cssi/SciSciGPT-SciSciNet huggingface dataset:
Transforming Growth Factor-β1 (TGF-β1) Utilizes Distinct Pathways for the Transcriptional Activation of MicroRNA 143/145 in Human Coronary Artery Smooth Muscle Cells *

MicroRNA 143/145 (miR143/145) is restricted to adult smooth muscle cell (SMC) lineages and mediates, in part, the expression of several SMC contractile genes. Although the function of miR143/145 has begun to be elucidated, its transcriptional regulation in response to various signaling inputs is poorly understood. In an effort to define a miR signature for SMC differentiation, we screened human coronary artery SMCs for miRs modulated by TGF-β1, a known stimulus for SMC differentiation. Array analysis revealed a number of TGF-β1-induced miRs, including miR143/145. Validation studies showed that TGF-β1 stimulated miR143/145 expression in a dose- and time-dependent manner. We utilized several chemical inhibitors and found that SB203580, a specific inhibitor of p38MAPK, significantly decreased TGF-β1-induced miR143/145 expression. siRNA studies demonstrated that the effect of TGF-β1 on miR143/145 was dependent upon the myocardin and serum response factor transcriptional switch as well as SMAD4. TGF-β1 stimulated a 580-bp human miR143/145 enhancer, and mutagenesis studies revealed a critical role for both a known CArG box and an adjacent SMAD-binding element for full TGF-β1-dependent activation of the enhancer. Chromatin immunoprecipitation assays documented TGF-β1-mediated enrichment of SMAD3 and SMAD4 binding over the enhancer region containing the SMAD-binding element. Pre-miR145 strongly promoted SMC differentiation, whereas an anti-miR145 partially blocked TGF-β1-induced SMC differentiation. These results demonstrate a dual pathway for TGF-β1-induced transcription of miR143/145, thus revealing a novel mechanism underlying TGF-β1-induced human vascular SMC differentiation.
Trends in science education: some observations of exemplary programmes in the United States

The National Science Teachers Association in the United States undertook a major new project in 1982‐a Search for Excellence in Science Education. For the first year Project Synthesis desired state descriptions were used as criteria for searches conducted in each state. Subsequently, new task forces were at work defining excellence and developing search criteria from a variety of views. A total of 104 exemplary programmes have been selected to date. An analysis of the Focus on Excellence monographs reveals some national trends in school science. These major trends include: (1) significant involvement of local communities in programme development and instruction; (2) science/technology/society as a curriculum focus; (3) laboratories defined as the real world; and (4) a focus first on qualitative considerations and later on quantitative ones. These trends are discussed, analysed and exemplified with the exemplary programmes identified across the United States.
Connectivity and piezoelectric-pyroelectric composites

Abstract Connectivity is a critical parameter in composites designed for use as piezoelectric transducers or as pyroelectric detectors. There are ten important connectivity patterns in diphasic solids, ranging from a 0-0 unconnected checkerboard pattern to a 3-3 pattern in which both phases are three dimensionally self-connected. Processing methods for manufacturing some of these patterns are described. Series and parallel models for composite piezoelectrics and pyroelectrics lead to several interesting results, such as a diphasic pyroelectric in which neither phase is pyroelectric. The models are also helpful in interpreting the structure-property relations in single-phase materials where the crystal structures mimic certain connectivity patterns.
Observation and LEED I–V analysis of the Ge(111)-1×1-Sb system

Abstract When antimony is adsorbed at submonolayer coverage on a cleaved Ge(111) surface, the clean (2 × 1) surface transforms to a (1 × 1) structure. A dynamical low energy electron diffraction (LEED) intensity anlysis was performed to study this system. The results suggest that Sb adatoms replace the outermost Ge atoms, resulting in a well-ordered bulk-like (1 × 1) surface. This system, like that of a Sb overlayer on Si(111) surfaces, demonstrates that adatoms can remove a surface reconstruction.
Evidence-based management of thrombosis in the antiphospholipid antibody syndrome.

Recommendations for the management of thrombosis in the antiphospholipid antibody syndrome have been based largely on retrospective case series. Several clinical trials have been recently published on the management of thrombosis in general. Two clinical trials have specifically addressed thrombosis in antiphospholipid antibody syndrome, and one is underway. These new clinical trials have challenged the previous dogma of a target International Normalized Ratio of 3 to 4 (“high-intensity” warfarin).
RANKL Employs Distinct Binding Modes to Engage RANK and the Osteoprotegerin Decoy Receptor

Summary Osteoprotegerin (OPG) and receptor activator of nuclear factor κB (RANK) are members of the tumor necrosis factor receptor (TNFR) superfamily that regulate osteoclast formation and function by competing for RANK ligand (RANKL). RANKL promotes osteoclast development through RANK activation, while OPG inhibits this process by sequestering RANKL. For comparison, we solved crystal structures of RANKL with RANK and RANKL with OPG. Complementary biochemical and functional studies reveal that the monomeric cytokine-binding region of OPG binds RANKL with ∼500-fold higher affinity than RANK and inhibits RANKL-stimulated osteoclastogenesis ∼150 times more effectively, in part because the binding cleft of RANKL makes unique contacts with OPG. Several side chains as well as the C-D and D-E loops of RANKL occupy different orientations when bound to OPG versus RANK. High affinity OPG binding requires a 90s loop Phe residue that is mutated in juvenile Paget's disease. These results suggest cytokine plasticity may help to fine-tune specific tumor necrosis factor (TNF)-family cytokine/receptor pair selectivity.
Adaptive response time control for metadata matching in information dissemination systems

Information dissemination is of increasing importance to our society. Existing work mainly focuses on delivering information from sources to sinks in a timely manner based on established subscriptions, with the assumption that those subscriptions are persistent. However, the bottleneck of many information dissemination systems is actually the matching process to continuously reevaluate such subscriptions between numerous sources and numerous sinks, in response to dynamically varying information attributes at runtime. In this paper, we propose an adaptive control architecture to meet the response time constraints on metadata matching in an example information dissemination system. Our adaptive controller features a rigorous design based on well-established control theory for guaranteed control accuracy and system stability. Furthermore, our controller can adapt to changes in the system model without reconfiguration and profiling. Empirical results on a physical testbed demonstrate that our controller has more accurate control and improved system quality of service than both an open-loop solution and a typical heuristic solution.
Treating schizophrenia symptoms with an α7 nicotinic agonist, from mice to men

Current antipsychotic treatments fail to fully address the range of symptoms of schizophrenia, particularly with respect to social and occupational dysfunctions. Recent work has highlighted the role of nicotinie in both cognitive and attentional deficits as well as deficient processing of repetitive sensory information. The predilection for schizophrenia patients to be extremely heavy cigarette smokers may be related to their attempt to compensate for a reduction in hippocampal α7 nicotinic cholinergic receptors by delivering exogenous ligand to the remaining receptors. Studies in rodent models of both learning and memory deficits and deficits in sensory inhibition have confirmed a role for the α7 subtype of the nicotinic cholinergic receptor in these processes. Rodent studies also demonstrated the efficacy of a selective partial α7 nicotinic agonist, DMXBA, to improve these deficits. Subsequent human clinical trials demonstrated improved sensory inhibition in 12 schizophrenia patients and showed improvement in several subtests of the RBANS learning and memory assessment instrument. These data suggest that therapeutic agents selected for α7 nicotinic activity may have utility in treating certain symptoms of schizophrenia.
The economics of costly risk sorting in competitive insurance markets

In the last twenty years, state and federal policy makers have often been asked to restrict the criteria, or tests, on which insurance companies may base their risk categorization. Insurance companies have responded that it is fair and reasonable to charge groups with different probabilities of death or accident actuarially fair rates for each group. The companies argue that if they are not allowed to make these distinctions, the result will be adverse selection with low-risk individuals self-insuring to a greater extent than is efficient and high-risk individuals overinsuring. This paper analyzes the efficiency of insurance companies’ incentives to use certain types of sorting devices-those that are themselves costly to society. Genetic screening, tests for the HIV (AIDS) virus, and criteria that require extensive monitoring of behavior (e.g., cigarette smoking habits) all use real resources to separate risk groups. Such sorting devices do not necessarily enhance efficiency. Though the decline in adverse selection does increase total surplus, this increase may be more than offset by the resource costs associated with determining individuals’ risk levels. Still, the test may be used in private insurance markets, because the gains to low-risk individuals from the sorting come not just from the increase in total surplus but also include a transfer of wealth from highrisk people. So long as the low-risk people would be made better off by distinguishing themselves, they will do so, and competitive firms will find it profitable to offer them lower insurance rates. The analysis is in the tradition of Spence’s (1973) signalling theory.’ Just as education yields a greater private return than social return in Spence’s model, the next section demonstrates that risk-sorting yields a greater return to low-risk individuals than to society as a whole. The basic point of inefficient costly risksorting has been made by Cracker and Snow (1986) who have also shown that price/quantity bundling to induce self-selective sorting, as proposed by Rothschild and Stiglitz (1976), may be imposed inefficiently. Section II gives some intuition for these results. Sections III and IV extend the Cracker and Snow analysis in two directions. Section III considers the role of a consumer’s information about his own risk
Whole-Field Residual Stress Measurements In Silicon Wafers During Integrated Circuit Fabrication

An optical method is proposed which generates the two-dimensional out-of-plane partial contours of silicon wafers and requires only a single numerical differentiation to compute the whole-field residual stress distribution. The optical arrangement for the method requires the use of either a linear or a crossed grating and two large lenses. At the recording stage, this arrangement results in an instantaneous reconstruction of the grating lines into the contours of partial slopes of the wafer. Visual inspection of these contours allows an immediate qualitative evaluation of the local stress variations. Contours with good contrast are obtained even for wafers with circuits printed on them. The partial curvatures are obtained by numerically differentiating the slope contour data. The wafer is modelled as a composite structure consisting of a thin film deposited on the silicon substrate. The two-dimensional residual stress distributions in the film and the substrate are obtained from the curvatures using a plate bending theory approach. The proposed method was used to follow the development of residual stresses in silicon wafers during integrated circuit fabrication using an n-MOS silicon gate process. It was found that the local oxidation step introduced maximum residual stresses whereas the metalization step had a small counter influence on the stresses. The local residual stress variations were enough to cause the conventional average measure to be in error by a factor of two even for wafers without stacking faults. This method can be a valuable tool for a fast and accurate quality control of incoming and outgoing wafers, and can provide useful guidelines for wafer fabrication process research.
Collective excitations in the accumulation layer of InAs(110): Nonlocal response theory.

We discuss plasmon and phonon modes in the accumulation layer of a model semiconductor with the aid of calculations based on a nonlocal description of dielectric response in the random-phase approximation. The first model we consider is that of a polarizable jellium slab at finite temperature with surface charges that bend the bands downward; lattice vibrations are ignored. Choosing model parameters appropriate to lightly doped InAs(110) at room temperature, we obtain intersubband as well as intrasubband plasmons and discuss their dispersion relations, localization, and line shapes. Evidence for two-dimensional and ``acoustic'' plasmons is presented: dispersion relations that have square-root and linear behavior at long wavelengths, respectively. All plasmon modes are strongly damped when their dispersion curves enter the single-particle continua. When the dynamical response of the lattice is included in the model, we obtain coupled plasmon-phonon modes or ``plasmarons'' and study their dispersion and line shapes. Our results confirm and extend the interpretation of high-resolution electron-energy-loss spectroscopy data reported recently for InAs(110) exposed to atomic hydrogen.
High-pressure structural and electronic properties of carbon

The high-pressure properties of carbon in eight different structures are calculated using an ab initio pseudopotential local-orbital method. In particular, the structural properties of hexagonal diamond and variation of its fundamental band gap with pressure are calculated for the first time. The variation of the fundamental gap in hexagonal diamond is found to have the opposite sign to that in cubic diamond, although the cubic and hexagonal forms have almost identical structural properties. Among the structures examined, diamond is found to transform under hydrostatic pressure first to the fourfold coordinated bc-8 (or Si-III) structure. The bc-8 form is favored at pressures greater than 11.1 Mbar. This is a slightly lower transformation pressure than that recently calculated using the pseudopotential plane-wave method. The sixfold coordinated structures, simple cubic and \ensuremath{\beta}-tin, are found at low pressure to be kinetically unstable, transforming spontaneously, without an energy barrier, into the cubic diamond structure. This result suggests that sixfold coordination of liquid carbon will be unlikely to occur at moderate pressure and temperature. Similarly, sixfold coordination is not expected in carbon clusters. A method of fully utilizing crystal symmetry to reduce the amount of computation in evaluating two- and three-center integrals needed in the local-orbital method is developed for the present calculations.
Dual targeting of the PI3K/Akt/mTOR pathway as an antitumor strategy in Waldenstrom macroglobulinemia

We have previously shown clinical activity of a mammalian target of rapamycin (mTOR) complex 1 inhibitor in Waldenstrom macroglobulinemia (WM). However, 50% of patients did not respond to therapy. We therefore examined mechanisms of activation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR in WM, and mechanisms of overcoming resistance to therapy. We first demonstrated that primary WM cells show constitutive activation of the PI3K/Akt pathway, supported by decreased expression of phosphate and tensin homolog tumor suppressor gene (PTEN) at the gene and protein levels, together with constitutive activation of Akt and mTOR. We illustrated that dual targeting of the PI3K/mTOR pathway by the novel inhibitor NVP-BEZ235 showed higher cytotoxicity on WM cells compared with inhibition of the PI3K or mTOR pathways alone. In addition, NVP-BEZ235 inhibited both rictor and raptor, thus abrogating the rictor-induced Akt phosphorylation. NVP-BEZ235 also induced significant cytotoxicity in WM cells in a caspase-dependent and -independent manner, through targeting the Forkhead box transcription factors. In addition, NVP-BEZ235 targeted WM cells in the context of bone marrow microenvironment, leading to significant inhibition of migration, adhesion in vitro, and homing in vivo. These studies therefore show that dual targeting of the PI3K/mTOR pathway is a better modality of targeted therapy for tumors that harbor activation of the PI3K/mTOR signaling cascade, such as WM.
Fish Oil and Extruded Soybeans Fed in Combination Increase Conjugated Linoleic Acids in Milk of Dairy Cows More Than When Fed Separately

Eight multiparous Holstein and four multiparous Brown Swiss (78 ± 43 DIM) cows were used in a 4 x 4 Latin square with 28-d periods to evaluate if feeding fish oil with a source of linoleic acid (extruded soybeans) would stimulate additional amounts of conjugated linoleic acid in milk. Four treatments consisted of a control diet with a 50:50 ratio of forage to concentrate (DM basis), a control diet with 2% added fat from either menhaden fish oil or extruded soybeans, or a combination of fish oil and extruded soybeans each adding 1% fat. DM intake (24.3, 21.6, 24.5, and 22.5 kg/d, for control, fish oil, extruded soybeans, and combination diets, respectively), milk production (32.1, 29.1, 34.6, and 31.1 kg/d), and milk fat content (3.51, 2.79, 3.27, and 3.14%) were lower for cows that consumed either fish oil-containing diet, especially the 2% fish oil diet. The proportion of n-3 fatty acids in milk fat increased similarly among all three fat-supplemented diets. Concentrations of transvaccenic acid (1.00, 4.16, 2.17, and 3.51 g/100 g of fatty acids) and cis-9, trans-11 conjugated linoleic acid (0.60, 2.03, 1.16, and 1.82 g/100 g of fatty acids) in milk fat increased more with fish oil than with extruded soybeans. When fed the combination diet, these fatty acids were approximately 50% higher than expected for Holsteins, whereas concentrations were similar for Brown Swiss compared with feeding each fat source separately. These data indicated that fish oil modifies ruminal or systemic functions, stimulating increased conversion of linoleic acid into transvaccenic and conjugated linoleic acids.
Heart disease during pregnancy. Which cardiovascular changes are normal or transient

A normal, uncomplicated pregnancy causes many physiologic cardiovascular changes and symptoms. For example, maternal blood volume, heart rate, and cardiac output increase, and fatigue, orthopnea, and presyncope often occur. In general, these findings are innocuous. Physicians need to recognize those that are not typically associated with pregnancy, such as diastolic murmurs, paroxysmal nocturnal dyspnea, and syncope. Diagnostic evaluation of pregnant women must be approached cautiously to avoid risk to the fetus. Methods using ionizing radiation should be avoided whenever possible. Hypertension, one of the most common complications of pregnancy, may be transient and benign, or it may be chronic or gestational. Early recognition and intervention are beneficial to both the mother and the child.
Temperature Dependence of the Thermal Conductivity of Materials for Microelectronic Packaging: Measuring and Modelling Effects of Microstructure and Impurities

The materials studied in this research, having a wide range of thermal conductivities, permit a study of the mechanisms which affect their behavior. Data on the thermal conductivity of several substrate materials, over a wide temperature range, were analyzed using the Klemens model. Parameters in this model, which include crystallite size and impurity concentration, are determined through a nonlinear least squares fitting routine and related, where possible, to values obtained by other techniques. This analysis predicts an achievable upper limit of 290 W/m.K for very high purity sintered AlN with 5 micron crystallites.
U(1) lattice gauge theory in the electric-field representation

The Hamiltonian formulation of U(1) lattice gauge theory is studied in a basis of eigenstates of the electric-field operator. The guided-random-walk algorithm of Chin et al. is transcribed to the electric-field basis, and exact ground-state properties of the theory in three space dimensions are calculated. A novel variational scheme is used to compute the potential between two static charges for two space dimensions.
A geometric approach to the almost convexity and growth of some nilpotent groups

Cannon I-3] has defined the property of almost convexity for the Cayley graph of a group with a given generating set. One takes the combinatorial ball of radius n in the Cayley graph and asks the following question: If two vertices in this ball are distance 2 from each other in the Cayley graph, how far must we travel inside the ball of radius n to get from one to the other? If this number is bounded independent of n, the group is said to be almost convex. Almost convexity relates metric properties of the Cayley graph to the efficiency with which that graph can be constructed, and therefore to the efficiency of algorithms for calculating in the group. The following sorts of groups are known I-3] to be almost convex: finite groups, HNN extensions and free products with amalgamation of finite groups, free groups, abelian groups, co-compact hyperbolic groups, and small cancellation groups. Recently Cannon, Floyd, Grayson and Thurston 1-5] have shown that groups acting as Solv geometry isometrics are not almost convex. Of Thurston's eight geometries [7], this leaves Nil and PSL2R. We will show that in certain generating sets, discrete co-compact groups of Nil isometries are almost convex. We will also see how to compute growth functions in these generating sets. Benson 1-1] has shown how to compute the growth for N z with respect to the generating set {x, y} (see below) x. Our method is more explicit, and we are able to extend the result to additional groups. The key to our approach is that
Learning New Tricks from Old Dogs: β-Adrenergic Receptors Teach New Lessons on Firing Up Adipose Tissue Metabolism

The three βAR (β-adrenergic receptor) subtypes (β1AR, β2AR, and β3AR) are members of the large family of G protein-coupled receptors, each of which is coupled to Gαs and increases in intracellular cAMP levels. In white adipose tissues, catecholamine activation of the βARs leads to the mobilization of stored fatty acids and regulates release of several adipokines, whereas in brown adipose tissue they stimulate the specialized process of adaptive nonshivering thermogenesis. Noteworthy, in most models of obesity the βAR system is dysfunctional, and its ability to stimulate lipolysis and thermogenesis are both impaired. Nevertheless, selective agonists for the β3AR, a subtype that is found predominantly in adipocytes, have been able to prevent or reverse obesity and accompanying insulin resistance in animal models. Whether this is a viable therapeutic option for human obesity is much debated with regard to the existence of brown adipocytes in humans or their ability to be recruited. Nevertheless, probing the ...
DFT and NMR studies of 2JCOH, 3JHCOH, and 3JCCOH spin-couplings in saccharides: C-O torsional bias and H-bonding in aqueous solution.

Density functional theory (DFT) has been used to investigate the structural dependencies of NMR spin-coupling constants (J-couplings) involving the exchangeable hydroxyl protons of saccharides. 3JHCOH, 3JCCOH, and 2JCOH values were calculated at different positions in model aldopyranosyl rings as a function of one or more torsion angles, and results support the use of a generalized Karplus equation to treat 3JHCOH involving the non-anomeric OH groups. The presence of O5 appended to the H1−C1−O1−H coupling pathway introduces asymmetry in 3JH1,O1H Karplus curves due to internal electronegative substituent effects on the gauche couplings, thus requiring separate equations to treat this coupling. 3JCCOH values depend not only on the C−C−O−H torsion angle but also on the orientation of terminal substituents on the coupled carbon, similar to 3JCOCC studied previously (Bose et al., J. Am. Chem. Soc. 1998, 120, 11158−11173). “In-plane” oxygen increased 3JCCOH by ∼3−4 Hz, whereas “in-plane” carbon gave more modest...
Green Web Services: Modeling and Estimating Power Consumption of Web Services

Service-oriented computing enables organizations to package their offerings as modular, self-contained services. As these organizational capabilities are more commonly distributed, perhaps redundantly, across cloud environments, there is an opportunity to provision services in locations that maximize energy-efficiency. In this paper, we introduce a process, model, and power estimation techniques to facilitate a priori decision support with respect to provisioning software services in context of the server on which they reside. Favorable results from our experiments demonstrate the ability to estimate the power consumption of web services while differentiating energy-efficiency of redundant instances.
CONSTRUCTION OF COMPLETE EMBEDDED SELF-SIMILAR SURFACES UNDER MEAN CURVATURE FLOW. PART I

We carry out the first main step towards the construc- tion of new examples of complete embedded self-similar surfaces under mean curvature flow. An approximate solution is obtained by taking two known examples of self-similar surfaces and desin- gularizing the intersection circle using an appropriately modified singly periodic Scherk surface, called the core. Using an inverse function theorem, we show that for small boundary conditions on the core, there is an embedded surface close to the core that is a solution of the equation for self-similar surfaces. This provides us with an adequate central piece to substitute for the intersection.
Value of health, incidence of depression, and level of self-esteem in low-income mothers of preschool children

Nurses are continually promoting health and healthy lifestyles. This contribution requires that nurses understand client values and priorities. Traditionally, women have had responsibility for their own and their families' health. Nurses must recognize and understand the complex influences shaping the value women place on health. The literature indicates that women want to participate actively in their own health care by assuming more responsibility for their health and well-being.
Commercial exploitation of manatees Trichechus in Brazil c. 1785–1973

Abstract All available published statistics on the exploitation of the Amazonian manatee Trichechus inunguis are collected and analysed to determine the major trends in exploitation and, if possible, their effects on the species. The manatee's role in the Amazonian economy has traiditionally been on the level of subsistnce hunting for local consumption; export of surplus manatee products has been limited and sporadic, and keeping of records has been even more so. Unknown quantities of manatee meat were shipped to the Guianas and West Indies in the 17th century, At least from the 1780s to about 1925, the only manatee product common in Amazonian commerce was mixira (fried meat packed in lard). From 1935 to 1954, manatee hides were exported to southern Brazil and elsewhere for the manufacture of heavy-duty leather. From 1954 to the legal banning of manatee hunting in 1973, manatees were again heavily exploited for meat. At no time did manatee products make up more than a small fraction of a percent of the Amazon region's trade. Numbers of animals killed per year cannot be determined with any precision, but early statistics on mixira reflect no more than 1000/year, while the peak years of hide and meat production probably required 4000–7000 manatees/year, exclusive of unrecorded subsistence hunting. Taking the latter into account, it is likely that actual mortality ran to several thousand animals per year throughout the past two centuries. Decline of meat production in the 1960s may reflect overexploitation. Evidence was also found of some exploitation for meat of West Indian manatees T. manatus in the states of Alagoas and Bahia, Brazil, the latter constituting the southernmost record of the species since the early 19th century.
Rhinovirus Inhibits Antigen-Specific T Cell Proliferation through an Intercellular Adhesion Molecule-1-Dependent Mechanism

To determine whether binding of human rhinovirus (HRV) to intracellular adhesion molecule-1 might disrupt airway immune processes, effects of a major HRV group, HRV-16, on T cell proliferation and cytotoxicity were defined. HRV (1-10 TCID50/cell) significantly inhibited T cell proliferation induced by antigen but not proliferation secondary to mitogens, interleukin-2, or an irradiated allogeneic T cell line. Noninfectious (UV-irradiated) HRV had similar effects. Inhibition of T cell proliferation was dependent on HRV binding to intercellular adhesion molecule-1 on monocytes, indicating that the virus interferes with lymphocyte activation indirectly through effects on antigen-presenting cells. In addition, HRV inhibited T cell cytotoxic responses but not NK cell activity. If these effects also occur in vivo, the resulting disturbance in local airway immunity could increase the chances of successful viral replication, and might also be a factor in the pathogenesis of secondary viral or bacterial respiratory tract infections.
The tensor force between two protons at long range

The interaction energy due to long range tensor forces between two protons as accurately measured in molecular H2 agrees fully with that expected from the interaction of the measured magnetic moments of the two protons. This agreement sets an upper limit on the maximum possible long range tensor force which might be mediated by the exchange of an intermediate particle of mass less than 0.2 electron mass. A general expression is given for the limit as a function of the parameters assumed for the radial dependence of the interaction energy and the mass of the mediating particle provided the effects of molecular vibration are neglected; typical limits are tabulated. In a few specific cases the effects of molecular vibration are calculated and more severe limits are then obtained.
LUNAR RADIO BEACON LOCATION BY DOPPLER MEASUREMENTS

A feasibility analysis points up the fact that, although the overall Doppler shift of a signal originating from a beacon on the moon is quite significant, the portion of the shift which is sensitive to the selenographic latitude and longitude of the beacon is much smaller. In fact, the basic transmitter frequency would have to be held constant (including noise) to one part in 10 for even marginal performance of the beacon location system. The feasibility analysis also shows, qualitatively, that there exist optimum times of the month for most accurately determining the selenographic coordinates of a beacon. The detailed formalism for a differential correction procedure is given in which the first-estimate values of the beacon coordinates are obtained, e.g., from the trajectory ephemeris of the vehicle setting the beacon upon the moon.
Biomechanical evaluation of meniscal repair systems : A comparison of the meniscal viper repair system, the vertical mattress FasT-Fix device, and vertical mattress ethibond sutures

Background: The biomechanical characteristics of the Meniscal Viper Repair System have not been previously studied.Hypothesis: Comparable meniscal lesion fixation standards will exist among the Meniscal Viper Repair System, the vertical FasT-Fix device, and vertical mattress sutures.Study Design: Controlled laboratory study.Methods: Porcine menisci (3 groups of 7 menisci each) were repaired using different devices. A servohydraulic device cycled each construct between 5 N and 50 N for 500 cycles before load to failure (5 mm/min). Group differences were evaluated with 1-way analysis of variance and Tukey post hoc tests.Results: During cyclic testing, the vertical mattress suture group (2.3 ± 0.2 mm) showed less mean displacement than did the vertical FasT-Fix or the Viper system groups (3.9 ± 0.7 mm and 3.9 ± 0.5 mm, respectively); the vertical mattress suture group (21.8 ± 2 N/mm) also displayed superior mean stiffness to the vertical FasT-Fix or the Viper system groups (13.2 ± 2 N/mm and 13.1 ± 1.8 N/mm,...
²2 Adrenergic Receptor Agonists And Steroids Inhibit CAFO Dust-Mediated Bronchial Epithelial Inflammation In Vitro

Agricultural workers employed in concentrated animal feeding operations (CAFOs) are repeatedly exposed to aerosolized dust, Rationale: and are susceptible to inflammatory lung diseases including COPD. Aqueous extracts of agricultural dust collected from swine CAFOs (HDE) have been shown to be potent inflammatory stimulators in human cells and mouse models. HDE exposure augments in vivo proinflammatory cytokine release, ICAM-1 expression, PKC activation, and lymphocyte and neutrophil adhesion to airway epithelial cells. Because adrenergic receptor agonists (β-agonists) alone, and in combination with corticosteroids, have been used to treat COPD, we 2 examined the ability of these agents to diminish the inflammatory effects of HDE in human epithelial cells and mouse lungs i . n vitro Immortalized human bronchial epithelial cells (Beas-2B) were grown in serum-free medium lacking the growth supplements Methods: hydrocortisone and epinephrine (LHC-7HE). Mouse lung slice cultures were prepared by making precise 150-μm sections through agarose-infused intact mouse lungs, and cultured for up to two weeks in serum-free medium. Cultured cells or lung slice cultures were pretreated with one of several -agonists [salbutamol,10 M, (SB); salmeterol, 0.01–10 M, (SM)) alone or in combination with the steroid fluticasone propionate (1 M, (FP)] for one hour prior to challenge with a 5% solution of HDE for an additional 24 hours. Supernatant medium was assayed for human IL-6 and IL-8, or for murine IL-6, KC, MIP-2, and TNFby ELISA. Cells were harvested for ICAM-1 expression by flow cytometry, and cell lysates were analyzed for protein kinase A (PKA) activity. Pretreatment of epithelial cells with the long-acting -agonist SM significantly inhibited the HDE-induced release of inflammatory Results: cytokines both timeand dose-dependently (63%, IL-8; and 72%, IL-6, at 10 M SM; from 12 to 24 hours). Pretreatment with the steroid FP in combination with SM further decreased the proinflammatory effect. Likewise, mouse lung slice cultures treated with SM or the short-acting SB, alone and in combination with FP, exhibited a blunted response to subsequent 24-h HDE challenge for all four cytokines measured (a 48-71% decrement, depending on the cytokine measured). In addition, SB pretreatment markedly decreased the HDE-enhanced ICAM-1 surface expression on Beas-2B cells, whereas intracellular PKA activity was significantly increased. Long-acting β-agonists alone, or in combination with steroids, are a potentially useful therapy for the treatment or Conclusions: prevention of chronic inflammatory lung disease in workers exposed to dust from CAFO buildings.
Changes and predictive value of dispersion of repolarization parameters for appropriate therapy in patients with biventricular implantable cardioverter-defibrillators.

Background The impact of cardiac resynchronization therapy (CRT) on dispersion of repolarization is controversial. The benefit of CRT on sudden cardiac death has been demonstrated only after 3 years follow-up. Objective The purpose of this study was to explore the immediate effect of CRT on dispersion of repolarization and to define the value of dispersion of repolarization parameters as predictors of appropriate implantable cardioverter-defibrillator (ICD) therapy. Methods Data from 100 patients who underwent CRT-ICD placement were analyzed retrospectively. Patients had symptoms of New York Heart Association functional class III or IV heart failure, left ventricular ejection fraction ≤35%, and QRS duration >130 ms or QRS ≤130 ms with left intraventricular dyssynchrony. ECG indices of dispersion of repolarization before and immediately after CRT implantation (QT dispersion, Tpeak–Tend [Tp–e], and Tp–e dispersion) were measured. Results In patients who were upgraded to a biventricular system, Tp–e did not increase significantly after CRT. However, Tp–e increased significantly after CRT in patients with left bundle branch block or narrow QRS at baseline. After 12-month follow-up, 22 patients had received appropriate ICD therapy. ICD therapy and no ICD therapy groups had similar baseline characteristics, such as secondary prevention and ischemic cardiomyopathy. Postimplantation Tp–e was the only independent predictor of future ICD therapy ( P = .02). Conclusion Immediately after CRT, Tp–e did not increase in patients who received a biventricular upgrade; however, Tp–e did increase in patients with preimplantation left bundle branch block or narrow QRS. Postimplantation Tp–e was the only independent predictor of appropriate ICD therapy.
External versus endoscopic dacryocystorhinostomy for acquired nasolacrimal duct obstruction in a tertiary referral center.

Purpose To compare success rates of external dacryocystorhinostomy (DCR) and endoscopic endonasal DCR for acquired nasolacrimal duct obstruction (NLDO). Design Retrospective, comparative, nonrandomized clinical study. Participants One hundred forty-three patients (176 surgeries) operated for acquired NLDO. Methods A review of electronic medical records of patients with acquired NLDO who underwent DCR at the Jules Stein Eye Institute from 1999 to 2004 was performed. Data regarding the lacrimal drainage system, comprehensive eye examination, surgical outcome, and postoperative nasal endoscopy were analyzed. Main Outcome Measures Surgery failure was defined as (1) no marked improvement in tearing or any episode of postoperative dacryocystitis, (2) inability to irrigate the lacrimal system postoperatively, and (3) postoperative nasal endoscopy with scarring in the intranasal osteotomy or no visualization of fluorescein dye. Postoperative nasal endoscopy was performed in all failed cases and in >50% of all patients. Results One hundred forty-three patients (48 male and 95 female; mean age, 63 years) underwent 176 DCR surgeries for acquired NLDO. Success was achieved in 135 cases (76.7%), and failure in 41 (23.3%). Of the 41 failed cases, anatomical obstruction at the fistula site was found in 20 (49% of failed cases), whereas functional failure with no evidence of obstruction was found in 21 (51%). Surgery revision was performed in 22 cases (12.5%), but it was successful in only 9 (5.1%); patients who failed the first revision were likely to fail additional revisions ( P = 0.02). History of facial trauma was associated with surgery failure. In our patients, endoscopic DCR (86 cases) had a significantly higher success rate than external DCR (90 cases), 84% versus 70% ( P = 0.03). Complications included 1 patient with nose bleeding on the first postoperative day that resolved with nasal packing and 2 patients with sump syndrome that resolved after endoscopic revision. Conclusions The success rate of DCR for acquired NLDO in our group of patients was 77%, lower than reported in previous studies, with endoscopic surgery showing better results. Success rates of revision surgery were relatively low (
Characterization of Empty Adenovirus Particles Assembled in the Absence of a Functional Adenovirus IVa2 Protein

ABSTRACT The molecular mechanism for packaging of the adenovirus (Ad) genome into the capsid is likely similar to that of DNA bacteriophages and herpesviruses—the insertion of viral DNA through a portal structure into a preformed prohead driven by an ATP-hydrolyzing molecular machine. It is speculated that the IVa2 protein of adenovirus is the ATPase providing the power stroke of the packaging machinery. Purified IVa2 binds ATP in vitro and, along with a second Ad protein, the L4 22-kilodalton protein (L4-22K), binds specifically to sequences in the Ad genome that are essential for packaging. The efficiency of binding of these proteins in vitro was correlated with the efficiency of packaging in vivo. By utilizing a virus unable to express IVa2, pm 8002, it was reported that IVa2 plays a role in assembly of the empty virion. We wanted to address the question of whether the ATP binding, and hence the putative ATPase activity, of IVa2 was required for its role in virus assembly. Our results show that ATPase activity was not required for the assembly of empty virus particles. In addition, we present evidence that particles were assembled in the absence of IVa2 by using two viruses null for IVa2—a deletion mutant virus, ΔIVa2, and the previously described mutant virus, pm 8002. Empty virus particles produced by these IVa2 mutant viruses did not contain detectable viral DNA. We conclude that the major role of IVa2 is in viral DNA packaging. A characterization of the empty particles obtained from the IVa2 mutant viruses compared to wild-type empty particles is presented.
Developing peptide-based multivalent antagonists of proliferating cell nuclear antigen and a fluorescence-based PCNA binding assay

Proliferating cell nuclear antigen (PCNA) is a critical player in cell proliferation. It interacts with a myriad of cellular proteins in genomic DNA replication and cell cycle control. This makes PCNA an attractive target for developing antiproliferative therapeutics. Indeed the binding of a human tumor suppressor protein, p21, to PCNA contributes to its antiproliferative effect in cells. In this work we reported a fluorescence polarization-based binding assay for determining the affinity between the p21 peptide and human PCNA. In order to improve the potency of the p21-based PCNA antagonist, we exploited the homotrimeric structure of PCNA and developed multivalent peptide-based PCNA antagonists. The di- and trivalent p21-based antagonists bind to PCNA with low nanomolar dissociation constant. Moreover, we showed that the multivalent PCNA antagonists inhibited PCNA-dependent DNA synthesis in a human cell extract with improved avidity when compared to the monovalent p21 peptide. The fluorescence polarization assay holds promise for the discovery of potent small-molecule PCNA inhibitors given its ready adaptability to a high-throughput screening format.
Comprehensive assessment of the components of energy expenditure in infants using a new infant respiratory chamber.

Background: Current methods for energy expenditure (EE) measurements in term infants do not include simultaneous measurements of basal and sleeping metabolic rates (BMR and SMR) or a measure of physical activity (PA). Furthermore, prediction equations for calculating EE are not appropriate for use in infants with metabolic disorders.Objective: To develop and utilize a new infant respiratory chamber for simultaneous measurements of EE (kJ/d), preprandial BMR (kJ/d), SMR (kJ/d) and an index of PA (oscillations/min/kg body weight) in infants with a variety of metabolic disorders, for up to four hours in a hospital setting, while allowing parental interaction in a comfortable environment.Methods: We obtained simultaneous measurements of EE, BMR, SMR and PA in 21 infants (66±73 days of age, 4.5±1.7 kg body weight, 55±8 cm in length and 16±7% body fat) using our new infant respiratory chamber. Six of these infants were healthy, seven had thyroid dysfunction, five were HIV-exposed, one had AIDS, one had intraute...
Why do nitric oxide synthases use tetrahydrobiopterin

Abstract We are combining stopped-flow, stop-quench, and rapid-freezing kinetic methods to help clarify the unique redox roles of tetrahydrobiopterin (H4B) in NO synthesis, which occurs via the consecutive oxidation of l -arginine (Arg) and N-hydroxy- l -arginine (NOHA). In the Arg reaction, H4B radical formation is coupled to reduction of a heme FeIIO2 intermediate. The tempo of this electron transfer is important for coupling FeIIO2 formation to Arg hydroxylation. Because H4B provides this electron faster than can the NOS reductase domain, H4B appears to be a kinetically preferred source of the second electron for oxygen activation during Arg hydroxylation. A conserved Trp (W457 in mouse inducible NOS) has been shown to influence product formation by controlling the kinetics of H4B electron transfer to the FeIIO2 intermediate. This shows that the NOS protein tunes H4B redox function. In the NOHA reaction the role of H4B is more obscure. However, existing evidence suggests that H4B may perform consecutive electron donor and acceptor functions to reduce the FeIIO2 intermediate and then ensure that NO is produced from NOHA.
Evidence for proctolin-like substances in the central nervous system of the leech Hirudo medicinalis.

The distribution of proctolin-like immunoreactive (PLI) cells was mapped in the central nervous system of the leech Hirudo medicinalis. In segmental ganglia, PLI cells can be divided into two groups: cells that stain repeatedly in every successive ganglion, and cells that stain only in specific segmental ganglia. The number of PLI cells, therefore, ranged from eight to 20 cells per ganglion. One bilateral pair of PLI cells (cells PLI-1) was further characterized morphologically by Lucifer yellow and horseradish peroxidase cell injections. Cell PLI-1 conforms in soma position, morphology, and physiological properties with cell 101, which has been previously classified as an inhibitory motoneuron to the flattener muscles. A locust bioassay (O'Shea and Adams, Science 213:567–569, 1981) was used to detect the presence of proctolin-like bioactivity. Extracts of leech ganglia when applied to the extensor tibial is muscle of the locust leg induced a proctolin-like response similar to the responses induced by proctolin standards. This work extends the finding of proctolin-like substances to the annelid phylum.
RELATIVISTIC DENSITY FUNCTIONAL STUDY OF THE GEOMETRY, ELECTRONIC TRANSITIONS, IONIZATION ENERGIES, AND VIBRATIONAL FREQUENCIES OF PROTACTINOCENE, PA( ETA 8-C8H8)2

The geometric structure and electronic properties of the 5f 1 complex protactinocene, Pa(COT)2 (COT = η8-C8H8), have been investigated using gradient-corrected density functional methods with the inclusion of spin−orbit coupling. The calculated structure of Pa(COT)2 with scalar relativistic corrections is intermediate between those of Th(COT)2 and U(COT)2. Spin−orbit effects are essential for the calculation of state energies of Pa(COT)2. Under D8h* double-group symmetry, the ground state is found to be an E5/2u state that corresponds to an (fφ)1 electron configuration. The first excited state (E1/2u) lies only about 0.05 eV above the ground state. The low-lying states follow the ordering of E5/2u (fφ) < E1/2u (fσ+fπ) ≪ E3/2u (fπ) ∼ E7/2u (fφ) < 2E1/2u (fπ+fσ) < E1/2g (dσ) ≪ 2E3/2u (fδ) < 2E5/2u (fδ). The lowest-energy electric-dipole-allowed f → d electronic transition is calculated to occur at 368 nm, which is in excellent agreement with the experimental estimation of 365 nm. The first 20 vertical ioniz...