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Impact of Teachers' Common Planning Time on the Academic Performance of Students in a Middle School Setting
The purpose of this study was to assess the impact of the common planning time for a team of middle school teachers by comparing the standardized test scores of middle school students selected from two school districts located in North Texas. An analysis of variance (ANOVA) 2 * 4 design was utilized to measure the Texas Assessment of Knowledge and Skills (TAKS) math and reading scale score for 7th grade students from the test administered in spring 2005. The data for this study were compared by the variables of school, gender, and ethnicity. The measuring tool utilized in this study determined the ratio of the amount of variance of the scores for individuals of between-groups as opposed to the amount of variance of within-groups, indicating if there were a statistically significant difference on the scores in any one particular variable compared to the variances of scores for the other variables in this study. The statistical results indicated that there were no statistical significant differences in the scores of students attending a middle school where the teachers received a common planning time. However, there was a noted difference in the percentage ratings on the Academic Excellence Indicator System (AEIS) report published by TEA for the African American students who attended the school with the common planning time. These students had higher scores on the TAKS reading test. The TAKS math scores did not indicate any notable differences
Improved detection of tryptic immunoglobulin variable region peptides by chromatographic and gas-phase fractionation techniques
The polyclonal repertoire of circulating antibodies potentially holds valuable information about an individual's humoral immune state. While bottom-up proteomics is well suited for serum proteomics, the vast number of antibodies and dynamic range of serum challenge this analysis. To acquire the serum proteome more comprehensively, we incorporated high-field asymmetric waveform ion-mobility spectrometry (FAIMS) or two-dimensional chromatography into standard trypsin-based bottom-up proteomics. Thereby, the number of variable region (VR)-related spectra increased 1.7-fold with FAIMS and 10-fold with chromatography fractionation. To match antibody VRs to spectra, we combined de novo searching and BLAST alignment. Validation of this approach showed that, as peptide length increased, the de novo accuracy decreased and BLAST performance increased. Through in silico calculations on antibody repository sequences, we determined the uniqueness of tryptic VR peptides and their suitability as antibody surrogate. Approximately one-third of these peptides were unique, and about one-third of all antibodies contained at least one unique peptide.</p
Improved detection of tryptic immunoglobulin variable region peptides by chromatographic and gas-phase fractionation techniques
The polyclonal repertoire of circulating antibodies potentially holds valuable information about an individual's humoral immune state. While bottom-up proteomics is well suited for serum proteomics, the vast number of antibodies and dynamic range of serum challenge this analysis. To acquire the serum proteome more comprehensively, we incorporated high-field asymmetric waveform ion-mobility spectrometry (FAIMS) or two-dimensional chromatography into standard trypsin-based bottom-up proteomics. Thereby, the number of variable region (VR)-related spectra increased 1.7-fold with FAIMS and 10-fold with chromatography fractionation. To match antibody VRs to spectra, we combined de novo searching and BLAST alignment. Validation of this approach showed that, as peptide length increased, the de novo accuracy decreased and BLAST performance increased. Through in silico calculations on antibody repository sequences, we determined the uniqueness of tryptic VR peptides and their suitability as antibody surrogate. Approximately one-third of these peptides were unique, and about one-third of all antibodies contained at least one unique peptide.</p
A Novel Connexin 26 Mutation in a Patient Diagnosed with KeratitisâIchthyosisâDeafness Syndrome
Keratitisâichthyosisâdeafness syndrome is a rare disorder characterized by erythrokeratoderma, deafness, and keratitis. Scarring alopecia and squamous cell carcinoma can also occur. Most cases described so far were sporadic. Here we present evidence that keratitisâichthyosisâdeafness syndrome is caused by a mutation in the connexin 26 gene. This finding expands the spectrum of disorders caused by defects in connexin 26 and implies the gene in normal corneal function, hair growth, and carcinogenesis
Label-free peptide profiling of Orbitrap⢠full mass spectra
Background. We developed a new version of the open source software package Peptrix that can yet compare large numbers of Orbitrap⢠LC-MS data. The peptide profiling results for Peptrix on MS1 spectra were compared with those obtained from a small selection of open source and commercial software packages: msInspect, Sieve⢠and Progenesisâ˘. The properties compared in these packages were speed, total number of detected masses, redundancy of masses, reproducibility in numbers and CV of intensity, overlap of masses, and differences in peptide peak intensities. Reproducibility measurements were taken for the different MS1 software applications by measuring in triplicate a complex peptide mixture of immunoglobulin on the Orbitrap⢠mass spectrometer. Values of peptide masses detected from the high intensity peaks of the MS1 spectra by peptide profiling were verified with values of the MS2 fragmented and sequenced masses that resulted in protein identifications with a significant score. Findings. Peptrix finds about the same number of peptide features as the other packages, but peptide masses are in some cases approximately 5 to 10 times less redundant present in the peptide profile matrix. The Peptrix profile matrix displays the largest overlap when comparing the number of masses in a pair between two software applications. The overlap of peptide masses between software packages of low intensity peaks in the spectra is remarkably low with about 50% of the detected masses in the individual packages. Peptrix does not differ from the other packages in detecting 96% of the masses that relate to highly abundant sequenced proteins. MS1 peak intensities vary between the applications in a non linear way as they are not processed using the same method. Conclusions. Peptrix is capable of peptide profiling using Orbitrap⢠files and finding differential expressed peptides in body fluid and tissue samples. The number of peptide masses detected in Orbitrap⢠files can be increased by using more MS1 peptide profiling applications, including Peptrix, since it appears from the comparison of Peptrix with the other applications that all software packages have likely a high false negative rate of low intensity peptide peaks (missing peptides)
Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo) Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer
Purpose Trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprising the cytotoxic agent DM1, a stable linker, and trastuzumab, has demonstrated substantial activity in human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer, raising interest in evaluating the feasibility and cardiac safety of T-DM1 in early-stage breast cancer (EBC). Patients and Methods Patients (N = 153) with HER2-positive EBC and prechemotherapy left ventricular ejection fraction (LVEF) \u3e= 55% received (neo) adjuvant doxorubicin plus cyclophosphamide or fluorouracil plus epirubicin plus cyclophosphamide followed by T-DM1 for four cycles. Patients could then receive three to four cycles of optional docetaxel with or without trastuzumab. T-DM1 was then resumed with optional radiotherapy (sequential or concurrent) for 1 year (planned) of HER2-directed therapy. The coprimary end points were rate of prespecified cardiac events and safety. Results Median follow-up was 24.6 months. No prespecified cardiac events or symptomatic congestive heart failures were reported. Four patients (2.7%) had asymptomatic LVEF declines (\u3e= 10 percentage points from baseline to LVEF\u3c 50%), leading to T-DM1 discontinuation in one patient. Of 148 patients who received \u3e= one cycle of T-DM1, 82.4% completed the planned 1-year duration of HER2-directed therapy. During T-DM1 treatment, 38.5% and 2.7% of patients experienced grade 3 and 4 adverse events, respectively. Approximately 95% of patients receiving T-DM1 plus radiotherapy completed \u3e= 95% of the planned radiation dose with dela
A software application for comparing large numbers of high resolution MALDI-FTICR MS spectra demonstrated by searching candidate biomarkers for glioma blood vessel formation
Background: A Java⢠application is presented, which compares large numbers (n > 100) of raw FTICR mass spectra from patients and controls. Two peptide profile matrices can be produced simultaneously, one with occurrences of peptide masses in samples and another with the intensity of common peak masses in all the measured samples, using the peak- and background intensities of the raw data. In latter way, more significantly differentially expressed peptides are found between groups than just using the presence or absence in samples of common peak masses. The software application is tested by searching angiogenesis related proteins in glioma by comparing laser capture micro dissected- and enzymatic by trypsin digested tissue sections. Results: By hierarchical clustering of the presence-absence matrix, it appears that proteins, such as hemoglobin alpha and delta subunit, fibrinogen beta and gamma chain precursor, tubulin specific chaperone A, epidermal fatty acid binding protein, neutrophil gelatinase-associated lipocalin prec
No evidence for circulating HuD-specific CD8+ T cells in patients with paraneoplastic neurological syndromes and Hu antibodies
Aim: In paraneoplastic neurological syndromes (PNS) associated with small cell lung cancer (SCLC) and Hu antibodies (Hu-PNS), Hu antigens expressed by the tumour hypothetically trigger an immune response that also reacts with Hu antigens in the nervous system, resulting in tumour suppression and neuronal damage. To gain more insight into the hypothesized CD8+T cell-mediated immune pathogenesis of these syndromes, we searched for circulating HuD-specific CD8+T cells in a large cohort of Hu-PNS patients and controls. Patients and methods: Blood was tested from 43 Hu-PNS patients, 31 Hu antibody negativ
Immunotherapy in Glioblastoma: Current Shortcomings and Future Perspectives
Glioblastomas are aggressive, fast-growing primary brain tumors. After standard-of-care
treatment with radiation in combination with temozolomide, the overall prognosis of newly diagnosed
patients remains poor, with a 2-year survival rate of less than 20%. The remarkable survival benefit
gained with immunotherapy in several extracranial tumor types spurred a variety of experimental
intervention studies in glioblastoma patients. These ranged from immune checkpoint inhibition to
vaccinations and adoptive T cell therapies. Unfortunately, almost all clinical outcomes were universally
disappointing. In this perspective, we provide an overview of immune interventions performed
to date in glioblastoma patients and re-evaluate their performance. We argue that shortcomings of
current immune therapies in glioblastoma are related to three major determinants of resistance, namely:
low immunogenicity; immune privilege of the central nervous system; and immunosuppressive
micro-environment. In this perspective, we propose strategies that are guided by exact shortcomings
to sensitize glioblastoma prior to treatment with therapies that enhance numbers and/or activation
state of CD8 T cells
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