Sequence-Specific Gene Correction of Cystic Fibrosis Airway Basal Cells

Cystic fibrosis (CF) is a lethal monogenic disease resulting from mutations in the CFTR gene which encodes a protein involved in regulating anion trans-epithelial transport. A three-base deletion in CFTR (termed as ΔF508 mutation), wherein CFTR protein is misfolded leading to its pre-mature degradation in the endoplasmic reticulum (ER), is the most common cause of this debilitating disease. Since CFTR is expressed in multiple body systems, CF affects different organs, but lung pathology is the greatest cause of death in affected patients. We achieved site-specific gene correction with an efficiency of ~10 % in CF airway basal cells homozygous for the ΔF508 mutation. Basal cells are a multipotent stem cell population of the respiratory epithelium and therefore, their gene correction could provide a long-term, permanent remedy for CF. Delivery of engineered sequence-specific zinc finger nucleases (ZFNs) and single-stranded oligo DNA (ssODN) carrying the correcting sequence via electroporation facilitated the correction. The gene-corrected cells upon in vitro differentiation using air-liquid interface showed presence of fully-glycosylated mature CFTR protein as opposed to differentiated mutant cells which synthesized only the core-glycosylated immature form. Most importantly, we demonstrated CFTR ion channel activity in the gene-corrected cells by Ussing chamber electrophysiology

East African hydroclimatic variability: 1950-1999

The interannual variability in precipitation over East Africa is well-understood. Many studies have identified the factors influencing the interannual variability of precipitation such as El Niño – Southern Oscillation (ENSO), the Indian Ocean Dipole Mode (IODM), and Atlantic Ocean sea surface temperature and pressure variations. The relatively arid conditions in much of the East African region are not understood fully. The objective of present study is to determine the meteorological association of aridity over East Africa with regional hydroclimatic variables as well as to find global teleconnections affecting spatial distribution of aridity over East Africa. The East Africa Aridity index is calculated as the ratio of the mean seasonal precipitation to the mean seasonal potential evapotranspiration (after Budyko, 1974), and is used as a measure of aridity over East Africa. Principal components analysis was performed on the aridity index to identify characteristic modes of the temporal variability of the aridity index across East Africa. Correlation analysis was performed to identify the meteorological association in the interannual variability of aridity over East Africa and to find the global teleconnections, such as with ENSO, IODM, North Atlantic Oscillations (NAO), Tropical Atlantic SST Dipole (TASD), and Quasi Biennial Oscillations (QBO) in it. The first principal component of the aridity index was used for the correlation analysis. Correlations of the normalized difference vegetation index (NDVI) and Palmer Drought Severity Index (PDSI) with the first principal component of aridity index were calculated. The aridity index over East Africa is driven by precipitation rather than potential evapotranspiration (PET). The PET over East Africa is driven by precipitation rather than temperature. Aridity over East Africa is well correlated with the NDVI and PDSI. The ENSO influence on interannual variability of precipitation and hence on aridity is very much evident in all the seasons, while IODM influence is evident in the June – September season, the driest season for East Africa. Influence of NAO, TASD, and QBO was observed to be very small compared to that of ENSO and IODM. The teleconnections influencing the rainfall variability of East Africa also influenced variability in aridity

A Review of Security Mechanisms for Detection of Malicious Transactions in Database

Insider attacks formed the biggest threaten against database management systems. There are many mechanisms have been developed to detect and prevent the insider attacks called Detection of Malicious Activities in Database Systems DEMIDS. The DEMIDS consider as one of the last defenses mechanism of the database security system. There are many mechanisms that have been developed to detect and prevent the misuse activities like delete, and update data on the database systems. These mechanisms utilize auditing and profiling methods to detect and prevent the malicious activities. However these mechanisms still have problems to detect the misuse activities such as limit to detect the malicious data on authorized commands. This study will address these problems by propose a mechanism that utilizes dependency relationship among items to detect and prevent the malicious data by calculate a number of relations among data items. If the number of relations among items is not allowed any modification or deletion then the mechanism will detect activity as malicious activity. The evaluation parameters such as detect, false positive and false negative rate use to evaluate the accuracy of proposed mechanism

Engineering Ionomer Materials for Addressing Ohmic Resistances in Electrochemical Desalination and Waste Heat Recovery

Water scarcity and energy availability present important challenges that need to be addressed in the coming centuries. In the front of water technologies, desalting brackish water is of extreme importance for thermal electric power plants, chemical manufacturing plants, and other industrial operations that treat and reuse their water utilities. Membrane capacitive deionization (MCDI) is an energy efficient desalination technique that has drawn attention from commercial entities. Most material research studies on MCDI focus on enhancing electrode performance while little emphasis is given to rationale design of ion-exchange membranes (IEMs). In this work, the ionic conductivity, permselectivity, and thickness for three different IEM chemistries (polyaliphatic, poly (arylene ether), and perfluorinated) were correlated to MCDI performance attributes. A 5-10-fold reduction in area specific resistance (ASR), with unconventional perfluorinated and poly (arylene ether) IEMs reduced the energy expended per ion removed in MCDI by a factor of two, compared to conventional electrodialysis IEMs. For further advancement in energy efficiency of operation, ohmic resistance of the spacer channel needs to be addressed for which, ion-exchange resins bound by a polymeric binder termed resin wafers were explored. A new class of ion-exchange resin wafers (RWs) fabricated with ion-conductive binders were developed that exhibit exceptional ionic conductivities - a 3-5-fold improvement over conventional RWs containing a non-ionic polyethylene binder. Incorporation into a resin-wafer electrodeionization stack (RW-EDI) resulted in an increased desalination rate and reduced energy expenditure. Overall, this work demonstrates that ohmic resistances can be substantially curtailed with ionomer binder RWs at dilute salt concentrations. With respect to energy, thermally regenerative ammonia flow batteries (TRBs) are an emerging platform for extracting electrical energy from low-grade waste heat (T \u3c 130 °C). Previous TRB demonstrations suffered from poor heat to electrical energy conversion efficiency when benchmarked against state-of-the-art thermoelectric generators. This work reports the highest power density to date for a TRB (280 W m-2 at 55 °C) with a 5.7× improvement in power density over conventional designs and thermal efficiency (ηth) values as high as 2.99 % and 37.9 % relative to the Carnot efficiency (ηth/C). The gains made in TRB performance was ascribed to the zero gap design and deploying a low-resistant, inexpensive anion exchange membrane (AEM) separator and implementing a copper ion selective ionomer coating on the copper mesh electrodes. The improved TRB power density and the use of a low-cost materials represent significant milestones in low-grade waste heat recovery using electrochemical platforms

Patriarchy and the Power of Myth: Exploring the Significance of a Matriarchal Prehistory

Senior Project submitted to The Division of Social Studies of Bard College

Fuzzy clustering and fuzzy c-means partition cluster analysis and validation studies on a subset of citescore dataset

A hard partition clustering algorithm assigns equally distant points to one of the clusters, where each datum has the probability to appear in simultaneous assignment to further clusters. The fuzzy cluster analysis assigns membership coefficients of data points which are equidistant between two clusters so the information directs have a place toward in excess of one cluster in the meantime. For a subset of CiteScore dataset, fuzzy clustering (fanny) and fuzzy c-means (fcm) algorithms were implemented to study the data points that lie equally distant from each other. Before analysis, clusterability of the dataset was evaluated with Hopkins statistic which resulted in 0.4371, a value < 0.5, indicating that the data is highly clusterable. The optimal clusters were determined using NbClust package, where it is evidenced that 9 various indices proposed 3 cluster solutions as best clusters. Further, appropriate value of fuzziness parameter m was evaluated to determine the distribution of membership values with variation in m from 1 to 2. Coefficient of variation (CV), also known as relative variability was evaluated to study the spread of data. The time complexity of fuzzy clustering (fanny) and fuzzy c-means algorithms were evaluated by keeping data points constant and varying number of clusters

QUANTIFYING VULNERABILITY OF PENINSULAR MALAYSIA’S TIGER LANDSCAPE TO FUTURE FOREST LOSS

Agricultural expansion has been the dominant driver of tropical deforestation and increased consumption of commodities and resulting global trade have become distal drivers of land cover change. Habitat loss and fragmentation threaten biodiversity globally. Peninsular Malaysia, particularly, has a long history of land cover land use change and expansion of plantations like those of oil palm (Elaeis guineensis). Deforestation and plantation expansion threaten the Malayan tiger (Panthera tigris jacksonii), a critically endangered subspecies of the tiger endemic to the Malay Peninsula. Conservation of tigers and their long-term viability requires not only the protection of habitat patches but also maintenance of corridors connecting habitat patches. The goal of this dissertation was to understand patterns of recent forest loss and conversions, determine the drivers of these changes, and model future forest loss and changes to landscape connectivity for tigers. Satellite remote sensing data were used to map and estimate the extent of forest loss and forest conversions to plantations within Peninsular Malaysia. Mapped forest conversions to industrial oil palm plantations were used to model the factors influencing such conversions and the constraints to recent and future conversions. Finally, the mapped forest loss was used to model the deforestation probability for the region and develop scenarios of future forest loss. This study indicates that despite the history of land cover change and an extensive area under plantations, natural forest loss has continued within Peninsular Malaysia with about half of the cleared forests being converted to plantations. Proximity to pre-existing oil palm plantations is the most important determinant of forest conversions to oil palm. Such conversions are increasingly in more marginal lands indicating that biophysical suitability alone cannot determine where future conversions might take place. Forest conversions to oil palm plantations within the region are more constrained by accessibility to infrastructure rather than biophysical suitability for oil palm. The projected patterns of loss indicate lowland forests along the southeastern coast and in the center of the Peninsula are most vulnerable to future loss. This projected loss will likely reduce the connectivity between forest patches further isolating tiger populations in the southern part of the Peninsula. This study demonstrates the continued pressure on Peninsular Malaysia’s forests, the potential impact of persistent deforestation on forest connectivity, and draws attention to the need for conservation and restoration of forest linkages to ensure viability of the remaining Malayan tiger population

On Gosper's Pi(q) and Lambert series identities

In an interesting article entitled `Experiments and discoveries in q-trigonometry'', R. W. Gosper conjectured few beautiful Pi(q) and Lambert series identities. Many people have attempted confirming some of those identities in the Gosper's list, mainly by using Gosper's q-trigonometric identities. In this paper we either prove or disprove all the Pi(q) and Lambert series identities in the Gosper's list by mainly using S. Ramanujan's theta function identities and W. N. Bailey's summation formula. In the process, we obtain three new Gosper kind of identities