cssi/SciSciGPT-SciSciNet huggingface dataset:
Substitution as a Mechanism for Genetic Robustness: The Duplicated Deacetylases Hst1p and Sir2p in Saccharomyces cerevisiae

How duplicate genes provide genetic robustness remains an unresolved question. We have examined the duplicated histone deacetylases Sir2p and Hst1p in Saccharomyces cerevisiae and find that these paralogs with non-overlapping functions can provide genetic robustness against null mutations through a substitution mechanism. Hst1p is an NAD+-dependent histone deacetylase that acts with Sum1p to repress a subset of midsporulation genes. However, hst1Δ mutants show much weaker derepression of target loci than sum1Δ mutants. We show that this modest derepression of target loci in hst1Δ strains occurs in part because Sir2p substitutes for Hst1p. Sir2p contributes to repression of the midsporulation genes only in the absence of Hst1p and is recruited to target promoters by a physical interaction with the Sum1 complex. Furthermore, when Sir2p associates with the Sum1 complex, the complex continues to repress in a promoter-specific manner and does not spread. Our results imply that after the duplication, SIR2 and HST1 subfunctionalized. The single SIR2/HST1 gene from Kluyveromyces lactis, a closely related species that diverged prior to the duplication, can suppress an hst1Δ mutation in S. cerevisiae as well as interact with Sir4p in S. cerevisiae. In addition, the existence of two distinct protein interaction domains for the Sir and Sum1 complexes was revealed through the analysis of a chimeric Sir2–Hst1 molecule. Therefore, the ability of Sir2p to substitute for Hst1p probably results from a retained but reduced affinity for the Sum1 complex that is a consequence of subfunctionalization via the duplication, degeneration, and complementation mechanism. These results suggest that the evolutionary path of duplicate gene preservation may be an important indicator for the ability of duplicated genes to contribute to genetic robustness.
Microglia-induced IL-6 protects against neuronal loss following HSV-1 infection of neural progenitor cells

Herpes virus type 1 (HSV-1) is one of the most widespread human pathogens and accounts for more than 90% of cases of herpes simplex encephalitis (HSE) causing severe and permanent neurologic sequelae among surviving patients. We hypothesize such CNS deficits are due to HSV-1 infection of neural progenitor cells (NPCs). In vivo, HSV-1 infection was found to diminish NPC numbers in the subventricular zone. Upon culture of NPCs in conditions that stimulate their differentiation, we found HSV-1 infection of NPCs resulted in the loss of neuronal precursors with no significant change in the percentage of astrocytes or oligodendrocytes. We propose this is due a direct effect of HSV-1 on neuronal survival without alteration of the differentiation process. The neuronal loss was prevented by the addition of microglia or conditioned media from NPC/microglia co-cultures. Using neutralizing antibodies and recombinant cytokines, we identified interleukin-6 (IL-6) as responsible for the protective effect by microglia, likely through its downstream Signal Transducer and Activator of Transcription 3 (STAT3) cascade.
The C. Elegans dosage compensation complex mediates interphase X chromosome compaction

Background: Dosage compensation is a specialized gene regulatory mechanism which equalizes X-linked gene expression between sexes. In Caenorhabditis elegans, dosage compensation is achieved by the activity of the dosage compensation complex (DCC). The DCC localizes to both X chromosomes in hermaphrodites to downregulate gene expression by half. The DCC contains a subcomplex (condensin I DC ) similar to the evolutionarily conserved condensin complexes which play fundamental roles in chromosome dynamics during mitosis and meiosis. Therefore, mechanisms related to mitotic chromosome condensation have been long hypothesized to mediate dosage compensation. However experimental evidence was lacking. Results: Using 3D FISH microscopy to measure the volumes of X and chromosome I territories and to measure distances between individual loci, we show that hermaphrodite worms deficient in DCC proteins have enlarged interphase X chromosomes when compared to wild type. By contrast, chromosome I is unaffected. Interestingly, hermaphrodite worms depleted of condensin I or II show no phenotype. Therefore X chromosome compaction is specific to condensin I DC . In addition, we show that SET-1, SET-4, and SIR-2.1, histone modifiers whose activity is regulated by the DCC, need to be present for the compaction of the X chromosome territory. Conclusion: These results support the idea that condensin I DC , and the histone modifications regulated by the DCC, mediate interphase X chromosome compaction. Our results link condensin-mediated chromosome compaction, an activity connected to mitotic chromosome condensation, to chromosome-wide repression of gene expression in interphase.
Clinical Applications of Neuromodulation: Section on Angina and Peripheral Vascular Disease

Clinical neuromodulation refers to the use of electrical stimulation of a peripheral nerve, the spinal cord, or the brain for relief of pain. For centuries, physicians have been interested in deriving therapeutic benefit from the use of electrical impulses to treat a variety of diseases. In fact, the first medical use of electricity is credited to a Roman physician named Scribonius Largus who described the use of the electric torpedo fish in the treatment of headaches and gouty arthritis. In his work titled Compositiones Medicae [1], Scribonius described the placement of a fish across the forehead or affected area to deliver a shock that alleviated pain much like a modern transcutaneous electrical nerve stimulators (TENS). As human understanding and utilization of electricity evolved, so did its use in the treatment of various disease states.
Unexpected Benefits of Rotavirus Vaccination in the United States

The large-scale introduction of a new vaccine can uncover many secrets and surprises about the epidemiology of disease that might not be discovered in any other way. Examination of the outcome of a vaccine introduction can validate prior assumptions concerning the burden of disease and the economic consequences of the vaccination program, as well as determine herd effects of the program arising from either a reduction in the environmental load of the infectious agent or a decrease in the group of susceptibles that might blunt transmission of the agent. In this issue of the Journal, Lopman et al document the impact of the introduction of rotavirus vaccines in the United States and find some surprises that could not have been fully anticipated or predicted in advance [ 1 ]. In 2006, the United States introduced a new rotavirus vaccine that was immediately recommended for the routine immunization of all children [ 2 ]. Uptake was slow at first but by 2008, about 60% of American infants were being immunized. Small local surveys of diarrheal illnesses in children , 2y ears who had been immunized indicated a substantial reduction in hospitalizations and emergency room visits [ 3 ‐ 8 ], outcomes predicted by the large clinical trials that determined the vaccine’s efficacy to be 85% or more against severe disease [ 9 , 10 ]. However, this was not the whole story. Lopman et al at the Centers for Disease Control and Prevention have analyzed al arge database covering approximately 20% of all US hospital admissions and looked at the numbers of discharges coded for diarrhea due to rotavirus or for any unspecified cause among children from 0 to 24 years of age. They compared baseline rates of these hospital discharge records in the prevaccination years, 2000‐2006, versus the postvaccination year 2008, as well as the trend over the 2-year period when the vaccine was being introduced. From this analysis, they have made several remarkable observations on the indirect effects of the vaccine that could not have been anticipated before the vaccine was introduced.
Unmasking, Exposing, and Confronting: Critical Race Theory, Tribal Critical Race Theory and Multicultural Education

Critical Race Theory (CRT) and Tribal Critical Race Theory (TribalCrit) offer the possibility of unmasking, exposing, and confronting continued colonization within educational contexts and societal structures, thus, transforming those contexts and structures for Indigenous People. Utilizing CRT and TribalCrit to support and inform “Multicultural Education as social justice,” we rid ourselves, our educational institutions, and ultimately the larger society from the “food, fun, festivals, and foolishness” form of Multicultural Education that maintains or propagates colonization.
Generic Danger Detection for Mission Continuity

Mobile Ad-hoc Networks (MANETs) have become the environment of choice for providing edge connectivity to mobile forces. In particular, next-generation military systems leverage MANET technology to provide information assets to troops. However, MANETs face a number of serious security exposures, which are a superset of traditional networks. In prior work, we have described BITSI, the Biologically-Inspired Tactical Security Infrastructure, which attempts to address these challenges. BITSI uses a variety of techniques inspired by biological systems to provide effect-based security that is centered upon mission enablement. One of these techniques is the application of Danger Theory to mission continuity. In this paper, we explore different ways of implementing danger detection within BITSI, and show how generic approaches that are low-cost both computationally and in terms of implementation can provide acceptable results.
Toward Building a Model of Wind and Solar Energy Source

Generation of renewable energy sources are being adopted more widely in both large and small scales by federal agencies and private industries. We will explore to investigate what their impact would be by building a prototype model of wind and solar energy Source generation. This model will be integrated into our current model of the smart grid. The generation model consists of a solar panel and an array of wind turbines connected to a battery storage system. The energy output is being monitored and reported in real time. This energy will supply the already built model of the electric grid.Copyright © 2015 by ASME
Protective effects of intravascular pressure and nitric oxide in ischemic lung injury

Cessation of blood flow during ischemia will decrease both distending and shear forces exerted on endothelium and may worsen ischemic lung injury by decreasing production of nitric oxide (NO), whic...
The Arithmetic of Electoral Bias, with Applications to U.S. House Elections

This paper justifies and reports an arithmetic formulation for describing and analyzing electoral bias in two-party, single-member district systems. The formulation recovers a description for bias from three quantities: the system-wide vote percentage, the average vote percentage among districts, and the median-district vote percentage. The formulation can be used to go beyond description to analysis of the sources of bias, including malapportionment and gerrymandering. I illustrate the descriptive, analytical, and inferential insights from the arithmetic approach by applying it in broad gauge form to U.S. House elections from 1962 through 2006 and in more detailed form to the 2000-2006 House elections.
Climate Change Effects on Optimal High-Elevation Hydropower Generation in Sierra Nevada, California

Climate warming is expected to shift the runoff peak from spring to winter in California as a result of the reduction in snowpack. The Sierra’s high-elevation system supplies roughly 74 percent of California’s in-state hydropower supply and is composed of more than 150 power plants with relatively small reservoirs associated with them. Such low capacity reservoirs have been designed to take advantage of snowpack, the natural reservoir. With climate warming, the adaptability of the high-elevation hydropower system is in question as a shift in runoff peak can have important effects on generation and its economic value. A non-linear optimization model employing historic hourly energy prices is used to explore energy generation of 137 hydropower plants in California’s Sierra Nevada mountains for three climate warming scenarios (dry warming, wet warming, and warming only) over 15 years, spanning dry, wet and average hydrologic conditions. These results are compared to the historic generation to investigate the adaptability of Sierra’s high-elevation hydropower system to climate warming.
Genetics of Severe Myoclonic Epilepsy of Infancy

The role of SCN1A gene mutations in the etiology of severe myoclonic epilepsy of infancy (SMEI) was investigated in 93 patients followed at the Hopital Saint Vincent de Paul, Paris, and other centers in France and Italy.
Control of culture mites by cigarette paper barriers.

A method to exclude mites and other contaminants from test tube cultures is described. It consists in covering the mouths of the tubes with cigarette paper which is applied by pressing the flamed r...
3D Texture Mapping for Rapid Manufacturing

Inspired by the developments of biomimetic design and layer manufacturing, we present a microstructure design method which uses complex internal structures to achieve an optimal design. Similar to 2D texture mapping, our approach is based on mapping a 3D microstructure into a design space to generate internal structures. We develop a texture mapping design system which enables a designer to select a microstructure from a library. Accordingly the system automatically generates a CAD model of internal structures based on given design requirements. The system then combines internal structures with a given CAD model. The combined CAD model can be fabricated using a layer manufacturing system. The ability to design microstructures within a part creates tremendous potential for lightweight and high performance components and devices.
Motivations in seeking advanced pharmacy training.

We appreciate the feedback and additional information provided by Dr. Rindfuss. We agree that pharmacists are being used differently today than almost 20 years ago but also recognize that the standardization and utilization of clinical pharmacy services vary nationally. As mentioned in our
Analysis on the Surveillance of Adverse Events Following Immunization in Tianjin, 2011-2013

Objective The study was to analyze the characteristics of adverse events following immunization(AEFI) in Tianjin, and to evaluate the classification of AEFI diagnosis and immunization safety of vaccine. Methods AEFI data in 2011-2013 were collected through the national AEFI information management system, and the vaccination data were from the Tianjin immunization information management system. The descriptive methodology and chi square trend test was used for the analysis in the study.Results 4164 cases were collected from national AEFI information management system in 2011-2013, the total AEFI incidence was20.05, 31.35 and 50.51 per 100, 000 doses(χ2=560.57, P0.05). The incidence of common, minor vaccine reaction with symptoms of fever, local redness /swelling and local induration was 85.09%, and the incidence of the rare, serious vaccine reaction with anaphylactic rash was 13.32%. The incidence of severe vaccine reaction was between 4~5 per 100, 000 doses(χ2=5.86, P0.05).There were 44 cases of estimated serious vaccine reaction, with a total rate of 0.36 per 100, 000 doses, where the rate of Febrile Convulsion was 0.17 per 100, 000 doses, Thrombocytopenic Purpura 0.10 per 100, 000 doses, the others 0.10 per 100, 000 doses or lower. Conclusion The increasing Tianjin AEFI incidence is mainly due to the increase in the incidence of the common, minor vaccine reaction. The incidence of the rare, serious vaccine reaction was relatively constant. The classification of diagnosis should be strengthened, particularly to the estimated serious vaccine reaction. The classification and diagnosis criteria of the estimated serious vaccine reaction needs to be standardized to ensure the scientific solution to AEFI cases.
Bearing capacity test and stiffness research on CFRP strengthened existing reinforced concrete poles with joint

In order to reveal the bearing capacity and failure mechanism of CFRP strengthened existing reinforced concrete poles with corrosion steel collar joints,three poles from a road section of Southwest line in the Southern Power Grid were selected to conduct flexural capacity test research.Two pole specimens were pasted with double vertical CFRP and one pole specimen was pasted with single vertical CFRP.The whole process of forcing and failure mode of all specimens was observed by the test,and the important indicators,such as curves of load-deflection,curves of stiffness degeneration and ultimate bearing capacity,were obtained.Results indicated that the strengthened poles with connection joints were mainly bond failure between concrete and the external CFRP,the damage process is very fast,and the failure feature is brittle.These specimens' cross-sectional strains conform to the assumption of plane cross-section.Also,bearing capacity and stiffness of the strengthened specimens are much larger than those without CFRP.The bearing capacity of specimens pasted with double CFRPs is larger than that of the specimen with single CFRP.Comparing the initial stiffness and elastic-plastic stiffness,it is seen that the ones with double CFRPs are a little higher than the one with single CFRP.Weighting the cost-effective effect,it is determined that pasting single-layer CFRP longitudinally is more economical and reasonable.The results can provide a reference to the same type of existing reinforced concrete poles for reinforcing design.
Nondysraphic Intramedullary Cervical Cord Lipoma with Exophytic Component: Case Report.

Introduction Spinal intradural lipoma is a rare condition, accounting for < 1% of all spinal cord tumors. Spinal cord lipomas are frequently associated with dysraphism and occur in the thoracic spine. Another common finding is that spinal cord lipomas tend to present in the pediatric population. Isolated nondysraphic cervical lipomas are a rare entity. We discuss a case of nondysraphic cervical lipoma with an exophytic component. Case A 31 year-old woman presented with bilateral numbness in her hands and a burning and aching sensation in her arms for ∼ 6 months. The patient did not have any weakness or myelopathic signs. Magnetic resonance imaging T1 showed a T1 hyperintense, T2 hypointense, non-contrast-enhancing mass on the dorsal aspect of the spinal cord with significant compression. The patient underwent a dorsal cervical laminectomy with subtotal resection of an isolated cervical lipoma with an exophytic component. The pathology confirmed the diagnosis of a lipoma. Conclusions Surgical management of this rare pathology has a wide variety of options. Depending on the neurologic deficits, observation to gross total resection may be reasonable options. In our case, a subtotal resection was achieved with no further worsening of neurologic symptoms.
Debating Rights, Property, and the Law

The debate over natural and civil rights was a furious, ubiquitous exchange that dominated public discourse in the 1790s. Much was at stake in defining personal liberties and public duties: the configuration of the body politic and the direction of the modern state. One particular conflict that prevailed in the ensuing battle was a struggle between the family and the self-contained individual as the image and, more importantly, the site of political authority. From the essays of Sir Robert Filmer and John Locke on patriarchalism and government to the treatises on the social contract by Algernon Sidney, James Harrington, Jean-Jacques Rousseau, Edmund Burke and Thomas Paine, the exploration of the individual’s relation to the state maintained a vibrant momentum that peaked in the excitement of the French Revolution. By the 1790s, the notion of liberty was either safely protected in the “inherited rights” of Burke’s design or boldly redistributed to the “individual inalienable rights” advocated by Paine. One conception of rights was meant to contain the franchise, the other to extend it.
8 – Prefabricated and Relocatable Artificial Island Technology

Publisher Summary Artificial islands have a long history and are usually constructed by reclamation, which implies building up the island by depositing soil, sand, or other construction materials until the water surface is penetrated and an island surface created. To protect such reclaimed artificial islands, protection of the sides of the island by armoring with stone or concrete, containment of reclamation material within concrete walls or armored rubble mounds is usually employed. Similarly, to improve the footing of the island, foundation improvements by cement hardening of bottom material, sand and structural piling, or sand and gravel foundation carpet placements are used. Such artificial islands have been used as storm barriers, offshore fishing bases, foundations for offshore gun placements for coastal protection, lighthouse foundations, and more since time immemorial. In more recent years, reclaimed artificial islands have been constructed to serve as solid waste depositories or fills, sites for toxic industrial activities, nuclear power plants, refineries, marinas, and airports, such as the mammoth landfill for Kansai Airport in Osaka Bay.
Conservation of Resources Theory Applied to Major Stress

Abstract Conservation of resources (COR) theory informs our understanding of how individuals cope with major stress and trauma. COR theory asserts that traumatic stress occurs when events threaten and erode the basic resources human beings need for survival or self-integrity. This process occurs within an ecological framework, meaning that patterns of risk and resilience in the face of resource loss are intimately tied to an individual's family, community, and culture. The basic principles and corollaries of COR theory are reviewed to illustrate patterns of post-trauma adjustment over time. Finally, the use of COR theory in guiding individual and collective post-trauma interventions is explored.
Cost Allocation in a Service Industry

This article evaluates a firm’s service cost structure and the associated cost allocation methodology and its impact on pricing strategy, which manifests in revenues or market share, profitability, and customer satisfaction. We discuss a cost allocation methodology which will be useful in conjunction with other marketing tools in development of a pricing structure for a firm’s services against the backdrop of dynamic market conditions and with the goal of maximizing shareholder value.
RESAR: Reliable Storage at Exabyte Scale

Stored data needs to be protected against device failure and irrecoverable sector read errors, yet doing so at exabyte scale can be challenging given the large number of failures that must be handled. We have developed RESAR (Robust, Efficient, Scalable, Autonomous, Reliable) storage, an approach to storage system redundancy that only uses XOR-based parity and employs a graph to lay out data and parity. The RESAR layout offers greater robustness and higher flexibility for repair at the same overhead as a declustered version of RAID 6. For instance, a RESAR-based layout with 16 data disklets per stripe has about 50 times lower probability of suffering data loss in the presence of a fixed number of failures than a corresponding RAID 6 organization. RESAR uses a layer of virtual storage elements to achieve better manageability, a broader potential for energy savings, as well as easier adoption of heterogeneous storage devices.
No-Fly Zones: A New Model for Male Sexuality

The predominant paradigm nowadays for understanding male sexuality is derived from Kinsey's assumption that men can be classified as individuals with specific scores on a scale, scores that predict whether future partners will be male or female. Each man is defined by an essence, homo- or heterosexual or somewhere in between. However this is an incorrect view of male sexuality, because it makes us unable to say why a man is attracted to or has sex with a specific person: the same person can be attractive or unattrative depending on circumstances, and he can act or not act on his inclination depending on circumstances. The more correct view of male sexuality is thus of “fly” and “no-fly” zones, which understands male sexuality as defined by variable situations, not a score of the individual in all situations. This conception allows us to avoid the theoretical mistakes of the current assault on “sexual assault.”
Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies

Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell-mediated lymphoproliferative disorders. Ibrutinib, however, carries an increased bleeding risk compared with standard chemotherapy. Bleeding events range from minor mucocutaneous bleeding to life-threatening hemorrhage, due in large part to the effects of ibrutinib on several distinct platelet signaling pathways. There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk of vascular disease are unknown. Patients should be cautioned against using non-steroidal anti-inflammatory drugs, fish oils, vitamin E and aspirin-containing products, and consider replacing ibrutinib with a different agent if dual antiplatelet therapy is indicated. Patients should not take vitamin K antagonists concurrently with ibrutinib; direct oral anticoagulants should be used if extended anticoagulation is strongly indicated. In this review, we describe the pathophysiology of ibrutinib-mediated bleeding and suggest risk reduction strategies for common clinical scenarios associated with ibrutinib.
A New Role for the ER Unfolded Protein Response Mediator ATF6: Induction of a Generalized Antioxidant Program.

Optimal cellular health requires normal protein function, which, in turn, is dependent on proteins folding into their appropriate 3-dimensional conformations. Roughly a third of cellular proteins undergo folding in the lumen of the endoplasmic reticulum (ER). However, under stressful conditions, unfolded proteins sometimes accumulate. This initiates a process termed the unfolded protein response (UPR).1 One arm of the UPR is activated by the ER membrane protein ATF6 (activating transcription factor 6), a fragment of which moves to the nucleus where it functions as a transcription factor to activate genes that mediate protein folding. Unexpectedly, Jin et al2 report in the current issue of Circulation Research a new function for ATF6: to transcriptionally activate the expression of a repertoire of antioxidant genes, many of which encode proteins that reside outside of the ER. Moreover, data are presented supporting a model in which this antioxidant program attenuates myocardial damage from ischemia/reperfusion. Article, see p 862 Some of the information required for protein folding is intrinsic to its amino acid sequence, but chaperones are critical for most proteins to assume their appropriate conformation. Chaperones are a biochemically diverse group of proteins that reside in subcellular compartments where protein folding takes place (eg, cytosol, mitochondria, and ER). Essentially all proteins destined for various cellular membranes and most that will be secreted are directed to the ER by a signal sequence as they exit ribosomes in the cytoplasm. Folding in the ER is coordinated with post-translational modifications that include removal of the signal sequence, N-linked glycosylation, and disulfide bond formation.3 These events require the integrated actions of several classes of chaperones, oxidoreductases (including protein disulfide isomerases), and prolyl peptidyl cis–trans isomerases. When everything proceeds according to plan, high-quality proteins are produced, and the cell is happy. However, things can go awry. Although …
Causes of Interannual Variability over the Southern Hemispheric Tropospheric Ozone Maximum

Abstract. We examine the relative contribution of processes controlling the interannual variability (IAV) of tropospheric ozone over four sub-regions of the southern hemispheric tropospheric ozone maximum (SHTOM) over a 20-year period. Our study is based on hindcast simulations from the National Aeronautics and Space Administration Global Modeling Initiative chemistry transport model (NASA GMI-CTM) of tropospheric and stratospheric chemistry, driven by assimilated Modern Era Retrospective Analysis for Research and Applications (MERRA) meteorological fields. Our analysis shows that over SHTOM region, the IAV of the stratospheric contribution is the most important factor driving the IAV of upper tropospheric ozone (270 hPa), where ozone has a strong radiative effect. Over the South Atlantic region, the contribution from surface emissions to the IAV of ozone exceeds that from stratospheric input at and below 430 hPa. Over the South Indian Ocean, the IAV of stratospheric ozone makes the largest contribution to the IAV of ozone with little or no influence from surface emissions at 270 and 430 hPa in austral winter. Over the tropical South Atlantic region, the contribution from IAV of stratospheric input dominates in austral winter at 270 hPa and drops to less than half but is still significant at 430 hPa. Emission contributions are not significant at these two levels. The IAV of lightning over this region also contributes to the IAV of ozone in September and December. Over the tropical southeastern Pacific, the contribution of the IAV of stratospheric input is significant at 270 and 430 hPa in austral winter, and emissions have little influence.
Visualization in Genomics and Proteomics

In the age of high-throughput biological technology, experimental data have grown exponentially. Searching for data structures and succinctly presenting them is challenging but all the more essential. Genomic and proteomic data are by nature multi-dimensional. Different approaches and tools are needed for visualization to aid the exploration as well as quality assessment of the experimental data. The bon mot “A picture is worth a thousand words” expresses the importance of visualization in conveyance of information. Visualization tools not only help us to communicate but also help us to think, organize knowledge and discover new patterns. The indispensability of visualization is best attested by its extensive day-to-day use in presentations, papers and books. Recent discussion about ideas and tools pertaining to genomic and proteomic data can be found in (Gentleman et al., 2005); (Hahne et al, 2006).
Dynamin-Related Protein 1 Inhibition Attenuates Cardiovascular Calcification in the Presence of Oxidative Stress.

Rationale: Mitochondrial changes occur during cell differentiation and cardiovascular disease. Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission. We hypothesized that DRP1 plays a role in cardiovascular calcification, a process involving cell differentiation and a major clinical problem with high unmet needs. Objective: To examine the effects of osteogenic promoting conditions on DRP1, and whether DRP1 inhibition alters the development of cardiovascular calcification. Methods and Results: DRP1 was enriched in calcified regions of human carotid arteries, examined by immunohistochemistry. Osteogenic differentiation of primary human vascular smooth muscle cells (SMCs) increased DRP1 expression. DRP1 inhibition in human SMCs undergoing osteogenic differentiation attenuated matrix mineralization, cytoskeletal rearrangement, mitochondrial dysfunction, and reduced type 1 collagen secretion and alkaline phosphatase activity. DRP1 protein was observed in calcified human aortic valves, and DRP1 RNA interference reduced primary human valve interstitial cell calcification. Mice heterozygous for Drp1 deletion did not exhibit altered vascular pathology in a PCSK9 gain-of-function atherosclerosis model. However, when mineralization was induced via oxidative stress, DRP1 inhibition attenuated mouse and human SMC calcification. Femur bone density was unchanged in mice heterozygous for Drp1 deletion, and DRP1 inhibition attenuated oxidative stress-mediated dysfunction in human bone osteoblasts. Conclusions: We demonstrate a new function of DRP1 in regulating collagen secretion and cardiovascular calcification, a novel area of exploration for the potential development of new therapies to modify cellular fibrocalcific response in cardiovascular diseases. Our data also support a role of mitochondrial dynamics in regulating oxidative stress-mediated arterial calcium accrual and bone loss.
Interpretive Differences Between Patients and Radiologists Regarding the Diagnostic Confidence Associated With Commonly Used Phrases in the Radiology Report

OBJECTIVE. Despite patients' increasing interest in reading their own imaging results, little is known about how patients interpret the reporting terminology of radiologists. The purpose of this study was to survey patients and radiologists to improve understanding of how each group views commonly used phrases within the radiology report. SUBJECTS AND METHODS. Patients and radiologists were asked to assign a numerical likelihood of the presence of metastatic disease based on their understanding of radiology report phrasing. Commonly used qualifying phrases, such as “likely represents,” “concerning for,” and “cannot exclude” were evaluated to compare differences in interpretation between patients and radiologists. Potential responses for statistical likelihoods included 0–25%, 26–50%, 51–75%, 76–99%, and 100%. RESULTS. There was a significant difference between the two groups with respect to assigned statistical likelihoods for most phrases. Patients identified the phrase “probably meta-static disease” as ...
Positive and Negative Self-Conscious Emotion and Transmission Risk Following HIV Diagnosis.

While negative emotions are associated with risk behaviors and risk avoidance among people with HIV, emerging evidence indicates that negative self-conscious emotions, those evoked by self-reflection or self-evaluation (e.g., shame, guilt, and embarrassment), may differentially influence health-risk behaviors by producing avoidance or, conversely, pro-social behaviors. Positive emotions are associated with beneficial health behaviors, and may account for inconsistent findings related to negative self-conscious emotions. Using multinomial logistic regression, we tested whether positive emotion moderated the relationships between negative emotion and negative self-conscious emotions and level of condomless sex risk: (1) seroconcordant; (2) serodiscordant with undetectable viral load; and (3) serodiscordant with detectable viral load [potentially amplified transmission (PAT)] among people recently diagnosed with HIV (n = 276). While positive emotion did not moderate the relationship between negative emotion and condomless sex, it did moderate the relationship between negative self-conscious emotion and PAT (AOR = 0.60; 95% CI 0.41, 0.87); high negative self-conscious and high positive emotion were associated with lower PAT risk. Acknowledgment of both positive and negative self-conscious emotion may reduce transmission risk behavior among people with HIV.
Deaths From Pneumonia-New York City, 1999-2015.

Background "Pneumonia and influenza" are the third leading cause of death in New York City. Since 2012, pneumonia and influenza have been the only infectious diseases listed among the 10 leading causes of death in NYC. Most pneumonia and influenza deaths in NYC list pneumonia as the underlying cause of death, not influenza. We therefore analyzed death certificate data for pneumonia in NYC during 1999-2015. Methods We calculated annualized pneumonia death rates (overall and by sociodemographic subgroup) and examined the etiologic agent listed. Results There were 41 400 pneumonia deaths during the study period, corresponding to an annualized age-adjusted death rate of 29.7 per 100 000 population. Approximately 17.5% of pneumonia deaths specified an etiologic agent. Age-adjusted pneumonia death rate declined over the study period and across each borough. Males had an annualized age-adjusted pneumonia death rate 1.5 (95% confidence interval [CI], 1.5-1.5) times that of females. Non-Hispanic blacks had an annualized age-adjusted pneumonia death rate 1.2 (95% CI, 1.2-1.2) times that of non-Hispanic whites. The annualized pneumonia death rate increased with age group above 5-24 years and neighborhood-level poverty. Staten Island had an annualized age-adjusted pneumonia death rate 1.3 (95% CI, 1.2-1.3) times that of Manhattan. In the multivariable analysis, pneumonia deaths were more likely to occur among males, non-Hispanic blacks, persons aged ≥65 years, residents of neighborhoods with higher poverty levels, and in Staten Island. Conclusions While the accuracy of death certificates is unknown, investigation is needed to understand why certain populations are disproportionately recorded as dying from pneumonia in NYC.
Utilization and effectiveness of multimodal discharge analgesia for postoperative pain management.

Abstract Background Although evidence-based guidelines recommend a multimodal approach to pain management, limited information exists on adherence to these guidelines and its association with outcomes in a generalized population. We sought to assess the association between discharge multimodal analgesia and postoperative pain outcomes in two diverse health care settings. Methods We evaluated patients undergoing four common surgeries associated with high pain in electronic health records from an academic hospital (AH) and Veterans Health Administration (VHA). Multimodal analgesia at discharge was characterized as opioids in combination with acetaminophen (O + A) and nonsteroidal antiinflammatory (O + A + N) drugs. Hierarchical models estimated associations of analgesia with 45-d follow-up pain scores and 30-d readmissions. Results We identified 7893 patients at AH and 34,581 at VHA. In both settings, most patients were discharged with O + A (60.6% and 54.8%, respectively), yet a significant proportion received opioids alone (AH: 24.3% and VHA: 18.8%). Combining acetaminophen with opioids was associated with decreased follow-up pain in VHA (Odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.79, 0.93) and readmissions (AH OR: 0.74, CI: 0.60, 0.90; VHA OR: 0.89, CI: 0.82, 0.96). Further addition of nonsteroidal antiinflammatory drugs was associated with further decreased follow-up pain (AH OR: 0.71, CI: 0.53, 0.96; VHA OR: 0.77, CI: 0.69, 0.86) and readmissions (AH OR: 0.46, CI: 0.31, 0.69; VHA OR: 0.84, CI: 0.76, 0.93). In both systems, patients receiving multimodal analgesia received 10%-40% less opioids per day compared to opioids only. Conclusions A majority of surgical patients receive a multimodal pain approach at discharge yet many receive only opioids. Multimodal regimen at discharge was associated with better follow-up pain and all-cause readmissions compared to the opioid-only regimen.
Formulation strategies for solid oral dosage form using 3D printing technology: A mini-review

Abstract 3D printing: a layer-by-layer process to produce drug products has gained a lot of attention in recent years especially after its first FDA approval due to several advantages offered as an effort for an improved pharmacotherapy. This technology is indeed an old and widely used in other industries; however due to various regulations and complex application, it is yet to flourish in the pharmaceutical industry. Despite this fact, numerous dosage forms have been prepared and reported in the literature using this technology. This review highlights the various formulation strategies available at the disposal of the formulation scientists to manufacture solid oral dosage form with desired drug release profile. Also, it provides a basic understanding of the various 3D printing manufacturing techniques available to manufacture solid oral dosage forms. We have also attempted to summarize the most important practical consideration while formulating the pharmaceutical drug products using this technology.
Bringing Sociology into the Public Policy Process: a Relational Network Approach

How does evidence-based sociological research influence public policymaking either directly or indirectly? Based on an analysis of a 2014 NSF-funded public policy research workshop and written case studies by workshop participants, this article provides a conceptual roadmap and varied examples of the pathways through which social science research and social scientists can inform public policy decision-making. Pathways include networks and relationships among academics, social scientists employed in government, special interest groups and non-profits, and members of the media. Many sociologists are committed to using their evidence-based findings to inform solutions to societal problems, yet are often too narrowly trained to write only for scholarly communities and are often unaware of the relations, connections, and networks that can increase the use of sociological and other social science research in public discourse and in the public policy arena. The paper highlights lessons learned about effective networks, communication channels and dissemination strategies from the workshop and case studies in order to better equip those social scientists interested to bring their research into a public policy realm with the tools to do so. Given the current political climate, this resolve seems all the more important.
Ethics in Diagnosis: Bodily Integrity, Trust-Telling, and the Good Physician

In addition to the acquisition of differential knowledge on the part of a physician, medical diagnosis depends on the subtleties of the patient-physician encounter, the prevailing nosological and conceptual systems in which this encounter occurs, the current status of biomedical research, and the physician’s reliance on the accuracy, reliability, and validity of the available laboratory analyses. Indeed, one can also make the case that the process of medical diagnosis tacitly involves the normative presuppositions of the medical context, the uncertainties of questionable diagnoses that may lead to ill-effects (including the physician’s failure to obtain peer and family approval rooted in a lack of confidence in his or her diagnostic competence), the values of other health care practitioners involved in a patient’s case, the diagnostic modalities available in the clinical setting in which specific medical acts take place, and even postmortem procedures [8] (when no treatment is possible) as propaedeutic to future diagnoses that are often forgotten but critical to public health problems like today’s AIDS epidemic.
Methods for Censored Survival Time Data

This chapter deals with survival time data for which the inference cannot be made by any of the parametric and nonparametric methods that we learned in the past chapters.
Human Sarcomas Are Mosaic for Telomerase-Dependent and Telomerase-Independent Telomere Maintenance Mechanisms: Implications for Telomere-Based Therapies

Telomere shortening necessitates that tumor cells activate a telomere maintenance mechanism (TMM) to support immortalization. Although most tumor cells activate expression of the enzyme telomerase, some cells elongate telomeres in a telomerase-independent manner, termed alternative lengthening of telomeres (ALT). Previous studies have evaluated the presence of telomerase or ALT mechanisms or both in a variety of tumor types. Our studies also show that TMMs are not mutually exclusive in some tumors. In contrast, our IHC analyses of human sarcomas identified a subset of tumors with some cells containing ALT-associated PML bodies, a hallmark of ALT, and separate cells expressing telomerase in the same tumor. By using a second set of human osteosarcomas, we merged IHC and biochemical analyses to characterize more fully the tumor TMM. The IHC data reveal the presence of both telomerase- and ALT-positive tumor cells in samples that demonstrate characteristics of both telomerase and ALT in biochemical assays. These assays, which measure telomere length and telomerase activity of tumor extracts, are conventionally used to classify tumor TMM. Our results suggest that TMM is not a single or perhaps static characteristic of some tumors and that TMM heterogeneity should be considered in tumor stratification. Furthermore, clinical interest in telomere-based therapies may necessitate accurate characterization of tumor TMM before treatment to maximize therapeutic efficacy.
Thirteen Years Later: Status of the Moab UMTRA Project Long-term Remedial Action

For the past 13 years, the U.S. Department of Energy (DOE) has managed the Moab Uranium Mill Tailings Remedial Action (UMTRA) Project in Utah. As DOE designed and constructed tailings-removal and disposal systems, and now relocates the 14 million tonnes of uranium mill tailings away from the Colorado River, DOE has continued to place its highest priority on workplace safety. The project is ahead of the schedule and below the cost at completion, based on the approved lifecycle estimate.
Cauchy’s Theory of Dispersion Anticipated by Fresnel

In 1836 Augustin-Louis Cauchy (1789–1857), having left Paris and settled in Prague following the July Revolution, published a memoir on the dispersion of light under the auspices of Prague’s Royal Society of Sciences. In it he produced an equation that is even today known as Cauchy’s formula for dispersion. It works reasonably well for normally dispersive bodies and was only replaced towards the end of the 19th century following the discovery of anomalous dispersion in Denmark by C. Christiansen in 1870 and consequent changes in theory by Wolfgang Sellmeier and Hermann von Helmholtz (1821–1894) in Germany. In his publication Cauchy nowhere referred for inspiration to Augustin-Jean Fresnel (1788–1827), the originator in France of wave optics. Instead, he wrote that Gustave-Gaspard Coriolis (1792–1843), having read Cauchy’s earlier work on the equations of motion that govern a system of material points, suggested that terms which Cauchy had there neglected might account for dispersion – assuming that the medium, or ether, that was presumed to carry optical radiation is itself so constituted.