cssi/SciSciGPT-SciSciNet huggingface dataset:
SIRT1-PGC1α-NFκB Pathway of Oxidative and Inflammatory Stress during Trypanosoma cruzi Infection: Benefits of SIRT1-Targeted Therapy in Improving Heart Function in Chagas Disease

Chronic chagasic cardiomyopathy (CCM) is presented by increased oxidative/inflammatory stress and decreased mitochondrial bioenergetics. SIRT1 senses the redox changes and integrates mitochondrial metabolism and inflammation; and SIRT1 deficiency may be a major determinant in CCM. To test this, C57BL/6 mice were infected with Trypanosoma cruzi (Tc), treated with SIRT1 agonists (resveratrol or SRT1720), and monitored during chronic phase (~150 days post-infection). Resveratrol treatment was partially beneficial in controlling the pathologic processes in Chagas disease. The 3-weeks SRT1720 therapy provided significant benefits in restoring the left ventricular (LV) function (stroke volume, cardiac output, ejection fraction etc.) in chagasic mice, though cardiac hypertrophy presented by increased thickness of the interventricular septum and LV posterior wall, increased LV mass, and disproportionate synthesis of collagens was not controlled. SRT1720 treatment preserved the myocardial SIRT1 activity and PGC1α deacetylation (active-form) that were decreased by 53% and 9-fold respectively, in chagasic mice. Yet, SIRT1/PGC1α-dependent mitochondrial biogenesis (i.e., mitochondrial DNA content, and expression of subunits of the respiratory complexes and mtDNA replication machinery) was not improved in chronically-infected/SRT1720-treated mice. Instead, SRT1720 therapy resulted in 2-10-fold inhibition of Tc-induced oxidative (H2O2 and advanced oxidation protein products), nitrosative (inducible nitric oxide synthase, 4-hydroxynonenal, 3-nitrotyrosine), and inflammatory (IFNγ, IL1β, IL6 and TNFα) stress and inflammatory infiltrate in chagasic myocardium. These benefits were delivered through SIRT1-dependent inhibition of NFκB transcriptional activity. We conclude that Tc inhibition of SIRT1/PGC1α activity was not a key mechanism in mitochondrial biogenesis defects during Chagas disease. SRT1720-dependent SIRT1 activation led to suppression of NFκB transcriptional activity, and subsequently, oxidative/nitrosative and inflammatory pathology were subdued, and antioxidant status and LV function were enhanced in chronic chagasic cardiomyopathy.
Mouse Model of MYC-Deregulating Chromosomal Translocations Associated with Human Burkitt Lymphoma and Multiple Myeloma.

Purpose: Burkitt lymphoma (BL) is tightly associated with chromosomal t(8;14)(q24;q32) translocations that result in the deregulated expression of the MYC (c- myc ) oncogene due to its juxtaposition to enhancers of the immunoglobulin-heavy chain locus IGH . The t(8;14)(q24;q32) MYC-IGH translocation is widely believed to be the initiating event in the pathogenesis of BL. Multiple myeloma (MM) is a malignant neoplasm of plasma cells that is often associated with complex cytogenetic alterations that juxtapose MYC , analogous to the t(8;14)(q24;q32) translocation, to IGH enhancers. However, MYC-IGH rearrangements of this sort occur during the progression of MM, not as tumor-initiating events as in BL. Accurate mouse models of MYC deregulation associated with human BL and MM are needed to study the events involved in tumor initiation and progression and design new approaches for treatment and prevention. To that end, we have generated a new mouse model of human t(8;14)(q24;q32) translocation. Experimental procedure: We inserted a His 6 -tagged mouse Myc cDNA, Myc His , into two different locations of the mouse immunoglobulin heavy-chain locus, Igh , just 5′ of Eμ or Cμ. In the latter case, Eμ was deleted during gene targeting. The newly developed gene-insertion strains were designated iMyc Eμ and iMyc Cμ . The iMyc Eμ mice provide a specific model of the t(8;14)(q24;q32) observed in endemic BL (eBL). The iMyc Cμ mice mimic the t(8;14)(q24;q32) found in sporadic BL (sBL) and immunodeficiency-associated BL (iBL) (Fig. 1). Result: Both “iMyc” gene-insertion strains are prone to the spontaneous development of mature B cell and plasma cell tumors. However, in the Eμ-containing iMyc Eμ mice, tumors arose earlier and tumor incidence was higher compared to the Eμ-deleted iMyc Cμ (Fig. 2 left). This correlated well with the control of Myc His expression by Eμ, as Myc His mRNA levels were higher in B cells from iMyc Eμ than iMyc Cμ mice. Interestingly, the iMyc Cμ transgene was as effective in inducing inflammation-dependent peritoneal plasmacytomas as the iMyc Cμ transgene (Fig. 2 right). This indicated that host factors, such as chronic inflammation, can greatly enhance the transformation-inducing potency of a deregulated Myc gene that is only weakly oncogenic in spontaneous tumor development. Conclusion: The “iMyc” mice provide a model of Myc deregulation that is conducive to plasma cell tumors in mice. The mice may thus afford a good opportunity to identify the genes that collaborate with Myc in neoplastic plasma cell development. Combined with the transgenic expression of MM genes, such as DKK1 , the “iMyc” mice may also be useful as a platform for modelling human plasma cell neoplasms in mice.
Control of asynchronous sampled-data systems

This paper is concerned with the problem of controller design in the case of asynchronous sampled data systems. Optimal LQC controllers are obtained for the class of two-rate systems where all the control inputs are held at a rate which is asynchronously related to the rate with which all of the outputs are sampled. Furthermore for this class, a parametrization of all stabilizing controllers is provided. >
Richmond T. Prehn: In Memoriam (1922–2016)

![][1] On November 7, 2016, the cancer research community lost Dr. Richmond Prehn (Rich), a lifelong supporter of AACR and former member of its board, a penetrating theoretician, and a decisive experimentalist. Most scientists think in incremental steps and fear taking great leaps
On Specialized Legal Research

This brief essay explores the concept of "specialized legal research." What is it — the research done by a firm's practice group, the research defined by a collection of document types, or simply "the hard stuff"? I follow these musings with some practical tips for getting up to speed in a specialized area of legal research.
Defect-Induced Near-Infrared Photoluminescence of Single-Walled Carbon Nanotubes Treated with Polyunsaturated Fatty Acids.

Single-walled carbon nanotubes (SWCNTs) have been incorporated in many emerging applications in the biomedical field including chemical sensing, biological imaging, drug delivery, and photothermal therapy. To overcome inherent hydrophobicity and improve their biocompatibility, pristine SWCNTs are often coated with surfactants, polymers, DNA, proteins, or lipids. In this paper, we report the effect of polyunsaturated fatty acids (PUFAs) on SWCNT photoluminescence. A decrease in the SWCNT bandgap emission (E11) and a new red-shifted emission (E11–) were observed in the presence of PUFAs. We attribute the change in SWCNT photoluminescence to the formation of oxygen-containing defects by lipid hydroperoxides through photo-oxidation. The observed changes in near-infrared emission of SWCNTs are important for understanding the interaction between SWCNTs and lipid biocorona. Our results also indicate that photoexcited SWCNTs can catalyze lipid peroxidation similarly to lipoxygenases.
Some phonological aspects of the aquisition of Hausa

This paper will describe the order, manner, and length of time in which Hausa children acquire the liquids Ir, r, II and the glottalized consonants 16, d, R, ts, 'y/. It will also discuss how this acquisition process relates to other child language data, and to linguistic, particularly diachronic linguistic, theory. The children whose speech is reported in this paper were observed over a one and one-half year period in Birnin Kudu, Kano State, Northern Nigeria. About twelve children from six months to fifteen years were observed from time to time during that period. Two children who were about two and two-and-one half when the study was started were observed at least three times a week.
Low-power approaches for parallel free-space photonic interconnects

Future advances in the application of photonic interconnects will involve the insertion of parallel-channel links into Multi-Chip Modules (MCMs) and board-level parallel connections. Such applications will drive photonic link components into more compact forms that consume far less power than traditional telecommunication data links. These will make use of new device-level technologies such as vertical cavity surfaceemitting lasers and special low-power parallel photoreceiver circuits. Depending on the application, these device technologies will often be monolithically integrated to reduce the amount of board or module real estate required by the photonics. Highly parallel MCM and board-level applications will also require simplified drive circuitry, lower cost, and higher reliability than has been demonstrated in photonic and optoelectronic technologies. An example is found in two-dimensional point-to-point array interconnects for MCM stacking. These interconnects are based on high-efficiency Vertical Cavity Surface Emitting Lasers (VCSELs), Heterojunction Bipolar Transistor (HBT) photoreceivers, integrated micro-optics, and MCM-compatible packaging techniques. Individual channels have been demonstrated at 100 Mb/s, operating with a direct 3.3V CMOS electronic interface while using 45 mW of electrical power. These results demonstrate how optoelectronic device technologies can be optimized for low-power parallel link applications.
Evading the interferon response: hepatitis C virus and the interferon-induced protein kinase, PKR.

What’s a cell to do when faced with the prospect of being invaded by an army of determined viruses? A complex, multi-pronged defense is in order, and luckily, just such a defense is available. The cellular interferon response represents a powerful and multi-faceted approach to dealing with everyday stresses that range from viral infection to keeping cellular growth under control. Mediated by a family of negative growth regulators, collectively referred to as interferons, the interferon response is indeed complex. After binding to specific cell surface receptors, interferons set in motion a number of signal transduction pathways that lead to the induction of gene expression (reviewed in FOSTER 1997; HAQUE and WILLIAMS 1998; MULLER et al. 1994; VILCEK and SEN 1996). Although the majority of in-terferon-induced gene products have yet to be characterized, several have demonstrated antiviral properties. These include RNase L, 2′–5′ oligoadenylate synthetase, the Mx proteins, and the double-stranded (ds)RNA-activated protein kinase, PKR. Together, these proteins are capable of disrupting viral gene expression at multiple levels, including viral mRNA stability, transcription, and translation. Of course, viruses are not without weapons of their own, and many are capable of putting up a good fight, and even winning, in the face of such an arsenal. In this review, we will focus our attention on one particular component of the cellular antiviral response, the protein kinase known as PKR. PKR is one of the better characterized interferon-induced gene products and is critical component of the antiviral response.
Measuring the Implementation of Youth Empowerment Solutions

Scholars have increasingly emphasized the importance of using evidence-based programs to promote health and prevent disease. While theoretically and empirically based programs may be effective in carefully controlled conditions, many fail to achieve desired outcomes when implemented in real-world settings. Ensuring high-quality implementation of health promotion programs is critically important as variation in implementation is closely associated with program effectiveness. The purpose of this article is to present methods used to document and assess the implementation of the Youth Empowerment Solutions (YES) program. We collected process evaluation data on 25 YES groups from 12 schools over a period of 4 years. The evaluation assessed four key aspects of delivery: fidelity, dose delivered, dose received, and program quality. We found wide variations in delivery for some measures, while others were more consistent across groups. These indicators of program delivery provided a strong basis for evaluating program implementation, taking actions to improve it, and ultimately, deepening understanding of program effectiveness. The study suggests a model for using multiple methods to collect and analyze data about aspects of program delivery to guide future implementations.
The Perceived Impact of String Programs on K-12 Music Programs

We examined music teacher perceptions regarding the impact of string programs on overall music programs in K-12 schools. Research questions included: (1) What are the perceived positive and negativ...
Comments on the “Determination and correlation of the solubility and thermodynamic parameters of 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside in pure organic solvents”

Abstract Errors are discovered in the authors' calculated excess enthalpies based on the Buchowski-Ksiazcyak λh equation. The authors inadvertently subtracted the solute's enthalpy of fusion from the product universal gas constant (in Joules/(mole K)) times Buchowski-Ksiazcyak h parameter, without changing the units of solute's enthalpy of fusion to Joules/mole. As a result all of the 81 excess enthalpies given in Table 8 of the published paper by Huang and coworkers are in error.
The Evolution of Youth Friendship Networks from 6th to 12th Grade: School Transitions, Popularity and Centrality

This chapter examines adolescents’ friendship patterns from 6th through 12th grade, and investigates the impact on friendship networks of two transitions in the institutionalized life course, one from elementary to middle school and the other from middle to high school. Using information from 51 networks in 26 school districts, this study considers data from 13,214 students (PROSPER). Findings show that adolescent popularity and centrality tend to reach their maximum in early adolescence and then consistently decline until 12th grade. Results also demonstrate that both school transitions propel the process of declining centrality, by exacerbating the negative consequences to individual centrality. Furthermore, students who transition between 8th and 9th grade experience declines in social integration that persist until the end of high school. Thus, during the period of adolescence, people become less popular and are known by fewer people over time, and school transitions magnify these potentially problematic trends.
Fetal Leydig Cells

The discovery of adult Leydig cells by Franz Leydig in 1850 led to extensive research into the functions and regulation of this testis-specific cell type (1). In the early 1900s, Whitehead presented the first extensive analysis of fetal Leydig cells (FLCs) in pig embryos, staging the idea that a distinct Leydig cell population exists in fetal testes (2, 3). Since then, it is widely accepted that at least two populations of Leydig cells—fetal and adult types—exist at different developmental stages in most mammalian testes. Despite their differences in morphological and biochemical properties, fetal and adult Leydig cells share a common function, i.e., production of androgens. FLCs have been characterized in a wide range of mammalian species including human, monkey, pig, rabbit, guinea pig, hamster, rat, and mouse. This chapter focuses on the morphological characteristics, origin, specification, and functions of FLCs in rats and mice, species in which most physiological and genetic experiments are conducted.
Fate of DNA Sugar Radicals

Publisher Summary Oxidative damage to nucleic acids occurs at the nucleobase and at the sugar-phosphate backbone. While base damage dominates in frequency, the attack of oxidants at sugars in the nucleic acid backbone often leads to strand breaks that ultimately leave gaps or nicks that carry modified or “dirty” ends. When the damage is focused on the 2'-deoxyribose component of DNA, hydrogen atoms are abstracted from one of the five unique carbons of the pentose ring to deliver a highly reactive radical intermediate. Another important factor, which should be considered while attempting to make such predictions, is the identity of the oxidant. One of the most significant species to consider when discussing DNA oxidants is the hydroxyl radical. This reactive oxygen species is produced endogenously through cellular metabolism, at higher levels under conditions of oxidative stress, as a part of chronic inflammation and as a major outcome of the exposure of cells to ionizing radiation. The hydroxyl radical is small, highly diffusible, reactive, and capable of hydrogen atom abstraction at any position of 2'-deoxyribose moiety in DNA. Finally, the position of the C'5-radical relative to the nucleobase of DNA renders its reactivity toward the heterocyclic nucleic acid moieties very distinct as compared to the four other positions.
Conversion of the Electrohydraulic Electrode to an Electromechanical Stone Impactor: Basic Studies and a Case Report

AbstractA 3.3F electrohydraulic electrode (Wolf 2137.23) has been confined within a spring with a metal end cap, irrigated with water and covered with a 0.003-inch metal sheath (outside diameter 5F). The electrohydraulic lithotripsy discharge (Wolf Generator 2137.50) at El causes the metal cap to extend 3mm. at 1,500cm. per second and creates an impact pressure of 600 to 800 bar. Stone fragmentation efficiency of the electromechanical impactor was equivalent to unshielded electrohydraulic lithotripsy (gallstone 2.83mg. per pulse, struvite/apatite 1.41mg. per pulse, cystine 0.41mg. per pulse, uric acid 1.48mg. per pulse and 100% calcium oxalate monohydrate 0.10mg. per pulse).Studies of the discharge of the electromechanical impactor within the pig ureter showed that minimal ureteral submucosal edema and hemorrhage occurred at 300 shocks discharged at a single point, and disruption of the mucosa and partial injury to the muscle layer occurred after 600 shocks given at the site of a pinched pig ureter. Pushi...
The rate of convergence and the asymptotic normality of an estimator in a controlled investment model with time-varying parameters

The sample path rate of convergence is obtained for a strongly consistent, recursive estimator of a parameter in a bilinear stochastic differential equation. The bilinear stochastic differential equation arises in a model of portfolio selection and consumption. The parameters of this equation change with time and converge to limits. It is assumed that one of these parameters is unknown. In this case it is necessary simultaneously to estimate the unknown parameter and to control the state equation so there is the problem of adaptive control. Asymptotic normality for a parameter estimator is also given.
Mental Health in Chronic and End-Stage Liver Disease

Patients with chronic liver diseases experience common psychiatric disorders and specific symptoms that have psychiatric and psychological implications. Thus, mental health-care professionals must understand both the inherent liver disease process and the mental health disorders that commonly co-occur with liver diseases. For some types of liver diseases (e.g., Wilson’s disease, hepatic porphyrias), the presenting features may be neuropsychiatric in nature, and clinicians should be aware of the common characteristics of these diseases. Additionally, certain psychiatric disorders are relatively common in patients with liver disease, such as addiction disorders and depression. Specific consideration of the severity of liver disease for pharmacotherapeutic management is required. Patients with liver disease face specific challenges in their daily functioning and with psychological stressors. Interventions tailored to these issues may be most effective. Patients’ complex health-care needs may be best provided through collaborative care models capitalizing on the expertise of multiple disciplines.
Design Rules for One-Step Seeded Growth of Nanocrystals: Threading the Needle between Secondary Nucleation and Ripening

The heterogeneous growth of inorganic shells on seed nanocrystals is used to synthesize heterostructured nanocrystals such as core@shell quantum dots for applications ranging from biological imagin...
On Command Drug Delivery via Cell‐Conveyed Phototherapeutics

Herein, the use of red blood cells (RBCs) as carriers of cytoplasmically interned phototherapeutic agents is described. Photolysis promotes drug release from the RBC carrier thereby providing the means to target specific diseased sites. This strategy is realized with a vitamin B12-taxane conjugate (B12-TAX), in which the drug is linked to the vitamin via a photolabile CoC bond. The conjugate is introduced into mouse RBCs (mRBCs) via a pore-forming/pore-resealing procedure and is cytoplasmically retained due to the membrane impermeability of B12. Photolysis separates the taxane from the B12 cytoplasmic anchor, enabling the drug to exit the RBC carrier. A covalently appended Cy5 antenna sensitizes the conjugate (Cy5-B12-TAX) to far red light, thereby circumventing the intense light absorbing properties of hemoglobin (350-600 nm). Microscopy and imaging flow cytometry reveal that Cy5-B12-TAX-loaded mRBCs act as drug carriers. Furthermore, intravital imaging of mice furnish a real time assessment of circulating phototherapeutic-loaded mRBCs as well as evidence of the targeted photorelease of the taxane upon photolysis. Histopathology confirms that drug release occurs in a well resolved spatiotemporal fashion. Finally, acoustic angiography is employed to assess the consequences of taxane release at the tumor site in Nu/Nu-tumor-bearing mice.
Measuring industry co-location across county borders

The location quotient (LQ) measures regional industry concentration with the advantages of easy calculation and interpretation. However, it is a weak method for identifying industry clusters that c...
Head injury in prison: Gang membership and the role of prison violence

Abstract Purpose Serious head injuries, also known as traumatic brain injuries (TBIs), are associated with an increase in aggression and violent tendencies. The current study extends the literature on head injuries by examining whether gang membership is associated with an elevated risk of head injury in prison, and the extent to which this relationship is mediated by different forms of prison violence. Methods We use data from the LoneStar Project, a representative sample of 802 men imprisoned in Texas. We assess the gang membership-head injury link using logistic regression and Karlson-Holm-Breen (KHB) mediation. Results Prison gang members were >2.5 times as likely to report a head injury in prison compared to non-gang members (OR = 2.593; 95% CI = 1.220–5.509), net of controls. KHB mediation analyses reveal that violent misconduct and violent victimization collectively reduced the magnitude of the relationship between gang membership and in-prison head injury by 34.84%. Conclusions Prison gang members have a higher risk of head injury in prison, which we demonstrate is largely a function of their increased involvement in prison violence. Cognitive behavioral therapy (CBT) interventions should be used to lessen the negative repercussions from head injury and would be beneficial for reentry preparation.
Opioid prescription patterns among radiation oncologists in the United States.

BACKGROUND Radiation oncologists (ROs) play an important role in managing cancer pain; however, their opioid prescribing patterns remain poorly described. METHODS The 2016 Medicare Physician Compare National Downloadable and the 2016 Medicare Part D Prescriber Data files were cross-linked to identify RO-written opioid prescriptions. RESULTS Of 4,627 identified ROs, 1,360 (29.3%) wrote >10 opioid prescriptions. The average number of opioid prescriptions written was significantly (P ≤ .05) associated with the following RO characteristics: sex [13.1 ± 36.5 male vs 7.5 ± 16.9 female]; years since medical school graduation [4.5 ± 11.5 1-10 years vs 12.6 ± 26.0 11-24 years vs 13.3 ± 40.9 ≥25 years]; practice size [15.5 ± 44.6 size ≤10 vs 13.3 ± 25.9 size 11-49 vs 8.5 ± 12.7 size 50-99 vs 8.8 ± 26.9 size ≥100]; Medicare Physician Quality Reporting System (PQRS) participation [12.6 ± 31.8 yes vs 7.0 ± 35.4 no]; and practice location [17.4 ± 47.0 South vs 10.6 ± 29.4 Midwest vs 8.1 ± 13.9 West vs 6.9 ± 15.2 Northeast]. On multivariable regression modeling, male sex (RR 1.29, 95% CI 1.22-1.35, P < .001), ≥25 years since graduation (RR 0.78, 95% CI 0.64-0.70, 1-10 years vs ≥25 years; RR 1.00, 95% CI 0.96 - 1.04, 11-24 years vs ≥25 years; P < .001), practice size <10 members (RR 1.51, CI 1.44-1.59, ≤10 vs ≥100 members, RR 1.27, CI 1.20-1.34, 10-49 vs ≥100 members, RR 0.86, CI 0.80-0.92, 50-99 vs ≥100 members, P < .001), PQRS participation (RR 1.12, CI 1.04-1.19, P < .002), and Southern location (RR 0.67, CI 0.64-0.70, Midwest vs South; RR 0.39, CI 0.37-0.41, Northeast vs South; RR 0.43, CI 0.41-0.46, West vs South; P < .001) were predictive of higher opioid prescription rates. CONCLUSIONS Factors associated with increased number of RO-written opioid prescriptions were male sex, ≥25 years since graduation, group practice <10, PQRS participation, and Southern location. Additional research is required to establish optimal opioid prescribing practices for ROs.
Susceptibility of Serratia marcescens to Human Serum: Antagonism of Serum Bactericidal Activity by IgG Immunoglobulins of Homologous Rabbit Anti-O Sera

Absorption of fresh human serum with boiled or live homologous O-cells of Serratia marcescens in the cold (4 degrees C, 1 hour) completely abrogated killing activity against "delayed serum-sensitive" (DSS) strains of S. marcescens. In contrast, previously "promptly serum-sensitive" (PSS) strains of S. marcescens and the PSS control strain Escherichia coli C were killed kinetically in a slightly "delayed" fashion by antibody-depleted fresh human serum. Addition of 40 vol% of heat-inactivated homologous rabbit anti-O immune sera to 50 vol% of fresh human serum "blocked" bactericidal activity against DDS and PSS assay strains of S. marcescens. The "blocking" activity of rabbit anti-O immune sera was shown to reside in the crude gamma globulin fractions derived therefrom through precipitation with ammonium sulfate. Absorption of rabbit anti-O immune sera with boiled homologous O-cells failed to remove the "blocking" activity; the O-agglutination titers were reduced to nondetectable levels. However, dual absorptions of rabbit anti-O immune sera with killed cells of Staphylococcus aureus Cowan I (protein A) almost completely abolished "blocking" activity; the O-agglutinin titers of these immune sera were not reduced more than 4-fold. Immunoelectrophoresis and rocket electroimmuno assays. employing heavy chain-specific goat anti-rabbit IgG and IgM sera, respectively, established that dual protein A-absorption selectively removed rabbit IgG, but not rabbit IgM, immunoglobulins. It was concluded that rabbit immunoglobulins of the IgG class accounted for the observed in vitro antagonism of the bactericidal activity of fresh human serum against DSS and PSS strains of S. marcescens.
Mechano-stimulation initiated by extracellular adhesion and cationic conductance pathways influence astrocyte activation.

Abstract Traumatic brain injury (TBI) represents a major cause of long-term disability worldwide. Primary damage to brain tissue leads to complex secondary injury mechanisms involving inflammation, oxidative stress and cellular activation/reactivity. The molecular pathways that exacerbate brain cell dysfunction after injury are not well understood and provide challenges to developing TBI therapeutics. This study aimed to delineate mechanisms of astrocyte activation induced by mechano-stimulation, specifically involving extracellular adhesion and cationic transduction. An in vitro model was employed to investigate 2D and 3D cultures of primary astrocytes, in which cells were exposed to a single high-rate overpressure known to cause upregulation of structural and proliferative markers within 72 h of exposure. An inhibitor of focal adhesion kinase (FAK) phosphorylation, TAE226, was used to demonstrate a relationship between extracellular adhesion perturbations and structural reactivity in the novel 3D model. TAE226 mitigated upregulation of glial fibrillary acidic protein in 3D cultures by 72 h post-exposure. Alternatively, incubation with gadolinium (a cationic channel blocker) during overpressure, demonstrated a role for cationic transduction in reducing the increased levels of proliferating cell nuclear antigen that occur at 24 h post-stimulation. Furthermore, early changes in mitochondrial polarization at 15 min and in endogenous ATP levels at 4−6 h occur post-overpressure and may be linked to later changes in cell phenotype. By 24 h, there was evidence of increased amine metabolism and increased nicotinamide adenine dinucleotide phosphate oxidase (NOX4) production. The overproduction of NOX4 was counteracted by gadolinium during overpressure exposure. Altogether, the results of this study indicated that both extracellular adhesion (via FAK activation) and cationic conductance (via ion channels) contribute to early patterns of astrocyte activation following overpressure stimulation. Mechano-stimulation pathways are linked to bioenergetic and metabolic disruptions in astrocytes that influence downstream oxidative stress, aberrant proliferative capacity and structural reactivity.
Three Degrees External to the Posterior Condylar Axis Has Little Relevance in Femoral Component Rotation: A Computed Tomography-Based Total Knee Arthroplasty Simulation Study.

Abstract Background Femoral component rotation in total knee arthroplasty (TKA) has a significant impact on balance and patellofemoral kinematics. However, normal anatomic relationships between rotational axes are poorly understood. As such, we sought to characterize anatomic femoral rotational axes in patients undergoing primary TKA. Methods We identified 100 patients who underwent a primary TKA with a preoperative computed tomography scan. The angles between the surgical epicondylar axis (SEA) and the anterior-posterior (AP) axis to the posterior condylar axis (PCA) were measured independently by a musculoskeletal fellowship-trained radiologist and a fellowship-trained arthroplasty surgeon. We simulated an ideal TKA in which the femoral component was placed exactly 3° external to the PCA and measured resulting rotation. Results The SEA was on average 1.5° externally rotated to the PCA (range 3.1° internal to 7.0° external). The AP axis was on average 4.5° externally rotated to the PCA (range 2.3° internal to 10.3° external). The AP axis was a mean 2.7° externally rotated to the SEA (range 6.3° internal to 10.3° external). Routinely setting femoral rotation 3° external to the PCA would result in only 51 (51%) TKAs within ±2° of the SEA and 23 (23%) femoral components internally rotated relative to the SEA. Conclusion Normal anatomic rotational axes of arthritic knees are highly variable, with a 10° range in the SEA and 16° range in the AP axis. Routinely setting femoral rotation 3° external to the PCA will yield significant error in aligning the femoral component with either the SEA or AP axis.
Evolution of the Diagnostic Criteria in Multiple Sclerosis

The diagnostic criteria for multiple sclerosis provide a comprehensive framework to facilitate accurate diagnosis. The criteria have evolved since the original description of the syndrome by Charcot in 1868 into a multidimensional scheme that incorporates clinical presentation, imaging, and paraclinical evidence to aid in the diagnostic process. Additionally, the criteria were initially intended for use in research studies but are now intended for both research and clinical use. The key features of the criteria now include aspects of the clinical presentation, establishing dissemination in time and space, role of MRI, and utility of CSF and other paraclinical tests. There still are aspects that need refinement, including incorporation of the anterior visual system, applicability in diverse populations and presentations, and development of unique biomarkers and advanced imaging techniques. The development of the diagnostic criteria will continue to be an iterative process based on ongoing research with an emphasis on creating a practical approach facilitating early and accurate diagnosis of MS.
Investigation of strain-rate and pressure effects for high-strength concrete using a novel large-diameter triaxial Kolsky bar technique

Abstract Cementitious materials exposed to extreme loading conditions are subjected to a wide range of strain rates and confining pressures. To improve modeling capabilities, a triaxial Kolsky bar technique is provided to simultaneously investigate strain rate and pressure dependencies. A cylindrical specimen with diameter and length of 25.4 mm was investigated at quasi-static and dynamic strain rates with confining pressures up to 200 MPa. Annular pulse shapers were incorporated to ensure stress equilibrium under constant strain rate deformations. Furthermore, dynamic pressure variations were theoretically approximated and determined to be negligible. The dynamic increase factor was found to decrease as confining pressures increased. Additionally, a shift in the brittle-to-ductile transition point was also observed to show a more brittle failure mode under dynamic strain rates. Lastly, a dynamic failure surface is presented to illustrate the strain-rate and pressure dependencies of high-strength concrete.
Finite element analysis of the impact of bone nanostructure on its piezoelectric response

The piezoelectric response of bone at the submicron scale is analyzed under mechanical loadings using the finite element (FE) method. A new algorithm is presented to virtually reconstruct realistic bone nanostructures, consisting of collagen fibrils embedded in a hydroxyapatite mineral network. This algorithm takes into account potential misalignments between fibrils, as well the porous structure of the mineral phase. A parallel non-iterative mesh generation algorithm is utilized to create high-fidelity FE models for several representative volume elements (RVEs) of the bone with various fibrils volume fractions and misalignments. The piezoelectric response of each RVE is simulated under three types of loading: the longitudinal compression, lateral compression, and shear. The resulting homogenized stress and electric field in RVEs with aligned fibrils showed a linear variation with the fibrils volume fraction under all loading conditions. For RVEs with misaligned fibrils, although more oscillations were observed in homogenized results, their difference with the results of RVEs with aligned fibrils subject to lateral compression and shear loadings were negligible. However, under longitudinal compression, the electric field associated with RVEs with misaligned fibrils was notably higher than that of RVEs with aligned fibrils for the same volume fraction.
Phobos regolith simulants PGI-1 and PCA-1

Abstract The Martian moon Phobos is the target of the upcoming JAXA Martian Moons eXploration (MMX) mission. There are currently no known samples of Phobos, so spacecraft hardware testing and scientific studies require Phobos regolith simulants. Here, we present two new Phobos regolith simulants: Phobos Captured Asteroid-1 (PCA-1) and Phobos Giant Impact (PGI-1). These two simulants reflect the two hypotheses for Phobos’s formation, and thus the two broad possibilities for composition. This work follows previous efforts to document the development of mineralogically accurate simulants, in an effort to overcome past pitfalls with inappropriate uses of simulants. We report physical and geotechnical properties of PCA-1 and PGI-1, including their reflectance spectra, grain size distributions, abrasivity, cohesion, strength, and hardness. Our intent is for PCA-1 and PGI-1 to be open standards for Phobos simulants, and we present the simulant recipes and production methodology for use and modification by the community.
OAB-052: Impact of chromosome 1 abnormalities on newly diagnosed multiple myeloma treated with proteasome inhibitor, immunomodulatory drug, and dexamethasone: analysis from the ENDURANCE ECOG-ACRIN E1A11 trial

Background Chromosome 1 abnormalities (C1A) are frequently identified in multiple myeloma (MM). We assessed impact of C1A in a post hoc analysis of E1A11 trial. Methods E1A11 randomized newly diagnosed (ND) MM patients (pts) with traditional ‘standard risk’ features or t(4;14), not intended for upfront transplant, to bortezomib (V) or carfilzomib (K), in combination with lenalidomide (R) and dexamethasone (d), followed by indefinite or 2-year (y) R maintenance. Impact of C1A and ultra-high risk (UHR) MM [≥2 of the following: +1q [gain1q (3 copies) or amplification (amp)1q21 (≥4 copies)], deletion (del)1p and t(4;14)], was assessed. Results Of 1087 pts, 912 were evaluated for + 1q (gain1q or amp1q) and 774 for del1p. Gain1q, amp1q and del1p were noted in 23%, 7.5% and 9% pts, respectively. Best responses to VRd or KRd within each response category were similar, irrespective of +1q/del1p status. Within each arm, progression-free survival (PFS) was inferior for pts with +1q versus (v) pts without +1q; median 29 v 42 months (m) for both arms [VRd, HR 1.51 p 0.011; KRd, HR 1.63, p 0.002]. Corresponding 3y overall survival (OS) rates on VRd were 74 v 86% (HR 1.47, p 0.069) and 82 v 88% (HR 1.34, p 0.185) on KRd. Regarding copy number, pts with gain1q v those without +1q had inferior PFS with both VRd (median 29m, HR 1.59, p 0.012) and KRd (median 33m, HR 1.41, p 0.051). OS rates with gain1q were inferior within VRd arm only (3y 71%, HR 1.78, p 0.014; KRd 3y OS 89%, HR 1.02, p 0.93). By contrast, pts with amp1q, v pts without +1q, had inferior outcomes with KRd (median PFS 24m, HR 2.37, p Conclusion Gain1q or amp1q portends poor outcome among NDMM pts treated with either VRd or KRd. Specifically, pts with amp1q as a sole high-risk abnormality have distinctly poor outcomes with KRd. By contrast, KRd, but not VRd, appears to abrogate the adverse impact of del1p. Given the limitations of the trial design and post hoc subset analyses, longer follow up and confirmatory studies are warranted for definitive conclusions.
Reducing pig mortality through supervision during the perinatal period.

A study was undertaken on a commercial swine farm to investigate methods of reducing perinatal mortality. During a 12-wk period, 251 sows and gilts were assigned randomly to one of four treatment groups in a 2 x 2 factorial design : 1) supervised/induced, 2) supervised/non-induced, 3) unsupervised/induced, and 4) unsupervised/non-induced. Supervised groups of sows and their litters were observed constantly for a minimum of 3 h before and until at least 3 d after farrowing. The onset of farrowing was induced with 250 μg of cloprostenol administered into the vulvo-vestibular mucosa. There was an increase (P =.012) in the number of pigs weaned from supervised (10.17 pigs/litter) relative to unsupervised groups (9.44 pigs/litter). This increase was due to a reduction (P =.001) in both the number of stillborn pigs and the mortality of live-born pigs (P =.026). The latter resulted from fewer pigs being crushed by the sow (P =.009) and a decrease in the number of low-birth-weight, low-viability pigs that died (P =.003). Induction did not influence the mortality of pigs in the perinatal period in unsupervised groups. Induced sows farrowed an average of.43 d earlier than non-induced sows ( P =.029). The mean interval from prostaglandin treatment to farrowing was 23.87 h (SD = 10.96). The results of this study suggest that a controlled farrowing system, coupled with good supervision, can improve pig survival. Financial analyses, based on improvements in pig survival resulting from additional labor in the farrowing house, suggested that this method of reducing preweaning mortality is a viable option for improving the profitability of commercial pig farms.
Stimulation of hERG1 channel activity promotes a calcium- dependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells

// Mathew Perez-Neut 1 , Andrew Shum 2 , Bruce D. Cuevas 1 , Richard Miller 2 , Saverio Gentile 1 1 Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Maywood, IL, USA 2 Department of Pharmacology, Northwestern University, Chicago, IL, USA Correspondence to: Saverio Gentile, e-mail: sagentile@luc.edu Keywords: Cyclin E2, hERG1, breast cancer, calcium-dependent degradation Received: October 16, 2014 Accepted: November 27, 2014 Published: January 19, 2015 ABSTRACT Cyclin E2 gene amplification, but not cyclin E1, has been recently defined as marker for poor prognosis in breast cancer, and appears to play a major role in proliferation and therapeutic resistance in several breast cancer cells. Our laboratory has previously reported that stimulation of the hERG1 potassium channel with selective activators led to down-regulation of cyclin E2 in breast cancer cells. In this work, we demonstrate that stimulation of hERG1 promotes an ubiquitin-proteasome-dependent degradation of cyclin E2 in multiple breast cancer cell lines representing Luminal A, HER2+ and Trastuzumab-resistant breast cancer cells. In addition we have also reveal that hERG1 stimulation induces an increase in intracellular calcium that is required for cyclin E2 degradation. This novel function for hERG1 activity was specific for cyclin E2, as cyclins A, B, D E1 were unaltered by the treatment. Our results reveal a novel mechanism by which hERG1 activation impacts the tumor marker cyclin E2 that is independent of cyclin E1, and suggest a potential therapeutic use for hERG1 channel activators.
Mechanism of class I assembly with beta 2 microglobulin and loading with peptide.

Publisher Summary There has been remarkable progress in the elucidation of many of the key processes of class I peptide loading. In addition, gp48, the factor missing in the .220 cell line promises to be a critical contributor to class I assembly with β 2 m and loading with peptide. Using both chemical and genetic approaches, many of the details of peptide loading onto class I have been resolved. This chapter discusses the stoichiometric relationship and precise individual contributions of each of these accessory molecules. Some authors share their discovery illustrating that proteins lacking signals that target the secretory compartment can contribute peptide epitopes for presentation to the immune system via class I molecules at the cell surface. The chapter discusses recent evidence elucidating the mechanism of β 2 m assembly and peptide loading and the accessory molecules involved in these processes.
Screening for postpartum depression in military women with the Postpartum Depression Screening Scale.

ABSTRACT Each year, ∼16,000 women on active duty in the U.S. military experience the birth of a child. A descriptive, longitudinal, prospective design was used to gather data with the Postpartum Depression Screening Scale. Depression was measured after delivery but before hospital discharge (time 1), 2 weeks after delivery (time 2), and 6 to 8 weeks after delivery (time 3). Mothers were found to be experiencing the greatest severity of symptoms in the category of sleeping and eating disturbances. Almost one-half of the mothers in this study scored either significant postpartum depressive symptoms or positive screening for postpartum depression after delivery. This number remained virtually unchanged at time 2. By time 3, 40% of women still reported depressive symptoms. At 2 weeks and 6 weeks after delivery, 13% and 11% of mothers, respectively, had positive screening for postpartum depression, consistent with the national average of 10 to 15%. Future research is needed to examine issues surrounding postpa...
Dissemination Of Medical Information

The National Library of Medicine has taken an active role in the use of electronic media for the production of image libraries. Problems have been encountered in the adequacy of currently available technology to render an image of acceptable quality. Interim solutions are being used. The question is whether or not NLM should take a proactive role in the production and dissemination of image libraries through unstable, rapidly evolving, largely untested technology thereby adding some stability and direction to that technology's development.
On the verification and validation of protocols with high fault coverage using UIO sequences

Various new classes of unique input/output (UIO) sequences for verification and validation (conformance testing) of protocols modeled as finite state machines (FSMs) are presented. The proposed sequences are referred to as adaptive because test sequence generation is not a mere concatenation of test subsequences for all edges of the FSM, but rather subsequences are concatenated using appropriate conditions in the UIO sequence for length minimization and no degradation of fault coverage. >
Omega-3 DHA and EPA for cognition, behavior, and mood : Clinical findings and structural-functional synergies with cell membrane phospholipids

The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications.
PET Evidence for an Amodal Verbal Working Memory System

Current models of verbal working memory assume that modality-specific representations are translated into phonological representations before entering the working memory system. We report an experiment that tests this assumption. Positron emission tomography measures were taken while subjects performed a verbal working memory task. Stimuli were presented either visually or aurally, and a visual or auditory search tasks, respectively, was used as a control. Results revealed an almost complete overlap between the active memory areas regardless of input modality. These areas included dorsolateral frontal, Broca's area, SMA, and premotor cortex in the left hemisphere; bilateral superior and posterior parietal cortices and anterior cingulate; and right cerebellum. These results correspond well with previous research and suggest that verbal working memory is modality independent and is mediated by a circuit involving frontal, parietal, and cerebellar mechanisms.