cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract P1-04-02: The role of the mTORC1/S6K1 signaling pathway in ER-positive breast cancer.

The mammalian target of rapamycin complex 1 (mTORC1) is a central signaling node in mediating cellular responses to mitogens, hormones and nutrients. The 40S ribosomal S6 kinase 1 (S6K1) is a conserved serine/threonine protein kinase that belongs to the AGC family of protein kinases, which also includes Akt, RSK and many others. S6K1 is the principal kinase effector downstream mTORC1. S6K1 is sensitive to a wide range of signaling inputs, including growth factors, amino acids, energy levels, and hypoxia. S6K1 relays these signals to regulate a growing list of substrates and interacting proteins in control of oncogenic processes, such as cell growth and proliferation, cell survival and apoptosis, and cell migration and invasion. Growing evidence indicates that there exists a close interaction between the mTORC1/S6K1 pathway and estrogen receptor (ER) signaling. Notably, endocrine resistance is often associated with ligand-independent activation of ERα signaling due to hyperactivation of the mTORC1 signaling pathway, and can be reversed by the mTORC1 inhibitor everolimus in vitro . Several lines of evidence suggest an important role for S6K1 in ER-positive breast cancer. We demonstrated that S6K1 directly phosphorylates ERα on Ser167, leading to activation of its transcriptional activity. While the MAPK-regulated p90 RSK also contributes to phosphorylation of this site, its contribution is early and transient, while the phosphorylation of Ser167 by S6K1 is prolonged and sustained. Intriguingly, we also found that S6K1 expression is estrogenically regulated. This regulation involves the transcription factor GATA-3 and others. Thus it appears that S6K1 expression is maintained in two modes: a basal level of expression, typical of normal cells, and an estrogen/ERα-dependent specific upregulation. Therefore, there exists a feed-forward regulatory loop whereby S6K1 activates ERα transcriptional activity, leading to increased expression of S6K1. This finding is of great interest since it not only sheds light on the mode of transcriptional regulation of S6K1 expression, but may help understand the role of S6K1 overexpression and activation in the development and progression of breast cancer. Therefore, hyperactivation of mTORC1/S6K1 signaling may be closely related to ER-positive status in breast cancer, and may be utilized as a marker for prognosis and a therapeutic target. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-04-02.
Efficient synthesis of fluorescent rosamines: multifunctional platforms for cellular imaging

Abstract Substituted rosamines are efficiently prepared through a new organometallic addition to an imine-substituted xanthone as a novel primary amine equivalent. The synthesis reduces the number of synthetic steps to the targeted rosamines, for convenient and facile access to potential libraries of rosamine dyes. The prepared rosamine derivatives represent unique multifunctional platforms that possess radiolabeling capability and fluorescence. Rosamines have (i) useful non-specific binding properties in mammalian cells and plant root hair, and (ii) positive uptake or binding properties in microbial systems.
Model Simulation and Projection of European Heat Waves in Present-Day and Future Climates

AbstractThe synoptic behavior of present-day heat waves (HW) over Europe is studied using the GFDL high-resolution atmospheric model (HiRAM) with 50-km grid spacing. Three regions of enhanced and coherent temperature variability are identified over western Russia, eastern Europe, and western Europe. The simulated HW characteristics are compared with those derived from Climate Forecast System Reanalysis products. Composite charts for outstanding HW episodes resemble well-known recurrent circulation types. The HW region is overlain by a prominent upper-level anticyclone, which blocks the passage of synoptic-scale transients. The altered eddy vorticity transports in turn reinforce the anticyclone. The anticyclone is part of a planetary-scale wave train. The successive downstream development of this wave train is indicative of Rossby wave dispersion.Additional runs of HiRAM are conducted for the “time slices” of 2026–35 and 2086–95 in the climate scenario corresponding to representative concentration pathway ...
Statistical analysis of data from the "before-after" type of experiments.

Summary: Statistical analysis of data from the “before-after” type of experiments. J. Lee, Aust. N.Z. J. Med., 1978, 8, pp. 641–645. There are many experiments in which the variable of interest is measured twice from each subject. Supposing a nutrition experiment were conducted to compare two diets on the mean gain in body weight. The body weight of each subject is recorded before the diets are given (initial weight, I) and then at the termination of the experiment (final weight, F). Comparison of mean weight gain is valid only if the distribution of initial weights were comparable between the two groups of subjects. Random allocation of subjects or matching (pairing) can be used at the design stage to enhance the comparability of the subjects in the two groups. However, random allocation does not ensure comparability, especially if the sample sizes were small. Matching does ensure comparability. But in many instances, matching may not be feasible for various logistic reasons. The likely situation is that the mean initial weights will not be comparable in the two groups being compared. Hence, some sort of statistical adjustment at the data-analytic stage is called for. Statistical adjustment is usually done by either one of these methods: (1) Compare mean weight gain by the usual unpaired X-test, where weight gain is computed by (F-l) for each subject, (2) Use covariance adjustment (analysis of covari-ance) of F using I as the covariate, (3) Compare mean relative (i.e. per cent) weight gain by the unpaired t-test, where per cent weight gain is computed by 100(F-1)/1 for each subject.
A Program for F Distributions with Fractional Degrees of Freedom

Surnnzary.-A FORTRAN 77 program is described that evaluates the F distribution, providing probability values given a computed F statistic and critical values of F given a probability value. The program is accurate for all F distributions and allows the user to input positive frnctional degrees of freedom. A FORTRAN 77 program is described that computes upper-tail probabilities of the F distribution, given an observed F statistic and the numerator and denominator degrees of freedom, vl and v2, respectively. In addition, the program computes critical values of the F distribution, given v,, v2, and an upper-tail probabhty value. Program FDIST is based on the incomplete beta function of Cran, Martin, and Thomas (1977) and incorporates the corrections of Berry, Mielke, and Cran (1990). The program allows for positive fractional degrees of freedom.
EXPERIENCE WITH NEONATAL THROMBOCYTOPENIA

Thrombocytopenia (TP) (Platelets < 100,000/cmm) occurred in 118 of 528 infants (22%) admitted to Bellevue Hospital High Risk infant Center 7/1/74-6/30/76. Possible etiologic factors were found in only 40 cases (34%) : maternal thiazide 5, immunologic 10, post exchange transfusion 10, DIC 15. Of TP babies 45.3% weighed < 1500 gm (cf. 22% of total admissions) and 24% were SGA. The majority had significant morbidity: Apgar < 4 (1 min) 20.5%, RDS 43.5%, meconium aspiration 10.2%, NEC 2.5%, systemic bacterial infection 14.5% (sepsis and/or meningitis 12, and pneumonia in 5 infants). Phototherapy was used in 58%. Umbilical catheters were placed in 68% of infants of which 1/3 developed some clinical evidence of vascular occlusion. Mortality was 37.3% (44/118) and was greater among those with <50,000 platelets. Of 33 autopsied babies 23 (84.8%) had significant hemorrhage, compared to 12/19 non-TP babies (63%) in the same period. Micro-thrombi indicating DIC were seen in 11 TP babies. TP Is common in high risk infants. It is most common in very small infants and is usually associated with serious illness. An apparent trend toward greater incidence of hemorrhage in TP babies was not statistically significant. The cause of TP is unknown in most cases.
Dissociation Pathways of 2,3-Dihydrofuran Measured by Chirped-Pulse Fourier Transform Microwave Spectroscopy

This experiment combines the use of an ultrabroadband chirped-pulse Fourier transform microwave (CP-FTMW) spectrometer with a pulsed discharge nozzle to study products formed during dissociation of 2,3-dihydrofuran (2,3-DHF). Molecules identified in the spectrum include cyclopropanecarboxaldehyde (CPCA), acrolein, crotonaldehyde (CA), formaldehyde, propene, propyne and cyclopropenylidene. Individual cis and trans isomers were detected for CPCA and acrolein, but only the trans isomer of CA was observed. Although cis forms of CPCA and CA would be the most likely structures produced from 2,3-DHF isomerization, our discharge provides enough energy for the molecules to convert into multiple conformers. The identification of formaldehyde in the spectrum supports a proposed mechanism to form propyne directly from 2,3-DHF ring-opening, a scheme that has been difficult to verify. Although acetylene cannot be detected because of the lack of a permanent dipole moment, the existence of cyclopropenylidene (C3H2) is in...
A role for Toll in autoimmunity

In some autoimmune diseases, antibodies form that recognize other self-antibodies or DNA. A recent report in Nature implicates the Toll-like receptor 9 and innate immunity as a possible key to understanding the initiation of this process.
Discriminative stimulus properties of midazolam are shared by a GABA-receptor positive steroid

3-Alpha-5-alpha-tetrahydrodeoxycorticosterone (alloTHDOC) is a 3-alpha ring A-reduced metabolite of deoxycorticosterone that has been shown to act via nongenomic mechanisms to modulate the GABAA receptor complex allosterically in vitro. Moreover, there are behavioral data consistent with the anxiolytic actions of GABA-receptor positive steroids. The drug discrimination paradigm was used in rats to demonstrate that effects of alloTHDOC are mediated by the GABAA receptor complex in the intact animal. In rats trained to discriminate 1.8 mg/kg of midazolam from saline, alloTHDOC substituted for the training stimulus.
Determination of the Number of Molecules Bonded to a CdSe Nanocrystallite Surface

Electron excited energy dispersive X-ray spectrometry (EDS) was used to determine the atomic species present in 35 A diameter CdSe nanocrystallites. Both theoretical modeling and experimental calibration with standard materials were used to relate the relative X-ray intensities to the atomic fractions present in the sample. The EDS results were normalized to those found by elemental analysis, which also detects light elements. With different surface models, and the atomic fractions found by EDS, the number of surface groups per nanocrystallite was determined.
Combined image representation using edgelets and wavelets

Recently many new methods of image representation have been proposed, including wavelets, cosine packets, brushlets, edgelets, and ridgelets. Typically each of these is good for a specific class of features, but not good for others. We propose a method of combining two image representations based on 2-D wavelet transform and edgelet transform. The 2-D wavelet transform is good at capturing point singularities, while the newly proposed edgelet transform is good at capturing linear singularities (edges). Both transforms have fast algorithms for digital images. Wavelets and edgelets together form an overcomplete dictionary. To find a sparse representation, we have had success by minimizing the objective function: ∥y - Φx∥2/2 + λρ(x), where y is the image, Φ is the matrix formed from all the basis vectors in both image representations, x is the vector of coefficients and ρ(x) is a convex, l 1 -like, and separable function of x. Sparsity in coefficients is achieved by adding the penalty term on the x: λρ(x). To develop an efficient algorithm to solve this problem, we utilized insights from interior point methods in constrained convex nonlinear optimization and conjugate gradient solvers from computational linear algebra. These methods combine to give a fast algorithm for our problem. Preliminary numerical experiments give promising results.
Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats

Recent advances in deriving induced pluripotent stem (iPS) cells from patients offer new possibilities for biomedical research and clinical applications, as these cells could be used for autologous transplantation. We differentiated iPS cells from patients with Parkinson's disease (PD) into dopaminergic (DA) neurons and show that these DA neurons can be transplanted without signs of neurodegeneration into the adult rodent striatum. The PD patient iPS (PDiPS) cell-derived DA neurons survived at high numbers, showed arborization, and mediated functional effects in an animal model of PD as determined by reduction of amphetamine- and apomorphine-induced rotational asymmetry, but only a few DA neurons projected into the host striatum at 16 wk after transplantation. We next applied FACS for the neural cell adhesion molecule NCAM on differentiated PDiPS cells before transplantation, which resulted in surviving DA neurons with functional effects on amphetamine-induced rotational asymmetry in a 6-OHDA animal model of PD. Morphologically, we found that PDiPS cell-derived non-DA neurons send axons along white matter tracts into specific close and remote gray matter target areas in the adult brain. Such findings establish the transplantation of human PDiPS cell-derived neurons as a long-term in vivo method to analyze potential disease-related changes in a physiological context. Our data also demonstrate proof of principle of survival and functional effects of PDiPS cell-derived DA neurons in an animal model of PD and encourage further development of differentiation protocols to enhance growth and function of implanted PDiPS cell-derived DA neurons in regard to potential therapeutic applications.
Human Ventricular Fibrillation Wandering Wavelets, Mother Rotors, or Both?

A major controversy in cardiac electrophysiology is whether ventricular fibrillation (VF) is maintained by wandering wavelets or mother rotors. On the basis of a computer model of atrial fibrillation by Moe1 developed in 1962, fibrillation was hypothesized to be maintained by multiple small, wandering wavelets, in which the activation pattern is constantly changing. According to the wandering wavelet hypothesis, fibrillation is maintained by constantly changing reentrant circuits formed by some of the wandering wavelets. Because this random reentry can occur anywhere within the cardiac muscle, this hypothesis suggests that all parts of the ventricular myocardium are equally important for the maintenance of VF. Article p 536 The mother rotor hypothesis was put forward for the maintenance of atrial fibrillation first by Lewis2 and later by Gurvich.3 Recently, this hypothesis has been applied to VF by Jalife’s group.4 This group reported that in isolated guinea pig hearts and in isolated right ventricular slabs of sheep, a long-lived, stationary, stable reentrant circuit that they called a “mother rotor” was present.5,6 The mother rotor gave rise to daughter wavefronts that propagated into the remainder of the myocardium. As opposed to the mother rotor, these daughter wavefronts did not have regular, repeating activation sequences. Instead, activation of the daughter wavefronts was less organized, with changing activation sequences, conduction block, and fractionation. It was these unstable daughter wavefronts that gave rise to the disorganized pattern in the ECG. The region containing the mother rotor had a shorter refractory period than the remainder of the myocardium. Jalife’s group postulated that the reason activation was less organized in the regions outside of the mother rotor was that the longer refractory periods in these regions did not allow them to keep up with the mother rotor, whose cycle length was shorter than their …
IMPAIRMENT OF ANTIGEN-SPECIFIC CELLULAR IMMUNE RESPONSES UNDER SIMULATED MICROGRAVITY CONDITIONS

Microgravity has been implicated to play a role in the observed immune dysfunction of astronauts and cosmonauts after either short-term or long-term space travel. These reports, together with studies describing increased levels of microorganisms in the space cabin environment suggest potential risk for in-flight incidences of infectious diseases. In order to understand the mechanism underlying these immune defects, it is important to have a ground-based model that would reliably mimic the effects of microgravity on antigen-specific immune function. We tested the utility of the rotating wall vessel (RWV) technology developed at NASA as a model system because in the RWV the culture medium and the cells rotate synchronously with the vessel, thereby creating simulated microgravity conditions. We compared the RWV to the conventional tissue culture flask (T-flask), for culturing immune precursor cells with cytotoxic T lymphocyte (CTL) activity against synthetic viral peptides. We observed a significant loss of antigen-specific CTL activity in RWV cultures, but not in those from the T-flask, irrespective of the peptide immunogen used for inducing the primary immune response in different mouse strains. Loss of CTL activity in RWV cultures coincided with a significant reduction in CD8+ cells as well as CD4+ cells and DEC205+ dendritic cells, suggesting adverse effects of RWV culturing on both the effector and accessory cells for the loss of antigen-specific CTL function. These results provide a strong parallel to the reported defects in cell-mediated immunity during space travel and strongly support the utility of the RWV technology as an effective ground-based model for identifying key steps in immune cell dysfunction related to microgravity.
Muscle contributions to propulsion and support during running

Muscles actuate running by developing forces that propel the body forward while supporting the body’s weight. To understand how muscles contribute to propulsion (i.e., forward acceleration of the mass center) and support (i.e., upward acceleration of the mass center) during running we developed a threedimensional muscle-actuated simulation of the running gait cycle. The simulation is driven by 92 musculotendon actuators of the lower extremities and torso and includes the dynamics of arm motion. We analyzed the simulation to determine how each muscle contributed to the acceleration of the body mass center. During the early part of the stance phase, the quadriceps muscle group was the largest contributor to braking (i.e., backward acceleration of the mass center) and support. During the second half of the stance phase, the soleus and gastrocnemius muscles were the greatest contributors to propulsion and support. The arms did not contribute substantially to either propulsion or support, generating less than 1% of the peak mass center acceleration. However, the arms effectively counterbalanced the vertical angular momentum of the lower extremities. Our analysis reveals that the quadriceps and plantarflexors are the major contributors to acceleration of the body mass center during running.
CMOS interface circuitry for a low-voltage micromachined tunneling accelerometer

This paper describes the design and development of three types of complementary metal-oxide-semiconductor (CMOS) interface circuitry for low-voltage micromachined tunneling accelerometers. Using a simple inductance-capacitance-resistance (LCR) circuit as well as two nonlinear current/voltage-controlled current sources, an electromechanical model enables simulating and predicting the performance of the accelerometer with CMOS interface circuitry. Of the three types of interface circuitry, the one utilizing a pn-junction diode as a logarithmic current-to-voltage converter has the best performance. The hybrid sensor-circuit module can be incorporated into a portable battery-operated multisensor instrumentation microsystem. Only one 12-V power supply is required for device operation with a power dissipation of 2.5 mW. The accelerometer has a sensitivity of 125 mV/g and bandwidth of 2.5 kHz with a measurement range of 30 g. The noise spectral density with a 1/f behavior drops from 4 mg//spl radic/(Hz) (at 0.5 Hz) to 0.1 mg//spl radic/(Hz) (at 2.5 kHz). The accelerometer in turn provides a dynamic range over 71 dB with a minimum detectable acceleration of 8 mg in a bandwidth of 2.5 kHz. In continuous operation over 720 h, the long-term variations of the output offset voltage and device sensitivity are /spl plusmn/10 mV (0.12%) and /spl plusmn/0.2 mV/g (0.15%), respectively.
Imperfection, practice and humility in clinical ethics

Summary In this essay, I provide a description of the discipline of ethics using the philosophies of Aristotle and the American pragmatist John Dewey. Specifically, I argue that ethics is an active undertaking that is ambiguous and pluralistic. I then normatively prescribe the way in which clinical ethicists ought to approach their work in medicine. Rather than endeavouring to become, or behaving as if they are, experts, clinical ethicists must be humble. They must practise ethics. That is, they must admit ethics is the study and pursuit of the good life but that this study and pursuit occurs imperfectly in the face of problematic situations.
The effect of bathymetric filtering on nearshore process model results

Nearshore wave and flow model results are shown to exhibit a strong sensitivity to the resolution of the input bathymetry. In this analysis, bathymetric resolution was varied by applying smoothing filters to high-resolution survey data to produce a number of bathymetric grid surfaces. We demonstrate that the sensitivity of model-predicted wave height and flow to variations in bathymetric resolution had different characteristics. Wave height predictions were most sensitive to resolution of cross-shore variability associated with the structure of nearshore sandbars. Flow predictions were most sensitive to the resolution of intermediate scale alongshore variability associated with the prominent sandbar rhythmicity. Flow sensitivity increased in cases where a sandbar was closer to shore and shallower. Perhaps the most surprising implication of these results is that the interpolation and smoothing of bathymetric data could be optimized differently for the wave and flow models. We show that errors between observed and modeled flow and wave heights are well predicted by comparing model simulation results using progressively filtered bathymetry to results from the highest resolution simulation. The damage done by over smoothing or inadequate sampling can therefore be estimated using model simulations. We conclude that the ability to quantify prediction errors will be useful for supporting future data assimilation efforts that require this information.
What has happened to family planning since Cairo and what are the prospects for the future

I believe that [the 1994 International Conference on Population and Development in] Cairo effectively signaled the end of the family planning movement and replaced it with what we know today as the reproductive health and rights movement sometimes expanded to also include sexual health and rights - what we now often refer to as sexual and reproductive health and rights or SRHR. While family planning is included in all definitions of reproductive health and rights the SRHR concept is much broader encompassing not only other reproductive services such as emergency obstetrical care and sexually transmitted disease (STD) diagnosis and treatment but also the fundamental right to be free from coercion and to have access to the highest possible level of reproductive health care. What effectively ended at Cairo was the strong linkage between family planning services and efforts to reduce high birth rates. I believe that without intending to do so the architects of the Cairo consensus as it is often called transformed family planning from what had been seen as a global imperative to one among many desirable but nonessential public services. The crisis mentality that had sustained such high levels of support and so high a priority for family planning in the years before Cairo was no longer present at Cairo and it has almost entirely disappeared in the years since Cairo. (excerpt)
On the computation of the many-channelS- matrix

Then-channels-wave radial Sohrodinger equation is transformed into a Riccati equation for a matrix functionS(K, r) which approaches theS-niatrix asymptotically asr→ ∞. It is pointed out that under rather general conditions, S(K, r) is completely determined by a single functionf(K, r) which approaches the Fredholm determinant asr→∞ The problem of parametrization ofS(K, r) is briefly discussed, and, by making use of the algebraic relations betweenS(K, r) andf(K, r), the two-ohannel problem is reduced to the solution of three coupled first-order equations for three real bounded parameters which determine the (S-matrix. These equations are especially convenient for numerical computations.
Constrained optimization in pattern classification using ART

Pattern classification problems involve constrained optimization in the form of minimization of chosen cost functions. Such embedded constraints in integrated neural-fuzzy pattern recognition systems improve the performance of these systems. The comparative performance of an ART-based pattern classifier integrated with fuzzy optimization constraints is demonstrated in designing vector quantizers.
An evaluation of the new FORTRAN 90 standard relative to DSP algorithm implementations

The FORTRAN 90 language definition has now been accepted as a national standard (ANSI) and as an international standard (ISO). This new standard includes a number of very significant additions to the language such as dynamic array location, recursion, single-step array operations, and pointer variables. The author evaluates the new FORTRAN standard particularly with reference to developing and implementing digital signal processing algorithms. FORTRAN 90 is a language with significant new capabilities for solving DSP problems. >
Major Binding Sites for the Nuclear Import Receptor Are the Internal Nucleoporin Nup153 and the Adjacent Nuclear Filament Protein Tpr

A major question in nuclear import concerns the identity of the nucleoporin(s) that interact with the nuclear localization sequences (NLS) receptor and its cargo as they traverse the nuclear pore. Ligand blotting and solution binding studies of isolated proteins have attempted to gain clues to the identities of these nucleoporins, but the studies have from necessity probed binding events far from an in vivo context. Here we have asked what binding events occur in the more physiological context of a Xenopus egg extract, which contains nuclear pore subcomplexes in an assembly competent state. We have then assessed our conclusions in the context of assembled nuclear pores themselves. We have used immunoprecipitation to identify physiologically relevant complexes of nucleoporins and importin subunits. In parallel, we have demonstrated that it is possible to obtain immunofluorescence localization of nucleoporins to subregions of the nuclear pore and its associated structures. By immunoprecipitation, we find the nucleoporin Nup153 and the pore-associated filament protein Tpr, previously shown to reside at distinct sites on the intranuclear side of assembled pores, are each in stable subcomplexes with importin α and β in Xenopus egg extracts. Importin subunits are not in stable complexes with nucleoporins Nup62, Nup93, Nup98, or Nup214/CAN, either in egg extracts or in extracts of assembled nuclear pores. In characterizing the Nup153 complex, we find that Nup153 can bind to a complete import complex containing importin α, β, and an NLS substrate, consistent with an involvement of this nucleoporin in a terminal step of nuclear import. Importin β binds directly to Nup153 and in vitro can do so at multiple sites in the Nup153 FXFG repeat region. Tpr, which has no FXFG repeats, binds to importin β and to importin α/β heterodimers, but only to those that do not carry an NLS substrate. That the complex of Tpr with importin β is fundamentally different from that of Nup153 is additionally demonstrated by the finding that recombinant β or β45–462 fragment freely exchanges with the endogenous importin β/Nup153 complex, but cannot displace endogenous importin β from a Tpr complex. However, the GTP analogue GMP-PNP is able to disassemble both Nup153– and Tpr–importin β complexes. Importantly, analysis of extracts of isolated nuclei indicates that Nup153– and Tpr–importin β complexes exist in assembled nuclear pores. Thus, Nup153 and Tpr are major physiological binding sites for importin β. Models for the roles of these interactions are discussed.
G-Protein–Effector Coupling in the Vertebrate Phototransduction Cascade

For many years, the rod phototransduction cascade has served as a valuable model to study the mechanisms of cellular signaling by G-protein-coupled receptors (GPCRs). Our understanding of the key steps of signal transfer from GPCRs to G proteins and further downstream to G protein effectors has been greatly advanced through extensive biochemical studies in rod photoreceptors. This review focuses on the coupling of the visual G protein transducin to its classical effector phosphodiesterase 6. A new level of mechanistic insight has been achieved from the atomic structures of the signaling molecules. Recent studies on light-dependent translocation of transducin in rods raise a possibility for noncanonical transducin signaling and partners in the photoreceptor synaptic terminal.
A Schutzian Theory of Psychotherapy

Psychotherapy can be based on social psychology that has basic concepts and distinctive methods of Schutzian conception and this is shown with an introductory text. An analysis by Schutz of how consociates interact within the We-relation appears to fit the practice of this discipline.
Infrared Laser Photodesorption of Adsorbed Phases

An infrared laser generated from a Nd:YAG laser mixing with a dye laser has been used as a tunable coherent pulsed laser source to photodesorb ammonia from a Cu(100) surface after excitation of the ν3 mode. Time-resolved quadrupole mass spectrometry is sucessfully applied to determine the translational temperatures of the desorbing species from a monolayer coverage on the metal surface. Evidence for desorption induced by vibrational excitation has been obtained and the results are discussed in terms of rapid energy transfer mechanisms.
Longevity predictors. Implications for practice.

Among strong predictors of longevity are general physical health, intellectual and cognitive functioning, and work satisfaction. Findings suggest that maintaining a meaningful social role keeps the aging person physically active and intellectually stimulated and maintains his motivation to take care of himself, all of which tend to extend his life.
Atrophic Acne Scarring: A Review of Treatment Options

Background: Scarring is an unfortunate and frequent complication of acne, resulting in significant psychological distress for patients. Fortunately, numerous treatment options exist for acne scarring. Objectives: To extensively review the literature on treatment options for atrophic acne scarring. Materials and methods: A comprehensive literature search was conducted on the following topics: dermabrasion, subcision, punch techniques, chemical peels, tissue augmentation, and lasers. Results: The literature supports the use of various treatment modalities; superior results may be achieved when multiple modalities are combined for a multi-step approach to scarring. Conclusion: The safety and efficacy of various treatment devices for acne scarring is well established, but there is a paucity of split-face trials comparing modalities.
Urban High-polluted Fuel Forbidden Area: Planning Methodology and Case Study

On the basis of summarizing the experience and methods in planning of high-polluted fuel forbidden area and analyzing the limitations,a methodological framework for planning of high-polluted fuel forbidden area with the use of scenario analysis,model simulation and geographic information system(GIS) is developed,which has been applied in Zhuhai City,Guangdong Province and shows its good maneuverability and feasibility in practice.The framework and case study will provide methodological supports for other cities in China to plan high-polluted fuel forbidden areas.
On the Major Artistic Features of LI Qing-zhao's Later-Period Ci(Lyrics)

After the government of the Song Dynasty was forced to move the capital to the south of China, LI Qing zhao, a great female Ci composer of the Song Dynasty, was doomed to suffer a host of misfortunes. She had to suffer not only the subjugation of her country, but also the decline of her family and the death of her beloved husband, all of which led her to live in great solitude in her later years. In narrating the bitterness and hardship, she underwent in the turmoil and chaos of war. Her Ci (lyrics) revealed that she was always fondly thinking of her native place in the North and yearning for the past good old days while lamenting over the miserable wandering life. We can savor and sense great depression, bitterness and sentiment between the lines. Compared with her early works, LI Qing zhao's later period Ci works attained a higher level in terms of both the depth of thinking and the artistic condensation; moreover, her lively, graceful and restrained literary style had also become a more sentimental and sorrowful one.
Hormonal stimulation of zinc uptake in mammalian cell cultures.

Adrenal steroid hormones with glucocorticoid activity increase the uptake of Zn++ in certain mammalian cell cultures. Whereas in the absence of added hormones the Zn++ content of HeLa S3 cells is approximately 8- to 20-fold greater than that of an equivalent volume of medium, after growth in the presence of prednisolone the cellular Zn++ content doubles or triples. Kinetic studies suggest that cells must grow 8-12 hr in the presence of prednisolone before an increased Zn++ uptake becomes apparent. Accumulation of Zn++ is markedly depressed at low temperatures and in the presence of sulfhydryl-blocking agents. Inhibitors of either glycolysis or oxidative metabolism have little effect on Zn++ uptake. However, if both glycolysis and oxidative metabolism are inhibited, Zn++ accumulation is decreased. 65Z++ taken up by mammalian cells is readily exchangeable and is nearly all soluble in trichloracetic acid. Hormonal effects on Zn++ uptake are selective in that (a) only those steroid hormones with potent glucocorticoid effects stimulate Zn++ uptake while the degree of effectiveness of each hormone parallels its glucocorticoid activity; (b) susceptibility to hormone effects on Zn++ accumulation was confined to certain established "epithelium-like" cell lines; and (c) the uptake of several other cations, for example, 45Ca++ and 36Rb++, was not significantly enhanced by the steroid hormone, and a number of monovalent and divalent cations did not compete with 65Zn++. Certain effects of hydrocortisone on cells may be explained by an increase in the Zn++ content of cells. ACKNOWLEDGMENTS This investigation was supported by Research Grant GM 15508 from the United States Public Health Service and Research Contract U-1296 with the Health Research Council of the City of New York. I wish to acknowledge the valuable technical assistance of Dr. Adriana Ruckenstein and Mrs. Maude Levy. I thank Drs. P. Elsbach, E. Simon, D. Schacter, M. J. Griffin, and J. King for their discussion and advice.
Treatment of Pilon Fracture in External Fixator

A 79-year-old female sustained a mechanical trip down four steps resulting in immediate pain, swelling, and inability to bear weight on her left leg. She is a nonsmoker with a medical history significant only for hypertension. She first presented to the local emergency department where it was confirmed that she sustained an isolated left leg injury. X-rays revealed a left pilon fracture with shaft extension. She was transferred to the emergency department at our tertiary care center for definitive management.
Comparison of molecular typing methods for the analyses of Acinetobacter baumannii from ICU patients

Acinetobacter baumannii has emerged as an important cause of healthcare-associated infections causing great morbidity and mortality. Despite its clinical importance, it is still unknown which molecular typing method is the best to determine or confirm institutional outbreaks as well as to identify epidemiologically related isolates from different geographical areas. To determine the most discriminatory molecular typing method, we isolated A. baumannii from perianal swabs collected from intensive care unit (ICU) patients in a cohort study during 2002 and 2008. Strains from each year were analyzed by pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), and multi-locus variable-number tandem repeat analysis (MLVA). Genetic relatedness of the isolates was consistent between PFGE and MLST as well as between analyses of loci containing MLVA and MLST. Our data show that PFGE and MLVA are similar when discriminating between isolates and are both good methods to use when questioning whether two isolates are indistinguishable.
Generation of stochastic mobility maps for large-scale route planning of ground vehicles: A case study

Abstract This paper describes a simple and efficient methodology to generate a mobility map accounting for two sources of uncertainty, namely measurement errors (RMSE of a Digital Elevation Model) and interpolation error (kriging method). The proposed methodology means a general-purpose solution since it works with standard and publicly-available Digital Elevation Models (DEMs). The different regions in the map are classified according to the geometry of the surface (i.e. slope) and the soil type. A real USGS DEM demonstrates the suitability of the proposed methodology: (1) interpolation of a 26 × 40 -km 2 DEM to a finer resolution (30-m to 20-m); (2) analysis of the number of random realizations to account for the variability of the data; (3) efficient computation time (4-million-point DEM requires less than 30 min to complete the whole process); (4) route planning using the stochastic mobility map (constraints in slope and soil properties). UNCLASSIFIED: Distribution Statement A. Approved for public release; distribution is unlimited. #27681
Does treatment of paradoxical vocal fold movement disorder decrease asthma medication use

Objectives/Hypothesis To determine whether diagnosis and treatment of paradoxical vocal fold movement disorder (PVFMD) leads to decreased asthma medication use. Secondary objectives include determining initial rate of asthma medication use, characterizing symptom improvement, and correlating with pulmonary function testing (PFT). Study Design Prospective observational study. Methods Patients newly diagnosed with PVFMD at a single institution were recruited to participate. Medication questionnaires were completed at the initial visit, at the first return visit for therapy, and at 6 months. PFTs were reviewed when available. Results Sixty-six patients were recruited; the study was closed early because findings reached significance. Fifty-six patients (85%) were taking asthma medication at presentation. Forty-four patients presented with PFTs, and two-thirds were normal. Forty-two patients completed follow-up questionnaires; 79% decreased asthma medication use (P < .001), and 82% reported symptom improvement. Seventy-seven percent of patients participated in therapy and 23% did not, with equal rates of decrease in asthma medication use between these groups. Outcomes did not vary based on PFT pattern (i.e., obstructive vs. nonobstructive, P = .75). Conclusions Diagnosis and treatment of PVFMD lead to a decline in asthma medication use. This decrease occurred alongside symptom improvement and irrespective of PFT findings. Use of asthma medication in this patient population is high, at 85%. Level of Evidence 4. Laryngoscope, 127:1531–1537, 2017
Do Firms Still Save Cash out of Cash Flows? An Updated Investigation into the Cash Flow Sensitivity of Cash

Almeida, Campello, and Weisbach (2004) show that cash flow sensitivities are higher for firms that are financially constrained. This paper updates and extends the work of Almeida, Campello, and Weisbach to account for possible misspecification of financial constraints as well as changes in firm and industry characteristics. Using an updated sample period along with new measurements of financial constraints, I show that the schemes originally provided to measure firms as financially constrained are subject to misspecification in the original sample period. However, in employing the same methodology to a contemporary sample period, the results support ACW. I also investigate whether these classification schemes as well other contemporary classification schemes of financial constraint hold up using a sample of non-manufacturing firms. Overall, the results are consistent with Chen and Chen (2012), in that the overall cash-flow sensitivity has declined over the years for both manufacturing and non-manufacturing firms.
Overexpression of Rasgrf1, a Guanine Nucleotide Exchange Factor in Chronic Lymphocytic Leukemia.

Abstract 1253 Poster Board I-275 We performed microarray expression analysis to identify genes which are differentially expressed in chronic lymphocytic leukemia (CLL) cells. A number of genes from the cohort of maximally upregulated genes were members of the Ras superfamily of proteins function which function as switches between active GTP-complexed and inactive GDP-complexed states. One of the genes upregulated on the microarray analysis in all the CLL cells as compared to normal B cells was RASGRF1. This ras protein specific guanine nucleotide release factor stimulates the dissociation of GDP and activates Ras signaling pathway. To confirm our microarray analysis results, we performed real time PCR analysis on 35 CLL specimens and observed a 10-50 fold upregulation of rasgrf1 RNA as compared to human peripheral blood B cells. This high expression is consistently observed in all CLL specimens regardless of stage indicating that this upregulation is an early important event in the pathogenesis of CLL. Rasgrf1 protein expression was also higher in CLL cells as compared to normal B cells by western blot analysis. Interestingly the rasgrf1 gene is genomically imprinted during development in certain tissues and the expression is downregulated. Demethylation of normal peripheral blood B cells by treatment with azacytidine resulted in increased expression of rasgrf1 with no change in expression of rasgrf1 in CLL cells implying imprinting in normal B cells. Thus malignant transformation of B cells to CLL cells results in a loss of genomic imprinting and an aberrant upregulation of rasgrf1 in CLL cells. One important downstream effect of rasgrf1 upregulation is ERK activation via Ras-MAPK pathway. B cell receptor signaling in CLL results in activation of a number of pro-survival pathways including ERK which is more active in poor prognosis, unmutated immunoglobulin heavy chain CLL. Our results indicate that ERK phosphorylation is also increased in CLL specimens with rasgrf1 overexpression. Disclosures No relevant conflicts of interest to declare.
Understanding How Domestic Violence Support Services Promote Survivor Well-being: A Conceptual Model

Domestic violence (DV) victim service programs have been increasingly expected by legislators and funders to demonstrate that they are making a significant difference in the lives of those using their services. Alongside this expectation, they are being asked to describe the Theory of Change guiding how they believe their practices lead to positive results for survivors and their children. Having a widely accepted conceptual model is not just potentially useful to funders and policy makers as they help shape policy and practice -- it can also help programs continually reflect upon and improve their work. This paper describes the iterative and collaborative process undertaken to generate a conceptual model describing how DV victim services are expected to improve survivors’ lives. The Social and Emotional Well-Being Framework guiding the model is an ideal structure to use to describe the goals and practices of DV programs because this framework: (1) accurately represents DV programs’ goal of helping survivors and their children thrive; and (2) recognizes the importance of community, social, and societal context in influencing individuals’ social and emotional well-being. The model was designed to guide practice and to generate new questions for research and evaluation that address individual, community, and systems factors that promote or hinder survivor safety and well-being.
Pseudoexstrophy: a forme fruste of bladder exstrophy.

A 10-year-old male presented with a long-standing history of functional periumbilical abdominal pain without associated symptoms. Medical history, surgical history and family history were unremarkable. Pertinent findings on examination included normal lower extremity strength and reflexes, no spine abnormality, normal positioned anus with an intact anal wink and undescended testes. The umbilicus was inferiorly displaced with a palpable circular defect. There were prominent soft tissue masses inferior …
Abstract 294: Hematopoietic Cells Are Required For Proper Development Of Coronary Vasculature

Objective: We examined whether the hematopoietic cells induce the coronary artery formation using genetically modified mouse models of hematopoietic ablation in vivo and ex vivo . Methods: As a model of for hematopoietic cell deficient animals, we used Runx1 (a transcription factor required for definitive hematopoiesis) knockout embryos and Vav1-cre; R26-DTA embryos, which ablates 2/3 of CD45+ hematopoietic cells. The coronary growth and the hematopoietic cells were evaluated in whole-mount, section and ex vivo explant culture. Results: The developing coronary endothelial cells form blood-island-like structure at around E12.5 in the subepicardial region. Interestingly, however, the histological analyses suggest that the first Ter119+ and CD45+ blood cells appear in the subendocardial area at E10.5, even before the formation of coronary channels. These initial hematopoietic cells in the heart are not likely derived from the epicardium, as the sorted epicardial cells yielded no hematopoietic cell in colony formation assay. These observations raised a question whether these heart-resident hematopoietic cells rather play an inductive role during coronary formation. To examine this possibility, we analyzed two hematopoietic ablation models. Both Runx1 knockout embryos and Vav1-cre; R26-DTA embryos revealed disorganized, hypoplastic microvasculature of coronary vessels on section and whole-mount stainings. Furthermore, coronary explant experiments showed that the mouse heart explants from Runx1 knockout embryos and Vav1-cre; R26-DTA embryos exhibited impaired coronary formation ex vivo. Conclusion: Hematopoietic cells are not merely transported via coronary vessels, but substantially involved in the induction of the coronary vessels during cardiogenesis.
Pig Killing and Surviving Modernity: Jude the Obscure

In the final chapter, the anxieties brought about by the shift in population from a rural to a predominantly urban one will be demonstrated by Jude and Sue’s inability in Jude the Obscure to adapt to a changing environment. This will be achieved through an examination of food, primarily Farmer Troughtham’s ‘utilitarian’ field and the ‘Christminster Cakes’ that Jude bakes when he is unable to work as a stone mason. Conversely, Arabella’s ability to survive in the modern world will be examined through her association with pigs and other foodstuffs. Hardy’s own concerns with the treatment of livestock is clearly illustrated in this novel as well as his anxiety over Britain’s inability to produce enough food to feed its growing population.