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Coagulation factor VII (FVII) is a key enzyme of the extrinsic coagulation cascade that is predominantly produced by hepatocytes. The F7 gene mutations cause FVII deficiency with considerable molecular and phenotypic heterogeneity. We characterized the molecular alterations of the F7 gene and their corresponding mRNA transcripts in Iranian patients from eight unrelated families. The mutations were detected by polymerase chain reaction (PCR)-sequencing of all F7 gene exons, their flanking intronic sequences, as well as their corresponding cDNA fragments. Homozygous P303T, C91S and R304Q mutations were detected in patient 2, patient 5, and patient 6, respectively. Patient 7 was a compound heterozygote for S282R and H348R and patient 8 was a compound heterozygote for R304Q and IVS7+7A>G mutations. Furthermore, our investigation revealed three heterozygous individuals, patient 1 and patient 3 with the A244V mutation who were symptomatic and patient 4 with V(–39)I mutation who was also asymptomatic. The F7 mRNA expression analysis revealed that, except the transcript of V(–39)I, other mutation-harboring transcripts were expressed at detectable levels. In conclusion, this report reinforces the genetic and phenotypic heterogeneity of FVII deficiency. The findings of the mRNA study implied that decreased FVII protein activity subsequent to missense mutations does not completely reflect the degradation of mutation-harboring mRNA.

Keyhaneh Karimi, Edina Pallagi, Piroska Szabó-Révész, Ildikó Csóka, Rita Ambrus Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Szeged, Hungary Abstract: Pulmonary drug delivery of ciprofloxacin hydrochloride offers effective local antibacterial activity and convenience of easy application. Spray drying is a trustworthy technique for the production of ciprofloxacin hydrochloride microparticles. Quality by design (QbD), an up-to-date regulatory-based quality management method, was used to predict the final quality of the product. According to the QbD-based theoretical preliminary parameter ranking and priority classification, dry powder inhalation formulation tests were successfully performed in practice. When focusing on the critical parameters, the practical development was more effective and was in correlation with our previous findings. Spray drying produced spherical microparticles. The dry powder formulations prepared were examined by particle size analysis, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction, differential scanning calorimetry, and in vitro drug release and aerodynamic particle size analyses were also performed. These formulations showed an appropriate particle size ranging between 2 and 4 µm and displayed an enhanced aerosol performance with fine particle fraction up to 80%. Keywords: antibiotic, carrier-free formulation, quality by design, aerodynamic evaluation, dry powder for inhalation

Cryopreservation of cartilage has been investigated for decades and is currently an established protocol. However, the reliability and applicability of cartilage cryopreservation for the use in electromechanical reshaping (EMR) has not been studied exclusively. A system to cryopreserve large numbers of tissue specimens provides a steady source of cartilage of similar quality for experimentation at later dates. This will reduce error that may arise from different cartilage stock, and has the potential to maximize efficiency under time constraints. Our study utilizes a unique methodology to cryopreserve septal cartilage for use in EMR studies. Rabbit septal cartilage specimens were harvested and standardized to 20 x 8 x 1 mm, and placed in one of three solutions (normal saline, PBS, 10% DMSO in PBS) for four hours in a cold storage room at 4 degrees Celsius. Then, each cartilage specimen was vacuumed and sealed in an anti-frost plastic bag and stored in a freezer at -80 degrees Celsius for 1 to 3 weeks duration. EMR was performed using 2 and 6 volts for 2 minutes application time. Bend angle measurements of the cryopreserved cartilage specimens were compared to bend angles of fresh cartilage which underwent EMR using the same parameters. Results demonstrate that normal saline, phosphate buffered saline (PBS), and PBS with DMSO were effective in cryopreservation, and indicated no significant differences in bend angle measurements when compared to no cryopreservation. Our methodology to cryopreserve cartilage specimens provides a successful approach for use in conducting large-scale EMR studies. © 2010 Copyright SPIE - The International Society for Optical Engineering.

Electromechanical reshaping (EMR) of cartilage is a novel technique that has significant potential for use in facial reconstructive surgery. EMR achieves permanent shape change by initiating electrochemical redox reactions in the vicinity of stress concentrations, thereby altering mechanical properties of tissue matrix. This study reports the use of a six electrode needle-based geometric configuration to reshape cartilage. Rectangular samples (24 × 12 × 1 mm) of rabbit nasal septal cartilages were bent at a right angle in a precision-machined reshaping jig. Two parallel arrays of three platinum needle electrodes were each inserted into cartilage along the bend at 3 mm from the bend line. One array served as an anode and the other as cathode. Constant voltage at 1, 2, 4, 6, and 8 volts was applied to the arrays for 2 minutes. The specimens were then removed from the jig and rehydrated for 15 minutes in phosphate buffered saline. Following rehydration, bend angles and thicknesses were measured. Bend angle increased with increasing voltage and application time. No statistically significant bending was observed below 6 volts for 2 minutes application time. Maximum bend angle of 33 ± 8 degrees or reshaping degree of 33% was observed at 8 volts applied for 2 minutes. Current flow was small (< 0.1 A) for each case. Sample thickness was 0.9 ± 0.2 mm. ANOVA analysis showed that cartilage thickness had no significant impact on the extent of reshaping at given voltage and application time. The six needle electrode geometric configuration conforms to the voltage- and time-dependent trends predicted by previous EMR studies. In the future, the reshaping properties of other geometric configurations will be explored. © 2009 SPIE.

New methods of dietary calcium restriction to control hypocalcaemia and reproductive problems have always been the focus of research. This study was conducted to compare two new methods including two diets containing Zeolite and anionic salt with a conventional method of the low-Ca diet. Sixty periparturient cows were used through a completely randomized statistical design (CRD) with repeated measurements in time. Experimental diets were included: 1. low-Ca (Ca=0.44%), 2. anionic-Kipro (Ca=1%), 3. zeolite (Ca=0.44%). Traits were included: feed and nutrients intake, milk characteristics, plasma calcium concentration, body condition score (BCS), and incidence of reproductive problems. Feed, energy, and nutrient intake of low-Ca were higher than anionic-Kipro and zeolite groups (P≤0.01). Raw and corrected milk yield of anionic-Kipro was at maximum, but fat% and fat yield of zeolite was higher than other groups (P≤0.01). Total plasma and ionized calcium concentration at 6 and 12 hours after calving of low-Ca and zeolite diets were higher than the anionic-Kipro group (P≤0.01). BCS of zeolite and anionic-Kipro diets (2.98 and 2.95) was higher than the low-Ca diet (2.86) significantly (P≤0.01). The frequency of severe and subclinical hypocalcaemia and reproductive problems in two new proposed methods and younger cows was at least (P≤0.01). New dietary calcium limiting methods with zeolite and anionic-Kipro supplementation had good results on milk traits with better control on plasma calcium concentration and prevention of reproductive disorders and could be advised. [ABSTRACT FROM AUTHOR]

Many interesting but practically intractable problems can be reduced to that of finding the ground state of a system of interacting spins; however, finding such a ground state remains computationally difficult (1). It is believed that the ground state of some naturally occurring spin systems can be effectively attained through a process called quantum annealing (2,3). If it could be harnessed, quantum annealing might improve on known methods for solving certain types of problem (4,5). However, physical investigation of quantum annealing has been largely confined to microscopic spins in condensed-matter systems (6-12). Here we use quantum annealing to find the ground state of an artificial Ising spin system comprising an array of eight superconducting flux quantum bits with programmable spin-spin couplings. We observe a clear signature of quantum annealing, distinguishable from classical thermal annealing through the temperature dependence of the time at which the system dynamics freezes. Our implementation can be configured in situ to realize a wide variety of different spin networks, each of which can be monitored as it moves towards a low-energy configuration (13,14). This programmable artificial spin network bridges the gap between the theoretical study of ideal isolated spin networks and the experimental investigation of bulk magnetic samples. Moreover, with an increased number of spins, such a system may provide a practical physical means to implement a quantum algorithm, possibly allowing more-effective approaches to solving certain classes of hard combinatorial optimization problems., Physically interesting in their own right, systems of interacting spins also have practical importance for quantum computation (15). One widely studied example is the Ising spin model, where spins may [...]

Strawberry Anthracnose Fruit Rot (AFR) is one of the main limiting factors for strawberry production industry worldwide including Iran. Due to the restrictions associated with fungicides application across strawberry fields, their adverse effects on environment and the possible fungicides resistance development among fungal strains of the pathogen, the use of resistant cultivars is considered the most effective method for the management of this disease. In this study, reactions of 25 commercial strawberry cultivars were evaluated against the fungus Colletotrichum nymphaeae, causing strawberry AFR using fruit, leaf, and crown-based assays. According to the results of this study, the strawberry cultivars showed different reactions to the disease depending on the inoculation of their leaf, fruit, and crown with C. nymphaeae PET1 under in vivo and greenhouse conditions. However, fruit-based assay was a better indicator of AFR disease susceptibility due to nature of AFR disease caused by C. nymphaeae. Overall, ‘Blakemore’ and ‘Kurdistan’ cultivars were significantly more resistant compared with others, except ‘Aliso’, ‘Mrak’, ‘Diamant’, ‘Yallova’, ‘New Kurdistan’, ‘Mac Donance’ and ‘Ten Beauty’, respectively. On the contrary, ‘Gaviota’ cultivar was significantly the most susceptible than the rest, except ‘Camarosa’. The common commercial cultivars grown in Iran including ‘Camarosa’, ‘Paros’, ‘Pajaro’, and ‘Queen Eliza’ were categorized on the list of susceptible and highly susceptible cultivars in this study. To the best of our knowledge, this is the first study evaluating the reaction of some commercial strawberry cultivars against C. nymphaeae causing strawberry AFR. [ABSTRACT FROM AUTHOR]