cssi/SciSciGPT-SciSciNet huggingface dataset:
Analysis of rare variations reveals roles of amino acid residues in the N-terminal extracellular domain of nicotinic acetylcholine receptor (nAChR) alpha6 subunit in the functional expression of human alpha6*-nAChRs

Functional heterologous expression of naturally-expressed and apparently functional mammalian α6*-nicotinic acetylcholine receptors (nAChRs; where ‘*’ indicates presence of additional subunits) has been difficult. Here we wanted to investigate the role of N-terminal domain (NTD) residues of human (h) nAChR α6 subunit in the functional expression of hα6*-nAChRs. To this end, instead of adopting random mutagenesis as a tool, we used 15 NTD rare variations (i.e., Ser43Pro, Asn46Lys, Asp57Asn, Arg87Cys, Asp92Glu, Arg96His, Glu101Lys, Ala112Val, Ser156Arg, Asn171Lys, Ala184Asp, Asp199Tyr, Asn203Thr, Ile226Thr and Ser233Cys) in nAChR hα6 subunit to probe for their effect on the functional expression of hα6*-nAChRs. N-terminal α-helix (Asp57); complementary face/inner β-fold (Arg87 or Asp92) and principal face/outer β-fold (Ser156 or Asn171) residues in the hα6 subunit are crucial for functional expression of the hα6*-nAChRs as variations in these residues reduce or abrogate the function of hα6hβ2*-, hα6hβ4- and hα6hβ4hβ3-nAChRs. While variations at residues Ser43 or Asn46 (both in N-terminal α-helix) in hα6 subunit reduce hα6hβ2*-nAChRs function those at residues Arg96 (β2-β3 loop), Asp199 (loop F) or Ser233 (β10-strand) increase hα6hβ2*-nAChR function. Similarly substitution of NTD α-helix (Asn46), loop F (Asp199), loop A (Ala112), loop B (Ala184), or loop C (Ile226) residues in hα6 subunit increase the function of hα6hβ4-nAChRs. All other variations in hα6 subunit do not affect the function of hα6hβ2*- and hα6hβ4*-nAChRs. Incorporation of nAChR hβ3 subunits always increase the function of wild-type or variant hα6hβ4-nAChRs except for those of hα6(D57N, S156R, R87C or N171K)hβ4-nAChRs. It appears Asp57Lys, Ser156Arg or Asn171Lys variations in hα6 subunit drive the hα6hβ4hβ3-nAChRs into a nonfunctional state as at spontaneously open hα6(D57N, S156R or N171K)hβ4hβ3V9’S-nAChRs (V9’S; transmembrane II 9’ valine-to-serine mutation) agonists act as antagonists. Agonist sensitivity of hα6hβ4- and/or hα6hβ4hβ3-nAChRs is nominally increased due to Arg96His, Ala184Asp, Asp199Tyr or Ser233Cys variation in hα6 subunit. Hence investigating functional consequences of natural variations in nAChR hα6 subunit we have discovered additional bases for cell surface functional expression of various subtypes of hα6*-nAChRs. Variations (Asp57Asn, Arg87Cys, Asp92Glu, Ser156Arg or Asn171Lys) in hα6 subunit that compromise hα6*-nAChR function are expected to contribute to individual differences in responses to smoked nicotine.
One-cell zygote transfer from diabetic to nondiabetic mouse results in congenital malformations and growth retardation in offspring.

Fetuses of type 1 and 2 diabetic women experience higher incidences of malformations and fetal death as compared with nondiabetics, even when they achieve adequate glycemic control during the first trimester. We hypothesize that maternal diabetes adversely affects the earliest embryonic stage after fertilization and programs the fetus to experience these complications. To test this hypothesis, we transferred either one-cell mouse zygotes or blastocysts from either streptozotocin-induced diabetic or control mice into nondiabetic pseudopregnant female recipients. We then evaluated the fetuses at embryonic d 14.5 to assess fetal growth and the presence or absence of malformations. We found that fetuses from the diabetic mice transferred at the blastocyst stage but also as early as the one-cell zygote stage displayed significantly higher rates of malformations consistent with neural tube closure problems and abdominal wall and limb deformities. In addition, both these groups of fetuses were significantly grow...
What is Behind the Inverse Hall-Petch Behavior in Nanocrystalline Materials?

An inverse Hall-Petch effect has been observed for nanocrystalline materials by a large number of researchers. This effect implies that nanocrystalline materials get softer as grain size is reduced below a critical value. Postulated explanations for this behavior include dislocation-based models, diffusion-based models, grain boundary-based shearing models and two-phase based models. In this paper, we report an explanation for the inverse Hall-Petch effect based on the statistical absorption of dislocations by grain boundaries. We show that the yield strength is dependent on strain rate and temperature, and that it deviates from the Hall-Petch relationship at a critical grain size.
NYSE merger creates first transatlantic financial market

The recent merger of the New York Stock Exchange (NYSE) and Euronext N.V. has created the first transatlantic financial market. The authors believe it is a marriage with a priceless wedding gift. But what are the implications of this union? © 2008 Wiley Periodicals, Inc.
Detecting a light Higgs boson at the Fermilab Tevatron through enhanced decays to photon pairs

We analyze the prospects of the Fermilab Tevatron for finding a Higgs boson in the two photon decay mode. We conclude that the standard model (SM) Higgs boson will likely not be discovered in this mode. However, we motivate several theories beyond the SM, including the MSSM, which predict a Higgs boson with enhanced branching fractions into photons, and calculate the luminosity needed to discover a general Higgs boson at the Tevatron by a two-photon invariant mass peak at large transverse momentum. We find that a high luminosity Tevatron will play a significant role in proving or constraining these theories.
Citizen Responses to Dissatisfaction in Urban Communities: A Partial Test of a General Model

In this paper, we evaluate the Exit, Voice, Loyalty, and Neglect [EVLN] model of citizen responses to dissatisfaction developed by Lyons and Lowery (1986). After summarizing its key propositions, we test the model with data gathered from 10 separate surveys of citizens living in matched pairs of independent cities and neighborhoods. Considerable support is found for a respecified version of the EVLN model, support that is then used to develop an integrated understanding of citizen responses to dissatisfaction with public services in urban communities.
Influence of the Home Food Environment on Children’s Fruit and Vegetable Consumption: A Study of Rural Low-Income Families

Background. This investigation sought to identify micro-level built and sociocultural characteristics of a home food environment that have been theoretically linked with fruit and vegetable (F&V) c...
Dopamine as a prolactin (PRL) inhibitor.

Dopamine is a small and relatively simple molecule that fulfills diverse functions. Within the brain, it acts as a classical neurotransmitter whose attenuation or overactivity can result in disorders such as Parkinson’s disease and schizophrenia. Major advances in the cloning and characterization of biosynthetic enzymes, transporters, and receptors have increased our knowledge regarding the metabolism, release, reuptake, and mechanism of action of dopamine. Dopamine reaches the pituitary via hypophysial portal blood from several hypothalamic nerve tracts that are regulated by PRL itself, estrogens, and several neuropeptides and neurotransmitters. Dopamine binds to type-2 dopamine receptors that are functionally linked to membrane channels and G proteins and suppresses the high intrinsic secretory activity of the pituitary lactotrophs. In addition to inhibiting PRL release by controlling calcium fluxes, dopamine activates several interacting intracellular signaling pathways and suppresses PRL gene expression and lactotroph proliferation. Thus, PRL homeostasis should be viewed in the context of a fine balance between the action of dopamine as an inhibitor and the many hypothalamic, systemic, and local factors acting as stimulators, none of which has yet emerged as a primary PRL releasing factor. The generation of transgenic animals with overexpressed or mutated genes expanded our understanding of dopamine-PRL interactions and the physiological consequences of their perturbations. PRL release in humans, which differs in many respects from that in laboratory animals, is affected by several drugs used in clinical practice. Hyperprolactinemia is a major neuroendocrine-related cause of reproductive disturbances in both men and women. The treatment of hyperprolactinemia has greatly benefited from the generation of progressively more effective and selective dopaminergic drugs. (Endocrine Reviews 22: 724–763, 2001)
Propagation velocity profile in a cross-section of a cardiac muscle bundle from PSpice simulation

The effect of depth on propagation velocity within a bundle of cardiac muscle fibers is likely to be an important factor in the genesis of some heart arrhythmias. The velocity profile of simulated action potentials propagated down a bundle of parallel cardiac muscle fibers was examined in a cross-section of the bundle using a PSpice model. The model (20 × 10) consisted of 20 chains in parallel, each chain being 10 cells in length. All 20 chains were stimulated simultaneously at the left end of the bundle using rectangular current pulses (0.25 nA, 0.25 ms duration) applied intracellularly. The simulated bundle was symmetrical at the top and bottom (including two grounds), and voltage markers were placed intracellularly only in cells 1, 5 and 10 of each chain to limit the total number of traces to 60. All electrical parameters were standard values; the variables were (1) the number of longitudinal gap-junction (G-j) channels (0, 1, 10, 100), (2) the longitudinal resistance between the parallel chains (Rol2) (reflecting the closeness of the packing of the chains), and (3) the bundle termination resistance at the two ends of the bundle (RBT). The standard values for Rol2 and RBT were 200 KΩ. The velocity profile was bell-shaped when there was 0 or only 1 gj-channel. With standard Rol2 and RBT values, the velocity at the surface of the bundle (θ1 and θ20) was more than double (2.15 ×) that at the core of the bundle (θ10, θ11). This surface:core ratio of velocities was dependent on the values of Rol2 and RBT. When Rol2 was lowered 10-fold, θ1 increased slightly and θ2decreased slightly. When there were 100 gj-channels, the velocity profile was flat, i.e. the velocity at the core was about the same as that at the surface. Both velocities were more than 10-fold higher than in the absence of gj-channels. Varying Rol2 and RBT had almost no effect. When there were 10 gj-channels, the cross-sectional velocity profile was bullet-shaped, but with a low surface/core ratio, with standard Rol2 and RBT values. When there were no or few gj-channels (0 or 1), the profile was bell-shaped with the core velocity less than half that at the surface. In contrast, when there were many gj-channels (100), the profile was flat. Therefore, when some gj-channels close under pathophysiological conditions, this marked velocity profile could contribute to the genesis of arrhythmias.
Using Global Positioning System Travel Data to Assess Real-World Energy Use of Plug-In Hybrid Electric Vehicles

Plug-in hybrid electric vehicles (PHEVs) have received considerable recent attention for their potential to reduce petroleum consumption significantly and quickly in the transportation sector. Analysis to aid the design of such vehicles and predict their real-world performance and fuel displacement must consider the driving patterns the vehicles will typically encounter. This paper goes beyond consideration of standardized certification cycless by leveraging state-of-the-art travel survey techniques that use Global Positioning System (GPS) technology to obtain a large set of real-world drive cycles from the surveyed vehicle fleet. This study specifically extracts 24-h, second-by-second driving profiles from a set of 227 GPS-instrumented vehicles in the St. Louis, Missouri, metropolitan area. The performance of midsize conventional, hybrid electric, and PHEV models is then simulated over the 227 full-day driving profiles to assess fuel consumption and operating characteristics of these vehicle technologies...
Left behind, at-risk, and vulnerable elders in rural China

Migration of any distance separates family members for long periods of time. In China, institutional legacies continue to privilege the migration of working-age individuals who often leave children and elders behind in the rural areas. Up to now, the literature has treated children and elders analogously, labeling each group as “left-behind.” We argue that analysis of elder stayers needs to be more nuanced, distinguishing among differing groups of elders. Of these groups, those living alone without any adult children in the village are most at risk, while those living with other non-migrant adult children are much less affected by migration. Another group of elders, clearly affected by migration, are those caring for their grandchildren while the children's parents have migrated. Members of this latter group need to be distinguished from those living alone as they are dissimilar in many fundamental ways (age, working status, marital status) and face a very different set of challenges from those left behind (perhaps frail) and alone.
Mining data from 1000 genomes to identify the causal variant in regions under positive selection

The human genome contains hundreds of regions in which the patterns of genetic variation indicate recent positive natural selection, yet for most of these the underlying gene and the advantageous mutation remain unknown. We recently reported the development of a method, Composite of Multiple Signals (CMS), that combines tests for multiple signals of natural selection and increases resolution by up to 100-fold. Applying CMS to candidate selected regions from the International Haplotype Map, we localized several hundred signals to ~50-100 kb, identifying individual gene and polymorphism targets of selection. These regions included genes involved in processes known to be targets of selection, such as infectious disease, skin pigment, metabolism, and hair and sweat. We further identified many candidates that are similar to regulatory elements. In several regions, we identified variants that are significantly associated with the expression of nearby genes in the selected population. Moreover nearly half of the ~200 regions we examined localized to regions with no genes. Thirty of the regions contain long non-coding RNAs that have been shown to often regulate nearby genes, suggesting that variation within the RNAs might have functional consequences. With preliminary data now available from the 1000 Genomes Project, we are beginning to explore full sequence data, which should contains most if not all of the causal selected polymorphisms. We extended the CMS method to the preliminary data set, validating our previously identified candidates and identifying many new intriguing coding and regulatory variants.
Acute effects of intravenous nesiritide on cardiac contractility in heart failure

Abstract Background Although nesiritide is a potent vasodilator, studies using myocytes and isolated muscle strips have shown that recombinant B-type natriuretic peptide (BNP; nesiritide) decreases contractility. We sought to determine whether nesiritide decreases contractility in heart failure patients. Methods and Results Twenty-five heart failure patients underwent left heart catheterization (using a pressure-volume conductance catheter) and echocardiography at baseline and after a 2 mcg/kg bolus and 30-minute nesiritide infusion (0.01 mcg·kg·min). From invasive and noninvasive measurements, left ventricular (LV) systolic function indices were calculated, including ejection fraction, end-systolic elastance (E es ; single-beat invasive and noninvasive methods) and preload-recruitable stroke work (PRSW; noninvasive, single-beat method). The mean age was 60 ± 11 years, 48% were male, 56% had coronary disease, and 64% had hypertension. Although nesiritide did not change LV ejection fraction, it did decrease contractility on pressure-volume analysis. Noninvasive E es decreased from 2.6 ± 1.6 to 2.0 ± 1.4 mm Hg/mL ( P = .02). For those with reduced ejection fraction, E es decreased by invasive ( P = .006) and noninvasive ( P = .02) methods. PRSW decreased from 76 ± 37 to 62 ± 28 g/cm 2 ( P = .003). On tissue Doppler imaging, nesiritide reduced the systolic annular tissue velocity of the mitral annulus from 8.0 ± 1.9 to 6.9 ± 1.3 cm/s ( P = .04). Conclusions Nesiritide infusion acutely decreases derived measures of contractility and systolic function in patients with chronic heart failure.
Combining symbolic execution with model checking to verify parallel numerical programs

We present a method to verify the correctness of parallel programs that perform complex numerical computations, including computations involving floating-point arithmetic. This method requires that a sequential version of the program be provided, to serve as the specification for the parallel one. The key idea is to use model checking, together with symbolic execution, to establish the equivalence of the two programs. In this approach the path condition from symbolic execution of the sequential program is used to constrain the search through the parallel program. To handle floating-point operations, three different types of equivalence are supported. Several examples are presented, demonstrating the approach and actual errors that were found. Limitations and directions for future research are also described.
Effect of Stacking Sequence and Lay-Up Angle on Free Edge Stresses Around a Hole in a Laminated Plate Under Tension

One mode of failure in fiber reinforced laminated plates is delamination initiating at a free edge. Experimental results and theoretical stress investi gations found in the literature indicate that the interlaminar normal stress, σz, is a factor in this mode of failure. In this paper, the stress behavior around a circular hole in a laminated plate is investigated using a three- dimensional finite element stress analysis. First, computed results for the tangential strain distribution around a circular hole for a (0/±45/0) s lamin ate under uniaxial loading are compared with laboratory data to provide a level of confidence in the analysis. Next, attention is focused on the inter laminar normal stress distribution around the free edge of the circular hole and the effects of changes in stacking sequence and lay-up angle. Initially, laminates with stacking sequences of (0/90)s are analyzed. Graphite/epoxy laminates of the type (02/±θ/∓θ)S, (±θ/∓θ/0 2)S, (902/±θ/∓θ) 2 , and (±θ/∓θ/902)S where θ is 30° , 45°, an...
Oncospace: All Patients on Trial for Analysis of Outcomes, Toxicities, and IMRT Plan Quality

Results: Web pages have been developed that allow navigation through toxicity data providing insight into the clinical practice. For example, one can select a subgroup of patients based on diagnosis and staging, clinical trial, attending physician and the web page updates with the patient distribution of maximum grade for the selected toxicities. In this way, physician’s can monitor the various toxicity rates of their clinical patients in real time. With the treatment planning data, we are able to find similar patients in the database based on the shape relationships between targets and critical structures. We have shown that we can use this data for insuring dosimetric quality for new patients based on similar prior patients. With the full extent of the data in the system, we expect to be able to correlate more sophisticated dosimetric attributes with toxicity. For example, we may be able to show characteristic dose volume histograms for given toxicity levels. Conclusions:The overall goal is to integrate accurate data collection into the clinical process to treat all patients as if they are on a clinical trial, and to provide tools to easily recall these past experiences to eventually impact the care of new patients. This work represents our progress to date in achieving this goal. Already, we are able to provide tools that can impact our clinical practice.
Nesting Ecology of Common Black-Hawks in Relation to Landscape Features

Abstract Despite considerable conservation interest, the Common Black-Hawk (Buteogallus anthracinus) and its breeding ecology remain understudied in its United States range. I studied the nest-site preference and nesting success of pairs breeding in the Cliff-Gila Valley, New Mexico, during 2000–01. Using data from 39 breeding attempts in 31 nests of 22 pairs, I modeled differences in nest locations relative to landscape features between nests and available non-used sites, reused and non-reused nests, and successful and unsuccessful nests. I found that Common Black-Hawk nests were in larger riparian forest patches, farther from open areas, and closer to water than non-used sites. I found no relationship between nest reuse and landscape features, but found that successful nests were in larger patches than unsuccessful nests. Correlations of nest success and nest-site preference indicated that birds had higher nest success in preferred nest sites. Although limited to one study area and two breeding seasons,...
The small slope approximation reflection coefficient for scattering from a "Pierson-Moskowitz" sea surface

First- and second-order reflection coefficients are presented for the small slope approximation. The first-order reflection coefficient is identical to the Kirchhoff, or physical optics, result, and the second-order reflection coefficient reduces to those of perturbation theory and the Kirchhoff approximation in the appropriate limits. Numerical results are obtained for acoustic or TE-polarized electromagnetic scattering from one-dimensional, "Pierson-Moskowitz" sea surfaces at low grazing angles. Comparison with exact integral equation results shows that the second-order small slope approximation is extremely accurate and better than both the perturbation and Kirchhoff methods. >
Specific binding of molecularly targeted agents to pancreas tumors and impact on observed optical contrast

In optical imaging it is thought that optimum tumor contrast can be achieved with the use of small-labeled molecular tracers that have high affinity to their targets and fast clearance rates from the blood stream and healthy tissues. An example of this is fluorescently tagged EGF to monitor the molecular activity of tumors, such as pancreatic cancer. Extensive fluorescence contrast analysis for fluorescence molecular tomography has been performed on the AsPC-1 pancreas tumor, grown orthotopically in mice; yet, the binding dynamics of the EGF-fluorescent agent in vivo is not completely known. The bulk pancreatic tumor displays 3:1 contrast relative to the normal pancreas at long times after injection; however, even higher levels of fluorescence in the liver, kidney and intestine suggest that molecular specificity for the tumor may be low. Mice were administered a fluorescently labeled EGF agent and were sacrificed at various time points post-injection. To analyze the amount of specific binding at each time point frozen tissue samples were fluorescently imaged, washed with saline to remove the interstitially distributed contrast agent, and then imaged again. This technique demonstrated that approximately ~10% of the molecular target was firmly bound to the cell, while 90% was mobile or unbound. This low binding ratio suggests that the contrast observed is from inherent properties of the tumor (i.e. enhanced permeability and retention effect) and not from specific bound contrast as previously anticipated. The use of EGF contrast agents in MRI-guided fluorescence tomography and the impact of low binding specificity are discussed.
Making use of scenarios for validating analysis and design

Scenarios can help remedy the most serious obstacle in the design process that is a chronic lack of knowledge of the application domain. Moreover, scenarios can be employed in analysis and design to serve both illustrating the context of an envisaged usage (user's perspective) and demonstrating the design proposal in terms of the intended usage (analyst's perspective). In contrasting both perspectives by means of a dialectic process a synthesis can be achieved that incorporates a shared understanding. Validation is a process to achieve such an understanding. The semantic structure of types of scenarios is investigated thus illustrating how a context of use analysis according to ISO 9241-11 can be exploited for validation purposes. The role of scenarios in usability engineering is contrasted with traditional concepts of systems analysis as an attempt to narrow the bridge between software engineering and usability engineering.
Temperature scaling of nanoscale silicon MOSFETs

We have combined a 1D model of double-gate MOSFETs with ultrathin intrinsic channel, with a simple model of power consumption in digital integrated circuits, to calculate the temperature dependence of the minimum total (static + dynamic) power P and the optimal power supply voltage V DD . The results are strongly dependent on the circuit speed assumptions. If the current trend of speed scaling with the critical size reduction is sustained, both P and V DD saturate as soon as T is decreased below 100 K. On the other hand, if the high speed condition is removed, transistors may operate in the subthreshold region and minimum value of P scales as T 2 while the optimum value of V DD drops as T. This reduction is, however, limited by thermal fluctuations, leading to a different scaling, V DD T 1/2 and P T 1 , for low temperatures and/or large circuit densities. Because of this limitation, deep cooling of CMOS circuits may make sense only in very special cases.
Lifestyle Medicine Education

The actual causes of premature adult deaths, the preponderance of noncommunicable chronic diseases, and their associated costs are related to unhealthy behaviors, such as poor nutrition, physical inactivity, and tobacco use. Although recommended as the first line of prevention and management, providers often do not provide behavioral change counseling in their care. Medical education in lifestyle medicine is, therefore, proposed as a necessary intervention to allow all health providers to learn how to effectively and efficiently counsel their patients toward adopting and sustaining healthier behaviors. Lifestyle medicine curricula, including exercise, nutrition, behavioral change, and self-care, have recently evolved in all levels of medical education, together with implementation initiatives like Exercise is Medicine and the Lifestyle Medicine Education (LMEd) Collaborative. The goal of this review is to summarize the existing literature and to provide knowledge and tools to deans, administrators, faculty members, and students interested in pursuing lifestyle medicine training or establishing and improving an LMEd program within their institution.
Ambulance use among road injury victims: results from Pakistan National Emergency Departments Surveillance

Ambulance use in low-and middle-income countries is very low. This study assesses characteristics of road traffic injury (RTI) victims coming to emergency departments (EDs) by ambulance and compares with RTI victims coming via alternative modes of transportation. The Pakistan National Emergency Departments Surveillance (Pak-NEDS) was a surveillance conducted in seven major tertiary-care EDs in six main cities of Pakistan from November 2010-March 2011. Univariate and multivariate logistic regression was carried out to investigate the factors associated with ambulance use in RTI patients. The variables used for regression gender, age groups, cities, hospital type, road user type and disposition. There were four age categories; ≤18 years, 19 -45 years, 45 - R years and ≥65 years. RTI patients were divided into two road-user groups; VRUs (pedestrian, motorcycle driver and passenger, bicyclists) and non-vulnerable road-users (non-VRUs) including four-wheel vehicles' driver and passengers. Level of significance was set at 0.05. Ethical approval was obtained at all participating sites. Pak-NEDS enrolled 9769 RTI patients. The mode of arrival was known for 92.2% (n=9009) RTI patients, of which 9.1%(n=821) were brought to the ED by ambulance. The mean age was higher in the ambulance group (33.3±16.9 versus 28.8±14.1 years, p-value 65 years of age (p-value Language: en
High-power laser interaction with low-density C–Cu foams

We study the propagation of high-power laser beams in micro-structured carbon foams by monitoring the x-ray output from deliberately introduced Cu content. In particular, we characterize this phenomenon measuring absolute time-resolved x-ray yields, time-resolved x-ray imaging, and x-ray spectroscopy. New experimental results for C–Cu foams show a faster heat front velocity than simulation that assumed homogeneous plasma. We suggest the foam micro-structure may explain this trend.
Family practice and the health care system. Implications of health reform for family practice.

The United States presidential and congressional elections have triggered much speculation and cautious optimism about the likelihood and substance of health care reform during the Clinton administration. The reflections in this article are drawn from conversations with many health policy analysts and those representing special interests in Washington, DC, who were interviewed from September to November 1992 as part of the orientation of the 1992-93 Robert Wood Johnson Health Policy Fellowship Program. My comments are also in larger part personal reflections of an academic family physician on sabbatical exposed to a wholly political view of health care. Impressions of the current position of family practice at the federal level and the repercussions of health care reform on clinical family practice, family practice education, and research are discussed together with suggestions for actions that family practice can take to achieve a leadership position in primary care. It may be a surprise to some that few in Washington have the slightest idea what family practice is. Many are confounded by the meaning of "primary care" or "generalist physician." There are many reasons for this confusion. Organized family medicine has only relatively recendy been established as a political presence within Washington. Few at this time would say that this presence is weighty. Second, the organizational home of family practice is located quite far from the nation's capital. Sporadic or even regular visits to
Synthesis and Biological Analysis of Prostate-Specific Membrane Antigen-Targeted Anticancer Prodrugs

Ligand-targeted therapeutics have increased in prominence because of their potential for improved potency and reduced toxicity. However, with the advent of personalized medicine, a need for greater versatility in ligand-targeted drug design has emerged, where each tumor-targeting ligand should be capable of delivering a variety of therapeutic agents to the same tumor, each therapeutic agent being selected for its activity on a specific patient's cancer. In this report, we describe the use of a prostate-specific membrane antigen (PSMA)-targeting ligand to deliver multiple unrelated cytotoxic drugs to human prostate cancer (LNCaP) cells. We demonstrate that the PSMA-specific ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid, is capable of mediating the targeted killing of LNCaP cells with many different therapeutic warheads. These results suggest that flexibility can be designed into ligand-targeted therapeutics, enabling adaptation of a single targeting ligand for the treatment of patients with...
A Duoprocess Model for Paired-Associate Learning: A Correction:

Corrections should be made in two formulas reported in an earlier paper (Nahinsky, 1964). The right hand side of the formula for expected number of total errors on the bottom of p. 469 should read (j - 1)/2c rather than (j - l)/c as is shown. The latter value wo~lld accually result fro111 uniprocess assumptions which consistently require a c value twice as great as that for the duoprocess model. The second value on p. 470, which is for expected number of all Rs for unlearned association trials, should read j(k + 1)/2c rather than j(k + 1 )/c, which is the value shown.
Standard in vitro assays for protein-nucleic acid interactions--gel shift assays for RNA and DNA binding.

The characterization of protein-nucleic acid interactions is necessary for the study of a wide variety of biological processes. One straightforward and widely used approach to this problem is the electrophoretic mobility shift assay (EMSA), in which the binding of a nucleic acid to one or more proteins changes its mobility through a nondenaturing gel matrix. Usually, the mobility of the nucleic acid is reduced, but examples of increased mobility do exist. This type of assay can be used to investigate the affinity of the interaction between the protein and nucleic acid, the specificity of the interaction, the minimal binding site, and the kinetics of the interaction. One particular advantage of EMSA is the ability to analyze multiple proteins, or protein complexes, binding to nucleic acids. This assay is relatively quick and easy and utilizes equipment available in most laboratories; however, there are many variables that can only be determined empirically; therefore, optimization is necessary and can be highly dependent upon the system. The protocol described here is for the poly(A)-binding protein (PABP) binding to an unstructured RNA probe of 43 bases. While this may be a useful protocol for some additional assays, it is recommended that both reaction conditions and gel running conditions be tailored to the individual interaction to be probed.
On Upper Bound of Calibrated American Put Values Under Stochastic Rates

We prove that in calibrated diffusive models with non-negative spot-rate correlation the calibrated American put values decrease with increasing short rate volatility and attain their maximum in the pure local volatility model. The result holds for Bermudan put options.
Improved Calibration Method for the Nonlinear Regime of a Single-Beam Optical Trap Allows Higher Force Applications

Optical traps allow for the precise application and measurement of pico-Newton forces to microscale objects, and are essential tools for a wide range of biophysical measurements of motor proteins and cells. Nearly all experiments exploit the linear regime of the optical trap, where force and displacement are related by a simple spring constant that does not depend on the displacement of the trapped object. This typically limits the useful force range to < 100 pN for high-NA objective lenses and reasonable laser powers. However, higher forces are often desired--for example to study collective behavior of multiple motor proteins, to activate mechanotransduction pathways in cells, or to probe the viscoelastic properties of cytoskeletal networks and other stiff polymeric materials--but these are not accessible in the linear regime of the trap. The best means to extend the maximum force is to increase the displacement of the particle from the trap center and make use of the nonlinear range of the trapping potential; however, current techniques for calibrating the nonlinear regime are limited. Here we report a new method for calibrating the nonlinear trap region that uses the fluctuations of the position of a trapped object when it is displaced from the center of a single gradient optical trap by controlled flow. From the position fluctuations, we measure the local trap stiffness, in both the linear and non-linear regimes. This approach requires only an estimate of the system temperature, and is especially useful for measurements involving trapped objects of unknown size, or objects in a fluid of unknown viscosity.
Grazing incidence X-ray absorption characterization of amorphous Zn-Sn-O thin film

We report a surface structure study of an amorphous Zn-Sn-O (a-ZTO) transparent conducting film using the grazing incidence X-ray absorption spectroscopy technique. By setting the measuring angles far below the critical angle at which the total external reflection occurs, the details of the surface structure of a film or bulk can be successfully accessed. The results show that unlike in the film where Zn is severely under coordinated (N < 4), it is fully coordinated (N = 4) near the surface while the coordination number around Sn is slightly smaller near the surface than in the film. Despite a 30% Zn doping, the local structure in the film is rutile-like.
An Intention-Based Account of Perspective-Taking: Why Perspective-Taking Can Both Decrease and Increase Moral Condemnation

Perspective-taking often increases generosity in behavior and attributions. We present an intentions-based account to explain how perspective-taking can both decrease and increase moral condemnation. Consistent with past research, we predicted perspective-taking would reduce condemnation when the perspective-taker initially attributed benevolent intent to a transgressor. However, we predicted perspective-taking would increase condemnation when malevolent intentions were initially attributed to the wrongdoer. We propose that perspective-taking amplifies the intentions initially attributed to a transgressor. Three studies measured and manipulated intention attributions and found that perspective-taking increased condemnation when malevolent intentions were initially attributed to a transgressor. Perspective-taking also increased costly punishment of a transgressor, an effect mediated by malevolent intentions. In contrast, empathy did not increase punitive responses, supporting its conceptual distinction fro...
Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice

Stability of neuronal connectivity is critical for brain functions, and morphological perturbations are associated with neurodegenerative disorders. However, how neuronal morphology is maintained in the adult brain remains poorly understood. Here, we identify Wnt5a, a member of the Wnt family of secreted morphogens, as an essential factor in maintaining dendritic architecture in the adult hippocampus and for related cognitive functions in mice. Wnt5a expression in hippocampal neurons begins postnatally, and its deletion attenuated CaMKII and Rac1 activity, reduced GluN1 glutamate receptor expression, and impaired synaptic plasticity and spatial learning and memory in 3-mo-old mice. With increased age, Wnt5a loss caused progressive attrition of dendrite arbors and spines in Cornu Ammonis (CA)1 pyramidal neurons and exacerbated behavioral defects. Wnt5a functions cell-autonomously to maintain CA1 dendrites, and exogenous Wnt5a expression corrected structural anomalies even at late-adult stages. These findings reveal a maintenance factor in the adult brain, and highlight a trophic pathway that can be targeted to ameliorate dendrite loss in pathological conditions.
Between the World and Me; Ghetto: The Invention of a Place, the History of an Idea; Knocking the Hustle: Against the Neoliberal Turn in Black Politics; and The Cook Up: A Crack Rock Memoir

Between the World and Me. Ta-Nehisi Coates. New York, NY: Spiegel & Grau, 2015. xii and 164 pp., photos. $24.00 cloth (ISBN 978-0-8129-9354-7).Ghetto: The Invention of a Place, the History of an Id...
Introduction, Gas Turbines, Applications, Types

Gas turbines are engines within which the chemical energy of the fuel is converted either into mechanical energy in terms of shaft power or into kinetic energy. Gas turbines that produce shaft power are power generation gas turbines. Gas turbines that convert the fuel energy into kinetic energy are used for generation of thrust to propel an aircraft.
DNA-informed breeding of rosaceous crops: promises, progress and prospects

Crops of the Rosaceae family provide valuable contributions to rural economies and human health and enjoyment. Sustained solutions to production challenges and market demands can be met with genetically improved new cultivars. Traditional rosaceous crop breeding is expensive and time-consuming and would benefit from improvements in efficiency and accuracy. Use of DNA information is becoming conventional in rosaceous crop breeding, contributing to many decisions and operations, but only after past decades of solved challenges and generation of sufficient resources. Successes in deployment of DNA-based knowledge and tools have arisen when the 'chasm' between genomics discoveries and practical application is bridged systematically. Key steps are establishing breeder desire for use of DNA information, adapting tools to local breeding utility, identifying efficient application schemes, accessing effective services in DNA-based diagnostics and gaining experience in integrating DNA information into breeding operations and decisions. DNA-informed germplasm characterization for revealing identity and relatedness has benefitted many programs and provides a compelling entry point to reaping benefits of genomics research. DNA-informed germplasm evaluation for predicting trait performance has enabled effective reallocation of breeding resources when applied in pioneering programs. DNA-based diagnostics is now expanding from specific loci to genome-wide considerations. Realizing the full potential of this expansion will require improved accuracy of predictions, multi-trait DNA profiling capabilities, streamlined breeding information management systems, strategies that overcome plant-based features that limit breeding progress and widespread training of current and future breeding personnel and allied scientists.
Concave Mirror Measurement Using Transverse Translation Diverse Phase Retrieval

Surface topography of a concave, spherical mirror is measured using transverse translation diverse phase retrieval, an image-based wavefront sensing technique. Phase retrieval results show quantitative agreement with independent interferometric measurements of the same optic.
Why do good employees stay in bad organizations

Abstract Family and work are two of society's most important institutions. It is understandable, then, that some similarities would exist between the two. One unfortunate aspect of such relationships is that families and organizations may be abusive to members. When this occurs in familial relationships, research has identified dynamics that keep people in the abusive situation. We consider here how those same dynamics can occur in abusive organizations to identify factors that keep employees in unhealthy work environments. We then examine intervention techniques and concepts that can be used to enable people to recognize an abusive organization, the long-term damage such organizations can inflict on employees, and ways to assist individuals in exiting an abusive organization setting. Our intention is to create awareness of the harm that can be caused by abusive organizations and provide a framework that will enable people caught in a pattern of organizational abuse to understand their choices and behaviors.
Health and Safety in Organic Farming: A Qualitative Study.

Objective: To explore health and safety issues in organic farming, particularly among small farmers in central New Mexico. Methods: Participants included 10 certified organic producers and ...
Update on Myosin Motors: Molecular Mechanisms and Physiological Functions.

The cytoskeleton is the main organizing principle that defines not only the distribution of cellular components within cells but also the overall shape and growth pattern of cells and entire multicellular organisms. This function is particularly evident in plant cells, where, for example, the
Structure and Function of the Bacillithiol-S-Transferase BstA from Staphylococcus aureus.

Bacillithiol is a low-molecular weight thiol produced by many gram-positive organisms, including Staphylococcus aureus and Bacillus anthracis. It is the major thiol responsible for maintaining redox homeostasis and cellular detoxification, including inactivation of the antibiotic fosfomycin. The metal-dependent bacillithiol transferase BstA is likely involved in these sorts of detoxification processes, but the exact substrates and enzyme mechanism have not been identified. Here we report the 1.34 A resolution X-ray crystallographic structure of BstA from S. aureus. Our structure confirms that BstA belongs to the YfiT-like metal-dependent hydrolase superfamily. Like YfiT, our structure contains nickel within its active site, but our functional data suggest that BstA utilizes zinc for activity. Although BstA and YfiT both contain a core four helix bundle and coordinate their metal ions in the same fashion, significant differences between the protein structures are described here.
Survival implications of staging lymphadenectomy for non-endometrioid endometrial cancers.

Abstract Purpose To determine, in patients with non-endometrioid endometrial carcinoma, 1) survival benefit associated with pelvic lymphadenectomy (LND), 2) survival benefit for para-aortic lymphadenectomy performed in addition to pelvic lymphadenectomy, and 3) association between number of lymph nodes removed and survival. Methods Patients with clinical stage I serous carcinoma, clear cell carcinoma, or carcinosarcoma who underwent hysterectomy from 2010 to 2013 were identified from the National Cancer Database. Hazard ratio (HR) for death was assessed using propensity score-weighted multivariable Cox regression models. Subgroup analyses assessed for differences in risk of death among histologic subtypes. Results 7250 patients met study criteria. 930 (13%) did not undergo LND; 2177 (30%) underwent pelvic LND alone; 4143 (57%) underwent pelvic+para-aortic LND. On propensity score-weighted analysis, pelvic LND was associated with decreased risk of death (HR=0.65, 95% CI: 0.59–0.71) compared to no LND. Pelvic+para-aortic LND was associated with decreased risk of death (HR=0.85, 95% CI: 0.79–0.91) compared to pelvic LND for patients with serous carcinoma. Removal of >15 nodes was independently associated with decreased HR for death (HR=0.86, 95% CI: 0.77–0.96); this association persisted when analysis was limited to patients with node-positive disease (HR=0.78, 95% CI: 0.63–0.95). Conclusions LND is associated with survival benefit in patients with non-endometrioid endometrial cancers. Addition of para-aortic LND to pelvic LND may be most beneficial for patients with serous carcinoma. Systematic lymphadenectomy may be associated with survival benefit through detection and microscopic cytoreduction of occult disease.
Advancing catalytic fast pyrolysis through integrated multiscale modeling and experimentation: Challenges, progress, and perspectives

Catalytic fast pyrolysis (CFP) is a conversion process that integrates rapid thermochemical depolymerization of solid feedstocks with catalytic transformation to yield small molecules for fuel and chemical products. This process is well‐suited for the conversion of nonfossil feedstocks such as biomass and waste plastics, and thereby holds great potential for the production of renewable commodities. In spite of many technological developments in various aspects of CFP achieved over decades of research, this technology has yet to attain commercial success for the production of fuels and chemicals from renewable feedstocks. Effective CFP processes require careful coordination of chemical and physical phenomena that span very large length and time scales. A broad spectrum of scientific progress in both pyrolysis and catalytic upgrading has provided the foundation for successful deployment of CFP, although additional progress in process‐scale integration is yet required for commercial realization. Modeling and simulation tools provide an important framework wherein the CFP technologies by be better understood and evaluated from a holistic perspective. Here we provide a detailed description of the multiscale phenomena underlying CFP, describe challenges and associated technical progress, and suggest strategies for an integrated approach to advance this technology toward commercialization. This article is categorized under: Bioenergy > Systems and Infrastructure Bioenergy > Science and Materials