Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis.

Angiogenesis is an important process in chronic inflammatory diseases. We observed that sera from patients with systemic vasculitis stimulated angiogenesis in an in vitro model using human umbilical vein endothelial cells cultured on a basement membrane (Matrigel) substrate. After 40% ammonium sulfate precipitation, angiogenic activity remained in the low molecular weight fraction and could be inactivated by heat. SDS-page of serum FPLC fractions exhibiting maximal angiogenic activity demonstrated two prominent species of 45 and 16-20 kD in patients' sera. These bands were much less apparent in sera obtained from control subjects. Amino-terminal sequencing of the 45-kD protein demonstrated that it was haptoglobin. Purified haptoglobin stimulated angiogenesis in a dose-dependent manner. The angiogenic activity of vasculitis patients' sera was partially inhibited by an antihaptoglobin antibody. Furthermore, serum haptoglobin levels in vasculitis patients correlated both with disease and angiogenic activity. Haptoglobin angiogenic activity was confirmed in two in vivo models using an implanted disc and a subcutaneous injection of basement membrane. Stimulation of angiogenesis is a newly recognized biological function of haptoglobin. The increased levels of haptoglobin found in chronic inflammatory conditions may play an important role in tissue repair. In systemic vasculitis, haptoglobin might also compensate for ischemia by promoting development of collateral vessels.

Identification of myxobacteria-derived HIV inhibitors by a high-throughput two-step infectivity assay

Drug-resistance and therapy failure due to drug-drug interactions are the main challenges in current treatment against Human Immunodeficiency Virus (HIV) infection. As such, there is a continuous need for the development of new and more potent anti-HIV drugs. Here we established a high-throughput screen based on the highly permissive TZM-bl cell line to identify novel HIV inhibitors. The assay allows discriminating compounds acting on early and/or late steps of the HIV replication cycle. The platform was used to screen a unique library of secondary metabolites derived from myxobacteria. Several hits with good anti-HIV profiles were identified. Five of the initial hits were tested for their antiviral potency. Four myxobacterial compounds, sulfangolid C, soraphen F, epothilon D and spirangien B, showed EC50 values in the nM range with SI > 15. Interestingly, we found a high amount of overlapping hits compared with a previous screen for Hepatitis C Virus (HCV) using the same library. The unique structures and mode-of-actions of these natural compounds make myxobacteria an attractive source of chemicals for the development of broad-spectrum antivirals. Further biological and structural studies of our initial hits might help recognize smaller drug-like derivatives that in turn could be synthesized and further optimized.

Molecular identification of an endemic Alpine mammal, Apodemus alpicola, using a PCR-based RFLP method

The ability of a PCR-based restriction fragment length polymorphism (RFLP) analysis of the cytochrome b (mtDNA) to distinguish Apodemus alpicola from two other Apodemus species was investigated. The partial sequencing of the cytochrome b allowed the identification of one enzyme as being potentially diagnostic. This was supported by an analysis of 131 specimens previously identified using morphometric and/or allozymic data, indicating that the PCR-based RFLP method provides a rapid and reliable tool for distinguishing A. alpicola from its two co-occurring congenerics. The method is applicable to samples taken in the field for ecological studies, and could easily be adapted to the identification of museum samples.

Motivic analysis and its relevance to raga identification in carnatic music

A raga is a collective melodic expression consisting of motifs. A raga can be identified using motifs which areunique to it. Motifs can be thought of as signature prosodic phrases. Different ragas may be composed of the same setof notes, or even phrases, but the prosody may be completely different. In this paper, an attempt is made to determinethe characteristic motifs that enable identification of a raga and distinguish between them. To determine this, motifs are first manually marked for a set of five popular raga by a professional musician. The motifs are then normalisedwith respect to the tonic. HMMs are trained for each motif using 80% of the data and about 20% are used for testing. The results do indicate that about 80% of the motifs are identified as belonging to a specific raga accurately.

A knowledge based signal processing approach to tonic identification in indian classical music

In this paper, we describe several techniques for detecting tonic pitch value in Indian classical music. In Indian music, the raga is the basic melodic framework and it is built on the tonic. Tonic detection is therefore fundamental for any melodic analysis in Indian classical music. This workexplores detection of tonic by processing the pitch histograms of Indian classic music. Processing of pitch histograms using group delay functions and its ability to amplify certain traits of Indian music in the pitch histogram, is discussed. Three different strategies to detect tonic, namely, the concert method, the template matching and segmented histogram method are proposed. The concert method exploits the fact that the tonic is constant over a piece/concert.templatematchingmethod and segmented histogrammethodsuse the properties: (i) the tonic is always present in the background, (ii) some notes are less inflected and dominant, to detect the tonic of individual pieces. All the three methods yield good results for Carnatic music (90−100% accuracy), while for Hindustanimusic, the templatemethod works best, provided the v¯adi samv¯adi notes for a given piece are known (85%).

Polyembryony and identification of Volkamerian lemon zygotic and nucellar seedlings using RAPD

The objectives of this work were to evaluate the frequency of polyembryony, and to identify zygotic and nucellar seedlings of Citrus volkameriana using RAPD. Twenty-five polyembryonic and eight monoembryonic seeds were cultivated in vitrofor six months. DNA from seedlings was extracted and used in combination with five RAPD primers to identify zygotic or nucellar origin of the seedlings. Environmental conditions of the year affected significantly (P<0.05) the morphological characteristics of fruitsand the number ofembryos per seed. Polyembryonic seeds ranged from 30.9%, 44.8% to 54.4% over three years. Morphological characteristic was not correlated with polyembryony. In vitro culture enable all embryos of each seed to grow, favoring the percentage of seedlings identified as zygotic. In polyembryonic and monoembryonic seeds, 25.9% and 87.5% of the seedlings, respectively, were sexually originated. In polyembryonic seeds, not all zygotic seedlings were produced by small embryos located at the micropyle.

Automated identification of minimal myocardial motion for improved image quality on MR angiography at 3 T

OBJECTIVE: Imaging during a period of minimal myocardial motion is of paramount importance for coronary MR angiography (MRA). The objective of our study was to evaluate the utility of FREEZE, a custom-built automated tool for the identification of the period of minimal myocardial motion, in both a moving phantom at 1.5 T and 10 healthy adults (nine men, one woman; mean age, 24.9 years; age range, 21-32 years) at 3 T. CONCLUSION: Quantitative analysis of the moving phantom showed that dimension measurements approached those obtained in the static phantom when using FREEZE. In vitro, vessel sharpness, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were significantly improved when coronary MRA was performed during the software-prescribed period of minimal myocardial motion (p < 0.05). Consistent with these objective findings, image quality assessments by consensus review also improved significantly when using the automated prescription of the period of minimal myocardial motion. The use of FREEZE improves image quality of coronary MRA. Simultaneously, operator dependence can be minimized while the ease of use is improved.

Late side-effects after curative intent radiotherapy: Identification of hypersensitive patients for personalized strategy.

Radiation therapy undeniably enhances local control and thus improves overall survival in cancer patients. However, some long-term cancer survivors (less than 10%) develop severe late radio-induced toxicities altering their quality of life. Therefore, there is a need to identify patients who are sensitive to those toxicities and who could benefit from adapted care. In this review, we address all available techniques aiming to detect patients' hyper-radiosensitivity and present the scientific rationales these techniques are based on.

Towards the identification of a genetic basis for Landau-Kleffner syndrome.

OBJECTIVE: To establish the genetic basis of Landau-Kleffner syndrome (LKS) in a cohort of two discordant monozygotic (MZ) twin pairs and 11 isolated cases. METHODS: We used a multifaceted approach to identify genetic risk factors for LKS. Array comparative genomic hybridization (CGH) was performed using the Agilent 180K array. Whole genome methylation profiling was undertaken in the two discordant twin pairs, three isolated LKS cases, and 12 control samples using the Illumina 27K array. Exome sequencing was undertaken in 13 patients with LKS including two sets of discordant MZ twins. Data were analyzed with respect to novel and rare variants, overlapping genes, variants in reported epilepsy genes, and pathway enrichment. RESULTS: A variant (cG1553A) was found in a single patient in the GRIN2A gene, causing an arginine to histidine change at site 518, a predicted glutamate binding site. Following copy number variation (CNV), methylation, and exome sequencing analysis, no single candidate gene was identified to cause LKS in the remaining cohort. However, a number of interesting additional candidate variants were identified including variants in RELN, BSN, EPHB2, and NID2. SIGNIFICANCE: A single mutation was identified in the GRIN2A gene. This study has identified a number of additional candidate genes including RELN, BSN, EPHB2, and NID2. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Application of the Mutual Information Minimization to speaker recognition / identification improvement

In this paper we propose the inversion of nonlinear distortions in order to improve the recognition rates of a speaker recognizer system. We study the effect of saturations on the test signals, trying to take into account real situations where the training material has been recorded in a controlled situation but the testing signals present some mismatch with the input signal level (saturations). The experimental results for speaker recognition shows that a combination of several strategies can improve the recognition rates with saturated test sentences from 80% to 89.39%, while the results with clean speech (without saturation) is 87.76% for one microphone, and for speaker identification can reduce the minimum detection cost function with saturated test sentences from 6.42% to 4.15%, while the results with clean speech (without saturation) is 5.74% for one microphone and 7.02% for the other one.

Identification and staining of distinct populations of secretory organelles in astrocytes.

Increasing evidence indicates that astrocytes, the most abundant glial cell type in the brain, respond to an elevation in cytoplasmic calcium concentration ([Ca(2+)]i) by releasing chemical transmitters (also called gliotransmitters) via regulated exocytosis of heterogeneous classes of organelles. By this process, astrocytes exert modulatory influences on neighboring cells and are thought to participate in the control of synaptic circuits and cerebral blood flow. Studying the properties of exocytosis in astrocytes is a challenge, because the cell biological basis of this process is incompletely defined. Astrocytic exocytosis involves multiple populations of secretory vesicles, including synaptic-like microvesicles (SLMVs), dense-core granules (DCGs), and lysosomes. Here we summarize the available information for identifying individual populations of secretory organelles in astrocytes, including DCGs, SLMVs, and lysosomes, and present experimental procedures for specifically staining such populations.

High-Resolution Mass Spectrometry applied to the identification of new metabolites and transformation products of quinolones in chicken muscle tissues

The aim of this work was the identification of new metabolites and transformation products (TPs) in chicken muscle from Enrofloxacin (ENR), Ciprofloxacin (CIP), Difloxacin (DIF) and Sarafloxacin (SAR), which are antibiotics that belong to the fluoroquinolones family. The stability of ENR, CIP, DIF and SAR standard solutions versus pH degradation process (from pH 1.5 to 8.0, simulating the pH since the drug is administered until its excretion) and freeze-thawing (F/T) cycles was tested. In addition, chicken muscle samples from medicated animals with ENR were analyzed in order to identify new metabolites and TPs. The identification of the different metabolites and TPs was accomplished by comparison of mass spectral data from samples and blanks, using liquid chromatography coupled to quadrupole time-of-flight (LC-QqToF) and Multiple Mass Defect Filter (MMDF) technique as a pre-filter to remove most of the background noise and endogenous components. Confirmation and structure elucidation was performed by liquid chromatography coupled to linear ion trap quadrupole Orbitrap (LC-LTQ-Orbitrap), due to its mass accuracy and MS/MS capacity for elemental composition determination. As a result, 21 TPs from ENR, 6 TPs from CIP, 14 TPs from DIF and 12 TPs from SAR were identified due to the pH shock and F/T cycles. On the other hand, 14 metabolites were identified from the medicated chicken muscle samples. Formation of CIP and SAR, from ENR and DIF, respectively, and the formation of desethylene-quinolone were the most remarkable identified compounds.

Highway/Railroad Grade Crossings Identification and Signing, HR-254, 1987

In 1982, Iowa's crossing warning identification system and signage at rail crossings were outdated, inconsistent and inadequate. Iowa's railroad system had been reduced and reorganized during the 1970's and many of the surviving railroad companies were unable to install new signs or devote staff to updating information. The preliminary engineering part of this project improved the information inventory about each crossing, provided for installation of identification tags and resulted in a comprehensive list of posts and signs eligible for replacement. The sign installation portion of this project resulted in erection of nearly 10,000 new crossbuck signs and 10,000 advance warning signs with high intensity reflectorization. In addition, new posts and multiple track signs were replaced where appropriate. Increased visibility of crossings for the motoring public has resulted from proper sign placement and use of high intensity reflectorization. The tagging has provided a consistent correct identification of crossings for accident reporting. The computer inventory of information about the crossings is now correct and provides for informed decision making to administrators of Federal and State crossing safety funds.