cssi/SciSciGPT-SciSciNet huggingface dataset:
A conserved element in Myc that negatively regulates its proapoptotic activity

Myc is an oncoprotein transcription factor that promotes cell proliferation and apoptosis. Analysis of highly conserved elements within vertebrate Myc proteins has been instrumental in defining the functions of the Myc protein. Here, we probe the role of a highly conserved, but little studied, element within the central region of c-Myc, termed 'Myc box III' (MbIII). We show that MbIII is important for transcriptional repression by Myc, and for transformation both in vitro and in a mouse model of lymphomagenesis. Curiously, disruption of MbIII decreases transformation activity by increasing the efficiency with which Myc can induce apoptosis, suggesting that MbIII is a negative regulator of programmed cell death. These findings reveal a role for MbIII in Myc biology, and establish that the oncogenic capacity of Myc is linked directly to its ability to temper the apoptotic response.
Preparation of nuclear research materials with a laboratory-type isotope separator

Abstract Laboratory electromagnetic isotope separators have come into extensive use during the last several years. Factors influencing the enrichment for a specific isotope are discussed, particularly vacuum pressure and collection efficiency. It is shown that for maximum isotopic purity it is essential to start with the highest attainable specific activity and to process the source material with a minimum of delay. The influence of irradiation time on isotopic purity is also discussed. Various methods of ion-beam collection are described, and some techniques for preparing suitable targets on carbon film are presented.
Electronic, optical, and structural properties of some wurtzite crystals.

Using the first-principles orthogonalized linear-combination-of-atomic-orbitals method in the local-density approximation, the electronic structures and the linear-optical properties of ten wurtzite crystals, BeO, BN, SiC, AlN, GaN, InN, ZnO, ZnS, CdS, and CdSe are investigated. Results on band structures, density of states, effective masses, charge-density distributions, and effective charges are presented and compared. Optical properties of the ten wurtzite crystals up to a photon energy of 40 eV are calculated and the dielectric functions are resolved into components perpendicular and parallel to the z axis. The calculated results are compared with the available experimental data and other recent calculations. The structural properties of the wurtzite crystals are also studied by means of local-density total-energy calculations. It is shown that the calculated equilibrium volume and the bulk modulus are in good agreement with recent experimental data.
A planar subharmonically-pumped 71 GHz receiver with integral feed antenna

A planar, subharmonically-pumped, hybrid millimeter-wave receiver with integral antenna is described. Coplanar waveguide filters are used to isolate the ports and provide image enhancement. The integral planar antenna has 12 dB gain and is suited for use as a feed. The main lobe is normal to the substrate surface. The receiver is designed for an instantaneous bandwidth of 10 GHz. Experiments at 71 GHz indicate single-sideband mixer conversion loss of 6.5 dB. We believe that this represents the highest level of integration yet demonstrated in this frequency range.
A novel Mycoplasma sp. associated with proliferative tracheitis and pneumonia in a burmese python (Python molurus bivittatus)

Proliferative lymphocytic tracheitis and pneumonia were observed histologically in the respiratory tract of a captive Burmese python (Python molurus bivittatus). A mycoplasma species was isolated from the respiratory tissue. Polymerase chain reaction analysis of the 16S rRNA gene sequence of the isolate showed 0.90 similarity to Mycoplasma agassizii, an organism previously shown to cause respiratory disease in reptiles. Based on these findings, a novel Mycoplasma species was suspected to be the causative agent of respiratory disease in this snake.
Obesity-related systemic factors promote an invasive phenotype in prostate cancer cells

Obesity is associated with larger tumors, shorter time to PSA failure, and higher Gleason scores. However, the mechanism(s) by which obesity promotes aggressive prostate cancer remains unknown. We hypothesize that circulating factors related to obesity promote prostate cancer progression by modulating components of the metastatic cascade. Male C57BL/6 mice (6 weeks) were fed an ad libitum diet-induced obesity (60% fat) or control diet (10% fat) for 12 weeks. Serum was collected, metabolic and inflammatory proteins were measured by an antibody array. Sera were used to measure, in vitro, characteristics of a metastatic phenotype. Comparable to obese men, obese sera contained higher levels or leptin, vascular endothelial growth factor, PAI-1, interleukin-6 (IL-6) and lower levels of testosterone. In prostate cells, serum was used to assess: proliferation, invasion, migration, epithelial-mesenchymal-transition (EMT) and matrix metalloproteinase (MMP) activity. LNCaP and PacMetUT1 cells exposed to obese sera increased proliferation, whereas PrEC and DU145 were unaffected. LNCaP, PacMetUT1 and DU145 cancer cells exposed to obese sera resulted in increased invasion, migration and MMP-9 activity. Prostate cancer cells exposed to obese sera showed increased vimentin, dispersion of e-cadherin and β-catenin from the plasma membrane. We report, prostate cancer cells exposed to sera from obese mice increases proliferation, invasion, migration, MMP activity and induces changes in proteins critical for EMT.
Significance of reduced dimensionality in reaction kinetics: impact of multi-site particles

This review examines novel kinetic properties of enzymes on membrane surfaces or states of restricted diffusion. A leading feature is the presence of multiple enzymes and/or substrates per particle. In these states, enzymes can be influenced by parameters such as the number of substrates or enzymes per particle, particle size, the rates of exchange of substrate or enzyme from the particle, or substrate diffusion to the particle. These steps are independent of the enzyme site parameters which are described by classical enzymology. The results make it clear that non-classical behaviors are important to biological systems, are the basis for some enzyme expression levels and are determinants of cellular design. To identify more unique functions of these states, descriptions of catalysis in the non-solution state should become a part of kinetic education in biology.
Hans Christian Andersen: The Misunderstood Storyteller

The 2005 bicentenary of Hans Christian Andersen's birth is an opportunity to re-evaluate the achievement of one of the great figures of the fairy tale and storytelling tradition, a beloved writer famous for The Snow Queen and The Little Mermaid, The Ugly Duckling and The Red Shoes and many other now classic tales. Jack Zipes broadens our understanding of Andersen by exploring the relation of the Danish writer's work to the development of literature and of the fairy tale in particular. Based on thirty-five years of researching and writing on Andersen, this new book is a welcome reconsideration of Andersen's place and of his reception in English-speaking countries and on film.
Patient adherence and reimbursement amount for antidiabetic fixed-dose combination products compared with dual therapy among texas medicaid recipients

Abstract Background: Little is known about the potential for improved adherence with and cost savings of fixed-dose combination therapy (FDCT) products compared with analogous dual therapy for type 2 diabetes mellitus. Objectives: The objectives of this study were as follows: (1) to describe patient adherence to various oral antidiabetic regimens (ie, dual therapy and FDCT); (2) to determine whether there is a difference in medication adherence between FDCT users and analogous dual-therapy users; and (3) to assess whether there is a difference in reimbursement amounts between an FDCT product and its individual components. Methods: This study was a retrospective cohort analysis using the Texas Medicaid prescription claims database. The study subjects included those who used antidiabetic FDCT or dual therapy from August 1, 2000, to July 31, 2004. The identification period of study subjects was between August 1, 2000, and July 31, 2004, including 12 months before and after the index date, so that the overall time frame was from August 1, 1999, through July 31, 2005. Prescription claims were analyzed over a 12-month preindex and 12-month postindex period. Adherence was measured using medication possession ratio (MPR), and regimen costs per tablet were assessed utilizing the index prescription. Results: Overall, 7570 FDCT users and 14,762 dual-therapy users were identified. Regarding the postindex period, FDCT users had 1.8% higher MPR compared with dual-therapy users (78.6% vs 77.2%). Patients who switched from monotherapy to FDCT had a 1.5% decrease in adherence (from 79.7% to 78.5%), whereas those who switched from monotherapy to dual therapy had a 10.0% decrease in adherence (from 83.0% to 74.7%). Those who switched from dual therapy to FDCT had a 12.4% increase in adherence (from 72.7% to 81.7%). Multivariate logistic regression analyses revealed that among preindex monotherapy users, FDCT users were significantly more likely to have higher adherence than dual-therapy users (odds ratio [OR] = 1.867; 95% CI, 1.716-2.032) after controlling for covariates, and the results were similar among preindex dual-therapy users (OR = 1.551; 95% CI, 1.204-1.999). From the perspective of the third-party payer, all FDCT products were significantly less expensive than their equivalent individual components (P Conclusions: Among these Texas Medicaid beneficiaries, antidiabetic FDCT users were more adherent to their regimen than dual-therapy users, and FDCT was less expensive than the analogous dual therapy. Because multiple agents are often required to achieve adequate glycemic control, it may be clinically and economically beneficial to treat eligible patients with FDCT products.
The Sixteen Strivings for God

Abstract. A psychological theory of religious experiences, sensitivity theory, is proposed. Whereas other theories maintain that religious motivation is about a few overarching desires, sensitivity theory provides a multifaceted analysis consistent with the diversity, richness, and individuality of religious experiences. Sixteen basic desires show the psychological foundations of meaningful experience. Each basic desire is embraced by every person, but to different extents. How we prioritize the basic desires expresses our individuality and influences our attraction to various religious images and activities. Each basic desire is associated with a basic goal and a unique joy, such as love, self-worth, relaxation, or strength. We do not seek to experience joys infinitely; we regulate joys, in accordance with our core values, to sixteen balance points (sensitivities) that vary based on individuality. Religions help persons of faith regulate the sixteen basic joys by providing some images that strengthen joyful experiences and others that weaken them. We can strengthen our experience of self- worth, for example, by contemplating God in the image of savior; we can weaken our experience of self-worth by contemplating original sin. The theory of sixteen basic desires is testable scientifically and suggests such philosophical concepts as value-based happiness.
Apoptosis in Mycobacterium tuberculosis infection in mice exhibiting varied immunopathology

This study examined mechanisms contributing to pulmonary immunopathology following acute Mycobacterium tuberculosis (MTB) infection in vivo in a murine model. A/J and C57BL/6 mice were intravenously infected with MTB (Erdman). Pathological differences were found between strains, unrelated to pulmonary load of bacilli. A/J mice developed progressive interstitial pneumonitis, while C57BL/6 mice maintained granuloma formation. The contribution of FAS and FAS ligand-mediated apoptosis was assessed via bioluminescent reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemical staining, and TUNEL assessment of DNA fragmentation. Cytokine messages for pulmonary tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as well as for the lytic molecules perforin and granzyme B, were quantified. Immunohistochemical staining for CD3 receptor was performed to monitor lymphocytic lung infiltration. Soon after infection, A/J mice exhibited increased pulmonary IFN-γ message, concurrent with the appearance of CD3+ lymphocytes distributed throughout the lung. C57BL/6 mice exhibited perivascular cuffing, with no accompanying increase in IFN-γ message. A/J mice also had elevated levels of FAS and FAS ligand message and protein early after infection, while the C57BL/6 mice had no increased expression of these molecules. Both strains exhibited qualitatively similar numbers of TUNEL-positive cells throughout infection, with a marked increase on day 7. Apoptotic cells appeared to co-localize with acid fast bacilli. It is therefore proposed that apoptosis during initial granuloma formation following MTB infection may occur through a FAS/FAS ligand-independent pathway. Moreover, a failure of completion of the FAS/FAS ligand-mediated apoptosis pathway in the A/J mice may contribute to inefficient elimination of lymphocytes, thus further aggravating pulmonary pathology. Copyright © 2000 John Wiley & Sons, Ltd.
Cysteine Conjugate β-Lyase Activity of Rat Erythrocytes and Formation of β-Lyase-Derived Globin Monoadducts and Cross-Links after in Vitro Exposure of Erythrocytes to S-(1,2-Dichlorovinyl)-L-cysteine

S-(1,2-Dichlorovinyl)-l-cysteine (DCVC), a mutagenic and nephrotoxic metabolite of trichloroethylene, can be bioactivated to reactive metabolites, S-(1,2-dichlorovinyl)-l-cysteine sulfoxide (DCVCS) or chlorothioketene and/or 2-chlorothionoacetyl chloride, by cysteine conjugate S-oxidase (S-oxidase) and cysteine conjugate β-lyase (β-lyase), respectively. Previously, we characterized the reactivity of DCVCS with Hb upon incubation of erythrocytes with DCVCS and provided evidence for the formation of distinct DCVCS-Hb monoadducts and cross-links in both isolated erythrocytes and rats given DCVCS. In the present study, we investigated DCVC bioactivation and Hb adduct formation in isolated rat erythrocytes incubated with DCVC (9 and 450 μM) at 37 °C and pH 7.4. The results suggested that no DCVCS monoadducts or cross-links were formed; however, LC/electrospray ionization/MS and matrix-assisted laser desorption/ionization/MS of trypsin-digested globin peptides revealed the presence of β-lyase-derived globin mon...
Structure of the Integrin beta3 Transmembrane Segment in Phospholipid Bicelles and Detergent Micelles

Integrin adhesion receptors transduce bidirectional signals across the plasma membrane, with the integrin transmembrane domains acting as conduits in this process. Here, we report the first high-resolution structure of an integrin transmembrane domain. To assess the influence of the membrane model system, structure determinations of the beta3 integrin transmembrane segment and flanking sequences were carried out in both phospholipid bicelles and detergent micelles. In bicelles, a 30-residue linear alpha-helix, encompassing residues I693-H772, is adopted, of which I693-I721 appear embedded in the hydrophobic bicelle core. This relatively long transmembrane helix implies a pronounced helix tilt within a typical lipid bilayer, which facilitates the snorkeling of K716's charged side chain out of the lipid core while simultaneously immersing hydrophobic L717-I721 in the membrane. A shortening of bicelle lipid hydrocarbon tails does not lead to the transfer of L717-I721 into the aqueous phase, suggesting that the reported embedding represents the preferred beta3 state. The nature of the lipid headgroup affected only the intracellular part of the transmembrane helix, indicating that an asymmetric lipid distribution is not required for studying the beta3 transmembrane segment. In the micelle, residues L717-I721 are also embedded but deviate from linear alpha-helical conformation in contrast to I693-K716, which closely resemble the bicelle structure.
The Multiple Absorption Coefficient Zonal Method (MACZM), an Efficient Computational Approach for the Analysis of Radiative Heat Transfer in Multidimensional Inhomogeneous Nongray Media

ABSTRACT The formulation of a multiple absorption coefficient zonal method (MACZM) is presented. The concept of generic exchange factors (GEF) is introduced. Utilizing the GEF concept, the MACZM is shown to be effective in simulating accurately the physics of radiative exchange in multidimensional, inhomogeneous, nongray media. The method can be applied directly to a fine-grid finite-difference or finite-element computation. It is thus suitable for direction implementation in an existing computational fluid dynamics (CFD) code for analysis of radiative heat transfer in practical engineering systems. The feasibility of the method is demonstrated by calculating the radiative exchange between a high-temperature (∼3,000 K) molten nuclear fuel (UO2) and water (with a large variation in absorption coefficient from the visible to the infrared) in a highly three-dimensional and inhomogeneous environment simulating the premixing phase of a steam explosion.
Variational methods for controlled thermonuclear reactor blanket studies

Variational procedures for neutron and photon transport calculations in CTR blanket studies are considered. The procedures can be readily implemented to yield accurate results in an efficient manner and will be especially useful in performing sensitivity studies and survey calculations. They are applicable to multidimensional problems and to the time-dependent, as well as the steady-state, case. The use of the dual-space approach for certain sensitivity studies is also considered. Numerical results are presented to demonstrate the efficacy of the procedures discussed.
ENDOTHELIN-1 (ET-1) RECEPTOR BLOCKADE ATTENUATES LPS AND HYPOXIA (H)-INDUCED INTESTINAL INJURY IN RATS. • 759

ET-1 is a potent vasoconstrictor peptide with multiple biologic effects. Since ET-1 stimulates the inflammatory cascade and promotes intestinal vasoconstriction, we hypothesized that endogenous ET-1 plays an important role in endotoxin and hypoxia-induced intestinal injury. Male Sprague Dawley rats weighing 150-250 grams were anesthetized with pentobarbital and treated in the following groups: 1) control (ventilated with 21% O2), 2) LPS (2mg/kg i.v.) + H (ventilated with 10% O2), and 3) ET-1 receptor blockade, BQ123 (1 mg/kg i.v.) + LPS + H. Mean arterial blood pressure and superior mesenteric artery (SMA) blood flow were continuously recorded, and at 90 minutes an arterial blood gas was obtained, the rats euthanized and intestine harvested for gross and histological analysis. The mean arterial pressure for controls decreased to 87.1% of baseline over 90 min, whereas MAP in group 2 and group 3 decreased to 30.9% and 33.8% of baseline, respectively. Similarly, the SMA blood flow in controls fell to 68.9% of baseline, while group 2 and 3 showed more pronounced intestinal vasoconstriction (SMA flow 32.3% and 38.8% of baseline). At 90 minutes control animals had normal acid-base balance and oxygenation (mean pH 7.341, pO2=141 torr), while groups 2 and 3 developed acidosis and hypoxemia (group 2: pH 7.04, pO2 70; group 3: pH 7.10, pO2 78). However, gross inspection of the intestine was normal in the controls, showed moderate to severe damage in 5/6 animals of group 2, and mild damage to all specimens in group 3. Histological data was scored as follows: 0-normal intestine; 1+-mild epithelial sloughing; and 2+-mid-villous necrosis. The control group had normal or minimal damage in all animals, group 2 showed 2+ damage in 5 out of 6 animals, and group 3 ranged from 0 to 1+ in 6 out of 6 animals (p < 0.05 compared to group 2). These results suggest that BQ123 pretreatment prevents intestinal injury without affecting the hemodynamic decompensation following the stress with LPS and hypoxia in this protocol. We speculate that BQ123 may prevent intestinal damage by blocking the inflammatory cascade.
Theoretical and methodological perspectives in the interpretive study of children

Conceptual and methodological issues central to the interpretive study of childhood socialization are presented, providing a general orientation to the other chapters in this volume.
A Gaming Evaluation of Colorado River Drought Management Institutional Options

: Researchers representing each of the Colorado River Basin states as well as the Secretary of the Interior were presented with an interactive computer simulation of a progressively increasing drought and were given the collective opportunity to change the ways in which basin-wide and within-state water management were conducted. The purpose of this “gaming” exercise was to identify rules for managing the Colorado River which are effective in preventing drought-caused damages to basin water users. This water management game was conducted three times, varying the collective choice roles for management of the river yet staying substantially within the current institution for management of the Colorado River known as the “Law of the River.” The Law of the River was quite effective in minimizing drought impacts upon consumptive water uses. Additional effective drought-coping measures to protect consumptive uses consisted mostly of intrastate water management improvements which states were able to implement independently. The Law of the River did not protect non-consumptive water uses, such as hydroelectric power generation, water-based recreation, endangered species, and water quality from drought, as well as it protected consumptive water uses. Players reached collective choice decisions to cope with rising salinity, equalize storage between the upper and lower basins, and protect endangered species. While these measures had some success, only reductions in withdrawals for consumptive uses, particularly in the upper basin, could have substantially lessened adverse impacts.
NMR Structure Determination for Larger Proteins Using Backbone-Only Data

Conventional protein structure determination from nuclear magnetic resonance data relies heavily on side-chain proton-to-proton distances. The necessary side-chain resonance assignment, however, is labor intensive and prone to error. Here we show that structures can be accurately determined without nuclear magnetic resonance (NMR) information on the side chains for proteins up to 25 kilodaltons by incorporating backbone chemical shifts, residual dipolar couplings, and amide proton distances into the Rosetta protein structure modeling methodology. These data, which are too sparse for conventional methods, serve only to guide conformational search toward the lowest-energy conformations in the folding landscape; the details of the computed models are determined by the physical chemistry implicit in the Rosetta all-atom energy function. The new method is not hindered by the deuteration required to suppress nuclear relaxation processes for proteins greater than 15 kilodaltons and should enable routine NMR structure determination for larger proteins.
Chapter 2.5 Measurements and control in freeze—desalination plants

Abstract This chapter presents the basic flow diagram for freeze-desalination processed and describes the physical and chemical principles which determine the characteristics of the process equipment employed. The functions and design of the major process components (feed precooler, freezer, wash separation column, melter/condenser, primary compressor and heat reject system) are discussed individually in detail. Variations in equipment design are considered based on the characteristics of the refrigerant selected. The refrigerants considered include water (vacuum freezing) and various hydrocarbons (secondary refrigerant freezing) which are either lighter or heavier than the water to be desalted. Although mechanical design has been considered and discussed where appropriate, the emphasis has been placed on process design and the factors which dictate the nature and requirements of the process control system and the characteristics of the instrumentation required to affect adequate control of a commercial desalination plant. Instrumentation and control system diagrams are provided for all equipment items and the variations required by refrigerant selection.
Identification of putative cis-regulatory elements in Cryptosporidium parvum by de novo pattern finding

Cryptosporidium parvum is a unicellular eukaryote in the phylum Apicomplexa. It is an obligate intracellular parasite that causes diarrhea and is a significant AIDS-related pathogen. Cryptosporidium parvum is not amenable to long-term laboratory cultivation or classical molecular genetic analysis. The parasite exhibits a complex life cycle, a broad host range, and fundamental mechanisms of gene regulation remain unknown. We have used data from the recently sequenced genome of this organism to uncover clues about gene regulation in C. parvum. We have applied two pattern finding algorithms MEME and AlignACE to identify conserved, over-represented motifs in the 5' upstream regions of genes in C. parvum. To support our findings, we have established comparative real-time -PCR expression profiles for the groups of genes examined computationally. We find that groups of genes that share a function or belong to a common pathway share upstream motifs. Different motifs are conserved upstream of different groups of genes. Comparative real-time PCR studies show co-expression of genes within each group (in sub-sets) during the life cycle of the parasite, suggesting co-regulation of these genes may be driven by the use of conserved upstream motifs. This is one of the first attempts to characterize cis-regulatory elements in the absence of any previously characterized elements and with very limited expression data (seven genes only). Using de novo pattern finding algorithms, we have identified specific DNA motifs that are conserved upstream of genes belonging to the same metabolic pathway or gene family. We have demonstrated the co-expression of these genes (often in subsets) using comparative real-time-PCR experiments thus establishing evidence for these conserved motifs as putative cis-regulatory elements. Given the lack of prior information concerning expression patterns and organization of promoters in C. parvum we present one of the first investigations of gene regulation in this important human pathogen.
Adverb code-switching among Miami's Haitian Creole–English second generation

The findings for adverbs and adverbial phrases in a naturalistic corpus of Miami Haitian Creole–English code-switching show that one language, Haitian Creole, asymmetrically supplies the grammatical frame while the other language, English, asymmetrically supplies mixed lexical categories like adverbs. Traces of code-switching with an English frame and Haitian Creole lexical categories suggest that code-switching is abstractly BIDIRECTIONAL. A quantitative methodology that codes the language-indexation of the token in addition to the surrounding lexical items was used for all mixed (e.g. xYx/yXy, xYy/yXx, yYx/xXy) and unmixed (xXx/yYy) adverbs. Discourse position, especially the left-periphery, is found to be a significant factor in adverb code-switching. Sociolinguistic and psycholinguistic analyses which acknowledge the ‘low’ status of one language and the ‘high’ status of the other explain better the frequency of mixed English adverbs in a Haitian Creole frame and the rarity of mixed Haitian Creole adverbs in an English frame than a minimalist approach, such as MacSwan's (1999 and subsequent work), which uses phi-feature valuation and entails asymmetry without bidirectionality. While I provide confirmation for Myers-Scotton's (1993) Matrix Language Frame approach, I emphasize that trace bidirectional data need to be accounted for by a theory that is grounded in the sociolinguistic and psycholinguistic realities.
Quasiconical free interaction between a swept shock and a turbulent boundary layer

Previous observations that fin-generated interactions are quasi-conical in nature were further confirmed by surface pressure measurements spanning Mach 2.5-3.5, which encompassed unseparated through strongly separated interactions. For strongly separated interactions in which the shock wave is bifurcated into a lambda-foot structure, the conical free interaction hypothesis was validated through an appropriate scaling of the far-field surface pressure distribution. The behavior of the lambda-foot structure, such as the decrease of the slope of the separation shock with interaction strength, was explained by invoking the conical free interaction hypothesis. Through the conical free interaction hypothesis, it was further shown that the triple-shock intersection behaves in a complicated manner with changes in interaction strength.
Measuring the wisdom of the crowds in network-based gene function inference

MOTIVATION: Network-based gene function inference methods have proliferated in recent years, but measurable progress remains elusive. We wished to better explore performance trends by controlling data and algorithm implementation, with a particular focus on the performance of aggregate predictions. RESULTS: Hypothesizing that popular methods would perform well without hand-tuning, we used well-characterized algorithms to produce verifiably 'untweaked' results. We find that most state-of-the-art machine learning methods obtain 'gold standard' performance as measured in critical assessments in defined tasks. Across a broad range of tests, we see close alignment in algorithm performances after controlling for the underlying data being used. We find that algorithm aggregation provides only modest benefits, with a 17% increase in AUROC above the mean AUROC. In contrast, data aggregation gains are enormous with an 88% improvement in mean AUROC. Altogether, we find substantial evidence to support the view that additional algorithm development has little to offer for gene function prediction. Availability and Implementation: The supplementary information contains a description of the algorithms, the network data parsed from different biological data resources, and a guide to the source code (available at: http://gillislab.cshl.edu/supplements/) CONTACT: jgillis@cshl.edu.
Metabolic and functional differences between brain and spinal cord mitochondria underlie different predisposition to pathology

Mitochondrial dysfunctions contribute to neurodegeneration, the locations of which vary among neurodegenerative diseases. To begin to understand what mechanisms may underlie higher vulnerability of...
Function of Proline Residues of MotA in Torque Generation by the Flagellar Motor of Escherichia coli

Bacterial flagellar motors obtain energy for rotation from the membrane gradient of protons or, in some species, sodium ions. The molecular mechanism of flagellar rotation is not understood. MotA and MotB are integral membrane proteins that function in proton conduction and are believed to form the stator of the motor. Previous mutational studies identified two conserved proline residues in MotA (Pro 173 and Pro 222 in the protein from Escherichia coli) and a conserved aspartic acid residue in MotB (Asp 32) that are important for function. Asp 32 of MotB probably forms part of the proton path through the motor. To learn more about the roles of the conserved proline residues of MotA, we examined motor function in Pro 173 and Pro 222 mutants, making measurements of torque at high load, speed at low and intermediate loads, and solvent-isotope effects (D2O versus H2O). Proton conduction by wild-type and mutant MotA-MotB channels was also assayed, by a growth defect that occurs upon overexpression. Several different mutations of Pro 173 reduced the torque of the motor under high load, and a few prevented motor rotation but still allowed proton flow through the MotA-MotB channels. These and other properties of the mutants suggest that Pro 173 has a pivotal role in coupling proton flow to motor rotation and is positioned in the channel near Asp 32 of MotB. Replacements of Pro 222 abolished function in all assays and were strongly dominant. Certain Pro 222 mutant proteins prevented swimming almost completely when expressed at moderate levels in wild-type cells. This dominance might be caused by rotor-stator jamming, because it was weaker when FliG carried a mutation believed to increase rotor-stator clearance. We propose a mechanism for torque generation, in which specific functions are suggested for the proline residues of MotA and Asp32 of MotB.
β-VLDL and acetylated-LDL binding to pigeon monocyte macrophages

Abstract Blood-derived monocytes are an important source of foam cells in atherosclerotic lesions of White Carneau pigeons. Based upon studies with cultured blood monocytes (monocyte macrophages) and peritoneal macrophages from a variety of mammalian species, it has been proposed that these cells become loaded with cholesteryl esters through the uptake of lipoproteins including, β-migrating very low density lipoproteins (β-VLDL) and low density lipoproteins that have been chemically modified in a manner analogous to experimental acetylation (Ac-LDL). The purpose of this study was to determine whether similar mechanisms functioned in pigeon monocyte macrophages. Radioiodinated pigeon β-VLDL and Ac-LDL were incubated with White Carneau pigeon monocyte macrophages that had been maintained in culture for 7 days. Scatchard analysis of the specific binding data revealed the presence of specific and saturable receptors for both β-VLDL and Ac-LDL. β-VLDL receptors had both low and high affinity binding components, whereas Ac-LDL receptors displayed a single class of high affinity binding sites. β-VLDL binding remained relatively constant from 3 to 10 days in culture while Ac-LDL binding increased with time in culture. Competition studies demonstrated a high degree of binding specificity for 125 I-Ac-LDL, but less for 125 I-β-VLDL. Binding of 125 I-β-VLDL was not competed for by Ac-LDL, but was by β-VLDL and by low density lipoproteins from both normal and hypercholesterolemic pigeons. Following binding of β-VLDL and Ac-LDL, the lipoproteins were rapidly internalized and degraded. Although the majority of degradation was secondary to internalization by the monocyte macrophages, approx. 5% of the degradation resulted from enzymatic activity in the culture medium, presumably due to secretion of proteolytic enzymes by the cells. As measured by esterification of [ 14 C]oleate to cholesterol, it was shown that the cholesterol liberated from the degradation of both β-VLDL and Ac-LDL stimulated cholesteryl ester synthesis in pigeon monocyte macrophages. These studies confirm the existence of specific β-VLDL and Ac-LDL receptors on the surface of pigeon monocyte macrophages which facilitate both internalization of the lipoproteins and subsequent stimulation of cholesteryl ester synthesis. This is the first demonstration of β-VLDL and Ac-LDL receptors on monocyte macrophages from an avian species, and the findings support the potential role for the receptor-mediated uptake of a variety of abnormal lipoproteins in the formation of monocyte-derived foam cells in the arterial wall of White Carneau pigeons during the development of atherosclerosis.
Improving virtual machine performance using a cross-run profile repository

Virtual machines for languages such as the Java programming language make extensive use of online profiling and dynamic optimization to improve program performance. But despite the important role that profiling plays in achieving high performance, current virtual machines discard a program's profile data at the end of execution, wasting the opportunity to use past knowledge to improve future performance. In this paper, we present a fully automated architecture for exploiting cross-run profile data in virtual machines. Our work addresses a number of challenges that previously limited the practicality of such an approach.We apply this architecture to address the problem of selective optimization, and describe our implementation in IBM's J9 Java virtual machine. Our results demonstrate substantial performance improvements on a broad suite of Java programs, with the average performance ranging from 8.8% -- 16.6% depending on the execution scenario.
Black beauty out of Mycobacterium fortuitum Cruz.

A black-pigmented strain developed spontaneously from a typical strain of Mycobacterium fortuitum.
Checklists, safety, my culture and me

The world is not flat. Hierarchy is a fact of life in society and in healthcare institutions. National, specialty-specific and institutional cultures may play an important role in shaping today's patient-safety climate. The influence of power distance on safety interventions is under-studied. Checklists may make power distance-hampered negotiations easier by providing a standardised aviation-like framework for communications and by democratising the environment. By using surveys and simulation, we might discover patterns of potentially hidden yet problematic interactions that might foster maintenance of the error swamp. We need to understand how people interact as members of a group as this is crucial for the development of generalisable safety interventions.
A novel reconfigurable power amplifier structure for multi-band and multi-mode portable wireless applications using a reconfigurable die and a switchable output matching network

A novel reconfigurable power amplifier structure for multi-band and multi-mode applications is presented. Included in the design are a reconfigurable output matching network and a reconfigurable die. To demonstrate the feasibility of the concept, a 900MHz/1.6GHz reconfigurable power amplifier with 33.8dBm/29.4dBm output power has been designed as a multi-chip module to validate the multi-band and multi-mode application. The new topology makes possible a 50% size reduction of the GaAs die and at least a 20% size reduction of the modules for two or more services. The topology is flexible and can be easily expanded to cover additional standards.
Infinite Prandtl number thermal convection in a spherical shell

A Galerkin technique is used to calculate the steady-state axisymmetric nonlinear convective motions in an infinite-Prandtl-number Boussinesq fluid in a relatively thick spherical shell heated from below. A reasonably complete study of the properties of the even and general axisymmetric steady states is carried out for a range of moderately supercritical Rayleigh numbers. In addition, stability analyses are conducted to determine which form of axisymmetric steady convection is the preferred one and whether the axisymmetric steady flows are unstable to azimuthal perturbations.
A comparison of three approaches for simulating fine-scale surface winds in support of wildland fire management: Part I. Model formulation and comparison against measurements

For this study three types of wind models have been defined for simulating surface wind flow in support of wildland fire management: (1) a uniform wind field (typically acquired from coarse-resolution (~4km) weather service forecast models); (2) a newly developed mass-conserving model and (3) a newly developed mass and momentum-conserving model (referred to as the momentum-conserving model). The technical foundation for the two new modelling approaches is described, simulated surface wind fields are compared to field measurements, and the sensitivity of the new model types to mesh resolution and aspect ratio (second type only) is discussed. Both of the newly developed models assume neutral stability and are designed to be run by casual users on standard personal computers. Simulation times vary from a few seconds for the mass-conserving model to ~1h for the momentum-conserving model using consumer-grade computers. Applications for this technology include use in real-time fire spread prediction models to support fire management activities, mapping local wind fields to identify areas of concern for firefighter safety and exploring best-case weather scenarios to achieve prescribed fire objectives. Both models performed best on the upwind side and top of terrain features and had reduced accuracy on the lee side. The momentum-conserving model performed better than the mass-conserving model on the lee side.
Self-Organizing Dynamics of Lexical Access in Normals and Aphasics

The goal of this article is to illustrate the application of self-organizing dynamics in the design of a model of lexical access. We focus particularly on the mapping of sound structure on to the lexicon and the influence of that structure on lexical access. The approach is tested in a series of two sets of simulations that explicate how lexical access might occur in normal subjects and aphasic patients. Both sets of simulations address the behavioral effects of both phonological and phonetic variability of prime stimuli on the magnitude of semantic priming. Results show that the model can successfully account for the behavioral effects associated with several kinds of acoustic manipulation, competitor presence, and the unfolding of those effects over time - primarily because it balances three important control parameters: resting lexical activation, positive feedback, and negative feedback. These simulations are offered as support (in the form of an existence proof) that deficits in the degree of lexical activation can account for the lexical processing impairments shown by Broca's aphasics who have reduced lexical activation, and Wernicke's aphasics who have increased lexical activation. Overall, results suggest that the present approach promises to offer a coherent theoretical framework within which to link empirical evidence in language processing and cognitive neuroscience in terms of possible underlying mechanisms.
Multi-Layer Inkjet Printed Contacts for Silicon Solar Cells

Ag, Cu, and Ni metallizations were inkjet printed with near vacuum deposition quality. The approach developed can be easily extended to other conductors such as Pt, Pd, Au, etc. Thick highly conducting lines of Ag and Cu demonstrating good adhesion to glass, Si, and printed circuit board (PCB) have been printed at 100-200degC in air and N2 respectively. Ag grids were inkjet-printed on Si solar cells and fired through the silicon nitride AR layer at 850degC, resulting in 8% cells. Next generation inks, including an ink that etches silicon nitride, have now been developed. Multi-layer inkjet printing of the etching ink followed by Ag ink produced contacts under milder conditions and gave solar cells with efficiencies as high as 12%
Challenges in Testing of Mixed Mode Analog/Digital ICs

Testing of digital and analog ICs has became an extremely complex and often expensive activity. Testing of mixed digital/analog ICs is even more complex because of an interaction between two different environments - digital and analog - generating new failure modes. This paper examines - from a testing standpoint basic characteristics of mixed digital/analog ICs. Out of the presented examination a possible new testing scenario, suitable for mixed ICs, is derived. It is argued that new mixed IC testing strategies must be build based on DFT techniques and that concepts successful in the digital domain must be expanded to cover entire mixed digital/analog testing arena.
Estimating design time for system circuits

System design complexity is growing rapidly. As a result, current development costs are constantly increasing. It is becoming increasingly difficult to estimate how much time it will take to design and verify these designs, which are getting denser and increasingly more complex. To compound this problem, circuit design cost estimation still does not have a quantitative approach. Although designing a system is very resource consuming, there is little work invested in measuring, understanding, and estimating the effort required. To address part of the current shortcomings, this paper introduces μPCBComplexity, a methodology to measure and estimate PCB (printed circuit board) design effort. PCBs are the central component of many systems and require large amounts of resources to properly design and verify. μPCBComplexity consists of two main parts; a procedure to account for the contributions of the different elements in the design, and a non-linear statistical regression of experimental measures in order to determine a good design effort metric. We use μPCBComplexity to evaluate a series of design effort estimators for twelve PCB designs. By using the proposed μPCBComplexity metric, designers can estimate PCB design effort.
Measuring substantial reductions in functioning in patients with chronic fatigue syndrome.

Purpose. All the major current case definitions for chronic fatigue syndrome (CFS) specify substantial reductions in previous levels of occupational, educational, social, or personal activities to meet criteria. Difficulties have been encountered in operationalizing ‘substantial reductions.’ For example, the Medical Outcomes Study Short Form-36 Health Survey (SF-36) has been used to determine whether individuals met the CFS disability criterion. However, previous methods of using the SF-36 have been prone to including people without substantial reductions in key areas of physical functioning when diagnosing CFS. This study sought to empirically identify the most appropriate SF-36 subscales for measuring substantial reductions in patients with CFS.Method. The SF-36 was administered to two samples of patients with CFS: one recruited from tertiary care and the other a community-based sample; as well as a non-fatigued control group. Receiver operating characteristics were used to determine the optimal cutoff ...
A 5 GHz class-AB power amplifier in 90 nm CMOS with digitally-assisted AM-PM correction

This paper presents a technique for correcting AM-PM distortion in power amplifiers. The technique uses a varactor as part of a tuned circuit to introduce a phase shift that counteracts the AM-PM distortion of the PA. The varactor is controlled by the amplitude of the IQ baseband data in a feedforward fashion. The technique has been demonstrated in a class-AB CMOS power amplifier designed for WEAN applications and implemented in a 90 nm CMOS process. The PA delivers 10.5 dBm of average power while transmitting at 54 Mbps (64 QAM). The proposed technique is shown to improve the efficiency of the PA by a factor of 2
The Measurements of the Intensity of Light

The wave theory’s ability to explain diffraction had long been considered one of the most important facts in favor of the theory. Even some opponents of the wave theory, such as Brewster, had to admit the advantage of the wave theory in explaining this phenomenon. Although diffraction seemed to be the last area where disputes between the two rival theories of light could occur, the wave account of diffraction was still challenged in the early 1840s. It was Richard Potter, Professor of Natural Philosophy and Astronomy at University College, London, who launched a series of attacks, based on his photometric experiments. The debate between Potter and wave theorists was quite unusual because it centered on diffraction, the stronghold of the wave theory.
Criminal Prosecutors: Experts or Elected Officials?

Prosecutors make an array of decisions impacting the lives of citizens. Should their decisions be subjected to popular oversight and control though democratic election or should prosecutors be members of professional bureaucracies insulated from the electorate? The evidence concerning the election of prosecutors suggests that the public is ill-served by them: Most incumbent chief prosecutors run unopposed, most incumbents who are opposed win, and the elections are mostly popularity contests. Elections might be improved, but having prosecutors trained and overseen by other officials knowledgeable about the demands of due process and committed to its values seems a better alternative. However, rule by prosecutorial experts itself raises a variety of questions, especially in democratic societies. Though I favor the expertise model, I concede that some of the decisions made by prosecutors are ones about which citizens in democratic societies ought to have input.