cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulation of cGMP-dependent Protein Kinase Expression by Rho and Krüppel-like Transcription Factor-4

Type I cGMP-dependent protein kinase (PKG I) plays a major role in vascular homeostasis by mediating smooth muscle relaxation in response to nitric oxide, but little is known about the regulation of PKG I expression in smooth muscle cells. We found opposing effects of RhoA and Rac1 on cellular PKG I expression: (i) cell density-dependent changes in PKG I expression varied directly with Rac1 activity and inversely with RhoA activity; (ii) RhoA activation by calpeptin suppressed PKG I, whereas RhoA down-regulation by small interfering RNA increased PKG I expression; and (iii) PKG I promoter activity was suppressed in cells expressing active RhoA or Rho-kinase but was enhanced in cells expressing active Rac1 or a dominant negative RhoA. Sp1 consensus sequences in the PKG I promoter were required for Rho regulation and bound nuclear proteins in a cell density-dependent manner, including the Kruppel-like factor 4 (KLF4). KLF4 was identified as a major trans-acting factor at two proximal Sp1 sites; active RhoA suppressed KLF4 DNA binding and trans-activation potential on the PKG I promoter. Experiments with actin-binding agents suggested that RhoA could regulate KLF4 via its ability to induce actin polymerization. Regulation of PKG I expression by RhoA may explain decreased PKG I levels in vascular smooth muscle cells found in some models of hypertension and vascular injury.
The sustainability of privilege: Reflections on the environment, the third world city, and poverty

Abstract Urbanization, problems of the environment, and poverty have all grown dramatically over the past quarter century in many countries. We combine discussion of these three phenomena, using concepts of social class to make the connections. This approach stresses the human element over matters of inanimate technology or nature. By disaggregating society into computing groups it reveals environmental problems to be essentially those of people and social and political organization, not of nature and technology. We conclude that improvement of the environment in large cities of the Third World will require social change.
Stereoselective synthesis of the phorboxazole A macrolide by ring-closing metathesis.

Described is a regio- and stereoselective ring-closing metathesis (RCM) to form the C2−C3 alkene of the macrolide-containing domain of phorboxazole A. This work demonstrates a dramatic effect of reaction solvent on RCM product (E/Z)-selectivity. This process offers an alternative assembly of the macrolide-containing domain of phorboxazole A, one of the most potent anticancer agents known.
Calcium influence on neuronal sensitivity to ethanol in selectively bred mouse lines

Sensitivity to ethanol, as measured by blood ethanol concentration at loss of righting reflex, was increased significantly in SS but not LS mice following intracerebroventricular (ICV) administration of calcium chloride or A23187, a calcium ionophore. Magnesium chloride or lanthanum chloride, ICV, did not alter sensitivity to ethanol in either SS or LS mice, further indicating a specificity for calcium cation. Calcium was without effect on sensitivity to halothane narcosis in LS or SS mice. Endogenous brain calcium content was similar in these mouse lines, and ethanol administration either in vivo or in vitro did not alter brain calcium concentration. These results indicate that differences in brain sensitivity to ethanol are mediated, in part, by genetic differences in calcium-related processes and support the hypothesis that ethanol-induced narcosis may be due to alterations in calcium metabolism in the CNS.
Inflammatory breast cancer treated with surgery, chemotherapy and allogeneic tumor cell/BCG immunotherapy

Thirteen consecutive patients with inflammatory breast cancer were treated with a regimen consisting of cyclic chemotherapy, extended simple mastectomy, and immunotherapy utilizing irradiated allogeneic breast cancer cells admixed with BCG. When surgery was performed after two or more cycles of 5-U, doxorubicin hydrochloride, and cyclophosphamide, there was complete eradication of detectable tumor in three of 11 operative specimens. Two patients had surgery prior to our evaluation and four had prior chemotherapy. Chest wall radiation was initiated after 8-10+ months of chemotherapy at the doxorubicin cardiotoxicity limits. Seven untreated patients, all premenopausal, were compared to our previous series which employed either irradiation after several courses of chemotherapy or irradiation alone. The current series has two relapses (eight months, 25 months) at a median follow-up time of 21 months (range, 8-26 months). In the previous chemoradiotherapy trial, all nine premenopausal patients had relapsed within 25 months, with a median disease free interval of 17 months. In the trial using radiotherapy alone, all ten patients had relapsed by 19 months (median disease free interval, nine months). The present regimen appears to improve control of the disease and further investigation of both surgery and immunotherapy intercalated with cyclic chemotherapy appears warranted in this disease.
Cholesterol modulated antibody binding in supported lipid membranes as determined by total internal reflectance microscopy on a microfabricated high-throughput glass chip.

A high-throughput microfabricated all-glass microchip, lipid biochip, was created and used to measure fluorescently tagged antibody binding to dinitrophenol (DNP) haptens in planar supported phospholipid/cholesterol lipid bilayers as a function of cholesterol-to-lipid molar ratio (XCHOL). Multiple parallel microchannels etched in the lipid biochip allowed simultaneous measurement of antibody binding to hapten-containing and hapten-free lipid bilayers, for a range of aqueous antibody concentrations. Specific and nonspecific antibody binding to the supported lipid bilayers was determined from the internally calibrated intensity of the surface fluorescence using total internal reflectance fluorescence (TIRF) microscopy. The TIRF intensity data of the specific antibody binding were fitted to the Langmuir isotherm and Hill equation models to determine the apparent dissociation constant Kd, the maximum fluorescence parameter F∞, and binding cooperativity n. As XCHOL increased from 0 to 0.50, Kd exhibited a mini...
Microtubule stabilization by taxol inhibits initiation of DNA synthesis by thrombin and by epidermal growth factor

Several observations have suggested that microtubule depolymerization might act as a regulator of cell proliferation. To determine whether microtubule depolymerization is required for growth-factor-induced initiation of DNA synthesis, we treated serum-free cultures of mouse embryo cells with taxol to stabilize their microtubules and measured the initiation of DNA synthesis by thrombin and epidermal growth factor (EGF). Pretreatment of quiescent cultures of mouse embryo cells with 10 microgram/ml taxol inhibited up to 60% of the thrombin-stimulated and 47% of the EGF-stimulated DNA synthesis. This inhibition was dose-dependent for taxol concentrations from 0.3 to 20 microgram/ml. Control experiments showed that taxol did not simply affect uptake of nucleotides, glucose or amino acids, nor did it nonspecifically affect protein synthesis, cell morphology or cell viability. Taxol did not affect binding and internalization of 125I-thrombin or 125I-EGF indicating that the drug does not alter receptor number, affinity or distribution after growth factor binding. Taxol also did not affect the proteolytic activity of thrombin. Thus it appears that the inhibitory effects of taxol are mediated by a direct effect of taxol on microtubules. To determine at what point microtubule stabilization was interrupting the initiation signal, we added taxol at various times after addition of thrombin or EGF. Taxol addition during the first 8 hr after growth factor addition inhibited initiation, but after 8 hr had little if any effect. These results confirm that taxol was not nonspecifically affecting transport or metabolism required for DNA synthesis and indicate that thrombin and EGF may initiate cell proliferation through a gradual microtubule depolymerization or rearrangement that is necessary to commit cells to a replicative cycle.
In vitro methylation assay to study protein arginine methylation.

Protein arginine methylation is one of the most abundant post-translational modifications in the nucleus. Protein arginine methylation can be identified and/or determined via proteomic approaches, and/or immunoblotting with methyl-arginine specific antibodies. However, these techniques sometimes can be misleading and often provide false positive results. Most importantly, these techniques cannot provide direct evidence in support of the PRMT substrate specificity. In vitro methylation assays, on the other hand, are useful biochemical assays, which are sensitive, and consistently reveal if the identified proteins are indeed PRMT substrates. A typical in vitro methylation assay includes purified, active PRMTs, purified substrate and a radioisotope labeled methyl donor (S-adenosyl-L-[methyl-3H] methionine). Here we describe a step-by-step protocol to isolate catalytically active PRMT1, a ubiquitously expressed PRMT family member. The methyl transferase activities of the purified PRMT1 were later tested on Ras-GTPase activating protein binding protein 1 (G3BP1), a known PRMT substrate, in the presence of S-adenosyl-L-[methyl-3H] methionine as the methyl donor. This protocol can be employed not only for establishing the methylation status of novel physiological PRMT1 substrates, but also for understanding the basic mechanism of protein arginine methylation.
Autoreactive factors identify tumor-host heterogeneity and responsiveness to immunotherapy

The heterogeneity of tumor-bearing animals was defined by the presence of an autoreactive antibody and cell agglutination factor in the sera of leukemic mice. The presence of this antibody, which could only be detected by its ability to lyse neuraminidase-treated spleen cells, correlated directly with the survival of the animals treated with active, specific immunotherapy. The results indicate that heterogeneity in hosts can be identified, and that autoreactive factors may be predictive for the individual response to immunotherapy and play a role in the establishment of the tumor-host relationship.
Validity of the Superiority and Goal Instability Scales as Measures of Defects in the Self

A series of four canonical correlation analyses was conducted to compare the Superiority and Goal Instability scales both with personality pattern and clinical syndrome scales from the Millon Clinical Multiaxial Inventory (MCMI) and with therapist ratings of personality traits and symptom patterns using 91 clients from a cross-section of outpatient and inpatient mental health agencies. The Superiority scale was related to a pattern of social gregariousness, interpersonal exploitation, and impulsivity and Goal Instability was related to a pattern of social withdrawal, depression, and lack of ambitions and goals. These results clarify the meaning of the two self-scales as well as providing preliminary data on self-pathology and character types.
Advances in magnetospheric storm and substorm research: 1989–1991

Recent advances in magnetospheric storm and substorm research is reviewed, with emphasis on how the large southward fields and high velocities produced in the solar wind influence the magnetosphere and cause the enhanced transfer of energy, momentum, and mass to the magnetosphere. Overwhelming evidence indicates that the southward interplanetary magnetic field is the primary controlling factor in the generation of substorms. The immediate cause of the expansion phase onset is controversial, but the suddenness of the onset is suggestive of an instability that disrupts the cross-tail currents. Measurements increasingly suggest the region of 7-10 R sub E near midnight as the likely point of origin, but it is not clear that the long-popular tearing mode can go unstable this close to the earth, where it may be stabilized by a small northward field component.
Quantitative imaging of concentration by planar laser-induced fluorescence

The planar laser-induced fluorescence (PLIF) technique is attractive for instantaneous and non-intrusive imaging of species concentration in gaseous flows. This paper provides a framework for determining the experimental resolution in PLIF experiments and gives error estimates for concentration measurements in turbulent jet mixing experiments using biacetyl as the molecular tracer. The procedures to correct for experimental artifacts in the PLIF images are outlined. Images of the instantaneous, average, rms, and dissipation of concentration in a turbulent jet are presented.
Sets of best L1-approximants

On considere un espace X du type L 1 (Ω, A, μ) et une partie convexe et fermee C de X. On sait que pour un grand nombre de choix de C il existe des meilleurs approximants dans C pour tout element de X. Ces approximants sont rarement determines de facon unique. Ici on compare les «distances» entre fonctions et entre ensembles d'approximants correspondants
Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach

Studies using high dose testosterone (T) administration in normal men as a male contraceptive have resulted in azoospermia rates of only 50-70%. Previous studies of T and progestogen combinations have shown comparable rates of azoospermia, but have been uncontrolled or used T in doses less than that associated with maximal suppression of sperm production. We conducted a randomized, placebo-controlled, single blind trial comparing 6 months of T enanthate administration (100 mg, im, weekly) with the same dose of T enanthate in conjunction with the progestogen levonorgestrel (LNG; 500 micrograms, orally, daily) in 36 normal men, aged 20-42 yr (n = 18 in each group). The primary end points were induction of azoospermia or severe oligospermia (< 3 million sperm/mL). The combination of T plus LNG was much more effective in suppressing sperm production than T alone. Sixty-seven percent of the T plus LNG group (12 of 18) and 33% of the T alone group (6 of 18) achieved azoospermia by 6 months (P = 0.06). Severe oligospermia or azoospermia developed in 94% of the T plus LNG (17 of 18) group compared to 61% of the T alone group (11 of 18; P < 0.05). T plus LNG also suppressed sperm production more rapidly than T alone. Time to azoospermia was 9.9 +/- 1.0 vs. 15.3 +/- 1.9 weeks in the T plus LNG and T alone groups, respectively (mean +/- SEM; P < 0.05). Serum high density lipoprotein cholesterol decreased 21.7 +/- 3.6% in men given T plus LNG (P < 0.05), compared to only a 1.8 +/- 3.8% decrease in men in the T alone group. Average weight gain was 5.3 +/- 0.8 kg in the T plus LNG group and 2.3 +/- 0.9 kg in the T alone group (P < 0.05). Acne and increase in hemoglobin were similar in the two groups. We conclude that combination hormonal therapy with T plus a progestogen might offer a reversible male contraceptive approach with a more rapid onset of action and more reliable induction of both azoospermia and severe oligospermia than T alone.
The effects of sublethal concentrations of five organophosphorus insecticides on temperature tolerance, reflexes, and orientation in Gambusia affinis affinis (Pisces: Poeciliidae)

Gambusia affinis were exposed to the insecticides ABATE®, fenthion, chlorpyrifos, methyl parathion, and malathion for 24 h at concentrations of 1, 5, and 10 ppb and for 48 h at 5 ppb. The thermal tolerance was lowered significantly for male and female G. affinis by the toxicants methyl parathion and chlorpyrifos at 5 and 10 ppb with 24 h exposure. Activity was restricted with fish exposed to methyl parathion and chlorpyrifos at concentrations of 10 ppb for 24 h and at 5 ppb for 48 h.
Genes for neural differentiation.

here are ,far more neurons in an animal s nervous system than there are genes in its nuclei, so it has been clear for a long time that the genetic specification of neuronal architecture and connec- tivity must be executed via epi- genetic mechanisms that keep the necessary 'instruction set' to man- ageable proportions. One approach to understanding the relationship between the information encoded in the genome and the processes of neural differentiation is to search for mutations that selectively per- turb these processes. Here we focus on two genes in Drosophila that have been defined by mu- tations producing specific altera- tions in the course of neuronal differentiation. The genes must act in different ways, since one of them encodes a membrane-associated protein and the other a nuclear one, but their mutations produce related phenotypes: they both cause specific cells to switch their fates from one cell type to another. A gene required for photoreceptor differentiation encodes a membrane protein The sevenless gene, whose mu- tations selectively affect eye devel- opment, was first identified in a mutagenesis experiment on the basis of a behavioral phenotype, reduction in phototaxis I. Histo- logical analysis revealed that photoreceptor cell R-7, one of the eight that are contained in each unit eye (i.e. ommatidium, Fig. 1A left) of the compound eye, was missing. The eight photorecep- tors, as well as the 12 cells that form the lens and the screening pigment of each ommatidium, are assembled from a pool of pluri- potent cells ~. The order in which they are added to each developing cell cluster is fixed, as is the exact pattern of cell-cell contacts formed by each specific cell of the 20 in each ommatidium 3. These findings suggest that the fate of any cell added to an ommatidial cluster is dependent on communication with the cells that are already present. In sevenless, the cell that should become photoreceptor R-7, ex- pressing a characteristic rhodop- sin, becomes instead a transparent cone cell that helps to secrete the pseudocone, an optical coupling
Lateral Tape Motion Control With Robust Performance Evaluation Based on RBode Plot

Magnetic tapes are still widely used in data storage facilities. A novel approach is presented for reducing the lateral tape motion (LTM) at the reel and thus for preventing the impacts between tape and reel flanges, which can easily damage the fragile tape edges. To measure the LTM, photonic sensors are employed, which have to be calibrated to compensate for nonlinearities and for the shift of the tape path between sensor probes while the reel winds and unwinds. Moreover, since a sensor cannot be placed as close to the reel as desired, the lateral tape position at the reel is estimated by extrapolating from two sensors. Actuation is provided by a tilted rotary guide. In this paper, first, the identified dynamics at the two sensors are combined to estimate the dynamics at the tape nip, and a complex proportional-integral-lead controller is implemented to compensate for the LTM at the extrapolated location. Then, the robust performance characteristics of the implemented controller is evaluated using the robust Bode plot, which accounts for the uncertainties embedded in the used system identification method based on frequency response data. Finally, the experimental results show a significant reduction above 60% in LTM at the reel.
Distributed sleep transistor network for power reduction

Sleep transistors are effective to reduce leakage power during standby modes. The cluster-based design was proposed to save sleep transistor area by clustering gates to minimize the simultaneous switching current per cluster and inserting a sleep transistor per cluster. In this paper, we propose a novel distributed sleep transistor network (DSTN), and show that DSTN is intrinsically better than the cluster-based design in terms of the sleep transistor area and circuit performance. We reveal properties of optimal DSTN designs, and then develop an efficient algorithm for gate level DSTN synthesis. The algorithm obtains DSTN designs with up to 70.7% sleep transistor area reduction compared to cluster-based designs. Furthermore, we present custom layout designs to verify the area reduction by DSTN.
The effect of prospective payment on rehabilitative care

Abstract Dobrez DG, Lo Sasso AT, Heinemann AW. The effect of prospective payment on rehabilitative care. Objectives To estimate the difference between cost and prospective payment system (PPS) reimbursements for rehabilitation care and to simulate potential consequences of cost-reducing strategies. Design A retrospective study to estimate costs and functional status at discharge from care. Setting An academic, urban, rehabilitation hospital. Participants Stroke patients on their first admission to a rehabilitation hospital between 1994 and 1998. Interventions Not applicable. Main outcome measures Cost was estimated from billing databases. Function was measured using the motor and cognitive components of the FIM instrument. Results PPS reimbursements were $10,825 (37%) lower than costs. No matter how much therapy was reduced, the costs were still greater than the mean PPS reimbursement. A reduction in length of stay by 9.6 days was required to bring costs in line with the PPS reimbursement, reducing discharge cognitive function by 1.1 points ( P P Conclusions Our study shows the large difference between costs and expected PPS reimbursements that would have been observed before the PPS. Institutions have many options that reduce costs, with little effect on function at discharge. Future studies should determine the impact of evolving reimbursement rules on facilities' financial status, and on patient outcomes.
The motion of Jupiter XIII (Leda), 1974 - 2000.

A revised orbit and extended ephemeris are calculated for Leda, the thirteenth satellite of Jupiter, by means of numerical integration. Thirty-one observations between September 1974 and December 1977 satisfy the new orbit to 0.9 arcsec on the average.
Evaluation of security features for new U.S. currency

Features for use in the first new design of United States currency in more than 60 years were selected from a field of over 130 possibilities. To narrow the field, individual features were subjected to a variety of evaluation methods, ranging from subjective to rigorous physical to limited production testing. Comprehensive evaluations were carried out by an independent committee of experts through a Treasury contract with the National Research Council (NRC) as well as by the interagency New Currency Design (NCD) Task Force of technical experts from currency production, issuing, processing and enforcement authorities. Features were also rated for effectiveness, durability, feasibility, intelligibility, security, production and processing impact and compatibility with design requirements. Through successive levels of evaluation, the original field was narrowed to 35 for scale-up testing to a handful for production testing. Full production testing and implementation schedule determined the final mix of features included in the new design Series 1996 $100 note.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Mapping the concentration profile at the poly(vinyl chloride)/poly(ethyl methacrylate) interface

The combination of transmission electron microscopy and energy-dispersive spectroscopy is used to map the concentration profile across the interface and measure the mutual diffusion coefficient for a compatible poly(vinyl chloride) and poly(ethyl methacrylate) polymer pair in the melt state. Preliminary results indicate that this technique has enhanced spatial resolution of 100 nanometers.
Realizing expressions of doubt in collaborative dialogue

One way to begin a negotiation subdialogue is to express doubt at a proposition. However, expressions of doubt occur in a variety of forms, each of which conveys information about the nature of the doubt that is important for the subsequent resolution of the conflict. This paper presents our work on realizing expressions of doubt appropriately in natural language dialogues.
A genetic map of melon (Cucumis melo L.) based on amplified fragment length polymorphism (AFLP) markers

Genetic maps facilitate the study of genome structure and evolution, and the identification of monogenic traits or Mendelian components of quantitative traits. We evaluated 228 RAPD, microsatellite and AFLP markers for linkage analysis in melon (Cucumis melo L.) varieties MR-1 (resistant to Fusarium wilt, powdery and downy mildews) and Ananas Yokneum (AY; susceptible to these diseases) and constructed a detailed genetic map. The mapping population consisted of 66 backcross progenies derived from AY×(MR-1×AY). Despite a relatively low level of polymorphism in the species, AFLP markers were found to be more efficient in mapping the melon genome than RAPD or microsatellite markers. The map contains 197 AFLPs, six RAPDs and one microsatellite marker assigned to 14 major and six minor linkage groups, and covers 1942 cM with the average distance between adjacent markers of approximately 10 cM. The maximum distance allowed between markers is 27.5 cM. About 11% of the intervals (20 out of 173) are over 20 cM (but less than 27.5 cM). The map has immediate utility for identifying markers linked to disease resistance genes that are suitable for marker-assisted breeding. The use of microsatellite markers for integration with other maps is also discussed.
Phosphoinositide signaling and the regulation of membrane trafficking in yeast

Phosphoinositides are key regulators of diverse cellular processes in eukaryotic cells. Genetic studies in yeast have advanced our understanding of how phosphoinositide-signaling pathways regulate membrane trafficking. Enzymes required for the synthesis (kinases) and turnover (phosphatases) of distinct phosphoinositides have been identified and several downstream effector molecules linked to phosphoinositide signaling have recently been characterized.
The intersection of strategic management and supply chain management

Strategic management and supply chain management (SCM) have overlapping interests, yet there has been little exchange between them. We examine areas of overlap and suggest how insights from each field can complement and support the other. Specifically, several of strategic management’s theories and its emphasis on explaining firm profits should be useful to SCM. SCM offers to strategic management a new level of analysis and possibly a new type of organization. Overall, we argue that increased interaction between these important areas will benefit knowledge development in both and thereby enhance organizations’ ability to meet their goals.
Magnesium-independent activation of inward-rectifying K+ channels in Vicia faba guard cells

The activation of inward-rectifying K+ channels in guard cells at membrane potentials negative of the K+ equilibrium potential is important for their cellular function as proton pump-driven K+ uptake pathways during stomatal opening. In animal cells the voltage-dependence of inward-rectifying K+ channels is produced to a large extent by intracellular magnesium block. In guard cells, when cytosolic Mg2+ was either 3 mM or < I μM, activation times, deactivation times and the steady-state voltage-dependence of K+ channels remained unchanged. It is discussed that the activation mechanism of inward-rectifying K+ channels in guard cells is independent of intracellular Mg2+ block.
Laparoscopic distal pancreatectomy.

Laparoscopic approach for benign and malignant lesions in the tail of the pancreas is becoming a more widely used approach. Multiple prospective studies have shown the feasibility and safety of LDP in single-center andmulticenter settings. Distal pancreatectomy (DP) is defined as the resection of the body/tail of the pancreas to the left of the superior mesenteric vein. LDP is a challenging procedure, because the pancreas is surrounded by critical structures and located in the retroperitoneum. Mishandling the pancreas itself can be unforgiving and may result in iatrogenic injury that may increase the risk of complications, such as pancreatic fistula. Distal pancreatic adenocarcinoma is an aggressive tumor and may not be appropriate for the laparoscopic
An approach to data visualization and interpretation for sensor networks

With the increase in applications for sensor networks, data manipulation and representation have become a crucial component of sensor networks. This paper explores an approach to process and interpret the data gathered by sensor networks. We have built sensor networks which consist of a series of sensor and communication units ("pods") deployed to monitor rare plants or other endangered species. The environmental data, such as temperature, rainfall, and sunlight, around the plants are sent by the wireless sensor networks to a base station which is able to access the Internet. The approach presented in this paper combines database management technology, geographic information system and Web development technology to visualize the data gathered by the wireless sensor networks. The resulting maps created by a GIS system, GRASS, connect the environmental data with the pods' geographic positions obtained from GPS (the global positioning system). Voronoi diagrams are used to partition the map into areas holding different weather attributes based on the data collected by the pods. The Web development technology /sub y/namic Web programming - is also adopted in this system to make the data available via the Internet. Finally, we sketch the design of an asynchronous collaborative discussion environment which supports online communities among the end users of our information interpretation system. The integration of our data visualization tools and the online collaborative discussion environment makes the system useful to different communities of potential users.
Cyclin D3 Maintains Growth-Inhibitory Activity of C/EBPα by Stabilizing C/EBPα-cdk2 and C/EBPα-Brm Complexes

C/EBP arrests proliferation of young livers by inhibition of cdk2. In old mice, C/EBP inhibits growth by repression of E2F-dependent promoters through the C/EBP-Brm complex. In this paper, we show that cyclin D3-cdk4/cdk6 supports the ability of C/EBP to inhibit liver proliferation in both age groups. Although cyclin D3-cdk4/cdk6 kinases are involved in the promotion of growth, they are expressed in terminally differentiated cells, suggesting that they have additional functions in these settings. We demonstrate that C/EBP represents a target for phosphorylation by cyclin D3-cdk4/cdk6 complexes in differentiated liver cells and in differentiated adipocytes. Cyclin D3-cdk4/cdk6 specifically phosphorylate C/EBP at Ser193 in vitro and in the liver and support growth-inhibitory C/EBP-cdk2 and C/EBP-Brm complexes. We found that cyclin D3 is increased in old livers and activates cdk4/cdk6, resulting in stabilization of the C/EBP-Brm complex. Old livers fail to reduce the activity of cyclin D3-cdk4/cdk6 after partial hepatectomy, leading to high levels of C/EBP-Brm complexes after partial hepatectomy, which correlate with weak proliferation. We examined the role of cyclin D3 in the stabilization of C/EBP-cdk2 and C/EBP-Brm by using 3T3-L1 differentiated cells. In these cells, cyclin D3 is increased during differentiation and phosphorylates C/EBP at Ser193, leading to the formation of growth-inhibitory C/EBP-cdk2 and C/EBP-Brm complexes. The inhibition of cyclin D3 blocks the formation of these complexes. Thus, these studies provide a new function of cyclin D3, which is to support the growth-inhibitory activity of C/EBP.
Dapagliflozin for the Treatment of Type 2 Diabetes

Objective:To review the literature and describe the pharmacologic, pharmacokinetic, and pharmacodynamic properties; clinical safety; and efficacy of dapagliflozin, a new drug currently under review by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes.Data Sources:A MEDLINE (1995-November 2011) and ClinicalTrials.gov search was conducted using the terms dapagliflozin, sodium-glucose cotransporter 2 inhibitor, and SGLT2 inhibitor. Reference citations from publications identified were also reviewed.Study Selection and Data Extraction:All English-language studies, including abstracts, evaluating dapagliflozin use in humans were included in this review.Data Synthesis:Dapagliflozin is the first-in-class oral sodium-glucose cotransporter 2 (SGLT2) inhibitor that represents a new potential therapeutic option for the treatment of type 2 diabetes mellitus. Its mechanism of action is insulin- and insulin-sensitivity independent. Preliminary data suggest that dapagliflozin decreases hemoglob...
Novel Phosphoinositide 3-Kinase δ,γ Inhibitor: Potent Anti-Inflammatory Effects and Joint Protection in Models of Rheumatoid Arthritis

Phosphoinositide 3-kinases γ and δ (PI3Kγ and PI3Kδ) are expressed in rheumatoid arthritis (RA) synovium and regulate innate and adaptive immune responses. We determined the effect of a potent PI3Kδ,γ inhibitor, IPI-145, in two preclinical models of RA. IPI-145 was administered orally in rat adjuvant-induced arthritis (AA) and intraperitoneally in mouse collagen-induced arthritis (CIA). Efficacy was assessed by paw swelling, clinical scores, histopathology and radiography, and microcomputed tomography scanning. Gene expression and Akt phosphorylation in joint tissues were determined by quantitative real-time polymerase chain reaction and Western blot analysis. Serum concentrations of anti-type II collagen (CII) IgG and IgE were measured by immunoassay. T-cell responses to CII were assayed using thymidine incorporation and immunoassay. IPI-145 significantly reduced arthritis severity in both RA models using dosing regimens initiated before onset of clinical disease. Treatment of established arthritis with IPI-145 in AA, but not CIA, significantly decreased arthritis progression. In AA, histology scores, radiographic joint damage, and matrix metalloproteinase (MMP)-13 expression were reduced in IPI-145-treated rats. In CIA, joint histology scores and expression of MMP-3 and MMP-13 mRNA were lower in the IPI-145 early treatment group than in the vehicle group. The ratio of anti-CII IgG2a to total IgG in CIA was modestly reduced. Interleukin-17 production in response to CII was decreased in the IPI-145-treated group, suggesting an inhibitory effect on T-helper cell 17 differentiation. These data show that PI3Kδ,γ inhibition suppresses inflammatory arthritis, as well as bone and cartilage damage, through effects on innate and adaptive immunity and that IPI-145 is a potential therapy for RA.
Floral Scent Production in Clarkia breweri (Onagraceae) (II. Localization and Developmental Modulation of the Enzyme S-Adenosyl-L-Methionine:(Iso)Eugenol O-Methyltransferase and Phenylpropanoid Emission)

We have previously shown (R.A. Raguso, E. Pichersky [1995] Plant Syst Evol 194: 55-67) that the strong, sweet fragrance of Clarkia breweri (Onagraceae), an annual plant native to California, consists of 8 to 12 volatile compounds, including 4 phenylpropanoids. Although some C. breweri plants emit all 4 phenylpropanoids (eugenol, isoeugenol, methyleugenol, and isomethyleugenol), other C. breweri plants do not emit the latter 2 compounds. Here we report that petal tissue was responsible for the bulk of the phenylpropanoid emission. The activity of S-adenosyl-L-methionine: (iso)eugenol O-methyltransferase (IEMT), a novel enzyme that catalyzes the methylation of the para-4'-hydroxyl of both eugenol and (iso)eugenol to methyleugenol and isomethyleugenol, respectively, was also highest in petal tissue. IEMT activity was absent from floral tissues of plants not emitting (iso)methyleugenol. A C. breweri cDNA clone encoding IEMT was isolated, and its sequence was shown to have 70% identity to S-adenosyl-L-methionine:caffeic acid O-methyltransferase. The protein encoded by this cDNA can use eugenol and isoeugenol as substrates, but not caffeic acid. Steady-state IEMT mRNA levels were positively correlated with levels of IEMT activity in the tissues, and no IEMT mRNA was observed in flowers that do not emit (iso)methyleugenol. Overall, the data show that the floral emission of (iso)methyleugenol is controlled at the site of emission, that a positive correlation exists between volatile emission and IEMT activity, and that control of the level of IEMT activity is exerted at a pretranslational step.
Global MINMAX interframe bit allocation for embedded video coding

We present three new bit allocation techniques, the multistage algorithm, the ratio algorithm, and the Pseudo I-frame method. The multistage and ratio algorithms are global interframe bit allocation algorithms for embedded video coders, which attempt to minimize the maximum distortion of any frame. The Pseudo I-frame method breaks a video into segments where bit allocation algorithms should be run, and segments where constant rate bit allocation will suffice. We present experiments, using the group testing for video coder (G. Shavit, et al., 2004), that compare our techniques to constant rate allocation and to a bit allocation algorithm due to Yang and Hemami (Y. Yang, et al., 1999).
Relationship between race and ethnicity and forensic clinical triage dispositions

OBJECTIVE: Racial and ethnic disparities in the criminal justice system have been widely reported, as have racial and ethnic disparities in diagnoses and certain aspects of clinical management. This study examined the association between race and ethnicity and dispositions for pretrial defendants who were referred for forensic mental health evaluations. METHODS: Available data were reviewed for all defendants in Massachusetts who were referred to a Massachusetts court clinic from 1994 to 2001 for a screening evaluation of their competence to stand trial, their criminal responsibility, or both. Logistic regression models were developed to assess the relationship between defendants' race and ethnicity and the likelihood that they would be referred for inpatient evaluation and the likelihood that they would be evaluated within a strict-security facility. Race or ethnicity of the pretrial defendants was identified by clinicians. RESULTS: Blacks, but not Hispanics, were significantly more likely than whites to...
Molecular basis for three-dimensional elaboration of the Aquilegia petal spur

By enforcing specific pollinator interactions, Aquilegia petal nectar spurs maintain reproductive isolation between species. Spur development is the result of three-dimensional elaboration from a c...
Understanding the Influence of National Culture on the Development of Trust

Increasingly, researchers from a variety of business disciplines are finding that trust can lower transaction costs, facilitate interorganizational relationships, and enhance manager-subordinate relationships. At the same time, we see a growing trend toward globalization—in establishing alliances, managing and hiring employees, and entering new markets. These trends suggest a need to view the concept of trust from the perspective of national culture. Drawing on theories from several disciplines, we develop a framework that identifies and describes five cognitive trust-building processes that help explain how trust develops in business contexts. We include a series of research propositions demonstrating how societal norms and values influence application of the trust-building processes, and we discuss implications for theory and practice.
Estradiol Suppresses MCP-1 Expression In Vivo: Implications for Atherosclerosis

The mechanisms by which 17beta-estradiol retards atherogenesis are not known. The adhesion of monocytes to endothelial cells followed by the migration of monocytes into the artery wall are key cellular events that occur throughout the entire atherogenic process and may be responsive to estradiol. Monocyte chemoattractant protein-1 (MCP-1), a chemokine that is expressed in atherosclerotic lesions, is thought to play a major role in stimulating the migration of blood monocytes into developing atherosclerotic lesions. We therefore assessed the effects of estradiol in vivo on MCP-1 protein and mRNA expression in the descending thoracic aorta of rabbits fed a cholesterol-enriched (0.5%) diet for 6 weeks and in animals fed normal chow. MCP-1 protein was quantified by Western blot analysis and monocyte chemotaxis bioassay, and reverse transcription-polymerase chain reaction was used to ascertain the level of MCP-1 mRNA expression. We observed that in both ovary-intact and ovariectomized (OVX) animals, MCP-1 protein and mRNA expression were significantly increased by 6 weeks in animals fed a high-cholesterol diet. The cholesterol-induced increase in MCP-1 protein and mRNA expression was significantly attenuated in OVX rabbits supplemented with estradiol pellets (1.5- and 10.0-mg 60-day-release pellets), which yielded a range of estradiol concentrations encompassing the physiological levels. MCP-1 protein and mRNA expression were increased in normocholesterolemic OVX rabbits compared with normocholesterolemic ovary-intact animals, and this increase was prevented in OVX animals supplemented with estradiol pellets. Our observations indicate that both basal and hypercholesterolemia-induced increases in MCP-1 protein are modulated by physiological concentrations of estradiol.
Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation

Our blood contains many different types of cells. Red blood cells carry oxygen around the body, whereas white blood cells are a key part of our immune system. All these different types of blood cells are derived from special cells in our bone marrow called hematopoietic stem cells. The type of blood cell that the stem cell becomes depends on the genes that are expressed as proteins in that stem cell. Gene expression can be controlled in a number of ways, including epigenetic process that influence the expression of genes without altering the underlying sequence of bases in the DNA. For example, DNA is wrapped around histone proteins and the addition of a methyl group to these proteins, a process known as histone methylation, can increase the expression of a gene, whereas the removal of a methyl group (demethylation) can repress gene expression. Lysine-specific demethylase 1 (Lsd1) is an enzyme that is known to mediate the demethylation of lysine amino acids on histone proteins. The role of Lsd1 in embryonic stem cells has been widely studied, and deletion of the gene that codes for Lsd1 is known to result in the death of mice embryos. However, very little is known about its roles in the later stages of mammalian development. Here, Kerenyi et al. use new genetic tools to knock out the gene for Lsd1 at different stages of development in order to examine its impact on the formation of new blood cells. They find that Lsd1 is required for the successful differentiation of hematopoietic stem cells into different types of blood cells, and that knocking out Lsd1 results in a severe loss of white and red blood cells. Moreover, they show that the lack of Lsd1 causes problems during both the early and later stages of development. Kerenyi et al. go on to demonstrate that Lsd1 regulates the activity of promoters and enhancers of various genes associated with hematopoietic stem cells. They also show that knocking out the Lsd1 gene results in impaired silencing of these genes, and that the incomplete expression of these genes is not compatible with the maturation of blood cells. Lsd1 has recently been proposed as the potential target for the treatment of leukemia and other blood disorders. However, the fact that a loss of Lsd1 function has adverse effects during both the early and later stages of blood cell development suggests that research into drugs that target Lsd1 should not begin until a suitable time window for the administration of such drugs can be identified.
Three new species of Sphaerosyllis (Polychaeta, Syllidae) from mangrove habitats in Belize

Three new species of Sphaerosyllis Claparede, 1863, S. belizensis, S. longilamina, and S. parvoculata, are described from mangrove and adjacent shallow-water habitats of Twin Cays, Belize.
Elevated or Erased? A Content Analysis of the Portrayal of Men in Introduction to Social Work Textbooks

As conveyors of knowledge, beliefs, and skills of the profession, textbooks play an instrumental role in educating soon-to-be-practicing students. A content analysis of references to men and women ...
Prevalence and correlates of a lifetime cannabis use disorder among pregnant former tobacco smokers

Abstract Background Following tobacco and alcohol, cannabis is the most commonly used substance during pregnancy. Given the high prevalence of concurrent cannabis and tobacco use as well as the health consequences associated with prenatal substance use, we sought to document the relative contributions of psychosocial and psychiatric factors commonly associated with cannabis use in predicting a lifetime cannabis use disorder (CUD) among women who had quit smoking tobacco as a result of pregnancy. Methods Pregnant former tobacco smokers (n = 273) enrolled in a larger randomized controlled trial for postpartum tobacco relapse prevention completed semi-structured psychiatric interviews and self-reported demographic, pregnancy, health, psychosocial, and tobacco use factors during their third trimester of pregnancy. Results In total, 14% (n = 38) of women met criteria for a lifetime CUD. The strongest predictors of a lifetime CUD were a history of having multiple psychiatric disorders (OR = 36.44; 95% CI = 5.03–264.27; p Conclusions Women with a history of both cannabis and tobacco dependence may represent a subset of women who need more specialized treatment during the perinatal period to improve substance use outcomes.
Crank-Angle Resolved Imaging of Fuel Distribution, Ignition and Combustion in a Direct-Injection Spark-Ignition Engine

A combination of imaging techniques for investigations of highly transient processes and cyclic variations in internal combustion engines is presented. The single high-speed camera setup uses a CMOS camera combined with a two-stage image-intensifier and two excimer lasers. Fuel mixing, ignition and combustion were monitored via planar laser induced fluorescence imaging of toluene as a tracer that was added to iso-octane in combination with the simultaneous recording of light emission from the spark plasma and OH chemiluminescence of the developing flame. Image frame rates of 12 kHz for hundreds of cycles were achieved. Application to misfire events in a spray-guided gasoline direct-injection engine is described to illustrate the merits of the technique.