cssi/SciSciGPT-SciSciNet huggingface dataset:
Relationship between microstructure and formability in two high-strength, low-alloy steels

Variations in the strain hardening behavior of GM 980X and a vanadium-strengthened SAE 980X steel were investigated as a function of strain. Changes in the microstructural deformation characteristics of the two steels were evaluated by scanning electron microscopy after biaxial and uniaxial deformation. Plastic deformation was found to occur in the SAE 980X steel by deformation of the ferrite matrix, while in GM 980X it occurred by deformation of both the ferrite and martensite phases. The GM 980X ferrite matrix was found to have a much higher work-hardening rate than that of the SAE 980X steel. Failure occurred in the SAE 980X steel when the ferrite was highly strained. In GM 980X it occurred after more extensive deformation had occurred, and the martensite phase was also highly strained. It was concluded that the higher work-hardening coefficient of the ferrite matrix and the deformable martensite phase combine to give GM 980X its superior formability.
"That's Kind of One of Our Jobs": Sexual Activity as a Form of Care Work Among Women with Sexual Difficulties.

Willing engagement in unwanted or undesired sexual activity, often associated with fulfilling a partner’s needs or sustaining intimate relationships, is common. Acquiescence with undesired sexual activity can be conceptualized as sexual care work, that is, domestic “labor” that women undertake with the goal of caring for their partners’ well-being. Drawing on interviews with 53 women with dyspareunia (pain experienced during intercourse) and low desire, the aim of this study was to examine how women with sexual difficulties engage in sexual care work, the implications of the inability to perform such work for gender identity, and the ways in which sexual care work may blur the lines between women’s perceptions of coercion and consent. The women in this study engaged in sexual activity for a number of reasons, including the pursuit of intimacy, to care for their partner, and to fulfill their perceived sexual obligations. Sexual compliance was conceptualized as a form of work, similar to other forms of unpaid care work such as housework or childcare, which negatively affected women’s gender identities when it could not be performed. For many women, sex was simultaneously wanted and unwanted, contributing to women’s ambivalence regarding the meaning of consent. Further exploration of these issues may lead to a better understanding of how gender is achieved through normative sexuality.
Characterization of Co-existing In2O3-ZnO Nanostructures

In this study, we report the simultaneous growth of both In2O3 and ZnO nanostructures on the same substrate when attempting to achieve heavily Zn-doped In2O3 nanowires with Zn. These oxide structures were synthesized by vapor–liquid–solid growth. Scanning electron microscope imaging and transmission electron microscopy shows the presence of nanostructures with different morphologies while energy-dispersive x-ray and x-ray photoelectron spectroscopy study confirms the elemental structure. Room-temperature photoluminescence (PL) study reveals the presence of oxygen vacancies and surface defects in the structures. Emission related to free and bound excitons as well as the donor–acceptor transitions were observed using temperature-dependent PL. Raman spectroscopy measurement using 442-nm non-resonant excitation sources shows the presence of four phonon modes associated with a cubic In2O3 lattice structure along with the observation of the dominant E 2 high and quasi-longitudinal optical phonon modes associated with wurtzite ZnO. We find that the introduction of high zinc content results in the formation of ZnO nanowires in addition to the In2O3 nanowires, and not the formation of a highly doped In2O3 nanowires.
Low Noise Dc Squids for the 1990S

In the 1980s we have seen the successful introduction of planar coupling schemes for dc SQUIDs, the achievement of coupled energy sensitivity near the quantum limit, significant advances in integrated SQUID detectors, and a shift from Pb-alloy to all-refractory technology. The discovery of high-Tc superconductivity in 1986 was soon followed by the demonstration of high-Tc SQUIDs, with bulk and thin-film versions now operating at or above 77K. The 1990s will bring practical low-Tc dc SQUIDs, 0.05mm2 or less in area, with tightly coupled 2/iH input coils, smooth, well-behaved voltage-flux characteristics, very small flux creep related hysteresis, and coupled energy sensitivity at or near the quantum limit at 4.2K. There will be an increased emphasis on the design and development of application specific integrated detectors. All-refractory Nb-based technology will dominate the low-Tc arena and direct coupling to semiconductor capability should quicken the pace and lower the cost of SQUID development and production. High-Tc SQUIDs will follow suit with a significant time delay as our understanding of high-Tc materials and our ability to work with them advances.
Darker Skin Tone Increases Perceived Discrimination among Male but Not Female Caribbean Black Youth.

Background: Among most minority groups, males seem to report higher levels of exposure and vulnerability to racial discrimination. Although darker skin tone may increase exposure to racial discrimination, it is yet unknown whether skin tone similarly influences perceived discrimination among male and female Caribbean Black youth. Objective: The current cross-sectional study tests the role of gender on the effects of skin tone on perceived discrimination among Caribbean Black youth. Methods: Data came from the National Survey of American Life-Adolescent Supplement (NSAL-A), 2003–2004, which included 360 Caribbean Black youth (ages 13 to 17). Demographic factors (age and gender), socioeconomic status (SES; family income, income to needs ratio, and subjective SES), skin tone, and perceived everyday discrimination were measured. Linear regressions were used for data analysis. Results: In the pooled sample, darker skin tone was associated with higher levels of perceived discrimination among Caribbean Black youth (b = 0.48; 95% Confidence Interval (CI) = 0.07–0.89). A significant interaction was found between gender and skin tone (b = 1.17; 95% CI = 0.49–1.86), suggesting a larger effect of skin tone on perceived discrimination for males than females. In stratified models, darker skin tone was associated with more perceived discrimination for males (b = 1.20; 95% CI = 0.69–0.72) but not females (b = 0.06; 95% CI = −0.42–0.55). Conclusion: Similar to the literature documenting male gender as a vulnerability factor to the effects of racial discrimination, we found that male but not female Caribbean Black youth with darker skin tones perceive more discrimination.
A kinetic view of acid-mediated tumor invasion

According to the acid-mediated tumor invasion hypothesis, tumor-induced alteration of microenvironmental pH may provide a simple, yet complete mechanism for tumor invasion. The acid-mediation hypothesis analyzes the tumor growth and invasion process from a reaction-diffusion system perspective, where it incorporates the H+ ion concentration as a reaction factor and adds density-dependent diffusion parameters to the reaction terms, yielding independent reaction-diffusion equations for the normal, tumor, and acid populations. In this article, we apply the dynamical stability theory to the acid-mediation hypothesis. For reasonable biological parameters, we study the fixed points central to the model and their stability by calculating the eigenvalues of the Jacobian matrix of the partial differential equations that represent how these three populations evolve with time. For the case where a malignant behavior has not already taken place yet (the time rates of change of the densities of the three populations are equal to zero), our numerical results convey two different, yet possible configurations in three-dimensional space: stable and unstable dynamical equilibriums, and we discuss possible prospective trajectories for the normal and tumor populations starting from each configuration. Moreover, we discuss potential applications of our approach.
Neuropsychological Assessment and Rehabilitation

The role of clinical neuropsychological assessment in rehabilitation settings is not a novel concept. The post World War I and World War II eras were characterized by a focusing of interest upon rehabilitation of traumatically injured military personnel. Goldstein (Goldstein & Scheerer, 1941) and later Luria (1963) were the most prominent of the early investigators who concerned themselves with the identification of the location and effects of penetrating missile wounds of the head. As the various brain-imaging techniques (pneumoencephalography, angiography, electroencephalography, and isotope brain scans) became increasingly available and accepted, the need to identify or localize brain lesions became less prominent. With the introduction of computerized tomographic (CT) and position emission transaxial tomographic (PETT) scans in the middle 1970s, the need for localization of brain lesions with neuropsychologic techniques virtually ceased to be an issue.
Life span of thrombocytes and erythrocytes in normal and thrombocytopenic calves.

1. Bovine thrombocytes and erythrocytes became labeled with P32 following an intramuscular injection of DFP.32 2. The life span of bovine thrombocytes calculated from survival curves of DFP32-labeled thrombocytes was about 10 days. 3. The life span of bovine erythrocytes calculated from the linear portion of the survival curve was about 110 to 120 days. 4. There was no significant difference between the life span of the thrombocytes and erythrocytes from normal calves and those from calves with thrombocytopenia induced by the feeding of trichloroethylene-extracted soybean oil meal.
TECTONICS | Propagating Rifts and Microplates At Mid-Ocean Ridges

Abstract Propagating rifts are extensional plate boundaries that gradually break through lithospheric plates. They rearrange plate boundaries in various tectonic settings on scales ranging from km to thousands of km, including migrating overlapping spreading centers, classic oceanic propagators that replace pre-existing mid-ocean ridges, microplate initiation propagators, and continental breakup propagators. Although the propagating rift hypothesis is a small change to plate tectonic theory, it has important implications for plate tectonic evolution. Rift propagation provides quantitative explanations for the existence of several classes of structures, including pseudofaults, failed rifts, and zones of transferred lithosphere, that are oblique to ridges and transform faults and thus were incompatible with simple plate tectonic theory. It explains why passive continental margins are not parallel to the oldest seafloor isochrons, but are instead pseudofaults, bounding lithosphere created on propagating spreading centers and indicating the direction of the continental breakup propagators. It explains both the origination and the termination of many fracture zones. It explains how transient microplates form along midocean ridges that appear to be the modern analogues of large-scale ridge jumps. This hypothesis provides a mechanistic explanation for the way in which most ridge jumps occur, why they occur in systematic patterns, and how spreading centers reorient when the direction of seafloor spreading changes. Rift propagation is the primary mechanism that reorganizes Earth's accretional plate boundary geometry.
Uterus Transplantation: A Step Too Far

Bruno and Arora (2018) discuss the ethical issues related to donor source in uterus transplantation (UTx), assuming the ethics of UTx itself are settled. We disagree with this initial premise itsel...
Abstract 4870: Targeted MDM2 degradation as a novel and efficacious cancer therapy

The E3 ubiquitin ligase MDM2 (Murine Double Minute 2) is the most important negative regulator of p53 tumor suppressor primarily by targeting it for ubiquitination and proteasomal degradation. Amplification or overexpression of the MDM2 gene occurs in many human cancers contributing to tumor development, progression and metastasis. Targeting MDM2 to restore p53 function has become an attractive therapeutic strategy for cancers harboring wild-type TP53. Currently, numerous drugs inhibiting the MDM2-p53 interaction, such as RG7112 (Hoffmann-La Roche), MI-773 (Sanofi) and DS-3032b (Daiichi Sankyo), have entered different stages of clinical trials. However, even in p53 wild-type tumors, MDM2 inhibitors can exert limited efficacy as monotherapy in some models, probably due to inadequate p53 induction and side effects. Therefore novel and improved strategies to effectively target the MDM2-p53 pathway are needed. Recently, we have designed a series of MDM2 degraders by conjugating a small molecule MDM2 inhibitor to phthalimide. The phthalimide moiety interacts with its target protein Cereblon (CRBN) and recruits the CUL4-DDB1-CRBN (also known as CRL4CRBN) E3 ubiquitin ligase complex to promote ubiquitination and proteasome degradation of MDM2. Our initial evaluation focused on acute leukemias that are mostly p53 wild-type and express high levels of MDM2. The MDM2 degraders exert significantly improved growth inhibitory activity compared to the inhibitor in human acute leukemia cell lines with IC50s Citation Format: Jiuling Yang, Yangbing Li, Angelo Aguilar, Donna McEachern, Sally Przybranowski, Ester Fernandez-Salas, Jianfeng Lu. Targeted MDM2 degradation as a novel and efficacious cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4870.
Abstract PR05: T-cells engineered to overcome death signaling within the tumor microenvironment enhance adoptive cancer immunotherapy

Across clinical trials, T-cell expansion and persistence following adoptive cell transfer (ACT) has correlated with superior patient outcomes. Herein, we undertook a pan-cancer analysis across human tumors to identify potentially actionable ligand/receptor pairs that might limit T-cell function and persistence following ACT. We discovered that FASLG, the gene encoding the apoptosis-inducing ligand FasL, is overexpressed within the majority of human tumor microenvironments. Further, we uncovered that Fas, the receptor for FasL, is highly expressed on patient-derived T-cells used for ACT. We hypothesized that a cognate Fas-FasL interaction within the tumor microenvironment might limit both T-cell persistence and antitumor efficacy. We discovered that genetic engineering of Fas variants impaired the ability to bind FADD function as dominant negative receptors (DNRs) in Fas-competent mouse and human T-cells, rescuing cells from FasL-induced apoptosis. Fas DNR-engineered T-cells exhibited enhanced persistence within tumors following ACT, resulting in superior cancer regression and overall survival in solid and hematologic malignancies treated with TCR or CAR-modified cells. Despite enhanced longevity, Fas DNR-engineered T-cells did not undergo aberrant clonal expansion, demonstrating the safety of this approach. Thus, cell-intrinsic “insulation” of T-cells from the negative influence of FasL is a potentially universal strategy to enhance ACT efficacy across a broad range of human malignancies. Citation Format: Christopher A. Klebanoff. T-cells engineered to overcome death signaling within the tumor microenvironment enhance adoptive cancer immunotherapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr PR05.
The role of gender in risk for substance use among justice-involved youth

Abstract Much research on gender and risk factors in adolescent substance use focuses on either normative community samples or high-risk, primarily male samples. This literature shows in general that both contextual and personal risk factors increase likelihood for adolescent substance use. However, a broader understanding of the relationship between gender and substance use risk will aid in designing more appropriate interventions and policy, especially with regards to females involved in the clinical or juvenile justice systems. In this study, we analyze data from a sample of 421 youth referred by the justice system for mental health treatment. Analyses show that gender moderates relations between personal and contextual risk factors and substance use outcomes. Implications of these findings for researchers and clinical practitioners are discussed.
Nanocrystalline grain boundary engineering: Increasing Σ3 boundary fraction in pure Ni with thermomechanical treatments

Abstract Grain boundary networks should play a dominant role in determining the mechanical properties of nanocrystalline metals. However, these networks are difficult to characterize and their response to deformation is incompletely understood. In this work, we study the grain boundary network of nanocrystalline Ni and explore whether it can be modified by plastic deformation. Mechanical cycling at room temperature did not lead to structural evolution, but elevated temperature cycling did alter the grain boundary network. In addition to mechanically driven grain growth, mechanical cycling at 100 °C led to a 48% increase in Σ3 boundaries, determined with transmission Kikuchi diffraction. The extent of boundary modification was a function of the number of applied loading cycles and the testing temperature, with more cycles at higher temperatures leading to more special grain boundaries. The results presented here suggest a path to grain boundary engineering in nanocrystalline materials.
Optimization and Characterization of Calcium Phosphate Transfection in Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have been used as a therapy to modulate diverse biological processes. To fulfill the requirements for different MSC therapies, safe and effective gene transfer methods...
Efficiency over generosity? Evidence of electoral accountability from typhoon dayoff in Taiwan

Even though voters may irrationally blame the incumbent for natural disasters, democratic accountability can still hold if voters also reward the government for good responses. This article approac...
Testosterone Therapy in Male Infertility

Normal spermatogenesis is dependent upon production of endogenous testosterone and elevated concentrations of intratesticular testosterone. Testosterone levels typically begin to decrease over time in men starting in their late 30s; however, as many as 12.4% of men below the age of 39 suffer the effects of low testosterone and seek treatment. This statistic suggests that a significant number of men seeking treatment for low testosterone are within their reproductive years, underscoring the importance of appropriate counseling for patients seeking testosterone therapy as it pertains to family planning. The standard treatment for men with low testosterone and symptoms of hypogonadism is administration of exogenous testosterone. The challenge for testosterone replacement among men who desire fertility is that exogenous testosterone is a known contraceptive. The key for treatment of low testosterone while preserving fertility is maintenance of high concentrations of intratesticular testosterone and promotion of endogenous testosterone production. Therapies that accomplish this goal include administration of gonadotropins like GnRH and hCG, selective estrogen receptor modulators like clomiphene citrate, and aromatase inhibitors like anastrozole. Experimental therapies include intranasal testosterone gels and Leydig stem cell transplantation.
Castable and Printable Dielectric Composites Exhibiting High Thermal Conductivity via Percolation-Enabled Phonon Transport

Summary High-power-density electronics used in modern cellular devices and radiofrequency electronics generate tremendous localized thermal energy (up to 300 W/cm2), posing serious concerns regarding performance, life cycle, and safety. Further increasing the power density of these communications electronics requires effective methods to conduct generated heat away from critical components. In this work, a magneto-vibrational mold-casting technique is used to produce aligned and percolated thermal pathways through hexagonal boron nitride particles for effective steady-state passive cooling from high-density electronics. Additionally, 3D magnetic printing is used to produce custom thermal pathways. Thermal interface material testing (ASTM D5470) is utilized to determine system-level through-thickness thermal conductivity (K⊥, including interfacial resistances) of up to 9 W/m-K, a >3-fold increase versus unaligned controls. These described new manufacturing approaches produce a unique class of castable and printable dielectric composites with high thermal conductivity.
Furosemide administration results in a transient alteration in calcium balance in mature horses.

Previous research documented that furosemide negatively impacted calcium balance for 3 days but did not determine when calcium balance returned to baseline. This study hypothesized that furosemide's impact on calcium would return to control values before 7 days post-administration. Ten mature geldings were assigned to either control (CON, n = 5) or treatment (FUR, n = 5) for the first of two 8-day total collections in crossover design. Treatment horses received one administration of furosemide (1 mg/kg, IV). A 10% sample of pooled faeces and urine from each day was kept. Calcium concentrations in hay, faeces and urine were determined by an atomic absorption spectrophotometer. Data were analysed using mixed-model-repeated measures ANOVA to determine influence of day and treatment. For urine output, FUR urinated twice as much during the 24 hr after administration than CON (p .10) but were lower in FUR on day 7 as compared to day 1 (4.8 ± 1.3 and 7.3 ± 1.3 g/kg, respectively; p < .001), indicating a potential mechanism to restore calcium balance. These findings corroborate previous studies on furosemide and calcium balance and provide evidence for a possible mechanism to recover net calcium losses after furosemide administration. Since calcium balance returns to baseline in 3 days and previous results have examined frequent, long-term use, furosemide may not negatively impact bone mineral content even if used over long periods.
Postacute Care Disposition for Total Hip and Total Knee Replacement Surgery for Asian Americans

This study explored differences in postacute disposition for total hip arthroplasty (THA) and total knee arthroplasty (TKA) with a focus on whether Asian Americans (AS) experience joint replacement...
Exacerbated obesogenic response in female mice exposed to early life stress is linked to fat depot-specific upregulation of leptin protein expression

Early life stress (ELS) is an independent risk factor for increased BMI and cardiometabolic disease risk later in life. We have previously shown that a mouse model of ELS, maternal separation and early weaning (MSEW), exacerbates high-fat diet (HF)-induced obesity only in adult female mice. Therefore, the aim of this study was to investigate 1) whether the short- and long-term effects of HF on leptin expression are influenced by MSEW in a sex-specific manner and 2) the potential epigenetic mechanisms underlying the MSEW-induced changes in leptin expression. After 1 wk of HF, both MSEW male and female mice displayed increased fat mass compared with controls (P < 0.05). However, only MSEW female mice showed elevated leptin mRNA expression in gonadal white adipose tissue (gWAT; P < 0.05). After 12 wk of HF, fat mass remained increased only in female mice (P < 0.05). Moreover, plasma leptin and both leptin mRNA and protein expression in gWAT were augmented in MSEW female mice compered to controls (P < 0.05), but not in MSEW male mice. This association was not present in subcutaneous WAT. Furthermore, among 16 CpG sites in the leptin promoter, we identified three hypomethylated sites in tissue from HF-fed MSEW female mice compared with controls (3, 15, and 16, P < 0.05). These hypomethylated sites showed greater binding of key adipogenic factors such as PPARγ (P < 0.05). Taken together, our study reveals that MSEW superimposed to HF increases leptin protein expression in a sex- and fat depot-specific fashion. Our data suggest that the mechanism by which MSEW increases leptin expression could be epigenetic.
“Who made these rules? We’re so confused.”: An Introduction to the Special Issue on Critical Race Media Literacy

In this introductory essay, editors of the special issue on critical race media literacy frame the current global contexts of race, racism, and media in which this issue is situated. Building from the work of authors included in this special issue, this essay calls readers to engage and disrupt racism in popular, educational, and other forms of media, both inside and beyond the classroom.
Strategies for Improving Nutrition in Inner-City Populations

The social, economic, cultural, and historic reasons for why inner-city communities have struggled with poor nutrition and health outcomes are complex. Creating successful programs to address these problems requires a better understanding of the gaps that exist and formulating solutions to improve access to nutritious food options. Studies have demonstrated that aggressive evidence-based nutrition can decrease factors linked to cardiovascular diseases, but improving access to these nutritious resources and prioritizing health literacy and behavior modification related to meal choices are just as essential. Government programs and community interventions have shown promise through creating supermarkets, farmers’ markets, and community gardens, but not all inner-city areas have such programs in place. The poor state of inner-city nutrition and health is a true public health crisis. Creation of innovative strategies to improve education on and sustainable access to nutritious foods is essential in order to improve health disparities and outcomes.
Counting Fixed Points and Rooted Closed Walks of the Singular Map $$x \mapsto {x^{{x^n}}}$$x↦xxn Modulo Powers of a Prime

The “self-power” map x ⟼ xx modulo m and its generalized form $$x \mapsto {x^{{x^n}}}$$ modulo m are of considerable interest for both theoretical reasons and for potential applications to cryptography. In this paper, we use p-adic methods, primarily p-adic interpolation, Hensel’s lemma, and lifting singular points modulo p, to count fixed points and rooted closed walks of equations related to these maps when m is a prime power. In particular, we introduce a new technique for lifting singular solutions of several congruences in several unknowns using the left kernel of the Jacobian matrix.
Appearance-preserving tactile optimization

Textures are encountered often on various common objects and surfaces. Many textures combine visual and tactile aspects, each serving important purposes; most obviously, a texture alters the object's appearance or tactile feeling as well as serving for visual or tactile identification and improving usability. The tactile feel and visual appearance of objects are often linked, but they may interact in unpredictable ways. Advances in high-resolution 3D printing enable highly flexible control of geometry to permit manipulation of both visual appearance and tactile properties. In this paper, we propose an optimization method to independently control the tactile properties and visual appearance of a texture. Our optimization is enabled by neural network-based models, and allows the creation of textures with a desired tactile feeling while preserving a desired visual appearance at a relatively low computational cost, for use in a variety of applications.
Screening and characterization of polyhydroxyalkanoate granules, and phylogenetic analysis of polyhydroxyalkanoate synthase gene PhaC in cyanobacteria.

Using Nile Red and BODIPY 493/503 dye-staining and fluorescence microscopy, twenty cyanobacterial strains, including ten commercially available strains and ten environmental isolates from estuaries, freshwater ponds, and lagoons, were screened for the accumulation of ecologically important and potentially biotechnologically significant carbon storage granules such as polyhydroxyalkanoates (PHA). Dye-staining granules were observed in six strains. Three Synechocystis, spp. strains WHSYN, LSNM, and CGF-1, and a Phormidium-like sp. CGFILA were isolated from environmental sources and found to produce granules of polyhydroxyalkanoate (PHA) according to PHA synthase gene (phaC) PCR screening and 1 H NMR analyses. The environmental isolate, Nodularia sp. Las Olas and commercially available Phormidium cf. iriguum CCALA 759 displayed granules but screened negative for PHA according to phaC PCR and 1 H NMR analyses. Partial polyhydroxyalkanoate synthase subunit C (phaC) and 16S rRNA gene sequences obtained from the PHA-accumulating strains and analyzed alongside publicly available phaC, phaE, 16S rRNA, and 23S rRNA data help in understanding the distribution and evolutionary history of PHA biosynthesis within the phylum Cyanobacteria. The data show that the presence of phaC is highly conserved within the genus Synechocystis, and present in at least one isolate of Phormidium. Maximum likelihood analyses and cophylogenetic modeling of PHA synthase gene sequences provide evidence of a recent horizontal gene transfer event between distant genera of cyanobacteria related to Pleurocapsa sp. PCC 7327 and Phormidium-like sp. CGFILA. These findings will help guide additional screening for PHA producers, and may explain why some Phormidium species produce PHAs, while others do not.
miR-146a Dysregulates Energy Metabolism During Neuroinflammation

Alzheimer's disease (AD) and other neurodegenerative diseases are characterized by chronic neuroinflammation and a reduction in brain energy metabolism. An important role has emerged for small, non-coding RNA molecules known as microRNAs (miRNAs) in the pathophysiology of many neurodegenerative disorders. As epigenetic regulators, miRNAs possess the capacity to regulate and fine tune protein production by inhibiting translation. Several miRNAs, which include miR-146a, are elevated in the brain, CSF, and plasma of AD patients. miR-146a participates in pathways that regulate immune activation and has several mRNA targets which encode for proteins involved in cellular energy metabolism. An additional role for extracellular vesicles (EVs) has also emerged in the progression AD, as EVs can transfer functionally active proteins and RNAs from diseased to healthy cells. In the current study, we exposed various cell types present within the CNS to immunomodulatory molecules and observed significant upregulation of miR-146a expression, both within cells and within their secreted EVs. Further, we assessed the effects of miR-146a overexpression on bioenergetic function in primary rat glial cells and found significant reductions in oxidative phosphorylation and glycolysis. Lastly, we correlated miR-146a expression levels within various regions of the AD brain to disease staging and found significant, positive correlations. These novel results demonstrate that the modulation of miR-146a in response to neuroinflammatory stimuli may mediate the loss of mitochondrial integrity and function in cells, thereby contributing to the progression of beta-amyloid and tau pathology in the AD brain. Multiple inflammatory stimuli can upregulate miRNA-146a expression within neurons, mixed glial cells, and brain endothelial cells, which is either retained within these cells or released from them as extracellular vesicle cargo. The upregulation of miR-146a disrupts cellular bioenergetics in mixed glial cells. This mechanism may play a critical role in the neuroinflammatory response observed during Alzheimer's disease.
Chapter 15 Pathogenesis and Pathophysiological Role of Hypoaldosteronism in Syndromes of Renal Hyperkalemia

Publisher Summary This chapter focuses on the pathogenesis and pathophysiological role of mineralocorticoid deficiency (hypoaldosteronism) in the abnormalities of potassium (K) homeostasis in humans. The chapter reveals that pathophysiological mechanisms potentially cause renal hyperkalemia. The chapter presents the syndromes of hypoaldosteronism divided conveniently into those that result from a primary adrenal abnormality, either a generalized disorder or one localized to the adrenal zona glomerulosa, and those that occur secondary to impaired function of the renin-angiotensin system, the major trophic influence on aldosterone secretion in humans. The separation of these two pathophysiologically distinct subtypes is achieved readily by the measurement of plasma renin activity (PRA), which is usually markedly elevated in the former and reduced in the latter. The hyperkalemia of renal origin that fails to respond to superphysiological doses of mineralocorticoid is called pseudohypoaldosteronism.
Protocols and hospital mortality in critically ill patients: The United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study

Objective: Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized ICUs have superior patient outcomes compared with less highly protocolized ICUs. Design: Observational study in which participating ICUs completed a general assessment and enrolled new patients 1 day each week. Patients: A total of 6,179 critically ill patients. Setting: Fifty-nine ICUs in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. Interventions: None. Measurements and Main Results: The primary exposure was the number of ICU protocols; the primary outcome was hospital mortality. A total of 5,809 participants were followed prospectively, and 5,454 patients in 57 ICUs had complete outcome data. The median number of protocols per ICU was 19 (interquartile range, 15–21.5). In single-variable analyses, there were no differences in ICU and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in ICUs with a high versus low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p = 0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between ICUs with high versus low numbers of protocols for lung protective ventilation in acute respiratory distress syndrome (47% vs 52%; p = 0.28) and for spontaneous breathing trials (55% vs 51%; p = 0.27). Conclusions: Clinical protocols are highly prevalent in U.S. ICUs. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality.
Father's education and children's human capital: evidence from the World War II GI Bill

Children who grow up in more highly educated families have better labor market outcomes as adults than those who grow up in less educated families, but we do not know whether this is because education bestows parents with skills that make them better parents or because unobservable endowments that contribute to the parents' education levels are shared by their children. This paper attempts to improve our understanding of the causal processes that contribute to intergenerational mobility by exploiting variation in fathers' education induced by the WWII G.I. Bill. Identificatin rests on the timing of the war: the GI Bill had different effects on different cohorts depending on their likelihood of military service and the probability that schooling had been completed before the war began. I find that a one year increase in a father's education reduces the probability that his child is retained in school by about 2-3 percentage points. This implies that parental schooling levels have an affect on children's outcomes that is independent of their innate ability and suggests that public policies aimed at increasing educational attainment may have important intergenerational effects.
Structure of a recombinant calmodulin from Drosophila melanogaster refined at 2.2-A resolution.

Abstract The crystal structure of calmodulin (Mr 16,700, 148 residues) from Drosophila melanogaster as expressed in a bacterial system has been determined and refined at 2.2-A resolution. Starting with the structure of mammalian calmodulin, we produced an extensively refitted and refined model with a conventional crystallographic R value of 0.197 for the 5,239 reflections (F greater than or equal to 2 sigma (F)) within the 10.0-2.2-A resolution range. The model includes 1,164 protein atoms, 4 calcium ions, and 78 water molecules and has root mean square deviations from standard values of 0.018 A for bond lengths and 0.043 A for angle distances. The overall structure is similar to mammalian calmodulin, with a seven-turn central helix connecting the two calcium-binding domains. The "dumb-bell" shaped molecule contains seven alpha-helices and four "EF hand" calcium-binding sites. Although the amino acid sequences of mammalian and Drosophila calmodulins differ by only three conservative amino acid changes, the refined model reveals a number of significant differences between the two structures. Superimposition of the structures yields a root mean square deviation of 1.22 A for the 1,120 equivalent atoms. The calcium-binding domains have a root mean square deviation of 0.85 A for the 353 equivalent atoms. There are also differences in the amino terminus, the bend of the central alpha-helix, and the orientations of some of the side chains.
Electron microscopic studies of the binding of Escherichia coli RNA polymerase to DNA. II. Formation of multiple promoter-like complexes at non-promoter sites.

Abstract The interactions between Escherichia coli RNA polymerase holoenzyme and a 3800 base-pair restriction fragment of bacteriophage T7 DNA (Mbo-IC) have been examined by electron microscopy. In addition to exhibiting weak, non-specific interactions (Ka ∼ 104 M−1), RNA polymerase is able to form up to 15 to 20 relatively stable complexes with this template (Ka est 109 M−1). Only one of these complexes is formed at the T7 promoter E, that maps at 92.2 ± 1% on the conventionalgenome. The remaining complexes seem to be situated non-randomly on this fragment and possibly involve interactions with specific DNA sequences. The association kinetics of formation have been examined and give rise to a second-order rate constant of ∼ 105 M−1 s−1. Formation of these complexes is markedly reduced at low temperatures. Under standard binding conditions (50 mM-NaCl) the dissociation rate of these complexes is slow ( t 1 2 ~ 30 min ), but increases rapidly with increasing salt concentration and at reduced temperatures. It is unaffected by the presence of heparin up to 5 μg/ml. Thus it appears that E. coli RNA polymerase can form complexes with promoter-like properties at many different sites on T7 DNA.
Meningococcal pericarditis: Report of 2 cases, 1 complicated by acute constrictive pericarditis

Abstract Two patients with pericarditis complicating meningococcal meningitis are reported. In 1, acute constrictive pericarditis developed 1 month after pericardiocentesis for cardiac tamponade. He was successfully treated and represents the only known survivor. Forty-three cases of pericarditis complicating meningoccocal infections have been reported, 9 of which have occurred in children. In 2, acute constrictive pericarditis developed; in 1, the entity was recognized at postmortem examination; the second case is reported herein.
High-tech development politics: new strategies and persistent structures in Brazilian informatics

This article examines the current nature of dependency in the context of global restructuring, where technological change in computers and telecommunications has made those sectors central for global economic competition. The Brazilian policy to promote computer manufacturing and software development, or informatics, is an example of a strategy to transform dependency in this context. This article examines the political and economic conditions that affected implementation of the Brazilian informatics policy after it became the object of a U.S. trade investigation in 1985. It identifies three sets of structural constraints on policy choices and outcomes: trade conflicts with the U.S. government, rapidly changing international product markets, and trade dependence. These constraints were found to persist, despite proficient and flexible political efforts to adapt to changing market conditions and manage ties with foreign capital.
Reaction Kinetics of Primary Rock-forming Minerals under Ambient Conditions

This article firstly discusses the general techniques for measurement of dissolution and precipitation rates of rock-forming silicates and carbonates, and then, seven of these nine factors are discussed sequentially. Full discussions of the last two phenomena, transport and biologic processes, are not included. Throughout the article, it also discusses how surface complexation models can now be used to understand the reactive sites on mineral surfaces. Nonetheless, the intent here is mostly to emphasize simpler rate equations that emphasize solution chemistry instead of surface chemistry because these are often used in reactive transport codes. Techniques to predict the rates of mineral dissolution for mineral compositions where data are unavailable are summarized.
Residual circulation in western Long Island Sound

[1] Current, salinity and temperature measurements from repeated ship transects, complemented by observations from long duration current profilers, are used to characterize the variability and structure of subtidal flow in western Long Island Sound, a region prone to seasonal hypoxia. Subtidal flow plays a leading role in the transport of oxygen and organic matter and must, therefore, be simulated as accurately as possible. We show that during periods of light wind in March and July, the subtidal along-sound flow is vertically and horizontally sheared with lower salinity water in the top 7 m moving eastward toward the ocean at approximately 10 cm s−1 with a counterflow of similar magnitude elsewhere. Velocity contours were found to slope downward to the south, and maximum eastward velocities were found near the surface on the southern half of the section. We find that there is a net transport in the direction of the East River (westward.) The velocity distribution is broadly consistent with theoretical predictions for the steady, frictional, baroclinic pressure gradient driven flow modified by Coriolis acceleration, despite its neglect of advective effects which were found to be important in the present observational analysis. Our estimates of the pressure gradient, the Coriolis acceleration and stress divergence have similar magnitudes. Observation-based estimates of terms in the momentum balance suggest that advection is more important to along-estuary momentum than across-estuary momentum. Along-estuary advection is overestimated in recent hydrodynamic simulations when compared to observed values at sampling locations.
Abstract 4000: Biological basis of aggressive phenotype in African-American prostate cancer cell line

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Introduction: It is well established that African American men (AAM) with prostate cancer (PC) present more frequently with higher grade tumors compared to Caucasians. While the disparity is likely multifactorial, the biological basis is perhaps the strongest contender. Protein kinase D1 (PKD1) is a tumor and metastasis suppressor in PC. Down regulation of PKD1 was shown to increased cell proliferation, migration and metastasis in PC. Aim and experimental procedure: In order to address the fundamental question whether PC in AAM is inherently aggressive, we compared the proliferation, invasion and the expression of PKD1-centered signaling based 13-biomarker panel in primary and metastatic AAM cell lines (E006AA and MDApca2b) to benign (RWPE) and metastatic Caucasian cell lines (LNCaP and C4-2) using Western blot within different cell compartments. The results were further validated by RT-PCR and immunofluoroscent staining. Results: The proliferation, viability and invasion assays showed that E006AA cells proliferate and invade matrigel significantly more rapidly than metastatic LNCaP and MDAPca2b cells. The 13-biomarker panel analysis showed PKD1-centered dysregulaiton in AAM prostate cancer cell lines. Although E006AA is a primary PC cell line, PKD1 was down regulated similar to more aggressive C4-2 cells. Nuclear androgen receptor (AR), which shows active AR, was higher in LNCaP and MD2Pca2b; Vimentin showed higher expression in C4-2 and E006AA. Localization of E-Cadherin, N-Cadherin, T120 phosphorylated s- Catenin, MMP-2 and S11 phosphorylated snail in MD2Pca2b was similar to LNCaP cells but different to C4-2 and E006AA. Conclusion: Our Data demonstrates that the dysregulaiton of PKD1-centered signaling occurs in primary AAM prostate cancer cell line E006AA is akin to other metastatic PC cell lines suggesting an inherently aggressive nature of PC in AAM. Acknowledgment: Authors would like to thank Dr. Shahriar Koochekpour (Roswell park institute, University at Buffalo,State University of NewYork) for his kind gift E006AA cell line. Citation Format: Bita Nickkholgh, Xiaolan Fang, Kenneth Gyabaah, K.C. Balaji. Biological basis of aggressive phenotype in African-American prostate cancer cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4000. doi:10.1158/1538-7445.AM2014-4000
Spatial chirp effects in virtually-imaged phased-array wavelength demultiplexors

We observe a novel spatial chirp effect, in which different spatial portions of the output beam from a virtually imaged phased array (VIPA) etalon contribute to different optical frequencies in its frequency demultiplexing response.
Potential benefits of strategic problem resolution in aircraft automation

Assuring safety in every phase of modern aviation is always a high priority, and avionics systems play a central role in these efforts. Although great progress has been made in using automation on the flight deck, every accident and incident reminds us that these systems could be still safer. Some accidents such as the loss of Air France 447 (AF447) in 2009 have inspired calls for reduced automation, or expanded training to better prepare pilots for its absence. However, other accidents show that seemingly minor misunderstandings of an aircraft's automated systems can lead to deadly outcomes even without equipment failures.