Structure-mechanics relationships of collagen fibrils in the Osteogenesis Imperfecta Mouse model

The collagen molecule, which is the building block of collagen fibrils, is a triple helix of two α1(I) chains and one α2(I) chain. However, in the severe mouse model of osteogenesis imperfecta (OIM), deletion of the COL1A2 gene results in the substitution of the α2(I) chain by one α1(I) chain. As this substitution severely impairs the structure and mechanics of collagen-rich tissues at the tissue and organ level, the main aim of this study was to investigate how the structure and mechanics are altered in OIM collagen fibrils. Comparing results from atomic force microscopy imaging and cantilever-based nanoindentation on collagen fibrils from OIM and wild-type (WT) animals, we found a 33% lower indentation modulus in OIM when air-dried (bound water present) and an almost fivefold higher indentation modulus in OIM collagen fibrils when fully hydrated (bound and unbound water present) in phosphate-buffered saline solution (PBS) compared with WT collagen fibrils. These mechanical changes were accompanied by an impaired swelling upon hydration within PBS. Our experimental and atomistic simulation results show how the structure and mechanics are altered at the individual collagen fibril level as a result of collagen gene mutation in OIM. We envisage that the combination of experimental and modelling approaches could allow mechanical phenotyping at the collagen fibril level of virtually any alteration of collagen structure or chemistry.United States. Dept. of Defense. Presidential Early Career Award for Scientists and EngineersNational Science Foundation (U.S.) (CAREER Award

Considerations for the bioprocessing, manufacture and translation of extracellular vesicles for therapeutic applications

There is growing interest in the potential and use of extracellular vesicles (EVs) for a range of diagnostic and therapeutic applications. EVs have been shown, in some instances, to mediate the regenerative effects elicited by stem cell therapies. As such, they are being studied to identify the extent to which these extracellular bodies can be employed as a therapeutic entity, and significant R&D activity is underway to further understand their clinical and commercial potential. However, successful translation will first require further characterization and standardization of EV production, as well as addressing some of the major challenges associated with their reproducible manufacture. This includes the capacity to produce EVs at a scale that is both clinically and commercially effective. This article will highlight some of the bioprocessing and manufacturing considerations and challenges associated with the standardized production of EVs

The Role of Bile in the Regulation of Exocrine Pancreatic Secretion

As early as 1926 Mellanby (1) was able to show that introduction of bile into the duodenum of anesthetized cats produces a copious flow of pancreatic juice. In conscious dogs, Ivy & Lueth (2) reported, bile is only a weak stimulant of pancreatic secretion. Diversion of bile from the duodenum, however, did not influence pancreatic volume secretion stimulated by a meal (3,4). Moreover, Thomas & Crider (5) observed that bile not only failed to stimulate the secretion of pancreatic juice but also abolished the pancreatic response to intraduodenally administered peptone or soap

Changes in mediators of inflammation and pro-thrombosis after 12 months of dietary modification in adults with metabolic syndrome.

Objective: This study evaluated the effects of a 12-month dietary modification on indices of inflammation and pro-thrombosis in adults with metabolic syndrome (MS). Materials and methods: This longitudinal study involved 252 adults with MS recruited from the Bodija market, Ibadan and its environs. Participants were placed on 20%, 30% and 50% calories obtained from protein, total fat and carbohydrate respectively and were followed up monthly for 12 months. Anthropometry and blood pressure were measured using standard methods. Fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), fibrinogen, plasminogen activator inhibitor-1 (PAI-1)], interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured using spectrophotometric methods and ELISA as appropriate. Data was analysed using ANCOVA, Student\u2019s t-test, Mann-Whitney U and Wilcoxon signed-rank tests. P-values less than 0.05 were considered significant. Results: After 6 months of dietary modification, there was a significant reduction in waist circumference (WC), while the levels of HDL-C, fibrinogen and PAI-1 were significantly increased when compared with the corresponding baseline values. However, WC and fibrinogen reduced significantly, while HDL-C and IL-10 significantly increased after 12 months of dietary modification as compared with the respective baseline values. Conclusion: Long-term regular dietary modification may be beneficial in ameliorating inflammation and pro-thrombosis in metabolic syndrome

Oral maxillofacial neoplasms in an East African population a 10 year retrospective study of 1863 cases using histopathological reports

<p>Abstract</p> <p>Background</p> <p>Neoplasms of the oral maxillofacial area are an interesting entity characterized by differences in nomenclature and classification at different centers.</p> <p>We report neoplastic histopathological diagnoses seen at the departments of oral maxillofacial surgery of Muhimbili and Mulago referral hospitals in Tanzania and Uganda respectively over a 10-year period.</p> <p>Methods</p> <p>We retrieved histopathological reports archived at the departments of oral maxillofacial surgery of Muhimbili and Mulago referral hospitals in Tanzania and Uganda respectively over a 10-year period from June 1989–July 1999.</p> <p>Results</p> <p>In the period between June 1989 and July 1999, 565 and 1298 neoplastic oro-facial cases were retrieved of which 284 (50.53%) and 967 (74.54%) were malignant neoplasms at Muhimbili and Mulago hospitals respectively. Overall 67.28% of the diagnoses recorded were malignant with Kaposi's sarcoma (21.98%), Burkiits lymphoma (20.45%), and squamous cell carcinoma (15.22%) dominating that group while ameloblastoma (9.23%), fibromas (7.3%) and pleomorphic adenoma (4.95%) dominated the benign group.</p> <p>The high frequency of malignancies could be due to inclusion criteria and the clinical practice of selective histopathology investigation. However, it may also be due to higher chances of referrals in case of malignancies.</p> <p>Conclusion</p> <p>There is need to reexamine the slides in these two centers in order to bring them in line with the most recent WHO classification so as to allow for comparison with reports from else where.</p

Myofibromatosis: imaging characteristics

Background : Infantile myofibromatosis is the most common fibrous tumor of infancy. It can involve the skin, muscle, bone, and viscera. This uncommon entity is subdivided into solitary and multicentric forms, with or without visceral involvement. Objective : To describe the imaging characteristics of extracranial myofibromatosis. Materials and methods : Six infants, aged 1 day–1 week, were evaluated by imaging. All six patients had evaluation of one of the masses by US; four patients had CT evaluation of at least one of the masses; and five patients had evaluation by MRI. Results : The US appearance of the myofibromas included a mass with a purely anechoic center with a thick wall, a mass with a partially anechoic center, and a mass without anechoic components. On enhanced CT, the masses had lower or similar attenuation compared to adjacent muscle, with some masses exhibiting peripheral enhancement. The MR appearance consisted of low signal on T1-weighted imaging. On T2-weighted imaging, two had low signal of the center and the other three had high signal. All masses showed peripheral enhancement after gadolinium administration. Conclusions : Myofibromas have variable appearance on US, with a mass with an anechoic center being the most common feature. On CT, the mass can exhibit peripheral enhancement, calcifications, and erosion of adjacent bone. The MR appearance consisted of low signal on T1-weighted imaging and high or low signal of the center on T2-weighted imaging. All masses showed peripheral enhancement after gadolinium administration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46718/1/247_2004_Article_1357.pd

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques