Numerical Model to Predict Hemolysis and Transport in a Membrane-Based Microfluidic Device

Microfluidics has become an increasingly popular tool in the design and development of medical devices and artificial organs. Two promising applications of microfluidics are dialyzers and oxygenators. As a step toward portable dialysis treatment, continuous microfluidic dialysis may resolve many clinical issues with current dialysis treatments. Additionally, commercially available oxygenators exceed the blood volume of neonatal patients; low-volume microfluidic devices may safely deliver oxygen to these patients. Two critical parameters in the development of these devices is mechanical hemolysis and membrane diffusion, which are intricately connected to the geometry, flow rate, properties of the membrane, and each other. A computational model is developed to elucidate the connection between these phenomena to guide the design and optimization of these devices. In vitro experiments are conducted to validate the model. Importantly, a subset of hemolysis models agrees with experimental data, which is consistent with the literature. Additionally, the effect of microfluidic mixing elements that perturb flow near the membrane interface are studied in silico and in vitro. These data reveal that herringbone mixing elements increase hemolysis by 10% and flux across the membrane interface by 38% in silico and a statistically significant difference between smooth and herringbone devices is observed for a subset of devices tested. Furthermore, 10 of 18 computational models of hemolysis are shown to be statistically similar to experimental data. The agreement of these results suggest that finite element analysis may be able to quantitively model important factors in the design of microfluidic oxygenators and dialyzers

Retrorectal tumours: literature review and Vilnius University Hospital "Santariskiu klinikos" experience of 14 cases

<p>Abstract</p> <p>Objective</p> <p>Retrorectal tumours are rare lesions in adults. The diagnosis of retrorectal lesion is often difficult and misdiagnosis is common. We present significant number of cases in view of scarce information available on this matter.</p> <p>Methods</p> <p>14 patients were treated at Vilnius university hospital "Santariskiu klinikos" Centre of abdominal surgery from 1997 to 2010. The case notes of patients who underwent surgery for a retrorectal tumour were reviewed retrospectively. Surgical histories, operations, histological tumour type, surgical time, weight of the specimen, blood loss, length of stay were analysed.</p> <p>Results</p> <p>13 patients underwent laparotomy, 1 patient had combined perineal approach and laparotomy. The most common types of the tumour were fibroma (3 cases), leiomyosarcoma (2 cases). 5 tumours (35,7%) were found to be malignant. 57% of the patients had undergone at least one operation prior to definitive treatment. 5 female patients were initially admitted under gynaecologists. Hospital stay varied from 14 days to 22 days (mean 16,2 days). A report of a representative case is presented.</p> <p>Conclusions</p> <p>Retrorectal lesions in female patients can mimic gynaecological pathology. Patients with this rare pathology are to be treated in a major tertiary hospital by surgeons, who are able to operate safely in the retrorectal space.</p

Structural health monitoring of non-linear hysteretic structures.

Ensuring life safety is the primary design and maintenance requirement for civil structures designed to be serviceable for a specific lifetime. However, structures subjected to a number of factors may experience quicker or more gradual deterioration than anticipated, or even a premature loss of function. Scheduled visual inspection is the oldest and most commonly used damage monitoring technique, but has significant disadvantages when quick damage assessment and certainty are needed, such as after a major seismic event. Quick, accurate and quantitative determination of the damage state is vital following an earthquake, to estimate damage, remaining life-time, and ensure safe re-occupancy, if possible. Rapid development of sensor technology and increasing computing power has enabled continuous structural monitoring using various sensing techniques. The measured data can be analyzed using structural health monitoring (SHM) methods. SHM refers to all elements of the process of identifying mechanical properties of a structural system, comparing it with previous states, detecting changes/abnormalities, and relating these to damage. A successful SHM method should be able to automatically identify and locate damage after large, non-linear response events. The majority of existing, primarily vibration based, SHM techniques have serious limitations in situations where a quick, accurate, and quantitative assessment is needed. More specifically, many SHM techniques perform well when structures behave linearly and are subjected to ambient loads, but this does not apply to earthquake events. Moreover, some methods can only work off-line, involve significant computational effort and/or human input, and/or do not provide any indication of damage location and/or severity. To address these limitations, this thesis explores the application of a novel SHM implementation strategy composed of a novel modal parameter identification and its subsequent application to a proven hysteresis loop analysis (HLA) method. The study demonstrates the proposed strategy can be readily used to track the performance of non-linear degrading structures subjected to strong ground motion, essentially in real-time and without human input. Thus, the proposed tools can be used to support/replace visual inspection results, reduce downtime, minimize business disruptions and, most importantly, maximize life safety. More specifically, this thesis proposes and analyses the application of a novel modal parameter identification technique, which performs in near real-time and, most importantly, is efficient when approximating non-linear structures subjected to relatively short duration ground motion inputs. The technique operates in modal space and is based on a pre-defined optimization process, which decouples frequency response spectra of interfering, generally higher frequency, modes. Optimization can be realized over relatively short time windows to provide continuous monitoring of highly non-linear, degrading structures. In particular, identified modal parameters can be readily used to identify damage. However, modal parameters can have very poor sensitivity to damage and are often difficult to interpret. Thus, it is challenging to infer the location and severity of damage based on detected changes/variation in modal parameters alone. In this research, the identified time-varying modal parameters are used to decompose the structural response and reconstruct single mode dominant restoring force-deformation hysteresis loops, which can be readily analyzed using recently developed hysteresis loops analysis (HLA). The versatility and robustness of HLA has been explored in a number of studies. However, the analyzed case structures employed in these validation cases exhibited very small contribution from the higher modes, which typically can cause significant irregularities, and make effective implementation of HLA more problematic. Hence, this thesis aims to improve the robustness of HLA, using mode segregation and reconstruction of single mode dominant, regular shape hysteresis loops from non-linear structural response. First, this research develops a modal parameter output-only identification technique, which is validated for a simple time-invariant linear structure. Second, the output-only method is extended to an input-output method enabling operators to carry out near-real time identification of non-linear structures, which is validated for a simple time-varying non-linear structure. Third, the input-output method is validated using the simulation results of a more complex non-linear multi-degree-of-freedom structure, formulated using fiber elements. Finally, the proposed SHM strategy, consisting of continuous modal parameter identification and subsequent application of HLA is validated for two experimental non-linear structures. Overall, this thesis proposes a novel system identification technique, which performs outputonly identification of linear structures and, more importantly, provides input-output real-time modal parameter tracking of highly non-linear structures. Thus, the method extends the application of modal SHM methods to non-linear cases. The proposed technique performs successfully without operator input and can be easily automated to provide continuous modal tracking and damage detection. The technique performs both as stand-alone for damage detection and in combination with HLA for damage quantification as demonstrated for highly non-linear cases

Locus of control and expectation of control in EMG biofeedback

This study examined the importance of cognitions in the feelings of self-control on task performance and on certain subjective states, via electromyographic (EMG) biofeedback training. Subjects in a "misled” EMG feedback group were led to believe that they had successfully reduced their EMG levels (induced cognition of self control); in actuality, the subjects in the misled group were yoked to subjects receiving feedback contingent oii their ovv'n EMG levels; thus, the feedback received by the misled group ’vvas that of their contingent EMG feedback counterparts. The effects of this treatment v/ere explored in relation to feelings of self control via Rotter's I-E scale, EMG task performance during two training trials, state-trait anxiety levels via the 3tate-Tra.it Anxiety Inventory (STAI), and other subjective states via some self-report questionnaires. These data were compared to those of the EMG group receiving feedback contingent on their own EMG levels and to a control group which was also yoked to the contingent feedback group, but who were informed that this was the case

Prokaryotic expression and characterization of the heterodimeric construction of ZnT8 and its application for autoantibodies detection in diabetes mellitus

Background: In the present work we described the recombinant production and characterization of heterodimeric construction ZnT8-Arg-Trp325 fused to thioredoxin using a high-performance expression system such as Escherichia coli. In addition, we apply this novel recombinant antigen in a non-radiometric method, with high sensitivity, low operational complexity and lower costs. Results: ZnT8 was expressed in E. coli as a fusion protein with thioredoxin (TrxZnT8). After 3 h for induction, recombinant protein was obtained from the intracellular soluble fraction and from inclusion bodies and purified by affinity chromatography. The expression and purification steps, analyzed by SDS-PAGE and western blot, revealed a band compatible with TrxZnT8 expected theoretical molecular weight (≈ 36.8 kDa). The immunochemical ability of TrxZnT8 to compete with [35S]ZnT8 (synthesized with rabbit reticulocyte lysate system) was assessed qualitatively by incubating ZnT8A positive patient sera in the presence of 0.2-0.3 μM TrxZnT8. Results were expressed as standard deviation scores (SDs). All sera became virtually negative under antigen excess (19.26-1.29 for TrxZnT8). Also, radiometric quantitative competition assays with ZnT8A positive patient sera were performed by adding TrxZnT8 (37.0 pM-2.2 μM), using [35S]ZnT8. All dose-response curves showed similar protein concentration that caused 50% inhibition (14.9-0.15 nM for TrxZnT8). On the other hand, preincubated bridge ELISA for ZnT8A detection was developed. This assay showed 51.7% of sensitivity and 97.1% of specificity. Conclusions: It was possible to obtain with high-yield purified heterodimeric construction of ZnT8 in E. coli and it was applied in cost-effective immunoassay for ZnT8A detection.Fil: Faccinetti, Natalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Guerra, Luciano Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Sabljic, Adriana Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Bombicino, Silvina Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Rovitto, Bruno David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Iacono, Ruben Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Trabucchi, Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Valdez, Silvina Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentin

X-ray structure of the mature ectodomain of phogrin

Phogrin/IA-2β and ICA512/IA-2 are two paralogs receptor-type protein-tyrosine phosphatases (RPTP) that localize in secretory granules of various neuroendocrine cells. In pancreatic islet β-cells, they participate in the regulation of insulin secretion, ensuring proper granulogenesis, and β-cell proliferation. The role of their cytoplasmic tail has been partially unveiled, while that of their luminal region remains unclear. To advance the understanding of its structure-function relationship, the X-ray structure of the mature ectodomain of phogrin (ME phogrin) at pH 7.4 and 4.6 has been solved at 1.95- and 2.01-Å resolution, respectively. Similarly to the ME of ICA512, ME phogrin adopts a ferredoxin-like fold: a sheet of four antiparallel β-strands packed against two α-helices. Sequence conservation among vertebrates, plants and insects suggests that the structural similarity extends to all the receptor family. Crystallized ME phogrin is monomeric, in agreement with solution studies but in striking contrast with the behavior of homodimeric ME ICA512. The structural details that may cause the quaternary structure differences are analyzed. The results provide a basis for building models of the overall orientation and oligomerization state of the receptor in biological membranes

influence of the light-activation mode

This study analyzed the relationship between the degree of conversion (DC), solubility, and salivary sorption of a hybrid (Filtek P 60) and a nanofilled resin composite (Filtek Supreme), and evaluated the influence of the light-activation mode on these properties. Two light-activation modes were used: Conventional (C; 850 mW/cm² for 20 s) and Soft-start (SS; 100-1,000 mW/cm² for 10 s + 1,000 mW/cm² for 10 s). The DC (%) was evaluated by FT-Raman spectroscopy. The solubility and salivary sorption were measured after immersion in artificial saliva for 7 days. Data were analyzed by ANOVA and Student-Newman-Keuls' test and linear regression analysis (a = 0.05). The DC varied from 50.52% (nanofilled composite) to 57.15% (hybrid composite), and was influenced by the light-activation mode: C >; SS. The solubility (0.45 mg/mm³) and salivary sorption (8.04 mg/mm³) of the nanofilled composite were greater than those of the hybrid composite (0.40 mg/mm³ / 6.87 mg/mm³), and were influenced by the light-activation mode: SS >; C. Correlation was found between DC and solubility (r = - 0.89,

Profundidade de polimerização de compósitos restauradores submetidos a diferentes métodos de fotoativação

OBJECTIVE: This study evaluated the depth of cure of five dental composites submitted to different light-curing modes. MATERIAL AND METHODS: Canal-shaped cavities with 5mm of length were prepared on the buccal surfaces of extracted third molars, and restored using P-60, A-110, Admira, Z-250 and Supreme resin composites. Materials were light-cured from the top, according to three modes (Group 1- Conventional (C): 500 mW/cm² / 40 s; Group 2 - Soft-Start (SS): 250 mW/cm²/ 20 s + 500 mW/cm²/ 20 s + 500 mW/cm²/ 10 s and Group 3 - LED: 250 mW/cm²/ 40 s). After that, cavity longitudinal surfaces were polished and marked with a millimeter scale of 4mm of length. Depth of cure was evaluated by means of Knoop hardness number (KHN), so that five indentations were performed at each millimeter. Original data were submitted to three-way ANOVA and Fisher's LSD test (alpha = 0.01). RESULTS: All materials presented a significant reduction on KHN from first to third millimeter. Regarding depth of cure, the results obtained for Conventional and Soft-Start modes were similar, but statistically superiors to those found for group 3 (LED). CONCLUSION: This performance may be related to the differences among energy densities obtained with different light-curing modes.OBJETVO: Este estudo avaliou a profundidade de polimerização de cinco compósitos fotopolimerizáveis submetidos a diferentes métodos de fotoativação. MATERIAL E MÉTODO: Cavidades em forma de canaleta com 5 mm de comprimento, preparadas nas faces vestibulares de terceiros molares, foram restauradas com os compósitos P-60, A-110, Admira, Z-250 e Supreme. Os materiais foram fotoativados pelo topo das cavidades com três técnicas (Grupo 1 - Convencional (C): 500 mW / cm² / 40 s; Grupo 2 - Soft-Start (SS): 250 mW / cm² / 20 s + 500 mW / cm² / 20 s + 500 mW / cm² / 10 s e Grupo 3 - LED: 250 mW / cm² / 40 s). Após a fotoativação, as superfícies longitudinais dos materiais foram polidas e marcadas com uma escala milimetrada com 4 mm de comprimento. A profundidade de polimerização foi avaliada através do número de dureza Knoop (NDK), com cinco indentações a cada milímetro. Os dados originais foram submetidos à Análise de Variância de três fatores e teste de Fisher para comparações entre médias (alfa = 0,01). RESULTADOS: Todos os materiais apresentaram diminuição do NDK do primeiro para o terceiro milímetro (p < 0,01). Os resultados obtidos com os Grupos Convencional e Soft-Start foram similares e superiores ao Grupo LED (p < 0,01). CONCLUSÃO: Este desempenho pode ser relacionado às diferenças nas densidades de energia obtidas com os métodos de fotoativação utilizados