cssi/SciSciGPT-SciSciNet huggingface dataset:
Enzyme aspects of acute intermittent porphyria.

Patients with acute intermittent porphyria are now known to have a decrease of the third enzyme and, in liver, an increase of the first enzyme of the heme biosynthetic pathway. It is possible that the induction of the first enzyme (ALA synthetase) in the liver of these patients results from the partial block in heme synthesis, since heme is known to be involved in the repression of hepatic ALA synthetase via a closed negative feedback loop. Presumably, an increase of hepatic ALA synthetase allows the delivery of a higher substrate concentration to the enzyme at the level of the block, thus raising the rate of the synthesis of end product toward “normal”. Using a simplified Michaelis-Menten model of an irreversible pathway in a homogeneous system, quantitative relationships between the degree of block and the magnitude of induction of the first enzyme necessary to return the steady state rate of the pathway to normal have been developed. This is intended as a point of departure for refinements which may ultimately lead to more accurate quantitative relationships.
Association by movement: evidence from NPI-licensing

‘Only’ associates with focus and licenses NPIs. This paper looks at the distributional pattern of NPIs under ‘only’ and presents evidence for the movement theory of focus association and against an in situ approach. NPIs are licensed in the ‘scope’ (or the second argument) of ‘only’, but not in the complement (or its first argument), which I will call the ‘syntactic restrictor’. While earlier approaches argued that ‘only’ licenses NPIs in the unfocused part of the sentence it occurs in except in its focus, evidence from DP-‘only’ shows that NPIs are also not licensed in the unfocused part of the syntactic restrictor. The distribution of NPIs provides a test for the size of the syntactic restrictor, and this test is applied to the case of VP-‘only’. The evidence shows that (i) the restrictor can be smaller than the entire VP and is not necessarily identical to the surface complement of ‘only’; (ii) in the case of association with a head the restrictor comprises an XP containing the head; and (iii) in cases of association into an island, the restrictor comprises the entire island. Generalizations (i)–(iii) can be captured straightforwardly by a movement approach but are incompatible with an in situ analysis. Contextual domain- restriction of the kind used in in situ approaches accounts for the appropriate semantics in cases where the semantic focus is properly contained in the syntactic restrictor of ‘only’.
Reflexive -st verbs in Icelandic

The -st morpheme in Icelandic resembles Romance and Slavic reflexive clitics and some Germanic simplex reflexives in that it is associated with a number of different uses on various verbs; this includes, among other uses, a middle/anticausative, a reciprocal, and a reflexive use. The reflexive use of -st is, however, much more restricted than that of typical reflexive clitics. In this article, I discuss in detail one particular class of reflexive -st verb, which I will refer to as the ‘figure reflexive’. With figure reflexive constructions, the subject bears an external agentive Θ-role and is also understood as a ‘figure’ with respect to a spatial ‘ground’, in the sense of Talmy (1985). I discuss two questions that reflexive -st verbs raise for a syntactic view of argument structure: what is the relationship between anticausatives and reflexives, and where does lexical idiosyncrasy arise? For the first question, I propose to analyze -st as an argument expletive, which in figure reflexive constructions is merged in SpecpP (cf. Svenonius 2003, 2007), but in anticausatives is merged in SpecVoiceP. Only in the former case can the Θ-role survive in semantics, which is argued to derive from the fact that VoiceP dominates pP, and not the other way around. For the second question, I argue that there are two separate issues: the first is the syntactic distribution of -st (which limits the kinds of reflexive -st verbs that can exist) and the second is the integration of roots into abstract event structure. This analysis supports a model of grammar where the semantics interprets the syntax, but the syntax operates autonomously from semantics: interpretation is determined ‘late’, just like phonological forms are.
Luteinizing hormone (LH) in the reptilian pituitary gland.

Abstract The luteinizing hormone (LH) activity of pituitary glands from three orders of Reptilia was studied by means of the induction of ovulation in vitro from the ovaries of the frogs Hyla regilla and Xenopus laevis. Representatives from several families including both suborders of Chelonia (turtles) and several Crocodilia had relatively high concentrations of LH activity in the pituitary. In contrast, ovulation could not be induced with pituitaries from any of the Squamata (snakes and lizards) tested, although these glands had high levels of gonadotropins in other bioassays. Thus, there appears to be a major dichotomy between Squamata and other reptiles either in the levels at which LH is stored in the gland, in the structure of the LH molecule, or in whether LH exists. The lack of bioassayable LH in snakes and lizards distinguishes them from all other orders of tetrapods examined. Previous cytological studies of the reptilian pituitary indicated a regional distribution of LH-cells (luteotropes), but measurement of LH in different regions of the pars distalis from three families of turtles revealed a uniform distribution of this hormonal activity.
Vibration-rotation intensities for “hot” bands☆

Abstract Vibration-rotation transition moments for “hot” bands are presented assuming the Dunham potential and a power series expansion for the dipole moment function. These results are applied to an analysis of CO intensities where a unique dipole moment function is determined from the experimental slope of the Herman-Wallis factors and the integrated intensities of the fundamental and overtone bands. This is then used together with the theoretical expressions to calculate the “hot” band dipole moment matrix elements which are found to be in good agreement with the experimental results.
Individual difference variables, affective differentiation, and the structures of affect.

Methodological arguments are usually invoked to explain variations in the structure of affect. Using self-rated affect from Italian samples (N = 600), we show that individual difference variables related to affective differentiation can moderate the observed structure. Indices of circumplexity (Browne, 1992) and congruence coefficients to the hypothesized target were used to quantify the observed structures. Results did not support the circumplex model as a universal structure. A circular structure with axes of activation and valence was approximated only among more affectively differentiated groups: students and respondents with high scores on Openness to Feelings and measures of negative emotionality. A different structure, with unipolar Positive Affect and Negative Affect factors, was observed among adults and respondents with low Openness to Feelings and negative emotionality. The observed structure of affect will depend in part on the nature of the sample studied.
Phosphorylation of RGS13 by the Cyclic AMP-dependent Protein Kinase Inhibits RGS13 Degradation

Regulators of G-protein signaling (RGS) proteins are scaffolds that control diverse signaling pathways by modulating signalosome formation and by accelerating the GTPase activity of heterotrimeric G proteins. Although expression of many RGS proteins is relatively low in quiescent cells, transcriptional and post-translational responses to environmental cues regulate both their abundance and activity. We found previously that RGS13, one of the smallest RGS proteins in the family, inhibited cyclic AMP-dependent protein kinase (PKA)-induced gene expression through interactions with the transcription factor cAMP-response element-binding (CREB) protein. Here, we show that PKA activation also leads to increased steady-state RGS13 expression through RGS13 phosphorylation, which inhibits RGS13 protein degradation. RGS13 turnover was significantly reduced in cells stimulated with cAMP, which was reversed by expression of the PKA-specific inhibitory peptide PKI. RGS13 phosphorylation was diminished by mutation of an N-terminal Thr residue (T41) identified as a phosphorylation site by mass spectrometry. Mutation of Thr41 in RGS13 to Ala (T41A) reduced steady-state RGS13 levels and its ability to inhibit M2 muscarinic receptor-mediated Erk phosphorylation compared with wild-type RGS13 by attenuating the protective effect of cAMP on RGS13 degradation. RGS13 underwent ubiquitylation, indicating that it is a likely target of the proteasome. These studies are the first to demonstrate post-translational mechanisms controlling the expression of RGS13. Stabilization of RGS13 through PKA-mediated phosphorylation could enhance RGS13 functions, providing negative feedback regulation that promotes cellular desensitization.
CARD15 gene mutations and risk for early surgery in pediatric-onset Crohn's disease.

Background & Aims: The risk for Crohn's disease (CD) is determined in part by genetic factors. Three recently described mutations in the CARD15(NOD2) gene have been associated with adult-onset CD. We investigated the effect of CARD15 mutations on disease manifestation, disease progression, and the risk for early surgery in childhood-onset CD. Methods: Genotyping for 3 CARD15 mutations: R702W, G908R, and 3020insC, was performed in 186 children with CD from a prospective cohort. A transmission-disequilibrium test was used to test for association with CD. Genotype with disease location and behavior was tested with logistic regression analysis. The effect of mutations on surgical outcome was evaluated using a Cox proportional hazard analysis. Results: The mean age at CD diagnosis was 12.4 years. The frequency of allelic mutations observed was 6.6% for R702W, 6% for G908R, and 13.1% for 3020insC. Of Caucasian CD children, 42% had at least one CARD15 mutation. None of the non-Caucasian children with CD had any CARD15 mutation. A significant association was detected for 3020insC ( P = .0045). Ileal location (odds ratio, 4.3; P = .003) and stricturing disease (odds ratio, 6.6; P = .0001) was more frequent and the risk for surgery was higher (hazard ratio, 5.8; P
Towards a heterogeneous common/shared storage system architecture

Storage management for our scientific, general, and signals processing complexes in the past has been addressed on a system-by-system, complex-by-complex basis. Over the years, the time-phased introduction of a wide variety of heterogeneous computer systems, each of which was selected to solve a unique operational problem, has created a most challenging environment from the storage management perspective. Each processor had its own dedicated storage subsystems, and in the main, its own custom-software solution to its storage management. A walking tour of our major complexes would expose one of almost every type of computer and almost every imaginable data-processing application type, each with its own robotic tape and disk subsystems. Our current challenge is to design and implement a coherent mass storage architecture (across all of the processing complexes) that flexible, repartitionable, and easier to manage. We are in the midst of that challenge now. From the 1970s to the present, our approach to storage has changed considerably, shaped in large measure by the products that have arisen in the commercial marketplace. This paper discusses our corporate adaptation to change and presents our current strategy in this vital area of high-performance/high-capacity computing.
Fast-Switching Electrochromic Li + -Doped NiO Films by Ultrasonic Spray Deposition

A low cost, high throughput deposition method for films of nickel oxide NiO and lithium-doped nickel oxide with improved electrochromic performance is demonstrated. This method is based on ultrasonic spray deposition of aqueous-based precursor solutions in air at atmospheric pressure, which represents a significant cost savings compared to vacuum deposition methods. The resultant materials are characterized by X-ray diffraction, Raman spectroscopy, electron microscopy, and electrochemical measurements. Electrochromic performance is demonstrated with in situ optical transmission measurements during electrochemical characterization. Nickel oxide materials color anodically and are thereby ideally suited to be used as counter electrode for the well-known tungsten oxide WO3 system in “smart” window applications. The coloration of nickel oxide materials is known to be slow when compared to WO3 and thereby limits the overall response time of a NiO/WO3 tandem device. The analysis of potential step response data shows that our lithium-doped nickel oxide material achieves 90% of its total coloration change in 29 s, which is comparable to reported measurements for WO3. These results significantly mitigate a potential bottleneck to the adoption of metal oxide electrochromic windows not only by demonstrating similar performance between NiO and WO3, but by achieving this result via low cost, highly scalable processing methods.
Carotid angioplasty and stenting versus carotid endarterectomy for treatment of asymptomatic carotid stenosis : A randomized trial in a community hospital

The authors conducted a study to determine if carotid artery stenting (CAS) is equivalent to carotid endarterectomy (CEA) in reducing the risk of stroke in asymptomatic patients with carotid stenosis, Patients (n = 85) were randomized to CAS or CEA and followed for 48 months. Both procedures were well-tolerated. No major complications occurred. Hospital stay was similar. Stenosis decreased to an average of 5% after CAS and the patency of the reconstructed artery remained satisfactory regardless of the technique. The authors concluded that an experienced cerebrovascular team may effectively treat CAS with results similar to those achieved with CEA.
The Lower Silurian Osmundsberg K-bentonite. Part II: mineralogy, geochemistry, chemostratigraphy and tectonomagmatic significance

The Lower Silurian Osmundsberg K-bentonite is a widespread ash bed that occurs throughout Baltoscandia and parts of northern Europe. This paper describes its characteristics at its type locality in the Province of Dalarna, Sweden. It contains mineralogical and chemical characteristics that permit its regional correlation in sections elsewhere in Sweden as well as Norway, Estonia, Denmark and Great Britain. The < 2 µm clay fraction of the Osmundsberg bed contains abundant kaolinite in addition to randomly ordered (RO) illite/smectite (I/S). Modelling of the X-ray diffraction tracings showed the I/S consists of 18 % illite and 82 % smectite. The high smectite and kaolinite content is indicative of a history with minimal burial temperatures. Analytical data from both pristine melt inclusions in primary quartz grains as well as whole rock samples can be used to constrain both the parental magma composition and the probable tectonic set- ting of the source volcanoes. The parental ash was dacitic to rhyolitic in composition and originated in a tec- tonically active collision margin setting. Whole rock chemical fingerprinting of coeval beds elsewhere in Baltoscandia produced a pronounced clustering of these samples in the Osmundsberg field of the discriminant analysis diagram. This, together with well-constrained biostratigraphic and lithostratigraphic data, provides the basis for regional correlation and supports the conclusion that the Osmundsberg K-bentonite is one of the most extensive fallout ash beds in the early Phanerozoic. The source volcano probably lay to the west of Baltica as part of the subduction complex associated with the closure of Iapetus.
HORMONES AND SHIFTING ECOLOGY THROUGHOUT PLANT DEVELOPMENT

Hormones modulate complex suites of ecologically relevant behaviors through interactive cascades of signal transduction; evolutionary changes in the function of a single hormone can result in multiple changes in plant traits. Sites of hormone action and tissue sensitivity change throughout plant ontogeny, as embryos, seedlings, and reproductively mature plants cope with shifting suites of environmental variables and resource availability. Phenotypic plasticity and correlations and trade-offs between life history traits (such as resource use efficiency and allocation to growth and differentiation of meristems) also change as plants age; hormonal changes are central to these shifts. I synthesize evidence from the molecular and physiology literature and present novel data on mangrove propagules, seedlings, saplings, and trees. Together, these data demonstrate that several ecologically important traits are hormonally mediated (both in the short term and over evolutionary time) in the diversification of plant lineages. I focus on two hormones with contrasting action: (1) abscisic acid (ABA), which regulates internal plant osmotic stability, membrane integrity, seed dormancy, and stomatal conductance; and (2) cytokinins (zeatin and allied adenine derivatives), which promote cell division, stimulate growth, delay leaf senescence, enhance the capacity of tissues to act as N sinks, and help to transduce signals of light and nutrient availability. ABA and cytokinin levels are correlated with patterns of osmotic tolerance, photosynthesis, growth, and leaf longevity, and their concentrations in specific tissues change throughout plant development. Ecologists and evolutionary biologists are in a strong position now to creatively comprehend, predict, and potentially engineer plant strategies and adaptive trade-offs over plant lifetimes in light of emerging knowledge of hormones.
Uniform Dynamic Deployment of Web and Grid Services

The Web services resource framework (WSRF) has redefined grid computing standards, making Web services more suitable for grid applications by adding persistent state management. However, it is still difficult to build, deploy, and evolve such services, since different Web and grid services containers require that the services they host be written in specific languages, to target particular internal interfaces for state management. Therefore, services must be built and deployed differently for each hosting environment. This paper describes uniform dynamic service code deployment on three Web services containers (namely, Tomcat, ASP.NET and a gSOAP based C++ container), and two grid services containers (namely, GT4 and WSRF.NET). Containers receive the code in an XML-based standard intermediate form, and then generate container-specific native code in different languages, without exposing these details to applications and grid services programmers. The dynamically deployed code can access state managed by the hosting container, can utilize functionalities exposed by statically deployed services, and can communicate with other dynamically deployed modules, running either in the same container or in different containers. A performance study shows that the newly deployed mobile code can run nearly as efficiently as it would if it had been deployed statically, through container-specific mechanisms.
First Report of Infection of Kiwifruit by Pestalotiopsis sp. in Turkey.

Circular to irregular brown leaf spots, 0.2 to 1.5 cm in diameter, were commonly observed on kiwifruit (Actinidia deliciosa) cv. Hayward plants in the Artvin-Arhavi region of northeastern Turkey. Leaf spots sometimes covered large portions of infected leaves, giving them a blighted appearance. Fruit symptoms consisted of brown, sunken, shriveled areas that were 0.5 to 3 cm in diameter. A fungus, later identified as a Pestalotiopsis sp. (1), was consistently isolated from diseased tissues. Pathogenicity tests were performed on 2-year-old kiwifruit plants and mature fruits at 18/22°C (day/night). A spore suspension (1 × 106 conidia per ml) was sprayed on leaves of 2-year-old kiwifruit plants. Agar pieces, 3 mm in diameter, from 10-day-old cultures also were applied to the leaves. Controls were treated with water and agar alone. Plants were covered with plastic bags for 3 days to ensure high humidity. After 2 weeks, disease symptoms were observed on inoculated leaves. Pestalotiopsis sp. was consistently isol...
The Thread & Cut Method: Syntheses of Molecular Knot Precursors

A novel approach to molecular knots is described. This method may allow access to smaller and more complex knots. Two knot precursors, 1a and 1b, are efficiently prepared in overall yields of 9.6 % and 8.7 %, respectively. The convergent six-step syntheses utilize Frechet-type etherifications, alkyne/azide click cycloadditions, and bis-macrolactonizations.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Determining Factors for Hospital Discharge Status After Radical Cystectomy in a Large Contemporary Cohort

Purpose: We describe hospital discharge status in patients after radical cystectomy for bladder cancer. We determined factors affecting discharge status.Materials and Methods: The 445 patients underwent radical cystectomy for urothelial carcinoma from January 2004 to December 2007. Patients were grouped by hospital discharge status into 1 of 4 groups, including home under self-care without services, home with home health services, subacute, rehabilitation or skilled nursing facility, or hospice/in-hospital mortality. We compared clinical, perioperative and pathological variables in these groups. We also examined the association of discharge status with the hospital readmission rate and 90-day mortality.Results: Of the 440 patients 250 (56.8%), 145 (32.9%), 39 (8.9%) and 6 (1.4%) were in the home without services, home with services, facility and mortality groups, respectively. On multivariate analysis older age, lower preoperative albumin, unmarried status and higher Charlson comorbidity index were predic...
A new unstable haemoglobin variant: Hb Shanghai [beta 131(H9)Gln----Pro] found in China

A 34-year-old woman patient was found to have a chronic hereditary haemolytic anaemia. No abnormal haemoglobin band was detected by conventional electrophoresis, but a slow beta chain could be separated on urea-carboxymethyl cellulose chromatography. Investigations of the patient's haemoglobin revealed an unstable component. Analyses of chemical structure, including isolation and TPCK trypsin digestion of the abnormal globin chain. HPL chromatography, amino acid composition as well as sequence determination of the abnormal peptide, indicated that a glutamine was replaced by a proline at position beta 131 (H9). Biosynthesis studies demonstrated a normal rate of synthesis but relatively fast degradation of the mutant beta chain. The new variant is named as Hb Shanghai according to the place where it was discovered.
Performance simulation of nuclear containments for security

Under blast loading, nuclear containment structures are subjected to cyclic flexural, axial, and shear forces. Less attention has been paid to modeling the cyclic behavior of reinforced concrete elements in which shear deformations are significant, such as in nuclear containments. Research has demonstrated that the strength of concrete in the principal compression direction is softened by tension in the lateral direction. This interaction has been considered for monotonic loading for many years. To consider this interaction for cyclic loading, the material laws recently derived by Mansour et al. in 2001 for the cyclic softened membrane model (CSMM) can be used. Both fire and explosion effects resulting from blast loading can also be incorporated into the constitutive models of concrete and reinforcing bars. This paper presents a method to implement the CSMM model, so that it can be used to simulate the performance of nuclear containments for security by the design communities.
Webpage-based benchmarks for mobile device design

Computers are currently designed using benchmarks and specification styles that are decades old, even as computers are being used in fundamentally different ways. By investigating the content, structure and usage of webpages, we observe that webpages represent a fundamentally different standard for performance evaluation of computers. We gathered data and modeled typical webpage content in order to characterize what is becoming a uniquely important design space. We then included this data in a set of simulations that also included models of a variety of scheduler types and heterogeneous multiprocessor architectures. To this, we proposed usage patterns that we believe typify the way people access the Internet on mobile devices. Considering only modern-day content in webpages, we found that specialized architectures can improve performance up to 70% over a homogeneous multiprocessor composed of general purpose processors with 25% additional improvement over the next best architecture when individual user preferences are also considered. This trend will increase as webpages become more differentiated in purpose and more complex in content. A new model of performance evaluation of computing must be developed, based upon webpage content and webpage access patterns.
Targeted Plasmid Integration into the Human Genome by Engineered Recombinases

The targeted integration of transgenes into cellular genomes is central to numerous applications in biotechnology, basic science, and medicine. In recent years, a variety of advances have improved upon conventional methods for site-specific transgene integration. Most of these methods involve nucleases that cleave DNA to activate DNA repair pathways including homologous recombination or integrases that fully catalyze the integration reaction but are limited in their capacity to target new sites in the genome. Recently, zinc-finger recombinases have emerged as a class of engineered enzymes that combines the strengths of both of these previous methods. Zinc-finger recombinases can fully and autonomously catalyze plasmid integration into the genome of mammalian cells without creating free DNA breaks. In addition, they can be engineered to target new genomic recognition sites by exchanging the modular and programmable DNA-binding domain and through directed evolution of the serine recombinase catalytic domain. This chapter reviews the development of the zinc-finger recombinase technology, including discussions of its strengths and weaknesses and the future directions necessary to translate this technology into routine use for transgene integration into cellular genomes.
CO Oxidation at the Au/TiO2 Boundary: The Role of the Au/Ti5c Site

Density functional theory is used to determine the reaction mechanisms of CO oxidation and the active oxygen species on a Au/TiO2 model catalyst. The model consists of a Au rod supported along the TiO2 [110] direction of the TiO2(110) surface. An interfacial Au/Ti5c site at the interface boundary is identified to be particularly active toward O2 adsorption and dissociation. At this site, O2 dissociation has an energy barrier of 0.5 eV, which is facile at room temperature. The resulting adsorbed Au/O/Ti5c oxygen species are shown to be stable and active for CO oxidation under relevant reaction conditions with an activation energy of 0.24 eV. Furthermore, the adsorbed Au/O/Ti5c oxygen species functions as an electron reservoir, and it lowers the oxygen vacancy formation energy of a surface lattice oxygen (Obri), as well as the Ti interstitial formation energy, due to electron transfer from high-energy defect states to low-energy p-states of the adsorbed Au/O/Ti5c oxygen species. Hence, the Obri species is ...
DN-03MUTANT IDH1-DRIVEN CELLULAR TRANSFORMATION INCREASES RAD51-MEDIATED HOMOLOGOUS RECOMBINATION AND TEMOZOLOMIDE RESISTANCE

BACKGROUND: IDH1 mutation is noted in roughly 75% of all lower-grade glioma and is considered to be an early and driving event in the genesis of these tumors. In clinical studies IDH1 mutation correlates with increased overall survival, progression-free survival, and upfront response to TMZ implying that mutant IDH1 directly contributes to drug sensitivity. IDH1 mutant gliomas, however, have a different underlying biology than comparable IDH1 WT glioma, complicating any analysis of the contribution of IDH1 mutation to drug sensitivity. To more accurately determine if and how IDH1 mutation alters drug sensitivity, we employed a system widely for the study of cellular transformation and IDH biology. In this system normal human astrocytes immortalized by introduction of virally-encoded E6, E7 and hTERT can be transformed by additional expression of oncogenic H-Ras or by mutant IDH1, the latter of which induces epigenetic changes similar to those noted in lower-grade glioma. We therefore used these cells to determine if mutant IDH1 expression and/or the transformative events it sets in place were sufficient to alter TMZ sensitivity. METHODS: E6/E7/hTERT-immortalized, untransformed human astrocytes, and the same cells transformed by prior introduction of oncogenic V12H-Ras, were infected with lentiviral constructs encoding WT or mutant (R132H) IDH1, then monitored for transformation status and, following TMZ exposure (100 uM, 3hrs), for DNA damage and repair, cell cycle response, and TMZ sensitivity. RESULTS: The TMZ-sensitive immortalized, untransformed parental cells exhibited DNA damage (H2AX foci) and a prolonged G2 cell cycle arrest that began 2 days after TMZ exposure and persisted for 5 days. The same cells transformed by mutant IDH1 exhibited the same levels of initial DNA damage and cell cycle arrest as controls, although both events resolved significantly faster in the IDH1 mutant cells in association with increased clonagenic survival. The increases in DNA damage processing, cell cycle progression, and clonagenicity were unique to cells transformed by mutant IDH1, and were not noted following introduction of mutant IDH1 into Ras-transformed or established GBM cells. The changes were, however, associated with increased homologous recombination (HR) and could be reversed by the genetic suppression of Rad51, the rate limiting protein in HR. CONCLUSIONS: Mutant IDH1 drives a unique set of transformative events that indirectly enhance HR and increase repair of TMZ-induced DNA damage and TMZ resistance. Inhibitors of HR may therefore be a viable means to further enhance TMZ response in IDH1 mutant glioma. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.
Urbanization and Retail Specialization

participation in voluntary associations and community life? Does this mode of living have a unifying or atomizing effect on the family group? Is this pattern of living more or less conducive to successful personal adjustment? What bearing does it have on the health of the individuals? These questions represent hypotheses that would be useful as starting points for further investigation. Some of our own data (not included in this paper) throw light on the associational relationships of the open-country families, but for the most part these questions are unanswered.
The Research about Potentially Hazardous Foods

This article described the history of the development of the American definition of potential hazards food, as well as the U.S. Food and Drug Administration, U.S. Department of Agriculture and the U.S. states on the potential hazards of food concepts and laws and regulations, and Australia, Canada, the United Kingdom,with the potential hazards food similar to the relevant laws and regulations, played a reference aimed at the formulation of relevant laws and regulations of China's food industry and catering industry "potentially hazardous food " and food processing operations.
Staving off acute otitis media. When is prophylaxis with antibiotics desirable

Acute otitis media affects most young children and is the condition for which children are most frequently treated with antibiotics. A pattern of recurrent acute ear infections develops in some children and is a source of frustration for parents and physicians. Recurrent episodes can exacerbate asthma or other underlying medical problems, and long-term effects can include chronic otitis media with permanent middle-ear injury and, possibly, delay in psychomotor and language development. Antibiotic prophylaxis can reduce the number of episodes of acute otitis media in children at high risk for recurrent infection. There is no perfect antibiotic to prevent acute otitis media. However, the risks associated with the drugs described in this article are low. Prophylaxis with antibiotics does not prevent all episodes of acute otitis media but can reduce the number of episodes by 50%.
Computational out-of-focus imaging increases the space–bandwidth product in lens-based coherent microscopy

The space–bandwidth product (SBP) of modern objective lenses is often significantly larger than the pixel count of opto-electronic image sensor chips, and, therefore, much of the information transmitted by the optical system cannot be adequately sampled or digitized. To resolve this mismatch, microscopes are in general designed to maintain the resolution of the optical system while significantly wasting the field of view (FOV) and SBP of the objective lens. We introduce a wide-field and high-resolution coherent imaging method that uses a stack of out-of-focus images to provide much better utilization of the SBP of an objective lens. We demonstrate our approach on a benchtop microscope by using a demagnification camera adapter to match the active area of the image sensor chip to the FOV of an objective lens. We show that the resulting spatial undersampling caused by capturing a large FOV can be mitigated through an iterative pixel super-resolution algorithm that uses e.g., ∼three to five slightly out-of-focus images, yielding an ∼8-fold increase in the SBP of the microscope. Furthermore, the same pixel super-resolution algorithm also achieves phase retrieval, revealing the optical phase information of the specimen. We compared our method against traditional off-axis and phase-shifting digital holographic microscopy modalities and demonstrated at least 3-fold reduction in the number of images required to achieve the same SBP. This technique could be used to maximize the throughput and SBP of lens-based coherent imaging and holography systems and inspire new microscopy designs that benefit from the inherent autofocusing steps of a scanning microscope to increase its SBP.
Leveraging experience for computationally efficient adaptive nonlinear model predictive control

This work presents Experience-driven Predictive Control (EPC) as a fast technique for solving nonlinear model predictive control (NMPC) problems with uncertain system dynamics. EPC leverages an affine dynamics model that is updated online via Locally Weighted Projection Regression (LWPR) to capture nonlinearities, uncertainty, and changes in the system dynamics. This model enables the NMPC problem to be re-cast as a quadratic program (QP). The QP can then be solved via multi-parametric techniques to generate a mapping from state, reference, and dynamics model to a locally optimal, affine feedback control law. These mappings, in conjunction with the basis functions learned via LWPR, define a notion of experience for the controller as they capture the full input-output relationship for previous actions the controller has taken. The resulting experience database allows EPC to avoid solving redundant optimization problems, and as it is constructed online, enables the system to operate more efficiently over time. We demonstrate the performance of EPC through a set of hardware-in-the-loop simulation studies of a quadrotor micro air vehicle that is subjected to unmodeled exogenous perturbations.
Entangled but Finicky Ingression Protein Complexes for Successful Cytokinesis

Cytokinesis is the final stage of mitosis that leads to the physical separation of two daughter cells and comprises a...
Promoting a culture of collaboration between point-of-care clinicians and industry partners:

Interdisciplinary patient-centric collaboration extends beyond the boundaries of hospital walls to include industry partners. Point-of-care clinicians utilizing patient-monitoring technology routin...
Equivalent mortality and complication rates following periprosthetic distal femur fractures managed with either lateral locked plating or a distal femoral replacement.

Abstract Introduction Management of distal femur fractures above total knee arthroplasty (TKA) remains challenging. Two common surgical options are locked lateral plating (LLP) and distal femoral arthroplasty (DFR). Unfortunately, approximately 30–50% of patients may die within one year of injury, require further surgery, or not regain prior mobility performance. We compared 87 LLP to 53 DFR patients – to our knowledge the largest comparative study – focusing on 90- and 365-day mortality, mobility maintenance, and further surgery. Methods We performed a retrospective review of patients at least 55 years old who sustained femur fractures near a primary TKA (essentially OTA-33 or Su types 1, 2, or 3) from 2000 to 2015 assigning cohort based on treatment: LLP or DFR. We excluded patients having prior care for the injury, whose surgery was not for fracture (e.g. loosening), or having other surgical intervention (e.g. intramedullary nail). Results Results Cohorts were similar based on body mass index and age adjusted Charlson Comorbidity Index (aaCCI). LLP was more common than DFR for fractures above and at the level of the implant, but similar for fractures within the implant for patients with aaCCI ≥ 5. LLP and DFR had similar mortality at 90 days (9% vs 4%) and 365 days (22% vs 10%), need for additional surgery (9% vs 3%), and survivors maintaining ambulation (77% vs 81%). Patients whose surgery occurred 3 or more days after presentation had similar mortality risk to those whose surgery was before 3 days. The mean age of one year survivors was 77 whereas for patients who died it was 85. Neither surgical choice nor aaCCI was associated with increased risk in time to surgery. Conclusions Fracture location, remaining bone stock, and patient’s prior mobility and current comorbidities must guide treatment. Our study suggests that 90- and 365-day mortality, final mobility, and re-operation rate are not statistically different with LLP vs DFR management.
The Dynamics of Inter-Societal Systems

Even though there were less than ten million people on earth for the first 185,000 years of human existence, hunter-gatherers from different sets of bands would inevitably make contact; and if this contact persisted for a time, then these early relations constituted the first inter-societal systems. The label, inter-societal system, connotes that it is societies as a whole that make contact and form relations; and such may have been the case when societies were very small. But even in these early contacts, it was actors within institutional domains that were forging the relations that define an inter-societal system. There can be many varieties of relationships and networks emerging among actors in key institutional domains. For example, small societies may exchange women in marriage, thus indicating that it is actors in the respective kinship domains that are forming relations. Similarly, when religion spreads from one society to another, it is actors operating within the religious domain that are the core of the inter-societal system. When students migrate from one society to another for education, the educational domain is the core of this inter-societal system. When teams from different countries compete in sports, this too is an inter-societal system created by the institutional domains of sport in each society. There can also be a demographic dimension to inter-societal systems, as when members of one population migrate to another; but typically, there is a “reason” for the migration – political, kinship, religion, or economic – and this reason almost always involves the structure and culture of one or more institutional domains. Inter-societal systems can also involve more purely cultural relations, as is the case when individuals from the same ethnic subpopulation or some other categoric designation like tribe or religion become partitioned in two separate societies and, yet, still maintain contact.
Recanalization of Tandem Vertebrobasilar Occlusions with Contralateral Vertebral Occlusion or Hypoplasia via either Direct Passage or the SHERPA Technique

Introduction: Tandem vertebral ostial disease with acute intracranial vertebrobasilar occlusion with contralateral vertebral occlusion or hypoplasia presents a unique challenge to the interventionalist. Methods: The authors queried a prospectively maintained institutional endovascular database from August 2013 to June 2018 for cases of endovascularly treated acute tandem vertebrobasilar occlusions in the presence of contralateral vertebral occlusive disease or hypoplasia. Demographic and presentation data, the technique, results, and clinical outcome were extracted. Results: Tandem recanalization was attempted and achieved in 5 patients with a thrombolysis in cerebral infarction (TICI) 3 result in 4 patients and a TICI 2c result in 1 patient. To facilitate effective manual aspiration thrombectomy for the tandem basilar occlusion, performed in all cases in 1 or 2 passes, the Neuron TM MAX sheath was advanced into the V2 after Dotter or balloon angioplasty of the diseased origin. In cases where the origin cannot be crossed/visualized, the Synchro Helper to Evaluate via Retrograde Passage an Arterial origin (SHERPA) technique, entailing the passage of a microwire retrograde via the hypoplastic contralateral vertebral artery was utilized to delineate the vertebral ostium ( n = 2 cases). All but 1 patient had substantial improvement in the National Institutes of Health Stroke Scale score after the procedure. Conclusion: Recanalization of tandem vertebrobasilar occlusions with contralateral occlusion or hypoplasia is feasible. Intracranial recanalization is facilitated by the passage of a long 6F sheath into V2, and retrograde delineation of an occluded vertebral origin with a microwire may serve as a crucial adjunct.
Examining novice programmers' software design strategies through verbal protocol analysis

This paper describes the change in software design strategies used by novice programmers over the course of one semesterby using verbal protocol analysis. Our participants were nine first-year undergraduate students (novices), and two experts.Overall, we observed that two types of strategy were used by the novice programmers. The most common strategy observedin our participants, at the beginning of the semester, was a UI-based strategy that focused on system components from theuser’s perspective. This strategy is often overly simplified with little operational and technical details. Another type ofstrategy used by novices later in the study was a functional-centered strategy in which novices incorporated programmingconcepts into their design. Novices who used the latter strategy were able to provide more operational detail than when theUI-based strategy was used. We also found that, due to lack of experience, the designs were still very preliminary. Inaddition, the novices also exhibited opportunistic design behavior more often than systematic behavior (i.e., a top-down orbottom-up strategy) during the semester. We argue that teaching programming knowledge and skills alone will not developstudents’ software design knowledge effectively.
JSF and the United States

This chapter chronicles and documents the successes and failures experienced by the US JSF program from the 1990s to 2018. Chapter contents include JSF technical capabilities; cost overruns; versions used by the Air Force, Marine Corps, and Navy; and DOD responses to program developments and congressional oversight and attempted legislative remedies including the 2009 Weapons Systems Acquisition Reform Act (WSARA). Detailed coverage and analysis are also provided concerning oversight of this program provided by the Department of Defense Office of Inspector General and Government Accountability Office. Additional emphasis is placed on the wide geographic dispersion of the JSF industrial base, aerospace industry consolidation, and political campaign contributions received by key members of Congress from the aerospace industry.
Abstract B44: Regulation of macrophage activation by vascular niche in glioblastoma

Spatiotemporal regulation of tumor immunity remains largely unexplored. Here we identify a vascular niche that controls alternative macrophage activation in glioblastoma (GBM). We show that tumor-promoting macrophages are spatially proximate to GBM-associated endothelial cells (ECs), permissive for angiocrine-induced macrophage polarization. We identify ECs as a major source for interleukin (IL)-6 expression in GBM microenvironment. Furthermore, we reveal that colony stimulating factor-1 (CSF-1) and angiocrine IL-6 induce robust arginase-1 expression and macrophage alternative activation, mediated through peroxisome proliferator-activated receptor (PPAR)-γ-dependent transcriptional activation of hypoxia-inducible factor (HIF)-2α. Finally, utilizing a genetic murine GBM model, we show that EC-specific knockout of IL-6 inhibits macrophage alternative activation and improves survival in the GBM-bearing mice. These findings illustrate a vascular niche-dependent mechanism for alternative macrophage activation and cancer progression, and suggest that targeting endothelial IL-6 may offer a selective and efficient therapeutic strategy for GBM, and possibly other solid malignant tumors. Note: This abstract was not presented at the conference. Citation Format: Qirui Wang, Yanqing Anna Gong, Yi Fan. Regulation of macrophage activation by vascular niche in glioblastoma [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B44.
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Adjunctive Pimavanserin in Patients With Major Depressive Disorder and an Inadequate Response to Therapy (CLARITY)

OBJECTIVE Pimavanserin is a 5-hydroxytryptamine-2A antagonist and inverse receptor agonist. This phase 2 study examined the efficacy and safety of pimavanserin as adjunctive therapy in patients with major depressive disorder (MDD). METHODS This was a multicenter, randomized, double-blind, placebo-controlled study in patients with DSM-5-defined MDD and an inadequate response to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). Using a 2-stage sequential parallel-comparison design, patients were initially randomized in a 3:1 ratio to placebo or pimavanserin added to ongoing SSRI or SNRI therapy; at 5 weeks, placebo nonresponders were re-randomized to placebo or pimavanserin for an additional 5 weeks. Key endpoints were change from baseline to the end of each stage in 17-item Hamilton Depression Rating Scale (HDRS-17) total score and Sheehan Disability Scale (SDS) score. RESULTS Between December 2016 and October 2018, 207 patients were randomized. For the prespecified pooled Sequential Parallel Comparison Design analyses of Stages 1 and 2, the least squares (LS) mean (SE) difference for the HDRS-17 total score was -1.7 (0.85) (P = .039) and for the SDS score was -0.8 (0.29) (P = .004). At week 5 of Stage 1, LS mean (SE) difference for pimavanserin versus placebo was significant for changes on the HDRS-17 (-4.0 [1.09], P = .0003) and SDS (-1.2 [0.40], P = .0036) with effect sizes of 0.626 and 0.498, respectively. Early and sustained separation of pimavanserin from placebo (P < .05) occurred at 1 week. The most common adverse events with pimavanserin were dry mouth, nausea, and headache. CONCLUSIONS Pimavanserin demonstrated robust efficacy in patients with MDD and an inadequate response to an SSRI or SNRI. Tolerability was consistent with previous experience. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03018340.