Leading indicator properties of US high-yield credit spread

In this paper we examine the out-of-sample forecast performance of high-yield credit spreads regarding employment and industrial production in the US, using both a point forecast and a probability forecast exercise. Our main findings suggest the use of few factors obtained by pooling information from a number of sector-specific high-yield credit spreads. This can be justified by observing that there is a gain from using a principal components model fitted to high-yield credit spreads compared to the prediction produced by benchmarks, such as an AR, and ARDL models that use either the term spread or the aggregate high-yield spread as exogenous regressor

Detection of Functional Significance of Coronary Stenoses Using Dynamic 13N-Ammonia Stress-PET/CT with Absolute Values of Myocardial Blood Flow and Coronary Flow Reserve

Objectives. The aim of the study was to compare the values of myocardial blood flow (MBF) at stress, MBF at rest and coronary flow reserve (CFR) obtained by 13Nammonia stress-PET/CT in patients with various degrees of coronary stenosis and in healthy patients. And thus to estimate the possible contribution of the stress-PET/CT quantitative data to the detection of functionally significant coronary stenoses in patients with coronary artery disease (CAD). Materials and methods. 63 patients (mean age 64±9 years) with known CAD underwent dynamic 13N-ammonia stress-PET/CT followed by calculation of MBF both at stress and at rest in absolute units and CFR. We compared quantitative values in two groups of patients with coronary artery stenosis: 1) ≥75% (n = 36) and 2) <75% (n = 27) confirmed by invasive coronary angiography and in group of healthy patients (n = 11). Results. MBF at stress was significantly lower in group with ≥75% diameter stenoses (median 1,44 [1,21; 1,85] mL/min per g) compared with group with <75% diameter stenoses (2,42 [1,75; 2,89] mL/min/g) and the normal group (2,54 [2,31; 2,86] mL/min/g), (p <0,001). There was no reliable difference in MBF at rest between the three groups (p = NS). CFR was significantly lower in the group of patients with severe ≥75% stenoses (1,85 [1,54; 2,31]) in comparison with patients group with stenoses of intermediate <75% severity (2,73 [2,19; 3,21]), and also in comparison with the normal group (3,12 [2,75; 3,23]), (p <0,001). Conclusion. The values of MBF at stress and CFR are significantly lower in patients with severe coronary arteries stenoses comparing with the group of patients with mild and moderate stenoses. The value of MBF at rest used independently has no diagnostic utility for detection of functional significance of coronary artery stenoses. Keywords: myocardial blood flow, coronary flow reserve, PET/CT, 13N-ammonia, coronary stenosis

11C-Choline Pet/Ct in the Detection of Prostate Cancer Relapse in Patients After Radical Treatment With Psa Level < 10 Ng/Ml

Purpose: To evaluate the usefulness of 11C-Choline PET/CT in the detection of recurrent prostate cancer (PCa) in patients with biochemical relapse after radical treatment. Materials and methods: This retrospective study included 217 PCa patients who underwent 11C-Choline PET/CT in the Department of Nuclear Medicine of Bakoulev Scientific Centre. All patients had biochemical relapse 3±2 years after radical treatment for locally advanced PCa (T1–3 N0–1 M0): radical prostatectomy (n = 159) and radiation therapy (n = 58). The mean PSA value in the group was 2.1±2.5 (0.2–9.7) ng/ml, median – 1.9 ng/ml. Imaging was performed on PET/CT scanner (Biograph-64, Siemens) 10 min after injection of 11C-Choline (400–550 Mbq). Results: Overall, according to 11C-Choline PET/CT results PCa relapse was detected in 56% (121/217) of cases: in 50% (80/159) after radical prostatectomy and in 71% (41/58) after radiation therapy. The mean PSA value in PET-positive cases was 3.1±2.2 (0.2–9.7) ng/ml, while in PETnegative cases – 1.8±1.7 (0.2–4.6) ng/ml. The majority – 68% (65/96) patients with PET-negative scan had low PSA levels (&lt; 2 ng/ml). PET/CT results were positive in 43% (50/115) patients with PSA of &lt; 2 ng/ml, in 63% (45/72) with PSA of 2 to 5 ng/ml, and in 87% (26/30) with PSA of &gt; 5 ng/ml. Local relapse was detected in 51% (62/121) patients, distant metastases – in 28% (34/121) of cases, both local and distant metastases – in 21% (25/121) of cases. Lymph node metastases were detected in 38% (86/217) of all patients included in the analysis, of which 28% (24/86) had lesions in lymph node of normal size (median 7 mm). Of all PET-positive patients bone metastases were detected in 33% (40/121), of which 60% (24/40) had isolated skeletal involvement. Importantly, that 27% (11/40) of PETpositive patients with bone metastases had no structural abnormalities on CT images (CT-negative cases), corresponding to isolated involvement of bone marrow. And half of these CT-negative patients (5/11) had single lesions. The mean PSA value in patients with bone metastases was 5.0±3.7 (0.4–9.1) ng/ml, median – 3.8 ng/ml. According to 11C-Choline PET/CT results oligometastatic PCa recurrence was revealed in 38% (82/217) of all patients, of which 62% (51/82) had local relapse only. Distant oligometastatic lesions were detected in 38% (31/82), of which 13% (4/31) were presented by normal-size lymph nodes and 19% (6/31) – by early bone marrow metastases. 48% (58/121) of PET-positive results were confirmed by data of repeated PET/CT examinations. Conclusion: 11C-Choline PET/CT has been shown to be a single noninvasive accurate technique for detection of recurrent PCa in patients with rising PSA after radical treatment, which allows to differentiate patients with local and distant metastases in one study, as well as identify oligometastatic process, and therefore was useful in determining the further personalized therapeutic approach. Keywords: prostate cancer, PET/CT, 11C-Choline, biochemical recurrence, PSA

Quick and Clean Cloning: A Ligation-Independent Cloning Strategy for Selective Cloning of Specific PCR Products from Non-Specific Mixes

We have developed an efficient strategy for cloning of PCR products that contain an unknown region flanked by a known sequence. As with ligation-independent cloning, the strategy is based on homology between sequences present in both the vector and the insert. However, in contrast to ligation-independent cloning, the cloning vector has homology with only one of the two primers used for amplification of the insert. The other side of the linearized cloning vector has homology with a sequence present in the insert, but nested and non-overlapping with the gene-specific primer used for amplification. Since only specific products contain this sequence, but none of the non-specific products, only specific products can be cloned. Cloning is performed using a one-step reaction that only requires incubation for 10 minutes at room temperature in the presence of T4 DNA polymerase to generate single-stranded extensions at the ends of the vector and insert. The reaction mix is then directly transformed into E. coli where the annealed vector-insert complex is repaired and ligated. We have tested this method, which we call quick and clean cloning (QC cloning), for cloning of the variable regions of immunoglobulins expressed in non-Hodgkin lymphoma tumor samples. This method can also be applied to identify the flanking sequence of DNA elements such as T-DNA or transposon insertions, or be used for cloning of any PCR product with high specificity

Single Tube, High Throughput Cloning of Inverted Repeat Constructs for Double-Stranded RNA Expression

BACKGROUND: RNA interference (RNAi) has emerged as a powerful tool for the targeted knockout of genes for functional genomics, system biology studies and drug discovery applications. To meet the requirements for high throughput screening in plants we have developed a new method for the rapid assembly of inverted repeat-containing constructs for the in vivo production of dsRNAs. METHODOLOGY/PRINCIPAL FINDINGS: The procedure that we describe is based on tagging the sense and antisense fragments with unique single-stranded (ss) tails which are then assembled in a single tube Ligase Independent Cloning (LIC) reaction. Since the assembly reaction is based on the annealing of unique complementary single stranded tails which can only assemble in one orientation, greater than ninety percent of the resultant clones contain the desired insert. CONCLUSION/SIGNIFICANCE: Our single-tube reaction provides a highly efficient method for the assembly of inverted repeat constructs for gene suppression applications. The single tube assembly is directional, highly efficient and readily adapted for high throughput applications

Observational study on variability between biobanks in the estimation of DNA concentration.

BACKGROUND: There is little confidence in the consistency of estimation of DNA concentrations when samples move between laboratories. Evidence on this consistency is largely anecdotal. Therefore there is a need first to measure this consistency among different laboratories and then identify and implement remedies. A pilot experiment to test logistics and provide initial data on consistency was therefore conceived. METHODS: DNA aliquots at nominal concentrations between 10 and 300 ng/mul were dispensed into the wells of 96-well plates by one participant - the coordinating centre. Participants estimated the concentration in each well and returned estimates to the coordinating centre. RESULTS: Considerable overall variability was observed among estimates. There were statistically significant differences between participants' measurements and between fluorescence emission and absorption spectroscopy. CONCLUSION: Anecdotal evidence of variability in DNA concentration estimation has been substantiated. Reduction in variability between participants will require the identification of major sources of variation, specification of effective remedies and their implementation

Circular Polymerase Extension Cloning of Complex Gene Libraries and Pathways

High-throughput genomics and the emerging field of synthetic biology demand ever more convenient, economical, and efficient technologies to assemble and clone genes, gene libraries and synthetic pathways. Here, we describe the development of a novel and extremely simple cloning method, circular polymerase extension cloning (CPEC). This method uses a single polymerase to assemble and clone multiple inserts with any vector in a one-step reaction in vitro. No restriction digestion, ligation, or single-stranded homologous recombination is required. In this study, we elucidate the CPEC reaction mechanism and demonstrate its usage in demanding synthetic biology applications such as one-step assembly and cloning of complex combinatorial libraries and multi-component pathways

Processing DNA molecules as text

Polymerase Chain Reaction (PCR) is the DNA-equivalent of Gutenberg’s movable type printing, both allowing large-scale replication of a piece of text. De novo DNA synthesis is the DNA-equivalent of mechanical typesetting, both ease the setting of text for replication. What is the DNA-equivalent of the word processor? Biology labs engage daily in DNA processing—the creation of variations and combinations of existing DNA—using a plethora of manual labor-intensive methods such as site-directed mutagenesis, error-prone PCR, assembly PCR, overlap extension PCR, cleavage and ligation, homologous recombination, and others. So far no universal method for DNA processing has been proposed and, consequently, no engineering discipline that could eliminate this manual labor has emerged. Here we present a novel operation on DNA molecules, called Y, which joins two DNA fragments into one, and show that it provides a foundation for DNA processing as it can implement all basic text processing operations on DNA molecules including insert, delete, replace, cut and paste and copy and paste. In addition, complicated DNA processing tasks such as the creation of libraries of DNA variants, chimeras and extensions can be accomplished with DNA processing plans consisting of multiple Y operations, which can be executed automatically under computer control. The resulting DNA processing system, which incorporates our earlier work on recursive DNA composition and error correction, is the first demonstration of a unified approach to DNA synthesis, editing, and library construction

An ensemble of structures of Burkholderia pseudomallei 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase

An ensemble of crystal structures are reported for 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase from B. pseudomallei. The structures include two vanadate complexes, revealing the structure of a close analogue of the transition state for phosphate transfer