cssi/SciSciGPT-SciSciNet huggingface dataset:
Neurobiological basis of depression: an update

The past 5 years have seen unprecedented advances in our knowledge about the neurobiology of depression. Significant breakthroughs have been made in genomics, imaging, and the identification of key neural systems involved in cognition, emotion, and behavior. In addition, novel targets have been identified for the development of new pharmacological and behavioral treatments. Genetic variations associated with most mental disorders are being identified, and reliable tests for early detection of risk and disease are now on the horizon. New neurobiological concepts have emerged, as they relate to these advances in mental health research such as the serotonin transporter receptor, a genetic variant of which doubles the risk of depression. Brain neurochemicals, including neurotropic factors (implicated in several mental disorders), and anatomical studies involving imaging of the amygdala and the hippocampus and prefrontal cortex are now at the forefront. Several brain neurotransmitters systems: glutamate, gamma -aminobutyric acid, serotonin, norepinephrine, and dopamine have been implicated in depression and mania. These transmitter systems, as well as other neurochemical systems such as membrane-bound signal transduction systems and intracellular signaling systems that modulate gene transcription and protein synthesis, play an important role in the etiology of depression. This new knowledge is expected to provide important clues for the development of selective pharmacological interventions. Neuroimaging studies of depressed patients have shown several abnormalities of regional cerebral blood flow and glucose metabolism--a surrogate of neuronal function--in various brain regions, including the limbic cortex, the prefrontal cortex, the hippocampus, the amygdala, and the anterior cingulate cortex. At this time, a considerable amount of new information is converging--derived from animal models of mood disorders, genetics, basic behavioral research, and neuroscience. It is inevitable that the next step in this progression will be the integration of these basic advances in clinical management and the application of this new information in the context of the depressed patient.
Behavior problems at 3 and 6 years: Prevalence and continuity in full-terms and preterms

Results are reported for a 3-year prospective longitudinal study of behavior problems in a group of children born at very low birthweight (<1,500 g) and a full-term control. Behavior problems were assessed with the Behavior Screening Questionnaire (BSQ) at 3 years and with the Child Behavior Checklist (CBCL) and the hyperactivity index from the Conners parent and teacher scales at 6 years. The findings indicate that the preterms manifested more behavior problems than full-terms at both ages and that the overall prevalence of clinically significant problems increased with age. Although cross-age continuity on parent rating scales was similar and modest for both groups (r = .24–.35), the persistence of significant problems was quite high (50%). Early BSQ scores predicted later externalizing problems, even after the effects of prematurity, socioeconomic status, and family stress were removed, but not later internalizing problems. The latter were more strongly influenced by low SES and family stress. Findings for the full-terms, who had received the CBCL as well as the BSQ at 3 years, suggest that these two instruments may tap somewhat different dimensions of behavior disturbance at age 3.
Slow and fast stability in singular systems

We consider the problem of robust feedback control of LTI systems in the presence of parasitics. An essential related concept is that of fast stability -- a type of stability characterizing parasitics or high-frequency effects. A rigorous definition of fast stability is formulated in terms of topologies on a certain differentiable manifold and is connected with the robust feedback problem. A generic solution is given along with illustrative examples.
A sample path theory for time-average Markov decision processes

Considered are time-average Markov Decision Processes (MDPs) with finite state and action spaces. It is shown that the state space has a natural partition into strongly communicating classes and a set of states which is transient under all stationary policies. For every policy, any associated recurrent class must be a subset of one of the strongly communicating classes; moreover, there exists a stationary policy whose recurrent classes are the strongly communicating classes. A polynomial-time algorithm is given to determine the partition. The decomposition theory is utilized to investigate MDPs with a sample-path constraint. Here, both a cost and a reward are accumulated at each decision epoch. A policy is feasible if the time-average cost is below a specified value with probability one. The optimization problem is to maximize the expected average reward over all feasible policies. For MDPs with arbitrary recurrent structures, it is shown that there exists an ?-optimal stationary policy for each ? > 0 if and only if there exists a feasible policy. Further, verifiable conditions are given for the existence of an optimal stationary policy.
CrowdScape: interactively visualizing user behavior and output

Crowdsourcing has become a powerful paradigm for accomplishing work quickly and at scale, but involves significant challenges in quality control. Researchers have developed algorithmic quality control approaches based on either worker outputs (such as gold standards or worker agreement) or worker behavior (such as task fingerprinting), but each approach has serious limitations, especially for complex or creative work. Human evaluation addresses these limitations but does not scale well with increasing numbers of workers. We present CrowdScape, a system that supports the human evaluation of complex crowd work through interactive visualization and mixed initiative machine learning. The system combines information about worker behavior with worker outputs, helping users to better understand and harness the crowd. We describe the system and discuss its utility through grounded case studies. We explore other contexts where CrowdScape's visualizations might be useful, such as in user studies.
Detection of Molecular Markers of Drug Resistance in 2009 Pandemic Influenza A (H1N1) Viruses by Pyrosequencing

The M2 blockers amantadine and rimantadine and the neuraminidase (NA) inhibitors (NAIs) oseltamivir and zanamivir are approved by the FDA for use for the control of influenza A virus infections. The 2009 pandemic influenza A (H1N1) viruses (H1N1pdm) are reassortants that acquired M and NA gene segments from a Eurasian adamantane-resistant swine influenza virus. NAI resistance in the H1N1pdm viruses has been rare, and its occurrence is mainly limited to oseltamivir-exposed patients. The pyrosequencing assay has been proven to be a useful tool in surveillance for drug resistance in seasonal influenza A viruses. We provide a protocol which allows the detection of adamantane resistance markers as well as the I43T change, which is unique to the H1N1pdm M2 protein. The protocol also allows the detection of changes at residues V116, I117, E119, Q136, K150, D151, D199, I223, H275, and N295 in the NA, known to alter NAI drug susceptibility. We report on the detection of the first cases of the oseltamivir resistance-conferring mutation H275Y and the I223V change in viruses from the United States using the approach described in this study. Moreover, the assay permits the quick identification of the major NA group (V106/N248, I106/D248, or I106/N248) to which a pandemic virus belongs. Pyrosequencing is well suited for the detection of drug resistance markers and signature mutations in the M and NA gene segments of the pandemic H1N1 influenza viruses.
Dynamic assessment of L2 development:bringing the past into the future

The present paper outlines a theoretical framework for the application of dynamic assessment procedures to second language assessment and pedagogy. Dynamic assessment (DA) is grounded in Vygotskyâ€™s writings on the zone of proximal development (ZPD) and has been widely researched in psychology and education. DA distinguishes itself from other approaches to assessment by insisting that mediation of the examineeâ€™s performance prompts, hints, leading questions etc. â€“ during the assessment procedure is crucial to understanding his/her abilities and for promoting development during the assessment process itself. In this paper, the major approaches to DA are reviewed and some key studies are reported on. The few language-acquisition DA studies that have been carried out to date are then considered. Th e paper concludes with a discussion of some of the criticisms leveled against DA and recommendations for further research into DAâ€™s potential contributions to applied linguistics.
Alumina volatility in water vapor at elevated temperatures

The volatility of alumina in high temperature water vapor was determined by a weight loss technique. Sapphire coupons were exposed at temperatures between 1250 and 1500 C, water partial pressures between 0.15 and 0.68 atm in oxygen, total pressure of 1 atm, and flowing gas velocities of 4.4 cm/s. The pressure dependence of sapphire volatility was consistent with AI(OH)3(g) formation. The enthalpy of reaction to form Al(OH)3(g) from sapphire and water vapor was determined to be 210 +/- 20 kJ/mol, comparing favorably to other studies. Microstructural examination of tested sapphire coupons revealed surface etching features consistent with a volatilization process.
Reducing international graduate students’ language anxiety through oral pronunciation corrections

Abstract This mixed methods study examines the relationships between teachers' oral corrective feedback (CF) and changes in international graduate students' language anxiety levels. The participants were sixty advanced-level adult ESL students, all of whom were training to be teaching assistants (TAs) at a large Midwestern US university. The data were collected through classroom observations, survey questionnaires (pre- and post-surveys), and in-depth follow-up interviews with 40 of the 60 students. The study revealed that most of the teachers' oral CF had positive impacts on the students' affective variables, specifically lowering their anxiety about speaking English. However, certain clarification requests increased the students’ anxiety instead. These results highlight the potential affective risks of CF, and the study suggests how ESL instructors can use CF to encourage or even create positive emotional states in their ESL students.
Thai stick: surfers, scammers, and the untold story of the marijuana trade

With the appearance more than a decade ago of bestselling books on salt, cod, oil, and tulips, American publishing discovered the hidden life of things. Such works are the closest the American main...
Tax Incentives for Small Businesses Exporting: A Capital Budgeting Decision Analysis

Exporting is important to the health of the U.S. economy. Prior research indicates that the export potential is substantial in the small business sector. Through analysis of a base case scenario, this study presents the incremental net present value of cash flow from exporting through two tax entities specifically designed to encourage small businesses to export--the small foreign sales corporation (SFSC) and the interest-charge domestic international sales corporation (ICD). Then, the separate variables constituting the base case are allowed to vary to examine their sensitivity. In contrast to some studies, the results indicate that the SFSC results in a higher net present value of cash flow than the ICD across a broad range of variables. However, as the forecasted sales level increases and the hurdle rate gets very large, the ICD can become the optimal business form for exporting.
Methylation in hMLH1 promoter interferes with its binding to transcription factor CBF and inhibits gene expression

Microsatellite instability (MSI) is caused by the dysfunction of mismatch repair genes, such as hMLH1, hMSH2. Loss of hMLH1 expression and methylation of CpG sites in hMLH1 promoter are frequently present in sporadic colorectal cancer with MSI. In this study, by transient transfection assay with constructs containing different lengths of hMLH1 promoter and a luciferase reporter gene, we located a proximal region of hMLH1 promoter, which plays a main role in regulating the gene. The fact that luciferase activities were high in all host cell lines regardless of their hMLH1 expression levels indicates that the transcription machinery is intact even in non-expressing cells. When hMLH1 promoter was in vitro methylated before transfection, the luciferase activities in the transfectants were significantly reduced. This observation indicates that methylation causes the inhibition of hMLH1 promoter activity. By electrophoretic mobility shift assay (EMSA), we identified a CCAAT box in this region, which specifically bound transcription factor CBF. Mutations in CCAAT box not only inhibited its binding to CBF factor, but also reduced its ability to drive the expression of luciferase gene. The role of CBF in activating transcription was further substantiated by inhibition of promoter activity with a plasmid expressing a dominant negative CBF-B mutant. Methylation at a CpG site two base pairs upstream of the CCAAT box inhibited the binding of CBF to CCAAT box. We conclude that methylation of an adjacent CpG site inhibits binding of the CBF transcription to the corresponding CCAAT box, and is one of the causes of hMLH1 gene silencing in colon cancer cells.
Retrograde memory for public events in mild cognitive impairment and its relationship to anterograde memory and neuroanatomy.

OBJECTIVE The study characterized the status of retrograde amnesia (RA) in amnestic mild cognitive impairment (MCI). METHOD We measured RA, anterograde amnesia (AA), brain measures, apolipoprotein-E status (ApoE), and conversion to probable Alzheimer's disease (AD) across 3 years in 15 individuals with MCI. We compared the severity of amnesia and brain atrophy in MCI to a group of patients with limited damage to the hippocampus (H) or more extensive damage to the medial temporal lobe (MTL). RESULTS The MCI group exhibited modest AA, together with severe RA, covering nearly 4 decades before their diagnosis. Compared with H-MTL patients, the temporal extent of RA was disproportionate to the severity of AA. The MCI group exhibited more modest AA and MTL atrophy than H-MTL patients, together with more severe RA and neocortical atrophy than H-MTL patients. The severity of AA corresponded to the integrity of MTL structures, whereas the severity of RA corresponded to the integrity of both MTL and neocortical structures. RA (but not AA, nor measures of cognitive status) was related to ApoE status and subsequent diagnosis of probable AD. RA was predicted by heritable risk for AD, in addition to the integrity of MTL and neocortical structures. CONCLUSIONS Compared with H-MTL patients, the MCI group exhibited RA that was disproportionate to their AA and that was more severe than would be expected if their atrophy were limited primarily to the MTL. Heritable risk for AD, as well as the integrity of brain regions within and beyond the MTL, are important for understanding RA in MCI.
An In-Situ X-Ray Microtomography Study of Split Cylinder Fracture in Cement-Based Materials

In an effort to quantify microstructure-property relationships, three dimensional imaging experiments were conducted on small cylinder specimens subjected to split cylinder fracture. 3-D images were made using synchrotron-based x-ray microtomography, and the experiments were conducted with an in-situ frame such that a specimen could be examined while under load at varying degrees of damage. The specimens were made of fine-grained portland cement mortar and 0.5 mm glass beads, which served as aggregates. The diameter of the specimens was 5 mm. 3-D image analysis routines were developed or adapted to characterize microstructure and internal damage, which could then be related to bulk splitting strength and fracture energy. For fracture energy calculation, crack surface area could be measured in a way that accounted for roughness, branching, and fragmentation. Results showed that, for the specimens tested, aggregate surface roughness had little effect on strength but significant effect on fracture energy. Split cylinder strength showed correlation with specimen porosity, although there was considerable scatter. Strength did not correlate with maximum flaw size, although flaw location was not evaluated.
Revegetation of coal mine soil with forest litter

Forest litter, a good source of organic matter and seeds, was applied on undisturbed soil and on coal mine (spoils) in experiments conducted on the Black Mesa Coal Mine near Kayenta, Arizona over a 2-year period (1977–1978). Germination, seedling establishment, plant height and ground cover were evaluated for two seeding treatments (forest litter and no forest litter) and two soil moisture treatments (natural rainfall and natural rainfall plus irrigation). The forest litter was obtained at random from the Coconino National Forest, broadcast over the surface of the soil materials and incorporated into the surface 5 cm of each soil material. Germination, seedling establishment, plant height and ground cover on undisturbed soil and coal mine soil were higher when forest litter was applied than when it was not applied and when natural rainfall was supplemented with sprinkler irrigation than when rainfall was not supplemented with irrigation. Applications of forest litter and supplemental irrigation may ensure successful establishment of vegetation on areas disturbed by open-pit coal mining.
Arc fault and flash detection in photovoltaic systems using wavelet transform and support vector machines

Arc faults pose significant reliability and safety issues in today's photovoltaic (PV) systems. This paper presents an effective method based on wavelet transform and support vector machines (SVM) for detection of arc faults in DC PV systems. Because of its advantages in time-frequency signal processing, wavelet transform is applied to extract the characteristic features from system voltage/current signals. SVM is then used to identify arc faults. The performance of the proposed technique is compared with traditional Fourier transform based approaches.
On the Study of Ethnic Enterprise: Unresolved Issues

In their own essays, editors tend to discuss the articles in their collection in light of the existing literature. To provide this sort of overview here, however, would be duplicating existing work (e.g., Bonacich and Modell, 1980; Portes's piece in this issue; Waldinger, 1986; Zenner, 1980). A more productive approach, in my view, is to discuss the preceding essays in the light of unresolved issues in the study of ethnic enterprise. In pointing out existing dubious assumptions, contradictions, and other uncertainties, I hope to stimulate badly needed dialogue about these problems in the study of ethnic enterprise.
Forage Performance in Crop–Livestock Systems Designed to Reduce Water Withdrawals From a Declining Aquifer☆

On the Ground • In the semiarid Texas High Plains, integrating crops with grazing systems could conserve irrigation water and increase perennial grassland. • We combined irrigated and nonirrigated exotic and native grasses with cotton production. • We grazed and hayed the grasses, harvested grass seed, and harvested cotton. • Strategically combining different forages, fertilizer, and water inputs can extend the grazing season, improve the quality of available forage, and provide a buffer against moderate drought. • Nonirrigated, seeded native grass mixtures can provide valuable grazing and decrease total water use of an integrated crop-livestock system.
Toward automated detection of logic vulnerabilities in web applications

Web applications are the most common way to make services and data available on the Internet. Unfortunately, with the increase in the number and complexity of these applications, there has also been an increase in the number and complexity of vulnerabilities. Current techniques to identify security problems in web applications have mostly focused on input validation flaws, such as crosssite scripting and SQL injection, with much less attention devoted to application logic vulnerabilities. Application logic vulnerabilities are an important class of defects that are the result of faulty application logic. These vulnerabilities are specific to the functionality of particular web applications, and, thus, they are extremely difficult to characterize and identify. In this paper, we propose a first step toward the automated detection of application logic vulnerabilities. To this end, we first use dynamic analysis and observe the normal operation of a web application to infer a simple set of behavioral specifications. Then, leveraging the knowledge about the typical execution paradigm of web applications, we filter the learned specifications to reduce false positives, and we use model checking over symbolic input to identify program paths that are likely to violate these specifications under specific conditions, indicating the presence of a certain type of web application logic flaws. We developed a tool, called Waler, based on our ideas, and we applied it to a number of web applications, finding previously-unknown logic vulnerabilities.
Terahertz endoscopic imaging for colorectal cancer detection: Current status and future perspectives.

Terahertz endoscopic imaging for colorectal cancer detection: Current status and future perspectives
Abstract 434: Sirt4 Accelerates Ang II-induced Pathological Cardiac Hypertrophy by Inhibiting Mnsod Activity

Aims: Oxidative stress contributes to the development of cardiac hypertrophy and heart failure. One of the mitochondrial sirtuins, Sirt4, is highly expressed in the heart, but its function remains unknown. The aim of the present study was to investigate the role of Sirt4 in the pathogenesis of pathological cardiac hypertrophy and the molecular mechanism by which Sirt4 regulates mitochondrial oxidative stress. Methods and results: Male C57BL/6 Sirt4 knockout mice, transgenic mice exhibiting cardiac-specific overexpression of Sirt4 (Sirt4-Tg) and their respective controls were treated with angiotensin II (Ang II). At 4 weeks, hypertrophic growth of cardiomyocytes, fibrosis and cardiac function were analyzed. Sirt4 deficiency conferred resistance to Ang II infusion by significantly suppressing hypertrophic growth, and the deposition of fibrosis. In Sirt4-Tg mice, aggravated hypertrophy and reduced cardiac function were observed compared with non-transgenic mice following Ang II treatment. Mechanistically, Sirt4 inhibited the binding of manganese superoxide dismutase (MnSOD) to Sirt3, another member of the mitochondrial sirtuins, and increased MnSOD acetylation levels to reduce its activity, resulting in elevated reactive oxygen species (ROS) accumulation upon Ang II stimulation. Furthermore, inhibition of ROS with MnTBAP, a mimetic of SOD, blocked the Sirt4-mediated aggravation of the hypertrophic response in Ang II-treated Sirt4-Tg mice. Conclusions: Sirt4 promotes hypertrophic growth and cardiac dysfunction by increasing ROS levels upon pathological stimulation. These findings reveal a role of Sirt4 in pathological cardiac hypertrophy, providing a new potential therapeutic strategy for this disease.
Development of a broadly accessible Venezuelan equine encephalitis virus replicon particle vaccine platform

Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine, strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the VRP 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. Importantly, packaging under biosafety level 2 (BSL2) conditions distinguishes VRP 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. In addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated VRP approaches. Taking these results together, the VRP 3526 platform represents a safe and highly portable system that can be rapidly deployed under BSL2 conditions for generation of candidate vaccines against emerging microbial pathogens.IMPORTANCE While VEE virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. In this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. Importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. Together, the new system represents a highly portable, safe system for use in the context of disease emergence.
Towards a theory of trust in networks of humans and computers (transcript of discussion)

When I first noticed this year's SPW theme I realized that not only Alice isn't living here anymore, but that we do not really know who Alice is, after all these years. Is she a fictitious character of Oscar Wilde's Importance of being Earnest (1895) who tries to avoid the obligations of Victorian-era social protocols? Or maybe the fickle character of the Duke of Mantua's aria in Verdi's Rigoletto (1851)? Or, perhaps the fictitious and equally fickle character of our past Security Protocols Workshops who changes her goals and behavior from year to year? Whichever the case may be, one thing is clear: Alice may not always be trustworthy--as she sometimes seems to be involved in shady activities--but she must always be accountable in our protocols. Hence, we must look into what makes Alice accountable in networks that do not provide accountability for protocol participants by default; e.g., in the Internet. In particular, I argue that we could locate Alice in a multi-dimensional accountability space similar in spirit to that used in online behavioral advertising (OBA). Since in security protocols we often deal with networks of computers and humans, it seems useful to look at OBA, which also captures the behaviour of humans and computers well enough to become a source of (possibly anonymous) identity.
Histopathology in the Theiler’s Virus Model of Demyelination

The Theiler’s virus model shows all the major features of MS pathology - demyelination, inflammation, axonal injury, and remyelination. Extensive qualitative and quantitative characterization of the pathology has provided important insights into disease mechanisms, particularly how they relate to neurological function.
Portfolio and Project Planning and Management in the Drug Discovery, Development, and Review Process

Publisher Summary A well-planned and -managed pharmaceutical research and development (R&D) portfolio can be defined as “The combination of all R&D projects, which is based on past company and industry performance and will predictably yield valuable new products at the rate needed to support the planned growth of the organization.” Project planning is the application of knowledge, skills, tools, and techniques to project activities to meet or exceed stakeholder needs and expectations from a project. Portfolio value is maximized by appropriately prioritizing the projects within the portfolio based on the future potential financial value of each project multiplied by its probability of success. Once the portfolio vision and design have been defined, the organization can focus on the way to build that portfolio. As projects mature from one stage to the next or are terminated because of the lack of success, additional projects need to be added to the various stages of the portfolio to ensure a portfolio of adequate size at each stage. The portfolio optimization using sensitivity analysis is also elaborated in the chapter and several tools that are useful in the planning and management of biopharmaceutical projects are described.
The State of State Advisory Commissions on Intergovernmental Relations: Do They Continue to Have a Role in the U.S. Federal System?

This paper focuses on the organizational, structural, financial, and staffing aspects of existing state Advisory Commissions on Intergovernmental Relations agencies, and on identifying those factors which - at least from the perception of agencies and agency directors themselves - most contribute to successful performance. The paper in conclusion speculates on the continued and future role of state ACIRs in the American federal system. Results reported herein are based on face to face interviews, phone interviews, e-mail correspondence, web-site analysis, and mailed surveys of directors and other staff members of state Advisory Commissions on Intergovernmental Relations (ACIRs) active as of the spring of 2009, and interviews with as many directors and staff personnel of terminated state ACIRs as were possible to obtain.
Valuating fire suppression risk data

Abstract Efficient and effective wildland fire response requires interregional coordination of suppression resources. We developed a mathematical model to examine how scarce resources are shared. Best-fit models describe regional resource allocation according to driving risk factors. By regressing a linear system of ordinary differential equations with GIS-data for demand predictors like suppression resource use, ongoing fire activity, fire weather metrics, accessibility, and population density onto pre-smoothed Resource Ordering Status System (ROSS) wildfire personnel and equipment requests, we fit a national scale model. We report statistical properties of the best-fit parameters and indicate how these findings might be interpreted for personnel and equipment sharing by examining test cases for national, central/southern Rockies, and California interregional sharing. Abrupt switching behavior across medium and high alert levels was found in test cases for national, central/southern Rockies, and California interregional sharing.
CellPAINT: Interactive Illustration of Dynamic Mesoscale Cellular Environments

CellPAINT allows nonexpert users to create interactive mesoscale illustrations that integrate a variety of biological data. Like popular digital painting software, scenes are created using a palette of molecular “brushes.” The current release allows creation of animated scenes with an HIV virion, blood plasma, and a simplified T-cell.
CRISPR/Cas9-mediated targeted T-DNA integration in rice.

Combining with a CRISPR/Cas9 system, Agrobacterium-mediated transformation can lead to precise targeted T-DNA integration in the rice genome. Agrobacterium-mediated T-DNA integration into the plant genomes is random, which often causes variable transgene expression and insertional mutagenesis. Because T-DNA preferentially integrates into double-strand DNA breaks, we adapted a CRISPR/Cas9 system to demonstrate that targeted T-DNA integration can be achieved in the rice genome. Using a standard Agrobacterium binary vector, we constructed a T-DNA that contains a CRISPR/Cas9 system using SpCas9 and a gRNA targeting the exon of the rice AP2 domain-containing protein gene Os01g04020. The T-DNA also carried a red fluorescent protein and a hygromycin resistance (hptII) gene. One version of the vector had hptII expression driven by an OsAct2 promoter. In an effort to detect targeted T-DNA insertion events, we built another T-DNA with a promoterless hptII gene adjacent to the T-DNA right border such that integration of T-DNA into the targeted exon sequence in-frame with the hptII gene would allow hptII expression. Our results showed that these constructs could produce targeted T-DNA insertions with frequencies ranging between 4 and 5.3% of transgenic callus events, in addition to generating a high frequency (50−80%) of targeted indel mutations. Sequencing analyses showed that four out of five sequenced T-DNA/gDNA junctions carry a single copy of full-length T-DNA at the target site. Our results indicate that Agrobacterium-mediated transformation combined with a CRISPR/Cas9 system can efficiently generate targeted T-DNA insertions.
Communication Surrounding Prognostication in the ICU: More Than Mere Talk?

Quality patient care in the cardiothoracic intensive care unit (CTICU) requires providers to attend to not only biomedical, but psychological and social needs of the patient. Furthermore, in determining the trajectory and goals of care, providers must give prognostic estimates and stand with patients and surrogates to reach appropriate and value-affirming decisions. Here, we review the literature surrounding communication of prognostic information and make evidence based recommendations for the provider in the CTICU.
ICF-inspired goal-setting in developmental rehabilitation: an innovative framework for pediatric therapists.

Background:Collaborative goal-setting is a fundamental component of developmental physical and occupational therapy practice. Evidence suggests, however, that therapists struggle to elicit patient and family goals, and they often establish goals that are not reflective of patient and caregiver functional preferences. Training and efficiency also act as barriers to collaborative goal-setting. A number of solutions have been proposed to enhance the goal-setting process, but none specifically address relevant areas of functioning within the International Classification of Functioning, Disability and Health (ICF), a robust, multidimensional tool that emphasizes the importance of function. To support pediatric therapists in the collaborative establishment of functionally relevant goals, an ICF-inspired goal-setting tool was developed through the assimilation of a large body of existing scientific evidence, ICF Core Sets, and expert consensus. Objective:The aims of this paper are to: 1) describe an ICF-inspired framework for collaborative goal-setting in developmental rehabilitation that seeks to reduce the methodological challenges frequently associated with goal-setting; and 2) discuss the conditions for the use of the framework in daily therapeutic practice. Conclusions:The goal-setting framework presented in this paper may help pediatric therapists to create meaningful goals in collaboration with patients and families. Importantly, the goal-setting framework described promotes the use of the ICF in therapeutic practice.
Increasing Management Retention: The Mediating Role of Organizational Embeddedness on Coworker Support and Turnover Intention

The hospitality industry continues to grow, but high turnover still persists including within managers and supervisors. Despite their importance, research often focuses on hourly front line employe...
Republished: A lumbar arteriovenous fistula presenting with intraventricular hemorrhage and hydrocephalus

Pediatric spinal vascular malformations are rare entities that typically present with symptoms from their effect on surrounding structures. Here we report a unique case of lumbar spinal dural/perimedullary arteriovenous fistula (AVF) that presented with intraventricular hemorrhage and hydrocephalus. The previously healthy child presented with lethargy and headache, and initial imaging revealed only ventriculomegaly with trace intraventricular blood. His mental status improved with CSF diversion via an external ventricular drain. Further workup revealed a spinal AVF that was treated via endovascular embolization. His course was complicated by vasospasm requiring endovascular treatment and he eventually required ventriculoperitoneal shunt placement. He made a full recovery and has returned to his normal activities. This is a unique case of spinal AVF presentation and highlights the importance of considering imaging of the entire neuroaxis during workup for hydrocephalus.
Immunoglobulin G/albumin staining in tubular protein reabsorption droplets in minimal change disease and focal segmental glomerulosclerosis.

BACKGROUND Some renal biopsies cannot distinguish minimal change disease (MCD) from primary focal segmental glomerulosclerosis (FSGS) because of inadequate sampling and/or a lack of sampled glomeruli with segmental sclerosis. As protein excretion in MCD has been described as being albumin-selective, we examined whether the ratio of immunoglobulin G (IgG)/albumin staining in protein reabsorption droplets (tPRD) might help distinguish MCD from FSGS. METHODS Frozen tissue from 144 native renal biopsies from patients with nephrotic syndrome and a diagnosis of MCD or FSGS [73 MCD, 30 FSGS tip variant (FSGS-tip), 38 FSGS-not otherwise specified (FSGS-NOS), 3 FSGS collapsing] was retrospectively stained by direct immunofluorescence for IgG and albumin; none of these samples showed diagnostic lesions of FSGS. IgG and albumin staining of tPRD were graded on a scale of 0 to 3+ based on the distribution and intensity of staining. RESULTS Mean (standard deviation) IgG/albumin staining ratios were 0.186 ± 0.239 for MCD, 0.423 ± 0.334 for FSGS-tip (P = 0.0001 versus MCD) and 0.693 ± 0.297 for FSGS-NOS (P < 0.0001 versus MCD; P = 0.0001 versus FSGS-tip). Of 84 biopsies with a ratio ≤0.33, 63 (75%) showed MCD, whereas among 21 with a ratio of 1.0, all but one showed FSGS (15 FSGS-NOS). CONCLUSIONS In summary, IgG/albumin staining in tPRD was correlated with histologic diagnosis in renal biopsies with MCD and FSGS. A ratio of ≤0.33 was associated with MCD, whereas a ratio of 1.0 was most often seen with FSGS-NOS.
P237 Enzyme complexes of alcohol metabolism protect against liver injury in animal models fed acute alcohol and anti-HIV drugs

Background A significant portion of AIDS patients under anti-HIV therapies consume or abuse alcohol, which causes liver injuries. This study was to evaluate effects of eliminating blood alcohol on anti-HIV drugs and alcohol-induced liver injuries through utilizing nanoparticles of enzyme complexes of alcohol metabolism that were developed previously. Methods The enzyme nanoparticles were intravenously injected into mouse models of acute alcohol binge or chronic alcohol and antiviral feeding in the presence of antivirals (ritonavir-boosted lopinavir). Parameters for liver pathologies were examined. Results In the acute model, the enzyme nanoparticles significantly reduced the blood alcohol concentration (BAC) within four hours compared to control. No significant effects of the anti-HIV drugs on BAC were observed in the acute alcohol binge model. Plasma alanine aminotransferase (ALT) and expression of liver TNFα were both significantly increased in the alcohol fed mice, which were normalized by the enzyme nanoparticles. In the presence of the antivirals, ALT was partially reduced by the enzyme nanoparticles. In the chronic alcohol feeding, alcohol induced inflammation, fatty liver and increase of ALT, which were deteriorated by the antivirals. the enzyme nanoparticles slightly reduced BAC, ALT and expression of inflammation markers of TNFα, F4/80 and IL-6 and lipogenic factors of ACC, LXRa and SREBP1. In addition, the anti-HIV drugs potentiated alcohol induced expression of cellular organelle stress markers of CHOP, sXBP-1, ATF6 and GCP60, which were not reduced by the application of the enzyme complexes. Conclusion Eliminating blood alcohol by the enzyme nanoparticles protects the liver against acute alcohol-induced liver injuries, and the protection is much less effective under chronic alcohol feeding or combination of alcohol and antiviral use due to severe cellular stresses in the liver. Disclosure No significant relationships.
Updating the Cost Effectiveness of Oral Anticoagulants for Patients with Atrial Fibrillation Based on Varying Stroke and Bleed Risk Profiles.

Previous investigations into the cost effectiveness of direct oral anticoagulants only considered individual stroke risk but not bleed risk even though bleeding is an important and potentially fatal side effect for anticoagulated patients. This study aimed to evaluate the cost effectiveness of dabigatran, rivaroxaban, apixaban, and edoxaban vs warfarin in patients with atrial fibrillation with varying stroke/bleed risk profiles over a lifetime horizon. A Markov micro-simulation was adapted to examine the lifetime costs and quality-adjusted survival of five anticoagulants from a US private payer’s perspective. The study hypothetical cohort consisted of 10,000 patients with atrial fibrillation with age, CHA2DS2-VASc, and HAS-BLED scores similar to a commercially insured patient with atrial fibrillation cohort. Model input parameters including the efficacy and safety of each strategy, utilities, and cost were estimated from public sources, published literature, and analysis conducted in the IBM MarketScan database. Lifetime cost, quality-adjusted life-years, and incremental cost-effectiveness ratios were assessed for each treatment strategy. Subgroup analyses stratified by age, stroke risk score alone, bleed risk score alone and both were performed. Uncertainty was assessed by a deterministic sensitivity analysis and a probabilistic sensitivity analysis. The base-case analysis suggested dabigatran was the optimal treatment with an incremental cost-effectiveness ratio of $35,055 per quality-adjusted life-year relative to warfarin. Subgroup analyses stratified by age, stroke risk score, and bleed risk score alone were largely consistent with the base-case analysis. Subgroup analyses stratified by both stroke and bleed risk score showed edoxaban was the preferred treatment in patients with a low stroke and a low or medium bleed risk, and patients with a high stroke and low bleed risk. Apixaban was the preferred treatment in patients with a medium stroke and high bleed risk. Results of the deterministic sensitivity analysis indicate the model results were most sensitive to the drug cost and hazard ratio for stroke and bleeding event. Results of the probability sensitivity analysis showed dabigatran is cost effective vs. other treatments in 32.8% and 42.4% of iterations at a willingness to pay of $50,000/quality-adjusted life-year and a willingness to pay of $100,000/quality-adjusted life year, respectively. From a US private payer’s perspective, dabigatran appears cost effective compared with other anticoagulants. This study indicated risk stratification especially considering both stroke and bleed risk simultaneously is important not only in clinical practice but also in health technology assessment exercises among patients with atrial fibrillation.
The error-related negativity as a neuromarker of risk or resilience in young children.

Introduction The error‐related negativity (ERN) is a neural response that reflects error monitoring. Contradictorily, an enlarged (more negative) ERN has been cited as both a risk factor and a protective factor, which hinders its utility as a predictive indicator. The aim of the current study was to examine the associations between ERN measured in early childhood with the development of cognitive control (CC), emotion regulation, and internalizing/externalizing symptoms over 1–2 years.
Skyshine Calculations for a Large Spent Nuclear Fuel Storage Facility with SCALE 6.2.3

The SCALE code system developed at Oak Ridge National Laboratory includes state-of-the-art capabilities for radiation source term and radiation transport simulations that can be used in numerous ap...
Factor Structure and Measurement Invariance of the Academic Time Management and Procrastination Measure

Students’ ability to effectively allocate time toward educational tasks and reduction of maladaptive behaviors such as procrastination are important predictors of successful educational outcomes. T...
Dreams and Power Between Jacob and Joseph, a Speculative Interpretation

This chapter offers a speculative critique of the dominant interpretation of the stories of Jacob and Joseph in the book of Genesis. The chapter argues that Joseph is not a continuation of the patriarchal line, but a tyrannical figure and enemy of the faith of Jacob. By seeing Joseph in this light, the chapter presents a new reading of Jacob and his dream of the ladder as suggesting a more immediate, non-hierarchical, and open conception of faith. It is precisely this anarchistic conception of faith that the Joseph tradition seeks to bury in the text through the interpolation of the dream-texts and, with it, the idea of divinely controlled history. The radical politics of Jacob’s dreamscape, however, continue to present emancipatory possibilities despite the authoritarian exegetical tradition.
Sustainability, Big Data, and Local Community: A Simulation Case Study of a Growing Higher Education Institution

Higher education institutions are core elements in the sustainable development paradigm because they prepare the future decision-makers of the local, national, or international societies. At the same time, many colleges and universities just declare their sustainability support and rarely use a quantitative approach to analyze/manage this area. It is happening because of sustainable development paradigm complexity, reusability problems of already created tools/models, and some methodological difficulties to use already available big data. This paper introduces an approach where we use simulation as a united methodological platform to combine sustainability, big data, and local community needs for particular numerical analysis. Within the simulation case study, we analyze the transportation system as a part of the sustainability of a young fast-growing higher education institution, the USA.
Stage-specific disruption of X chromosome expression during spermatogenesis in sterile house mouse hybrids

Hybrid sterility is a complex phenotype that can result from the breakdown of spermatogenesis at multiple developmental stages. Here, we disentangle two proposed hybrid male sterility mechanisms in the house mice, Mus musculus domesticus and M. m. musculus, by comparing patterns of gene expression in sterile F1 hybrids from a reciprocal cross. We found that hybrid males from both cross directions showed disrupted X chromosome expression during prophase of meiosis I consistent with a loss of Meiotic Sex Chromosome Inactivation (MSCI) and Prdm9-associated sterility, but that the degree of disruption was greater in mice with an M. m. musculus X chromosome consistent with previous studies. During postmeiotic development, gene expression on the X chromosome was only disrupted in one cross direction, suggesting that misexpression at this later stage was genotype-specific and not a simple downstream consequence of MSCI disruption which was observed in both reciprocal crosses. Instead, disrupted postmeiotic expression may depend on the magnitude of earlier disrupted MSCI, or the disruption of particular X-linked genes or gene networks. Alternatively, only hybrids with a potential deficit of Sly copies, a Y-linked ampliconic gene family, showed overexpression in postmeiotic cells, consistent with a previously proposed model of antagonistic coevolution between the X and Y-linked ampliconic genes contributing to disrupted expression late in spermatogenesis. The relative contributions of these two regulatory mechanisms and their impact on sterility phenotypes awaits further study. Our results further support the hypothesis that X-linked hybrid sterility in house mice has a variable genetic basis, and that genotype-specific disruption of gene regulation contributes to overexpression of the X chromosome at different stages of development. Overall, these findings underscore the critical role of epigenetic regulation of the X chromosome during spermatogenesis and suggest that these processes are prone to disruption in hybrids.