Searching for Standards: Disclosure in the Municipal Securities Market

Prokrastinering, eller att mot bättre vetande skjuta upp något, är ett stort problem i samhället i allmänhet och för studenter i synnerhet. I denna artikel beskriver vi en utbildningsmodul om prokrastinering som vi introducerat på två civilingenjörsprogram på KTH, varav denna rapport behandlar datateknikprogrammet där 466 studenter deltog. Utvärderingen hade 100% svarsfrekvens, och visar att 95% av studenterna hade problem med prokrastinering varav 43% hade stora eller mycket stora problem. 88% ansåg att prokrastinering var ett bra tema att ha med i utbildningen, och 57% ansåg att momentet haft positiva effekter på deras studievanor. Endast 7% ansåg att momentet inte hade gett några märkbara effekter på studierna. Då modulen endast kräver ca 8 timmars arbete från studenternas sida anser vi att fördelarna är så stora att denna eller en liknande modul borde ingå i samtliga utbildningsprogram.QC 20131216</p

J/psi dissociation by light mesons in an extended Nambu Jona-Lasinio model

An alternative model for the dissociation of the J/psi is proposed. Chiral symmetry is properly implemented. Abnormal parity interactions and mesonic form factors naturally arise from the underlying quark sub-structure. Analytic confinement for the light quarks is generated by appropriately chosen the quark interaction kernels. Dissociation cross sections of the J/psi by either a pion or a rho meson are then evaluated and discussed.Comment: 24 pages, 13 figures, final versio

Structure of Mandelate Racemase with Bound Intermediate Analogues Benzohydroxamate and Cupferron

Mandelate racemase (MR, EC 5.1.2.2) from Pseudomonas putida catalyzes the Mg2+-dependent interconversion of the enantiomers of mandelate, stabilizing the altered substrate in the transition state by 26 kcal/mol relative to the substrate in the ground state. To understand the origins of this binding discrimination, we determined the X-ray crystal structures of wild-type MR complexed with two analogues of the putative aci-carboxylate intermediate, benzohydroxamate and Cupferron, to 2.2-Å resolution. Benzohydroxamate is shown to be a reasonable mimic of the transition state and/or intermediate because its binding affinity for 21 MR variants correlates well with changes in the free energy of transition state stabilization afforded by these variants. Both benzohydroxamate and Cupferron chelate the active site divalent metal ion and are bound in a conformation with the phenyl ring coplanar with the hydroxamate and diazeniumdiolate moieties, respectively. Structural overlays of MR complexed with benzohydroxamate, Cupferron, and the ground state analogue (S)-atrolactate reveal that the para carbon of the substrate phenyl ring moves by 0.8−1.2 Å between the ground state and intermediate state, consistent with the proposal that the phenyl ring moves during MR catalysis while the polar groups remain relatively fixed. Although the overall protein structure of MR with bound intermediate analogues is very similar to that of MR with bound (S)-atrolactate, the intermediate−Mg2+ distance becomes shorter, suggesting a tighter complex with the catalytic Mg2+. In addition, Tyr 54 moves closer to the phenyl ring of the bound intermediate analogues, contributing to an overall constriction of the active site cavity. However, site-directed mutagenesis experiments revealed that the role of Tyr 54 in MR catalysis is relatively minor, suggesting that alterations in enzyme structure that contribute to discrimination between the altered substrate in the transition state and the ground state by this proficient enzyme are extremely subtle

Success in the DREAM3 Signaling Response Challenge Using Simple Weighted-Average Imputation: Lessons for Community-Wide Experiments in Systems Biology

Our group produced the best predictions overall in the DREAM3 signaling response challenge, being tops by a substantial margin in the cytokine sub-challenge and nearly tied for best in the phosphoprotein sub-challenge. We achieved this success using a simple interpolation strategy. For each combination of a stimulus and inhibitor for which predictions were required, we had noted there were six other datasets using the same stimulus (but different inhibitor treatments) and six other datasets using the same inhibitor (but different stimuli). Therefore, for each treatment combination for which values were to be predicted, we calculated rank correlations for the data that were in common between the treatment combination and each of the 12 related combinations. The data from the 12 related combinations were then used to calculate missing values, weighting the contributions from each experiment based on the rank correlation coefficients. The success of this simple method suggests that the missing data were largely over-determined by similarities in the treatments. We offer some thoughts on the current state and future development of DREAM that are based on our success in this challenge, our success in the earlier DREAM2 transcription factor target challenge, and our experience as the data provider for the gene expression challenge in DREAM3

Mechanisms Linking Lipid Metabolism and Longevity in Yeast

Proper control of lipid metabolism in the endoplasmic reticulum, lipid bodies, peroxisomes and mitochondria is essential for longevity regulation. However, the molecular mechanisms linking longevity and lipid metabolism in these organelles have not been defined prior to studies described here. The establishment of such mechanisms operating in chronologically aging yeast was the objective of my thesis. To develop a tool for quantitative monitoring of the age-related dynamics of changes in the cellular and organellar lipidomes of chronologically aging yeast, I was able to solve the inherent limitations of the currently used methods for lipidomic analysis (including the limitations characteristic of mass spectrometry-based techniques) by devising a survey-scan electrospray ionization mass spectrometry method for quantitative lipidomics. This novel method enables within a very limited period of time and using a very low number of cells to resolve, unequivocally identify and accurately quantitate all molecular forms of lipid species composing yeast lipidome and the majority of molecular forms of lipid species composing the lipidome of cultured human cells. Using a combination of the functional genetic, cell biological, electron and fluorescence microscopical, proteomic, lipidomic, and metabolomic analyses, I established three molecular mechanisms linking longevity and lipid metabolism confined to the endoplasmic reticulum, lipid bodies, peroxisomes and mitochondria. One of these mechanisms underlies the ability of a caloric restriction diet to extend longevity of iv chronologically aging yeast by specifically remodeling the metabolism of neutral lipids in the endoplasmic reticulum, lipid bodies and peroxisomes. The other mechanism underlies the ability of lithocholic acid, a novel anti-aging compound that my research enabled to identify, to extend yeast chronological life span by targeting the longevity-defining aspects of lipid metabolism confined to the endoplasmic reticulum, lipid bodies and peroxisomes. The third mechanism underlies the ability of lithocholic acid to extend yeast chronological life span under caloric restriction conditions by remodeling lipid metabolism in the mitochondrial membrane, thereby altering the repertoire of membrane lipids in mitochondria and influencing several longevity-defining processes confined to these organelles

Xenohormetic, hormetic and cytostatic selective forces driving longevity at the ecosystemic level

We recently found that lithocholic acid (LCA), a bile acid, extends yeast longevity. Unlike mammals, yeast do not synthesize bile acids. We therefore propose that bile acids released into the environment by mammals may act as interspecies chemical signals providing longevity benefits to yeast and, perhaps, other species within an ecosystem

Spatially Extended Low Ionization Emission Regions (LIERs) at z∼0.9z\sim0.9

We present spatially resolved emission diagnostics for eight $z\sim0.9$ galaxies that demonstrate extended low ionization emission-line regions (LIERs) over kpc scales. Eight candidates are selected based on their spatial extent and emission line fluxes from slitless spectroscopic observations with the HST/WFC3 G141 and G800L grisms in the well-studied GOODS survey fields. Five of the candidates (62.5%) are matched to X-ray counterparts in the \textit{Chandra X-Ray Observatory} Deep Fields. We modify the traditional Baldwin-Philips-Terlevich (BPT) emission line diagnostic diagram to use [SII]/(H$\alpha$+[NII]) instead of [NII]/H$\alpha$ to overcome the blending of [NII] and H$\alpha$+[NII] in the low resolution slitless grism spectra. We construct emission line ratio maps and place the individual pixels in the modified BPT. The extended LINER-like emission present in all of our candidates, coupled with X-Ray properties consistent with star-forming galaxies and weak [OIII]$\lambda$5007\AA\ detections, is inconsistent with purely nuclear sources (LINERs) driven by active galactic nuclei. While recent ground-based integral field unit spectroscopic surveys have revealed significant evidence for diffuse LINER-like emission in galaxies within the local universe $(z\sim0.04)$, this work provides the first evidence for the non-AGN origin of LINER-like emission out to high redshifts.Comment: 11 pages, 1 table, 6 figures, accepted for publication in the Astrophysics Journal (ApJ

Benefits and barriers in the design of harmonized access agreements for international data sharing

In the past decade, there has been a surge in the number of sensitive human genomic and health datasets available to researchers via Data Access Agreements (DAAs) and managed by Data Access Committees (DACs). As this form of sharing increases, so do the challenges of achieving a reasonable level of data protection, particularly in the context of international data sharing. Here, we consider how excessive variation across DAAs can hinder these goals, and suggest a core set of clauses that could prove useful in future attempts to harmonize data governance