The granulocytic inducer C/EBPalpha inactivates the myeloid master regulator PU.1

Verschiedene Transkriptionsfaktoren spielen eine Rolle in der Entwicklung myeloischer Zellen. PU.1, ein Transkriptionsfaktor aus der ETS-Familie, ist sowohl für die Entwicklung lymphatischer als auch für die Entwicklung myeloischer Zellen von Bedeutung. Der Transkriptions faktor C/EBPalpha, ein an den CCAAT-Enhancer bindendes Protein, ist hingegen wesentlich verantwortlich für die Entwicklung von Granulozyten. Wir stellen hier den ersten Nachweis dafür vor, dass C/EBPalpha die Funktion von PU.1 blockiert. PU.1 und C/EBPalpha können einander binden und sind in myeloischen Zellen kolokalisiert. Wenn C/EBPalpha PU.1 bindet, kann PU.1 einen minimalen Promotor mit Bindungsstelle für PU.1 nicht mehr aktivieren. Wir zeigen, dass der Leuzin-Zipper in der DNA-bindenden Domäne von C/EBPalpha mit der beta3/beta4-Region in der DNA-bindenden Domäne von PU.1 interagieren kann. Dadurch wird der Koaktivator von PU.1, c-jun, aus seiner Bindung mit PU.1 verdrängt. C/EBPalpha hemmt PU.1 nicht, indem es Korepressoren rekrutiert. Vielmehr vermindert C/EBPalpha die Expression von PU.1 in U-937-Zellen mit induzierbarem C/EBPalpha, indem es den autoregulatorischen Effekt PU.1 auf den PU.1-Promotor hemmt. Ausserdem blockiert C/EBPalpha die durch PU.1 bedingte Entwicklung dendritischer Zellen aus CD34+ menschlichen Nabel blutzellen. Diese funktionelle Blockade von PU.1 durch C/EBPalpha könnte einer der Mechanismen sein, mit denen C/EBPalpha den durch PU.1 determinierten Weg der Zelldifferenzierung hemmt und sich Zellen unter dem Einfluss von C/EBPalpha zu Granulozyten entwickeln.Several transcription factors have been shown to play a role in myelopoiesis. PU.1, an ets-family transcription factor, is required for the development of both myeloid and lymphoid lineages while the transcription factor CCAAT/enhancer binding protein family member C/EBPalpha is essential for granulocytic development. We present here the first evidence that C/EBPalpha blocks the function of PU.1. PU.1 and C/EBPalpha interact physically and co-localize in myeloid cells. As a consequence of this interaction C/EBPalpha can inhibit the function of PU.1 to activate a minimal promoter containing only PU.1 DNA binding sites. We further demonstrate that the leucine zipper in the DNA binding domain of C/EBPalpha interacts with the beta3/beta4 region in the DNA binding domain of PU.1, and as a result displaces the PU.1 co-activator c-Jun. Finally, C/EBPalpha blocks PU.1 induced dendritic cell development from CD34+ human cord blood cells. The functional blocking of PU.1 by C/EBPalpha could be the mechanism by which C/EBPalpha inhibits the cell fates specified by PU.1, and directs cell development to the granulocytic lineage

Formal Verification of a MESI-based Cache Implementation

Cache coherency is crucial to multi-core systems with a shared memory programming model. Coherency protocols have been formally verified at the architectural level with relative ease. However, several subtle issues creep into the hardware realization of cache in a multi-processor environment. The assumption, made in the abstract model, that state transitions are atomic, is invalid for the HDL implementation. Each transition is composed of many concurrent multi-core operations. As a result, even with a blocking bus, several transient states come into existence. Most modern processors optimize communication with a split-transaction bus, this results in further transient states and race conditions. Therefore, the design and verification of cache coherency is increasingly complex and challenging. Simulation techniques are insufficient to ensure memory consistency and the absence of deadlock, livelock, and starvation. At best, it is tediously complex and time consuming to reach confidence in functionality with simulation. Formal methods are ideally suited to identify the numerous race conditions and subtle failures. In this study, we perform formal property verification on the RTL of a multi-core level-1 cache design based on snooping MESI protocol. We demonstrate full-proof verification of the coherence module in JasperGold using complexity reduction techniques through parameterization. We verify that the assumptions needed to constrain inputs of the stand-alone cache coherence module are satisfied as valid assertions in the instantiation environment. We compare results obtained from formal property verification against a state-of-the-art UVM environment. We highlight the benefits of a synergistic collaboration between simulation and formal techniques. We present formal analysis as a generic toolkit with numerous usage models in the digital design process

Advancing Pharmaceutical Dry Milling by Process Analytics and Robustness Testing

The objectives of this work were to implement on-line dynamic image analysis and to introduce a novel at-line flowability analyzer in pharmaceutical dry milling. We used a pilot-scale conical mill and flowability of a placebo granulate was monitored using a powder avalanching analyzer. Experiments were designed and evaluated by means of response surface methodology in conjunction with robustness testing. The process parameters impeller speed and screen size significantly affected the particle size distribution and flow rate of the milled granules. Feeder speed did not affect the particle size, but displayed a statistically significant influence on the flow responses. Robustness testing was able to capture the effect of noise factors on the responses and showed clear differences between different lots of the placebo granulate in addition to temperature-dependent changes in flow behavior. Thus, on-line dynamic image analysis and at-line flowability characterization, together as complementary process analytical tools, provided valuable information. The combined analysis was of particular interest for testing the process and noise factors so that future process development can profit from this advancement in dry millin

Efficient design and implementation of image processing algorithms on reconfigurable hardware using Handel-C

Computer manipulation of images is generally defined as Digital Image Processing (DIP). DIP is used in variety of applications, including video surveillance, target recognition, and image enhancement. These applications are usually implemented in software but may use special purpose hardware for speed. With advances in the VLSI technology hardware implementation has become an attractive alternative. Assigning complex computation tasks to hardware and exploiting the parallelism and pipelining in algorithms yield significant speedup in running times. In this thesis the image processing algorithms like median filter, basic morphological operators, convolution and edge detection algorithms are implemented on FPGA. A pipelined architecture of these algorithms is presented. The proposed architectures are capable of producing one output on every clock cycle. The hardware modeling was accomplished using Handel-C (DK2 environment). The algorithm was tested on standard image processing benchmarks and the results are compared with that obtained on software

STUDY OF ANTIMICROBIAL, ANALGESIC AND ANTICONVULSANT ACTIVITY OF NOVEL ISATIN DERIVATIVES

Isatin is an endogenous compound and possess a wide variety of biological activities. In the present investigation, a different isatin derivatives suchas novel isatin 3-[N-(4-substituted)-hydrazinyl-3-oxo prop 1-en-2yl) benzamides and their antimicrobial, analgesic and anticonvulsant activity wasevaluated in different animal models. Antimicrobial activity by cup plate agar diffusion method. The analgesic activity was measured by Eddy's hotplate method, and reaction time was recorded when the animals licked their for and hind paws and jumped at before 0 hr, 0.5 hr, 1 hr and 2 hrsafter administration of test drugs. 4-aminopyridine chemical induction method was employed for anticonvulsant activity. All the compounds werescreened, among the screened compounds some compounds showed antimicrobial, analgesic and anticonvulsant activity with dose-dependent effectwhen compared with the control group.Keywords: Isatin, Antibacterial, Antifungal, Analgesic, Anticonvulsant activity

A 2D across-the-channel model of a polymer electrolyte membrane fuel cell : water transport and power consumption in the membrane

The anisotropic mass transport issues inside a fuel cell membrane have been studied in this thesis using computer modelling. The polymer electrolyte membrane (PEM) conductivity of a PEM fuel cell (PEMFC) depends on the hydration state of the hydrophilic charged sites distributed in the pores of the membrane. Water humidification of these charged sites is crucial for sustaining the membrane conductivity and reducing concerning voltage losses of the cell. During the operation of a PEMFC, the transport of humidified inlet gases (fuel/oxidant) is influenced by external design factors such as flow field plate geometry of the gas circulating channels. As a result, there arises a distribution in the mass transport of water inside the membrane electrode assembly. A two-dimensional, cross-the-channel, fuel cell membrane layer mass transport model, developed in this work, helps the study of the impact of factors causing the distribution in the membrane ionic conductivity on ohmic losses.The governing equations of the membrane mathematical model stem from the multicomponent framework of concentrated solution theory. All mass transport driving forces within the vapour and/or liquid equilibrated phases have been accounted in this research. A computational model, based on the finite control volume method, has been implemented using a line-by-line approach for solving the dependent variables of the mass transport equations in the two-dimensional membrane domain. The required boundary conditions for performing the anisotropic mass transport analysis have been obtained from a detailed agglomerate model of the cathode catalyst layer available in the literature.The results obtained using boundary conditions with various flow field plate channel-land configurations revealed that the anisotropic water transport in the cathode half-cell severely affects the ohmic losses within the membrane. A partially humidified vapour equilibrated membrane simulation results show that a smaller channel-land ratio (1:1) sustains a better membrane performance compared to that with a larger one (2:1 or 4:1). Resistance calculations using the computer model revealed that ohmic losses across the membrane also depend on its physical parameters such as thickness. It was observed that the resistance offered by a thinner membrane towards vapour phase mass transport is comparatively lower than that offered by a thicker membrane. A further analysis accounting the practical aspects such as membrane swelling constraints, imposed by design limitations of a fuel cell, revealed that the membrane water content and ionic conductivity are altered with an increase in the compression constraint effects acting upon a free swelling membrane

An Experience at a Tertiary Level Hospital NRC in Management of Severe Acute Malnutrition in Children Aged between 6-59 Months Adopting World Health Organization Recommendations

Objectives: To study the outcome indicators of a nutritional rehabilitation center and to assess its performance.Design: Retrospective case study.Period: One year period from Jan 2014 to Dec 2014.Methods: Data of 254 children aged between 6-59 months with severe acute malnutrition admitted in nutritional rehabilitation center at department of pediatrics, Gandhi hospital, was analyzed retrospectively. Identification and treatment of severe acute malnutrition was done according to world health organization recommendations.Results: The recovery rate, death rate, defaulter rate, mean (SD) weight gain & mean (SD) duration of stay in the nutritional rehabilitation center were 51.42%, 3.54%, 28.57%, 8g/kg/day, 14.2 days respectively.Conclusions: Nutritional rehabilitation centers are effective in management of severe malnutrition and also in decreasing the case fatality rates

Studies on Aspergillus oryzae Mutants for the Production of Single Cell Proteins from Deoiled Rice Bran

Ethyl methyl sulphonate was used to induce point mutation in Aspergillus oryzae (MTCC 1846). Incubation with ethyl methyl sulphonate for 1 h resulted in 98 % killing of spores. By screening the survived colonies three hypermorphs were found (Shan1, Shan2 and Shan3). These three mutants along with the A. oryzae (MTCC 1846) were used for the production of single cell proteins. They grew profusely on deoiled rice bran and produced higher percentage of protein. Among the three mutants Shan2 had higher protein content in the pH range of 3–7 and temperatures 36–45 °C, maintaining low quantities of nucleic acids. The specific growth rate of Shan2 was higher on the media containing substrates like glucose, maltose and cellulose. Shan2 had higher content of amino acids when compared with FAO standard and A. oryzae (MTCC 1846), but the amino acid content of Shan2 was approximately equal to that of soyabean meal. The comparative protein content of Shan2 and A. oryzae (MTCC 1846) was 57 and 43 %, respectively, while their nucleic acid content was 3 and 7.2 %, respectively. Protein enrichment of 18.9 % in Shan2 resulted from the cultivation on deoiled rice bran as compared to protein content of the A. oryzae (MTCC1846) indicating that Shan2 possessed good amenability for SCP production

Two Essays on the Mispricing of the S&p 500 Futures Contract

This dissertation demonstrates that mispricing of the S&P 500 futures contract can result from structural dissimilanties between the. New York Stock Exchange and the Chicago Mercantile Exchange. These related markets are linked through the agency of stock index arbitrage.Methodologies based upon the emerging science of nonlinear dynamics and system simulation are used to support this proposition. Because of the underlying deterministic (as oppo&ed to a stochastic) slant of the methodologies, it is possible to generate policy implications regarding the regulation of the financial markets. The conclusions from this dissertation can be used to support a free market regulatory stance.Business Administratio