Statistical Communication Theory

Contains reports on one completed research project and one current research project.Joint Services Electronics Programs (U.S. Army, U.S. Navy, and U.S. Air Force) under Contract DA 28-043-AMC-02536(E)National Aeronautics and Space Administration (Grant NsG-496

New factors enhancing the reactivity of cysteines in molten globule-like structures

Protein cysteines often play crucial functional and structural roles, so they are emerging targets to design covalent thiol ligands that are able to modulate enzyme or protein functions. Some of these residues, especially those involved in enzyme mechanisms-including nucleophilic and reductive catalysis and thiol-disulfide exchange-display unusual hyper-reactivity; such a property is expected to result from a low pK(a)and from a great accessibility to a given reagent. New findings and previous evidence clearly indicate that pK(a)perturbations can only produce two-four-times increased reactivity at physiological pH values, far from the hundred and even thousand-times kinetic enhancements observed for some protein cysteines. The data from the molten globule-like structures of ribonuclease, lysozyme, bovine serum albumin and chymotrypsinogen identified new speeding agents, i.e., hydrophobic/electrostatic interactions and productive complex formations involving the protein and thiol reagent, which were able to confer exceptional reactivity to structural cysteines which were only intended to form disulfides. This study, for the first time, evaluates quantitatively the different contributions of pK(a)and other factors to the overall reactivity. These findings may help to clarify the mechanisms that allow a rapid disulfide formation during the oxidative folding of many proteins

Ant colony optimisation and local search for bin-packing and cutting stock problems

The Bin Packing Problem and the Cutting Stock Problem are two related classes of NP-hard combinatorial optimization problems. Exact solution methods can only be used for very small instances, so for real-world problems, we have to rely on heuristic methods. In recent years, researchers have started to apply evolutionary approaches to these problems, including Genetic Algorithms and Evolutionary Programming. In the work presented here, we used an ant colony optimization (ACO) approach to solve both Bin Packing and Cutting Stock Problems. We present a pure ACO approach, as well as an ACO approach augmented with a simple but very effective local search algorithm. It is shown that the pure ACO approach can compete with existing evolutionary methods, whereas the hybrid approach can outperform the best-known hybrid evolutionary solution methods for certain problem classes. The hybrid ACO approach is also shown to require different parameter values from the pure ACO approach and to give a more robust performance across different problems with a single set of parameter values. The local search algorithm is also run with random restarts and shown to perform significantly worse than when combined with ACO

Anti-Ri-associated paraneoplastic ophthalmoplegia-ataxia syndrome in a woman with breast cancer. A case report and review of the literature

Background: Breast cancer is the most common cancer in women. However, in the management of breast cancer, paraneoplastic neurological syndromes represent a diagnostic and therapeutic challenge. The diagnosis of paraneoplastic neurological syndromes is difficult due to the heterogeneity of symptoms, the timing of presentation, and the absence of antibodies, and it generally occurs before the diagnosis of breast cancer in 80% of patients who develop paraneoplastic neurological syndromes. We describe a 72-year-old woman with subacute ophthalmoplegia-ataxia syndrome who was subsequently diagnosed as having breast cancer and anti-Ri antibodies. Case presentation: A 72-year-old post-menopausal Caucasian woman, with a positive medical history for diabetes mellitus and hypertension, presented with a 3-month onset of blurred vision, diplopia, and progressive gait disturbance. Serological tests were positive for well-characterized onconeural antibodies (anti-Ri). A whole-body computed tomography scan revealed a nodular opacity under her left nipple and axillary adenopathy. A biopsy of her left breast was performed, and histological examination showed ductal carcinoma. She underwent a superoexternal quadrantectomy with left axillary dissection. The final diagnosis showed infiltrating ductal carcinoma of the breast (T1c N1 M0, stage IIA) associated with paraneoplastic ophthalmoplegia-ataxia syndrome. At a 6-month follow-up, she showed no clinical or instrumental evidence of neoplastic recurrence with partial clinical improvement of neurological symptoms, such as ataxia and diplopia. Conclusion: The diagnosis of paraneoplastic neurological syndromes is often late, as in this patient, but treatment at an early stage may provide a good prognosis. Furthermore, this is one of several cases of an anti-Ri paraneoplastic neurological syndrome not associated with myoclonus, which reinforces the belief that opsoclonus myoclonus syndrome is not pathognomonic of the associated anti-Ri paraneoplastic neurological syndromes

A single-cell analysis of breast cancer cell lines to study tumour heterogeneity and drug response

Cancer cells within a tumour have heterogeneous phenotypes and exhibit dynamic plasticity. How to evaluate such heterogeneity and its impact on outcome and drug response is still unclear. Here, we transcriptionally profile 35,276 individual cells from 32 breast cancer cell lines to yield a single cell atlas. We find high degree of heterogeneity in the expression of biomarkers. We then train a deconvolution algorithm on the atlas to determine cell line composition from bulk gene expression profiles of tumour biopsies, thus enabling cell line-based patient stratification. Finally, we link results from large-scale in vitro drug screening in cell lines to the single cell data to computationally predict drug responses starting from single-cell profiles. We find that transcriptional heterogeneity enables cells with differential drug sensitivity to co-exist in the same population. Our work provides a framework to determine tumour heterogeneity in terms of cell line composition and drug response

Bibliometric Evaluation vs. Informed Peer Review:Evidence from Italy

A relevant question for the organization of large scale research assessments is whether bibliometric evaluation and informed peer review where reviewers know where the work was published, yield similar results. It would suggest, for instance, that less costly bibliometric evaluation might - at least partly - replace informed peer review, or that bibliometric evaluation could reliably monitor research in between assessment exercises. We draw on our experience of evaluating Italian research in Economics, Business and Statistics, where almost 12,000 publications dated 2004-2010 were assessed. A random sample from the available population of journal articles shows that informed peer review and bibliometric analysis produce similar evaluations of the same set of papers. Whether because of independent convergence in assessment, or the influence of bibliometric information on the community of reviewers, the implication for the organization of these exercises is that these two approaches are substitutes