cssi/SciSciGPT-SciSciNet huggingface dataset:
Adenylosuccinate Synthetase 1 (ADSS1) gene is deleted in lung adenocarcinoma: A potential role in metabolic stress tolerance

2727 Molecular genetic studies have implicated human chromosome 14q32 and its orthologous region on mouse chromosome 12F2 as the site of a tumor suppressor gene. We performed high density deletion mapping of these regions in lung adenocarcinomas and identified the Adenylosuccinate Synthetase 1 (ADSS1) locus as the minimal site of homozygous deletion (HD). HDs of Adss1 were detected in 6 out of 13 (46%) mouse lung adenocarcinoma cell lines, and in 4 out of 43 (9.3%) mouse primary lung adenocarcinomas. Clonal HDs included the nearest flanking genes, Siva1 and Fh2bd, in 15% and 0% of the cell lines, respectively. Also, partial deletions (PD) of Adss1, including both hemizygous and sub-clonal homozygous losses, were detected in 24 out of 43 (56%) mouse primary lung adenocarcinomas, and in 6 out of 13 of the cell lines. In human lung adenocarcinomas and cell lines ADSS1 HDs occurred in 3 out of 24 (12.5%), and PDs in 10 out of 24 (42%) cases. Again less frequent deletion of nearest neighboring genes indicated that ADSS1 was the primary target of inactivation. ADSS1 is a key enzyme in the de novo synthesis of adenosine monophosphate (AMP), an essential cellular metabolite. An elevated ratio of AMP/ATP activates the cellular system for restricting energy use and suppressing tumor growth under metabolic stress conditions, such as hypoxia. Reduced AMP levels and increased tolerance to hypoxia was observed in immortalized lung epithelial cells following ADDS1 knock-down. Conversely, restoration of ADSS1 expression in lung adenocarcinoma cell lines increased cellular AMP production and stimulated apoptosis. These results suggest that ADSS1 inactivation disrupts the AMP-dependent response to metabolic stress, which favors tumor survival and growth under otherwise prohibitive metabolic conditions.
Aeroacoustics: Fan noise and control; Duct acoustics; Rotor noise

The recent progress in duct acoustic research is reflected by fourteen papers which cover essentially the areas of linear duct acoustics, the characteristics of absorbent materials, and nonlinear duct acoustics. With respect to propagation in ducts, emphasis is placed on computational methods aimed at attaining effective economical modeling of propagation in variable-geometry and in hard-wall or soft-wall ducts. Computational methods developed to reduce computer processing and storage requirements are outlined, along with a wave envelope technique for reducing processing and storage needs. The latter technique is applied to the optimum segmented acoustic duct linear design. A finite difference technique is used in combination with conformal mapping to compute the optimum multisection duct linear design.
The Solar System Beyond The Planets

The Kuiper belt contains a vast number of objects in a flattened, ring-like volume beyond the orbit of Neptune. These objects are collisionally processed relics from the accretion disk of the Sun and, as such, they can reveal much about early conditions in the Solar system. At the cryogenic temperatures prevailing beyond Neptune, volatile ices have been able to survive since the formation epoch 4.5 Gyr ago. The Kuiper belt is the source of the Centaurs and the Jupiter-family comets. It is also a local analogue of the dust disks present around some nearby main-sequence stars. While most Kuiper belt objects are small, roughly a dozen known examples have diameters of order 1000 km or more, including Pluto and the recently discovered (and possibly larger) giant Kuiper belt objects 2003 UB313, 2003 EL61 (a binary and a triple system, resp.) and 2005 FY9.
Enhancing economic literacy of classroom teachers

For the past two summers, the Division of Education and the Division of Business and Economics at Indiana University at Kokomo have collaborated to produce an intense teamtaught summer economics course for pre-service education majors and in-service classroom teachers. The dual emphasis on content and application allows economics to integrate every aspect of the classroom and allows Praxis achievement. This paper explores the essential nature of Praxis in making the content or practice link—so critical for successful implementation of economics in K-12 classrooms. To determine their attitudes toward and knowledge of economics education, a pretest and post-test format was adopted. In addition, the institutional enhancers and inhibitors that dramatically affected the development and implementation of the new course of study are presented.
All-optical clock recovery and regeneration

In this paper we will present ultrafast all-optical clock recovery up to 100 Gb/s using two-section gain-coupled DFB lasers. Both the coherent and incoherent schemes will be described. The two-section DFB laser can be used in combination with semiconductor optical amplifier so that clock recovery for both the RZ and NRZ formats can be achieved. For the RZ format, the sensitivity of clock recovery is 50 ?W, the jitter is less than 1 ps at 40 Gb/s. We use parametric amplification for all-optical regeneration. Extinction ratio improvement over 11 dB has been achieved.
Enrichments and enhancements for older adults beyond the classroom

Attending college is most often associated with the young, but the number of college programs for older adults continues to increase as the growing number of older learners discover the benefits of pursuing educational study. The following article by Barbara R. Ginsberg demonstrates how one community college campus enriches and enhances the lives of older adults in an academic setting.
INTERACTION OF WARFARIN STEREOISOMERS WITH HUMAN ALBUMIN

Edward M. Sellers,2M.D. , Ph.D., Jan Koch-Weser, M.D. Clinical Institute, Addiction Research Foundation, Toronto, and Departments of Medicine and Pharmacology, Harvard Medical School and the Clinical Pharmacology Unit, Massachusetts General Hospital, Boston, Mass., U.S.A. Received 5 May 1975 In the ra?? S(-) warfarin has approximately six times the hypoprothrombinemic acticity of R(+) warfarin. (Breckenridge and Orme, 1972). In man S(-) warfarin is 3.4 times more potent than R(+) warfarin. (O'Reilly 1969, O'Reilly 1974). One simple explanation of this difference in potency would be a lesser degree of S isomer binding to human albumin with higher free concentrations of S available at the site of action. A precedent for differences in isomer binding exists. (Karush 1952). Rat-warfarin is highly bound to human albumin. (O'Reilly 1967, 1969). Results of previous binding studies did not resolve the question of whether there is a difference in the isomer binding of warfarin to human albumin since the results were obtained at pH 10.0 and 27'C and no statistical analysis was applied. (O'l'eilly 1969, O'Reilly 1971). An unexplained aspect of the results was that the calculated standard free energies (&Fe,) for the R (-7.28 kcal/mole) and S (-7.39 kcal/mole) isomers were lower than reported for the racpreparation (-7.16 kcal/mole) (O'Reilly 1969). Our experiments were performed to determine if there are differences in R and S isomers binding and indicate that the binding of S(-) warfain to human album is significantly greater than for the R(+) isomer.
Workshop examines warming of lakes worldwide

First Global Lake Temperature Collaboration (GLTC) Workshop; Lincoln, Nebraska, 1–5 June 2012 It is widely recognized that climate change is affecting terrestrial and aquatic ecosystems. Recent studies have revealed significant warming of lakes throughout the world, and this rate of warming is often larger than that of the ambient air temperature (up to 2–3 times more rapid). Although hypotheses have been proposed to explain these high rates of lake warming (e.g., ice albedo feedbacks or changes in cloud cover), the fundamental drivers remain poorly understood. Furthermore, these rapid warming rates have profound implications for lake hydrodynamics, productivity, and biotic communities. It is essential therefore that global data sets of water temperature be compiled to monitor and understand these long-term changes in lakes, reservoirs, and other inland water bodies.
Integrin regulation of polymorphonuclear leukocyte apoxis during hypoxia is primarily dependent on very late activation antigens 3 and 5

Abstract Background. Apoptosis is thought to be a central mechanism that leads to resolution of the inflammatory response. The regulation of polymorphonuclear leukocyte (PMN) apoptosis during hypoxia has not been previously characterized, and we hypothesized that integrin signaling by matrix proteins (laminin) would regulate PMN apoptosis. Methods. PMNs at 1 × 105/ml were adhered on plastic or laminin for 12 hours during normoxia or hypoxia. Apoptosis was determined both by cellular histologic evaluation and the TUNEL assays (Tdt). Phagocytosis in apoptotic PMNs was determined with two-color flow cytometric analyses with rhodamine-labeled heat-killed Escherichia coli (511 nm) and the Tdt reagent (563 nm). Western blot analyses were performed on nine apoptotic regulatory proteins with monoclonal antibodies directed against each protein, and tyrosine phosphorylation was assessed after integrin receptor cross-linkage. Results. Adherence of PMNs to laminin reduced apoptosis by cellular histologic evaluation and the Tdt method (% apoptosis = 19 ± 1.0 versus 63 ± 4.2 by histologic evaluation, 38 ± 3.8 versus 60 ± 10.5 by flow cytometry ± adherence to laminin). Apoptosis-positive PMNs exhibited significantly greater phagocytosis than apoptosis-negative PMNs ± laminin. Western blot analyses demonstrated increased p53 expression after 2 and 4 hours of hypoxia. Cross-linkage of very late activation antigen-3 ( α 3 β 1 ) resulted in the phosphorylation of 53 kd, 44 kd, and 39 kd proteins at 30 seconds. Conclusions. (1) Chemotaxis of PMNs into the interstitium during hypoxia not only provides a means of ensuring PMN-pathogen contact but also provides a mechanism for improved survival by reducing apoptosis. (2) The reduction of apoptosis is mediated primarily by very late activation antigen-3, which leads to a subsequent increase in the intracellular expression of p53 and increased bacterial phagocytosis.
Within‐ and across‐language acoustic variability of vowels spoken in different phonetic and prosodic contexts: American English, North German, and Parisian French

This project investigates the acoustic variability of vowels produced in multisyllabic nonsense words /cvC1VC2(v)/ in carrier sentences by speakers of American English (AE), Parisian French (PF), and North German (NG). Variables under examination are (1) immediate phonetic context (C1=b,d; C2=b,d,p,t), (2) sentence prominence (narrow focus versus postfocus), and speaking rate (normal vs rapid). Preliminary results show that for AE vowels, phonetic context produces large differences (2–3 bark) in midpoint F2 values for mid‐to‐high back vowels, reflecting allophonic fronting of these vowels in alveolar context. Much smaller increases in F2 (∼1 bark) were found for both PF and NG mid/high back vowels in alveolar contexts. Most AE speakers showed little or no effect of sentence focus or speaking rate on the degree of fronting of back vowels in alveolar context. PF speakers produced more fronted mid/high back vowels in postfocused context than did NG and AE speakers. NG and PF speakers showed relatively greater F1 undershoot in low vowels in postfocus context than for AE speakers. These within‐ and across‐language differences in the effect of prosodic and phonetic context on vowel acoustics reflect both language‐universal constraints and language‐specific rules for contextual warping of vowel spaces.
Distinct myogenic programs of embryonic and fetal mouse muscle cells: Expression of the perinatal myosin heavy chain isoform in vitro

Early embryonic and late fetal mouse myogenic cells showed distinct patterns of perinatal myosin heavy chain (MHC) isoform expression upon differentiation in vitro. In cultures of somite or limb muscle cells isolated from Day 9 to Day 12 embryos, differentiated cells that expressed perinatal MHC were rare and perinatal MHC was not detectable by immunoblotting. In cultures of limb muscle cells isolated from Day 13 to Day 18 fetuses, in contrast, the perinatal MHC isoform was easily detected and was expressed in a substantial percentage of myocytes and myotubes. Analyses of clonally derived muscle colonies and cytosine arabinoside-treated fetal muscle cell cultures suggested that different fetal muscle cell nuclei initiated perinatal MHC expression at different times. In both embryonic and fetal cell cultures, the embryonic MHC isoform was expressed by all differentiated cells examined. A small number of myotubes in fetal muscle cell cultures showed a mosaic distribution of MHC isoform accumulation in which the perinatal MHC isoform accumulated in a restricted region of the myotube near particular nuclei, whereas the embryonic MHC isoform accumulated throughout the myotube. Thus, the myogenic program of fetal, but not embryonic, mouse myogenic cells includes expression of the perinatal MHC isoform upon differentiation in culture.
The Use of Anabolic Steroids as a Strategy in Reversing Denervation Atrophy after Delayed Nerve Repair

Background Denervation atrophy is one factor contributing to suboptimal motor recovery following major nerve repair. The hypertrophic effects of anabolic steroids may have a potential role in improving reinnervated muscle strength after delayed repair.
Development and evaluation of reverse polyethylene samplers for marine phase ii whole‐sediment toxicity identification evaluations

Marine and estuarine sediments accumulate contaminants and act as a sink for a wide range of toxic chemicals. As a result, the sediments themselves can become a source of contamination. At sufficient levels, contaminated sediments can cause benthic impairments and toxicity to marine organisms. Among the wide range of contaminants, nonionic organic contaminants (NOCs) are a primary cause of toxicity in marine sediments. Toxicity identification evaluations (TIEs) are used to characterize and identify chemicals causing toxicity in effluents, interstitial waters, and whole sediments using whole-organism endpoints. Phase I whole-sediment TIE methods for NOCs exist, but the development of phase II TIE methods for NOCs is a current research challenge. In the present study, the use of reverse polyethylene samplers (RePES) for phase II methods is examined. Various RePES designs were evaluated in an experimental design study with NOC chemical solutions. Based on equilibration time and proximity of measured NOC water concentrations in the reconstituted system to theoretical concentrations, a nontriolein design with loading of chemical solutions on the inside of the polyethylene tubing was chosen as most effective. A partitioning study demonstrated NOCs partitioned between the RePES and water as well as between the water and air, as expected using this nontriolein RePES design. Finally, a sediment toxicity study comparing the nontriolein RePES to contaminant-spiked sediments was conducted. The nontriolein RePES design was capable of successfully recreating the toxicity and water concentrations observed with the intact sediments.
FURTHER EVIDENCE FOR PARAPHYLY OF THE FORMICARIIDAE (PASSERIFORMES)

Abstract The historical relationships of ground antbirds and their relatives have long been unresolved. Here, I present a phylogenetic analysis of ground antbird (Formicariidae) relationships based on DNA sequence data from the cytochrome-b and ND2 genes. Results support novel hypotheses of historical relationships, including two revisions of suboscine taxonomy: (1) paraphyly of the Formicariidae with the tentative inclusion of at least some rhinocryptids (Liosceles, Rhinocrypta, and Scytalopus) in the ground antbird lineage, and (2) placement of Pittasoma with Conopophaga in the Conopophagidae.
Polynomial functions that preserve commuting pairs of matrices

(1977). Polynomial functions that preserve commuting pairs of matrices. Linear and Multilinear Algebra: Vol. 5, No. 2, pp. 87-90.
Interaction between glycogen and glycogen phosphorylase of Tetrahymena.

Abstract The glycogen phosphorylase of Tetrahymena pyriformis complexes with glycogen as judged by its elution pattern from columns of Sepharose 6B. Complex formation does not occur with starch, amylose, or amylopectin, and neither do these polyglucans serve as primers for the enzyme. To study the association between the phosphorylase and glycogen particles in situ, Tetrahymena were grown under differing physiological conditions, phosphorylase was isolated and chromatographed on a Sepharose 6B column. Phosphorylase activity isolated from cells grown in the absence of glucose was only partially associated with glycogen, while in cells exposed to glucose for 30 min or more all the phosphorylase activity was associated with glycogen. The effects of culture age and anaerobiosis on the relative amounts of free and glycogen-bound enzyme in the cells were also studied. It was concluded from the in vivo experiments that there was no simple relation between the fraction of enzyme bound to glycogen and between cell glycogen content.
Use of a simple symptom questionnaire to predict Barrett's esophagus in patients with symptoms of gastroesophageal reflux.

Use of a simple symptom questionnaire to predict Barrett's esophagus in patients with symptoms of gastroesophageal reflux
Extracellular perfusion of rat brain nuclei using microdialysis: a method for studying differential neurotransmitter release in response to neurotoxins.

Abstract Microdialysis probes, stereotactically placed in rat brain nuclei, allow detailed kinetic comparisons of neurotransmitter release from in situ chemical lesioning over a continuum from acute early changes (minutes) to chronic late changes (days). This technique insures a localized mechanism of action independent of systemic effects apparent with other routes of administration and independent of mechanical damage patterns encountered in conventional chemical lesioning. The example provided compares changes in extracellular γ-aminobutyric acid (GABA) concentrations in the striatum in response to quinolinic acid (QA, 0.24 M) and 3-nitropropionic acid (3-NPA, 0.25 M). These examples of chemical lesioning represent two theoretical mechanisms of neurodeterioration in Huntington's disease, QA representing the excitotoxic component, and 3-NPA representing the impaired mitochondrial energy component [M.F. Beal, N.W. Kowall, D.W. Ellison, M.F. Mazurek, K.J. Swartz, J.M. Martin, Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid, Nature 321 (1986) 168–171; M.F. Beal, E. Brouillet, B.G. Jenkins, R.J. Ferrante, N.W. Kowall, J.M. Miller, E. Storey, R. Srivastava, B.R. Rosen, B.T. Hyman, Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci. 13 (1993) 4181–4192; N.C. Reynolds, W. Lin, C.M. Cameron, D.L. Roerig, Differential responses of extracellular GABA to intrastriatal perfusions of 3-nitropropionic acid and quinolinic acid in the rat, Brain Res. 778 (1997) 140–149]. An auxillary microdialysis probe implanted in the ipsilateral nucleus accumbens is used to define the physiologic extent of the cytotoxic lesion. Pre-column derivatization of perfusate fractions with o-phthalaldehyde/t-butylthiol (OPA) provides electroactivity to the OPA-GABA conjugate and facilitates electrochemical detection following high performance liquid chromatography [J.M. Peinado, K.T. McManus, R.B. Myers, Rapid method for microanalysis of endogenous amino acid neurotransmitters in brain perfusates in the rat by isocratic HPLC-EC, J. Neurosci. Methods 18 (1986) 269–276]. Theme: Disorders of the nervous system Topic: Degenerative disease: other
The mechanism of photohydrosilylation on silicon and porous silicon surfaces.

Visible or UV light activates H-terminated Si surfaces because of the presence of a photogenerated hole in a Si–Si back-bond. Enhancing the lifetime of this hole at the surface increases reactivity. On the basis of photodynamics and electron transfer theory, the prevalence of two mechanisms of photoactivation (internal photoemission versus interband photoexcitation followed by electron transfer) are explored. To act as an effective trap, an acceptor state for the excited electron must either be populated directly by photoexcitation or the state must lie in a band gap (or both). It is predicted that oxidants with a properly positioned acceptor level will enhance the reactivity of porous silicon or silicon nanocrystals in a size selective manner.
Chronic administration of transforming growth factor‐beta suppresses erythropoietin‐dependent erythropoiesis and induces tumour necrosis factor in vivo

Transforming growth factor beta is a known inhibitor of the proliferation and differentiation of early haematopoietic progenitors but has no effect on mature erythroid cells in vitro. Mice injected with rhTGF beta 1 exhibited severe and progressive suppression of erythropoiesis manifested by a decline of reticulocyte count, marrow erythroblasts and marrow and spleen CFU-E, which could be prevented by administration of erythropoietin. This suppression of erythropoiesis was associated with the appearance of tumour necrosis factor in the blood, development of pronounced cachexia and depression of serum erythropoietin levels. TGF beta induces TNF in vivo that leads to cachexia, decrease of serum erythropoietin levels and suppression of erythropoietin dependent erythropoiesis.
Gaining Access to One's Children: An Evaluation of a Visitation Program for Noncustodial Parents

Children born out of wedlock often suffer due to infrequent and limited interaction with the noncustodial parent. To address this issue, progams have been developed at the federal and state level t...
The laminar source of efferent projections from the avian Wulst

Abstract Following horseradish peroxidase injections into the pigeon tractus septomesencephalicus, the efferent outflow bundle of the avian Wulst, retrogradely labeled neurons within the Wulst were confined to the superficialmost layer, the hypertriatum accessorium. These results suggest that the hyperstriatum accessorium is the source of Wulst efferent projections. In similarity to the laminar organization of mammalian striate cortex, this efferent layer is juxtaposed to the thalamorecipient layer of Wulst.
CUEING THE CONSUMER: THE ROLE OF SALIENT CUES IN CONSUMER PERCEPTION

Consumers buy what they perceive, and what they perceive is heavily influenced by the cues — brand name, packaging, color — that marketers send to them. This article reports on an empirical study that demonstrates the influence of color in cueing consumers to the taste of pudding. Vanilla pudding, colored to look like chocolate pudding, was perceived by consumers as tasting like chocolate pudding. The results indicate that color is a more influential cue than taste in the consumers' perception of the flavor of the pudding.
Fast (3 Hz and 10 Hz) and slow (respiratory) rhythms in cervical sympathetic nerve and unit discharges of the cat.

1In seven decerebrate cats, recordings were taken from the preganglionic cervical sympathetic (CSy) nerves and from 74 individual CSy fibres. Correlation and spectral analyses showed that nerve and fibre discharges had several types of rhythm that were coherent (correlated) between population and unit activity: respiratory, ‘3 Hz’ (2–6 Hz, usually cardiac related), and ‘10 Hz’ (7–13 Hz). 2Almost all units (73/74) had respiratory modulation of their discharge, either phasic (firing during only one phase) or tonic (firing during both the inspiratory (I) and expiratory (E) phases). The most common pattern consisted of tonic I-modulated firing. When the vagi were intact, lung afferent input during I greatly reduced CSy unit and nerve discharge, as evaluated by the no-inflation test. 3The incidence of unit-nerve coherent fast rhythms (3 Hz or 10 Hz ranges) depended on unit discharge pattern: they were present in an appreciable fraction (30/58 or 52 %) of tonic units, but in only a small fraction (2/15 or 13 %) of phasic units. 4When baroreceptor innervation (aortic depressor amd carotid sinus nerves) was intact, rhythms correlated to the cardiac cycle frequency were found in 20/34 (59 %) of units. The cardiac origin of these rhythms was confirmed by residual autospectral and partial coherence analysis and by their absence after baroreceptor denervation. 5The 10 Hz coherent rhythm was found in 7/34 units when baroreceptor innervation was intact, where it co-existed with the cardiac-locked rhythm; after barodenervation it was found in 9/50 neurones. Where both rhythms were present, the 10 Hz component was sometimes synchronized in a 3:1 ratio to the 3 Hz (cardiac-related) frequency component. 6The tonic and phasic CSy units seem to form distinct populations, as indicated by the differential responses to cardiac-related afferent inputs when baroreceptor innervation is intact. The high incidence of cardiac-related correlation found among tonic units suggests that they are involved in vasomotor regulation. The high incidence of respiratory modulation of discharge suggests that the CSy units may be involved in regulation of the nasal vasculature and consequent ventilation-related control of nasal airway resistance.
Fuzzy multiple level programming

The use of fuzzy set concept to overcome the computational difficulties of multi-level optimization for large systems appears to be a powerful approach and can solve practical large problems in a very simplified manner. Furthermore, unlike the duo-ploy or multi-ploy approaches, the proposed interactive concept provides flexibility, which is essential due to the different styles of management in different organizations. The approach is formulated based on exploring the fuzziness or indefiniteness, which is almost always present in a decentralized large hierarchy organization. The advantage of this approach is that, not only the problem is much more simplified for solution purposes, the original problem is also much more realistically represented.
Herpes simplex virus: a histopathologic study of the depth of herpetic wounds.

Background Herpes is a prevalent, infectious disease that can occur anywhere on the body; it is found primarily on the face and genitalia. Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are the DNA viruses that cause human herpes. Clinically, HSV-1 and HSV-2 infections produce lesions generally located on the mucocutaneous junctions of the face and genitalia. At times, vesicular lesions may ulcerate, leaving recalcitrant wounds that are challenging to treat. Until now, the basis of treatment has been related to the eradication of the viral infection. Little attention has focused on the consequence of the viral infection and the resulting wounds, specifically whether this represents an epidermal or dermal injury. Methods Using 10 herpetic lesions from different individuals, we studied the depth of the injury via routine hematoxylin and eosin stains, as well as periodic acid–Schiff (PAS) and type IV collagen stains, which demonstrate the presence of the basement membrane. Results In all cases, we found an inflammatory infiltrate in the dermis and selective disruption of the basement membrane. Conclusion This suggests that herpetic lesions involve the dermis and are best classified as partial-thickness wounds.
The X-Face: An improved planar passive mechanical connector for modular self-reconfigurable robots

There is a need in the field of modular robotics for a low-profile docking face with a wide range of performance. Mechanical self-aligning geometry features for docking faces of modular reconfigurable robot systems can be varied to improve the reliability of connection systems. This paper presents a new two-layer mating face design for robots that are constrained to move in a plane. It has a provably larger area of acceptance than any to date. We present an analysis of both position and orientation misalignments with simulated results over a two parameter design space comparing this connector with two other best-in-class shapes. The results show an average acceptance area increase approximately 88% over gendered mating faces and approximately 138% over non-gendered mating faces.
Mechanistic Studies of the Biosynthesis of 3,6‐Dideoxysugars in Bacteria: Exploration of a Novel C‐O Bond Cleavage Event

Deoxy sugars are ubiquitous in nature and contribute to diverse biological activities. Attempts to design systems to control or to mimic their functions are hampered, however, by the lack of biosynthetic knowledge of these unique sugars. To elucidate the mechanism by which the sugar deoxygenation is effected, we have initiated a study to explore the biosynthesis of CDP-ascarylose, a 3,6-dideoxyhexose found in the lipopolysaccharides of Yersinia pseudotuberculosis, and our initial focus centered on C-3 deoxygenation catalyzed by E1 and E3. We have now purified the wild-type enzymes, cloned the corresponding genes (ascC for E1 and ascD for E3), and overexpressed the gene products in Escherichia coli. The purified E3 is a flavoprotein comprising an iron-sulfur center and E1 is an iron-sulfur containing, pyridoxamine 5′-phosphate-de-pendent enzyme. Since these iron-sulfur clusters are well known one-electron carriers, reactions mediated by E1 and E3 must proceed via a radical mechanism. Recently, EPR analysis of E1/E3 catalysis indicated a potential new redox role for pyridoxamine as a cofactor. These findings make this system unique from two perspectives: E1 is the only coenzyme B6-dependent catalyst that interacts with a sugar and not with an amino acid, and it is the first example in which coenzyme B6 may facilitate one-electron redox chemistry. Thus, the unprecedented mechanisms of E1 and E3 distinguish this system as a novel radical deoxygenation with potentially interesting future developments.
The morphosyntax of mood in early grammar with special reference to Swahili

In this paper we explore the development of the morphosyntax-semantics interface by comparing development in 4 typologically diverse languages: Dutch (a Germanic V2 language), Greek, Italian (a Romance pro-drop language) and Swahili (a Bantu language), with particular emphasis on Swahili, a relatively understudied language whose morphosyntactic structure is particularly relevant to the questions we address. We show that children acquiring these different languages all adhere to a morphosyntax-semantics mapping principle that forces a complementarity between the expression of mood and the expression of tense n the Semantic Opposition Hypothesis (SOH), following Hyams (2002). Our findings support the hypothesis that linguistic development is guided by universal principles which lie at the interface of semantico-conceptual structure and morphosyntax.
PI3K/Akt responses to oxytocin stimulation in Caco2BB gut cells.

Recently, we discovered oxytocin receptor (OTR) expression in the developing gut villus epithelium that emerges in villus-crypt junctions after weaning. Oxytocin (OT) and OTR regulate many physiological functions in various tissues; however, their function in gut epithelium is unknown. We explored responses of PI3K and Akt phosphoisoforms to OT stimuli in the Caco2BB human gut cell line. In Caco2BB cells, PI3K and pAkt levels peaked at 62.5 nM OT. At higher concentrations, PI3K decreased more gradually than pAkt(S473) suggesting that the pAkt(S473) response is separate from PI3K. At ≤7.8 nM OT, pAkt(T308) increased while pAkt(S473) decreased. Using a specific OTR antagonist, we demonstrated that responses of pAkt(T308) to OT depend on OTR in contrast to the partial OTR-dependence of the pAkt(S473) response. Differential pAkt phosphoisoform responses included pAkt phosphoserine 473 persistently free of phosphothreonine 308. The reduction in PI3K after 62.5 nM OT for 30 min coincided with OTR internalization. The PI3K/Akt activation profile was somewhat different in other cell lines (MCF-7 breast cancer cells, HT29 gut cells), which have PI3K activating mutations, that were examined to establish experimental parameters. In Caco2BB cells, the divergent effects of OT upon pAkt phosphoisoforms suggests separate sub-pathways; pAkt (T308) activation depends on OTR via the PI3K pathway and pAkt(S473) presumably results from its specific kinase mTORC2 (mammalian target of rapamycin complex 2). Thus, OT may modulate gut cell functions downstream of mTOR complexes (e.g., translation control as suggested by others in uterine cells). We will next explore OT-stimulated kinase activities downstream of mTOR related to pAkt phosphoisoforms.
Beauty and Charisma: A Comment on A. Schweitzer's ‘Theory of Political Charisma’

A charismatic leader is like a beautiful woman. Taken as a whole and looked on from afar we can all agree as to the extraordinary nature of the creature. Yet once we begin a detailed analysis of each part we find we have difficulty pointing to exactly those elements that produce the effect. Clinical descriptions may incline us to lust or disgust, but they may fail to inform us as to the ephemeral nature of the phenomenon. For that we often engage, as here, in metaphor. For charisma to become a useful concept for historical and sociological study, however, it must have more than metaphorical meaning. The purpose of this brief comment is not to pursue this need in the intricate detail the concept deserves. That task falls to Professor Schweitzer. Rather this comment will discuss some difficulties with the study of a concept like charisma which are highlighted by Professor Schweitzer's study. First we must ask what are we to study when studying charisma? As Professor Schweitzer observes, whatever else charisma is, it is not solely an attribute of a person. Without a following we may have a genius, a seer or even a saint, but we do not have a charismatic leader. Thus the greatest historical charismatic leader of all can at the last moment (or at what appeared to be the last moment) be abandoned and left alone by his followers. Only what, by all standards, was an extraordinary deed brought them back.
A Lifted Linear Programming Branch-and-Bound Algorithm for Mixed-Integer Conic Quadratic Programs

This paper develops a linear-programming-based branch-and-bound algorithm for mixed-integer conic quadratic programs. The algorithm is based on a known higher-dimensional or lifted polyhedral relaxation of conic quadratic constraints. The algorithm is different from other linear-programming-based branch-and-bound algorithms for mixed-integer nonlinear programs in that it is not based on cuts from gradient inequalities and it sometimes branches on integer feasible solutions. The algorithm is tested on a series of portfolio optimization problems. It is shown that it significantly outperforms commercial and open-source solvers based on both linear and nonlinear relaxations.
Production of single heavy charged leptons at a linear collider

A sequential fourth generation of quarks and leptons is allowed by precision electroweak constraints if the mass splitting between the heavy quarks is between 50 and 80 GeV. Although heavy quarks can be easily detected at the LHC, it is very difficult to detect a sequential heavy charged lepton, $L$, due to large backgrounds. Should the $L$ mass be above 250 GeV, it cannot be pair-produced at a 500 GeV ILC. We calculate the cross section for the one-loop process ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}L\ensuremath{\tau}$. Although the cross section is small, it may be detectable. We also consider contributions from the two-Higgs doublet model and the Randall-Sundrum model, in which case the cross section can be substantially higher.
Clinical and biochemical aspects of primary and secondary hyperammonemic disorders

An increased concentration of ammonia is a non-specific laboratory sign indicating the presence of potentially toxic free ammonia that is not normally removed. This does occur in many different conditions for which hyperammonemia is a surrogate marker. Hyperammonemia can occur due to increased production or impaired detoxification of ammonia and should, if associated with clinical symptoms, be regarded as an emergency. The conditions can be classified into primary or secondary hyperammonemias depending on the underlying pathophysiology. If the urea cycle is directly affected by a defect of any of the involved enzymes or transporters, this results in primary hyperammonemia. If however the function of the urea cycle is inhibited by toxic metabolites or by substrate deficiencies, the situation is described as secondary hyperammonemia. For removal of ammonia, mammals require the action of glutamine synthetase in addition to the urea cycle, in order to ensure lowering of plasma ammonia concentrations to the normal range. Independent of its etiology, hyperammonemia may result in irreversible brain damage if not treated early and thoroughly. Thus, early recognition of a hyperammonemic state and immediate initiation of the specific management are of utmost importance. The main prognostic factors are, irrespective of the underlying cause, the duration of the hyperammonemic coma and the extent of ammonia accumulation. This paper will discuss the biochemical background of primary and secondary hyperammonemia and will give an overview of the various underlying conditions including a brief clinical outline and information on the genetic backgrounds.
EDS: A reduced package for exterior differential systems

Abstract The EDS package for symbolic analysis of differential equations using the geometrical approach of exterior differential systems is described. The package implements much of exterior differential systems theory, including prolongation and involution analysis, and has been optimised for large, nonlinear problems. Besides the description of the facilities in the package, two nontrivial sample calculations arising from relativity are presented.
Structural sensitivity analysis in design synthesis

Abstract Structural sensitivity analysis is an analysis procedure developed for use in process structural synthesis (flow sheet synthesis). The primary problem treated is that of determining, without reoptimizing the modified system, whether a feasible structural modification (generated automatically by a computer or manually by an engineer) to a given feasible structure appreciates return. The method proposed is to generate alternately dual (using generalized dual bounding procedures) and primal bounds for the modified system until a decision is possible on the value of the modification. Based on this approach, the paper presents a strategy which fully exploits dual bounding information to select the best of several proposed modifications at each step in the synthesis of a process flow sheet. Thus it is a local procedure for use in synthesis. It is demonstrated on three heat exchanger network synthesis problems.
Abstract 909: ErbB-2 restricts Mib-1 and Jagged-1 association to inhibit Notch-1 activation in ErbB-2 positive breast cancer

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL We have recently published that Notch could be an important target in recurrent, or possibly trastuzumab resistant, ErbB-2-positive breast cancer to prevent disease progression. Coincidentally, co-overexpression of Notch-1 ligand, Jagged-1, in breast cancer have been associated with the poorest overall survival. Preliminary results from our lab demonstrated that trastuzumab or lapatinib treatment of SKBr3 cells increased Jagged-1 protein expression by Flow Cytometry. Cell surface biotinylation assays showed that Jagged-1 was enriched on the cell surface in response to trastuzumab treatment and this was mimicked by expression of K44A Dynamin. The precise role of Jagged-1 in ErbB-2-mediated inhibition of Notch-1 is not yet known. The results showed that a combined inhibition of Jagged-1 by siRNA and ErbB-2 by trastuzumab, inhibited cell proliferation and induced apoptosis in 95% of SKBR3 cells. Thus, we asked what is the molecular mechanism by which ErbB-2 inhibits Notch activity. Specifically, ErbB-2 inhibited the association of Mib1, an E3 ubiquitin ligase that is necessary for Notch activation, with Jagged-1 and this was reversed in response to trastuzumab or lapatanib. Recent evidence suggests that ErbB-2 activates PKC∈ and that PKC∈ is critical for ErbB-2-mediated cancer cell invasion. We observed that ErbB-2 increased the amount of PKC∈ found in a complex with Jagged-1. This result suggests that PKC may phosphorylate Jagged-1 or other associated proteins to restrict Jagged-1/Mib1 interaction and thus restrict Notch activation. Interestingly, we identified a substrate of PKC∈ kinase activity, approximately 100 kDa, which was in a complex with Jagged-1 in response to lapatinib treatment. Taken together, these results suggest a possible the role for PKC∈ in ErbB-2-mediated suppression of Notch-1 activity by inhibiting the ability of Jagged-1 to interact with Mib-1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 909. doi:1538-7445.AM2012-909
Communicating Results of All Radiologic Examinations Directly to Patients: Has the Time Come?

riting in Radiology 41 years ago, New York radiologist Robert Sherman [1] prophetically observed that radiologists “can do an injustice to the patient by withholding our superior knowledge.” Asking rhetorically “Is it not really the patient we are obligated to serve above all others?” Sherman pointed out that it is the “radiologist who is legally and ethically responsible to [patients]...for their diagnosis.” Five months later, North Carolina radiologist William Sprunt [2] retorted that a “personal relationship between a patient and his doctor...cannot be satisfactorily developed in diagnostic radiology,” and that radiologists “are not required to listen to prolonged descriptions of vague symptoms and systems reviews nor to make complete physical examinations. Anyone who wants to do these things should be something other than a radiologist.” A decade later, Berlin [3] described two unrelated medical malpractice lawsuits filed against Chicago-area radiologists, each alleging negligence because the radiologist had failed to directly inform a patient of the results of his or her radiologic examination. “Because the responsibilities of radiologists have expanded,” suggested Berlin, “it seems possible that radiologists may eventually be charged with directly informing patients of the results of procedures as well.” Exactly 13 years later, writing in the April 1990 issue of the ACR [American College of Radiology] Bulletin, Wyoming radiologist and member of the ACR Professional Liability Data Collection Committee Steven Liston [4] called the radiology community’s attention to a type of litigation that until that time had received little notice: A new kind of legal action against radiologists seems to be emerging. It has been claimed that radiologists who find a cancer are at fault for failing to assure proper communication of their diagnoses.... Damage awards were made because the radiologist did not effectively communicate a finding...or because effective communication was not documented in a permanent record.... In the cases we have seen, the radiologist was held responsible for assuring the report of possible cancer was received and understood, not just that it was sent.
Resonant Laser Excitation/Ionization and Mass Spectrometry in Isotope Geochemistry and Cosmochemistry

SCOPE OF REVIEW This paper reviews the coupling of resonant laser ionization and laserexcited fluorescence with mass spectrometry to make difficult isotopic-ratio measurements. To keep this review focused and manageable in size, it covers only metal and noble-gas isotopic analyses that find applications in isotope geochemistry and cosmochemisty. Many research groups are applying lasers and mass spectrometry to atomic, molecular, and isotopic analyses that address problems in nuclear physics [1], materials science [2-4], biology [5,6], environmental science, and other areas of geochemistry and cosmochemistry [7,8]. Several previous reviews and monographs cover the basic principles and instrumentation of resonant laser processes and mass spectrometry in more breadth [9-12]. The latest Analytical Chemistry Fundamental Reviews [13] and the published proceedings of the biannual International Symposium on Resonance Ionization Spectroscopy and Its Applications provide updates of other recent work [8]. This revie...
Concept formation by kindergarten children in a card-sorting task

Abstract Fifty children in kindergarten learned to sort cards according to one of four attributes on each of three different dimensions. Geometrical cards had the dimensions shape, border and color, and “people” cards depicted men, women, and children, wearing clothes of various colors and engaging in different activities. For the first two sets of problems, information was presented to the subject by two positive examples. Half of the sample had geometric problems first while the other half began with “people” problems. For both groups positive transfer occurred from the first set of problems to the second set. Problems with “people” cards were more difficult than problems with geometrical cards. After reaching criterion on the first two sets of problems, subjects quickly mastered problems with a positive example and a negative one. An all-or-none model was found to be inadequate as a description of the learning process. Subjects achieved few correct solutions, however, before reaching criterion and correct responses tended to occur in the last phase of the experiment.
The isomorphism problem for Cayley digraphs on groups of prime-squared order

Abstract Given any prime p , there are two non-isomorphic groups of order p 2 . We determine precisely when a Cayley digraph on one of these groups is isomorphic to a Cayley digraph on the other group. Namely, let X = Cay( G : T ) be a Cayley digraph on a group G of order p 2 with generating set T . We prove that X is isomorphic to a Cayley digraph on both Z p 2 and Z p × Z p if and only if X is a lexicographic product of two Cayley digraphs of order p . Equivalently, there exists a subgroup H of G of order p such that for every t ϵ TβH , we have tH ⊆ T .
ROTATIONAL ENERGY, PULSARS, AND ACTIVE NEBULAE.

A number of different expressions for the rotational energy of a slowly rotating star have appeared in the literature. Here it is shown that these expressions are equivalent. Application to pulsars and the Crab Nebulae are discussed.
Crossing the blood-brain barrier: a potential application of myristoylated polyarginine for in vivo neuroimaging.

Abstract As basic neurological research continues to reveal novel targets for therapy, the need to deliver therapeutic agents across the blood–brain barrier (BBB) becomes increasingly important. If developed, delivery modules would bring targeting molecules across the BBB to their respective active sites. In addition, it would be highly advantageous if the bioavailability of these delivered agents could be monitored over time using non-invasive imaging techniques. Here, we describe a versatile delivery module based on a myristoylated polyarginine backbone, which crosses the BBB. Incorporation of the fatty acid group was achieved using a Schotten–Bauman reaction with quantitative yield, and the peptide was further synthesized by conventional solid phase peptide synthesis (SPPS). We report for the first time the in vivo distribution of the delivery module over time into mouse brain using near-infrared (NIR) fluorescence imaging. The fluorescent cargo was detected in vivo from 24–48 h post IV injection and was further characterized in perfused brains. Immunohistochemical staining of excised brain showed that the delivery module primarily accumulated in neurons with occasional localization in astrocytes and endothelial cells. We conclude that this approach can be used for the delivery of imaging probes and potentially targeted therapeutics across the BBB.