Prognostic significance of atypical leukemic cell morphology in chronic lymphocytic leukemia.

CHARLES UNIVERSITY IN PRAGUE Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Health Care Bioanalytics Candidate: Bc. Nikola Fučíková Supervisor: doc. MUDr. Lukáš Smolej, Ph.D. Title of diploma thesis: Prognostic significance of atypical leukemic cell morphology in chronic lymphocytic leukemia The aim of this thesis is to evaluate the prognostic significance of atypical cell morphology and smudge cells in patients with untreated chronic lymphocytic leukemia. We performed differential leukocytes count and classified lymphocytes as typical and atypical in a cohort of 101 patients (median age, 66 years; males, 69%, Rai III/IV stages, 18%). For atypical CLL, we used the 15% threshold and 59% of patients were classified as atypical CLL (aCLL). For smudge cells, we chose the 30% threshold and 33% of patients were classified as smudge cells positive. Patients in early clinical Rai stage (0) had significantly higher number of smudge cells (p=0.04). We didn't find a significant association between aCLL / smudge cells with modern prognostic indicators. We didn't find a relationship between aCLL and the time to first-line therapy (p=0.394). However, patients with aCLL had a significantly shorter overall survival (p=0.0397). There was a trend toward shorter..

Additional file 3 of “gnparser”: a powerful parser for scientific names based on Parsing Expression Grammar

1,000 name-strings randomly selected from GNI and used to determine Accuracy, Precision and Recall data (Table 1). (TXT 32 kb

Phase Dependence of Double-Resonance Experiments in Rotational Spectroscopy

We here report on double-resonance experiments using broadband chirped pulse Fourier transform microwave spectroscopy that can facilitate spectral assignment and yield information about weak transitions with high resolution and sensitivity. Using the diastereomers menthone and isomenthone, we investigate the dependence of pumping a radio frequency transition on both the amplitude and phase of the signal from a microwave transition with which it shares a common rotational level. We observe a strong phase change when scanning the radio frequency through molecular resonance. The direction of the phase change depends on the energy level arrangement, that is, if it is progressive or regressive. The experimental results can be simulated using the three-level optical Bloch equations and described with the AC Stark effect, giving rise to an Autler–Townes splitting

Miller et al 2014 Paleobiology SOM and Appendices

Supplemental Online Materials and Appendices for "Ecological fidelity of functional traits based on species presence-absence in a modern mammalian bone assemblage (Amboseli, Kenya).

Draft policy on Open Access for data and information

<p>At present, national provisions on copyright and database protection regarding exceptions and limitations for research purposes differ both in detail and substance. Scientists within the EU working with copyright protected works or with protected databases have to be aware that regulations may vary considerably from country to country. This can be a major stumbling block to international collaboration in science.</p> <p>The document addresses legal issues that hamper an integrative system for managing biodiversity knowledge in Europe. It describes the importance for scientists to have access to documents and data in order to synthesize disparate information and to facilitate data mining (or similar research techniques). It explores some aspects of copyright and database protection that influence access to and re-use of biodiversity data and information and refers to exceptions and limitations of copyright or database protection provided for within the relevant EU Directives.</p

Structural and Biochemical Characterization of Human Adenylosuccinate Lyase (ADSL) and the R303C ADSL Deficiency-Associated Mutation

Adenylosuccinate lyase (ADSL) deficiency is a rare autosomal recessive disorder, which causes a defect in purine metabolism resulting in neurological and physiological symptoms. ADSL executes two nonsequential steps in the de novo synthesis of AMP: the conversion of phosphoribosylsuccinyl-aminoimidazole carboxamide (SAICAR) to phosphoribosylaminoimidazole carboxamide, which occurs in the de novo synthesis of IMP, and the conversion of adenylosuccinate to AMP, which occurs in the de novo synthesis of AMP and also in the purine nucleotide cycle, using the same active site. Mutation of ADSL’s arginine 303 to a cysteine is known to lead to ADSL deficiency. Interestingly, unlike other mutations leading to ADSL deficiency, the R303C mutation has been suggested to more significantly affect the enzyme’s ability to catalyze the conversion of succinyladenosine monophosphate than that of SAICAR to their respective products. To better understand the causation of disease due to the R303C mutation, as well as to gain insights into why the R303C mutation potentially has a disproportional decrease in activity toward its substrates, the wild type (WT) and the R303C mutant of ADSL were investigated enzymatically and thermodynamically. Additionally, the X-ray structures of ADSL in its apo form as well as with the R303C mutation were elucidated, providing insight into ADSL’s cooperativity. By utilizing this information, a model for the interaction between ADSL and SAICAR is proposed

CBS expression and activity in brain regions of Tg<i>hCBS</i>60.4 mice.

<p>(A, top) Immunoblots for CBS and β-actin in cerebellum (left panel), hippocampus (middle panel) and forebrain (right panel). Total CBS proteins (human CBS plus mouse CBS) were detected using the anti-hCBS polyclonal antibody that recognises both the human and mouse proteins. (A, bottom) Quantification of CBS proteins normalized to β-actin and relative to control mice in the three brain regions (<i>n</i> = 3 Tg<i>hCBS</i>60.4 and <i>n</i> = 3 control) (B) CBS activity in cerebellum (left panel), hippocampus (middle panel) and forebrain (right panel). Units are nanomoles of cystathionine formed per milligram of protein extract per hour. For cerebellum and forebrain, data represent mean ± S.E.M. of activity measurements in each group (<i>n</i> = 9 Tg<i>hCBS</i>60.4 and <i>n</i> = 7 control; <i>n</i> = 8 Tg<i>hCBS</i>60.4 and <i>n</i> = 8 control, respectively). For hippocampus, data represent mean ± S.E.M. of three experimental assays performed on same pooled hippocampi (<i>n</i> = 7 Tg<i>hCBS</i>60.4 and <i>n</i> = 8 control). *for <i>p</i><0.05. ***for <i>p</i><0.001.</p

Basal synaptic transmission in Tg<i>hCBS</i>60.4 mice.

<p>(A) Superimposed sample traces of evoked AMPA-R-mediated fEPSPs induced in a control (left) and a Tg<i>hCBS</i>60.4 mouse (right) by increased intensities of electrical stimulation of glutamate afferents (arrow). Traces are averages of 3 consecutive responses. (B) Comparison of synaptic efficacy as determined by the fEPSP/PFV ratio calculated at a stimulus intensity from 500 to 900 µA in Tg<i>hCBS</i>60.4 (23 slices/5 animals) and control (22 slices/5 animals) mice.</p