cssi/SciSciGPT-SciSciNet huggingface dataset:
The Effects of Comprehensive Information Reporting Systems and Economic Incentives on Managers' Time‐Planning Decisions

Recent innovations in management control systems, such as the Balanced Scorecard, are supposed to influence managers to redirect their attention among multiple objectives and areas. Extending prior studies that have examined behavior in only a single area, this study experimentally examines how comprehensive control systems influence managers as they allocate their time among multiple areas of responsibility. The results show that managers do not plan increases in their working week in response to increased monitoring or to performance‐based incentives, but rather they shift their time from areas that are not monitored or rewarded to areas that are. The results support Kaplan and Norton's assertion that the Balanced Scorecard can be used to influence the way managers allocate their attention between organizational objectives.
SU‐GG‐T‐520: Inhomogeneity Corrected/Non‐Corrected Plan Evaluation for Simple and Conformal Plans For Radiation Therapy of Lung Cancer

Purpose: To investigate the effects on dose to critical structures for density corrected planning on simple (APPA and off‐cord) and conformal (4–5 field) lung plans compared to historical experience assuming homogeneous density. Method and Materials: Ten patients were planned using both techniques with XIO CMS software. The conformal plans were normalized to percentage coverage of target volumes and the simple plans were calculated to midplane. All plans were calculated using homogeneous density as the standard. After planning, CT density corrections were implemented and monitor units were matched to the homogeneous plan; the plans were not re‐optimized. Dose volume histograms were reviewed for critical structures of cord, “hot spot” D5(PTV), and V20(lung). Plan uniformity was assessed by the slope of the PTV dose curve using the equation [(D5–D95)/Dmean]. Results: The V20 increased with corrections: 23.7±1.7 to 24.6±7.2 for complex plans; 25.2±10.8 to 26.1±11.3 for simple plans. The conformal plans degraded in uniformity by a factor twice that of the simple plans and D5 increased accordingly. Cord dose increased slightly in conformal plans (33.65Gy±12.0Gy to 34.38±12.2Gy) and remains similar in simple plans (37.83±16.5Gy to 38.11±16.8Gy). The range of cord dose variations in corrected conformal plans was from −0.22–3.24Gy; one increase raised the cord V1% from 45.95Gy to 48.84Gy. Additionally, since the simple plans historically were assumed to approximate zero cord dose for the off‐cord obliques, the calculated/delivered cord dose is much higher. The effect of density corrections increased notably in the conformal plans where more beams transverse the lung.Conclusion: Although the effect of homogeneity corrections are well documented, the outcome on plan uniformity and critical structure tolerances should be further examined when transitioning from simple to multi‐field beam arrangements including IMRT. This study provides clinical dosimetric reference for adoption of heterogeneity corrected planning.
Genetic algorithm application to controller optimization problems with non-analytic solutions

Genetic algorithms (GAs) offer a numerical search method which does not require a statement of the mathematical relationship between the performance criteria and the parameter update rule. The objective of this study is to demonstrate that GAs provide a method of optimizing control system problems with analytically intractable constraints. A linear missile airframe and actuator state space model is developed, and a reduced order linear feedback controller is implemented. A genetic algorithm is constructed to optimize the controller parameters, first with respect to a weighted linear quadratic performance index. Penalty functions are then developed to introduce performance constraints on the maximum rise time, allowable settling error, and peak actuator effort.
The IUCF Cooler-A Storage Ring with Electron Cooling for Internal Target Experiments

A project to construct a ring to store beams of light ions with magnetic rigidities up to 3.6 T-m is underway at the Indiana University Cyclotron Facility. Beams from the cyclotron will fill the ring, be adjusted in energy, then cooled by electron immersion while impinging on thin targets within the ring for nuclear interaction experiments. The motivation is to explore the potential for improved resolution and reduced background of the cold storage technique. The status of the project and of selected subsystem designs will be presented.
A general approach to the asymmetric synthesis of vancomycin-related arylglycines by enolate azidation

Abstract The asymmetric synthesis of vancomycin-related α-azido arylglycines by direct azide transfer methodology is reported. Procedures for the conversion of the azides to N-protected arylglycines are provided.
Alpha 4-integrins mediate antigen-induced late bronchial responses and prolonged airway hyperresponsiveness in sheep.

Eosinophils and T lymphocytes are thought to be involved in allergic airway inflammation. Both cells express the alpha 4 beta 1-integrin, very late antigen-4 (VLA-4, CD49d/CD29); alpha 4-integrins can promote cellular adhesion and activation. Therefore, we examined the in vivo effects of a blocking anti-alpha 4 monoclonal antibody, HP 1/2, on antigen-induced early and late bronchial responses, airway hyperresponsiveness, inflammatory cell influx, and peripheral leukocyte counts in allergic sheep. Sheep blood lymphocytes, monocytes, and eosinophils expressed alpha 4 and bound HP 1/2. In control sheep, Ascaris antigen challenge produced early and late increases in specific lung resistance of 380 +/- 42% and 175 +/- 16% over baseline immediately and 7 h after challenge, respectively, as well as airway hyperresponsiveness continuing for 14 d after antigen challenge. Treatment with HP 1/2 (1 mg/kg, i.v.) 30 min before antigen challenge did not affect the early increase in specific lung resistance but inhibited the late-phase increase at 5-8 h by 75% (P < 0.05) and inhibited the post-antigen-induced airway hyperresponsiveness at 1, 2, 7, and 14 d (P < 0.05, for each time). Intravenous HP 1/2 given 2 h after antigen challenge likewise blocked late-phase airway changes and postchallenge airway hyperresponsiveness. Airway administration of HP 1/2 (16-mg dose) was also effective in blocking these antigen-induced changes. Response to HP 1/2 was specific since an isotypic monoclonal antibody, 1E6, was ineffective by intravenous and aerosol administration. Inhibition of leukocyte recruitment did not totally account for the activity of anti-alpha 4 antibody since HP 1/2 neither diminished the eosinopenia or lymphopenia that followed antigen challenge nor consistently altered the composition of leukocytes recovered by bronchoalveolar lavage. Because airway administration of HP 1/2 was also active, HP 1/2 may have inhibited cell activation. Reduction of platelet-activating factor-induced eosinophil peroxidase release from HP 1/2-treated eosinophils supports such a mechanism. These findings indicate a role for alpha 4-integrins in processes that lead to airway late phase responses and persisting airway hyperresponsiveness after antigen challenge.
“I’m not sure that I can figure out how to do that”: Pursuit of work among people with mental illnesses leaving jail

Restoring people with mental illnesses to community life after detention in jail is fraught with significant challenges. Many of these challenges mirror those faced by anyone else who has been detained in jail. Among these are the particular challenge of seeking gainful employment and financial support for day-to-day life. This challenge is intensified when individuals return from jail to impoverished communities where employment prospects are already limited for residents, and where either a criminal record or a mental illness creates still additional barriers to work. To understand these barriers more fully, this study examined the process of seeking employment among people with mental illnesses leaving jail. Seventeen individuals with a history of mental health problems and with recent jail incarcerations were recruited from either a community based employment program or a mental health service setting. The informants were interviewed using life history interview techniques. Results show that connections to the paid workforce were tenuous at best for these respondents, both before and after their jail detention. While psychiatric symptoms, addiction, and the lack of productive social connections were individual-level factors that affected employment, the most pernicious impediments were rooted in policy, community structures, stigma and other social and economic realities.. If employment interventions are to have any traction at all in these settings, interventionists need to dig for innovative ways to address these factors, which are not complications, but bedrock realities that undergird all else.
Parallel Hybrid Network Traffic Models

Fluid-based network traffic models are attractive due to their execution efficiency. They run much faster than the corresponding discrete-event packet-oriented simulation, especially when we study the aggregate traffic behavior of large-scale network scenarios. The efficiency, however, comes at a cost: fluid modeling does not include packet-level details. The ability to accurately capture the interaction between the packets and the network routers and hosts visited by the packets is essential for real-time network simulations, where the simulator must be able to interact with real applications in real time. In particular, the virtual network must be able to carry real packets subject to proper delays and losses and be able to react to these real packets (such as traceroute). Previously, we presented a hybrid network traffic model that combines a continuous-time fluid model and the discrete-event packet-oriented simulation. In this article, we examine a parallel processing method for simulations of large-scale networks using the hybrid model. Our method benefits from the observation that the time it takes to propagate fluid characteristics along the path taken by the traffic flows has a lower bound equal to the minimum link delay as manifested by the governing ordinary differential equations (ODEs). A better lookahead can thus be used to allow parallel simulation of the hybrid model to run without more synchronization overhead than the corresponding discrete-event packet-oriented model. We derive an analytical model comparing the fluid model and the packet-oriented model both for sequential and parallel simulations. We demonstrate the benefit of the parallel hybrid model through a series of simulation experiments of a large-scale network consisting of over 170 000 hosts and 1.6 million traffic flows on a small parallel cluster.
THE PERIODONTAL CONDITION OF INSTITUTIONALIZED CHILDREN; IMPROVEMENT THROUGH ORAL HYGIENE*

If time and expense can be managed, the periodontal condition of mongoloid children can be improved.
SITUATIONAL JUDGMENT TESTS, RESPONSE INSTRUCTIONS, AND VALIDITY: A META‐ANALYSIS

Situational judgment tests (SJTs) are personnel selection instruments that present job applicants with work-related situations and possible responses to the situations. There are typically 2 types of instructions: behavioral tendency and knowledge. Behavioral tendency instructions ask respondents to identify how they would likely behave in a given situation. Knowledge instructions ask respondents to evaluate the effectiveness of possible responses to a given situation. Results showed that response instructions influenced the constructs measured by the tests. Tests with knowledge instructions had higher correlations with cognitive ability. Tests with behavioral tendency instructions showed higher correlations with personality constructs. Results also showed that response instructions had little moderating effect on criterion-related validity. Supplemental analyses showed that the moderating effect of response instructions on construct validity was not due to systematic differences in item content. SJTs have incremental validity over cognitive ability, the Big 5, and over a composite of cognitive ability and the Big 5.
Super spaces: a middleware for large-scale pervasive computing environments

In previous work [M. Roman et al., (2002)], we introduced a distributed middleware infrastructure for managing physically-bounded, standalone pervasive computing environments, which we refer to as Active Spaces. We extend this middleware to support the organization, management and interactions of large-scale pervasive computing systems built from multiple Active Spaces or other pervasive computing components.
Design assistance for CAD frameworks

Decision-making support based on prediction and advice is a fundamental resource that can be used to reduce search in the design space. The authors discuss the advantages of providing CAD frameworks with a general design assistance facility and the basic methodology that should underlay the implementation of such a facility. A general purpose design assistance metal-tool that successfully realizes the proposed methodology is described. This tool has been integrated into the Odyssey CAD Framework. >
Eicosanoid pathways regulate adaptive immunity to Mycobacterium tuberculosis

The fate of infected macrophages has an essential role in protection against Mycobacterium tuberculosis by regulating innate and adaptive immunity. M. tuberculosis exploits cell necrosis to exit from macrophages and spread. In contrast, apoptosis, which is characterized by an intact plasma membrane, is an innate mechanism that results in lower bacterial viability. Virulent M. tuberculosis inhibits apoptosis and promotes necrotic cell death by inhibiting production of prostaglandin E(2). Here we show that by activating the 5-lipoxygenase pathway, M. tuberculosis not only inhibited apoptosis but also prevented cross-presentation of its antigens by dendritic cells, which impeded the initiation of T cell immunity. Our results explain why T cell priming in response to M. tuberculosis is delayed and emphasize the importance of early immunity.
Augmenting Functional Broadside Tests for Transition Fault Coverage with Bounded Switching Activity

For most purposes, it is sufficient for a low-power test set to ensure that the power dissipation during test application will not exceed that possible during functional operation. This is guaranteed for the fast functional capture cycles of functional broadside tests. This paper describes a procedure that generates broadside test sets with bounded switching activity during fast functional capture cycles based on the maximum switching activity of a functional broadside test set, targeting transition faults in full-scan circuits. The procedure first generates a compact functional broadside test set. It then extends the test set in steps in order to increase its fault coverage to that of an arbitrary broadside test set (a test set that includes non-functional broadside tests). During these steps, the maximum switching activity of the functional broadside test set is used for bounding the switching activity.
A benign method for maintaining ovulatory estrogen levels in cycling rhesus macaques

The goal of this study was to develop a relatively noninvasive technique for generating ovulatory estrogen levels in cycling females over extended periods of time. Eleven intact cycling rhesus macaques were given weekly injections of estradiol cypionate in an effort to obtain weekly levels which approximated ovulatory levels. A dose of 500 μg generated weekly estrogen values averaging 370 ± 18 pg/ml. This method is a satisfactory alternative to more traditional techniques. It involves no surgical procedures, it is relatively nonintrusive, it does not terminate a female's reproductive career, and it is not as time-consuming as daily injections. Female cycle state can be altered with a minimum of manipulation for studies involving the behavior of estrous females.
Unexpected Transformation of a Schiff Base Pyridine N-Oxide in the Presence of Pr(NO3)3 · 6H2O

Abstract The synthesis of (E)-((6-(((3-hydroxy-4-methoxybenzylidene)amino)methyl)-N-oxide-pyridin-2-yl)methyl)diphenylphosphine oxide 1 and its unexpected transformation during efforts to study the coordination chemistry with Pr(NO3)3·6H2O are described.
Aromatase Cytochrome P450 and Extragonadal Estrogen Play a Role in Ischemic Neuroprotection

Female animals are protected from many forms of neurological injury and degeneration relative to their male counterparts, in part attributable to their native estrogens. We hypothesized that estradiol aromatized from precursor androgens via the cytochrome P450 aromatase contributes to ischemic neuroprotection in the female. Female homozygous aromatase knock-out (ArKO) mice and randomly cycling, wild-type (WT) female littermates were treated with reversible middle cerebral artery occlusion (90 min; 22 hr reperfusion). Total and regional ischemic damage was greater in female ArKOs (total, 33.5 ± 4.8%; cortical, 47.4 ± 5.7%; striatal, 44.8 ± 7.8%) compared with WT (total, 14.2 ± 5%; cortical, 14.2 ± 4.5%; striatal, 17.5 ± 8%). Baseline blood pressure and intra-ischemic cortical perfusion were comparable in knock-outs and WT, suggesting that vascular factors do not explain ArKO ischemic sensitivity. Injury was smaller in ovariectomized WT than in ArKO, emphasizing that extragonadal local estradiol plays a critical role in females. Similar increases in cortical and striatal damage were observed in female WT mice chronically treated with the aromatase inhibitor fadrozole compared with vehicle-treated control mice. Restoration of plasma 17β-estradiol to physiological levels completely reversed the ArKO female9s susceptibility to injury. These findings indicate that the biosynthetic enzyme P450 aromatase is key to endogenous neuroprotection in females and suggest that enhancing local, nongonadal estrogen formation could have therapeutic implications is ischemic neuropathology.
15 kDa Granulysin Causes Differentiation of Monocytes to Dendritic Cells but Lacks Cytotoxic Activity

Granulysin is expressed as two isoforms by human cytotoxic cells: a single mRNA gives rise to 15 kDa granulysin, a portion of which is cleaved to a 9 kDa protein. Studies with recombinant 9 kDa granulysin have demonstrated its cytolytic and proinflammatory properties, but much less is known about the biologic function of the 15 kDa isoform. In this study, we show that the subcellular localization and functions of 9 and 15 kDa granulysin are largely distinct. Nine kilodalton granulysin is confined to cytolytic granules that are directionally released following target cell recognition. In contrast, 15 kDa granulysin is located in distinct granules that lack perforin and granzyme B and that are released by activated cytolytic cells. Although recombinant 9 kDa granulysin is cytolytic against a variety of tumors and microbes, recombinant 15 kDa granulysin is not. The 15 kDa isoform is a potent inducer of monocytic differentiation to dendritic cells, but the 9 kDa isoform is not. In vivo, mice expressing granulysin show markedly improved antitumor responses, with increased numbers of activated dendritic cells and cytokine-producing T cells. Thus, the distinct functions of granulysin isoforms have major implications for diagnosis and potential new therapies for human disease.
Optimal Order of Servers for Tandem Queues in Light Traffic

We study single-server stations in tandem, in which customers arrive according to a Poisson Process and are to be served at each of two servers. The order of the stations is assumed not to affect the quality of the service customers obtain. Using a light traffic approximation, we select for various joint distributions of service time the order of the stations that minimizes expected customer delay.
Hairy cell leukemia: Past, present and future

This brief review highlights the sequence of therapeutic milestones and advances in our understanding of the biology of hairy cell leukemia (HCL) with a focus on recent molecular findings and how these may be applied to improve disease outcomes in the future. Targeted therapy is discussed in the context of the recently identified BRAF mutation and other genetic findings.
Genome-Wide Transcriptome Analysis of Cotton (Gossypium hirsutum L.) Identifies Candidate Gene Signatures in Response to Aflatoxin Producing Fungus Aspergillus flavus

Aflatoxins are toxic and potent carcinogenic metabolites produced from the fungi Aspergillus flavus and A. parasiticus. Aflatoxins can contaminate cottonseed under conducive preharvest and postharvest conditions. United States federal regulations restrict the use of aflatoxin contaminated cottonseed at >20 ppb for animal feed. Several strategies have been proposed for controlling aflatoxin contamination, and much success has been achieved by the application of an atoxigenic strain of A. flavus in cotton, peanut and maize fields. Development of cultivars resistant to aflatoxin through overexpression of resistance associated genes and/or knocking down aflatoxin biosynthesis of A. flavus will be an effective strategy for controlling aflatoxin contamination in cotton. In this study, genome-wide transcriptome profiling was performed to identify differentially expressed genes in response to infection with both toxigenic and atoxigenic strains of A. flavus on cotton (Gossypium hirsutum L.) pericarp and seed. The genes involved in antifungal response, oxidative burst, transcription factors, defense signaling pathways and stress response were highly differentially expressed in pericarp and seed tissues in response to A. flavus infection. The cell-wall modifying genes and genes involved in the production of antimicrobial substances were more active in pericarp as compared to seed. The genes involved in auxin and cytokinin signaling were also induced. Most of the genes involved in defense response in cotton were highly induced in pericarp than in seed. The global gene expression analysis in response to fungal invasion in cotton will serve as a source for identifying biomarkers for breeding, potential candidate genes for transgenic manipulation, and will help in understanding complex plant-fungal interaction for future downstream research.
Absorption and circular dichroism spectra of ribonuclease-S at 77 degrees K.

The absorption and circular dichroism spectra of RNase-S and RNase-A were compared in the near ultraviolet at 77° K. The vibronic structure which emerges at 77° K is different in the two enzymes between 280 and 293 nm. Analysis of the vibronic structure shows that a single tyrosine residue (0-0 transition at 288.5 nm in RNase-A) has its bands shifted by approximately 2.5 nm to shorter wave lengths in RNase-S, indicating a change in the environment of this tyrosine resiin RNase-S. The x-ray data available on RNase-S strongly suggest that this residue is tyrosine 25.
Blood Transfusion and Risk of Non-Hodgkin's Lymphoma

A few epidemiologic studies have suggested that blood transfusion may be a risk factor for non-Hodgkin's lymphoma. The authors tested this hypothesis in a population-based, case-control study, using pathologically verified non-Hodgkin's lymphoma cases and transfusion documented via medical records. In 221 age- and sex-matched case-control pairs from Olmsted County, Minnesota, in 1975-1993, the authors observed an odds ratio of 0.84 (95% confidence interval 0.50-1.41) for history of transfusion and non-Hodgkin's lymphoma. There also was no apparent association between transfusion and non-Hodgkin's lymphoma in any subgroup analysis. Results do not support the hypothesis that blood transfusion contributes to the occurrence of non-Hodgkin's lymphoma.
A New Kind of Thinking about Harmony-Solidifying Management Theory on Uncertainty

In recent years,Many scientists focus their attention on complexity and uncertainty in different fields,This paper tries make the understanding of the complexity and uncertainly deeply,Then expand the thinking science to the society.We elaborate the uncertainty of the corpus thinking though analyzing the transition between divergent criterions and judgment criterions of thinking.The cognition diagram of the corpus thinking is provided to point out that the corpus thinking of anti-accumulations is a valid way of the indelete uncertainty in the.At last we discuss and put forward a new kind framework of Harmonious Solidifying management theory,providing a new way of thinking about uncertainty management
Epidemiological Characteristics and Control Status of Tuberculosis in Fu County of Shanxi Province during 2004—2008

[Objective]To understand the distribution of tuberculosis(TB)epidemic and its control status after the implementation of "TB control planning of China(2001—2010)",so as to provide evidence for improving and enhancing the implementation and planning.[Methods]The epidemiological characteristics for 424 clinic registered cases of tuberculosis and the control status in Fu County of Shannxi province during 2004—2008 was analyzed.[Results]The main distribution of the TB epidemic concentrated during July to December,occupied 54.95%;cases in rural area were much more than in urban area.TB high-risk population was 15~54 years age group,occupied 66.04%,male cases was more than female,the ratio was 1.77 ∶1;type of cases to the main was Type Ⅲ,accounted for 82.78%.The difference of curative rate between smear-positive patients and the retreated patients was significant(P0.01).[Conclusion] Sputum negative conversion rate increased with month increasing of treatment.Detection rate of new smear-positive patients and curative rate of smear-positive patients have achieved the planning targets.
Abstract 4147: T cell targeted peptides for monitoring immune response in melanoma

Melanoma develops the ability to evade immune recognition through multiple mechanisms, despite being highly immunogenic. This is demonstrated by the effective and additive response checkpoint blockade therapies have had during combination clinical trials in melanoma [1]. While the results of these trials have been promising, large portions of patients do not respond to treatment [1,2]. Additionally, many responders take months to show a response using standard criteria. In order to monitor patient response and understand the limitations of immunotherapy, we performed phage display to discover peptides targeted to tumor infiltrating lymphocytes (TILs) in melanoma tumors. To improve phage library characterization, we developed a method to deep sequence phage with the Ilumina MiSeq platform. Phage screens using PhD7 library (NEB) performed on HUVECS and on TILs, naive and effector T cells, and B cells harvested from mice. The phage libraries generated from these screens were deep sequenced using the Illumina MiSeq system. The sequencing data was analyzed with an efficient, custom MATLAB script, which arranges sequences by frequency determining peptide frequencies for each library. Peptide frequency was normalized to a reference library generated by amplifying an unscreened phage library. T cell screens were compared with B cell and endothelial cell screens in sequence frequency matrices. Top TIL targeting sequences were cloned into phage, and then fluorescently labeled along with insert-less control phage. Labeled phage were incubated with TILs, or effector T cells and analyzed for specificity using flow cytometry. Four phage clones were identified with at least four fold increased binding for TILs over effector T cells isolated from the spleen. Interestingly, only subsets of the TILs were bound by the targeted phage. We have identified and validated peptides that demonstrate specificity for CD8 TILs. These peptide sequences represent candidates for development into companion diagnostic imaging agents for use with checkpoint therapies. We are currently evaluating these peptides in an in vivo tumor model to further validate their specificity and to determine their biodistributions. Peptides that validate in vivo could be developed into useful imaging agents. After peptide sequences have been validated in vivo, we will determine the phage binding partner using a phage based pulldown. The peptide binding partners discovered through this approach will provide insight into the subset of TILs bound by the phage. [1] Wolchok, J. D. et al., N Engl J Med 2013; 369:122-133. [2] Drake, CG. et al., Clin Cancer Res November 15, 201117. Citation Format: Dustin Bauknight, Andrew Buckner, Lindsey Brinton, Timothy Bullock, Kimberly Kelly. T cell targeted peptides for monitoring immune response in melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4147.
Identification of gene-drug interactions that impact patient survival in TCGA

Background With the advent of large scale biological data collection for various diseases, data analysis pipelines and workflows need to be established to build frameworks for integrative analysis. Here the authors present a pipeline for identifying disease specific gene-drug interactions using CNV (Copy Number Variation) and clinical data from the TCGA (The Cancer Genome Atlas) project. Two cancer types were selected for analysis, LGG (Brain lower grade glioma) and GBM (Glioblastoma multiforme), due to the possible progression from LGG to GBM in some cases. The copy number and clinical data were then used to preform survival analysis on a gene by gene basis on sub-populations of patients exposed to a given drug.
Assessing the Risks New Products Face

OVERVIEW:New products that mesh with their external environment have a better chance of succeeding than those that do not. Companies that assess the external environment for potential new products effectively are more likely to market commercial winners than firms performing this activity ineffectively. Unfortunately, R&D programs often fail to recognize the importance of the external environment. Consequently, the authors provide a framework for companies to use to develop external environmental profiles for their new product candidates. Operational guidelines for developing these profiles are included, and recommendations as to how companies should scan their external environments are offered.
Abstract A08: Mechanistic basis of Palbociclib combinatorial activity in ER+ breast cancer and non-breast indications

Phosphorylation of the retinoblastoma protein (Rb) by cyclin-dependent kinases 4 and 6 (CDK4/6) is a critical checkpoint for G1/S cell cycle progression and commitment to cellular proliferation. Human malignancies often subvert these control mechanisms through a range of genetic and biochemical adaptations. Accordingly, tumors that depend on CDK4/6 activity for proliferation and survival are particularly sensitive to inhibition of this pathway by palbociclib (Ibrance™), a highly selective inhibitor of CDK4/6 kinase activities. Treatment regimen of palbociclib with letrozole significantly improved progression-free survival in a randomized phase 2 study of women with advanced estrogen receptor-positive (ER+), HER2-negative breast cancer. Likewise, in ER+ breast cancer models palbociclib and estrogen antagonists combine for greater anti-proliferative activity, increased hallmarks of cellular senescence and prolonged durability of response following drug removal. Dual inhibition of CDK4/6 and ER signaling demonstrated robust anti-tumor activity in xenograft studies. The addition of Palbociclib to other targeted therapeutics elicits improved activity in pre-clinical models of several non-breast indications and these effects also manifest through modulation of cellular proliferation, senescence and growth arrest. Data will be presented on the molecular basis of combination benefit with Palbociclib in ER+ breast and other oncology indications. Citation Format: Stephen Dann, John Chionis, Liu Choating, Enhong Chen, Ping Wei, Koleen Eisele, David J. Shields, Paul A. Rejto, Todd VanArsdale. Mechanistic basis of Palbociclib combinatorial activity in ER+ breast cancer and non-breast indications. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Cancer Cell Cycle - Tumor Progression and Therapeutic Response; Feb 28-Mar 2, 2016; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(11_Suppl):Abstract nr A08.
Probabilistic risk assessment on maritime spent nuclear fuel transportation—Part I: Transport cask damage probability

Abstract This paper proposes a methodology to assess and reduce risks on Spent Nuclear Fuel (SNF) packages from ship collisions with a probabilistic approach. A method to estimate the impact energy upon a collision was elaborated in consideration that whether ships slide or stuck to each other during collision. Structural crash-worthiness of the SNF ship was obtained through a non-linear finite element analysis. Cask damage probability was calculated based on frontal and side cask impact scenarios. This cask damage probability was investigated over various transport parameters which include the number of transport casks carried per shipment, cask stowage configuration, cask loading direction, and ship's cruise velocity. Collision case studies are presented by using reference models of the SNF package, the struck and striking ship. Most and least vulnerable stowage locations on the SNF ship were discovered. The number of casks in a shipment and their stowage method which suppressed cask damage probabilities were identified. The proposed methodology was successful in assisting decision making processes to minimize risks in maritime spent nuclear fuel transportation.
Dopaminergic Immunofluorescence Studies in Kidney Tissue

The kidney is a highly integrated system of specialized differentiated cells that are responsible for fluid and electrolyte balance in the body. While much of today's research focuses on isolated nephron segments or cells from nephron segments grown in tissue culture, an often overlooked technique that can provide a unique view of many cell types in the kidney is slice culture. Here, we describe techniques that use freshly excised kidney tissue from rats to perform a variety of experiments shortly after isolating the tissue. By slicing the rat kidney in a "bread loaf" format, multiple studies can be performed on slices from the same tissue in parallel. Cryosectioning and staining of the tissue allow for the evaluation of physiological or biochemical responses in a wide variety of specific nephron segments. The procedures described within this chapter can also be extended to human or mouse kidney tissue.
EMERGING CHALLENGES OF INDIAN HIGHER EDUCATIONAL INSTITUTIONS

The Indian higher education institution is in an urgent need of capable leaders who can lead and manage the university affairs in the era of globalization, thus the present paper is an attempt to identify the emerging challenges of Indian higher education institutions and the important role of academic leader in bringing about the required changes.
Erupting tattoos: a case report

Koebner phenomenon is the development of isomorphic pathologic lesions to traumatized skin of patients with a history of psoriasis Heinrich Koebner a German dermatologist first described this phenomenon in With the evolving popularity of tattoos which causes mechanical injury to the skin much discussion will be required to disseminate relevant information regarding Koebner phenomenon in obtaining an accurate clinical diagnosis
Fractures in a nationwide population-based cohort of users of breast cancer hormonal therapy.

Although users of aromatase inhibitors have higher total fracture risk in some randomized trials, little is known about their risk outside of clinical trials or in older higher-risk cohorts. In a population-based retrospective cohort study, we identified all older US Medicare D prescription drug insurance plan-enrolled women who had initial breast cancer surgery in 2006–2008 and began hormonal therapy (an aromatase inhibitor (AI) or tamoxifen) within the subsequent year. Total nonvertebral and hip fractures through 2012 were identified using a validated algorithm. The association of fracture outcomes with hormonal therapy type was assessed using competing risk regression models that accounted for differences in measured baseline covariates. Treatment assignment bias was reduced using inverse probability of treatment weighting computed from propensity scores. Among 23,378 women taking hormonal therapy (23.2% aged 80 or over), there were 3000 total and 436 hip fractures. Although AI users were younger and had lower comorbidity, after propensity score weighting, these and other covariates were balanced. Total nonvertebral risk was higher for users of AIs compared with tamoxifen, HR 1.11 (1.02–1.21), but the small increase in risk for hip fracture was not statistically significant, HR 1.04 (0.84–1.30). Although total nonvertebral fracture risk was higher among AI users, differences in hip fractures were not significant in a large population-based cohort of older women. Use of aromatase inhibitors by older women is associated with high risk for nonvertebral fracture that is increased compared with use of tamoxifen. Fracture risk should be assessed among patients taking these medications.
Adiabatic Spin Pump through a Molecular Antiferromagnet Ce3Mn8III

We show that the spin-dependent charging energy recently discovered in a molecular antiferromagnet enables an adiabatic spin pump, without requiring a magnetic field or tunable spin–orbit coupling, when the molecule is connected to two unpolarized electrodes with oscillating chemical potentials. Onsite Coulomb repulsion between electrons of opposite spin orientations causes a spin-dependent suppression of the current between the two leads, leading to a pumped spin current. Consequently, the Berry-phase-like geometric current is highly spin-polarized. We explore the space of driving parameters to demonstrate the generation of either a fully polarized or a pure spin current. Negative differential conductance is also predicted. These possibilities highlight the advantage of molecular antiferromagnets over ferromagnetic molecules and quantum dots in generating and manipulating low-power spin currents.
360° deterministic magnetization rotation in a three-ellipse magnetoelectric heterostructure

A magnetic dipole-coupled magnetoelectric heterostructure comprised of three closely spaced ellipse shapes was designed and shown to be capable of achieving deterministic in-plane magnetization rotation. The design approach used a combination of conventional micromagnetic simulations to obtain preliminary configurations followed by simulations using a fully strain-coupled, time domain micromagnetic code for a detailed assessment of performance. The conventional micromagnetic code has short run times and was used to refine the ellipse shape and orientation, but it does not accurately capture the effects of the strain gradients present in the piezoelectric and magnetostrictive layers that contribute to magnetization reorientation. The fully coupled code was used to assess the effects of strain and magnetic field gradients on precessional switching in the side ellipses and on the resulting dipole-field driven magnetization reorientation in the center ellipse. The work led to a geometry with a CoFeB ellipse (...
Implementation of a quality improvement project for universal genetic testing in women with ovarian cancer.

Abstract Objective The National Comprehensive Cancer Network recommends all women with ovarian cancer be offered genetic testing. Despite a decade of endorsement, many oncology practitioners have yet to make this a part of routine practice. Referral to genetic counseling and completion of genetic testing among patients at substantial risk of germline mutations are significantly lacking, adversely affecting patient care and squandering an opportunity to maximize cancer prevention efforts. This project determined the impact and feasibility of implementing a basic model for universal referral to genetic counseling and completion of genetic testing in women with a diagnosis of ovarian cancer in an academic gynecology oncology practice with access to electronic health records (EHRs). Methods Patients diagnosed with ovarian cancer from January 2008 to November 2013 were retrospectively reviewed to determine the baseline referral rate for genetic counseling and testing completion in our practice. Implementation of a process change model combining provider training , patient education , enhanced electronic health record documentation and improved patient appointment scheduling strategies were implemented. We then prospectively collected data on all newly diagnosed ovarian cancer patients that had not already undergone genetic testing presenting from December 1, 2013 to November 30, 2016. Results Genetic referral rates, genetic counseling and testing completion rates were markedly improved. Pre-implementation our genetic testing rate was 27% and post implementation our testing rate was 82% (p-value≤0.001). Conclusions Low cost interventions that target education of both providers and patients regarding the importance of genetic testing along with utilization of the EHR and streamlined patient appointment services can significantly increase rates of genetic testing completion.
Modafinil for treatment of residual excessive sleepiness in nasal continuous positive airway pressure-treated obstructive sleep apnea/hypopnea syndrome.

Study Objectives: Nasal continuous positive airway pressure (nCPAP) usually reduces sleepiness in patients with obstructive sleep apnea/hypopnea syndrome. However, even with regular use of nCPAP, some patients experience residual excessive sleepiness. We evaluated the efficacy and safety of the wake-promoting agent modafinil for treating residual excessive sleepiness in nCPAP-treated patients. Design: 12-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. Patients: Patients aged 18 to 70 years diagnosed with obstructive sleep apnea/hypopnea syndrome and having residual excessive sleepiness during nCPAP therapy were eligible. Interventions: Once-daily modafinil, 200 mg or 400 mg, or placebo. Measurements and Results: Assessments included the Maintenance of Wakefulness Test, Epworth Sleepiness Scale, Clinical Global Impression of Change, and Functional Outcomes of Sleep Questionnaire. Both doses of modafinil significantly improved mean (SD) sleep latency on the Maintenance of Wakefulness Test at weeks 4, 8, and 12 compared with placebo (week 12: modafinil 400 mg, 15.0 [5.3] minutes; 200 mg, 14.8 [5.3] minutes; placebo, 12.6 [5.8] minutes; P <.0001). The Epworth Sleepiness Scale score decreased more in patients taking modafinil compared with those in the placebo group (week 12: modafinil 400 mg, -4.5 [4.3]; 200 mg, -4.5 [4.7]; placebo, -1.8 [3.5]; P <.0001). At week 12, overall clinical condition improved for 61% and 68% of patients treated with modafinil 200 mg and 400 mg, respectively, versus 37% of placebo-treated patients (P <.001). Modafinil was generally well tolerated and did not adversely affect nighttime sleep or nCPAP use. Conclusions: These results confirm previous shorter-term controlled trials, indicating modafinil is a useful adjunct therapy for improving wakefulness in patients with residual excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome who were treated with nCPAP.
Questioning the “Sanctity” of long-term defense planning as practiced in Central and Eastern Europe

It is an article of faith amongst many defense officials that long-term defense planning constitutes the gold standard in the development and management of modern armed forces. That such a method h...
Accessibility and agglomeration: A theoretical framework for understanding the connection between transportation modes, agglomeration benefits, and types of businesses

While delineating the connection between transportation accessibility and economic activity has long been a topic of interest in geography and regional science, a better understanding of the agglomerative benefits of transportation systems is vital. This paper seeks to tie the concepts of accessibility and agglomeration together by arguing that accessibility benefits ultimately stem from the agglomerative potential created by various transportation investments. This line of reasoning provides an avenue to use the economic mechanisms described in agglomeration theory to analyze the effects of specific transportation modes. To do this, the paper traces the literature on the economic impacts of transportation systems and presents a theoretical framework for understanding the connection between specific transportation modes and specific agglomeration benefits. Ultimately, specific modes have unique features that are more or less conducive to specific agglomeration benefits, to which specific types of businesses also respond. These specific connections are particularly important to understand as the development of new urban transportation modes, for example, autonomous vehicles—and their potential economic impacts—increases rapidly.
Perseverance in solving Sudoku: role of grit and cognitive flexibility in problem solving

Problem solving is a higher order cognitive capacity with implications for everyday functioning. Although Grit predicts academic outcomes, the relation between facets of Grit, Consistency and Perse...
Can Genetics Modify the Influence of Healthy Lifestyle on Lipids in the Context of Obesity and Type 2 Diabetes

Recently, the Look AHEAD (Action for Health in Diabetes) trial tested whether randomized lifestyle intervention improves health outcomes among overweight or obese individuals with type 2 diabetes mellitus (T2D). The relatively large sample size for a clinical trial, excellent follow-up, and longitudinal measures make possible the analysis of whether genetic factors can modify behavioral change responses on common traits relevant to cardiovascular health. Despite challenges, emerging examples indicate that genetic factors may alter the magnitude of weight loss and lipid change in response to behavioral treatment. The current challenge is to develop better ways to identify genetic variants that modify lifestyle responses to maximize the clinical impact of genetic discovery.
A Deep Learning Convolutional Neural Network Can Recognize Common Patterns of Injury in Gastric Pathology

Context.— Most deep learning (DL) studies have focused on neoplastic pathology, with the realm of inflammatory pathology remaining largely untouched. Objective.— To investigate the use of DL for no...