cssi/SciSciGPT-SciSciNet huggingface dataset:
Multiple forms of the Menkes Cu-ATPase.

The 5′ region of MNK cDNAs has a 45 bp insert terminating at the 5′end with an AGATG sequence. The ATG in the sequence is in-frame with the ATG downstream identified by Vulpe et al (1993) as a translation start site for MNK mRNA. Inserts of 192 bp and 45 bp have been found in the 5′ region of MNK mRNAs from BeWo cells, Caco-2 cells and normal human fibroblasts. Extensions to the 5′ end of these mRNAs could foretell a modified N-ter-mini in certain forms of the Menkes Cu-ATPase These modified H2N-terminal extensions are postulated to be targeting signals for post-translational processing and cellular localization. In this report, we provide evidence that the primary Menkes transcript in non-Menkes cells undergoes post-transcriptional splicing that gives rise to multiple transcripts. The data suggest that the Menkes gene is a copper locus that codes for more than one form of the Menkes Cu-ATPase and one of these forms could be a small Cu transport protein.
Mechanisms of Ventricular Reserve Limitation in Cardiac Hypertrophy

Ventricular hypertrophy is usually characterized by resting abnormalities of diastolic function with preserved systolic performance. However, there are often profound limitations of both diastolic and systolic functional reserve to physiologic stress. One of the most well studied reserve limitations is to chronotropic stress. Rapid atrial pacing can result in marked elevation of diastolic pressure and stiffness in animal hypertrophy models and in humans with idiopathic asymmetric hypertrophy presenting with chest pain syndrome. In other patients with severe hypertrophy and congestive failure symptoms, diastolic function does not deteriorate with rapid pacing, suggesting that underlying etiology and severity of disease are important factors to this response. Systolic reserve limitations to pacing stress are also found in both animal and human hypertrophy. Raising heart rate from 80 to 160 min—1 increases endsystolic elastance by nearly 100% in normal humans, while it is virtually unchanged in hypertrophied hearts. Mechanisms that may underlie the loss of contractile reserve to chronotropic challenge are abnormal subendocardial perfusion, altered calcium cycling, and changes in myofilament proteins. Each mechanism is reviewed. In addition to chronotropic reserve limitations, the hypertrophied heart has limited preload and inotropic reserve due to increased end-systolic chamber stiffness. A high end-systolic stiffness results in minimal augmentation of pump function (i. e., cardiac output) when contractility is increased. Furthermore, such a heart is highly sensitive to preload change, with marked alterations in systolic pressure generation and thus wall stress resulting from relatively small changes in chamber diastolic filling. Current and future therapeutic approaches to this disorder need to consider all of these reserve limitation mechanisms.
The Complex Wave Number k and the Normalizing Factor Δ

The characteristics of antennas described and tabulated in this volume are obtained from solutions of Maxwell’s equations in an infinite, homogeneous, isotropic medium characterized by the complex permittivity e = e0er = e0(e r ʺ - je r ʹ ), the complex conductivity σ = σʹ — jσʺ, and the real permeability μ = μ0μr In such a medium Maxwell’s equations have the form $$\bigtriangledown \times E = -j\omega B,\;\;\;\;\bigtriangledown \cdot E = 0$$ $$\bigtriangledown \times B = \mu (\sigma + j\omega \varepsilon)E,\;\;\;\;\bigtriangledown \cdot B = 0$$
Development and Clinical Application of High Frequency Ventilation

The literature on the development of artificial respiration includes Genesis 4:7, and some other importants steps which may be listed briefly.
Impact of Different ERP Systems on Organizational Performance and Managerial Decision Making

It is the purpose of this paper to examine the differences in performance and decision making capabilities between companies that use SAP systems to those who use all other ERP systems in conjunction with their accounting systems. We will examine these differences in large manufacturing companies across variables that might shed light on various performance categories: business structure, growth characteristics, labor utilization factors, income characteristics, and efficiency measure. The latter of which will provide a proxy for accounting information transparency. We will examine these differences by employing a means difference test to examine both magnitude and statistical significance. We will also attempt to reveal managerial preferences toward ERP systems by employing a binary logistic regression. We find in this paper that differences do exist between companies that use SAP systems as compared to those who use other ERP systems, but the majority of these differences are not statistically significant and are somewhat contradictory. Further, we find that pinpointing managerial preferences toward an ERP system is not based on either organizational structure characteristics or organizational performance. This lead us to subsequently conclude that increasing accounting transparency in an organization is not a factor in choosing an ERP platform.
Considerations in surgery of the thyroid gland

The technique of thyroidectomy is covered in detail in various text-books and surgical atlases. The aim of this article is not to recount the details of the surgical procedure, but rather to emphasize important, pertinent surgical anatomy and discuss the management of various difficult situations and operative challenges that the thyroid surgeon may encounter from time to time.
Risk factors and select cardiac characteristics in dogs naturally infected with Trypanosoma cruzi presenting to a teaching hospital in Texas

Background Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, causes sudden death and chronic heart disease with no currently approved treatment. Objective To report epidemiologic and select cardiac characteristics associated with T. cruzi infection in dogs presenting to a teaching hospital in Texas. Animals Three hundred seventy-five client-owned dogs. Methods A retrospective search of medical records identified dogs tested for T. cruzi antibodies or with histologic T. cruzi parasites. Data retrieved included signalment, location of residence, reported reason for testing, cardiac troponin I (cTnI) concentration, and ECG abnormalities. Results Trypanosoma cruzi-infected dogs (N = 63, 16.8%) were significantly younger than negative dogs (N = 312) (mean, 5.9 ± 3.8 versus 7.4 ± 4.0 years; P = .007) with no difference by sex or breed. Ninety-one breeds were tested; the highest percent infected were non-sporting (10/35; 29%) and toy breed (10/42; 24%) groups. The odds of infection were 13 times greater among dogs with an infected housemate or littermate (95% confidence interval [CI], 3.94-50.45; P 0.129 ng/mL (ADVIA; OR, 10.71; 95% CI, 1.60-212.21; P = .035). Conclusions and clinical importance Dogs infected with T. cruzi were identified in Texas in many breed groups including breeds affected by well-described heart diseases that mimic Chagas disease suggesting a need for increased awareness, including knowledge of when to consider testing.
Maroon colonies and New Orleans neutral grounds: from a protosuburban past to a postsuburban future

This essay examines New Orleans maroon colonies as a precursor to the postsuburban constellations that shape the contemporary urban landscape. These communities served as the original neutral groun...
On Jack Welch's Watch: General Electric's Tax Strategy

On November 1, 2004, Judge S.R. Underhill ruled in favor of a subsidiary of General Electric Corporation in a tax case involving events that took place from 1993-1998 when Jack Welch was Chairman of GE's Board. The important issue is whether a corporation can ethically exploit features of the tax law (the actions were legal). In this case, GE shifted 98% of the taxable income to two non-taxable Dutch Banks, but did not shift 98% of the benefits. Also, the GE tax process resulted in fully depreciated airplanes being depreciated a second time. There are two remaining questions. Should GE have implemented this tax strategy (when Jack Welch was Chairman)? Secondly, should GE's current CEO authorize the payment (in lieu of taxes) to the U.S. Government of $62,000,000 even though Judge Underhill ruled in GE's favor?
A Response to Giorgios Kallis’ Notions of Socialism and Growth

ABSTRACTKallis’ discussion of degrowth in a transition to socialism is misleading and substantially detached from the current context, especially with recurring cataclysms due to climate change and...
What Is the Normal Ulnar Bow in Adult Patients

Background Rotation of the forearm is a result of the complex interaction among the radius, ulna, and interosseous membrane. Although the radius is recognized as curved, the ulna is generally thought of as a "straight bone." To better describe normal anatomy, which may lead to more successful anatomic fixation of forearm fractures, we aimed to apply a method of measuring the normal ulnar bow and determine the mean ulnar bow in adults. Questions/purposes (1) To what degree is the ulna bowed in the coronal and sagittal planes in normal adult forearms? (2) To what degree is the radius bowed in the coronal plane in normal adult forearms? Methods Radiographs of the forearms of adults taken during a 1-year period were initially obtained retrospectively. These radiographs were performed for various reasons, including forearm pain and routine radiographic follow-up. Radiographs were excluded if evidence of a fracture or post-fracture fixation was found, if a patient had missing AP or lateral images, or if a suboptimal technique was used. The coronal and sagittal bow of the ulna was measured with a method adapted from previous studies that assessed radial bow using AP and lateral radiographs, respectively. Similar measurements were made in the coronal plane for the radius. All measurements were performed independently by the four authors. There was excellent interobserver reliability for ulnar bow in the coronal and sagittal planes (interclass correlation coefficient = 0.96 and 0.97, respectively) and for radial bow in the coronal plane (interclass correlation coefficient = 0.90). Results The mean maximal coronal ulnar bow was 7 ± 2 mm and was located at 75% of the ulnar length, measured proximally to distally. The location of coronal bow was consistently distal to the radial bow location. The mean maximal sagittal ulnar bow was 6 ± 3 mm and was located at 39% of the ulnar length. The mean maximal coronal bow of the radius was 14 ± 2.0 mm and was 59% of the total length of the radius from proximal to distal. Conclusions The ulna is not a "straight bone," as is commonly thought, but rather has a bow in both the coronal and sagittal planes. Clinical relevance Knowledge of the standard ulnar bow may be pivotal to prevent malunion of the ulna during surgery. Future research using these data in preoperative planning may lead to changes in plate contouring and clinical outcomes in forearm fracture management.
PD-1 blockade-driven anti-tumor CD8+ T cell immunity requires XCR1+ dendritic cells

Abstract CD8+ T cells are required for effective anti-PD-1 (αPD-1) cancer immunotherapy. Type 1 conventional dendritic cells (cDC1s) bearing XCR1 critically mediate the initiation of protective anti-tumor CD8+ T cell responses in mice and humans. However, whether cDC1s contribute to evoking the effector function of CD8+ T cells during αPD-1 antibody therapy remains unclear. Here, by deleting cDC1s at the effector phase of αPD-1 therapy, we identify these cells as a crucial innate determinant for effective αPD-1 immunotherapy. αPD-1 treatment unleashed cDC1s to promote anti-tumor CD8+ T cell immunity, through the expansion of TCF1+ precursors and generation of TIM3+ terminally differentiated effectors. Furthermore, tumor cDC1 abundance was predictive of enhanced CD8+ T cell infiltration, higher survival, and improved clinical responses to αPD-1 therapy in human cancer patients. Together, this study reveals the requirement for cDC1s in PD-1 blockade therapy, through their ability to elicit CD8+ T cell effector responses that mediate tumor control, and highlight cDC1s as an attractive cellular target to be harnessed for novel immunotherapeutics.
Entropy-balanced accruals

This study assesses whether the accrual-generating process is adequately described by a linear model with respect to a range of underlying determinants examined by prior literature. We document substantial departures from linearity across the distributions of accrual determinants, including measures of size, performance, and growth. To incorporate non-linear relations, we employ a recently developed multivariate matching approach (entropy balancing) to adjust for determinants in place of relying on a linear model. Entropy balancing identifies weights for the control sample to equalize the distribution of determinants across treatment and control samples. In simulations drawing random samples from deciles where a linear model displays poor fit, we find that entropy balancing significantly improves accrual model specification by reducing coefficient bias relative to linear and propensity-score matched models. Consistent with entropy balancing retaining sufficient power, we find that its estimates detect seeded accrual manipulations and explain variation in accruals around equity issuances.
Proteomics-Based Insights Into the SARS-CoV-2-Mediated COVID-19 Pandemic: A Review of the First Year of Research.

In late 2019, a virus subsequently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and led to a worldwide pandemic of the disease termed coronavirus disease 2019. The global health threat posed by this pandemic led to an extremely rapid and robust mobilization of the scientific and medical communities as evidenced by the publication of more than 10,000 peer-reviewed articles and thousands of preprints in the first year of the pandemic alone. With the publication of the initial genome sequence of SARS-CoV-2, the proteomics community immediately joined this effort publishing, to date, more than 100 peer-reviewed proteomics studies and submitting many more preprints to preprint servers. In this review, we focus on peer-reviewed articles published on the proteome, glycoproteome, and glycome of SARS-CoV-2. At a basic level, proteomic studies provide valuable information on quantitative aspects of viral infection course; information on the identities, sites, and microheterogeneity of post-translational modifications; and, information on protein–protein interactions. At a biological systems level, these studies elucidate host cell and tissue responses, characterize antibodies and other immune system factors in infection, suggest biomarkers that may be useful for diagnosis and disease-course monitoring, and help in the development or repurposing of potential therapeutics. Here, we summarize results from selected early studies to provide a perspective on the current rapidly evolving literature.
Mitochondrial DNA copy number, metabolic syndrome, and insulin sensitivity: Insights from the Sugar, Hypertension, and Physical Exercise Studies

Mitochondrial DNA copy number (mtDNA-CN) measured in blood has been associated with many aging-related diseases, with higher mtDNA-CN typically associated with lower disease risk. Exercise training is an excellent preventative tool against aging-related disorders and has been shown to increase mitochondrial function in muscle. Using the Sugar, Hypertension, and Physical Exercise cohorts (N = 105), we evaluated the effect of 6-months of exercise intervention on mtDNA-CN measured in blood. Although there was no significant relationship between exercise intervention and mtDNA-CN change (P = 0.29), there was a nominally significant association between mtDNA-CN and metabolic syndrome (P = 0.04), which has been seen in previous literature. We also identified a nominally significant association between higher mtDNA-CN and higher insulin sensitivity (P = 0.02).
Rapid plate method for the isolation of lysogenic bacteriophages

We have devised a rapid plate method for the detection and isolation of lysogenic phages and have used the procedure to screen 15 strains of Staphylococcus aureus. This method should prove applicable to a wide variety of bacterial species and should be especially valuable for those pathogens for which no phage-typing system is available.
Importance of Physical Properties of Benzo(a)pyrene-Ferric Oxide Mixtures in Lung Tumor Induction

Summary Three mixtures of benzo(a)pyrene (BP) and ferric oxide with different physical properties were given intratracheally to Syrian golden hamsters for an examination of their neoplastic potential. Hamsters treated with a preparation containing large aggregates of BP and ferric oxide resulting from nucleation of BP on the particles showed an earlier onse tand higher incidence of respiratory tract tumors than animals given a mixture containing smaller aggregates prepared by hand-grinding. The greatest number of tumors were present in the trachea and the predominant type was the squamous carcinoma. A third preparation in which the carcinogen was not attached to the ferric oxide showed a low tumor incidence similar to that present after intratracheal intubation of BP in gelatin without a carrier particle. For this model system of respiratory carcinogenesis, the physical attachment of BP and the carrier dust is necessary for a high tumor yield.
Effect of Lactobacillus-fermented diets on bacterial translocation and intestinal flora in experimental prehepatic portal hypertension.

Spontaneous bacterial infections in cirrhosis and portal hypertension have been attributed to trans- location of gut-derived bacteria, a process promoted by intestinal bacterial overgrowth and disruption of the gut mucosal barrier. Bacteriotherapy with Lactobacillus has been reported to correct bacterial overgrowth, stabilize mucosal barrier function, and decrease bacterial translocation in rat models of acute liver injury and failure. In this study we investigated the effect of Lactobacillus-supplemented diets on intestinal flora and on bacterial translocation rate in portal vein ligated rats. Lactobacillus-fermented milk (yogurt) containing at least 2 × 109 colony forming units/ml or placebo (water) was adminstrated by gavage twice daily (2 ml) for 9 days. Portal vein ligation was performed on day 7 of treatment. Bacterial translocation to mesenteric lymph nodes and quantification of intestinal flora was assessed by standard bacteriological cultures. Bacterial translocation was not significantly different between animals that received yogurt (82%) and those that received placebo (75%). Yogurt did not induce any significant changes in intestinal flora, whether it was produced with Lactobacillus acidophilus or Lactobacillus GG. In conclusion, in acute prehepatic portal hypertension, bacteriotherapy with Lactobacillus was unable to induce changes in bacterial translocation probably because it was unable to induce changes in bacterial flora.
Developing Measures of Content Knowledge for Teaching Reading.

Abstract In this article we present results from a project to develop survey measures of the content knowledge teachers need to teach elementary reading. In areas such as mathematics and science, there has been great interest in the specialized ways teachers need to know a subject to teach it to others—often referred to as pedagogical content knowledge. However, little is known about what teachers need to know about reading to teach it effectively. We begin the article by discussing what might constitute content knowledge for teaching reading and by describing the survey items we wrote. Next, factor and scaling results are presented from a pilot study of 261 multiple‐choice items with 1,542 elementary teachers. We found that content knowledge for teaching reading included multiple dimensions, defined both by topic and by how teachers use knowledge in teaching practice. Items within these constructs formed reliable scales.
Catalase, superoxide dismutase, and hemolysin activities and heat susceptibility of Listeria monocytogenes after growth in media containing sodium chloride

The activities of catalase, superoxide dismutase, and a thiol-activated hemolysin produced by four strains of Listeria monocytogenes propagated in media containing various concentrations of sodium chloride were examined. L. monocytogenes 7644 showed an increase in catalase, superoxide dismutase, and thiol-activated hemolysin activities when grown in a medium containing 2.5% (wt/vol) NaCl followed by a decrease in activities when propagated in media containing salt concentrations higher than 2.5%. L. monocytogenes LCDC 81-861 demonstrated enhanced catalase activity when grown in media containing NaCl ranging from 1.5 to 4.6% and increased superoxide dismutase activity when propagated in media containing 1.5 to 3.5% NaCl. L. monocytogenes LCDC 81-861 did not exhibit any detectable hemolysin activity under the conditions tested. After growth in various NaCl-containing media, both strains were subjected to sublethal heat injury for 30 min at 55 degrees C. L. monocytogenes LCDC 81-861 showed increased sensitivity to the heat treatment when grown in media containing 4.6 and 6.5% NaCl, whereas L. monocytogenes 7644 did not exhibit enhanced heat lability.
Circular stack filters

Circular stack filters, which are subsets of stack filters, form sublattices of the stack filter lattice. The filters in these sublattices are spread more or less uniformly over the stack filter lattice and thus provide a wide variety of filtering operations without the penalty of the very large cardinality of the set of all stack filters. Circular stack filters are defined and some of their properties are explored. >
Possible muscarinic-cholinergic mediation of patterned aggressive reflexes in the cat

Abstract 1. 1. Adult female outbred cats were prepared with chronic hypothalamic stimulating electrodes and ventricular cannulae. 2. 2. Cats were restrained, and patterned aggressive reflexes of elicited head turning, biting, and paw striking to proximate stimulation were assessed under a variety of stimulation conditions. 3. 3. In comparison with vehicle injection cholinergic stimulation by arecoline facilitated the three reflexes and cholinergic blockade by scopolamine inhibited them. 4. 4. Cholinergic-muscarinic receptors may be involved as mediators of terminal (consummatory) behaviors in aggressive syndromes.
Reduced lactational performance following intravenous endotoxin administration to dairy cows.

Abstract Nonpregnant lactating cows were given 100 μg of endotoxin via the jugular vein to determine effects of intravenous endotoxin administration on mammary inflammation and lactational performance. At the first milking (11 h) posttreatment, milk yield was reduced 33%. Milk fat percentage was elevated at this time, but lactose concentration was decreased. Milk yield and composition returned to pretreatment levels within 2 d. Clinical mastitis was not induced by endotoxin treatment, but milk SCC, NAGase, serum albumin, and lactoferrin were increased by 50%. This increase was small compared with increases during mastitis and may have resulted from lower milk volume. These results support the hypothesis that part of the reduced lactational performance during endotoxin mastitis is mediated by systemic pathophysiological responses and indicate that intravenous endotoxin administration may be a useful model to study adverse effects of infectious disease on lactational performance.
Gene therapy for lung neoplasms

Approximately twenty years ago, advances in molecular genetics and gene transfer technology made the development of “gene therapy” (the modification of the genetic makeup of cells for therapeutic purposes) a clinical possibility. The disorders originally proposed as targets for gene therapy were the inherited, recessive disorders in which transfer of a normal copy of a single defective gene could potentially prevent or alter the course of a disease. Clear, but slow progress has been made in the areas of genetic diseases such as blindness1 and inherited immune deficiencies.2 It soon became apparent that the range of target diseases could be extended to acquired diseases, such ascancer, and many early phase clinical trials have now been conducted in various malignancies. The good news is that most trials have shown good safety. The bad news is that there has been relatively limited efficacy to date. Despite advances in chemotherapy, radiation therapy, and surgery for lung cancer, the 5-year survival rate remains poor at 15% and has improved only minimally over the last two decades. This coupled with the advances that have been made in the understanding of molecular events leading to cancer development, has led to great interest in gene therapy approaches for thoracic malignancies. Unfortunately, lung cancer is usually metastatic at the time of diagnosis and thus requires systemic, rather than local therapy. Systemic therapy using gene therapy has remained largely impossible to date. Malignant pleural mesothelioma (MPM) accounts for 80% of mesothelioma cases and usually presents in the fifth to seventh decade of life with dyspnea, pleural effusion, and non-pleuritic chest pain in the context of an asbestos exposure history. With a disease course affected only minimally by current treatments, MPM has a poor prognosis (median survival of 6–18 months) exceptin the rare cases where it can be completely resected. MPM is a potentially good disease target for gene therapy because the thin layer of mesothelial and malignant cells offers a large surface area for efficient, rapid, and diffuse gene transfer. The purpose of this article is to review the clinical experience in gene therapy for thoracic malignancies and to reflect on the future directions of this approach.
Modeling of a Cartwheel Flexural Pivot

A cartwheel flexural pivot has a small center shift as a function of loading and ease of manufacturing. This paper addresses an accurate model that includes the loading cases of a bending moment combined with both a horizontal force and a vertical force. First, a triangle flexural pivot is modeled as a single beam. Then, the model of cartwheel flexural pivot based on an equivalent model is developed by utilizing the results of the triangle pivot. The expressions for rotational displacement and center shift are derived to evaluate the primary motion and the parasitic motion; the maximum rotational angle is simply formulated to predicate the range of motion. Finally, the model is verified by finite element analysis. The relative error of the primary motion is less than 1.1% for various loading cases even if the rotational angle reaches ±20 deg, and the predicted errors for the two center shift components are less than 15.4% and 7.1%. The result shows that the model is accurate enough for designers to use for initial parametric design studies, such as for conceptual design.
Fifty years of systems science: further reflections

This paper was delivered as the Presidential Address for the 48th International Society for the Systems Sciences Annual Conference in Pacific Grove, California. The full theme of the 2004 conference of ISSS was Fifty Years of Systems Science: Honoring Tradition, Embracing the Future. This main theme was accompanied by two sub-themes of ‘Integration’ (or ‘Unification’), and ‘Continuity’. This paper follows the conference theme by discussing the original goals and challenges facing the founders of the Society 50 years ago, as well as our contemporary goals and challenges. The year 2004 marked 50 years since the precursor organization of the International Society of Systems Science held its first meeting. In an earlier paper I outlined 10 goals of systems science, along with 10 challenges that we face in attaining these goals. Five of these goals were the original goals of the founders of ISSS, as enunciated in 1954. I added five additional contemporary goals to the original five goals of the founders. Pursuant to the sub-theme of continuity, the present papers completes the task set forth in the prior paper by discussing how systems science in general, and ISSS in particular, can overcome the 10 challenges that confront us. Copyright © 2005 John Wiley & Sons, Ltd.
Effect Of Apertures On Gaussian Beams

ABSTRACT The theory of Gaussian beam propagation assumes a perfect, infinitely wide beam profile. In real life, when such beams pass through limiting apertures such as lenses, the profile is truncated. Even tiny amounts of truncation can have profound effects on subsequent beam parameters: clipping as little as one percent of the beam power, for example, can result in a ten percent divergence increase. Dark rings are created, and defocussing can create patterns with dark centers. For small truncation ratios (aperture/beam radius), the aperture is almost uniform and the focussed output approaches the traditional Airy disc pattern. In this paper, we will present a summary of the various truncation effects, with special attention to the most common case of a round aperture centered on a circularly symmetric beam. A computer program, based on one written at NASA, was used to generate plots of divergence versus truncation ratio for this case. Also discussed briefly are some of the possible deviations from circular symmetry: square beams and apertures, knife-edge obstructions, decentered apertures, and aberrations. Finally, the results reported by others have been summarized, with an extensive bibliography.
iTRAQ analysis of complex proteome alterations in 3xTgAD Alzheimer's mice: understanding the interface between physiology and disease.

Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with accumulation of amyloid β-peptide, synaptic degeneration and the death of neurons in the hippocampus, and temporal, parietal and frontal lobes of the cerebral cortex. Analysis of postmortem brain tissue from AD patients can provide information on molecular alterations present at the end of the disease process, but cannot discriminate between changes that are specifically involved in AD versus those that are simply a consequence of neuronal degeneration. Animal models of AD provide the opportunity to elucidate the molecular changes that occur in brain cells as the disease process is initiated and progresses. To this end, we used the 3xTgAD mouse model of AD to gain insight into the complex alterations in proteins that occur in the hippocampus and cortex in AD. The 3xTgAD mice express mutant presenilin-1, amyloid precursor protein and tau, and exhibit AD-like amyloid and tau pathology in the hippocampus and cortex, and associated cognitive impairment. Using the iTRAQ stable-isotope-based quantitative proteomic technique, we performed an in-depth proteomic analysis of hippocampal and cortical tissue from 16 month old 3xTgAD and non-transgenic control mice. We found that the most important groups of significantly altered proteins included those involved in synaptic plasticity, neurite outgrowth and microtubule dynamics. Our findings have elucidated some of the complex proteome changes that occur in a mouse model of AD, which could potentially illuminate novel therapeutic avenues for the treatment of AD and other neurodegenerative disorders.
A Radical Intermediate in Tyrosine Scission to the CO and CN− Ligands of FeFe Hydrogenase

The radical S -adenosylmethionine (SAM) enzyme HydG lyses free l-tyrosine to produce CO and CN − for the assembly of the catalytic H cluster of FeFe hydrogenase. We used electron paramagnetic resonance spectroscopy to detect and characterize HydG reaction intermediates generated with a set of 2 H, 13 C, and 15 N nuclear spin-labeled tyrosine substrates. We propose a detailed reaction mechanism in which the radical SAM reaction, initiated at an N-terminal 4Fe-4S cluster, generates a tyrosine radical bound to a C-terminal 4Fe-4S cluster. Heterolytic cleavage of this tyrosine radical at the C α -C β bond forms a transient 4-oxidobenzyl (4OB • ) radical and a dehydroglycine bound to the C-terminal 4Fe-4S cluster. Electron and proton transfer to this 4OB • radical forms p -cresol, with the conversion of this dehydroglycine ligand to Fe-bound CO and CN − , a key intermediate in the assembly of the 2Fe subunit of the H cluster.
Catalytically active supramolecular porphyrin boxes: acceleration of the methanolysis of phosphate triesters via a combination of increased local nucleophilicity and reactant encapsulation

Box-like tetrakis(metalloporphyrin) supramolecular assemblies possessing Zn and Al metal sites can catalyze the methanolysis of phosphate triesters with a high rate enhancement, up to 430 times faster than the uncatalyzed reaction. Mechanistic studies suggest that the observed rate enhancement can be attributed to a high local concentration of methoxide ion that operates in concert with a solvophobically driven encapsulation of substrates by the porphyrinic assembly.
Pharmacologic options available to treat symptomatic intradialytic hypotension

Treatment of symptomatic intradialytic hypotension (IDH) is a difficult task for the practicing nephrologist. Minimizing patient factors that precipitate IDH as well as dialysis procedure-related components that lower blood pressure are the initial approaches to this problem. However, despite these maneuvers, hypotension often persists in a group of high-risk patients. Pharmacologic interventions are often used to reduce IDH. Unfortunately, many of the available therapies are marginally effective and/or poorly tolerated. A few therapies appear to be efficacious and well tolerated-carnitine, sertraline, and midodrine. This article reviews the various pharmacologic therapies used for IDH and makes recommendations for treatment of this difficult problem.
Management of monocular congenital cataracts

Monocular congenital cataracts have been treated for the past two decades with early surgery, contact lens correction and patching of the unaffected eye. While an occasional patient has had a good visual outcome with this treatment regiment, the majority end up being legally blind in the aphakic eye. Intraocular lenses (IOLs) are increasingly being used as an alternative means of optically correcting aphakia during infancy. A growing body of literature suggests that an IOL correction is associated with an improved visual outcome and a relatively low incidence of post-operative complications. A monkey model has also been used to study the safety and feasibility of correcting aphakia in neonates with IOLs. These studies have revealed that the visual outcome is as good if not better with an IOL correction. A multi-centre clinical trial, the Infant Aphakia Treatment Study (IATS), is being organised in the United States to critically compare an IOL and contact lens correction for infantile aphakia.
Expression of matrix metalloproteinases during experimental Candida albicans keratitis.

Fungal infections of the eye are epidemiologically important diseases.1 Fungi such as Candida albicans that are commensals in the conjunctival flora2 3 can become pathogenic with ocular surface injury or dysfunction. Ophthalmic candidiasis is an opportunistic infection of the eye acquired through trauma, surgery, contact lens wear, and chronic keratopathy.4 A murine model of experimental keratitis using a human isolate of C. albicans to induce corneal infection is helpful in understanding the pathogenesis of oculomycosis.5 6 A key early event in posttraumatic C. albicans keratitis involves fungal morphogenesis and invasion that trigger inflammatory and wounding responses.7 We used this model to examine matrix metalloproteinases (MMPs) in the development of keratomycosis. MMPs are proteolytic enzymes involved in multiple physiological and pathologic processes. This family includes collagenases, gelatinases, stromelysins, and matrilysins that are grouped according to their structure and substrate and that are modulated, in part, by tissue inhibitors of metalloproteinases (TIMPs).8 TIMPs consist of a family of four glycoproteins that inhibit MMP activation or activity. TIMPs differ in their affinity for various MMPs; for example, TIMP-1 prevents activation of MMP-9 and can bind to the catalytic site of MMP-9 and other MMPs. Coordinated actions of MMPs and TIMPs are pivotal in maintaining structural homeostasis, and altered regulation disrupts connective tissue integrity through degradation of the extracellular matrix.9 Determining the roles of MMPs in infection and inflammation may lead to new opportunities for controlling corneal ulceration.10 Changes in MMPs occur after corneal trauma and during corneal infection.11 12 13 MMP-9 increases in acute Pseudomonas aeruginosa keratitis and potentiates the severity of bacterial keratitis by degrading corneal stroma and by stimulating the release of proinflammatory cytokines and chemokines that attract polymorphonuclear leukocytes.12 14 15 16 Studies of experimental and human fungal keratitis have also found increased levels of MMP-9 during corneal infection by yeasts and filamentous fungi.17 18 19 20 Hypothesizing that MMP-9 and other MMPs contribute to the initial manifestation of keratomycosis, we systematically examined the expression patterns of 18 MMPs and 4 TIMPs in murine C. albicans keratitis.
Nicotine alters the usual reciprocity between meal size and meal number in female rat.

Tobacco smoking reduces appetite and body weight (BW). Cessation of smoking leads to hyperphagia and weight gain. Daily food intake (FI) is a function of meal number (MN) and meal size (MZ), i.e., FI=MNxMZ. Under normal conditions, the female Fischer rat has a periodic reciprocal fluctuation between MZ and MN corresponding to phase of estrous cycle. Wide fluctuations between MZ and MN compensate each other to keep FI constant. Nicotine (5 mg/kg BW/day) was infused via osmotic minipump for 7 days. Controls received saline. FI, MZ, and MN were measured by an Automated Computerized Rat Eater Meter. Nicotine significantly decreased BW and FI via a decrease in MZ without compensatory increase of MN. Nicotine cessation led to hyperphagia, normalizing BW loss via an increase in MZ, which exceeded a compensatory decrease in MN. Nicotine significantly prolonged the estrous cycle by an extension of proestrous phase. Nicotine significantly lengthened the intermeal interval (IMI), delaying the start of the next meal and simultaneously decreasing subsequent MZ. Stopping nicotine led to normalization of IMI and MZ. Data show that nicotine alters the usual reciprocal regulation between MZ and MN and leads to a prolongation of the estrous cycle.
Sun-Care Product Advertising in Parenting Magazines: What Information Does It Provide About Sun Protection?

This study analyzed the content of sun-care product advertisements in five major U.S. parenting magazines with high circulation: Family Circle, Parents, Family Fun, Parenting (Early Years), and Parenting (School Years). The study examined what information sun-care product advertisements tell parents about skin cancer prevention and about sunscreen use for themselves or for their children based on the Health Belief Model concepts of perceived benefits and perceived barriers. Results showed that the most commonly mentioned benefit of the product was that it blocks ultraviolet A (UVA) and ultraviolet B (UVB) rays. One-third of the ads promoted the product's effectiveness in overcoming four of the barriers that prevent people from using sunscreens: eye irritation, skin irritation, an unpleasant smell, and the need to reapply sunscreen too often or after physical activity. However, only a few of the ads provided information about the consequences of unprotected sun exposure or mentioned methods of sun protecti...
Abstract 5389: Discovery of small molecule inhibitors of the interaction between PPARγ and SMRT

The gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) is a ligand-activated nuclear hormone receptor that plays central roles in regulating adipogenesis and maintaining lipid and glucose homeostasis. PPARγ is the molecular target for the thiazolidinedione (TZD) class of antidiabetic drugs. While clinically efficacious, the TZDs exhibit significant side effects that are mechanistically linked to PPARγ including weight gain, edema, and heart failure. SMRT (silencing mediator of retinoid acid and thyroid hormone receptor) and NCoR (nuclear receptor corepressor) are transcriptional corepressors that are critical for normal PPARγ function and act by repressing PPARγ-mediated transcriptional activity in the absence of agonist ligands. In order to explore an alternate method of activating PPARγ signaling, we designed a biochemical assay for the purpose of high-throughput screening (HTS) to identify inhibitors of the interaction between PPARγ and corepressors from our in-house library compounds (292K), which might act as pharmacological agonists. Herein, we report the use of this method to discover small molecule inhibitors of the corepressor interaction with PPARγ. Following hit validation and evaluation, we identified small molecule inhibitors acting through this novel mechanism that potently induce a cellular response similar to the known PPARγ agonist rosiglitazone. In addition, we also confirmed that our hit compound revealed induced adipogenesis in 3T3-L1 cell and reduced fat storage in C.elegans model. These findings highlight the potential of targeting the interaction of PPARγ and SMRT for the discovery of small molecule agonists of PPARγ. Citation Format: Jaeki Min, Ramy Naguib Attia, Leggy A Arnold, Kelly Teske, Michele Connelly, George Lemieux, Kaveh Ashrafi, Anang Shelat, R. Kiplin Guy. Discovery of small molecule inhibitors of the interaction between PPARγ and SMRT. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5389. doi:10.1158/1538-7445.AM2014-5389
On Approximate Nearest Neighbors under l∞ Norm

The nearest neighbor search (NNS) problem is the following: Given a set of n points P={p1, ?, pn} in some metric space X, preprocess P so as to efficiently answer queries which require finding a point in P closest to a query point q?X. The approximate nearest neighbor search (c-NNS) is a relaxation of NNS which allows to return any point within c times the distance to the nearest neighbor (called c-nearest neighbor). This problem is of major and growing importance to a variety of applications. In this paper, we give an algorithm for (4?log1+?log4d?+1)-NNS algorithm in ld∞ with O(dn1+?logO(1)n) storage and O(dlogO(1)n) query time. Moreover, we obtain an algorithm for 3-NNS for l∞ with nlogd+1 storage. The preprocessing time is close to linear in the size of the data structure. The algorithm can be also used (after simple modifications) to output the exact nearest neighbor in time bounded by O(dlogO(1)n) plus the number of (4?log1+?log4d?+1)-nearest neighbors of the query point. Building on this result, we also obtain an approximation algorithm for a general class of product metrics. Finally, we show that for any c<3 the c-NNS problem in l∞ is provably as hard as the subset query problem (also called the partial match problem). This indicates that obtaining a sublinear query time and subexponential (in d) space for c<3 might be hard.
Preparing Children for Surgery—an Integrative Research Review

ABSTRACT The purpose of this integrative research review was to determine the methodological and substantive characteristics of the research pertaining to preparation of children for surgery, examine pertinent research issues, and suggest recommendations for future research and practice. A total of 400 articles were reviewed using inclusion and exclusion criteria. Twenty-two studies, published between 1974 and 1995, met the criteria and, therefore, constituted the study corpus. The total sample comprised 1,263 subjects. Findings indicate that further research is needed to examine the efficacy of preparation strategies, address diverse populations, and include patient and parent involvement in the preparation process. AORN J 71(Feb 2000) 334–343.
EFFECTS OF CHOLINERGIC AND ANTICHOLINERGIC DRUGS ON THE SYNTHESIS OF SILK FIBROINS OF SPIDERS.

Abstract 1. 1. The rate of incorporation of C14-alanine into the silk fibroins of the spider (Araneus sericatus) was studied. Emptying the silk glands by pulling out the thread stimulates the gland to greater activity as measured by the rate of incorporation of alanine. 2. 2. Physostigmine, carbachol and paraoxon all increased the rate of incorporation of alanine to about the same extent as emptying the gland. It is therefore considered likely that the activation of this gland is under the control of a cholinergic mechanism. 3. 3. Attempts to depress the rate of synthesis with anticholinergic drugs were largely unsuccessful.
Unfolded state of polyalanine is a segmented polyproline II helix.

Definition of the unfolded state of proteins is essential for understanding their stability and folding on biological timescales. Here, we find that under near physiological conditions the configurational ensemble of the unfolded state of the simplest protein structure, polyalanine α-helix, cannot be described by the commonly used Flory random coil model, in which configurational probabilities are derived from conformational preferences of individual residues. We utilize novel effectively ergodic sampling algorithms in the presence of explicit aqueous solvation, and observe water-mediated formation of polyproline II helical (PII) structure in the natively unfolded state of polyalanine, and its facilitation of α-helix formation in longer peptides. The segmented PII helical coil preorganizes the unfolded state ensemble for folding pathway entry by reducing the conformational space available to the diffusive search. Thus, as much as half of the folding search in polyalanine is accomplished by preorganization of the unfolded state. Proteins 2004. © 2004 Wiley-Liss, Inc.
A generalized thermoelastic instability analysis

The onset of thermoelastic instability (TEI) is known to be directly related to the occurrence of hot spots in a variety of mechanical components such as brakes, seals and clutches. To gain some insight into this failure mechanism, an analytical model for both the symmetric and antisymmetric modes was developed to analyse a friction pair consisting of a conducting body of finite thickness rubbing against an insulating body in the presence of a lubricating agent. The effect of surface roughness, hydrodynamic pressure and viscous shear dissipation within the lubricating film is included in the formulation. The model provided in this paper is general and thus useful for investigating the TEI of a component at the design stage. Several new dimensionless parameters are introduced that allow one to characterize the behaviour of either dry or lubricated systems and their susceptibility to TEI.
UV light with oxygen treatment of phase shift photoblank for phase and transmission control: applicable to MxSi(1-x)OyN(y-1)

A method based on UV in air environment to improve the stability of the material of the photoreticles throughout cleans repeated over is suggested in this work. A typical aggressive clean was performed on two different Embedded Shifter materials, 193nm Molybdenum-Silicon-Oxy-Nitride (MoSiON) and 193nm Multilayer Silicon Nitride-Titanium Nitride (SiN-TiN). The variation of phase and transmission of each reticle is reported with the number of cleans. Given the appropriate exposure the phase and the transmission of the treated materials were significantly improved. All treated EAPSMs could stand cleans repeated over.