cssi/SciSciGPT-SciSciNet huggingface dataset:
A Robust and Efficient Feature Selection Algorithm for Microarray Data

In the past decades, a few synergistic feature selection algorithms have been published, which includes Cooperative Index (CI) and K-Top Scoring Pair (k-TSP). These algorithms consider the synergistic behavior of features when they are included in a feature panel. Although promising results have been shown for these algorithms, there is lack of a comprehensive and fair comparison with other feature selection algorithms across a large number of microarray datasets in terms of classification accuracy and computational complexity. There is a need in evaluating their performance and reducing the complexity of such algorithms. We compared the performance of synergistic feature selection algorithms with 11 other commonly used algorithms based on 22 microarray gene expression binary class datasets. The evaluation confirms that synergistic algorithms such as CI and k-TSP will gradually increase the classification performance as more features are used in the classifiers. Also, in order to cut down computational cost, we proposed a new feature selection ranking score called Positive Synergy Index (PSI). Testing results show that features selected using PSI as well as synergistic feature selection algorithms provide better performance compared to with all other methods, while PSI has a computational complexity significantly lower than that of other synergistic algorithms.
Long-Term Rural Superintendents: Characteristics and Attributes:

This paper presents the results of a study of superintendents who have served in one rural school district for twelve years or more. Superintendents in twenty-four districts were identified and int...
Aptamer-siRNA Chimeras: Discovery, Progress, and Future Prospects

Synthetic nucleic acid ligands (aptamers) have emerged as effective delivery tools for many therapeutic oligonucleotide-based drugs, including small interfering RNAs (siRNAs). In this review, we summarize recent progress in the aptamer selection technology that has made possible the identification of cell-specific, cell-internalizing aptamers for the cell-targeted delivery of therapeutic oligonucleotides. In addition, we review the original, proof-of-concept aptamer-siRNA delivery studies and discuss recent advances in aptamer-siRNA conjugate designs for applications ranging from cancer therapy to the development of targeted antivirals. Challenges and prospects of aptamer-targeted siRNA drugs for clinical development are further highlighted.
Cavity enhanced eigenmode multiplexing for volume holographic data storage

Previously, we proposed and experimentally demonstrated enhanced recording speeds by using a resonant optical cavity to semi-passively increase the reference beam power while recording image bearing holograms. In addition to enhancing the reference beam power the cavity supports the orthogonal reference beam families of its eigenmodes, which can be used as a degree of freedom to multiplex data pages and increase storage densities for volume Holographic Data Storage Systems (HDSS). While keeping the increased recording speed of a cavity enhanced reference arm, image bearing holograms are multiplexed by orthogonal phase code multiplexing via Hermite-Gaussian eigenmodes in a Fe:LiNbO3 medium with a 532 nm laser at two Bragg angles for expedited recording of four multiplexed holograms. We experimentally confirmed write rates are enhanced by an average factor of 1.1, and page crosstalk is about 2.5%. This hybrid multiplexing opens up a pathway to increase storage density while minimizing modifications to current angular multiplexing HDSS.
Human Immunodeficiency Virus and Aging in the Era of Effective Antiretroviral Therapy

Persons living with HIV (PLWH) have accentuated risks for age-associated comorbidities. Compared to the general population, PLWH have a 2-fold higher risk of cardiovascular disease, a 3-fold increased risk of fracture, and a risk of kidney disease that is comparable to that in diabetes. Some comorbidities may present at younger ages than among the general population, suggesting the possibility of accelerated aging with HIV infection.
Stopping LVAD Bleeding: A Piece of the Puzzle.

Left ventricular assist devices (LVADs) are efficient pumps that assist the circulation. They are rapidly evolving and being inserted into an increasing number of patients with advanced heart failure either as a bridge to transplantation or increasingly as destination therapy. The epidemic of heart failure is only likely to worsen as the population ages. Although medical therapy has improved the survival of many, there remain a large group of patients who, despite optimal medical therapy, deteriorate and develop advanced heart failure. Although heart transplantation is highly successful for these patients, unfortunately the number of useable donor hearts is totally inadequate for the population that need them. Article, see p 963 The number of pumps being implanted has particularly increased since the introduction of the continuous-flow (CF) pumps, which have almost replaced the pulsatile pumps. They have far better survival and longer durability but are associated with significant bleeding complications. Gastrointestinal bleeding is a huge problem after LVAD implantation. Its incidence has been estimated between 15% and 61%,1 and a meta-analysis has shown a pooled prevalence of 23% in LVAD recipients.2 The CF pumps are associated with a much higher incidence of gastrointestinal bleeding compared with the earlier pulsatile LVADs (where the incidence was ≈10%), and patients are 4.5 to 10× more likely to experience gastrointestinal bleeding depending on the series.2–4 LVAD recipients also have a greater severity of gastrointestinal bleeds than the general population, requiring an average of 2 to 4 U of packed red blood cells per admission and have a high rate of rebleeding of around 35%.4 LVAD-associated LVAD gastrointestinal bleeding is associated with significant morbidity, hospital readmissions, and cost. The increased morbidity …
The Ambivalence of Eros: Plato’s Natural Beginning(s)

“The Ambivalence of Eros: Plato’s Natural Beginning(s)” provides an account of φύσις in Plato, and draws upon the fruitful pairing of ἔρως with φύσις. Hayes argues that with the introduction of ἔρως into Plato’s account of nature, an alternative account of nature may be ventured, one which essentially disrupts the prevalence of the eidetic domain. Hayes subsequently reasons that the creation of the sensible cosmos by the erotically driven demiurge is a paradigm for the creation of the city in speech by the philosopher. If ἔρως is the common source of the creation of both sensible cosmos and city, then this has important cosmological and political implications. At the end of his chapter, Hayes suggests the ἔρως that humans feel to become one with the noumenal (and to become like a god) is the source of the insatiable greed (πλeονeξία) that ravages the earth today. The drive to immortalize ourselves through the excessive proliferation of our own species has blinded us to our own moral obligations and particularly to our duty to revere the earth as the mother of all things.
Circular inhomogeneity with Steigmann–Ogden interface: Local fields, neutrality, and Maxwell's type approximation formula

The boundary conditions for the [Steigmann, D.J., Ogden, R.W., 1997. Plain deformations of elastic solids with intrinsic boundary elasticity. Proc. R. Soc. London A 453, 853–877; Steigmann, D.J., Ogden, R.W., 1999. Elastic surface-substrate interactions. Proc. R. Soc. London A 455, 437–474.] model are re-derived for a two dimensional surface using general expression for surface energy that include surface tension. The model treats the interface as a shell of vanishing thickness possessing surface tension as well as membrane and bending stiffness. The two-dimensional plane strain problem of an infinite isotropic elastic domain subjected to the uniform far-field load and containing an isotropic elastic circular inhomogeneity whose interface is described by the Steigmann-Ogden model is solved analytically. Closed-form expressions for all elastic fields in the domain are obtained. Dimensionless parameters that govern the problem are identified. The Maxwell type approximation formula is obtained for the effective plane strain properties of the macroscopically isotropic materials containing multiple inhomogeneities with the Steigmann-Ogden interfaces. The “neutrality” conditions are analyzed. It is demonstrated that while the Steigmann-Ogden model theoretically reduces to the [Gurtin, M.E., Murdoch, A.I., 1975. A continuum theory of elastic material surfaces. Arch. Ration. Mech. Anal. 57, 291–323.; Gurtin, M.E., Murdoch, A.I., 1978. Surface stress in solids. Int. J. Solid. Struct. 14, 431–440.] model when the bending interphase effects are neglected, the two models (for the case of zero surface tension) describe two very different interphase regimes of seven regimes proposed by [Benveniste, Y., Miloh, T., 2001. Imperfect soft and stiff interfaces in two-dimensional elasticity. Mech. Mater. 33, 87–111.].
North-South Transatlantic Trajectories: Comparative South American Experiences

Shifting attention from Central America’s transatlantic engagements to South America helps explore the less discussed intra-American nature of transatlantic transactions, while also bringing the dominant east-west flows into the twenty-first century. Both dimensions expose several Central American patterns: the global-transatlantic connection, competition between today’s trading blocs resembling those between corporations and empires before, the transatlantic-transpacific marriage being resuscitated, and the growing intra-Latin flows that colonialism and nationalism previously prevented.
Concurrent nicotine and tobacco product use among homeless smokers and associations with cigarette dependence and other factors related to quitting.

Abstract Background Cigarette smoking rates among homeless adults are exceptionally high, contributing to health disparities experienced by this disadvantaged population. Concurrent nicotine and tobacco product use have been shown to result in greater health problems than cigarette smoking alone, and little is known about the rates, motives, and perceived impacts of concurrent use in this group. The purpose of this study is to explore concurrent use rates and constructs of interest among homeless adult daily smokers and to examine differences between concurrent users and non-concurrent users on cigarette dependence, perceived risk of smoking, readiness to quit, and the receipt of recent cessation intervention. Methods Participants (N = 396) were recruited from six homeless-serving agencies and/or shelters in Oklahoma City. Enrolled participants completed self-report questionnaires. Results The rate of concurrent use was high −67.2%. Participants most frequently endorsed lower cost and a desire to cut down on cigarette smoking as motives for concurrent product use. Concurrent users indicated both a greater likelihood of developing a smoking-related disease if they did not quit for good and a greater number of past year quit attempts relative to non-concurrent users. There was no significant difference between concurrent users and non-concurrent users on readiness to quit or having received recent smoking cessation intervention. Conclusion The need for cessation efforts that account for concurrent use for homeless adult smokers is great. Study findings indicate that concurrent users are commonly pursuing the reduction or elimination of cigarette usage and should be specifically targeted for cessation intervention.
Sexual Abuse in the Professional Relationship

This article collects numerous cases of widely varying types of professionals using their professional position as a means for sexual exploitation. It compares the court decisions by profession and uses this comparison to show the severity of penalty accorded to different professions.
Primary Kaposi’s Sarcoma of Lymph Nodes

An example of Kaposi’s sarcoma with primary involvement of lymph nodes is reported. The patient, a woman, was admitted because of generalized lymphadenopathy and anemia. She was also known to have congestive heart failure of rheumatic origin. SMA-12 screening disclosed hypercalcemia on several occasions during her hospitalization. Levels of circulating parathormone and prostaglandins E2 and F were markedly increased. Total bone scan was negative for involvement by tumor. Electronmicroscopic examination of an involved lymph node disclosed secretory bodies in the cytoplasm of malignant cells and other cells, with clear indication of endothelial origin. The rarity of Kaposi’s sarcoma with primary lymph nodal involvement in the United States is discussed. So far as is known by the authors, no example of Kaposi’s sarcoma has been associated with hypercalcemia due to ectopic endocrine production.
Biogenesis of Secretory Proteins and Cell Surface Receptors in Mammalian Cells: Posttranslational Modifications and Protein Folding within the Rough Endoplasmic Reticulum

In all eukaryotic cells secretory proteins and cell surface receptors are synthesized on ribosomes attached to the rough endoplasmic reticulum (ER) (15). The growing Polypeptide chain is extruded from the ribosome and transported in an unfolded state through a protein- lined channel in the ER membrane into the ER lumen; it is never exposed to the cytosol. Secretory proteins are completely transported into the ER lumen; membrane proteins become anchored in the ER membrane via one or more ∼23 amino acid hydrophobic segments that form membrane- spanning a- helixes. Once synthesis is complete, newly introduced Polypeptides in the membrane and lumen of the ER must be folded, matured, sorted, and transported. Secretory or membrane proteins undergo many modifications during their transit to the cell surface: (i) cleavage of signal sequences (ii) formation and rearrangement of disulfide bonds (iii) other protein folding steps, including formation of muluchain proteins (iv) addition and modification of N- and O- linked Oligosaccharides (v) other specific proteolytic cleavages.
Glioma Invasion: Mechanisms and Therapeutic Challenges

A hallmark of gliomas is the ability of individual tumor cells to infiltrate the neural tissue and extend beyond the visible borders of the tumor. Current treatments fail to remove these invasive cells, which almost invariably lead to tumor dissemination and therapy failure in the long term. The composition and properties of the extracellular matrix (ECM) in the adult central nervous system are notoriously inhibitory to cell motility and axonal extension. However, glioma cells are uniquely able to remodel this microenvironment by degradation of the neural ECM and production of a novel matrix that contains neural-specific and mesenchymal components. Structural signals from the ECM and soluble factors from the surrounding non-neoplastic cells regulate the molecular and cellular mechanisms of invasion, which include matrix remodeling, cytoskeletal reorganization, and phenotype transition from highly proliferative to migratory. Specific strategies against invading glioma cells are in their infancy due to the paucity of appropriate targets and the difficulty of predicting the effects of targeting this highly plastic cell population in vivo. Identification of the key molecular mechanisms necessary for cell invasion and the major switches that regulate the inter-conversion of migratory and proliferative phenotypes will provide a wealth of novel targets to direct therapies against brain tumor progression and improve long-term patient survival.
Music and the Social and Emotional Challenges of Undergraduate Instrumental Music Students.

This study explored perceptions of four undergraduate instrumental music students. The purpose of this study was to describe social and emotional challenges of college instrumental music students a...
Sleepless in Albuquerque: Diversity, Learning through Service, and Pedagogy of Exploration.

Community service trips are often viewed as educational because students supposedly cross socio-economic, racial, and other borders to engage with people of various backgrounds. However, diversity ...
Multiple orientation relationships among nanocrystals of manganese oxides

In a series of experiments[1,2] aimed at preparing anisotropic nanoparticles of transition metal oxides, we have produced nanorods of manganite (γ-MnOOH, monoclinic, space group P21/a, with a = 0.5304 nm, b = 0.5277 nm, c = 0.5304 nm, and β = 114 38 ) that nucleate and grow on octahedral hausmannite (Mn3O4, space group I41/amd, and a = 0.5762 nm, c = 0.9470 nm) crystals, as well as octahedral hausmannite crystals that nucleate and grow on manganite nanorods. We show that, even though it is possible to induce the nucleation of one onto the other, there seems to be no consistently observed crystallographic relationship between them. Hausmannite and manganite are both naturally occurring minerals, and they also may occur within the cathode materials of Li ion manganese oxide batteries, where the irreversible formation of these two phases is believed to contribute to the decrease in performance.
Enterprise Valuation, Risk, and the Modern E-Business

The following paper comprises three key parts, each drawing on those previous and, ultimately, culminating with a novel solution to the problem of valuating e-commerce startups. Because the text moves quickly from one aspect to another, a short overview may enable the reader to more clearly discern the value of each element, in combination, to the ultimate goal. First, analysis begins with an introduction of the difficulties present in valuation of e-commerce firms. The first portion of the text also introduces common risk factors within the e-commerce space, a concept which is critical to the subsequent developments. Next, the text delves into the methods applied to valuate technology startups, making note of the models applied. Further analysis of these methods examines the intricacies of the solutions posed and the difficulties found in application. Finally, the author presents a novel method of ascertaining the market risk of e-commerce startups. This proposition relies on the assumptions developed in the first portion of the text and contributes to bringing the methods identified in the second closer to fruition. Because the novel method could allow for valuation of e-commerce firms if applied by way of previous theory, the proposed solution may prove useful in the valuative exercise.
Effects of environmental temperature and ammoniation on utilization of straw by sheep

Eighteen sheep were used to compare diets based on ammoniated wheat straw (AWS) or untreated wheat straw (WS) at three thermal environments: hot (HE, 36 degrees C, 70% relative humidity (RH], thermoneutral (TNE, 24 degrees C, 70% RH) and cold (CE, 4 degrees C, 70% RH). Six sheep were housed in each environment for at least 21 d prior to the trial. Two periods of 28 d were used in a crossover design. Within each period, digestibility was measured both under ad libitum intake (collections on d 16 to 20) and at restricted intake (collections on d 24 to 28). Diets consisted of 59% straw, 20% alfalfa hay and 21% concentrate. Urea was added to the untreated straw diet (.75%) to compensate partially for the N present in the AWS. Rectal temperature and respiration rates indicated that sheep in the HE were heat-stressed. Sheep housed in the CE had lower rectal temperatures and respiration rates than sheep in the TNE, but they did not shiver or show other visible signs of cold stress. Voluntary DM intake increased from 604 to 806 g/d, and ad libitum DM digestibility increased from 55.5 to 58.2% when AWS was fed. At restricted intake, ammoniation increased diet digestibility from 58.8 to 61.4%. Voluntary intake was lower in the HE (588 g/d) compared to 763 g/d in the TNE and 764 g/d in the CE. Digestibility of DM at ad libitum intake was lower in the HE (54.6%) than in the TNE (57.5%) or CE (58.6%); respective results at restricted intake were 58.5, 61.0 and 60.7%.(ABSTRACT TRUNCATED AT 250 WORDS)
85 – Treponema pallidum

Publisher Summary Treponema pallidum subsp. pallidum is the causative agent of syphilis, a sexually transmitted infection (STI), with diverse clinical manifestations that occur in distinct stages. Just as many emerging infectious diseases, syphilis is at first highly virulent, but over time it becomes a more chronic infection. Regardless of its origin, syphilis spread across the world in the sixteenth century aided by human migrations associated with commerce and conflicts. Despite the advent of effective antibiotic therapies in the mid-twentieth century, syphilis continues to be a worldwide public health problem, particularly because of its association with infection by human immunodeficiency virus (HIV). The emergence of the HIV epidemic has re-emphasized the importance of syphilis as a health problem. Control of syphilis is currently based on sex education with promotion of condom use, diagnostic screening for blood donors, pregnant women, military recruits, high-risk groups, treatment of infected individuals, and partner notification and treatment.
Cardiac evaluation of patients with 22q11.2 duplication syndrome

The 22q11.2 duplication syndrome (22q11.2DupS) is characterized by phenotypic heterogeneity, from seemingly asymptomatic to severely affected patients. Our study sought to detail the cardiac phenotype associated with 22q11.2DupS, the prevalence of aortic arch anomalies and aortic root dilation in 22q11.2DupS, and to assess how frequently new congenital heart disease (CHD) is diagnosed at outpatient cardiac evaluation following genetic diagnosis. In our cohort of 85 patients, 20.0% had CHD, with a wide range of phenotypes. Sixty-eight patients had complete cardiac evaluations detailing aortic arch sidedness and branching pattern, of which 5 (7.4%) had an aortic arch anomaly, all of whom had concurrent intracardiac CHD. Of 53 patients without CHD who had complete cardiac evaluations, only 3 (5.7%) had evidence of aortic root dilation. Of 46 patients who underwent outpatient cardiac evaluation following diagnosis of 22q11.2DupS, only one (2.2%) was found to have CHD, an isolated bicuspid aortic valve without stenosis. Therefore, the CHD phenotype in 22q11.2DupS, when present, is heterogeneous. Aortic arch anomalies are uncommon, and no patient in our cohort had one in isolation. Isolated aortic root dilation is also uncommon. Finally, outpatient cardiac evaluation following genetic diagnosis without previously known CHD infrequently identified minor cardiac malformations.
Improving patient education for atopic dermatitis: A randomized controlled trial of a caregiver handbook.

Background/objectives Patient education is important to families' ability to manage and cope with pediatric atopic dermatitis (AD). We evaluated whether an educational handbook could improve AD symptoms, caregiver confidence in AD management skills, and AD-related quality of life. Methods Caregivers of children with AD ages 1 month to 16 years were randomly assigned to the intervention arm (handbook in addition to standard AD management) or the control arm (standard management alone). Caregivers completed self-report outcome questionnaires prior to a clinical visit for AD and at 3-month follow-up. Results 175 caregivers completed questionnaires at baseline and follow-up. AD symptoms measured by the Patient-Oriented Eczema Measure (POEM) improved in both the handbook and control arms. However, the decrease in the mean POEM score in the handbook arm (-4.4, 95% CI [-5.8, -3.0]) did not differ from that in the control arm (-3.4, 95% CI [-4.8, -2.03]; P = .343). Change in quality of life did not differ between study arms. Among caregivers attending a new patient visit for AD, mean confidence scores (measured from 0 to 100) increased more in the handbook arm (67 [95% CI {60, 74}] to 83 [95% CI {77, 88}]) relative to the control arm (74 [95% CI {65, 82}] to 75 [95% CI {67, 83}]; P = .012). The majority of caregivers rated the handbook as helpful in managing the child's AD. Conclusions Despite an adequate sample size, the handbook did not improve AD symptoms more than standard management alone. The handbook improved confidence in management skills for families attending new patient visits for AD.
Low ADAMTS-13 predicts adverse outcomes in hospitalized patients with suspected heparin-induced thrombocytopenia.

Background Heparin-induced thrombocytopenia (HIT) is a life-threatening thrombotic complication after heparin exposure. However, the role of ADAMTS-13 and von Willebrand factor (VWF) in the disease process and outcomes of HIT is not known. Objective To determine the potential role of ADAMTS-13 and VWF in hospitalized patients suspected with HIT. Methods Associations of the HIT tests, ADAMTS-13 activity, and VWF antigen or activity with other clinical parameters and outcomes in the patients suspected with HIT were determined. Results Of 261 patients, 87 (33.3%) were positive and 174 (66.7%) were negative for a HIT antibody determined by an enzyme immunoassay (EIA). Of these 87 EIA+ patients, 31 (35.6%) were also positive but 56 (64.4%) were negative for serotonin-releasing assay (SRA). There was no statistically significant difference among all three groups (i.e., EIA-, EIA+/SRA+, and EIA+/SRA-) as to their demographic features, reasons for admission to the hospital, type of procedures performed, and in-hospital mortality. Compared to those in the healthy controls, plasma ADAMTS-13 activity in patients suspected with HIT was significantly lower but plasma VWF antigen (VWFAg) and activity (VWFAc) in these patients were significantly higher. While there was no statistically significant difference among all three groups regarding plasma levels of ADAMTS-13 activity, VWFAg, and VWFAc, plasma levels of ADAMTS-13 activity <50% or the low ratios of ADAMTS-13 activity to VWFAg (or VWFAc) are highly predictive for a 90-day mortality rate, particularly in the EIA+SRA+ group. Conclusions These results demonstrate that relative deficiency of plasma ADAMTS-13 activity in hospitalized patients suspected with HIT is common, which may contribute at least in part to the adverse outcomes in this patient population, particularly in those with true HIT.
Glioblastoma-Astrocyte Connexin 43 Gap Junctions Promote Tumor Invasion.

Glioblastoma multiforme (GBM), classified as World Health Organization grade IV astrocytoma, is the deadliest adult cancer of the central nervous system. An important contributing factor to poor survival rates in GBM is extensive invasion, which decreases the efficacy of resection and subsequent adjuvant therapies. These treatments could be markedly improved with increased resolution of the genetic and molecular initiators and effectors of invasion. Connexin 43 (Cx43) is the principal astrocytic gap junction (GJ) protein. Despite the heterogeneity of GBM, a subpopulation of cells in almost all GBM tumors express Cx43. Functional GJs between GBM cells and astrocytes at the tumor edge are of critical interest for understanding invasion. In this study, we find that both in vitro and in ex vivo slice cultures, GBM is substantially less invasive when placed in a Cx43-deficient astrocyte environment. Furthermore, when Cx43 is deleted in GBM, the invasive phenotype is recovered. These data strongly suggest that there are opposing roles for Cx43 in GBM migration. We find that Cx43 is localized to the tumor edge in our ex vivo model, suggesting that GBM–astrocyte GJ communication at the tumor border is a driving force for invasion. Finally, we find that by a Cx43-dependent mechanism, but likely not direct channel-mediated diffusion, miRNAs associated with cell–matrix adhesion are transferred from GBM to astrocytes and miR-19b promotes invasion, revealing a role for post-transcriptional manipulation of astrocytes in fostering an invasion-permissive peritumoral niche. Implications: Cx43-mediated communication, specifically miRNA transfer, profoundly impacts glioblastoma invasion and may enable further therapeutic insight.
Sequence variations in the ETEC CS6 operon affect transcript and protein expression

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrheal disease in developing nations where it accounts for a significant disease burden in children between the ages of 0 to 59 months. It is also the number one bacterial causative agent of traveler's diarrhea. ETEC infects hosts through the fecal-oral route and utilizes colonization factors (CF) to adhere within the small intestine. Over 25 CFs have been identified; 7 are considered major CFs and a vaccine targeting these is predicted to provide protection against up to 66% of ETEC associated disease. Coli Surface Antigen 6 (CS6) is a major CF and is associated with disease-causing ETEC isolates. Analysis of the CS6 operon sequence led to the identification of two regions of variability among clinical isolates which we predicted exert effects on CS6 transcript and protein expression. A total of 7 recombinant E. coli strains were engineered to encode the CS6 operon in wild-type, hybrid, and mutant configurations. Western blot analysis and RT-qPCR provided evidence to support the importance of an intergenic hairpin structure on CS6 expression. Our results reveal the significance of CS6 sequence selection regarding ETEC vaccine development and present novel information regarding CS6 sequence variation in WT ETEC strains.
Is There Evidence to Support Brand to Generic Interchange of the Mycophenolic Acid Products

The uptake of generic immunosuppressants lags comparatively to other drug classes, despite that the Food and Drug Administration (FDA) uses identical bioequivalence standards for all drugs. Transplant societies acknowledge the cost savings associated with generic immunosuppressants and support their use following heart, lung, kidney, or bone marrow transplantation. Seven studies of the pharmacokinetics or clinical efficacy of generic mycophenolate mofetil compared to the innovator product are published; all studies and products were ex-United States. Three studies did not demonstrate any pharmacokinetic differences between generic and innovator products in healthy subjects, achieving FDA bioequivalence requirements. Two studies in renal allograft recipients demonstrated no difference in area under the curves between generic and innovator products, and in one, the maximum concentration (Cmax) fell outside the FDA regulatory range. Two studies revealed no difference in acute organ rejection or graft function in renal allograft recipients. Patient surveys indicate that cost is a barrier to immunosuppressant adherence. Generics present a viable method to reduce costs to payers, patients, and health care systems. Adherence to immunosuppressants is crucial to prevent graft failure. An affordable regimen potentially confers greater adherence. Concerns regarding the presumed inferiority of generic immunosuppressants should be assuaged by regulatory requirements for bioequivalency testing, transplant society position statements, and pharmacokinetic and clinical studies.
Thiol/disulfide exchange equilibria and disulfide bond stability

Publisher Summary Disulfide-bond formation is a versatile oxidation used biologically in diverse processes, such as enzyme catalysis, protection against oxidative damage, stabilization of extracellular proteins, and regulation of biological activity. Because disulfide formation is a reversible process, disulfide-bond stability often plays an important role in the biological utility of disulfide bonds. In turn, the ability to form and break a specific disulfide bond under appropriate biological conditions depends on the nature of the oxidant or reductant, the disulfide stability, the kinetics of the forward and reverse reactions, and the nature and redox state of the environment in which the reaction occurs. The stability of disulfide bonds in small molecules and proteins spans an enormous range, a factor of approximately 1011, corresponding to a free-energy difference of about 15 kcal/mol or a redox potential difference of 0.33 V. This chapter outlines the importance of reversible thiol/disulfide exchange and discusses some practical considerations in measuring disulfide bond stability.
Does Your “Backup” Method Have Your Back? Controversies Surrounding Backup of Rapid Antigen Detection Methods for Group A Streptococcus

Abstract Accurate diagnosis of streptococcal pharyngitis followed by appropriate antibiotic therapy is important for the prevention and control of group A streptococcus (GAS) infection and its sequelae. Rapid antigen detection methods (RADTs) for detection of GAS antigen are commonly used to speed the diagnosis of streptococcal pharyngitis; however, reports of false-negative antigen tests are common. In this review, we describe the conflicting strategies that surround GAS testing and reflexive backup testing for samples found to be negative for Streptococcus pyogenes antigen. We invite you to examine your GAS backup or reflexive testing strategy and ask yourself, "Does my laboratory's GAS backup method have my back?" More importantly, "Is reflexive testing designed to provide optimized diagnostic care for my patient population?"
Endocrine-Disrupting Chemicals: Testing to Protect Future Generations

Endocrine-disrupting chemicals (EDCs) are chemicals that interfere with human hormone processes. EDCs are omnipresent: pesticides, plastics, and drugs, among other common chemicals, all demonstrate endocrine-disrupting properties. Scientific studies have demonstrated the frightening effects EDCs have on human health, particularly for fetuses while they develop in utero. Given these health concerns, Congress passed the Food Quality Protection Act of 1996, which requires the EPA to test pesticides for their endocrine-disrupting properties. Frustratingly this testing, fifteen years later, has still not begun. Therefore this Note argues that citizens should bring suit under the Administrative Procedure Act to compel EPA to complete testing of pesticides for endocrine-disrupting properties, all with the goal of furthering effective regulation of EDCs.
Applying XBRL in an Accounting Information System Design Using the REA Approach: An Instructional Case*

The Church in Somewhere (CIS) is a small community church which uses an Excel spreadsheet to keep its financial records. The church administrator is considering moving from a spreadsheet accounting system to a relational database system that can easily be expanded to include more information in the future. In this paper we examine the transforming process in this hypothetical case by following a resource-event-agent (REA) modeling paradigm to create a database. We then link the REA model to financial reporting using Microsoft Access. In addition, using the financial report in the database, students prepare and validate an eXtensible Business Reporting Language (XBRL) document for CIS. Instead of applying the complex U.S. Generally Accepted Accounting Principles (GAAP) Taxonomies, Release 2009, the case uses a dedicated CIS Taxonomy to complete the mapping and tagging processes.
NMR confirms the presence of the aminoterminal helix of group II phospholipase A2 in solution

Publisher Summary In humans, the group I phospholipases A 2 (PLA 2 ) is present in the pancreas and the group II extracellular PLA 2 are found in platelets and arthritic synovial joints. The tertiary structure and disulfide bond pattern are similar among the two groups, with the following main differences: group II PLA 2 have an extension of approximately seven residues on the carboxy terminal part, which is also connected by a disulfide bond, group I PLA 2 have an insertion among the residues 54–56, and in group I the amino terminal helix is connected by a disulfide bond at residue 11. Recent nuclear magnetic resonance (NMR) determination of the solution structure of the pancreatic group I PLA 2 showed that, in contrast to the crystal structures, the beginning of the amino terminal helix is partly disordered. Moreover, the solution structure of the same PLA 2 complexed with the inhibitor and micelle displayed ordering of this region, which became more similar to the crystal structure. In this chapter, a NMR study has been performed on a group II PLA 2 from snake Agkistrodon piscivorus piscivorus , which has previously been extensively used in the biophysical studies on the membrane–protein interactions. In the present study, different techniques from the repertoire of the NMR methods have been used. Those techniques have provided independent data that are consistent and permitted reaching conclusion on the secondary structure of the protein. Improvement in production and refolding procedure for recombinant PLA 2 has allowed preparation of 13C and 15N labeled protein, allowing its assignment and measurement of several structural parameters that describe the conformation of the amino terminal helix. These parameters include NOE signal, main chain dihedral angles, coupling constants, amide hydrogen exchange rates and the deviation of the chemical shift, respectively. These data provide reliable conclusions about the secondary structure of the protein even before building the complete tertiary structure.
The Millennium Challenge Corporation and Ghana

A U.S. government agency, the Millennium Challenge Corporation (MCC), provides aid to developing countries, focusing on poverty reduction through economic growth. It measures results through an economic rate of return based on increases in farmer incomes anticipated over twenty years. As MCC and Ghana finalize a $547 million grant for agriculture and transportation infrastructure, they come up against an accountability and measurement problem: how to address an urgent request from Ghana to fund community services - such as schools and drinking water--for which the results will be more difficult to measure.
Selection and properties of Escherichia coli mutants defective in the synthesis of cyclopropane fatty acids

Mutants of Escherichia coli K-12 defective in the synthesis of cyclopropane fatty acids (CFA) have been selected and isolated by a L-[methyl-3H]methionine suicide procedure. Two mutants were isolated. Stationary-phase cultures of both mutants contain less than 0.7% of the CFA content found in the parental strain. The CFA deficiency is attributed to a deficiency of CFA synthetase activity. Extracts of both mutants contain less than 10% of the CFA synthetase activity found in extracts of the parental strain. Experiments in which parental and mutant extracts were mixed indicate that the lack of activity in the mutant strains is not due to an inhibitor of CFA synthetase present in the mutant extracts. We have not yet detected a physiological phenotype for these mutants. These strains grow normally at various temperatures in a variety of media. We have tested survival (colony-forming ability) in response to (i) prolonged incubation in stationary phase, (ii) exposure to drying, and (iii) exposure to detergents, heavy metals, low pH, high salt concentration, and a variety of other environmental conditions. The survival of both mutants is identical to that of the parental strain under all conditions tested. The compositions (excepting the CFA deficiency) and metabolic turnover rates of the phospholipids of both mutant strains are indistinguishable from those of the wild-type strain. The transport of several amino acids also seems normal in these mutants.
Quantum phase transition in the quantum compass model

In this work, we show that the quantum compass model on a square lattice can be mapped to a fermionic model with local-density interaction. We introduce a mean-field approximation where the most important fluctuations, those perpendicular to the ordering direction, are taken into account exactly. It is found that the quantum phase transition point at ${J}_{x}={J}_{z}$ marks a first-order phase transition. We also show that the mean-field result is robust against the remaining fluctuation corrections up to the second order.
Biology and homosexuality

not help but fuel further misperceptions about homosexuality. They read something like this: Biology was never thought to play a role in homosexuality, so LeVay's evidence in support of a biological substrate for homosexuality is surprising and adds a new element to the debate. It is also provocative because it suggests that homosexuality is innate and resistant to change. All in all, a biological basis for homosexuality is an "explosive notion." These senti-
How children learn the meanings of words

How do children learn that the word "dog" refers not to all four-legged animals, and not just to Ralph, but to all members of a particular species? How do they learn the meanings of verbs like "think," adjectives like "good," and words for abstract entities such as "mortgage" and "story"? The acquisition of word meaning is one of the fundamental issues in the study of mind. According to Paul Bloom, children learn words through sophisticated cognitive abilities that exist for other purposes. These include the ability to infer others' intentions, the ability to acquire concepts, an appreciation of syntactic structure, and certain general learning and memory abilities. Although other researchers have associated word learning with some of these capacities, Bloom is the first to show how a complete explanation requires all of them. The acquisition of even simple nouns requires rich conceptual, social, and linguistic capacities interacting in complex ways. This book requires no background in psychology or linguistics and is written in a clear, engaging style. Topics include the effects of language on spatial reasoning, the origin of essentialist beliefs, and the young child's understanding of representational art. The book should appeal to general readers interested in language and cognition as well as to researchers in the field.
Art in Science: The Doctor by Luke Fildes: Putting the Patient First.

The thoughtful and concerned gaze of the well-dressed physician upon the face of his ill, young patient dominates the center of The Doctor (Fig. 1), an iconic oil painting completed by the British artist Sir Samuel Luke Fildes (1843–1927) in 1891. The scene unfolds in the humble home of this distraught family, with one small area rug and the hanging laundry in a single modest-sized room used for all manner of everyday life.
Critical literature 2014

BACKGROUND The practice of hospital medicine is complex, and the number of clinical publications each year continues to grow. To maintain best practice it is necessary for hospitalists to stay abreast of the literature, but difficult to accomplish due to time. The annual Society of Hospital Medicine meeting offers a plenary session on Updates in Hospital Medicine. This article is a summary of those papers presented at the meeting. METHODS We reviewed articles published between January 2014 and January 2015 in the leading medical journals, searching for papers with good methodological quality, the potential to change practice, and papers that are thought provoking. The authors collectively agreed on 14 articles. The findings, cautions, and implications are discussed for each paper. RESULTS Key findings include: a novel neprilysin inhibitor and angiotensin receptor blocker combination drug reduces mortality in patients with heart failure; the concern for acute kidney injury after venous contrast may be overstated; the Confusion Assessment Method Severity score is an important tool for prognostication in delirious patients; ramelteon shows promise for lowering incident delirium among elderly medical patients; polyethylene glycol appears effective in rapidly resolving hepatic encephalopathy; cirrhotic patients on a nonselective β-blocker have increased mortality after they develop spontaneous bacterial peritonitis; current guidelines regarding prophylaxis against venous thromboembolism (VTE) in medical inpatients likely result in nonbeneficial use of medications; from a safety and efficacy perspective, direct oral anticoagulants perform quite well against conventional therapies in patients with VTE and atrial fibrillation, including in elderly populations; 2 new once-weekly antibiotics, dalbavancin and oritivancin, approved for skin and soft tissue infections, appear noninferior to vancomycin; offering family members of a patient undergoing cardiopulmonary resuscitation the opportunity to observe has durable impact on long-term psychological outcomes. CONCLUSIONS This update reviews key clinical articles published in 2014, selected by the authors for their methodological quality and potential for changing the practice of inpatient physicians. All of these articles add to the body of inpatient medical knowledge and contribute to the debate on best practices. Journal of Hospital Medicine 2015. © 2015 Society of Hospital Medicine
Practical Applications of Retirement Income for the Wealthy, Middle, and Poor

In this Practical Applications report, Meir Statman—Glenn Klimek Professor of Finance at Santa Clara University’s Leavey School of Business—addresses some of the realities of retirement savings across income groups. Statman proposes a mandatory defined-contribution (DC) plan to ensure adequate retirement savings among the middle and direct financial assistance to the poor. The source article appeared in The Journal of Retirement’s Winter 2014 issue. “It is time to switch from a nudge to shove and replace voluntary DC plans with mandatory DC plans,” Statman urges. Read this report to find out why he believes we should distinguish four income groups: The wealthy, the steady-middle, the precarious-middle and the poor.
Health Insurance Coverage and Take-Up: Lessons from Behavioral Economics

Context: Millions of uninsured Americans ostensibly have insurance available to them—many at very low cost—but do not take it up. Traditional economic analysis is based on the premise that these are rational decisions, but it is hard to reconcile observed enrollment patterns with this view. The policy prescriptions that the traditional model generates may thus fail to achieve their goals. Behavioral economics, which integrates insights from psychology into economic analysis, identifies important deviations from the traditional assumptions of rationality and can thus improve our understanding of what drives health insurance take-up and improved policy design. Methods: Rather than a systematic review of the coverage literature, this article is a primer for considering issues in health insurance coverage from a behavioral economics perspective, supplementing the standard model. We present relevant evidence on decision making and insurance take-up and use it to develop a behavioral approach to both the policy problem posed by the lack of health insurance coverage and possible policy solutions to that problem. Findings: We found that evidence from behavioral economics can shed light on both the sources of low take-up and the efficacy of different policy levers intended to expand coverage. We then applied these insights to policy design questions for public and private insurance coverage and to the implementation of the recently enacted health reform, focusing on the use of behavioral insights to maximize the value of spending on coverage. Conclusions: We concluded that the success of health insurance coverage reform depends crucially on understanding the behavioral barriers to take-up. The take-up process is likely governed by psychology as much as economics, and public resources can likely be used much more effectively with behaviorally informed policy design.