Fertilizer Recommendations for the Upper Rio Grande, and Trans Pecos.

4 p

The morphology and function of the quadrate ligament

There is a paucity of information in the literature regarding the quadrate ligament and the information that does exist is extremely conflicting. We dissected 30 cadavers (60 sides) to determine the morphology and function of this enigmatic ligament. A quadrate ligament (thickening of the elbow joint capsule) was found in all specimens. In all specimens this band was distinct from the circumferential fibres of the annular ligament. The length, width, and thickness of the quadrate ligament were found to be 11 mm, 8 mm, and 1 mm respectively. This ligament not only aided in securing the neck of the radius to the ulna but also resisted excessive supination and, to a lesser degree, pronation of the forearm. Following transection of the quadrate ligament, the head of the radius was secured to the ulna considerably less firmly and supination and pronation increased by 10 to 20 degrees and 5 to 8 degrees respectively. The quadrate ligament contributes to proximal radioulnar stability, limits the "spin" of this joint, and should be considered in manipulation, surgery, or imaging of the proximal forearm

Identification of a protein encoded in the EB-viral open reading frame BMRF2

Using monospecific rabbit sera against a peptide derived from a potential antigenic region of the Epstein-Barr viral amino acid sequence encoded in the open reading frame BMRF2 we could identify a protein-complex of 53/55 kDa in chemically induced B95-8, P3HR1 and Raji cell lines. This protein could be shown to be membrane-associated, as predicted by previous computer analysis of the secondary structure and hydrophilicity pattern, and may be a member of EBV-induced membrane proteins in lytically infected cells

Investigation of HIFU-induced anti-tumor immunity in a murine tumor model

<p>Abstract</p> <p>Background</p> <p>High intensity focused ultrasound (HIFU) is an emerging non-invasive treatment modality for localized treatment of cancers. While current clinical strategies employ HIFU exclusively for thermal ablation of the target sites, biological responses associated with both thermal and mechanical damage from focused ultrasound have not been thoroughly investigated. In particular, endogenous danger signals from HIFU-damaged tumor cells may trigger the activation of dendritic cells. This response may play a critical role in a HIFU-elicited anti-tumor immune response which can be harnessed for more effective treatment.</p> <p>Methods</p> <p>Mice bearing MC-38 colon adenocarcinoma tumors were treated with thermal and mechanical HIFU exposure settings in order to independently observe HIFU-induced effects on the host's immunological response. <it>In vivo </it>dendritic cell activity was assessed along with the host's response to challenge tumor growth.</p> <p>Results</p> <p>Thermal and mechanical HIFU were found to increase CD11c+ cells 3.1-fold and 4-fold, respectively, as compared to 1.5-fold observed for DC injection alone. In addition, thermal and mechanical HIFU increased CFSE+ DC accumulation in draining lymph nodes 5-fold and 10-fold, respectively. Moreover, focused ultrasound treatments not only caused a reduction in the growth of primary tumors, with tumor volume decreasing by 85% for thermal HIFU and 43% for mechanical HIFU, but they also provided protection against subcutaneous tumor re-challenge. Further immunological assays confirmed an enhanced CTL activity and increased tumor-specific IFN-γ-secreting cells in the mice treated by focused ultrasound, with cytotoxicity induced by mechanical HIFU reaching as high as 27% at a 10:1 effector:target ratio.</p> <p>Conclusion</p> <p>These studies present initial encouraging results confirming that focused ultrasound treatment can elicit a systemic anti-tumor immune response, and they suggest that this immunity is closely related to dendritic cell activation. Because DC activation was more pronounced when tumor cells were mechanically lysed by focused ultrasound treatment, mechanical HIFU in particular may be employed as a potential strategy in combination with subsequent thermal ablations for increasing the efficacy of HIFU cancer treatment by enhancing the host's anti-tumor immunity.</p

Supernova Remnants in the Sedov Expansion Phase: Thermal X-Ray Emission

Improved calculations of X-ray spectra for supernova remnants (SNRs) in the Sedov-Taylor phase are reported, which for the first time include reliable atomic data for Fe L-shell lines. This new set of Sedov models also allows for a partial collisionless heating of electrons at the blast wave and for energy transfer from ions to electrons through Coulomb collisions. X-ray emission calculations are based on the updated Hamilton-Sarazin spectral model. The calculated X-ray spectra are succesfully interpreted in terms of three distribution functions: the electron temperature and ionization timescale distributions, and the ionization timescale averaged electron temperature distribution. The comparison of Sedov models with a frequently used single nonequilibrium ionization (NEI) timescale model reveals that this simple model is generally not an appropriate approximation to X-ray spectra of SNRs. We find instead that plane-parallel shocks provide a useful approximation to X-ray spectra of SNRs, particularly for young SNRs. Sedov X-ray models described here, together with simpler plane shock and single ionization timescale models, have been implemented as standard models in the widely used XSPEC v11 spectral software package.Comment: 19 pages, 11 figures, submitted to Astrophysical Journa

Phase I clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibtion

<p>Abstract</p> <p>Background</p> <p>Patients with HER2-overexpressing metastatic breast cancer, despite initially benefiting from the monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor lapatinib, will eventually have progressive disease. HER2-based vaccines induce polyclonal antibody responses against HER2 that demonstrate enhanced anti-tumor activity when combined with lapatinib in murine models. We wished to test the clinical safety, immunogenicity, and activity of a HER2-based cancer vaccine, when combined with lapatinib.</p> <p>Methods</p> <p>We immunized women (n = 12) with metastatic, trastuzumab-refractory, HER2-overexpressing breast cancer with dHER2, a recombinant protein consisting of extracellular domain (ECD) and a portion of the intracellular domain (ICD) of HER2 combined with the adjuvant AS15, containing MPL, QS21, CpG and liposome. Lapatinib (1250 mg/day) was administered concurrently. Peripheral blood antibody and T cell responses were measured.</p> <p>Results</p> <p>This regimen was well tolerated, with no cardiotoxicity. Anti-HER2-specific antibody was induced in all patients whereas HER2-specific T cells were detected in one patient. Preliminary analyses of patient serum demonstrated downstream signaling inhibition in HER2 expressing tumor cells. The median time to progression was 55 days, with the majority of patients progressing prior to induction of peak anti-HER2 immune responses; however, 300-day overall survival was 92% (95% CI: 77-100%).</p> <p>Conclusions</p> <p>dHER2 combined with lapatinib was safe and immunogenic with promising long term survival in those with HER2-overexpressing breast cancers refractory to trastuzumab. Further studies to define the anticancer activity of the antibodies induced by HER2 vaccines along with lapatinib are underway.</p> <p>Trial registry</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00952692">NCT00952692</a></p

A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer

BACKGROUND: There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). METHODS: This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. RESULTS: Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1–2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52–665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. CONCLUSION: Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effector

Precision and linearity targets for validation of an IFNγ ELISPOT, cytokine flow cytometry, and tetramer assay using CMV peptides

<p>Abstract</p> <p>Background</p> <p>Single-cell assays of immune function are increasingly used to monitor T cell responses in immunotherapy clinical trials. Standardization and validation of such assays are therefore important to interpretation of the clinical trial data. Here we assess the levels of intra-assay, inter-assay, and inter-operator precision, as well as linearity, of CD8+ T cell IFNγ-based ELISPOT and cytokine flow cytometry (CFC), as well as tetramer assays.</p> <p>Results</p> <p>Precision was measured in cryopreserved PBMC with a low, medium, or high response level to a CMV pp65 peptide or peptide mixture. Intra-assay precision was assessed using 6 replicates per assay; inter-assay precision was assessed by performing 8 assays on different days; and inter-operator precision was assessed using 3 different operators working on the same day. Percent CV values ranged from 4% to 133% depending upon the assay and response level. Linearity was measured by diluting PBMC from a high responder into PBMC from a non-responder, and yielded R²values from 0.85 to 0.99 depending upon the assay and antigen.</p> <p>Conclusion</p> <p>These data provide target values for precision and linearity of single-cell assays for those wishing to validate these assays in their own laboratories. They also allow for comparison of the precision and linearity of ELISPOT, CFC, and tetramer across a range of response levels. There was a trend toward tetramer assays showing the highest precision, followed closely by CFC, and then ELISPOT; while all three assays had similar linearity. These findings are contingent upon the use of optimized protocols for each assay.</p

Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges

We investigated the diagnostic and clinical performance of exome sequencing (ES) in fetuses with sonographic abnormalities with normal karyotype, microarray and, in some cases, normal gene specific sequencing