Method of numerical correction of errors occasioned by delay of records during the monitoring of environmental variables of interest for animal production

Thermal and air conditions inside animal facilities change during the day due to the influence of the external environment. For statistical and geostatistical analyses to be representative, a large number of points spatially distributed in the facility area must be monitored. This work suggests that the time variation of environmental variables of interest for animal production, monitored within animal facility, can be modeled accurately from discrete-time records. The aim of this study was to develop a numerical method to correct the temporal variations of these environmental variables, transforming the data so that such observations are independent of the time spent during the measurement. The proposed method approached values recorded with time delays to those expected at the exact moment of interest, if the data were measured simultaneously at the moment at all points distributed spatially. The correction model for numerical environmental variables was validated for environmental air temperature parameter, and the values corrected by the method did not differ by Tukey's test at 5% significance of real values recorded by data loggers.

Design and characterization of large area position sensitive radiation detectors

Planar, large area, position sensitive silicon detectors are widely utilized in high energy physics research and in medical, computed tomography (CT). This thesis describes author's research work relating to development of such detector components. The key motivation and objective for the research work has been the development of novel, position sensitive detectors improving the performance of the instruments they are intended for. Silicon strip detectors are the key components of barrel-shaped tracking instruments which are typically the innermost structures of high energy physics experimental stations. Particle colliders such as the former LEP collider or present LHC produce particle collisions and the silicon strip detector based trackers locate the trajectories of particles emanating from such collisions. Medical CT has become a regular part of everyday medical care in all developed countries. CT scanning enables x-ray imaging of all parts of the human body with an outstanding structural resolution and contrast. Brain, chest and abdomen slice images with a resolution of 0.5 mm are possible and latest CT machines are able to image whole human heart between heart beats. The two application areas are presented shortly and the radiation detection properties of planar silicon detectors are discussed. Fabrication methods and preamplifier electronics of the planar detectors are presented. Designs of the developed, large area silicon detectors are presented and measurement results of the key operating parameters are discussed. Static and dynamic performance of the developed silicon strip detectors are shown to be very satisfactory for experimental physics applications. Results relating to the developed, novel CT detector chips are found to be very promising for further development and all key performance goals are met.

A rapid and sensitive diagnosis of bovine leukaemia virus infection using the nested shuttle polymerase chain reaction

Bovine leukaemia virus (BLV) is the causative agent of enzootic bovine leukosis (EBL). In Argentina, where a program to eradicate EBL has been introduced, sensitive and reliable diagnosis has attained high priority. Although the importance of the agar gel immunodiffusion test remains unchanged for routine work, an additional diagnostic technique is necessary to confirm cases of sera with equivocal results or of calves carrying maternal antibodies.Utilizing a nested shuttle polymerase chain reaction, the proviral DNA was detected from cows experimentally infected with as little as 5 ml of whole blood from BLV seropositive cows that were nonetheless normal in haematological terms. It proved to be a very sensitive technique, since it rapidly revealed the presence of the provirus, frequently at 2 weeks postinoculation and using a two-round procedure of nested PCR taking only 3 hours. Additionally, the primers used flanked a portion of the viral genome often employed to differentiate BLV type applying BamHI digestion. It is concluded that this method might offer a highly promising diagnostic tool for BLV infection.

Rapid and sensitive detection of Bordetella bronchiseptica by loop-mediated isothermal amplification (LAMP)

Bordetella bronchiseptica causes acute and chronic respiratory infections in diverse animal species and occasionally in humans. In this study, we described the establishment of a simple, sensitive and cost-efficient loop-mediated isothermal amplification (LAMP) assay for the detection of B. bronchiseptica. A set of primers towards a 235 bp region within the flagellum gene of B. bronchiseptica was designed with online software.. The specificity of the LAMP assay was examined by using 6 porcine pathogens and 100 nasal swabs collected from healthy pigs and suspect infected pigs. The results indicated that positive reactions were confirmed for all B. bronchiseptica and no cross-reactivity was observed from other non-B. bronchiseptica. In sensitivity evaluations, the technique successfully detected a serial dilutions of extracted B. bronchiseptica DNA with a detection limit of 9 copies, which was 10 times more sensitive than that of PCR. Compared with conventional PCR, the higher sensitivity of LAMP method and no need for the complex instrumentation make this LAMP assay a promising alternative for the diagnosis of B. bronchiseptica in rural areas and developing countries where there lacks of complex laboratory services.

Libyan breast cancer: Health services and biology. Diagnosis delay and prognostic value of DNA pploidy, S-phase fraction, and Ki-67 and Bcl-2 immunohistochemistry

The aim of this study was to investigate the diagnosis delay and its impact on the stage of disease. The study also evaluated a nuclear DNA content, immunohistochemical expression of Ki-67 and bcl-2, and the correlation of these biological features with the clinicopathological features and patient outcome. 200 Libyan women, diagnosed during 2008–2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. Also retrospective preclinical and clinical data were collected from medical records on a form (questionnaire) in association with the interview. Tumor material of the patients was collected and nuclear DNA content analysed using DNA image cytometry. The expression of Ki-67 and bcl-2 were assessed using immunohistochemistry (IHC). The studies described in this thesis show that the median of diagnosis time for women with breast cancer was 7.5 months and 56% of patients were diagnosed within a period longer than 6 months. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was also associated with initial breast symptom(s) that did not include a lump, old age, illiteracy, and history of benign fibrocystic disease. The patients who showed diagnosis delay had bigger tumour size (p<0.0001), positive lymph nodes (p<0.0001), and high incidence of late clinical stages (p<0.0001). Biologically, 82.7% of tumors were aneuploid and 17.3% were diploid. The median SPF of tumors was 11% while the median positivity of Ki-67 was 27.5%. High Ki-67 expression was found in 76% of patients, and high SPF values in 56% of patients. Positive bcl-2 expression was found in 62.4% of tumors. 72.2% of the bcl-2 positive samples were ER-positive. Patients who had tumor with DNA aneuploidy, high proliferative activity and negative bcl-2 expression were associated with a high grade of malignancy and short survival. The SPF value is useful cell proliferation marker in assessing prognosis, and the decision cut point of 11% for SPF in the Libyan material was clearly significant (p<0.0001). Bcl-2 is a powerful prognosticator and an independent predictor of breast cancer outcome in the Libyan material (p<0.0001). Libyan breast cancer was investigated in these studies from two different aspects: health services and biology. The results show that diagnosis delay is a very serious problem in Libya and is associated with complex interactions between many factors leading to advanced stages, and potentially to high mortality. Cytometric DNA variables, proliferative markers (Ki-67 and SPF), and oncoprotein bcl-2 negativity reflect the aggressive behavior of Libyan breast cancer and could be used with traditional factors to predict the outcome of individual patients, and to select appropriate therapy.

Control of Structures with Cubic and Quadratic Non-Linearities with Time Delay Consideration

This paper studies the effect of time delay on the active non-linear control of dynamically loaded flexible structures. The behavior of non-linear systems under state feedback control, considering a fixed time delay for the control force, is investigated. A control method based on non-linear optimal control, using a tensorial formulation and state feedback control is used. The state equations and the control forces are expressed in polynomial form and a performance index, quadratic in both state vector and control forces, is used. General polynomial representations of the non-linear control law are obtained and implemented for control algorithms up to the fifth order. This methodology is applied to systems with quadratic and cubic non-linearities. Strongly non-linear systems are tested and the effectiveness of the control system including a delay for the application of control forces is discussed. Numerical results indicate that the adopted control algorithm can be efficient for non-linear systems, chiefly in the presence of strong non-linearities but increasing time delay reduces the efficiency of the control system. Numerical results emphasize the importance of considering time delay in the project of active structural control systems.

Power semiconductor nonlinearities in active du/dt output filtering

This doctoral thesis introduces an improved control principle for active du/dt output filtering in variable-speed AC drives, together with performance comparisons with previous filtering methods. The effects of power semiconductor nonlinearities on the output filtering performance are investigated. The nonlinearities include the timing deviation and the voltage pulse waveform distortion in the variable-speed AC drive output bridge. Active du/dt output filtering (ADUDT) is a method to mitigate motor overvoltages in variable-speed AC drives with long motor cables. It is a quite recent addition to the du/dt reduction methods available. This thesis improves on the existing control method for the filter, and concentrates on the lowvoltage (below 1 kV AC) two-level voltage-source inverter implementation of the method. The ADUDT uses narrow voltage pulses having a duration in the order of a microsecond from an IGBT (insulated gate bipolar transistor) inverter to control the output voltage of a tuned LC filter circuit. The filter output voltage has thus increased slope transition times at the rising and falling edges, with an opportunity of no overshoot. The effect of the longer slope transition times is a reduction in the du/dt of the voltage fed to the motor cable. Lower du/dt values result in a reduction in the overvoltage effects on the motor terminals. Compared with traditional output filtering methods to accomplish this task, the active du/dt filtering provides lower inductance values and a smaller physical size of the filter itself. The filter circuit weight can also be reduced. However, the power semiconductor nonlinearities skew the filter control pulse pattern, resulting in control deviation. This deviation introduces unwanted overshoot and resonance in the filter. The controlmethod proposed in this thesis is able to directly compensate for the dead time-induced zero-current clamping (ZCC) effect in the pulse pattern. It gives more flexibility to the pattern structure, which could help in the timing deviation compensation design. Previous studies have shown that when a motor load current flows in the filter circuit and the inverter, the phase leg blanking times distort the voltage pulse sequence fed to the filter input. These blanking times are caused by excessively large dead time values between the IGBT control pulses. Moreover, the various switching timing distortions, present in realworld electronics when operating with a microsecond timescale, bring additional skew to the control. Left uncompensated, this results in distortion of the filter input voltage and a filter self-induced overvoltage in the form of an overshoot. This overshoot adds to the voltage appearing at the motor terminals, thus increasing the transient voltage amplitude at the motor. This doctoral thesis investigates the magnitude of such timing deviation effects. If the motor load current is left uncompensated in the control, the filter output voltage can overshoot up to double the input voltage amplitude. IGBT nonlinearities were observed to cause a smaller overshoot, in the order of 30%. This thesis introduces an improved ADUDT control method that is able to compensate for phase leg blanking times, giving flexibility to the pulse pattern structure and dead times. The control method is still sensitive to timing deviations, and their effect is investigated. A simple approach of using a fixed delay compensation value was tried in the test setup measurements. The ADUDT method with the new control algorithm was found to work in an actual motor drive application. Judging by the simulation results, with the delay compensation, the method should ultimately enable an output voltage performance and a du/dt reduction that are free from residual overshoot effects. The proposed control algorithm is not strictly required for successful ADUDT operation: It is possible to precalculate the pulse patterns by iteration and then for instance store them into a look-up table inside the control electronics. Rather, the newly developed control method is a mathematical tool for solving the ADUDT control pulses. It does not contain the timing deviation compensation (from the logic-level command to the phase leg output voltage), and as such is not able to remove the timing deviation effects that cause error and overshoot in the filter. When the timing deviation compensation has to be tuned-in in the control pattern, the precalculated iteration method could prove simpler and equally good (or even better) compared with the mathematical solution with a separate timing compensation module. One of the key findings in this thesis is the conclusion that the correctness of the pulse pattern structure, in the sense of ZCC and predicted pulse timings, cannot be separated from the timing deviations. The usefulness of the correctly calculated pattern is reduced by the voltage edge timing errors. The doctoral thesis provides an introductory background chapter on variable-speed AC drives and the problem of motor overvoltages and takes a look at traditional solutions for overvoltage mitigation. Previous results related to the active du/dt filtering are discussed. The basic operation principle and design of the filter have been studied previously. The effect of load current in the filter and the basic idea of compensation have been presented in the past. However, there was no direct way of including the dead time in the control (except for solving the pulse pattern manually by iteration), and the magnitude of nonlinearity effects had not been investigated. The enhanced control principle with the dead time handling capability and a case study of the test setup timing deviations are the main contributions of this doctoral thesis. The simulation and experimental setup results show that the proposed control method can be used in an actual drive. Loss measurements and a comparison of active du/dt output filtering with traditional output filtering methods are also presented in the work. Two different ADUDT filter designs are included, with ferrite core and air core inductors. Other filters included in the tests were a passive du/dtfilter and a passive sine filter. The loss measurements incorporated a silicon carbide diode-equipped IGBT module, and the results show lower losses with these new device technologies. The new control principle was measured in a 43 A load current motor drive system and was able to bring the filter output peak voltage from 980 V (the previous control principle) down to 680 V in a 540 V average DC link voltage variable-speed drive. A 200 m motor cable was used, and the filter losses for the active du/dt methods were 111W–126 W versus 184 W for the passive du/dt. In terms of inverter and filter losses, the active du/dt filtering method had a 1.82-fold increase in losses compared with an all-passive traditional du/dt output filter. The filter mass with the active du/dt method was 17% (2.4 kg, air-core inductors) compared with 14 kg of the passive du/dt method filter. Silicon carbide freewheeling diodes were found to reduce the inverter losses in the active du/dt filtering by 18% compared with the same IGBT module with silicon diodes. For a 200 m cable length, the average peak voltage at the motor terminals was 1050 V with no filter, 960 V for the all-passive du/dt filter, and 700 V for the active du/dt filtering applying the new control principle.

Computer programs for analysis of droplets sprayed on water sensitive papers

The use of water-sensitive papers is an important tool for assessing the quality of pesticide application on crops, but manual analysis is laborious and time-consuming. Thus, this study aimed to evaluate and compare the results obtained from four software programs for spray droplet analysis in different scanned images of water-sensitive papers. After spraying, papers with four droplet deposition patterns (varying droplet spectra and densities) were analyzed manually and by means of the following computer programs: CIR, e-Sprinkle, DepositScan and Conta-Gotas. The diameter of the volume and number medians and the number of droplets per target area were studied. There is a strong correlation between the values measured using the different programs and the manual analysis, but there is a great difference between the numerical values measured for the same paper. Thus, it is not advisable to compare results obtained from different programs.

Effect of pyloroplasty and fundectomy on the delay of gastric emptying and gastrointestinal transit of liquid elicited by acute blood volume expansion in awake rats

We evaluated the effects of fundectomy and pyloroplasty on the delay of gastric emptying (GE) and gastrointestinal (GI) transit of liquid due to blood volume (BV) expansion in awake rats. Male Wistar rats (N = 76, 180-250 g) were first submitted to fundectomy (N = 26), Heinecke-Mikulicz pyloroplasty (N = 25) or SHAM laparotomy (N = 25). After 6 days, the left external jugular vein was cannulated and the animals were fasted for 24 h with water ad libitum. The test meal was administered intragastrically (1.5 ml of a phenol red solution, 0.5 mg/ml in 5% glucose) to normovolemic control animals and to animals submitted to BV expansion (Ringer-bicarbonate, iv infusion, 1 ml/min, volume up to 5% body weight). BV expansion decreased GE and GI transit rates in SHAM laparotomized animals by 52 and 35.9% (P<0.05). Fundectomy increased GE and GI transit rates by 61.1 and 67.7% (P<0.05) and prevented the effect of expansion on GE but not on GI transit (13.9% reduction, P<0.05). Pyloroplasty also increased GE and GI transit rates by 33.9 and 44.8% (P<0.05) but did not prevent the effect of expansion on GE or GI transit (50.7 and 21.1% reduction, P<0.05). Subdiaphragmatic vagotomy blocked the effect of expansion on GE and GI transit in both SHAM laparotomized animals and animals submitted to pyloroplasty. In conclusion 1) the proximal stomach is involved in the GE delay due to BV expansion but is not essential for the establishment of a delay in GI transit, which suggests the activation of intestinal resistances, 2) pyloric modulation was not apparent, and 3) vagal pathways are involved

Acute blood volume expansion delays the gastrointestinal transit of a charcoal meal in awake rats

The present study evaluates the effect of blood volume expansion on the gastrointestinal transit of a charchoal meal (2.5 ml of an aqueous suspension consisting of 5% charcoal and 5% gum arabic) in awake male Wistar rats (200-270 g). On the day before the experiments, the rats were anesthetized with ether, submitted to left jugular vein cannulation and fasted with water ad libitum until 2 h before the gastrointestinal transit measurement. Blood volume expansion by iv infusion of 1 ml/min Ringer bicarbonate in volumes of 3, 4 or 5% body weight delayed gastrointestinal transit at 10 min after test meal administration by 21.3-26.7% (P<0.05), but no effect was observed after 1 or 2% body weight expansion. The effect of blood volume expansion (up to 5% body weight) on gastrointestinal transit lasted for at least 60 min (P<0.05). Mean arterial pressure increased transiently and central venous pressure increased and hematocrit decreased (P<0.05). Subdiaphragmatic vagotomy and yohimbine (3 mg/kg) prevented the delay caused by expansion on gastrointestinal transit, while atropine (0.5 mg/kg), L-NAME (2 mg/kg), hexamethonium (10 mg/kg), prazosin (1 mg/kg) or propranolol (2 mg/kg) were ineffective. These data show that blood volume expansion delays the gastrointestinal transit of a charcoal meal and that vagal and yohimbine-sensitive pathways appear to be involved in this phenomenon. The delay in gastrointestinal transit observed here, taken together with the modifications of gastrointestinal permeability to salt and water reported by others, may be part of the mechanisms involved in liquid excess management.

Delay in gallbladder emptying during the perimenopausal period

A pilot study has ascribed an important role in gallbladder motility and emptying to the perimenopausal period. To assess the effect of this period on gallbladder emptying and cholelithogenesis, 25 women in the perimenopausal period without gallbladder disease were submitted to cholangiography and two ultrasound exams. The time for gallbladder emptying and the presence of cholelithiasis were assessed. All patients presented a delay in gallbladder emptying with no relationship to the pre- or postmenopausal period. This finding was not related to lithogenesis. Gallbladder emptying time is longer during the perimenopausal period.

Catecholamine-induced vasoconstriction is sensitive to carbonic anhydrase I activation

We studied the relationship between alpha- and beta-adrenergic agonists and the activity of carbonic anhydrase I and II in erythrocyte, clinical and vessel studies. Kinetic studies were performed. Adrenergic agonists increased erythrocyte carbonic anhydrase as follows: adrenaline by 75%, noradrenaline by 68%, isoprenaline by 55%, and orciprenaline by 62%. The kinetic data indicated a non-competitive mechanism of action. In clinical studies carbonic anhydrase I from erythrocytes increased by 87% after noradrenaline administration, by 71% after orciprenaline and by 82% after isoprenaline. The increase in carbonic anhydrase I paralleled the increase in blood pressure. Similar results were obtained in vessel studies on piglet vascular smooth muscle. We believe that adrenergic agonists may have a dual mechanism of action: the first one consists of a catecholamine action on its receptor with the formation of a stimulus-receptor complex. The second mechanism proposed completes the first one. By this second component of the mechanism, the same stimulus directly acts on the carbonic anhydrase I isozyme (that might be functionally coupled with adrenergic receptors), so that its activation ensures an adequate pH for stimulus-receptor coupling for signal transduction into the cell, resulting in vasoconstriction.

High-dose cyclophosphamide followed by autologous peripheral blood progenitor cell transplantation improves the salvage treatment for persistent or sensitive relapsed malignant lymphoma

Trials have demonstrated that high-dose escalation followed by autologous transplantation can promote better long-term survival as salvage treatment in malignant lymphomas. The aim of the present nonrandomized clinical trial was to demonstrate the role of high-dose cyclophosphamide (HDCY) in reducing tumor burden and also to determine the effectiveness of HDCY followed by etoposide (VP-16) and methotrexate (MTX) in Hodgkin's disease plus high-dose therapy with peripheral blood progenitor cell (PBPC) transplantation as salvage treatment. From 1998 to 2000, 33 patients with a median age of 33 years (13-65) affected by aggressive non-Hodgkin's lymphoma (NHL) (60.6%) or persistent or relapsed Hodgkin's disease (39.4%) were enrolled and treated using high dose escalation (HDCY + HDVP-16 plus HDMTX in Hodgkin's disease) followed by autologous PBPC transplantation. On an "intention to treat" basis, 33 patients with malignant lymphomas were evaluated. The overall median follow-up was 400 days (40-1233). Thirty-one patients underwent autografting and received a median of 6.19 x 10(6)/kg (1.07-29.3) CD34+ cells. Patients who were chemosensitive to HDCY (N = 22) and patients who were chemoresistant (N = 11) presented an overall survival of 96 and 15%, respectively (P<0.0001). Overall survival was 92% for chemosensitive patients and 0% for patients who were still chemoresistant before transplantation (P<0.0001). Toxicity-related mortality was 12% (four patients), related to HDCY in two cases and to transplant in the other two. HDCY + HDVP-16 plus HDMTX in only Hodgkin's disease followed by autologous PBPC proved to be effective and safe as salvage treatment for chemosensitive patients affected by aggressive NHL and Hodgkin's disease, with acceptable mortality rates related to sequential treatment.

TRAP-silver staining, a highly sensitive assay for measuring telomerase activity in tumor tissue and cell lines

Measurement of telomerase activity in clinically obtained tumor samples may provide important information for use as both a diagnostic marker and a prognostic indicator for patient outcome. In order to evaluate telomerase activity in tumor tissue without radiolabeling the product, we developed a simple telomeric repeat amplification protocol-silver-staining assay that is less time-consuming, is safe and requires minimal equipment. In addition, we determined the sensitivity of the silver-staining method by using extracts of telomerase-positive thyroid carcinoma cell lines which were serially diluted from 5,000 to 10 cells. Telomerase activity was also assayed in 19 thyroid tumors, 2 normal controls and 27 bone marrow aspirates. The results indicate that the technique permits the detection of telomerase activity from 5000 to as few as 10 cells. We propose that it could be immediately applicable in many laboratories due to the minimal amount of equipment required.

Pollen mother cells of Tradescantia clone 4430 and Tradescantia pallida var. purpurea are equally sensitive to the clastogenic effects of X-rays

The Tradescantia micronucleus test is a sensitive bioassay for mutagenesis that may be employed both under field and laboratory conditions. This test has been standardized mostly on the basis of the results obtained with clone 4430. However, this clone is not well adapted to tropical weather, frequently showing problems with growth and flowering. In addition, it is attacked by parasites and insects, a fact that limits its use in field studies aiming at the biomonitoring of air pollution. In the city of São Paulo, Tradescantia pallida (Rose) Hunt. var. purpurea Boom is widely distributed as an ornamental plant in gardens and along roadsides and streets, mostly because of its natural resistance and its easy propagation. In this report, we present dose-response curves indicating that the sensitivity of T. pallida and clone 4430 to X-radiation (1, 10, 25 and 50 cGy) is similar. The results confirm our previous suggestion that T. pallida represents a good alternative for in situ mutagenesis testing in tropical regions, especially biomonitoring studies in which the exposure conditions may not be fully controllable.