Y-chromosomal Short Tandem Repeats have been widely used in forensic investigations, identification of males for criminal justice purpose and population genetics. Commercially available Y-STRs kits allow the identification of male pedigrees and has a limited application in forensic genetics because of its limitation in differentiating closely related male individuals. Recent research with the Rapidly Mutating Y-STRs (RM Y-STRs) have revealed that these loci deliver significantly higher discrimination capacity and haplotype diversity in worldwide populations when compared with the conventional Y-STRs. Although a number of RM Y-STRs have found their way in most updated commercial kits, there are still some loci that are not yet used in such kits. The aim of this study is to develop RM Y-STR haplotypes frequency database for the Pakistani population, in order to appraise the resolution power of these loci. A total of 212 unrelated males from the Pakistani population were typed with 13 RM Y-STRs which comprise DYF399S1, DYF387S1, DYS570, DYS576, DYS518, DYS526a + b, DYS626, DYS627, DYF403S1a + b, DYF404S1, DYS449, DYS547 and DYS612. 211 unique haplotypes were identified, out of which 1 haplotype was shared between two individuals, accounting for 0.9952 discrimination capacity (DC). Haplotype diversity was found to be 0.999925. Gene diversity (GD) values of all the loci were higher than 0.5, where the highest GD values were observed at DYF399S1, DYF403S1a and DYF404S1; with values of 0.99419, 0.98252 and 0.93061 respectively. Results of our study revealed that these 13 RM Y-STRs produced significantly stronger discriminatory power in Pakistani populations.

Special (lipid) delivery: The role of the ionizable lipid pK(a) in the in vivo delivery of siRNA by lipid nanoparticles has been studied with a large number of head group modifications to the lipids. A tight correlation between the lipid pK(a) value and silencing of the mouse FVII gene (FVII ED(50) ) was found, with an optimal pK(a) range of 6.2-6.5. The most potent cationic lipid from this study has ED(50) levels around 0.005 mg kg(-1) in mice and less than 0.03 mg kg(-1) in non-human primates.

Digital Radar Transceivers providing precise digital control over waveform amplitude, frequency and phase is critical for modern Phased Array Radar systems. A Plug-and-Play (PNP) Transceiver was developed to support the Air Force's objective to develop a Hybrid Multiple Input Multiple Output (MIMO) Phased Array Radar (HMPAR) system, where the full array is partitioned into multiple sub-arrays which can be driven by mission specific waveforms. This PNP Radar Transceiver has been integrated with the Lockheed Martin's Portable Search and Target Acquisition Radar (PSTAR) antenna array. Advanced Radar capabilities including transmit-receive digital beam-steering, direct digital L-band receiver and real-time digital signal processing with the integrated system have been successfully demonstrated. This paper discusses the overall PNP Radar Transceiver concept and highlights the successful phased-array test results when integrated with the PSTAR array.

We adopted a rational approach to design cationic lipids for use in formulations to deliver small interfering RNA (siRNA). Starting with the ionizable cationic lipid 1,2-dilinoleyloxy-3-dimethylaminopropane (DLinDMA), a key lipid component of stable nucleic acid lipid particles (SNALP) as a benchmark, we used the proposed in vivo mechanism of action of ionizable cationic lipids to guide the design of DLinDMA-based lipids with superior delivery capacity. The best-performing lipid recovered after screening (DLin-KC2-DMA) was formulated and characterized in SNALP and demonstrated to have in vivo activity at siRNA doses as low as 0.01 mg/kg in rodents and 0.1 mg/kg in nonhuman primates. To our knowledge, this represents a substantial improvement over previous reports of in vivo endogenous hepatic gene silencing.

Lipid nanoparticles (LNPs) have proven to be highly efficient carriers of short-interfering RNAs (siRNAs) to hepatocytes in vivo; however, the precise mechanism by which this efficient delivery occurs has yet to be elucidated. We found that apolipoprotein E (apoE), which plays a major role in the clearance and hepatocellular uptake of physiological lipoproteins, also acts as an endogenous targeting ligand for ionizable LNPs (iLNPs), but not cationic LNPs (cLNPs). The role of apoE was investigated using both in vitro studies employing recombinant apoE and in vivo studies in wild-type and apoE(-/-) mice. Receptor dependence was explored in vitro and in vivo using low-density lipoprotein receptor (LDLR(-/-))-deficient mice. As an alternative to endogenous apoE-based targeting, we developed a targeting approach using an exogenous ligand containing a multivalent N-acetylgalactosamine (GalNAc)-cluster, which binds with high affinity to the asialoglycoprotein receptor (ASGPR) expressed on hepatocytes. Both apoE-based endogenous and GalNAc-based exogenous targeting appear to be highly effective strategies for the delivery of iLNPs to liver.

An innovative approach for the suppression of ground clutter (GC) contributions from weather radar data is presented. Most of the existing adaptive spectral GC filters (GCF) need a prior knowledge of clutter position, strength and its spectral characteristics. This knowledge is irrelevant for the presented approach because the identification and suppression are entirely data driven. The new approach is referred to as data driven ground clutter filtering (DD-GCF). Before presenting this novel DDGCF, we provide a brief summary on the existing relevant methods and on the filtering needs of the future.

This study documents the use of biodegradable poly(lactide-co-glycolide) (PLG) microspheres as a novel, injectable scaffold for cartilage tissue engineering. Chondrocytes were delivered via injection to the subcutaneous space of athymic mice in the presence and absence of PLG microspheres. Tissue formation was evaluated up to 8 weeks post-injection. Progressive cartilage formation was observed in samples containing microspheres. The presence of microspheres increased the quantity of tissue formed, the amount of glycosaminoglycan that accumulated, and the uniformity of type II collagen deposition. Microsphere composition influenced the growth of the tissue engineered cartilage. Higher molecular weight PLG resulted in a larger mass of cartilage formed and a higher content of proteoglycans. Microspheres comprised PLG with methyl ester end groups yielded increased tissue mass and matrix accumulation, but did not display homogenous matrix deposition. The microencapsulation of Mg(OH)2 had negative effects on tissue mass and matrix accumulation. Matrix accumulation, cell number, and tissue mass were unchanged by microsphere size, but larger microspheres increased the frequency of central necrosis in implants. The data herein reflect the promising utility of an injectable PLG-chondrocyte system for tissue engineering applications.

The objective of this study was to examine the effects of formulation and process variables on particle size and other characteristics of a spray-dried model protein, bovine serum albumin (BSA), using a partial factorial design for experiments. Formulation variables tested include concentration and zinc:protein complexation ratio. Process variables explored were inlet temperature, liquid feed rate, drying air flow rate, and atomizing nitrogen pressure on a lab-scale spray dryer. Statistical data analysis was used to determine F ratios for each of the inputs, which provided a means of ranking the importance of variables relative to one another for each powder characteristic of interest. It was found that protein concentration and atomizing nitrogen pressure had the greatest effects on the particle size of the protein powder. For determining product yield, results showed that protein concentration was the critical variable. Finally, the outlet temperature was mostly influenced by inlet temperature and liquid feed rate. Mathematical models based on these input-output relationships were constructed; these models provide insight into some of the controllable variables of the spray-drying process.