cssi/SciSciGPT-SciSciNet huggingface dataset:
A Methodology for Multiscale Computational Design of Continuous Fiber SiC-Si 3 N 4 Ceramic Composites Based on the Variable Fidelity Model Management Framework

Research applications involving design tool development for multiple phase material design are at an early stage of development. The computational requirements of advanced numerical tools for simulating material behavior such as the finite element method (FEM) and the molecular dynamics method (MD) can prohibit direct integration of these tools in a design optimization procedure where multiple iterations are required. The complexity of multiphase material behavior at multiple scales restricts the development of a comprehensive meta-model that can be used to replace the multiscale analysis. One, therefore, requires a design approach that can incorporate multiple simulations (multiphysics) of varying fidelity such as FEM and MD in an iterative model management framework that can significantly reduce design cycle times. In this research a material design tool based on a variable fidelity model management framework is presented. In the variable fidelity material design tool, complex “high fidelity” FEM analyses are performed only to guide the analytic “low-fidelity” model toward the optimal material design. The tool is applied to obtain the optimal distribution of a second phase, consisting of silicon carbide (SiC) fibers, in a silicon-nitride (Si3N4) matrix to obtain continuous fiber SiC-Si3N4 ceramic composites (CFCCs) with optimal fracture toughness. Using the variable fidelity material design tool in application to one test problem, a reduction in design cycle time around 80 percent is achieved as compared to using a conventional design optimization approach that exclusively calls the high fidelity FEM. The optimal design obtained using the variable fidelity approach is the same as that obtained using the conventional procedure. The variable fidelity material design tool is extensible to multi-scale multi-phase material design by using MD based material performance analyses as the “high fidelity” analyses in order to guide “low-fidelity” continuum level numerical tools such as the FEM or FDM (finite difference method) with significant savings in the computational time.
Characterization of Coherent Structures in the Cardiovascular System

Recent advances in blood flow modeling have provided highly resolved, four-dimensional data of fluid mechanics in large vessels. The motivation for such modeling is often to better understand how flow conditions relate to health and disease, or to evaluate interventions that affect, or are affected by, blood flow mechanics. Vessel geometry and the pulsatile pumping of blood leads to complex flow, which is often difficult to characterize. This article discusses a computational method to better characterize blood flow kinematics. In particular, we compute Lagrangian coherent structures (LCS) to study flow in large vessels. We demonstrate that LCS can be used to characterize flow stagnation, flow separation, partitioning of fluid to downstream vasculature, and mechanisms governing stirring and mixing in vascular models. This perspective allows valuable understanding of flow features in large vessels beyond methods traditionally considered.
Changes in the Testis Interstitium of Sprague Dawley Rats from Birth to Sexual Maturity

Changes in the rat testis interstitium from birth to adulthood were studied using Sprague Dawley rats of 1, 7, 14, 21, 28, 40, 60, and 90 days of age. Our objectives were 1) to understand the fate of the fetal Leydig cells (FLC) in the postnatal rat testis, 2) to determine the volume changes in testicular interstitial components and testicular steroidogenic capacity in vitro with age, 3) to differentially quantify FLC, adult Leydig cells (ALC), and different connective tissue cell types by number and average volume, and 4) to investigate the relationship between mesenchymal and ALC numbers during testicular development. FLC were present in rat testes from birth to 90 days, and they were the only steroidogenic cells in the testis interstitium at Days 1 and 7. Except for FLC, all other interstitial cell numbers and volumes increased from birth to 90 days. The average volume of an FLC and the absolute volume of FLC per testis were similar at all ages except at Day 21, when lower values were observed for both parameters. FLC number per testis remained constant from birth through 90 days. The observations suggested that the significance of FLC in the neonatal-prepubertal rat testis is to produce testosterone to activate the hypothalamo-hypophyseal-testicular axis for the continued development of the male reproductive system. ALC were the abundant Leydig cell type by number and absolute volume per testis from Day 14 onwards. The absolute numbers of ALC and mesenchymal cells per testis increased linearly from birth to 90 days, with a slope ratio of 2:1, respectively, indicating that the rate of production of Leydig cells is 2-fold greater than that of mesenchymal cells in the postnatal rat testis through 90 days. In addition, this study showed that the mesenchymal cells are an active cell population during testis development and that their numbers do not decrease but increase with Leydig cell differentiation and testicular growth up to sexual maturity (90 days).
Building a Common Table: The Role for Planning in Community Food Systems

Tensions and conflicts are rampant in the U.S. food system, occurring at epistemological, political and institutional, socioeconomic, spatial, community, and organizational levels. Some tensions are based on differences in scale, fundamental values, power, or conflicting stakeholder frames, while others are a function of stakeholders with compatible interests failing to develop a common language and agenda. This article investigates the nature of these and other emerging food systems conflicts by exploring the major stakeholder groups and their values, interests, and positions. Applying environmental and public policy dispute resolution theory and techniques, the article explores opportunities for planners to bridge food systems tensions. The article recommends specific actions that planning practitioners and planning academics can take to foster food systems discourse and to build a more economically and environmentally sound and socially just food system.
The Effects of Varenicline on Alcohol Seeking and Self‐Administration in Baboons

Background—Nicotinic acetylcholine receptors (nAChRs) may play a critical role in alcohol reinforcement and consumption. The effects of varenicline, a nAChR partial agonist, on alcohol seeking and self-administration responses were evaluated in 2 groups of baboons trained under a 3-component chained schedule of reinforcement (CSR). Methods—Alcohol (4% w/v; n=4; alcohol group) or a preferred non-alcoholic beverage (n=4; control group) was available for self-administration only in component 3 of the CSR. Responses in component 2, required to gain access to alcohol, provided indices of seeking behavior. Varenicline (0.032 – 0.32 mg/kg; 0.32 mg/kg BID) and vehicle were administered before CSR sessions subchronically (5 consecutive days). Higher doses (0.56, 1.0 mg/kg) were attempted but discontinued due to adverse effects. Results—Subchronic varenicline administration significantly (p<0.05) decreased the seeking response rate and increased the time to complete the response requirement to gain access to the daily supply of alcohol at the higher doses (0.32 mg/kg, 0.32 mg/kg BID dosing) in the alcohol group compared to the control group. Mean number of drinks was significantly decreased (p<0.05), but effects did not differ between groups. The pattern of drinking was characterized by a high rate during an initial bout. Number of drinks during and duration of the initial bout were significantly decreased in the alcohol group, compared to the control group, at 0.32 mg/kg (p<0.05). Conclusions—Varenicline may be clinically useful for reducing alcohol seeking behaviors prior to alcohol exposure. Given the modest effects on drinking itself, varenicline may be better suited as a treatment in combination with a pharmacotherapy that significantly reduces alcohol consumption.
Ocular motor delayed-response task performance among patients with schizophrenia and their biological relatives

Schizophrenia patients and their relatives have saccadic abnormalities characterized by problems inhibiting a response. The dorsolateral prefrontal cortex and its associated circuitry ostensibly mediate inhibition and support correct delayed response performance. In this context, two components of delayed response task performance are of interest: memory saccade metrics and error saccades made during the delay. To evaluate these variables, an ocular motor delayed response task was presented to 23 schizophrenia patients, 25 of their first-degree biological relatives, and 19 normal subjects. The measure that best differentiated groups was an increased frequency of error saccades generated during the delay by schizophrenia subjects and relatives. Decreased memory saccade gain also characterized patients and relatives. The similar pattern of results demonstrated by the patients with schizophrenia and their relatives suggests that performance on ocular motor delayed response tasks, either alone or in combination with other saccadic variables, may provide useful information about neural substrates associated with a liability for developing schizophrenia.
CDK8 expression in 470 colorectal cancers in relation to β-catenin activation, other molecular alterations and patient survival

Alterations in the Wnt/β-catenin pathway define a key event in the pathogenesis of colon cancer. We have recently shown that CDK8, the gene encoding a cyclin-dependent kinase (CDK) component of the Mediator complex, acts as a colon cancer oncogene that is necessary for β-catenin activity. Here, we tested the hypothesis that colorectal cancers with CDK8 expression have distinct clinical, prognostic and molecular attributes. Among 470 colorectal cancers identified in 2 prospective cohort studies, CDK8 expression was detected in 329 (70%) tumors by immunohistochemistry. Cox proportional hazards model and backward stepwise elimination were used to compute hazard ratio (HR) of deaths according to CDK8 status, initially adjusted for various patient and molecular features, including β-catenin, p53, p21, p27 (CDK inhibitors), cyclin D1, fatty acid synthase (FASN), cyclooxygenase-2 (COX-2), microsatellite instability (MSI), CpG island methylator phenotype (CIMP), LINE-1 methylation, and mutations in KRAS, BRAF and PIK3CA. CDK8 expression in colorectal cancer was independently associated with β-catenin activation (p = 0.0002), female gender (p < 0.0001) and FASN overexpression (p = 0.0003). Among colon cancer patients, CDK8 expression significantly increased colon cancer-specific mortality in both univariate analysis [HR 1.70; 95% confidence interval (CI), 1.03–2.83; p = 0.039] and multivariate analysis (adjusted HR 2.05; 95% CI, 1.18–3.56; p = 0.011) that was adjusted for potential confounders including β-catenin, COX-2, FASN, LINE-1 hypomethylation, CIMP and MSI. CDK8 expression was unrelated with clinical outcome among rectal cancer patients. These data support a potential link between CDK8 and β-catenin, and suggest that CDK8 may identify a subset of colon cancer patients with a poor prognosis.
A Review of Water Reuse and Recycling, with Reference to Canadian Practice and Potential: 1. Incentives and Implementation

As a country on the whole, Canada enjoys abundant freshwater resources, yet there remain regions with severe discrepancies between supply and demand. One solution to insufficient water supplies that has been gaining in popularity in other areas of the world is that of water reuse. Reuse or recycling of treated wastewater reduces effluent discharges into receiving waters and offers a reliable alternative supply of water for applications that do not require high-quality water, freeing up limited potable water resources. As compared to other countries worldwide, water reuse is currently practised infrequently in Canada. Use of reclaimed water requires a clear definition of the quality of water required, and while water quality criteria typically focus on pathogen risk to human health, chemical contaminants may also limit suitability for some reuse applications. Both health and environmental risk assessments are important steps in designing criteria for reuse projects. Alberta and British Columbia have recently produced guidance documents for water reuse projects; the permitted applications are discussed and the water quality criteria are compared with other standards and guidelines. Various treatment technologies for on-site and central wastewater reclamation facilities are described. Additional considerations for implementation of water reuse projects include project feasibility and planning, infrastructure needs, economics, and public acceptance.
Quantum mechanical study of photodissociation of oriented ClNO(S1)

We report a full-dimensional, quantum mechanical study of the photodissociation dynamics of ClNO(S1) with the complete (JMK) selection of the parent state. Total cross-sections, product-state distributions, and photofragment angular distributions are computed. The influence of the parent rotation and orientation on the dissociation dynamics is analysed. The calculations were carried out using a time-independent propagation method based on Chebyshev polynomials, which combines the accuracy and efficiency essential for the type of problem considered.
The Nature of Fascist Thought

Although fascism is an undeniable, if not unpleasant and terrible part of our shared human past and a defining part of the first half of the Twentieth century, almost 80 years after the word had been coined by Benito Mussolini there is still no conclusive definition for the term. Over the years efforts at a definition have gradually given way to its use as mere pejorative devoid of meaning. Although it would be nice to believe that fascism is an incoherent ideology, it is simply not feasible that it would have caused such a worldwide uproar without some form of sensible basis. In this paper, we will propose a more cognitive as well as anthropological approach. We also reject the notion that fascism is just a political doctrine. Rather, we seek a conclusive definition for it as a philosophy, which rather than concerning itself with a party platform, seeks to completely reshape society for its purpose. Along these lines, fascist thought and discourse focus heavily on the metaphorical understanding of society as an organism or individual in and of itself, as well as they express the underlying romantically naturalistic currents that help shape the Social-Darwinist weltanschauung of fascist regimes. The elements of sacrifice and death also play prominent roles in the fascist thought, not unlike that of modern terrorists. With such and understanding of fascist thought, discourse, and behavior, we seek not only to understand the way that the old fascist regimes thought, but also the appeal of sacrifice and death as well man’s view of himself in the world. Fascists, as unappetizing as the thought may be, were part of our shared human past and their cognition needs to be interpreted in the general framework of the human mind and world.
Building Cognitive Models with the EPIC Architecture for Human Cognition and Performance

The EPIC (Executive Process-Interactive Control) cognitive architecture developed by Kieras and Meyer (1997) works especially well for modeling perceptual-motor intensive tasks, multiple tasks, and complex multimodal task environments with many objects and events. The underlying theory has inspired fundamental empirical work and influenced other cognitive architectures. This tutorial presents an opportunity to become acquainted with EPIC. The goal is for attendees to learn enough about EPIC to decide whether it will be useful in their research, and if so, to get quickly started in the full use of it. Hands-on exercises will alternate with presentations of EPIC's mechanisms and facilities and how to use them. The exercises will cover two topics: Visual search, in which non-uniform visual acuity and eye movements play a critical role, and dual-task performance, in which different executive strategies for task coordination determine the overall level of performance. The only programming involved is writing production rules, so fluency in a conventional programming language is not required. A laptop (Macintosh or Windows) will be necessary, individually or shared, for the hands-on exercises. The EPIC software will be provided. Useful readings and the software can be downloaded in advance at . Also, see and for more about EPIC.
Descriptive Representation and Regime Support in Latin America

Does descriptive representation matter? We analyze the impact of descriptive representation on regime support among women and the self-identified indigenous population in Latin America. We find that having a female president does not have a consistent impact on regime support among Latin American women, but that the election of an indigenous president has significantly boosted regime support among indigenous people in Bolivia. We suggest that ethnic representation has had a greater impact than gender representation on regime support in the region for a couple of reasons. First, in Latin America, ethnicity is much more highly correlated than gender with other variables that are known to shape political attitudes, such as class, education, region, and area of residence. Second, ethnicity has been a more salient factor in elections and governing than has gender in those countries that have elected indigenous or female presidents.
Functional analysis of mild-type and malignant glioma derived CDKN2Aβ alleles: Evidence for an RB-independent growth suppressive pathway

Functional analysis of wild-type and malignant glioma derived CDKN2Aβ alleles: Evidence for an RB-independent growth suppressive pathway
Difficulties in the diagnosis of neoplasms of the major and minor salivary glands and their mimics

Epithelial tumours of salivary glands (three paired major glands and minor salivary glands) exhibit remarkable morphologic and immunophenotypic diversity, often within the same tumour. The relative infrequency of these tumours, makes diagnosis more complicated for a surgical pathologist. Pleomorphic adenoma, the most common salivary gland neoplasm, shows a biphasic appearance with an irregular periphery. Glandular, ductal and squamous epithelium merge into a myxochondroid matrix. Carcinoma ex-pleomorphic adenoma shows a carcinomatous transformation within and/or invading beyond the capsule of a concurrent pleomorphic adenoma. Extent of invasion influences prognosis. Canalicular adenoma has an upper lip predilection, comprised of frequently multifocal nodules comprised of tubules of cuboidal-columnar cells with a ‘string-of-pearls’ appearance. Basal cell adenoma, comprised of larger and smaller basaloid cells, shows circumscription, peripheral cellular palisading, and sharp separation from the surrounding hyalinised stroma. Basal cell adenocarcinoma shows invasion (soft tissue, parenchyma, vascular, neural). Adenoid cystic carcinoma has cribriform, tubular, and solid patterns of hyperchromatic, angular nuclei set within a meandering stroma with reduplicated basement membrane material and basophilic pseudocysts. Invasion (perineural especially) is easily identified. Polymorphous low grade adenocarcinoma is non-destructively infiltrative, with concentric perineural invasion, a slate-grey matrix material, and nuclei with delicate, vesicular nuclear chromatin, exhibiting few mitoses.
On the anisotropy of van der Waals atomic radii of O, S, Se, F, Cl, Br, and I.

The Cambridge Structural Database (CSD) was used to obtain flattening factors to describe the overall anisotropy of nonbonding van der Waals (vdW) contacts between several main group elements. The method for obtaining the flattening factors is based on a novel minimization process. Results show that the vdW contact distances are significantly dependent on the environment and the orientations of the surrounding covalently bonded atoms: head-on vdW contacts are generally shorter than sideways contacts in overall agreement with earlier results by Nyburg and Faerman (Acta Crystallogr., Sect. B: Struct. Sci. 1985, 41, 274–279). With the exception of Se, we find flattening factors that are somewhat smaller than those found earlier. High-level ab initio quantum chemical calculations using Ar and Ne as a probe also confirm the flattening effect and its dependency on the environment. A dozen popular long-range corrected and dispersion supplemented density functionals are compared with the CCSD(T) data. While sever...
Optimal Design of Substation Layout Based on Noise Control

Nowadays,the influence of noise in substation on environment becomes more and more obvious,and has become an urgent environmental problem. Therefore,a method of noise control in planning stage of substation was proposed,in which the noise emission was reduced through the optimization of substation layout. First of all,the numerical model was built to predict the noise at substation boundary according to the planning and design scheme. Then,based on the prediction results and the noise emission standard,the substation layout was analyzed and its optimal design was proposed,in which the noise was reduced by changing the substation layout. Through the analysis of the optimization results,the reasonable layout of substation was suggested. The simulation analysis shows that this method plays significant effect on reducing substation noise,and has a certain application and development value.
Observation of Clinical Curative Effect About Combining Use of Two Medicines in Curing Atopic Dermatitis

Objective To observe the curative effect and safety of drug curing atopic dermatitis,econazole nitrate/TA Cream(Pevisone crem).Methods We used Pevisone crem and kenacomb to cure the patients with atopic dermatitis of 3 weeks,then observed and record the condition of the first day、one week later and two weeks later.Results The total effective rate of the Pevisone crem group was 70%,and the other was 58%.The complaint and physical sign had been obviously changed after the cure by the two medicines.But there had significant difference between the two group(P0.01).Conclusion When curing atopic dermatitis,the two medicines both had obviously curative effect,but Pevisone crem is more effective than kenacomb about the complaint improvement and the recovering degree of the skin damage.
The Construction of the Temple of Universal Peace and Its Artistic Features

As one of the temples of political and religious activities for Qing Dynasty,the Temple of Univer-sal Peace was the first one built by Emperor Qianlong.The thesis expounded the unique charming architecture,statue art and the profound historical background,and explained how the emperor realized the multi-national u-nity by monarchical power from God and the Tibetan Buddhism.
Maximizing the user's benefit in the mobile cloud computing

The increasing task computation complexity and limited battery has become a serious concern for smartphones. To reduce the task computation delay and save the smartphone battery usage, there have been many efforts to offload the tasks from the mobile device to the remote cloud with a much higher computation ability. However, offloading tasks to cloud will cause extra transmission delays and energy consumption. In reality, timely task execution is very important because the task's utility decays with time. Therefore, there exists a delay-energy trade-off. This paper addresses the aforementioned challenge. The smartphone should take advantage of the cloud in high computation speed so that the smartphone can achieve the maximum utility with limited battery. We get a 2-approximation schedule on expectation by using a LP rounding algorithm. The real trace experiments show the effectiveness of the proposed algorithms.
Color changing plasmonic surfaces utilizing liquid crystal(Conference Presentation)

Plasmonic structural color has recently garnered significant interest as an alternative to the organic dyes standard in print media and liquid crystal displays. These nanostructured metallic systems can produce diffraction limited images, be made polarization dependent, and exhibit resistance to color bleaching. Perhaps even more advantageous, their optical characteristics can also be tuned, post-fabrication, by altering the surrounding media's refractive index parallel to the local plasmonic fields. A common material with which to achieve this is liquid crystal. By reorienting the liquid crystal molecules through external electric fields, the optical resonances of the plasmonic filters can be dynamically controlled. Demonstrations of this phenomenon, however, have been limited to modest shifts in plasmon resonance. Here, we report a liquid crystal-plasmonic system with an enhanced tuning range through the use of a shallow array of nano-wells and high birefringent liquid crystal. The continuous metallic nanostructure maximizes the overlap between plasmonic fields and liquid crystal while also allowing full reorientation of the liquid crystal upon an applied electric field. Sweeping over structural dimensions and voltages results in a color palette for these dynamic reflective pixels that can further be exploited to create color tunable images. These advances make plasmonic-liquid crystal systems more attractive candidates for filter, display, and other tunable optical technologies.
Measuring the Security Harm of TLS Crypto Shortcuts

TLS has the potential to provide strong protection against network-based attackers and mass surveillance, but many implementations take security shortcuts in order to reduce the costs of cryptographic computations and network round trips. We report the results of a nine-week study that measures the use and security impact of these shortcuts for HTTPS sites among Alexa Top Million domains. We find widespread deployment of DHE and ECDHE private value reuse, TLS session resumption, and TLS session tickets. These practices greatly reduce the protection afforded by forward secrecy: connections to 38% of Top Million HTTPS sites are vulnerable to decryption if the server is compromised up to 24 hours later, and 10% up to 30 days later, regardless of the selected cipher suite. We also investigate the practice of TLS secrets and session state being shared across domains, finding that in some cases, the theft of a single secret value can compromise connections to tens of thousands of sites. These results suggest that site operators need to better understand the tradeoffs between optimizing TLS performance and providing strong security, particularly when faced with nation-state attackers with a history of aggressive, large-scale surveillance.
Abstract 2247: SHP2 expression and function in different subtypes of glioblastoma

SHP2, a Src-homology 2 domain (SH2)-containing tyrosine phosphatase encoded by PTPN11, is a ubiquitously expressed cytoplasmic enzyme that regulates events downstream of several growth factor and cytokine receptors involved in survival, pro-migratory and differentiation signaling. In the normal developing nervous system, SHP2 is involved in neural stem cell self renewal. Dysregulation of SHP2 function has been implicated in tumorigenesis and characterized as an activated downstream regulator of oncogenes in gastric carcinoma, anaplastic large-cell lymphoma, breast cancer and glioblastoma. In the context of glioblastoma, we have shown that SHP2, and specifically its phosphatase activity, is directly involved in EGFRvIII-induced oncogenesis. Our present research aims at understanding the function of SHP2 within different glioma cell types as well as the four characterized subtypes of glioblastoma (GBM). Genomic analysis of SHP2 expression using the TCGA GBM cohort shows differential expression among the recently characterized subtypes of GBMs, with higher SHP2 mRNA expression in the classical subtype. Additionally, SHP2 is preferentially expressed in glioma stem cells versus differentiated cells isolated from the same patients. Furthermore, our current analysis shows that reduction of SHP2 expression in glioma stem cells affects the expression of genes linked to stemness. SHP2 PTPase function may therefore be a link between normal stem cell proliferation and gliomagenesis induced by EGFR/RTK activated signaling. Citation Format: Laura Roccograndi, Yingtao Bi, Ramana Davuluri, Nadia Dahmane, Donald M. O9Rourke. SHP2 expression and function in different subtypes of glioblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2247. doi:10.1158/1538-7445.AM2015-2247
Brief mindfulness meditation group training in aphasia: exploring attention, language and psychophysiological outcomes

Background Stroke is currently the leading cause of long-term disability in adults in the United States. There is a need for accessible, low-cost treatments of stroke-related disabilities such as aphasia. Aims To explore an intervention for aphasia utilizing mindfulness meditation (MM). This preliminary study examines the feasibility of teaching MM to individuals with aphasia. Since physiological measures have not been collected for those with aphasia, the study was also an exploration of the potential attention, language and physiological changes after MM in adults with aphasia during a brief, daily group training. Methods & Procedures A 5-day MM group training was provided to adults with aphasia (n = 5) with a waitlist control group (n = (3) who engaged in ‘mind wandering’. Participants were assigned to groups in a pseudo-random manner. A double baseline (2 days apart) was administered prior to the training and/or control group beginning. Both the training and the control groups met in a group setting. Salivary cortisol, heart rate and heart rate variability were measured during each day for both groups. Measures of attention, auditory comprehension and fluency were collected immediately after the study period and 1 week post-completion. Outcome & Results This study reinforces findings from previous work indicating that adults with aphasia can learn MM. Although not statistically significant, the training group demonstrated improved fluency immediately after MM; however, changes were not maintained at follow-up. Physiological measures showed little effect associated with MM training. No changes in attention were observed for either group. Conclusion & Implications This is an emerging area of interest due to the potential low cost of MM training. Furthermore, MM is easily taught to patients, suggesting the possibility for widespread use in clinical practice as a supplement to existing language-focused interventions.
Design of Physical Properties and Solid Form Design

The selection of the solid form for development is a key milestone in the conversion of a new chemical entity into a drug product. An understanding of the materials science of a new active pharmaceutical is crucial at the interface of medicinal chemistry and pharmaceutical development. The physical and chemical properties of a new chemical entity that impact product performance and product robustness are strongly influenced by the solid state structure of the active pharmaceutical ingredient. Product performance can only be assured when the new chemical entity is delivered to the patient in a chemically and physically stable solid form. In this chapter we will attempt to integrate progress with cutting edge computational tools in academia to the best current industrial practices so that the medicinal chemist and pharmaceutical scientist can transform the journey from molecule to medicine.
Immune cell profiling in cancer: molecular approaches to cell-specific identification

The immune system has many important regulatory roles in cancer development and progression. Given the emergence of effective immune therapies against many cancers, reliable predictors of response are needed. One method of determining response is by evaluating immune cell populations from treated and untreated tumor samples. The amount of material obtained from tumor biopsies can be limited; therefore, gene-based or protein-based analyses may be attractive because they require minimal tissue. Cell-specific signatures are being analyzed with use of the latest technologies, including NanoString’s nCounter technology, intracellular staining flow cytometry, cytometry by time-of-flight, RNA-Seq, and barcoding antibody-based protein arrays. These signatures provide information about the contributions of specific types of immune cells to bulk tumor samples. To date, both tumor tissue and immune cells have been analyzed for molecular expression profiles that can assess genes and proteins that are specific to immune cells, yielding results of varying specificity. Here, we discuss the importance of profiling tumor tissue and immune cells to identify immune-cell-associated genes and proteins and specific gene profiles of immune cells. We also discuss the use of these signatures in cancer treatment and the challenges faced in molecular expression profiling of immune cell populations.
Fracturing, fluid flow and shear zone development: Relationships between chemical and mechanical processes in Proterozoic mafic dykes from southwestern Montana, USA

Fluids can play an important role in the localization of deformation in the deep crust, yet the specific mechanisms active during the complex interactions between metasomatism, metamorphism and deformation remain elusive. Precambrian metagabbronorite dykes in southwest Montana contain fractures filled with Hbl±Grt and discrete cm-scale shear zones with well-preserved strain gradients. This system offers an ideal opportunity to constrain the chemical and mechanical processes that facilitated strain localization. An early M1 assemblage of Grt1+Cpx1+Pl1+Qz developed at conditions of 0.51 – 0.85 GPa and 500 – 700 °C and is preserved largely as a static replacement of relict igneous phases (Opx, Pgt, Pl) in coronitic textures. An M2 assemblage characterized by Grt2+Pl2± Cpx2+Hbl+Scp+Qz developed at 0.86 – 1.00 GPa and 660 – 730 °C coincided with fluid flow and deformation associated with shear zone development. Microstructural observations in marginal protomylonite/mylonite and laminated ultramylonite suggest a shear zone evolution that involved 1) nucleation from preexisting fractures that were sites for major fluid infiltration, 2) initial widening coincident with grain-size reduction by microfracturing, dislocation creep, and synkinematic metamorphic reaction by solution transfer, and 3) a switch in the dominant deformation mechanisms active in the ultramylonite from grain size insensitive mechanisms to grain size sensitive granular flow accommodated by fluid-assisted diffusion. Throughout this evolution, the effective bulk compositions of the rock volumes responding to metamorphism changed through a combination of mechanical and metasomatic processes. This article is protected by copyright. All rights reserved.
The combined effects of acidification and hypoxia on pH and aragonite saturation in the coastal waters of the California current ecosystem and the northern Gulf of Mexico

Abstract Inorganic carbon chemistry data from the surface and subsurface waters of the West Coast of North America have been compared with similar data from the northern Gulf of Mexico to demonstrate how future changes in CO2 emissions will affect chemical changes in coastal waters affected by respiration-induced hypoxia ([O2] ≤ ~ 60 µmol kg−1). In surface waters, the percentage change in the carbon parameters due to increasing CO2 emissions are very similar for both regions even though the absolute decrease in aragonite saturation is much higher in the warmer waters of the Gulf of Mexico. However, in subsurface waters the changes are enhanced due to differences in the initial oxygen concentration and the changes in the buffer capacity (i.e., increasing Revelle Factor) with increasing respiration from the oxidation of organic matter, with the largest impacts on pH and CO2 partial pressure (pCO2) occurring in the colder West Coast waters. As anthropogenic CO2 concentrations begin to build up in subsurface waters, increased atmospheric CO2 will expose organisms to hypercapnic conditions (pCO2 >1000 µatm) within subsurface depths. Since the maintenance of the extracellular pH appears as the first line of defense against external stresses, many biological response studies have been focused on pCO2-induced hypercapnia. The extent of subsurface exposure will occur sooner and be more widespread in colder waters due to their capacity to hold more dissolved oxygen and the accompanying weaker acid-base buffer capacity. Under present conditions, organisms in the West Coast are exposed to hypercapnic conditions when oxygen concentrations are near 100 µmol kg−1 but will experience hypercapnia at oxygen concentrations of 260 µmol kg−1 by year 2100 under the highest elevated-CO2 conditions. Hypercapnia does not occur at present in the Gulf of Mexico but will occur at oxygen concentrations of 170 µmol kg−1 by the end of the century under similar conditions. The aragonite saturation horizon is currently above the hypoxic zone in the West Coast. With increasing atmospheric CO2, it is expected to shoal up close to surface waters under the IPCC Representative Concentration Pathway (RCP) 8.5 in West Coast waters, while aragonite saturation state will exhibit steeper gradients in the Gulf of Mexico. This study demonstrates how different biological thresholds (e.g., hypoxia, CaCO3 undersaturation, hypercapnia) will vary asymmetrically because of local initial conditions that are affected differently with increasing atmospheric CO2. The direction of change in amplitude of hypercapnia will be similar in both ecosystems, exposing both biological communities from the West Coast and Gulf of Mexico to intensification of stressful conditions. However, the region of lower Revelle factors (i.e., the Gulf of Mexico), currently provides an adequate refuge habitat that might no longer be the case under the most severe RCP scenarios.
Do End-of-Rotation and End-of-Shift Assessments Inform Clinical Competency Committees' (CCC) Decisions?

Author(s): Regan, Linda; Cope, Leslie; Omron, Rodney; Bright, Leah; Bayram, Jamil D. | Abstract: Introduction: Clinical Competency Committees (CCC) require reliable, objective data to inform decisions regarding assignment of milestone proficiency levels, which must be reported to the Accreditation Council for Graduate Medical Education. After the development of two new assessment methods, the end-of-shift (EOS) assessment and the end-of-rotation (EOR) assessment, we sought to evaluate their performance. We report data on the concordance between these assessments, as well as how each informs the final proficiency level determined in biannual CCC meetings. We hypothesized that there would be a high concordance level between the two assessment methods, including concordance of both the EOS and EOR with the final proficiency level designation by the CCC. Methods: The residency program is an urban academic four-year emergency medicine residency with 48 residents. After their shifts in the emergency department (ED), residents handed out EOS assessment forms asking about individual milestones from 15 subcompetencies to supervising physicians, as well as triggered electronic EOR-doctor (EORd) assessments to supervising doctors and EOR-nurse (EORn) to nurses they had worked with after each two-week ED block. EORd assessments contained the full proficiency level scale from 16 subcompetencies, while EORn assessments contained four subcompetencies. Data reports were generated after each six-month assessment period and data was aggregated. We calculated Spearman’s rank order correlations for correlations between assessment types and between assessments and final CCC proficiency levels.Results: Over 24 months, 5,234 assessments were completed. The strongest correlations with CCC proficiency levels were the EORd for the immediate six-month assessment period prior (rs 0.71-0.84), and the CCC proficiency levels from the previous six-months (rs 0.83-0.92). EOS assessments had weaker correlations (rs 0.49 to 0.62), as did EORn (rs 0.4 to 0.73).Conclusion: End-of-rotation assessments completed by supervising doctors are most highly correlated with final CCC proficiency level designations, while end-of-shift assessments and end-of-rotation assessments by nurses did not correlate strongly with final CCC proficiency levels, both with overestimation of levels noted. Every level of proficiency the CCC assigned appears to be highly correlated with the designated level in the immediate six-month period, perhaps implying CCC members are biased by previous level assignments. [West J Emerg Med.20XX;X(X)–0.]
Multiscale shape–material modeling by composition

Abstract We propose a formal framework for modeling multiscale material structures by recursive composition of two-scale material structures. The framework comprises three components: (1) single scale shape–material models, supported by single scale queries, to represent the geometry and spatial distribution of material property on each coarse and fine scales, (2) mechanisms to link the scales by establishing an explicit relationship between shape–material properties at fine scale and material properties at the coarse scale, and (3) multiscale queries abstracting fundamental multiscale operations by recursive composition. While the first component is consistent with classical solid heterogeneous material modeling, the second component manifests itself as a pair of conceptually new upscaling and downscaling functions. We show that classical solid modeling queries, exemplified by point membership testing, distance computation, and material evaluation, generalize to the corresponding multiscale queries that support implicit representations of multiscale structures as a composition of distinct single scale solid material models. The concept of neighborhood is indispensable in all three components. The framework provides a formal and consistent extension of solid modeling framework that underlies most commercial systems in use today, encompasses the variety of different approaches to multiscale modeling, identifies open issues and research problems with existing two-scale modeling methods, and provides foundations for next-generation systems by identifying key objects, classes, representation schemes, and API queries.
Potential Impacts of Misconfiguration of Inverter-Based Frequency Control

This paper focuses on a transmission system with a high penetration of converter-interfaced generators participating in its primary frequency regulation. In particular, the effects on system stability of widespread misconfiguration of frequency regulation schemes are considered. Failures in three separate primary frequency control schemes are analyzed by means of time domain simulations where control action was inverted by, for example, negating controller gain. The results indicate that in all cases the frequency response of the system is greatly deteriorated and, in multiple scenarios, the system loses synchronism. It is also shown that including limits to the control action can mitigate the deleterious effects of inverted control configurations.
Coordination polymers of Cd II and Pb II with croconate show remarkable differences in coordination patterns: a structural and spectroscopic study

The croconate dianion is a highly versatile ligand with two tautomeric forms making it useful for building large superstructures in the solid state. The single-crystal X-ray structures of PbII- and CdII-croconate coordination polymers, namely catena-poly[[[diaqualead(II)]-μ-croconato-κ4O1,O2:O3,O4] monohydrate], {[Pb(C5O5)(H2O)2]·H2O}n, 1, and catena-poly[[triaquacadmium(II)]-μ-croconato-κ4O1,O2:O3,O4], [Cd(C5O5)(H2O)3]n, 2, have been determined. Both polymers form one-dimensional (1D) structures; 1 is a nonplanar 1D zigzag coordination polymer extended along the crystallographic b axis, whereas 2 is a planar 1D ribbon parallel to the [101] direction. In 2, three H2O molecules are coordinated directly to the metal atom, while in 1, only two H2O molecules are directly coordinated to the metal atom. A third interstitial H2O molecule is involved in hydrogen bonding with O atoms of the croconate ligands of an adjacent layer and other H2O molecules, resulting in stacked double layers parallel to the [105] plane. Solid-state FT-IR and solution UV-Vis spectra also substantiate the croconate coordination.
Prevalence, risk factors, and ferritin testing to mitigate iron depletion in male plateletpheresis donors.

BACKGROUND Most single-donor platelet (SDP) donors transition to plateletpheresis after prior red blood cell (RBC) donation. Recruitment may follow identification of a high platelet count, a marker associated with iron depletion (ID). SDP donors may have underrecognized risk for iron depletion. STUDY DESIGN AND METHODS To assess the prevalence of ID, we performed ferritin testing on male plateletpheresis donors with hemoglobin levels less than 13.5 g/dL. Multivariable logistic regression identified risk factors for low ferritin (LF; ferritin ≤26 ng/mL) and absent iron stores (AIS; ferritin <12 ng/mL). To assess the impact of notifying donors of LF results, we compared donation behavior of "Test" subjects before and after sending an LF notification letter to that of "Control" subjects before and after increasing the minimum hemoglobin for male donors. An electronic survey to Test donors inquired about iron supplementation practices. RESULTS Prevalence of LF was 50% and AIS was 23%, with increase in risk associated with more frequent SDP donation, both controlling for RBC donation and in donors with no recent RBC donations. Donation frequency after intervention declined less in 1272 Test donors (19%, from 13.9 to 11.2 annualized donations) than in 878 Control donors (49%, from 12.3 to 6.3 donations). Only 20% of Test donors reported taking supplemental iron when they received the LF letter; 64% of those not taking iron initiated iron supplementation following the letter. CONCLUSIONS Donors were responsive to notification of LF and attendant messaging on iron supplementation. Ferritin testing potentially benefits donor health and a stable platelet supply.
115 – Dominant Balance

Publisher Summary This chapter discusses the procedure and yield of dominant balance. It is applicable to linear and nonlinear differential equations. It yields an approximation to the solution valid in a region. A differential equation with many terms in it might be well determined by only a few of those terms. It is found that if there are M terms in a differential equation, the differential equation in a region may be solved by only considering terms to be important in that region. It is suggested to discard all the other terms, and solve the differential equation with fewer terms. It is observed that after a solution is obtained, it is important to check that the discarded terms are actually smaller than the terms that were retained.
Recognising foreign-accented speech of varying intelligibility and linguistic complexity: insights from older listeners with or without hearing loss.

The goal of this study was to assess recognition of foreign-accented speech of varying intelligibility and linguistic complexity in older adults. It is important to understand the factors that infl...
The Role of Mestiza Consciousness in Three Dimensions of Educational Expectations:A Self-Narrative of Borderland Pedagogy

This manuscript examines the ways that a Queer Chicana teacher’s multiple identities and perceptions of race, gender, and sexuality shape her efforts to disrupt colonial models of education in the ...