Standardized evaluation methodology and reference database for evaluating IVUS image segmentation

This paper describes an evaluation framework that allows a standardized and quantitative comparison of IVUS lumen and media segmentation algorithms. This framework has been introduced at the MICCAI 2011 Computing and Visualization for (Intra)Vascular Imaging (CVII) workshop, comparing the results of eight teams that participated. We describe the available data-base comprising of multi-center, multi-vendor and multi-frequency IVUS datasets, their acquisition, the creation of the reference standard and the evaluation measures. The approaches address segmentation of the lumen, the media, or both borders; semi- or fully-automatic operation; and 2-D vs. 3-D methodology. Three performance measures for quantitative analysis have been proposed. The results of the evaluation indicate that segmentation of the vessel lumen and media is possible with an accuracy that is comparable to manual annotation when semi-automatic methods are used, as well as encouraging results can be obtained also in case of fully-automatic segmentation. The analysis performed in this paper also highlights the challenges in IVUS segmentation that remains to be solved.

Structural Insight into the Mode of Action of a Direct Inhibitor of Coregulator Binding to the Thyroid Hormone Receptor.

The development of nuclear hormone receptor antagonists that directly inhibit the association of the receptor with its essential coactivators would allow useful manipulation of nuclear hormone receptor signaling. We previously identified 3-(dibutylamino)-1-(4-hexylphenyl)-propan-1-one (DHPPA), an aromatic β-amino ketone that inhibits coactivator recruitment to thyroid hormone receptor β (TRβ), in a high-throughput screen. Initial evidence suggested that the aromatic β-enone 1-(4-hexylphenyl)-prop-2-en-1-one (HPPE), which alkylates a specific cysteine residue on the TRβ surface, is liberated from DHPPA. Nevertheless, aspects of the mechanism and specificity of action of DHPPA remained unclear. Here, we report an x-ray structure of TRβ with the inhibitor HPPE at 2.3-Å resolution. Unreacted HPPE is located at the interface that normally mediates binding between TRβ and its coactivator. Several lines of evidence, including experiments with TRβ mutants and mass spectroscopic analysis, showed that HPPE specifically alkylates cysteine residue 298 of TRβ, which is located near the activation function-2 pocket. We propose that this covalent adduct formation proceeds through a two-step mechanism: 1) β-elimination to form HPPE; and 2) a covalent bond slowly forms between HPPE and TRβ. DHPPA represents a novel class of potent TRβ antagonist, and its crystal structure suggests new ways to design antagonists that target the assembly of nuclear hormone receptor gene-regulatory complexes and block transcription.

Kaukolämmön pääsäädöt

Työssä keskitytään tarkastelemaan kaukolämmön pääsäätöjä, jotka ovat lämpötilan, paineen ja keskipaineen säädöt. Lisäksi työssä on pintapuolisesti käsitelty myös kaukolämpöön liittyviä perusasioita, toimintaperiaatteita, kaukolämmön erilaisia tuotantotapoja sekä varastointia. Lämpötilan säätöön liittyvät keskeisimmät tekijät ovat menoveden absoluuttisen ala- ja ylärajan määrittäminen, paluuveden alimman optimaalisen arvon määrittäminen, lämpötilan asetusarvon asettaminen, sekä lämpötilan muutosten vaikutus kaukolämmön tuotantoon. Lämpötilan muutoksilla on huomattava vaikutus kaukolämmön tuotannossa. Paine-erolla säädetään kaukolämpöveden virtausmäärää ja tehoa, jolla on merkittävä osuus kaukolämpöjärjestelmässä. Paine-eron säätö Salmisaaren voimalaitoksessa on toteutettu sumeaan logiikkaan perustuvalla tietokoneohjelmalla, joka automaattisesti valvoo paine-eron vaihteluita, säätöpoikkeamaa, säätötasoja ja seuraa paine-eron oloarvoa. Keskipaineen säätäminen on toteutettu siten, että Salmisaaren ja Hanasaaren voimalaitoksissa pystytään keskipainetta säätämään samanaikaisesti. Näin toimien on mahdollistettu suurempi toimintavarmuus ja parempi asetusarvossa pysyminen. Kaukolämpöverkoissa on yleensä vain yksi keskipaineen säätäjä, joten Helsingissä voimassa oleva järjestelmä on ainoa laatuaan. Työ on tehty pääosin haastattelemalla Salmisaaren voimalaitoksen automaatiomestari Guy Lindmania sekä automaatioverstaan muuta henkilöstöä. Työn tavoitteena on ollut saattaa kirjalliseen muotoon toistaiseksi dokumentoimatonta tietoa.

Preparação e caracterização de substratos SERS ativos: um estudo da adsorção do cristal violeta sobre nanopartículas de prata

The structural characterization of molecules used in the sterilization of blood for transfusions, such as crystal violet (CV), is relevant for understanding the action of these prophylactic drugs. The characterization is feasible by surface enhanced resonance Raman spectroscopy (SERRS) of CV in solution or on surfaces. The limit of detection of CV by SERRS, in the presence of colloidal particles, using 514.5 nm as excitation radiation, was found to be around 1 ppb. The characterization of CV was also made by SERS, by using different active-particles-containing substrates, proving the versatility of this technique for the study of such structures. The results suggest that the controlled production of highly efficient SERS-active substrates may allow qualitative and quantitative analysis, with high sensitivity, with potential applications in medical and environmental fields.

A human immune data-informed vaccine concept elicits strong and broad T-cell specificities associated with HIV-1 control in mice and macaques

Background: None of the HIV T-cell vaccine candidates that have reached advanced clinical testing have been able to induce protective T cell immunity. A major reason for these failures may have been suboptimal T cell immunogen designs. Methods: To overcome this problem, we used a novel immunogen design approach that is based on functional T cell response data from more than 1,000 HIV-1 clade B and C infected individuals and which aims to direct the T cell response to the most vulnerable sites of HIV-1. Results: Our approach identified 16 regions in Gag, Pol, Vif and Nef that were relatively conserved and predominantly targeted by individuals with reduced viral loads. These regions formed the basis of the HIVACAT T-cell Immunogen (HTI) sequence which is 529 amino acids in length, includes more than 50 optimally defined CD4+ and CD8+ T-cell epitopes restricted by a wide range of HLA class I and II molecules and covers viral sites where mutations led to a dramatic reduction in viral replicative fitness. In both, C57BL/6 mice and Indian rhesus macaques immunized with an HTI-expressing DNA plasmid (DNA.HTI) induced broad and balanced T-cell responses to several segments within Gag, Pol, and Vif. DNA.HTI induced robust CD4+ and CD8+ T cell responses that were increased by a booster vaccination using modified virus Ankara (MVA.HTI), expanding the DNA.HTI induced response to up to 3.2% IFN-γ T-cells in macaques. HTI-specific T cells showed a central and effector memory phenotype with a significant fraction of the IFN-γ+ CD8+ T cells being Granzyme B+ and able to degranulate (CD107a+). Conclusions: These data demonstrate the immunogenicity of a novel HIV-1 T cell vaccine concept that induced broadly balanced responses to vulnerable sites of HIV-1 while avoiding the induction of responses to potential decoy targets that may divert effective T-cell responses towards variable and less protective viral determinants.

Sirkustutkimusta, oho!

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