Targeted Assembly of Short Sequence Reads

As next-generation sequence (NGS) production continues to increase, analysis is becoming a significant bottleneck. However, in situations where information is required only for specific sequence variants, it is not necessary to assemble or align whole genome data sets in their entirety. Rather, NGS data sets can be mined for the presence of sequence variants of interest by localized assembly, which is a faster, easier, and more accurate approach. We present TASR, a streamlined assembler that interrogates very large NGS data sets for the presence of specific variants, by only considering reads within the sequence space of input target sequences provided by the user. The NGS data set is searched for reads with an exact match to all possible short words within the target sequence, and these reads are then assembled strin-gently to generate a consensus of the target and flanking sequence. Typically, variants of a particular locus are provided as different target sequences, and the presence of the variant in the data set being interrogated is revealed by a successful assembly outcome. However, TASR can also be used to find unknown sequences that flank a given target. We demonstrate that TASR has utility in finding or confirming ge-nomic mutations, polymorphism, fusion and integration events. Targeted assembly is a powerful method for interrogating large data sets for the presence of sequence variants of interest. TASR is a fast, flexible and easy to use tool for targeted assembly

Conflict-free connection numbers of line graphs

A path in an edge-colored graph is called \emph{conflict-free} if it contains at least one color used on exactly one of its edges. An edge-colored graph $G$ is \emph{conflict-free connected} if for any two distinct vertices of $G$, there is a conflict-free path connecting them. For a connected graph $G$, the \emph{conflict-free connection number} of $G$, denoted by $cfc(G)$, is defined as the minimum number of colors that are required to make $G$ conflict-free connected. In this paper, we investigate the conflict-free connection numbers of connected claw-free graphs, especially line graphs. We first show that for an arbitrary connected graph $G$, there exists a positive integer $k$ such that $cfc(L^k(G))\leq 2$. Secondly, we get the exact value of the conflict-free connection number of a connected claw-free graph, especially a connected line graph. Thirdly, we prove that for an arbitrary connected graph $G$ and an arbitrary positive integer $k$, we always have $cfc(L^{k+1}(G))\leq cfc(L^k(G))$, with only the exception that $G$ is isomorphic to a star of order at least~$5$ and $k=1$. Finally, we obtain the exact values of $cfc(L^k(G))$, and use them as an efficient tool to get the smallest nonnegative integer $k_0$ such that $cfc(L^{k_0}(G))=2$.Comment: 11 page

Acute Kidney Injury: Global Health Alert

Acute kidney injury (AKI) is increasingly prevalent in developing and developed countries and is associated with severe morbidity and mortality. Most etiologies of AKI can be prevented by interventions at the individual, community, regional and in-hospital levels. Effective measures must include community-wide efforts to increase an awareness of the devastating effects of AKI and provide guidance on preventive strategies, as well as early recognition and management. Efforts should be focused on minimizing causes of AKI, increasing awareness of the importance of serial measurements of serum creatinine in high risk patients, and documenting urine volume in acutely ill people to achieve early diagnosis; there is as yet no definitive role for alternative biomarkers. Protocols need to be developed to systematically manage prerenal conditions and specific infections. More accurate data about the true incidence and clinical impact of AKI will help to raise the importance of the disease in the community, increase awareness of AKI by governments, the public, general and family physicians and other health care professionals to help prevent the disease. Prevention is the key to avoid the heavy burden of mortality and morbidity associated with AKI

Coherent oscillations and giant edge magnetoresistance in singly connected topological insulators

A topological insulator has a pair of extended states at the edge in the bulk insulating regime. We study a geometry in which such edge states will manifest themselves in a qualitative manner through periodic oscillations in the magnetoconductance of a singly connected sample coupled to leads through narrow point contacts. Detailed calculations identify the parameters for which these oscillations are expected to be the strongest, and also show their robustness to disorder. Such oscillations can be used as a spectroscopic tool of the edge states. A large change in the device resistance at small B, termed giant edge magnetoresistance, can have potential for application. © 2009 The American Physical Society.published_or_final_versio

Cetuximab ameliorates suppressive phenotypes of myeloid antigen presenting cells in head and neck cancer patients

Background: Myeloid-derived suppressor cells (MDSC) and M2 monocytes/macrophages are two types of suppressive myeloid antigen presenting cells that have been shown to promote tumor progression and correlate with poor prognosis in cancer patients. Tumor antigen specific monoclonal antibodies (mAb) have emerged as important agents for cancer therapy. In addition to the direct inhibition of tumor growth, the Fc portions of the therapeutic mAbs, such as the IgG1 portion of the anti-epidermal growth factor receptor (EGFR) mAb cetuximab, might interact with the Fc-gamma receptors (FcγR) on myeloid cells and modulate their suppressive activity. Methods: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) on the UPCI 08-013 NCT01218048 trial were treated with single-agent cetuximab before surgery. Blood were collected pre- and post-cetuximab treatment to analyze frequency of monocytic MDSC (CD11b+CD14+HLA-DRlo/-), granulocytic MDSC (LIN-CD11b+CD15+) and CD11b+CD14+HLA-DRhi monocytes by flow cytometry. Besides, CD11b+CD14+HLA-DRhi monocytes were sorted for qPCR analysis of IL-10 and IL-12B transcripts. MDSC were generated in vitro with or without coated hIgG1 and tested for suppressive activity in mixed leukocyte reaction (MLR). Naïve monocytes from HNSCC patients co-cultured with tumor cell lines in the presence of cetuximab or hIgG1 were analyzed for M1/2 surface markers and cytokines. Results: We observed significantly increased monocytic MDSC in non-responders and decreased granulocytic MDSC in responders after cetuximab treatment. In addition, circulating CD11b+CD14+HLA-DRhi monocytes of cetuximab responders displayed attenuated M2 polarization, with decreased CD163+ expression and IL-10 transcripts after cetuximab treatment. This beneficial effect appeared to be FcγR dependent, since CD16 ligation reproduced the reversal of suppressive activity of MDSC in vitro. CD14+ naïve monocytes from the co-cultures of tumor cells, cetuximab and HNSCC patient PBMC or purified monocytes were skewed to an M1-like phenotype, with increased expression of HLA-DR, CD86 and production of IL-12 p70. Likewise, reduced M2 features (expression of CD163 and production of IL-10) were found after crosslinking CD16 on the surface of monocytes to cetuximab-coated tumor cells. Conclusion: Our studies demonstrate a novel function of cetuximab in ameliorating suppressive phenotypes of FcγR bearing myeloid cells in cancer patients, which is associated with better clinical outcome of cetuximab-treated patients. Clinical trial registry: # NCT01218048. Registered 7 October 2010

An experimental study of exhaled substance exposure between two standing manikins

Conference Theme: Airborne Infection Control - Ventilation, IAQ & EnergyTransmission of the exhaled substances from one person to another in indoor environment is influenced by many individual factors. The impacts of these factors for two face-to-face standing persons are investigated by evaluating the exposure of the substances in a room ventilated by displacement. Experiments employing two breathing thermal manikins are conducted in a full-scale test room. The geometry of the test room is 4.2 m (length) × 3.6 m (width) × 2.6 m (height). The distance between two manikins is 0.8 m, which is regarded as a common distance between two persons ...postprin

Mechanism of glycan receptor recognition and specificity switch for avian, swine, and human adapted influenza virus hemagglutinins: a molecular dynamics perspective.

Hemagglutinins (HA's) from duck, swine, and human influenza viruses have previously been shown to prefer avian and human glycan receptor analogues with distinct topological profiles, pentasaccharides LSTa (alpha-2,3 linkage) and LSTc (alpha-2,6 linkage), in comparative molecular dynamics studies. On the basis of detailed analyses of the dynamic motions of the receptor binding domains (RBDs) and interaction energy profiles with individual glycan residues, we have identified approximately 30 residue positions in the RBD that present distinct profiles with the receptor analogues. Glycan binding constrained the conformational space sampling by the HA. Electrostatic steering appeared to play a key role in glycan binding specificity. The complex dynamic behaviors of the major SSE and trimeric interfaces with or without bound glycans suggested that networks of interactions might account for species specificity in these low affinity and high avidity (multivalent) interactions between different HA and glycans. Contact frequency, energetic decomposition, and H-bond analyses revealed species-specific differences in HA-glycan interaction profiles, not readily discernible from crystal structures alone. Interaction energy profiles indicated that mutation events at the set of residues such as 145, 156, 158, and 222 would favor human or avian receptor analogues, often through interactions with distal asialo-residues. These results correlate well with existing experimental evidence, and suggest new opportunities for simulation-based vaccine and drug development

Perception of Cantonese Parkinsonian speech

Abstract no. 1pSC18published_or_final_versio

Shear waves induced by moving needle in MR Elastography

Magnetic Resonance Elastography (MRE) is a phase contrast-based method for observing shear wave propagation in a material to determine its stiffness. The objective of this study was to determine whether shear waves suitable for MRE can be induced using a moving acupuncture needle. Tissue-simulating bovine gel phantom and a 0.4mm diameter acupuncture needle were used in the experiment. The results showed that observable shear waves could be induced in the gel phantom by cyclic needle motion. The observed wavelength varied with excitation frequency, as expected. Generating shear waves using moving needles may be a useful tool to study the basic mechanism of acupuncture with MRE. Further study will be conducted to observe the wave motion in inhomogeneous media and acupuncture-induced effects in invivo studies.published_or_final_versio

Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.

Progress in the management of patients with myelodysplastic syndromes (MDS) has been hampered by the inability to detect cytogenetic abnormalities in 40-60% of cases. We prospectively analyzed matched pairs of bone marrow and buccal cell (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP) arrays, and identified somatically acquired clonal genomic abnormalities in 21 patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5 (15%) had clonal, somatically acquired aberrations by SNP array analysis, including 4 with segmental uniparental disomies (UPD) and 1 with three separate microdeletions. Each abnormality was detected more readily in CD34+ cells than in unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA from each patient was necessary to distinguish true clonal genomic abnormalities from inherited copy number variations and regions with apparent loss of heterozygosity. UPDs affecting chromosome 7q were identified in two patients who had a rapidly deteriorating clinical course despite a low-risk International Prognostic Scoring System score. Further studies of larger numbers of patients will be needed to determine whether 7q UPD detected by SNP array analysis will identify higher risk MDS patients at diagnosis, analogous to those with 7q cytogenetic abnormalities