The Spectral Correlation Function -- A New Tool for Analyzing Spectral-Line Maps

The "spectral correlation function" analysis we introduce in this paper is a new tool for analyzing spectral-line data cubes. Our initial tests, carried out on a suite of observed and simulated data cubes, indicate that the spectral correlation function [SCF] is likely to be a more discriminating statistic than other statistical methods normally applied. The SCF is a measure of similarity between neighboring spectra in the data cube. When the SCF is used to compare a data cube consisting of spectral-line observations of the ISM with a data cube derived from MHD simulations of molecular clouds, it can find differences that are not found by other analyses. The initial results presented here suggest that the inclusion of self-gravity in numerical simulations is critical for reproducing the correlation behavior of spectra in star-forming molecular clouds.Comment: 29 pages, including 4 figures (tar file submitted as source) See also: http://cfa-www.harvard.edu/~agoodman/scf/velocity_methods.htm

A CLINICAL PERSPECTIVE OF POSITIONING FOR THE ENDURANCE BICYCLIST

Optimal fitting of the endurance bicyclist to the bicycle is vital for improving performance, increasing control, avoiding overuse injuries, and promoting comfort. Neutral position of the bicyclist as well as static and dynamic fitting for the road and off-road bicyclist is important. Musculoskeletal screening procedures of the bicyclist are also important and emphasis will be placed on prevention and intervention of two common overuse injuries: anterior knee pain and lower back pain. Comparisons of bicycle fit and overuse injuries for the off-road bicyclist and racer will also be introduced

Prevalence of sacral dysmorphia in a prospective trauma population: Implications for a "safe" surgical corridor for sacro-iliac screw placement

<p>Abstract</p> <p>Background</p> <p>Percutaneous sacro-iliac (SI) screw fixation represents a widely used technique in the management of unstable posterior pelvic ring injuries and sacral fractures. The misplacement of SI-screws under fluoroscopic guidance represents a critical complication for these patients. This study was designed to determine the prevalence of sacral dysmorphia and the radiographic anatomy of surgical S1 and S2 corridors in a representative trauma population.</p> <p>Methods</p> <p>Prospective observational cohort study on a consecutive series of 344 skeletally mature trauma patients of both genders enrolled between January 1, 2007, to September 30, 2007, at a single academic level 1 trauma center. Inclusion criteria included a pelvic CT scan as part of the initial diagnostic trauma work-up. The prevalence of sacral dysmorphia was determined by plain radiographic pelvic films and CT scan analysis. The anatomy of sacral corridors was analyzed on 3 mm reconstruction sections derived from multislice CT scan, in the axial, coronal, and sagittal plane. "Safe" potential surgical corridors at S1 and S2 were calculated based on these measurements.</p> <p>Results</p> <p>Radiographic evidence of sacral dysmorphia was detected in 49 patients (14.5%). The prevalence of sacral dysmorphia was not significantly different between male and female patients (12.2% <it>vs</it>. 19.2%; <it>P </it>= 0.069). In contrast, significant gender-related differences were detected with regard to radiographic analysis of surgical corridors for SI-screw placement, with female trauma patients (<it>n </it>= 99) having significantly narrower corridors at S1 and S2 in all evaluated planes (axial, coronal, sagittal), compared to male counterparts (<it>n </it>= 245; <it>P </it>< 0.01). In addition, the mean S2 body height was higher in dysmorphic compared to normal sacra, albeit without statistical significance (<it>P </it>= 0.06), implying S2 as a safe surgical corridor of choice in patients with sacral dysmorphia.</p> <p>Conclusions</p> <p>These findings emphasize a high prevalence of sacral dysmorphia in a representative trauma population and imply a higher risk of SI-screw misplacement in female patients. Preoperative planning for percutaneous SI-screw fixation for unstable pelvic and sacral fractures must include a detailed CT scan analysis to determine the safety of surgical corridors.</p

Extracellular zinc and ATP-gated P2X receptor calcium entry channels: New zinc receptors as physiological sensors and therapeutic targets

In this review, we focus on two attributes of P2X receptor channel function, one essential and one novel. First, we propose that P2X receptors are extracellular sensors as well as receptors and ion channels. In particular, the large extracellular domain (that comprises 70% of the molecular mass of the receptor channel protein) lends itself to be a cellular sensor. Moreover, its exquisite sensitivity to extracellular pH, ionic strength, and multiple ligands evokes the function of a sensor. Second, we propose that P2X receptors are extracellular zinc receptors as well as receptors for nucleotides. We provide novel data in multiple publications and illustrative data in this invited review to suggest that zinc triggers ATP-independent activation of P2X receptor channel function. In this light, P2X receptors are the cellular site of integration between autocrine and paracrine zinc signaling and autocrine and paracrine purinergic signaling. P2X receptors may sense changes in these ligands as well as in extracellular pH and ionic strength and transduce these sensations via calcium and/or sodium entry and changes in membrane potential

Depressive symptomology and cancer incidence in men and women : Longitudinal evidence from the HUNT study

publishedVersio

Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining

Background. Previously, we developed a combined dictionary dubbed Chemlist for the identification of small molecules and drugs in text based on a number of publicly available databases and tested it on an annotated corpus. To achieve an acceptable recall and precision we used a number of automatic and semi-automatic processing steps together with disambiguation rules. However, it remained to be investigated which impact an extensive manual curation of a multi-source chemical dictionary would have on chemical term identification in text. ChemSpider is a chemical database that has undergone extensive manual curation aimed at establishing valid chemical name-to-structure relationships. Results. We acquired the component of ChemSpider containing only manually curated names and synonyms. Rule-based term filtering, semi-automatic manual curation, and disambiguation rules were applied. We tested the dictionary from ChemSpider on an annotated corpus and compared the results with those for the Chemlist dictionary. The ChemSpider dictionary of ca. 80 k names was only a 1/3 to a 1/4 the size of Chemlist at around 300 k. The ChemSpider dictionary had a precision of 0.43 and a recall of 0.19 before the application of filtering and disambiguation and a precision of 0.87 and a recall of 0.19 after filtering and disambiguation. The Chemlist dictionary had a precision of 0.20 and a recall of 0.47 before the application of filtering and disambiguation and a precision of 0.67 and a recall of 0.40 after filtering and disambiguation. Conclusions. We conclude the following: (1) The ChemSpider dictionary achieved the best precision but the Chemlist dictionary had a higher recall and the best F-score; (2) Rule-based filtering and disambiguation is necessary to achieve a high precision for both the automatically generated and the manually curated dictionary. ChemSpider is available as a web service at http://www.chemspider. com/ and the Chemlist dictionary is freely available as an XML file in Simple Knowledge Organization System format on the web at http://www.biosemantics.org/ chemlist

CYLD mutation characterizes a subset of HPV-positive head and neck squamous cell carcinomas with distinctive genomics and frequent cylindroma-like histologic features

Mutations in the tumor suppressor CYLD, known to be causative of cylindromas, were recently described in a subset of high-risk (hr) HPV-positive head and neck squamous cell carcinomas (HNSCC). Pathologic and genetic characterization of these CYLD-mutant carcinomas, however, remains limited. Here, we investigated whether CYLD mutations characterize a histopathologically and genomically distinct subset of hrHPV-positive HNSCC. Comprehensive genomic profiling via hybrid capture-based DNA sequencing was performed on 703 consecutive head and neck carcinomas with hrHPV sequences, identifying 148 unique cases (21%) harboring CYLD mutations. Clinical data, pathology reports, and histopathology were reviewed. CYLD mutations included homozygous deletions (n = 61/148; 41%), truncations (n = 52; 35%), missense (n = 26; 18%) and splice-site (n = 9; 6%) mutations, and in-frame deletion (n = 1; 1%). Among hrHPV-positive HNSCC, the CYLD-mutant cohort showed substantially lower tumor mutational burden than CYLD-wildtype cases (n = 555) (median 2.6 vs. 4.4 mut/Mb, p \u3c 0.00001) and less frequent alterations in PIK3CA (11% vs. 34%, p \u3c 0.0001), KMT2D (1% vs. 16%, p \u3c 0.0001), and FBXW7 (3% vs. 11%, p = 0.0018). Male predominance (94% vs. 87%), median age (58 vs. 60 years), and detection of HPV16 (95% vs. 89%) were similar. On available histopathology, 70% of CYLD-mutant HNSCC (98/141 cases) contained hyalinized material, consistent with basement membrane inclusions, within crowded aggregates of tumor cells. Only 7% of CYLD-wildtype cases demonstrated this distinctive pattern (p \u3c 0.0001). Histopathologic patterns of CYLD-mutant HNSCC lacking basement membrane inclusions included nonkeratinizing (n = 22, 16%), predominantly nonkeratinizing (nonkeratinizing SCC with focal maturation; n = 10, 7%), and keratinizing (n = 11, 8%) patterns. The latter two groups showed significantly higher frequency of PTEN alterations compared with other CYLD-mutant cases (38% [8/21] vs. 7% [8/120], p = 0.0004). Within our cohort of hrHPV-positive HNSCCs, CYLD mutations were frequent (21%) and demonstrated distinctive clinical, histopathologic, and genomic features that may inform future study of prognosis and treatment

NQO1-dependent, tumor-selective radiosensitization of non-small cell lung cancers

Purpose: Development of tumor-specific therapies for the treatment of recalcitrant non-small cell lung cancers (NSCLCs) are urgently needed. Here, we investigated the ability of ß-lapachone (ß-lap, ARQ761 in clinical form) to selectively potentiate the effects of ionizing radiation (IR, 1–3 Gy) in NSCLCs that over-express NAD(P)H:Quinone Oxidoreductase 1 (NQO1). Experimental Design: The mechanism of lethality of low dose IR in combination with sublethal doses of ß-lap were evaluated in NSCLC lines in vitro and validated in subcutaneous and orthotopic xenograph models in vivo. Pharmacokinetics and pharmacodynamics (PK/PD) studies comparing single versus co-treatments were performed to validate therapeutic efficacy and mechanism of action. Results: ß-Lap administration after IR treatment hyperactivated PARP, greatly lowered NAD+/ATP levels, and increased DSB lesions over time in vitro. Radiosensitization of orthotopic, as well as subcutaneous, NSCLCs occurred with high apparent cures (>70%), even though 1/8 ß-lap doses reach subcutaneous versus orthotopic tumors. No methemoglobinemia or long-term toxicities were noted in any normal tissues, including mouse liver that expresses the highest level of NQO1 (~12 Units) of any normal tissue. PK/PD responses confirm that IR + ß-lap treatments hyperactivate PARP activity, greatly lower NAD+/ATP levels and dramatically inhibit DSB repair in exposed NQO1+ cancer tissue, while low NQO1 levels and high levels of Catalase in associated normal tissue were protective. Conclusion: Our data suggest that combination of sublethal doses of ß-lap and IR is a viable approach to selectively treat NQO1-overexpressing NSCLC and warrant a clinical trial using low-dose IR + ß-lapachone against patients with NQO1+ NSCLCs