A novel role for the TIR domain in association with pathogen-derived elicitors

Plant innate immunity is mediated by Resistance (R) proteins, which bear a striking resemblance to animal molecules of similar function. Tobacco N is a TIR-NB-LRR R gene that confers resistance to Tobacco mosaic virus, specifically the p50 helicase domain. An intriguing question is how plant R proteins recognize the presence of pathogen-derived Avirulence (Avr) elicitor proteins. We have used biochemical cell fraction and immunoprecipitation in addition to confocal fluorescence microscopy of living tissue to examine the association between N and p50. Surprisingly, both N and p50 are cytoplasmic and nuclear proteins, and N's nuclear localization is required for its function. We also demonstrate an in planta association between N and p50. Further, we show that N's TIR domain is critical for this association, and indeed, it alone can associate with p50. Our results differ from current models for plant innate immunity that propose detection is mediated solely through the LRR domains of these molecules. The data we present support an intricate process of pathogen elicitor recognition by R proteins involving multiple subcellular compartments and the formation of multiple protein complexes. © 2007 Burch-Smith et al

Origins of Hidden Sector Dark Matter I: Cosmology

We present a systematic cosmological study of a universe in which the visible sector is coupled, albeit very weakly, to a hidden sector comprised of its own set of particles and interactions. Assuming that dark matter (DM) resides in the hidden sector and is charged under a stabilizing symmetry shared by both sectors, we determine all possible origins of weak-scale DM allowed within this broad framework. We show that DM can arise only through a handful of mechanisms, lending particular focus to Freeze-Out and Decay and Freeze-In, as well as their variations involving late time re-annihilations of DM and DM particle anti-particle asymmetries. Much like standard Freeze-Out, where the abundance of DM depends only on the annihilation cross-section of the DM particle, these mechanisms depend only on a very small subset of physical parameters, many of which may be measured directly at the LHC. In particular, we show that each DM production mechanism is associated with a distinctive window in lifetimes and cross-sections for particles which may be produced in the near future. We evaluate prospects for employing the LHC to definitively reconstruct the origin of DM in a companion paper.Comment: 32 pages, 19 figures; v2: references added, published versio

BUCCAL DRUG DELIVERY SYSTEM : HISTORY AND RECENT DEVELOPMENTS

Abstract                   Of the various routes of drug delivery, the oral route is most ancient as well as preferred by the patient being convenient to take. However, peroral administration of drugs has short comings such as hepatic first-pass metabolism and enzymatic degradation within the GI-tract which comprehend a hindrance to the absorption of peptides and protein group of drug. The drug absorption takesplace faster as it is in contact with the absorption surface. The drug delivery system helps the drug to remain at the same place of application longer for once or twice daily dosing. For some drugs alternate way of administration results in novel methods of action as opposed to the above said procedure. The characteristics of the oral mucosa as well as physicochemical properties of the drug poses as a hindrance to the oral mucosal administration of some drugs. Commercial availability of drug is restricted, although most of the drugs are qualitatively assessed for oral transmucosal delivery. The clinical benefit produced by an oral transmucosal dosage form is good eventhough the production of this dosage form is expensive. Transmucosal products are the recent drug delivery strategies. Delivery through transmucosal benefits the absorption four times than that of skin. Considering the availability of products, only some drugs are used for oral transmucosal delivery. So new drugs have to be processed and developed inorder to meet the limited transmucosal drug delivery. Present paper intends to emphasis the importance of oral transmucosal drug delivery and also highlights on the latest advancement in the field. Â

Generalised risk-sensitive control with full and partial state observation

This paper generalises the risk-sensitive cost functional by introducing noise dependent penalties on the state and control variables. The optimal control problems for the full and partial state observation are considered. Using a change of probability measure approach, explicit closed-form solutions are found in both cases. This has resulted in a new risk-sensitive regulator and filter, which are generalisations of the well-known classical results

Six years survival on imatinib with no disease progression after diagnosis of metastatic duodenal gastrointestinal stromal tumour: a case report

Introduction: A duodenal Gastrointestinal Stromal Tumour (GIST) is a rare finding and until recently advanced disease had a poor prognosis. A PubMed search revealed no reports of more than five years survival of inoperable GIST on chemotherapy with WHO performance status zero. Case Presentation: A 68 year old female was diagnosed with unresectable GIST in the duodenum with metastasis to liver, pancreas and omentum in November 2001. She was commenced on imatinib mesylate (Glivec) chemotherapy. This case report was prepared from the medical records and radiology reports. She had good tolerance with stable disease. After six years her CT scan showed no disease progression and her WHO performance status was zero. Conclusion: This report supports the view that imatinib is a safe and effective drug in controlling disease progression in advanced metastatic GIST and plays an important role in improving the patient's quality of life

Detection of coupling misalignment by extended orbits

In this paper a ‘SpectraQuest’ demonstrator is used to introduce misalignment into a rotating machinery set-up. Depending on the coupling used in the set-up, angular and/or parallel misalignment can be brought in the rotating system. Traditionally, the data captured by accelerometers is transferred into the frequency domain in order to interpret the vibrations measured by the accelerometers. The frequency domain has proven its usefulness but even the time domain can come in handy to draw the right conclusions regarding to misalignment in a rotating set-up. Orbit plots display the integrated data captured by accelerometers, in order to display the movement of the rotating shaft. The influence of the misalignment and imbalance on these orbits will be discussed

CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS

No abstract available

Surgery corrects asynchrony of ribcage secondary to extra-thoracic tumor but leads to expiratory dysfunction during exercise

BACKGROUND: The effect of chest wall tumours on chest wall mechanics is uncertain even less is known about the effects of resection and reconstruction. Our aim is to study how chest wall mechanics are altered in chest wall sarcoma and to determine the effect of chest wall reconstruction on chest wall kinetics. CASE PRESENTATION: Using Optoelectronic Plethysmography (OEP), total and regional chest wall volumes were measured in a patient with unilateral extra-thoracic chest wall sarcoma, before and 5 months after resection and reconstruction, during quiet breathing and exercise using cycle ergometry. During quiet breathing the unilateral tumour was associated with reduced in motion of the lower rib cage and abdominal compartments on both sides of the chest as well as asynchronous motion of the contralateral lower rib cage. Surgery corrected these abnormalities in quiet breathing. But during exercise there was a reduction in the upper rib cage motion compared to pre-operative measures from 0.43+/−0.06 to 0.36 +/− 0.02 L postoperatively (p <0.05). This impairment was characterised by a significant increase in the end expiratory volume on the operated side of the chest 5 months after surgery by 6.5 +/− 0.6 and 5.7 +/− 0.7 % during 50 and 100 % exercise respectively (p <0.0001) a finding that was not replicated in the non-operated side. CONCLUSION: This physiological study demonstrates the negative effect of chest wall tumours on global chest wall mechanics during quiet breathing and exercise and shows that surgery reverses this abnormality, but only at rest

Septic cardiomyopathy

Depression of left ventricular (LV) intrinsic contractility is constant in patients with septic shock. Because most parameters of cardiac function are strongly dependent on afterload, especially in this context, the cardiac performance evaluated at the bedside reflects intrinsic contractility, but also the degree of vasoplegia. Recent advances in echocardiography have allowed better characterization of septic cardiomyopathy. It is always reversible providing the patient's recovery. Unlike classic cardiomyopathy, it is not associated with high filling pressures, for two reasons: improvement in LV compliance and associated right ventricular dysfunction. Although, it is unclear to which extent it affects prognosis, a hyperkinetic state is indicative of a profound and persistent vasoplegia associated with a high mortality rate. Preliminary data suggest that the hemodynamic response to a dobutamine challenge has a prognostic value, but large studies are required to establish whether inotropic drugs should be used to treat this septic cardiac dysfunction