Miracle-dz/UniFAR-FTUs huggingface dataset:
Contribution of the M 1 Transmembrane Helix and PreM 1 Region to Positive Allosteric Modulation and Gating of N-Methyl-D-Aspartate Receptors s

N-methyl-D-aspartate (NMDA) receptors are glutamate-gated ion channels whose function is critical for normal excitatory synaptic transmission in the brain and whose dysfunction has been implicated in several neurologic conditions. NMDA receptor function is subject to extensive allosteric regulation both by endogenous compounds and by exogenous small molecules. Elucidating the structural determinants and mechanism of action by which allosteric regulators control gating will enhance our understanding of NMDA receptor activation and facilitate the development of novel therapeutics. Here, we investigated the structural determinants for (3-chlorophenyl)(6,7-dimethoxy-1-((4-methoxyphenoxy)methyl)3,4-dihydroisoquinolin-2(1H)-yl)methanone (CIQ), a GluN2C/ 2D-selective positive allosteric modulator. We show that CIQ does not bind to the amino-terminal domain of the NMDA receptor and does not share structural determinants with modulators acting at the agonist-binding domain dimer interface or ion channel pore. Rather, we identified critical determinants of CIQ modulation in the region near the first transmembrane helix of GluN2D, including in a putative preM1 cuff helix that may influence channel gating. We also show that mutations within the GluN2D pre-M1 region alter open probability of the NMDA receptor. These results suggest a novel site of action for potentiation of NMDA receptors by small molecules and implicate the pre-M1 region in NMDA receptor gating.
Petrology and Geochemistry of Rhizoliths from Plio-Pleistocene Fluvial and Marginal Lacustrine Deposits, East Lake Turkana, Kenya

ABSTRACT Recent studies of rhizoliths from the Koobi Fora Formation (Plio-Pleistocene) of East Lake Turkana, Kenya, indicate that their shapes vary with the depositional environment of their host sediment. Vertical rhizoliths are associated with channel-bar and overbank deposits of fluvial origin. These rhizoliths represent the tap roots of phreatophytes that lived in well-drained, upland settings. Horizontal rhizoliths predominate in facies ascribed to beaches, lagoons, and floodplains associated with ancient Lake Turkana. They are produced by water-emergent aquatic macrophytes and coastal grasses that grow in saturated or poorly drained soil environments. The rhizoliths consist of sparry and micritic calcite cements whose petrography and geochemistry reflect differences in diagenesis between the two types of root systems. The vertical roots contain little organic debris and have poorly developed meniscus and microstalactitic cements. These attributes reflect precipitation of the calcite in well-oxygenated, well-drained vadose conditions. In contrast, the cements of the horizontal root systems lack textures indicative of vadose conditions, contain abundant clay and plant debris, and display Mn concentrations as high as 4.5 cation percent. These features confirm that the horizontal rhizoliths developed in chemically reduced, water-saturated conditions. Bacterial decay of the plant debris maintained reduced Eh conditions while also supply ng abundant Mn2+ to the pore solutions. Groundwater that had moved through volcanic strata may have also contributed Mn2+. The Mn may have been incorporated in the calcite cements through a combined process of chemisorption and ionic substitution of Mn2+ as well as by inclusion of manganese oxides.
Investigation of the glyoxysome-peroxisome transition in germinating cucumber cotyledons using double-label immunoelectron microscopy

Microbodies in the cotyledons of cucumber seedlings perform two successive metabolic functions during early postgerminative development. During the first 4 or 5 d, glyoxylate cycle enzymes accumulate in microbodies called glyoxysomes. Beginning at about day 3, light-induced activities of enzymes involved in photorespiratory glycolate metabolism accumulate rapidly in microbodies. As the cotyledonary microbodies undergo a functional transition from glyoxysomal to peroxisomal metabolism, both sets of enzymes are present at the same time, either within two distinct populations of microbodies with different functions or within a single population of microbodies with a dual function. We have used protein A-gold immunoelectron microscopy to detect two glyoxylate cycle enzymes, isocitrate lyase (ICL) and malate synthase, and two glycolate pathway enzymes, serine:glyoxylate aminotransferase (SGAT) and hydroxypyruvate reductase, in microbodies of transition-stage (day 4) cotyledons. Double-label immunoelectron microscopy was used to demonstrate directly the co-existence of ICL and SGAT within individual microbodies, thereby discrediting the two-population hypothesis. Quantitation of protein A- gold labeling density confirmed that labeling was specific for microbodies. Quantitation of immunolabeling for ICL or SGAT in microbodies adjacent to lipid bodies, to chloroplasts, or to both organelles revealed very similar labeling densities in these three categories, suggesting that concentrations of glyoxysomal and peroxisomal enzymes in transition-stage microbodies probably cannot be predicted based on the apparent associations of microbodies with other organelles.
Database Concurrency Control in Multilevel Secure Database Management Systems

Concurrent execution of transactions in database management systems (DBMSs) may lead to contention for access to data, which in a multilevel secure DBMS (MLS/DBMS) may lead to insecurity. Security issues involved in database concurrency control for MLS/DBMSs are examined, and it is shown how a scheduler can affect security. Data conflict security, (DC-security), a property that implies a system is free of covert channels due to contention for access to data, is introduced. A definition of DC-security based on noninterference is presented. Two properties that constitute a necessary condition for DC-security are introduced along with two simpler necessary conditions. A class of schedulers called output-state-equivalent is identified for which another criterion implies DC-security. The criterion considers separately the behavior of the scheduler in response to those inputs that cause rollback and those that do not. The security properties of several existing scheduling protocols are characterized. Many are found to be insecure. >
Time-resolved resting-state brain networks

Significance Large-scale organizational properties of brain networks mapped with functional magnetic resonance imaging have been studied in a time-averaged sense. This is an oversimplification. We demonstrate that brain activity between multiple pairs of spatially distributed regions spontaneously fluctuates in and out of correlation over time in a globally coordinated manner, giving rise to sporadic intervals during which information can be efficiently exchanged between neuronal populations. We argue that dynamic fluctuations in the brain’s organizational properties may minimize metabolic requirements while maintaining the brain in a responsive state. Neuronal dynamics display a complex spatiotemporal structure involving the precise, context-dependent coordination of activation patterns across a large number of spatially distributed regions. Functional magnetic resonance imaging (fMRI) has played a central role in demonstrating the nontrivial spatial and topological structure of these interactions, but thus far has been limited in its capacity to study their temporal evolution. Here, using high-resolution resting-state fMRI data obtained from the Human Connectome Project, we mapped time-resolved functional connectivity across the entire brain at a subsecond resolution with the aim of understanding how nonstationary fluctuations in pairwise interactions between regions relate to large-scale topological properties of the human brain. We report evidence for a consistent set of functional connections that show pronounced fluctuations in their strength over time. The most dynamic connections are intermodular, linking elements from topologically separable subsystems, and localize to known hubs of default mode and fronto-parietal systems. We found that spatially distributed regions spontaneously increased, for brief intervals, the efficiency with which they can transfer information, producing temporary, globally efficient network states. Our findings suggest that brain dynamics give rise to variations in complex network properties over time, possibly achieving a balance between efficient information-processing and metabolic expenditure.
An improved aerodynamic evaporation technique for large lakes with application to the International Field Year for the Great Lakes

An improved bulk transfer technique was developed for large-lake evaporation based upon recent boundary layer research near the air-water interface. A variable bulk transfer coefficient, dependent upon atmospheric stability, is given as a function of the nondimensional wind speed gradient, the potential temperature gradient, and the Monin-Obukhov length. The technique, which requires the same data as the simplified mass transfer equation, can be readily applied to large lakes throughout the world. This technique has been applied to the Lake Ontario data set collected during the International Field Year for the Great Lakes. The inclusion of stability increases calculated evaporation during the unstable high-evaporation months and decreases calculated condensation during the stable late spring months to more realistic levels. Comparisons between the Lake Hefner mass transfer equation and the technique recommended here indicate that the mass transfer equation may overestimate Lake Ontario evaporation by approximately 20%.
The Competitive Effects of Not‐for‐Profit Hospital Mergers: A Case Study

Applying conventional horizontal merger enforcement rules to nonprofit hospitals is controversial. Critics contend that the different objective function of not-for-profits entities should mitigate competitive concerns about mergers involving nonprofit hospitals. We analyze a merger that reduced the number of competitors (both nonprofit) in the alleged relevant market from three to two. We find that the transaction was followed by significant price increases; we reject the hypothesis that these price increases reflect higher post-merger quality. This study should help policymakers assess the validity of current merger enforcement rules, especially as they apply to not-for-profit enterprises. Copyright 2001 by Blackwell Publishing Ltd
Women Infant and Children program participants' beliefs and consumption of soy milk : Application of the Theory of Planned Behavior

The purpose of this study was to determine if Theory of Planned Behavior (TPB) variables predict soy milk intake in a sample of WIC participants in 2 Illinois counties (n = 380). A cross-sectional survey was used, which examined soy foods intake, behavioral beliefs, subjective norms, motivation, and intention. Soy product intake was low at both sites, and many participants (40%) did not know that soy milk was WIC approved. Most (> 70%) wanted to comply with their health care providers, but didn't know their opinions about soy milk (50-66%). Intention was significantly correlated with intake (0.507, P ≤ 0.01; 0.308, P ≤ 0.05). Environmental beliefs (0.282 and 0.410, P ≤ 0.01) and expectancy beliefs (0.490 and 0.636, P ≤ 0.01) were correlated with intention. At site 1, 30% of the variance in intention to consume soy milk was explained by expectancy beliefs and subjective norm beliefs (P < 0.0001); at site 2, 40% of the variance in intention was explained by expectancy beliefs. The TPB variables of expectancy beliefs predicted intention to consume soy milk in WIC participants. Therefore, knowing more about the health benefits of soy and how to cook with soy milk would increase WIC participants' intention to consume soy milk. Positive messages about soy milk from health care providers could influence intake.
Hydric Conditions and Hydromorphic Properties within a Mollisol Catena in Southeastern Minnesota

Wetlands are characterized by wetland hydrology, hydrophytic vegetation, and hydric soils. The multiparameter approach to wetland identification and delineation requires independent evaluation of all three diagnostic characteristics. Hydric soils can be determined from data collected under saturated and anaerobic soil conditions or by using accepted field indicators. The objectives of this research were to: (i) evaluate the presence of wetland hydrology and hydric soil conditions, (ii) examine associations between observed soil hydrology and soil morphologic properties, and (iii) evaluate current field indicators of hydric soils for their applicability to presumed hydric Mollisols. We used wells, piezometers, and tensiometers to measure saturated conditions, and Pt electrodes to measure anaerobic and reducing conditions for five soils along a hillslope transect from summit to drainageway in southeastern Minnesota. Saturated conditions were observed within 25 cm of the soil surface for all five soils for at least a few days each year between 1992 and 1995, mainly in the early spring and the late fall when soil temperatures at 50 cm were not always >5°C. Only the soil in the drainageway was saturated and anaerobic during the microbial activity season in more than one year. Soil morphology reflects the presence of saturated and anaerobic conditions in the form of thick, black surface horizons. Absence of Fe concentrations and depletions in the upper 30 cm of presumed hydric soils may reflect the absence of Fe-reducing conditions as a result of saturated conditions when soil temperatures do not facilitate abundant microbial activity. Contribution no. 971250011 from the Minnesota Agric. Exp. Stn. , St. Paul.
Perlecan-Induced Suppression of Smooth Muscle Cell Proliferation Is Mediated Through Increased Activity of the Tumor Suppressor PTEN

Abstract— We were interested in the elucidation of the interaction between the heparan sulfate proteoglycan, perlecan, and PTEN in the regulation of vascular smooth muscle cell (SMC) growth. We verified serum-stimulated DNA synthesis, and Akt and FAK phosphorylation were significantly reduced in SMCs overexpressing wild-type PTEN. Our previous studies showed perlecan is a potent inhibitor of serum-stimulated SMC growth. We report in the present study, compared with SMCs plated on fibronectin, serum-stimulated SMCs plated on perlecan exhibited increased PTEN activity, decreased FAK and Akt activities, and high levels of p27, consistent with SMC growth arrest. Adenoviral-mediated overexpression of constitutively active Akt reversed perlecan-induced SMC growth arrest while morpholino antisense-mediated loss of endogenous PTEN resulted in increased growth and phosphorylation of FAK and Akt of SMCs on perlecan. Immunohistochemical and Western analyses of balloon-injured rat carotid artery tissues showed a transient increase in phosphoPTEN (inactive) after injury, correlating to high rates of neointimal cell replication; phosphoPTEN was largely limited to actively replicating SMCs. Similarly, in the developing rat aorta, we found increased PTEN activity associated with increased perlecan deposition and decreased SMC replication rates. However, significantly decreased PTEN activity was detected in aortas of perlecan-deficient mouse embryos, consistent with SMC hyperplasia observed in these animals, compared with E17.5 heterozygous controls that produce abundant amounts of perlecan at this developmental time point. Our data show PTEN is a potent endogenously produced inhibitor of SMC growth and increased PTEN activity mediates perlecan-induced suppression of SMC proliferation.
A Novel, Voltage‐Dependent Nonselective Cation Current Activated by Insulin in Guinea Pig Isolated Ventricular Myocytes

&NA; —Insulin regulates cardiac metabolism and function by targeting metabolic proteins or voltage‐gated ion channels. This study provides evidence for a novel, voltage‐dependent, nonselective cation channel (NSCC) in the heart. Under voltage clamp at 37°C and with major known conductances blocked, insulin (1 nmol/L to 1 &mgr;mol/L) activated an outwardly rectifying current (Iinsulin) in guinea pig ventricular myocytes. Iinsulin could be carried by Cs+, K+, Li+, and Na+ ions but not by NMDG+. It was inhibited by the NSCC blockers gadolinium and SKF96365 but not flufenamic acid. Iinsulin was largely blocked by the insulin receptor tyrosine kinase inhibitor HNMPA‐(AM)3 and by the phospholipase C inhibitor U73122 but not by its inactive analogue U73433. Staurosporine, a potent blocker of protein kinase C, did not prevent the activation of Iinsulin. Application of an analogue of diacylglycerol, 1‐oleoyl‐2‐acetyl‐sn‐glycerol, mimicked the effect of insulin. This activated an outwardly rectifying NSCC that could be carried by Cs+, K+, Li+, or Na+ and that was blocked by gadolinium but not by flufenamic acid or staurosporine. We conclude that the intracellular pathway leading to activation of this novel cardiac NSCC involves phospholipase C, is protein kinase C‐independent, and may depend on direct channel activation by diacylglycerol. (Circ Res. 2003;92:765–768.)
SFB 649 Discussion Paper 2005-054 Aid Effectiveness and Limited Enforceable Conditionality

This paper analyzes optimal foreign aid policy in a neoclassical framework with a conflict of interest between the donor and the recipient government. Aid conditionality is modelled as a limited enforceable contract. We define conditional aid policy to be self-enforcing if, at any point in time, the conditions imposed on aid funds are supportable by the threat of a permanent aid cutoff from then onward. Quantitative results show that the effectiveness of unconditional aid is low while self-enforcing conditional aid strongly stimulates the economy. However, increasing the welfare of the poor comes at high cost: to ensure aid effectiveness, less democratic political regimes receive permanently larger aid funds. JEL: E13, F35, O11, O19. ∗Address: Humboldt-University of Berlin, School of Business and Economics, Institute of Economic Policy, Spandauer Str. 1, 10178 Berlin. This research was supported by the Deutsche Forschungsgemeinschaft through the SFB 649 “Economic Risk”. I am especially grateful to Harald Uhlig for many helpful suggestions and comments. I thank Christian Stoltenberg, Ralf Brüggemann, Carsten Trenkler, Mirko Wiederholt and seminar participants at Humboldt-University for helpful comments. All errors are mine.
Medio-Lateral Postural Instability in Subjects with Tinnitus

Background: Many patients show modulation of tinnitus by gaze, jaw or neck movements, reflecting abnormal sensorimotor integration, and interaction between various inputs. Postural control is based on multi-sensory integration (visual, vestibular, somatosensory, and oculomotor) and indeed there is now evidence that posture can also be influenced by sound. Perhaps tinnitus influences posture similarly to external sound. This study examines the quality of postural performance in quiet stance in patients with modulated tinnitus. Methods: Twenty-three patients with highly modulated tinnitus were selected in the ENT service. Twelve reported exclusively or predominately left tinnitus, eight right, and three bilateral. Eighteen control subjects were also tested. Subjects were asked to fixate a target at 40 cm for 51 s; posturography was performed with the platform (Technoconcept, 40 Hz) for both the eyes open and eyes closed conditions. Results: For both conditions, tinnitus subjects showed abnormally high lateral body sway (SDx). This was corroborated by fast Fourrier Transformation (FFTx) and wavelet analysis. For patients with left tinnitus only, medio-lateral sway increased significantly when looking away from the center. Conclusion: Similarly to external sound stimulation, tinnitus could influence lateral sway by activating attention shift, and perhaps vestibular responses. Poor integration of sensorimotor signals is another possibility. Such abnormalities would be accentuated in left tinnitus because of the importance of the right cerebral cortex in processing both auditory–tinnitus eye position and attention.
Characterization and prognostic features of secondary acute myeloid leukemia in a population‐based setting: A report from the Swedish Acute Leukemia Registry

Patients with secondary acute myeloid leukemia (AML) often escape inclusion in clinical trials and thus, population‐based studies are crucial for its accurate characterization. In this first large population‐based study on secondary AML, we studied AML with an antecedent hematological disease (AHD‐AML) or therapy‐related AML (t‐AML) in the population‐based Swedish Acute Leukemia Registry. The study included 3,363 adult patients of which 2,474 (73.6%) had de novo AML, 630 (18.7%) AHD‐AML, and 259 (7.7%) t‐AML. Secondary AML differed significantly compared to de novo AML with respect to age, gender, and cytogenetic risk. Complete remission (CR) rates were significantly lower but early death rates similar in secondary AML. In a multivariable analysis, AHD‐AML (HR 1.51; 95% CI 1.26–1.79) and t‐AML (1.72; 1.38–2.15) were independent risk factors for poor survival. The negative impact of AHD‐AML and t‐AML on survival was highly age dependent with a considerable impact in younger patients, but without independent prognostic value in the elderly. Although patients with secondary leukemia did poorly with intensive treatment, early death rates and survival were significantly worse with palliative treatment. We conclude that secondary AML in a population‐based setting has a striking impact on survival in younger AML patients, whereas it lacks prognostic value among the elderly patients. Am. J. Hematol. 90:208–214, 2015. © 2014 Wiley Periodicals, Inc.
Effects of mobile phone use on brain tissue from the rat and a possible protective role of vitamin C – a preliminary study

Purpose: To evaluate effects of mobile phone use on brain tissue and a possible protective role of vitamin C. Materials and methods: Forty female rats were divided into four groups randomly (Control, mobile phone, mobile phone plus vitamin C and, vitamin C alone). The mobile phone group was exposed to a mobile phone signal (900 MHz), the mobile phone plus vitamin C group was exposed to a mobile phone signal (900 MHz) and treated with vitamin C administered orally (per os). The vitamin C group was also treated with vitamin C per os for four weeks. Then, the animals were sacrificed and brain tissues were dissected to be used in the analyses of malondialdehyde (MDA), antioxidant potential (AOP), superoxide dismutase, catalase (CAT), glutathione peroxidase (GSH-Px), xanthine oxidase, adenosine deaminase (ADA) and 5′nucleotidase (5′-NT). Results: Mobile phone use caused an inhibition in 5′-NT and CAT activities as compared to the control group. GSH-Px activity and the MDA level were also found to be reduced in the mobile phone group but not significantly. Vitamin C caused a significant increase in the activity of GSH-Px and non-significant increase in the activities of 5′-NT, ADA and CAT enzymes. Conclusion: Our results suggest that vitamin C may play a protective role against detrimental effects of mobile phone radiation in brain tissue.
Order of Magnitude Reductions in the Size of Enterprise Search Result Sets Through the Use of Subject Indexes

Keyword search has failed to adequately meet the needs of enterprise users. This is largely due to the indeterminate nature of languages. We argue a different approach needs to be taken, and draw on the success of previous library indexing concepts to propose a solution. We test our solution by performing search queries on a large research database. By incorporating readily available subject indexes into the search process, we obtain order of magnitude improvements in the performance of search queries. Our performance measure is the ratio of the number of documents returned without using subject indexes to the number of documents returned when subject indexes are used. We explain why the observed tenfold improvement in search performance on our research database can be expected to occur for searches on a wide variety of enterprise document stores.