is used to evaluate the time-dependent degradation of Des upon UV irradiation (254 nm) and found to be consistent with quantification by 1H NMR. This is the first characterized MALDI-MS2 method for quantification of Des and Isodes and illustrates the potential of MALDI-ion trap MS2 for effective quantification of biomolecules. The reported method represents improvement over current liquid chromatography-based methods with respect to analysis time and solvent consumption, while maintaining similar analytical characteristics.
Bubble-bubble pinch-off in symmetric and asymmetric microfluidic expansion channels for ordered foam generation.

By incorporating the techniques of geometrically mediated splitting and bubble–bubble breakup, the present work offers a novel microfluidic foam generation system via production of segregated, mono- or bidisperse bubbles at capacities exceeding 10 000 bubbles per second. Bubble–bubble pinch-off is precise at high capillary numbers (Ca > 0.065), generating monodisperse or bidisperse daughter bubbles for a symmetric or an asymmetric expansion respectively. Bi- or tridisperse foam is produced as pinch-off perfectly alternates such that the system contains twice the number of fragmented bubbles as intact bubbles. A relationship between the upstream bubble extension and the capillary number demarcates the different regimes of pinch-off defined with respect to frequency and precision: non-splitting, irregular, polydisperse, and monodisperse (or bidisperse for an asymmetric expansion). For tridisperse foam generation via a fixed asymmetric expansion geometry, the wall bubble confinement can be tuned to adjust the pinch-off accuracy in order to access a spectrum of fragmented bubble size ratios. The simplicity in operating and characterizing our system will enable studies on dynamic bubble interactions and ordered, wet foam applications.
Impacts of Wearable Augmented Reality Displays on operator performance, Situation Awareness, and communication in safety-critical systems.

Abstract Wearable Augmented Reality Displays (WARDs) present situated, real-time information visually, providing immediate access to information to support decision making. The impacts of WARD use on operator performance, Situation Awareness (SA), and communication in one safety-critical system, marine transportation, were examined in a real-time physical simulator. WARD use improved operator trackkeeping performance, the practice of good seamanship, and SA, although operator responsiveness decreased. WARD users who used more closed-loop communication and information sharing showed improved threat avoidance, suggesting that operators can avoid accidents and failure through WARD use that promotes sharing and confirming information. WARD use also promoted information source diversity, a means of developing requisite variety. These operational impacts are important in safety-critical settings where failures can be catastrophic.
Non-locality in Granular Flow: Phenomenology and modeling approaches

This paper reviews the emergence of non-local flow phenomena in granular materials and discusses a range of models that have been proposed to integrate an intrinsic length-scale into granular rheology. The frameworks discussed include micro-polar modeling, kinetic theory, three particular order-parameter-based models, and strongly non-local integral-based models. An extensive commentary is included discussing the current capabilities of these existing models as well as their implementational ease, physical motivation, and breadth of predictive ability.
Avascular Necrosis(AVN) and Surgical Intervention In Pediatric Acute Lymphoblastic Leukemia(ALL): A Retrospective Cohort Analysis From The Pediatric Health Information Systems (PHIS)

Cure rates for acute lymphoblastic leukemia (ALL) have improved dramatically, but the incidence of avascular necrosis (AVN) has increased over the past decade. No national administrative data on the incidence of AVN or surgical therapies for AVN exist. We sought to define the incidence of AVN and AVN surgical interventions after treatment for ALL in a national administrative data set. The Pediatric Health Information System (PHIS) is an administrative database including ICD-9 discharge diagnosis, procedure codes, and billing data for daily resource utilization from 43 free standing pediatric hospitals in the US. This study identified patients with an associated ICD-9 code for AVN (733.4X) in a cohort previously established by our group to have newly diagnosed ALL. Between January 1999 and September 2011 242(2.25%), of the 10,729 patients in the ALL cohort had at least one admission with AVN with a mean time of 1.6 years from first ALL treatment until a hospital admission with an associated AVN diagnosis. [Table 1][1] compares demographic and treatment characteristics between ALL patients with and without AVN diagnosis. Age 10-18.99 years and prednisone exposure during ALL induction were associated with increased incidence of AVN. Dexamethasone exposure was associated with a decreased incidence of AVN. AVN diagnosis was associated with a statistically significant increase in mortality. The rate of surgical intervention was 13.7%. The type and location of surgical intervention are reported in [Table 2][2]. View this table: Table 1 Demographics View this table: Table 2 Surgical Interventions during first AVN admission To our knowledge, this is the first report using a national administrative database to determine the incidence of AVN in ALL. As expected, age was associated with AVN risk. The association of increased in-hospital mortality was unexpected and warrants further study. Surgical interventions typically involved lower extremity procedures. Work is ongoing to define the rates of subsequent surgical procedures and complication rates. These data demonstrate the feasibility of using administrative data to study surgical interventions for patients with AVN. Disclosures: Rheingold: Novartis: Research Funding. [1]: #T1 [2]: #T2
Debugging: The key to unlocking the mind of a novice programmer?

Novice programmers must master two skills to show lasting success: writing code and, when that fails, the ability to debug it. Instructors spend much time teaching the details of writing code but debugging gets significantly less attention. But what if teaching debugging could implicitly teach other aspects of coding better than teaching a language teaching debugging? This paper explores a new theoretical framework, the Theory of Applied Mind for Programming (TAMP), which merges dual process theory with Jerome Bruner’s theory of representations to model the mind of a programmer. TAMP looks to provide greater explanatory power in why novices struggle and suggest pedagogy to bridge gaps in learning. This paper will provide an example of this by reinterpreting debugging literature using TAMP as a theoretical guide. Incorporating new view theoretical viewpoints from old studies suggests a “debugging-first” pedagogy can supplement existing methods of teaching programming and perhaps fill some of the mental gaps TAMP suggests hamper novice programmers.
Thermo-optical Tuning Effects in Photonic Nano-AFM Probe

Thermo-optic tuning manifests in nanoscale photonic AFM transducers at modest optical powers. We derive a frequency and power dependent transfer function, enabling dynamic data interpretation in high-power and high-sensitivity thermo-optical-nonlinear-regime. It paves the way for further improvement of the sensitivity of photonic sensing.
Comparisons of emotional health by diagnosis among women with early stage gynecological cancers.

Abstract Objective To assess self-reported emotional health in a cohort of women with early stage gynecologic cancers and to explore differences based on primary cancer type. Methods We analyzed survey data from a cohort study of gynecological cancer patients treated at an academic cancer center. Measures of emotional health included cancer-related quality of life, distress, depression, anxiety, posttraumatic stress disorder (PTSD), and posttraumatic growth. Univariate and multivariate linear regression models examined differences in emotional health measures by primary cancer site. Potential confounders considered for inclusion in the final models were age, stage, education, income, partner status, treatment status, and race. Results 242 patients with early stage disease completed the survey. Patients with cervical and vaginal/vulvar cancers reported greater cancer-related distress, anxiety and PTSD symptoms. Patients with endometrial cancer reported the lowest posttraumatic growth scores, which remained statistically significant after adjustment for demographic and clinical differences. No significant differences in cancer-related quality of life were observed among individuals with different primary cancer sites Conclusions These data suggest patients with early-stage gynecologic cancer face different psychosocial sequelae based on primary cancer site, though underlying clinical and sociodemographic factors may play a significant role in this observed relationship. Further research is needed to assess poorer emotional health among individuals with vaginal/vulvar cancers and the lower posttraumatic growth among patients with endometrial cancer as posttraumatic growth is considered a potentially beneficial psychosocial outcome of cancer.
Valuing Morbidity: An Integration of the Willingness-to-Pay and Health-Status Literatures

Note: The following text is a description of the paper and not the text of the abstract as printed in the Journal of Health Economics. Placing dollar values on human health has long been a controversial aspect of policy analysis and remains difficult, given the relatively small number of morbidity-valuation studies available. By combining both the economic and health literature, this paper offers an alternative approach to morbidity valuation and provides estimates for a wide range of short-term health conditions.
Cerebrospinal Fluid Hypocretin and Nightmares in Dementia Syndromes

Background/Aims: Hypocretin promotes wakefulness and modulates REM sleep. Alterations in the hypocretin system are increasingly implicated in dementia. We evaluated relationships among hypocretin, dementia biomarkers, and sleep symptoms in elderly participants, most of whom had dementia. Methods: One-hundred twenty-six adults (mean age 66.2 ± 8.4 years) were recruited from the Emory Cognitive Clinic. Diagnoses were Alzheimer disease (AD; n = 60), frontotemporal dementia (FTD; n = 21), and dementia with Lewy bodies (DLB; n = 20). We also included cognitively normal controls ( n = 25). Participants and/or caregivers completed sleep questionnaires and lumbar puncture was performed for cerebrospinal fluid (CSF) assessments. Results: Except for sleepiness (worst in DLB) and nocturia (worse in DLB and FTD) sleep symptoms did not differ by diagnosis. CSF hypocretin concentrations were available for 87 participants and normal in 70, intermediate in 16, and low in 1. Hypocretin levels did not differ by diagnosis. Hypocretin levels correlated with CSF total τ levels only in men ( r = 0.34; p = 0.02). Lower hypocretin levels were related to frequency of nightmares (203.9 ± 29.8 pg/mL in those with frequent nightmares vs. 240.4 ± 46.1 pg/mL in those without; p = 0.05) and vivid dreams (209.1 ± 28.3 vs. 239.5 ± 47.8 pg/mL; p = 0.014). Cholinesterase inhibitor use was not associated with nightmares or vivid dreaming. Conclusion: Hypocretin levels did not distinguish between dementia syndromes. Disturbing dreams in dementia patients may be related to lower hypocretin concentrations in CSF.
A Review of Hedge Fund Activism: Impact on Shareholders vs. Stakeholders

Hedge fund activism has attracted substantial public attention because of its large financial resources, and ambitious agendas for corporate change through shifts in strategy, productive efficiency, sales of non-performing assets, restructuring of boards and corporate governance mechanisms. The results of the earlier research suggest that hedge fund activism is not just a "stock market sideshow" but appears to induce real effects. Hedge fund activism also has product market and other externalities or effects, however. Theoretically, exogenous productive efficiency improvements and changes in business strategy can impact industry equilibrium and rival companies through a variety of channels; influence vertical relationships with customers and suppliers because of operating and financial interdependence across the value chain; sway debtholders by shifting the balance of power between shareholders and debtholders and exacerbating shareholder-debtholder conflicts; and hurt target employees both along the extensive (number of workers) and intensive margins (number of work hours) through shifts in business strategy. This chapter provides a brief review of recent developments on hedge fund activism, emphasizing its impact on shareholders (both in the short-run and long-run), other stakeholders, and industry rivals of target firms. The chapter closes with a discussion of recent trends in hedge fund activism in global capital markets.
Pancreatic Ductal Adenocarcinoma Highly Expresses Activin A: Implications in Adipose Tissue and Cancer Cachexia

Background: Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer death in the United States and is projected to become the second leading cause by the year 2030. Prognosis for patients with metastatic disease remains dismal. Cancer cachexia is seen in over 85% of PDAC patients who often have the most severe degrees of cachexia and experience adipose tissue loss prior to skeletal muscle loss early in the disease process. Several factors have been proposed to induce cachectic symptoms in human patients, including inhibin subunit βA, or activin A. Hypothesis: While muscle wasting has been the most frequently studied mechanism in cachexia research, changes in adipose tissue are increasingly understood as important components of body weight loss in cachectic patients. We hypothesized that there is a correlation between the marked increase in activin A production in PDAC patients and the remodeling of adipose tissue and consequent cancer-associated cachectic state. Experimental Design: We measured serum activin A levels of a cohort of PDAC patients and analyzed the expression of activin A in tumor-derived cell lines and biopsies of both humans and mice. We further investigated the effect of activin A on remodeling of adipose tissue secondary to tumor progression in PDAC patients and an orthotopic murine model. Results: We observed that PDAC cell lines express and secrete activin A. We recognized a loss of adipose tissue mass and adipocyte diameter in PDAC patients and our orthotopic PDAC mouse model in relation to increased circulating activin A. We also noted that both exogenous activin A and conditioned medium from pancreatic tumor-derived cell lines dampened adipocyte differentiation and lipid droplet formation via reduction of PPARγ expression in mouse mesenchymal stem cells. These treatment conditions also reduced lipid droplet size without upregulating traditional markers of adipose tissue browning and lipolysis such as UCP-1 and ATGL in mature mouse adipocytes. PPARγ, UCP-1, and ATGL expression are also heavily downregulated in adipose tissue of PDAC patients. Furthermore, our studies revealed that the expression of extracellular matrix proteins such as collagen I and fibronectin is dramatically upregulated in adipose tissue of PDAC patients and our orthotopic PDAC mouse model. Thus, we found that there is a clear correlation between elevated levels of activin A and the progression of cancer-associated cachexia in PDAC. Discussion: Our results reveal an imperative role of activin A in relation to the loss and remodeling of adipose tissue in the progression of cachexia in PDAC patients.