Current Problems in Securities Regulation

This comment analyzes four areas of central significance to adequate protection for the investor: (1) qualifications of those in the securities industry who deal with the public; (2) dissemination of corporate publicity; (3) dissemination of investment advice; and (4) selling practices in the securities industry. The findings and recommendations of the Special Study are given special attention insofar as they bear upon the problems covered. In certain areas, however, recent developments in court and Commission decisions have brought about changes equally as significant as the findings and recommendations of the Special Study. Thus each section covers the background and recent developments in the designated area, as well as the Special Study itself

Comparison of two label-free global quantitation methods, APEX and 2D gel electrophoresis, applied to the Shigella dysenteriae proteome

The in vitro stationary phase proteome of the human pathogen Shigella dysenteriae serotype 1 (SD1) was quantitatively analyzed in Coomassie Blue G250 (CBB)-stained 2D gels. More than four hundred and fifty proteins, of which 271 were associated with distinct gel spots, were identified. In parallel, we employed 2D-LC-MS/MS followed by the label-free computationally modified spectral counting method APEX for absolute protein expression measurements. Of the 4502 genome-predicted SD1 proteins, 1148 proteins were identified with a false positive discovery rate of 5% and quantitated using 2D-LC-MS/MS and APEX. The dynamic range of the APEX method was approximately one order of magnitude higher than that of CBB-stained spot intensity quantitation. A squared Pearson correlation analysis revealed a reasonably good correlation (R2 = 0.67) for protein quantities surveyed by both methods. The correlation was decreased for protein subsets with specific physicochemical properties, such as low Mr values and high hydropathy scores. Stoichiometric ratios of subunits of protein complexes characterized in E. coli were compared with APEX quantitative ratios of orthologous SD1 protein complexes. A high correlation was observed for subunits of soluble cellular protein complexes in several cases, demonstrating versatile applications of the APEX method in quantitative proteomics

Kloning Manusia

In the last few years, very rapid progress in the cloning technology and its development towards human cloning has become a hotly-debated issue. Cloning, which is the process of formation of a number of individuals with the same genetic structure, can be done by means of embryo-splitting method and nuclear transfer. Human cloning through the nuclear transfer method is directed towards two purposes, i.e. reproduction and therapy. The relatively new transgenic technology can be combined with the cloning technique to produce clones with new genes. However, pros and cons arise concerning the development of research on human cloning, particularly cloning for reproductive purposes. Therefore, there is need for a moratorium period before human cloning can be performed in order that solutions for all kinds of problems related to safety and ethics can be found

Monomer-on-Monomer (MoM) Mitsunobu Reaction: Facile Purification Utilizing Surface-Initiated Sequestration

A monomer-on-monomer (MoM) Mitsunobu reaction utilizing norbornenyl-tagged (Nb-tagged) reagents is reported, whereby purification was rapidly achieved by employing ring-opening metathesis polymerization which is initiated by any of three methods utilizing Grubbs catalyst (i) free catalyst in solution, (ii) surface-initiated catalyst-armed silica or (iii) surface-initiated catalyst-armed Co/C magnetic nanoparticles

VW Hyi: optical spectroscopy and Doppler tomography

We present high quality optical spectroscopy of the SU UMa-subtype dwarf nova, VW Hyi taken while the system was in quiescence. An S-wave is executed by the emission cores of the Hydrogen Balmer lines and by the emission lines of He I, Ca II, Fe II and He II. Using Doppler tomography we show it originates in the accretion stream-disc impact region. The He II emission is strongly phase-dependent, suggesting it originates exclusively within a hot cavity at the initial impact. We map the ionization structure of the stream-disc interaction region. One possible interpretation of this is that the Balmer hotspot lies downstream of the He II hotspot in the outer accretion disc, with the He I and Ca II hotspots at intermediate locations between the two. This suggests that Balmer emission is suppressed until material has cooled somewhat downstream of the impact site and is able to recombine. We favour a phase offset of 0.15+/-0.04 between the photometric ephemeris and inferior conjunction of the mass donor. The white dwarf contributes significantly to the optical continuum, with broad Balmer absorption and narrow Mg II 4481 absorption clearly apparent. This latter feature yields the gravitational redshift: v_grav=38+/-21 km s^-1, so M_1=0.71+0.18-0.26 M_sun. This implies M_2=0.11 +/- 0.03 M_sun and hence the donor is not a brown dwarf. A prominent Balmer jump is also observed. We note that the previously accepted system parameters for both VW Hyi and WX Hyi incoporate an algebraic error, and we provide a recalculated M_1(q) plane for WX Hyi.Comment: 10 pages (mn2e LaTeX), 9 figures, Accepted for publication in Monthly Notices of the Royal Astronomical Societ

Association of Genetic Variants Related to Gluteofemoral vs Abdominal Fat Distribution With Type 2 Diabetes, Coronary Disease, and Cardiovascular Risk Factors.

IMPORTANCE: Body fat distribution, usually measured using waist-to-hip ratio (WHR), is an important contributor to cardiometabolic disease independent of body mass index (BMI). Whether mechanisms that increase WHR via lower gluteofemoral (hip) or via higher abdominal (waist) fat distribution affect cardiometabolic risk is unknown. OBJECTIVE: To identify genetic variants associated with higher WHR specifically via lower gluteofemoral or higher abdominal fat distribution and estimate their association with cardiometabolic risk. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association studies (GWAS) for WHR combined data from the UK Biobank cohort and summary statistics from previous GWAS (data collection: 2006-2018). Specific polygenic scores for higher WHR via lower gluteofemoral or via higher abdominal fat distribution were derived using WHR-associated genetic variants showing specific association with hip or waist circumference. Associations of polygenic scores with outcomes were estimated in 3 population-based cohorts, a case-cohort study, and summary statistics from 6 GWAS (data collection: 1991-2018). EXPOSURES: More than 2.4 million common genetic variants (GWAS); polygenic scores for higher WHR (follow-up analyses). MAIN OUTCOMES AND MEASURES: BMI-adjusted WHR and unadjusted WHR (GWAS); compartmental fat mass measured by dual-energy x-ray absorptiometry, systolic and diastolic blood pressure, low-density lipoprotein cholesterol, triglycerides, fasting glucose, fasting insulin, type 2 diabetes, and coronary disease risk (follow-up analyses). RESULTS: Among 452 302 UK Biobank participants of European ancestry, the mean (SD) age was 57 (8) years and the mean (SD) WHR was 0.87 (0.09). In genome-wide analyses, 202 independent genetic variants were associated with higher BMI-adjusted WHR (n = 660 648) and unadjusted WHR (n = 663 598). In dual-energy x-ray absorptiometry analyses (n = 18 330), the hip- and waist-specific polygenic scores for higher WHR were specifically associated with lower gluteofemoral and higher abdominal fat, respectively. In follow-up analyses (n = 636 607), both polygenic scores were associated with higher blood pressure and triglyceride levels and higher risk of diabetes (waist-specific score: odds ratio [OR], 1.57 [95% CI, 1.34-1.83], absolute risk increase per 1000 participant-years [ARI], 4.4 [95% CI, 2.7-6.5], P < .001; hip-specific score: OR, 2.54 [95% CI, 2.17-2.96], ARI, 12.0 [95% CI, 9.1-15.3], P < .001) and coronary disease (waist-specific score: OR, 1.60 [95% CI, 1.39-1.84], ARI, 2.3 [95% CI, 1.5-3.3], P < .001; hip-specific score: OR, 1.76 [95% CI, 1.53-2.02], ARI, 3.0 [95% CI, 2.1-4.0], P < .001), per 1-SD increase in BMI-adjusted WHR. CONCLUSIONS AND RELEVANCE: Distinct genetic mechanisms may be linked to gluteofemoral and abdominal fat distribution that are the basis for the calculation of the WHR. These findings may improve risk assessment and treatment of diabetes and coronary disease.This study was funded by the United Kingdom’s Medical Research Council through grants MC_UU_12015/1, MC_PC_13046, MC_PC_13048 and MR/L00002/1. This work was supported by the MRC Metabolic Diseases Unit (MC_UU_12012/5) and the Cambridge NIHR Biomedical Research Centre and EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant: 115372). EPIC-InterAct Study funding: funding for the InterAct project was provided by the EU FP6 program (grant number LSHM_CT_2006_037197). D.B.S. and S.O’R. are supported by the Wellcome Trust (WT107064 and WT095515 respectively) the MRC Metabolic Disease Unit, the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and the NIHR Rare Disease Translational Research Collaboration

Reprogramming of Escherichia coli K-12 Metabolism during the Initial Phase of Transition from an Anaerobic to a Micro-Aerobic Environment

Background: Many bacteria undergo transitions between environments with differing O2 availabilities as part of their natural lifestyles and during biotechnological processes. However, the dynamics of adaptation when bacteria experience changes in O2 availability are understudied. The model bacterium and facultative anaerobe Escherichia coli K-12 provides an ideal system for exploring this process. Methods and Findings: Time-resolved transcript profiles of E. coli K-12 during the initial phase of transition from anaerobic to micro-aerobic conditions revealed a reprogramming of gene expression consistent with a switch from fermentative to respiratory metabolism. The changes in transcript abundance were matched by changes in the abundances of selected central metabolic proteins. A probabilistic state space model was used to infer the activities of two key regulators, FNR (O2 sensing) and PdhR (pyruvate sensing). The model implied that both regulators were rapidly inactivated during the transition from an anaerobic to a micro-aerobic environment. Analysis of the external metabolome and protein levels suggested that the cultures transit through different physiological states during the process of adaptation, characterized by the rapid inactivation of pyruvate formate-lyase (PFL), a slower induction of pyruvate dehydrogenase complex (PDHC) activity and transient excretion of pyruvate, consistent with the predicted inactivation of PdhR and FNR. Conclusion: Perturbation of anaerobic steady-state cultures by introduction of a limited supply of O2 combined with time-resolved transcript, protein and metabolite profiling, and probabilistic modeling has revealed that pyruvate (sensed by PdhR) is a key metabolic signal in coordinating the reprogramming of E. coli K-12 gene expression by working alongside the O2 sensor FNR during transition from anaerobic to micro-aerobic conditions

The Warden Attitude: An investigation of the value of interaction with everyday wildlife

Using a discrete choice experiment, we elicit valuations of engagement with ‘everyday wildlife’ through feeding garden birds. We find that bird-feeding is primarily but not exclusively motivated by the direct consumption value of interaction with wildlife. The implicit valuations given to different species suggest that people prefer birds that have aesthetic appeal and that evoke human feelings of protectiveness. These findings suggest that people derive wellbeing by adopting a warden-like role towards ‘their’ wildlife. We test for external validity by conducting a hedonic analysis of sales of bird food. We discuss some policy implications of the existence of warden attitudes

Mitochondrial Uncoupling Inhibits p53 Mitochondrial Translocation in TPA-Challenged Skin Epidermal JB6 Cells

The tumor suppressor p53 is known to be able to trigger apoptosis in response to DNA damage, oncogene activation, and certain chemotherapeutic drugs. In addition to its transcriptional activation, a fraction of p53 translocates to mitochondria at the very early stage of apoptosis, which eventually contributes to the loss of mitochondrial membrane potential, generation of reactive oxygen species (ROS), cytochrome c release, and caspase activation. However, the mitochondrial events that affect p53 translocation are still unclear. Since mitochondrial uncoupling has been suggested to contribute to cancer development, herein, we studied whether p53 mitochondrial translocation and subsequent apoptosis were affected by mitochondrial uncoupling using chemical protonophores, and further verified the results using a siRNA approach in murine skin epidermal JB6 cells. Our results showed that mitochondrial uncoupling blocked p53 mitochondrial translocation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA), a known tumor promoter to induce p53-mediated apoptosis in skin carcinogenesis. This blocking effect, in turn, led to preservation of mitochondrial functions, and eventually suppression of caspase activity and apoptosis. Moreover, uncoupling protein 2 (UCP2), a potential suppressor of ROS in mitochondria, is important for TPA-induced cell transformation in JB6 cells. UCP2 knock down cells showed enhanced p53 mitochondrial translocation, and were less prone to form colonies in soft agar after TPA treatment. Altogether, our data suggest that mitochondrial uncoupling may serve as an important regulator of p53 mitochondrial translocation and p53-mediated apoptosis during early tumor promotion. Therefore, targeting mitochondrial uncoupling may be considered as a novel treatment strategy for cancer