Holographic Brownian Motion in Magnetic Environments

Using the gauge/gravity correspondence, we study the dynamics of a heavy quark in two strongly-coupled systems at finite temperature: Super-Yang-Mills in the presence of a magnetic field and non-commutative Super-Yang-Mills. In the former, our results agree qualitatively with the expected behavior from weakly-coupled theories. In the latter, we propose a Langevin equation that accounts for the effects of non-commutativity and we find new interesting features. The equation resembles the structure of Brownian motion in the presence of a magnetic field and implies that the fluctuations along non-commutative directions are correlated. Moreover, our results show that the viscosity is smaller than the commutative case and that the diffusion properties of the quark are unaffected by non-commutativity. Finally, we compute the random force autocorrelator and verify that the fluctuation-dissipation theorem holds in the presence of non-commutativity.Comment: 34 pages. v2: typos corrected. v3: title and abstract slightly modified in order to better reflect the contents of the paper; footnote 3 and one reference were also added; version accepted for publication in JHE

Evaluating the Relationship between Spermatogenic Silencing of the X Chromosome and Evolution of the Y Chromosome in Chimpanzee and Human

Chimpanzees and humans are genetically very similar, with the striking exception of their Y chromosomes, which have diverged tremendously. The male-specific region (MSY), representing the greater part of the Y chromosome, is inherited from father to son in a clonal fashion, with natural selection acting on the MSY as a unit. Positive selection might involve the performance of the MSY in spermatogenesis. Chimpanzees have a highly polygamous mating behavior, so that sperm competition is thought to provide a strong selective force acting on the Y chromosome in the chimpanzee lineage. In consequence of evolution of the heterologous sex chromosomes in mammals, meiotic sex chromosome inactivation (MSCI) results in a transcriptionally silenced XY body in male meiotic prophase, and subsequently also in postmeiotic repression of the sex chromosomes in haploid spermatids. This has evolved to a situation where MSCI has become a prerequisite for spermatogenesis. Here, by analysis of microarray testicular expression data representing a small number of male chimpanzees and men, we obtained information indicating that meiotic and postmeiotic X chromosome silencing might be more effective in chimpanzee than in human spermatogenesis. From this, we suggest that the remarkable reorganization of the chimpanzee Y chromosome, compared to the human Y chromosome, might have an impact on its meiotic interactions with the X chromosome and thereby on X chromosome silencing in spermatogenesis. Further studies will be required to address comparative functional aspects of MSCI in chimpanzee, human, and other placental mammals

High Accuracy Mutation Detection in Leukemia on a Selected Panel of Cancer Genes

<div><p>With the advent of whole-genome and whole-exome sequencing, high-quality catalogs of recurrently mutated cancer genes are becoming available for many cancer types. Increasing access to sequencing technology, including bench-top sequencers, provide the opportunity to re-sequence a limited set of cancer genes across a patient cohort with limited processing time. Here, we re-sequenced a set of cancer genes in T-cell acute lymphoblastic leukemia (T-ALL) using Nimblegen sequence capture coupled with Roche/454 technology. First, we investigated how a maximal sensitivity and specificity of mutation detection can be achieved through a benchmark study. We tested nine combinations of different mapping and variant-calling methods, varied the variant calling parameters, and compared the predicted mutations with a large independent validation set obtained by capillary re-sequencing. We found that the combination of two mapping algorithms, namely <em>BWA-SW</em> and <em>SSAHA2</em>, coupled with the variant calling algorithm <em>Atlas-SNP2</em> yields the highest sensitivity (95%) and the highest specificity (93%). Next, we applied this analysis pipeline to identify mutations in a set of 58 cancer genes, in a panel of 18 T-ALL cell lines and 15 T-ALL patient samples. We confirmed mutations in known T-ALL drivers, including PHF6, NF1, FBXW7, NOTCH1, KRAS, NRAS, PIK3CA, and PTEN. Interestingly, we also found mutations in several cancer genes that had not been linked to T-ALL before, including JAK3. Finally, we re-sequenced a small set of 39 candidate genes and identified recurrent mutations in TET1, SPRY3 and SPRY4. In conclusion, we established an optimized analysis pipeline for Roche/454 data that can be applied to accurately detect gene mutations in cancer, which led to the identification of several new candidate T-ALL driver mutations.</p> </div

Haemophilic knee arthropathy: long-term outcome after total knee replacement

PURPOSE: The objective of this study was to evaluate the long-term outcome and prosthetic survival of primary total knee arthroplasty in haemophilic patients. It was hypothesized that the infection and revision rate are higher and the outcome inferior when compared with patients without haemophilia. METHODS: Between 1985 and 2004, forty-three consecutive primary total knee replacements were performed in thirty haemophilic patients. These patients' charts were reviewed retrospectively. Twenty-five patients (34 knees) were available for clinical and radiological follow-up. The outcome was assessed using the Knee Society score, WOMAC and Kaplan-Meier survivorship analysis. RESULTS: An haematogenous infection occurred in two patients. In three patients, component revision was needed: two because of an infection and one because of a mechanical failure. After a mean follow-up of 9.6 years (2-20), 94% of the patients rated their result as either excellent or good. At time of follow-up, the Knee Society Score averaged 73.3 points (range, 29-100) and showed a significant gain (p < 0.001) compared to preoperative. Flexion contracture could be reduced significantly (p < 0.001) from 18.1° preoperatively to 8.4° at follow-up, whereas flexion remained unchanged. When infection or any component replacement was set as endpoints, the 10 years prosthetic survival was 90 and 86%, respectively. CONCLUSION: Total knee arthroplasty in haemophilic patients is a reliable treatment that results in pain relief and functional improvement with a low risk of postoperative infection. However, neither the postoperative infection rate nor the functional result does reach the same level as in a population not affected by haemophilia