Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements

Complex genomic rearrangements (CGRs) consisting of two or more breakpoint junctions have been observed in genomic disorders. Recently, a chromosome catastrophe phenomenon termed chromothripsis, in which numerous genomic rearrangements are apparently acquired in one single catastrophic event, was described in multiple cancers. Here, we show that constitutionally acquired CGRs share similarities with cancer chromothripsis. In the 17 CGR cases investigated, we observed localization and multiple copy number changes including deletions, duplications, and/or triplications, as well as extensive translocations and inversions. Genomic rearrangements involved varied in size and complexities; in one case, array comparative genomic hybridization revealed 18 copy number changes. Breakpoint sequencing identified characteristic features, including small templated insertions at breakpoints and microhomology at breakpoint junctions, which have been attributed to replicative processes. The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism's life cycle.     

Enhancing the Strength of an Optical Trap by Truncation

Optical traps (tweezers) are beginning to be used with increasing efficacy in diverse studies in the biological and biomedical sciences. We report here results of a systematic study aimed at enhancing the efficiency with which dielectric (transparent) materials can be optically trapped. Specifically, we investigate how truncation of the incident laser beam affects the strength of an optical trap in the presence of a circular aperture. Apertures of various sizes have been used by us to alter the beam radius, thereby changing the effective numerical aperture and intensity profile. We observe significant enhancement of the radial and axial trap stiffness when an aperture is used to truncate the beam compared to when no aperture was used, keeping incident laser power constant. Enhancement in trap stiffness persists even when the beam intensity profile is modulated. The possibility of applying truncation to multiple traps is explored; to this end a wire mesh is utilized to produce multiple trapping that also alters the effective numerical aperture. The use of a mesh leads to reduction in trap stiffness compared to the case when no wire mesh is used. Our findings lead to a simple-to-implement and inexpensive method of significantly enhancing optical trapping efficiency under a wide range of circumstances.     

Possible Role of Interleukin-1β in Type 2 Diabetes Onset and Implications for Anti-inflammatory Therapy Strategies

Increasing evidence of a role of chronic inflammation in type 2 diabetes progression has led to the development of therapies targeting the immune system. We develop a model of interleukin-1β dynamics in order to explain principles of disease onset. The parameters in the model are derived from in vitro experiments and patient data. In the framework of this model, an IL-1β switch is sufficient and necessary to account for type 2 diabetes onset. The model suggests that treatments targeting glucose bear the potential of stopping progression from pre-diabetes to overt type 2 diabetes. However, once in overt type 2 diabetes, these treatments have to be complemented by adjuvant anti-inflammatory therapies in order to stop or decelerate disease progression. Moreover, the model suggests that while glucose-lowering therapy needs to be continued all the way, dose and duration of the anti-inflammatory therapy needs to be specifically controlled. The model proposes a framework for the discussion of clinical trial outcomes.     

Subclavian artery stenting: Immediate and mid term clinical follow-up results

BACKGROUND: Intravascular stents are increasingly being used to treat subclavian artery obstructive disease. This study aimed to assess the immediate and mid-term clinical outcome of subclavian artery stenting. METHODS AND RESULTS: Total occlusion of the subclavian artery was seen in 7 (28%) out of the 25 consecutive patients treated for subclavican artery stenosis. Mean lesion length was 14 +/- 4.3 mm. The mean preprocedure diameter stenosis was reduced from 83.2 +/- 14.9% to 9.6 +/- 5.4% postprocedure. Procedural success was achieved in all patients. Clinical follow-up was obtained in all patients. The initial success was maintained at follow-up (mean = 12 +/- 4 months) in 24 (96%) patients. Recurrence of symptoms occurred in 1 (4%) patient who had an angiographically documented restenosis four months after the procedure. It was successfully redilated. CONCLUSION: Stenting for subclavian artery obstructive disease is safe, technically feasible and has favorable clinical outcomes. It may be considered as the therapy of choice for subclavian artery obstructive disease.     

Microwave assisted nano (ZnO–TiO2) catalyzed synthesis of some new 4,5,6,7-tetrahydro-6-((5-substituted-1,3,4-oxadiazol-2-yl)methyl)thieno[2,3-c]pyridine as antimicrobial agents

Combined nano zinc oxide and titanium dioxide [nano (ZnO–TiO₂)] has been reported first time for the synthesis of novel series of 4,5,6,7-tetrahydro-6-((5-substituted-1,3,4-oxadiazol-2-yl)methyl)thieno[2,3-c]pyridine. All the synthesized compounds (7a–7m) are novel and were screened for their antimicrobial activity against four different strains like Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis and antifungal activity was determined against two strains Candida albicans and Aspergillus niger. SAR for the newly synthesised derivatives has been developed by comparing their MIC values with ampicillin, ciprofloxacin and miconazole for antibacterial and antifungal activities, respectively. Among the synthesized compounds, 2,6 dichlorophenyl analogue (7f), 4 fluorophenyl analogue (7k) and 2,6 dichlorophenyl analogue (7l) shows promising antibacterial as well as antifungal activity whereas thiophene substituted compound (7j) shows promising antibacterial activity.     

Improvement of Ratio-Type Estimators-II

This paper generalizes the results of AGARWAL (1980) and AGARWAL and KUMAR (1985) by constructing a multivariate ratiotype estimator which, to a first order of approximation, is as efficient as the regression estimator.     

Recanalization of chronic total coronary occlusions: the impact of a new specific guidewire on primary success rate

BACKGROUND: Although chronic total occlusions are encountered frequently in patients with coronary artery disease, an effective strategy to deal with them has yet to be devised. Various new guidewires have been designed in an attempt to negotiate chronic occlusions successfully. The authors have analysed the impact of the Athlete guidewire on procedural success in this lesion subset. METHODS: Sixty-two consecutive patients undergoing percutaneous intervention for chronic total occlusions over a two-year period were retrospectively studied. For the initial attempt, conventional guidewires were used. In case of failure, further attempts were made using the Athlete guidewire. Procedural success rates with the use of conventional and Athlete guidewires were assessed. RESULTS: Failure of the first attempt with the conventional guidewire occurred in 32 (51.6%) patients and success was achieved in 30 (48.4%) patients. In the former patients, a second attempt was made using the Athlete guidewire to cross the occlusion. The second attempt was successful in 20 patients (60%) in whom the first attempt was unsuccessful, while in the remaining 12 (40%) patients the occlusion could not be crossed even during the second attempt and the procedure was then terminated. Following the use of the Athlete guidewire, the success rate increased to 62% (p < 0.001). No complication occurred during the first attempt, while one patient had a coronary perforation using the Athlete guidewire, which was managed successfully without the need for bypass surgery. CONCLUSION: The use of the Athlete guidewire is feasible and safe, and enhances the chances of successfully treating chronic total occlusions during percutaneous coronary revascularization procedures.