cssi/SciSciGPT-SciSciNet huggingface dataset:
In vivo molecular implications of the combination of the hypo-methylating agent 5-aza-2’-deoxycytidine and the histone deacetylase inhibitor valproic acid in patients with leukemia: Results of a phase I/II study

3979 Epigenetic silencing can be reversed in vitro using agents with hypomethylating or histone deacetylase inhibitory (HDI) activity. The combination of 5-aza-2’-deoxycytidine (DAC), a potent hypomethylating agent, and valproic acid (VPA), an antiepileptic drug with HDI activity, has synergistic antileukemia activity in vitro. We have developed a phase I/II study of this combination in patients (pts) with leukemia. In this study, a fixed low dose of DAC (15 mg/m2 IV daily x 10) was combined with VPA. In the phase I portion of the study, three doses of VPA have been studied: 20, 35 and 50 mg/kg orally daily x 10 concomitant with DAC. The phase II portion uses the combination at its MTD level targeting a response rate of 30%. Responses are defined as complete remissions (CR) or hematological improvements (=CR without platelet recovery). The study stops if 0/10 pts, ≤ 3/20, or ≤ 5/30 respond. Forty-two pts with relapsed/refractory acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) and 9 untreated elderly pts with AML/MDS (total 51) have been registered. VPA doses up to 50 mg/kg orally daily have been combined with DAC with no excess toxicity. At these doses, 9 out of 28 evaluable pts responded. Three out of 4 untreated elderly pts responded to the therapy. So far no relapse has occurred (range 1 to 7+ months). Blood or bone marrow has been obtained on days 0,1,5,10,21 and 28 of each cycle. Free and bound VPA levels are available in 43 pts. Higher levels of both free and bound VPA were observed in responders than in non-responders (36 mg/L vs. 21; 127 ug/ml vs 104 respectively, p=0.02). Histone H3 and H4 acetylation was measured using Western blots in 38 pts. At VPA doses of 20 or 35 mg/kg, 1 out 11 pts (9%) had evidence of histone acetylation compared to 11 out 28 pts (37%) at the 50 mg/kg dose level (p=0.002). No association has been yet observed between histone acetylation and VPA blood levels or response. Subsequently, we evaluated the effects of the combination on global DNA methylation using a bisulfite-based pyrosequencing assay of LINE methylation. In the first 30 pts evaluated, a gradual median decline of 7% (+/− 5%) in LINE methylation is observed by day 10 of treatment. LINE methylation levels are restored to baseline by day 28. No DNMT1 trapping was observed in 10 patients evaluated. Finally, p21 induction was evaluated sequentially during therapy using a real-time PCR assay in 30 patients. An increase in more than 2 fold expression was observed in 20% of patients of 30 evaluated. So far no association between LINE hypomethylation or p21 induction and response has been observed. In summary, the combination of DAC and VPA is safe and has significant activity in patients with AML and MDS. In vivo, it induces histone acetylation, LINE hypomethylation and p21 induction in a significant fraction of patients. The study is ongoing.
Appearance-based gesture recognition in the compressed domain

We propose a novel appearance-based gesture recognition algorithm using compressed domain signal processing techniques. Gesture features are extracted directly from the compressed measurements, which are the block averages and the coded linear combinations of the image sensor's pixel values. We also improve both the computational efficiency and the memory requirement of the previous DTW-based K-NN gesture classifiers. Both simulation testing and hardware implementation strongly support the proposed algorithm.
Substance use among bi/multiracial youth in the United States: Profiles of psychosocial risk and protection

Background: Bi/multiracial youth face higher risk of engaging in substance use than most monoracial youth. Objectives: This study contrasts the prevalence of substance use among bi/multiracial yout...
Clonazepam: Benzodiazepine Therapy for the Restless Legs Syndrome

Clonazepam is one of several agents used for the treatment of the restless legs syndrome of ESRD. The drug's pharmacokinetic profile demonstrates safety in patients with altered kidney function. Future studies may provide an enhanced understanding of the physiological basis of the disorder to lead to improved pharmacological therapy. Other medication alternatives such as narcotics, dopamine agonists, clonidine, and gabepentin are available for patients unable to tolerate or receive benefit from clonazepam.
P141Kas three years later: life after the bolus effect

Aim The new Kidney Allocation System (KAS) resulted in a significant bolus in the transplantation of 99–100 CPRA candidates due to increased priority. We examined the impact of an individualized approach to maintain a high transplant rate for these candidates three years after KAS implementation. Methods The early post-KAS period (EPKAS) was defined as deceased donor transplants occurring in 2015 and 2 year post-KAS period (2YPKAS) as 2016 and 2017. Donor specific antibody positivity (DSA+) was defined by single antigen bead assays performed pre-transplant (±7 days) and 90 days post-transplant (±14 days). Flow cytometric crossmatches (FCXM) were performed using the pre-transplant serum, donor lymphocytes, and acquisition on a BD Canto instrument. Data from SRTR was used to assess outcome at 1 year for our center and nationally. Results Nationally, transplantation of 99–100 CPRA candidates rose sharply (17.7%) in the EPKAS period and has since tapered (10%) in the 2YPKAS period. At our center, we observed a similar increase in the EPKAS period (16%, n = 30) but this trend increased further during the 2YPKAS period (28%, n = 75). In the EPKAS period, 60% (n = 18) of 99–100 CPRA recipients were DSA+ and 39% (n = 7) of DSA+ recipients were also FCXM positive. 61% (n = 11) of DSA+ recipients during this period had persistent DSA at 90 + days post-transplant. In the 2YPKAS period, a similar percentage (57%, n = 43) of 99–100 CPRA recipients were DSA+ at time of transplant; however, fewer (8%, n = 6) DSA+ recipients were also FCXM+. Correspondingly, fewer (34%, n = 26) DSA+ recipients had persistent DSA at 90 + days post-transplant. A total of five (5%) candidates in the post-KAS era experienced a rise in DSA post-transplant that required intervention. The hazard ratio for 1 year graft survival was 1.05 for our center and 1.00 nationally. Conclusions Our center continues to successfully transplant 99–100 CPRA candidates at a rate higher than the national average. This has been achieved through a personalized approach for defining unacceptable antigens and assessing donor offers, transplanting across DSA barriers, and a stringent post-transplant monitoring protocol. Refinement in our approach in the 2 year post-KAS has resulted in more compatible transplants, less DSA persistence, and the maintenance of good clinical outcomes. A.M. Jackson: 3. Speaker’s Bureau; Company/Organization; Thermo-Fisher.
Autoimmune genetic variants as germline biomarkers of response in melanoma immunotherapy treatment.

3079Background: Immune checkpoint inhibition (ICI) has improved clinical outcomes for metastatic melanoma patients. However, ~ 60% of patients do not respond to ICI and 65-80% experience immune-rel...
Systemic and tissue microRNAs changes in early phase of breast cancer development.

e13548Background: MicroRNAs (miRs) and their distribution in circulation have been implicated in physiological and pathological processes. Recently, circulating miRs have emerged as potential bioma...
Thermal hydraulic performance analysis of a post-CHF heat transfer test facility

Abstract Post critical heat flux (post-CHF) heat transfer may occur in loss of coolant accidents (LOCAs) in water-cooled nuclear reactors when makeup water quenches the uncovered fuel rods in the reactor core. The post-CHF regimes are characterized by low heat transfer coefficient and high wall temperature due to the vapor-wall contact. A good understanding of the hydrodynamics and heat transfer process in the post-CHF regimes, especially low-quality film boiling, such as inverted annular film boiling (IAFB) and inverted slug film boiling (ISFB), is imperative for accurately modeling the post-CHF phenomena and predicting the fuel rod cladding temperature and void fraction during accidents. This paper first discusses limitations of existing post-CHF hydrodynamics and heat transfer models/correlations and then identifies needs of post-CHF experimental data under high-flow and high-pressure conditions for model improvement. To narrow down the gap in the available experimental data, a Post-CHF Heat Transfer (PCHT) test facility is designed to perform quasi-steady-state low-quality film boiling experiments under high-pressure (ranging from 0.14 to 3.45 MPa), high-flow (ranging from 150 to 2000 kg/m2-s), and high inlet subcooling (up to 50 °C) conditions. In addition to the experimental study, a numerical model using COMSOL Multiphysics tool is developed to inform the test section design and to investigate wall heat flux and wall temperature distributions in the post-CHF regimes. The COMSOL Multiphysics simulation results show that quasi-steady-state post-CHF phenomena can be achieved in the PCHT test section. Considering thermal non-equilibrium conditions in the post-CHF regimes, a one-dimensional two-fluid model is implemented into a computer code to predict the void fraction using the wall temperature information obtained from the COMSOL simulation results. A correlation for the liquid-side Nusselt number is obtained for the IAFB regime based on previous experimental data and is implemented into the code, which results in an improvement in the agreement between the calculated void fraction and corresponding experimental data. With the new Nusselt number correlation, a parametric study of the effects of the heat flux, pressure, mass flux, and inlet subcooling on the liquid-side Nusselt number is studied. In addition, flow regime transition in the post-CHF regimes is studied by comparing the existing correlation and experimental data. Furthermore, the Weber number and liquid-side Nusselt number are calculated to examine whether there exists any correlation between these two non-dimensional numbers and the flow regime transition. The simulation results provide insights for design improvement of the PCHT test section and assist the development of a test plan for future IAFB and ISFB tests under high-pressure, high-flow, and high-subcooling conditions in the PCHT test facility.
Shifting styles: Do auditor performance levels influence the review process?

We examine communication behaviors during the audit review process using a survey of audit partners, managers, and in‐charge/senior associates from each Big 4 accounting firm and one international accounting firm. We inquire about reviewers' preferred communication style when discussing review notes with preparers of varying performance levels, their likelihood of taking over the audit work of preparers due to either a lack of a response or an inappropriate response to a review note, and their propensity to self‐correct preparers' documentation along with the reasons for doing so instead of leaving a review note. Consistent with expectations, results indicate that reviewers are more likely to discuss review notes face to face with below‐average‐performing subordinates than with above‐average‐performing subordinates, and instead use alternative forms of communication with above‐average performers. Further, we find that reviewers self‐correct and/or update documentation themselves more frequently for below‐average subordinates than for above‐average subordinates. Supplemental analysis reveals that reviewers are likely to revise the work of subordinates, whether below average or above average, for a variety of reasons, including ease of doing so, efficiency, and pending deadlines.
Pyrimidine Biosynthesis Regulates the Small-Colony Variant and Mucoidy in Pseudomonas aeruginosa through Sigma Factor Competition.

ABSTRACT Mucoidy due to alginate overproduction by the Gram-negative bacterium Pseudomonas aeruginosa facilitates chronic lung infections in patients with cystic fibrosis (CF). We previously reported that disruption in de novo synthesis of pyrimidines resulted in conversion to a nonmucoid small-colony variant (SCV) in the mucoid P. aeruginosa strain (PAO581), which has a truncated anti-sigma factor, MucA25, that cannot sequester sigma factor AlgU (AlgT). Here, we showed that supplementation with the nitrogenous bases uracil or cytosine in growth medium complemented the SCV to normal growth, and nonmucoidy to mucoidy, in these mucA25 mutants. This conversion was associated with an increase in intracellular levels of UMP and UTP suggesting that nucleotide restoration occurred via a salvage pathway. In addition, supplemented pyrimidines caused an increase in activity of the alginate biosynthesis promoter (PalgD), but had no effect on PalgU, which controls transcription of algU. Cytosolic levels of AlgU were not influenced by uracil supplementation, yet levels of RpoN, a sigma factor that regulates nitrogen metabolism, increased with disruption of pyrimidine synthesis and decreased after supplementation of uracil. This suggested that an elevated level of RpoN in SCV may block alginate biosynthesis. To support this, we observed that overexpressing rpoN resulted in a phenotypic switch to nonmucoidy in PAO581 and in mucoid clinical isolates. Furthermore, transcription of an RpoN-regulated promoter increased in the mutants and decreased after uracil supplementation. These results suggest that the balance of RpoN and AlgU levels may regulate growth from SCV to mucoidy through sigma factor competition for PalgD. IMPORTANCE Chronic lung infections with P. aeruginosa are the main cause of morbidity and mortality in patients with cystic fibrosis. This bacterium overproduces a capsular polysaccharide called alginate (also known as mucoidy), which aids in bacterial persistence in the lungs and in resistance to therapeutic regimens and host immune responses. The current study explores a previously unknown link between pyrimidine biosynthesis and mucoidy at the level of transcriptional regulation. Identifying/characterizing this link could provide novel targets for the control of bacterial growth and mucoidy. Inhibiting mucoidy may improve antimicrobial efficacy and facilitate host defenses to clear the noncapsulated P. aeruginosa bacteria, leading to improved prognosis for patients with cystic fibrosis.
RATES OF EXUDATIVE RECURRENCE FOR EYES WITH INACTIVATED WET AGE-RELATED MACULAR DEGENERATION ON 12-WEEK INTERVAL DOSING WITH BEVACIZUMAB THERAPY.

Purpose To determine the recurrence rate of exudative age-related macular degeneration (wet AMD) in patients on 12-week dosing interval anti-vascular endothelial growth factor (anti-VEGF) bevacizumab therapy. Methods A retrospective chart review was performed on wet AMD patients treated with anti-VEGF therapy using a "treat-and-extend" methodology at one physician's practice site over 2 years (2012-2014). Charts were evaluated for visual acuity, anti-VEGF agent used, treatment interval, duration of treatment, trials off of anti-VEGF therapy, evidence of exudation, and wet AMD recurrence characteristics. Results Three hundred and twenty-one wet AMD patients were treated. Fifty-seven eyes were without active exudation by clinical examination or optical coherence tomography (OCT) and were maintained on repeating 12-week interval suppressive anti-VEGF therapy. Sixteen percent (8/49) showed exudation recurrence with an average 10% cumulative recurrence rate per year for eyes on bevacizumab. Eight eyes without active exudation were discontinued off of bevacizumab therapy. Sixty-three percent (5/8) demonstrated recurrence on average 4 months after stopping therapy. Conclusion The findings in this study suggest that if a patient can be extended to 12-week interval bevacizumab therapy, there is on average a 10% chance of recurrence with each successive year. If anti-VEGF therapy is discontinued in these patients, there is an increased chance of recurrence by 4 months.
Equitable revisited

The randomized k-paging algorithm EQUITABLE given by Achlioptas et al. is Hk-competitive and uses O(k2 log k) memory. This competitive ratio is best possible. The randomized algorithm RMARK given by Fiat et al. is (2Hk - 1)-competitive, but only uses O(k) memory. Borodin and El Yaniv [6] list as an open question whether there exists an Hk-competitive randomized algorithm which requires O(k) memory for k-paging. In this paper we answer this question in the affirmative by giving a modification of EQUITABLE.
Structural correlates of the orbitofrontal cortex and amygdala and personality in female adolescents.

The five-factor model consists of cognitive-affective-behavioral trait dimensions (neuroticism, extraversion, openness to experience, agreeableness, conscientiousness) that are central to models of psychopathology. In adults, individual differences in three of the Big Five traits, neuroticism, extraversion, and conscientiousness, have been linked to structural morphology and connectivity of the orbitofrontal cortex (OFC) and the amygdala, two brain regions critically involved in affective and regulatory processing. It is unclear whether these associations manifest in adolescence, a critical neurodevelopmental period during which many forms of psychiatric illness emerge. A total of 223 adolescent girls (ages 14-16 years) completed a multimodal neuroimaging study that utilized T1-weighted structural MRI (e.g., cortical thickness and volume) and tractography-based diffusion tensor imaging (64-direction). Cortical thickness and volume were extracted from the medial orbitofrontal cortex (mOFC) and amygdala and tractography-based fractional anisotropy was computed in the uncinate fasciculus (UF; the white matter tract connecting the OFC to the temporal lobe). We found that high neuroticism was associated with less mOFC volume (bilateral), and low conscientiousness was associated with higher white matter integrity in the UF, more amygdala volume, and less mOFC thickness (right hemisphere). Extraversion was not observed to share associations with OFC markers. These OFC-amygdala structural correlations to personality do not match those reported in adult samples. Multimodal neuroimaging techniques can help to clarify the underpinnings of personality development between adolescence and adulthood.
Sampling Designs for Landscape-level eDNA Monitoring Programs.

Effective natural resources management requires accurate information about species distributions. Environmental DNA (eDNA) analysis is a commonly used method to determine species presence and distribution. However, when understanding eDNA-based distribution data, managers must contend with imperfect detection in collection samples and subsamples (i.e., molecular analyses) impacting their ability to detect species and estimate occurrence. Occurrence models can estimate 3 probabilities: occurrence, capture, and eDNA detection. However, most occurrence models do not. To quantify imperfect detection in rare versus common species, we examined multiple field capture and detection probabilities. We studied this with 3 objectives: Determine sample sizes required to detect eDNA given imperfect detection, determine sample sizes required to estimate eDNA capture parameters, and examine performance of a 3-level occurrence model. We found detecting eDNA in ≥1 sample at a site required ≤15 samples per site for common species, but detecting eDNA when looking for rare species required 45 to 90 samples per site. Our occurrence model recovered known parameters unless capture and detection probabilities were 100 samples per site and ≥8 molecular replicates were required. Our findings illustrate the importance of sample size and molecular replication for eDNA-based work. Integr Environ Assess Manag 2019;15:760-771. Published 2019. This article is a US Government work and is in the public domain in the USA.
Validating a Measure of Perceived Parent–Child Political Socialization:

A growing body of research in political science is influenced by conceptual advances in socialization theory which posit that children can influence adults’ learning across a wide range of topics. ...
The structure of bovine β-lactoglobulin in crystals grown at pH 3.8 exhibiting novel threefold twinning.

Bovine β-lactoglobulin was crystallized from 3 M NaCl buffered at pH 3.8 with sodium citrate as thick hexagonal prisms of greater than 1 mm in edge length. Analyses of the X-ray diffraction intensities using three different current algorithms were unanimous in specifying the space group to be P6322, with unit-cell dimensions a = b = 75.47, c = 140.79 A. No progress could be made, however, towards an acceptable solution by molecular replacement using this symmetry. In the end, it was found that the true space group was C2221, a subgroup of P6322, with a = 65.89, b = 114.12, c = 140.51 A, with the apparent 622 symmetry arising from an unusual threefold or tritohedral twinning. An assembly based on a model of the protein in another crystal form (PDB entry 1beb) containing three molecules in the asymmetric unit was refined to 2.3 A resolution with a final R factor of 0.23 and Rfree of 0.26. NCS restraints were maintained throughout. For the most part, the molecules found in this crystal form are virtually the same as in PDB entry 1beb, although there are numerous local variations, particularly in loop elements, rotamer conformation differences and some alterations, including additions, at the termini.
The Role of Childhood Maltreatment in The Relationship Between Social Anxiety and Dissociation: A Novel Link

Children that have been maltreated may experience manifold negative effects later in life. Two such sequelae are social anxiety and dissociation. Recent studies have noted their frequent co-occurre...
Ethylene and Water Co-Adsorption on Ag/SSZ-13 Zeolites: A Theoretical Study

Zeolites are capable to selectively adsorb molecules and therefore are applicable to chemical separation challenges. In this work, two probe molecules, ethylene (C2H4) and water (H2O) are modeled f...
Current explorations of nutrition and the gut microbiome: a comprehensive evaluation of the review literature.

Context The ability to measure the gut microbiome led to a surge in understanding and knowledge of its role in health and disease. The diet is a source of fuel for and influencer of composition of the microbiome. Objective To assess the understanding of the interactions between nutrition and the gut microbiome in healthy adults. Data sources PubMed and Google Scholar searches were conducted in March and August 2018 and were limited to the following: English, 2010-2018, healthy adults, and reviews. Data extraction A total of 86 articles were independently screened for duplicates and relevance, based on preidentified inclusion criteria. Data analysis Research has focused on dietary fiber - microbiota fuel. The benefits of fiber center on short-chain fatty acids, which are required by colonocytes, improve absorption, and reduce intestinal transit time. Contrastingly, protein promotes microbial protein metabolism and potentially harmful by-products that can stagnate in the gut. The microbiota utilize and produce micronutrients; the bidirectional relationship between micronutrition and the gut microbiome is emerging. Conclusions Nutrition has profound effects on microbial composition, in turn affecting wide-ranging metabolic, hormonal, and neurological processes. There is no consensus on what defines a "healthy" gut microbiome. Future research must consider individual responses to diet.
Chapter 19 – Opportunity

Evolutionary biologists no longer accept that evolution has a planned direction or goal. Life forms evolve to be adapted to local environments in which they can survive and produce equally capable offspring. That being the case, environmental changes that are stochastic in nature often create new opportunities for some species. Sometimes opportunity occurs when other species die out, leaving ecological space unfilled. Opportunities can arise from both abiotic and biotic changes, which occur regularly over evolutionary time, and certain groups often seem obviously to have taken advantage of these opportunities—as mammals did after the extinction of the dinosaurs, or as arriving species have done on new volcanic islands. Our own species succeeds in large part by recognizing and taking advantages of opportunities.
Neuroinflammation associated with scrub typhus and spotted fever group rickettsioses

Scrub typhus and spotted fever rickettsioses (SFR) are understudied, vector-borne diseases of global significance. Over 1 billion individuals are at risk for scrub typhus alone in an endemic region, spanning across eastern and southern Asia to Northern Australia. While highly treatable, diagnostic challenges make timely antibiotic intervention difficult for these diseases. Delayed therapy may lead to severe outcomes affecting multiple organs, including the central nervous system (CNS), where infection and associated neuroinflammation may be lethal or lead to lasting sequelae. Meningitis and encephalitis are prevalent in both scrub typhus and SFR. Additionally, case reports detailing focal neurological deficits have come to light, with attention to both acute and chronic sequelae of infection. Despite the increasing number of clinical reports outlining neurologic consequences of these diseases, relatively little research has examined underlying mechanisms of neuroinflammation. Animal models of scrub typhus have identified cerebral T-cell infiltration and vascular damage associated with endothelial infection and neuropathogenesis. Differential gene expression analysis of brain tissues during murine scrub typhus have revealed selective increases in CXCR3 ligands, proinflammatory and type-1 cytokines and chemokines, and cytotoxicity molecules, as well as alterations in the complement pathway. In SFR, microglial expansion and macrophage infiltration contribute to neurological disease progression. This narrative Review highlights clinical neurologic features of scrub typhus and SFR and evaluates our current understanding of basic research into neuroinflammation for both diseases in animal models. Further investigation into key mediators of neuropathogenesis may yield prognostic markers and treatment regimens for severe patients.
User-Generated Crisis Communication: Exploring Crisis Frames on Twitter during Hurricane Harvey

Traditional mass media effect theories place the burden of crisis communication on the organization or media. Analysis of user-generated content alongside traditional media and organizational conte...
Non-targeted discovery of class-distinguishing metabolites in Argentinian pacu fish by comprehensive two-dimensional gas chromatography with principal component analysis

Abstract Pacu fish are an important source of revenue and food supply in Argentina, however the nutritional effects of raising these fish in an integrated rice-fish farming environment on the fish metabolome are still unclear. To investigate this issue, the discovery of class-distinguishing compounds between farmed and control pacu fish samples was performed by comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOFMS) followed by principal component analysis (PCA). Pacu fish muscle tissue samples were extracted and derivatized for a total of 10 farmed and 10 control fish prior to GC × GC-TOFMS analysis. The total ion current (TIC) and a diagnostic ion for sugars, mass channel (m/z) 217, data for each fish were input to PCA for the non-targeted discovery of metabolites that differentiated between the control and farmed samples. The scores revealed that the classes (farmed and control fish) separated best on PC2, with most of the variance captured on PC1 accounting for the within class variance when both the TIC and m/z 217 were used. The loadings were examined to retrieve the 50 most highly loaded analytes on PC1 and PC2 using the TIC and m/z 217 (a compiled list of the 20 most highly loaded variables on each PC for the TIC and m/z 217), which were subsequently identified and concentration ratios, [Farmed]/[Control], were calculated to determine how farming fish with rice affects metabolite concentrations in pacu fish muscle tissue. A majority of analytes are downregulated in the farmed pacu fish (39/50) with 30 of these passing a p-value threshold at the 95% confidence level while of the remaining 11 analytes that were upregulated, 4 analytes passed a p-value threshold (34 analytes total passing the p-value threshold). Many of these significant analytes were highly loaded on PC2 and are involved in important metabolic processes including protein catabolism or nucleotide metabolism and tissue repair. These PCA results provide meaningful insight into the effects of farming Argentinian pacu fish with rice fields on the fish metabolome.
Identification of Biomarkers in Patients with Thrombotic Thrombocytopenic Purpura Presenting with Large and Small Ischemic Stroke.

Background Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder resulting in organ damage including ischemic strokes. We sought to characterize the neuroimaging patterns of stroke in a large cohort of patients with immune-mediated TTP (iTTP) and determined their associations with clinical and laboratory parameters and outcomes. Methods We analyzed the Alabama TTP Registry who had laboratory confirmation of acute iTTP. We reviewed the neuroimaging patterns of those with ischemic stroke on MRI, clinical information, and laboratory results. Small ischemic strokes were ≤20 mm in their maximum diameter in the axial plane. Large ischemic strokes were >20 mm. Student t test, Mann-Whitney U test, and χ2 test were all used for data analysis. Results Of 108 iTTP patients, 21 had ischemic stroke on neuroimaging. The median platelet count in these patients was 12 × 109/L (interquartile range, IQR, 8.8-21 × 109/L), plasma ADAMTS13 activity 1.8 U/dL (IQR 0-4.5 U/dL), and the mean plasma level of anti-ADAMTS13 IgG was 6,595.8 U/mL (SD 3,448.9 U/mL). Comparison between patients with large ischemic strokes (n = 10) and small ischemic strokes (n = 11) revealed that patients with small stroke were older (p = 0.043) and had higher plasma levels of citrullinated histone 3 (p = 0.006) and histone/DNA complex (p = 0.014) than those with large strokes. There were no significant differences between 2 stroke groups in mortality or exacerbation. Conclusions iTTP patients can present with large ischemic strokes and are usually younger. Further research should be performed in assessing different etiologies of iTTP-associated stroke based on neutrophil extracellular trap formation biomarkers (e.g., histone markers) seen in small ischemic stroke.
Parking sensor-inspired approach to photoacoustic-guided hysterectomy demonstrated with human cadavers

Similar to the parking-assist sensors on modern automobiles, which alert drivers of impending impact to an object, we are developing an auditory photoacoustic-based guidance system to assist with avoidance of impending injuries to ureters during hysterectomy procedures. The contribution described in this paper considers international standards for medical alarms. The system was demonstrated during both open and laparoscopic hysterectomy procedures on two human cadavers. Using methylene blue to enhance ureter contrast, the proximity of a surgical tool tip to the ureter was measured using the visual information provided in photoacoustic images. Distance measurements were then successfully mapped to auditory signals, which increased in auditory frequency as the tool-to-ureter distance decreased to convey surgical tool proximity to the ureter. Fundamental frequencies increased from 150 Hz to 866 Hz for tool-to-ureter distances of 2.47 mm to 5 mm. These results are promising to assist with the avoidance of accidental ureteral injuries during hysterectomy and other procedures that suffer from similar challenges with regard to iatrogenic ureteral injuries.
Suicidal Behavior Among Homeless and Runaway Adolescents

The present study considered risk factors associated with suicidal ideation and the likelihood of a suicide attempt in a sample of 297 homeless and runaway youth from four Midwestern states. It was hypothesized that sociodemographic characteristics, family factors, suicide exposure, street factors, externalizing behavior, and internalizing behavior would be related to suicidal ideation and to the likelihood of a suicide attempt. It was also hypothesized that suicidal ideation would mediate the relationship between the other predictor variables and the likelihood of a suicide attempt. Over half the sample (53.9%) endorsed some level of suicidal ideation, and over one quarter (26.3%) attempted suicide in the year prior to the interview. Univariate and multivariate results indicated that sexual abuse by a family member, knowing a friend who attempted suicide, drug abuse, and internalization were highly related to suicidal ideation. In the absence of suicidal ideation, sexual abuse, sexual victimization while on their own, and internalization were highly related to the likelihood of a suicide attempt. Finally, the hypothesized mediating effect was found for both sexual abuse and internalization.
A review of experimental methodology in instructional task sequencing

A controversial problem in instructional research and development has been the sequencing of subject material to increase both effectiveness and efficiency of learning. Proponents of a learning sequence strategy have hypothesized various forms of hierarchal paradigms based upon identifiable behaviors. The Gagne (1970) model holds that for a learner to acquire a complex cognitive skill, such as problem solving, he must first advance through a series of enabling conditions. M. D. Merrill (1971) presents a model that concentrates on instructional strategies to promote desired behaviors regardless of subject matter content. His paradigm assumes that a learner's acquisition of content can be manipulated by appropriate variables within the levels of behavior. Higher order behaviors-e.g., concept learning, rule using, and problem solving-are dependent on learning prerequisite skills. To investigate empirically the prerequisite performances and hierarchies, researchers have refined traditional psychological methodologies and techniques (e.g., design of studies-a Campbell and Stanley (1963) approach; control of statistical analysis; measurement of subject (S) responses;
Exploring Language Dominance, English Literacy and Life Satisfaction Among Dominican Children of Immigrant Parents

ABSTRACT The purpose of this pilot study was to explore language dominance and English language literacy, and examine the effects of an intervention focused on facilitating English language acquisition among Dominican children. Eighteen first and second generation Dominican children, ages 7–11, participated in a school based after school literacy language immersion program. Following participation in the literacy language immersion intervention, participants demonstrated an increase in school satisfaction and improvements in English literacy levels. This article makes recommendations for the provision of school-based programs that focus on the specific needs of Latino students associated with Spanish language dominance.
The SIRT3 deacetylase blocks cardiac fibrosis by targeting TGFβ1-Smad3 signaling (1152.6)

Cardiac fibrosis after myocardial injury is a major challenge in the medicine today to preserve heart function. At the cellular level, activation of TGFβ1 signaling is considered a major contributo...
Catabolism of Mucopolysaccharides by Rat Liver Lysosomes in Vivo

Abstract Rats treated by injection of the radioactive mucopolysaccharides, 35S-labeled chrondroitin 4- or 6-sulfate and tritium-labeled chondroitin sulfate B, have been shown to be capable of concentrating about 1% of these materials within their liver lysosomes. The chondroitin 4-sulfate, which is a substrate for lysosomal hyaluronidase, was depleted from the lysosomes 4 days after injection, whereas, after this same time period, one-third of the chondroitin sulfate B remained in these cellular particles. The role of this phenomenon in Hurler's syndrome, a connective tissue disorder involving storage of chondroitin sulfate, is discussed.
Effects of Graphic and Verbal Probability Information on Command Decision Making

The performance effects of graphic and verbal representations of uncertainty were investigated within the context of a spatial problem., Sixteen experienced naval submarine officers acted as decisi...
Schooling Interruption, Work While in School and the Returns from Schooling

Recent suggestions for expanding the work experiences of school age youth make sense only if such experiences are in fact valuable or can be had at little real cost. These issues are explored using data from the Young Men NLS, focusing on the effects of school interruption and of work while in school on subsequent wage rates. While the interpretation of the results is clouded by self-selection problems, there is no evidence in the data that interruptions or work while in school lead to any negative effects. Expanding work opportunities for the young is unlikely to detract from their future academic and economic achievement.
Random Complex Fewnomials, I

We introduce several notions of ‘random f-nomials’, i.e., random polynomials with a fixed number f of monomials of degree = ≤N The f exponents are chosen at random and then the coefficients are chosen to be Gaussian random, mainly from the SU(m + 1) ensemble. The results give limiting formulas as N→∞ for the (normalized) expected distribution of complex zeros of a system of k random f-nomials in m variables (k≤ m). When k = m, for SU(m+ 1) polynomials, the limit is the Monge-Ampere measure of a toric Kahler potential on ℂℙ m obtained by averaging a ‘discrete Legendre transform’ of the Fubini-Study symplectic potential at f points of the unit simplex ∑ ⊂ ℝ
Genetic differentiation on multiple spatial scales in an ecotype-forming marine snail with limited dispersal: Littorina saxatilis

The population genetic structure of marine species lacking free-swimming larvae is expected to be strongly affected by random genetic drift among populations, resulting in genetic isolation by geographical distance. At the same time, ecological separation over microhabitats followed by direct selection on those parts of the genome that affect adaptation might also be strong. Here, we address the question of how the relative importance of stochastic vs. selective structuring forces varies at different geographical scales. We use microsatellite DNA and allozyme data from samples of the marine rocky shore snail Littorina saxatilis over distance scales ranging from metres to 1000 km, and we show that genetic drift is the most important structuring evolutionary force at distances > 1k m. On smaller geographical scales (< 1 km), divergent selection between contrasting habitats affects population genetic structure by impeding gene flow over microhabitat borders (microsatellite structure), or by directly favouring specific alleles of selected loci (allozyme structure). The results suggest that evolutionary drivers of population genetic structure cannot a priori be assumed to be equally important at different geographical scales. © 2008 The Linnean Society of London, Biological Journal of the Linnean Society, 2008, 94, 31-40.
A group sequential Holm procedure with multiple primary endpoints

We propose a group sequential Holm procedure when there are multiple primary endpoints. This method addresses multiplicities arising from multiple primary endpoints and from multiple analyses in a group sequential design. It has been shown to be a closed testing procedure and preserves the familywise error rate in the strong sense. When multiple endpoints are the only concern without an interim analysis, the method simplifies to the weighted Holm procedure. The proposed method is more powerful than the parallel group sequential method and avoids the need to anticipate the testing order as in the fixed sequence testing scheme.
The Orphan Legume Genome Whose Time Has Come: Symposium Highlights from the American Peanut Research & Education Society Annual Meeting

ABSTRACT The Peanut Genome Project was launched in 2012 and a genomics symposium was held at the 2012 annual meeting of the American Peanut Research and Education Society. Seven speakers presented a spectrum of topics covering peanut molecular tools and materials to which they have been applied, along with the challenges and benefits of a genome sequence to prebreeding and breeding of cultivated peanut. Highlights of the symposium are presented and are accompanied by three in-depth reviews of population development, utilization of wild species, and genetic mapping in Arachis.
The Foundation of the Sommerfeld Transformation

The analysis of the one-dimensional journal bearing leads to an interesting integral that is continuous but has an analytic singularity involving the inverse tangent at π/2. This difficulty was resolved by a clever and non-intuitive transformation attributed to Sommerfeld. In this technical brief we show that the transformation has its origin in the geometry of the ellipse and Kepler's equation that is based upon his observations of the planets in the Solar system. The derivation of the transformation is a problem or exercise in Sommerfeld's monograph, Mechanics. The transformation is the relation between the two angles that characterize the ellipse, the closed orbit of a body in a central inverse square force field. The angle measured about the focus is the true anomaly (angle) and the angle measured about the center is the eccentric anomaly (angle). We establish the analogy between the orbital radius in terms of the eccentric anomaly and the film thickness of the journal bearing in terms of its central angle.
Experimental allergic neuritis: Humoral and cellular immune responses to the cyanogen bromide peptides of the P2 protein

Lewis rats were immunized with P2 protein and peptides CN1, CN2 and CN3. In P2 immunized rats, antibody and cellular sensitivity to the P2 protein were seen prior to the appearance of clinical signs of EAN, during disease and during recovery. CN1 immunized rats had equal or more severe clinical and histological signs of EAN but lower antibody titers than P2 immunized animals. CN-1 elicited a greater blastogenic response in both P2 and CN-1 immunized animals. CN-2 and CN-3 immunized rats showed little clinical and histological evidence of EAN and no antibody. However, lymphocytes sensitive to the immunizing antigen and the P2 protein were present.
DEPRESSION AND EXPECTATIONS OF SATISFACTION

12 participants in an adult education class titled “Coping with Depression” reported their expectations of satisfaction for planned pleasant events. Based upon a median split of Beck Depression Inventory scores, subjects were divided into depressed and nondepressed categories. Consistent with current psychosocial theories of depression, depressed subjects expected a significantly lower satisfaction from planned events than did nondepressed subjects. Depression scores were significantly correlated —.60 with expectations. In addition, a group of 12 psychology graduate students and staff rated the events planned by the depressed and nondepressed subjects for their inherent satisfaction. No significant differences were found between mean ratings of the events planned by depressed and nondepressed subjects. The depressed groups' expectations closely matched the ratings of the graduate students and staff. In contrast, nondepressed subjects' expectations were far higher. These results are discussed in terms of w...
Hydrophobic Surfactant Proteins Induce a Phosphatidylethanolamine to Form Cubic Phases

The hydrophobic surfactant proteins SP-B and SP-C promote rapid adsorption of pulmonary surfactant to an air/water interface. Previous evidence suggests that they achieve this effect by facilitating the formation of a rate-limiting negatively curved stalk between the vesicular bilayer and the interface. To determine whether the proteins can alter the curvature of lipid leaflets, we used x-ray diffraction to investigate how the physiological mixture of these proteins affects structures formed by 1-palmitoyl-2-oleoyl phosphatidylethanolamine, which by itself undergoes the lamellar-to-inverse hexagonal phase transition at 71°C. In amounts as low as 0.03% (w:w) and at temperatures as low as 57°C, the proteins induce formation of bicontinuous inverse cubic phases. The proteins produce a dose-related shift of diffracted intensity to the cubic phases, with minimal evidence of other structures above 0.1% and 62°C, but no change in the lattice-constants of the lamellar or cubic phases. The induction of the bicontinuous cubic phases, in which the individual lipid leaflets have the same saddle-shaped curvature as the hypothetical stalk-intermediate, supports the proposed model of how the surfactant proteins promote adsorption.
Amine-Rich Polyelectrolyte Multilayer Nanoreactors for in Situ Gold Nanoparticle Synthesis

In situ synthesis of inorganic clusters in polyelectrolyte multilayers (PEMs) has typically relied on free carboxylic acid groups as the binding sites, limiting the scheme to the loading of cationic precursor reagents. The use of amine groups for similar purposes has not been demonstrated because of the challenge of incorporating free amine groups that are not paired with the oppositely charged groups residing on the polyanion of the PEM. In this paper, we use specific PEM assembly conditions to produce ultrathin conformal films of PAH/PAA (poly(allylamine hydrochloride)/poly(acrylic acid)) and PAH/PSS (poly(styrene sulfonate)) that upon suitable postassembly treatment undergo substantial molecular rearrangements that generate free amine groups in the films. These PEMs are capable of binding anionic precursors including complexes widely used for the synthesis of gold nanoparticles. On the basis of our understanding of the gold binding mechanisms, we demonstrate systematic control over the size and spatial...
Carbon-13 NMR studies of olefins having nitrile and methoxycarbonyl substituents. Additivity relationships

Carbon-13 NMR chemical shifts are reported for a series of seventeen olefins with tetra-, tri-, di- and mono-substitution by nitrile and methoxycarbonyl groups. Analyses of the data for the nitrile, methoxy and carbonyl chemical shifts by multiple linear regression provide a good correlation with the pattern of geminal, cisoid and transoid substitution. The olefinic shielding data are more complicated, and the analysis requires the introduction of pairwise additivity parameters. It scems likely that the greater complexity arises from steric effects associated with cisoid and geminal methoxycarbonyl substituents, which produce deviations from planarity. The empirical relationships, which are reported here, are useful in removing several ambiguities in the spectral assignments. In this series of compounds it is also observed that substituents which are cis to the nitrile, shift the nitrile resonance 1–2 ppm to high field of those for the trans substituents.
New developments in ochronosis: review of the literature

Ochronosis commonly affects all connective tissue. Recognition of changes secondary to the deposition of ochronotic pigments has increased with advances in diagnostic technology, allowing both improved imaging and early biochemical and genetics-based diagnosis of alkaptonuria, the cause of ochronosis. Successful symptomatic treatment of ochronotic arthropathy with joint replacement has been documented, and a new pharmacotherapeutic agent, nitisinone, is currently under investigation for both prevention and treatment of ochronosis. This review of the literature highlights recently recognized complications, new diagnostic techniques, and treatment options.