KSHV Genome Replication and Maintenance

Kaposi’s sarcoma associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) is a major etiological agent for multiple severe malignancies in immunocompromised patients. KSHV establishes lifetime persistence in the infected individuals and displays two distinct life cycles, generally a prolonged passive latent, and a short productive or lytic cycle. During latent phase, the viral episome is tethered to the host chromosome and replicates once during every cell division. Latency-associated nuclear antigen (LANA) is a predominant multifunctional nuclear protein expressed during latency, which plays a central role in episome tethering, replication and perpetual segregation of the episomes during cell division. LANA binds cooperatively to LANA binding sites (LBS) within the terminal repeat (TR) region of the viral episome as well as to the cellular nucleosomal proteins to tether viral episome to the host chromosome. LANA has been shown to modulate multiple cellular signaling pathways and recruits various cellular proteins such as chromatin modifying enzymes, replication factors, transcription factors and cellular mitotic framework to maintain a successful latent infection. Although many other regions within the KSHV genome can initiate replication, KSHV TR is important for latent DNA replication and possible segregation of the replicated episomes. Binding of LANA to LBS favors the recruitment of various replication factors to initiate LANA dependent DNA replication. In this review, we discuss the molecular mechanisms relevant to KSHV genome replication, segregation, and maintenance of latency

PAMAM Dendrimers as Promising Nanocarriers for RNAi Therapeutics

Therapeutics based on RNA interference mechanisms are highly promising for the management of several diseases including multi-drug resistant cancers. However, effective delivery of siRNAs and oligonucleotides still remains challenging. In this regard, hyper-branched, PAMAM dendrimers having unique three-dimensional architecture and nanoscale size, with cationic surface charge can potentially serve as siRNA condensing agents as well as robust nano-vectors for targeted delivery. In addition, their surface functionality permits conjugation of drugs and genes or development of hybrid systems for combination therapy. Thus far, in vitro cellular testing of dendrimer-mediated siRNA delivery has revealed great potential, with reports on their in vivo effectiveness starting to appear. These favorable outcomes portend a promising future for dendrimer mediated RNAi therapeutics

The NMDA receptor GluN2C subunit controls cortical excitatoryinhibitory balance, neuronal oscillations and cognitive function

Despite strong evidence for NMDA receptor (NMDAR) hypofunction as an underlying factor for cognitive disorders, the precise roles of various NMDAR subtypes remains unknown. The GluN2Ccontaining NMDARs exhibit unique biophysical properties and expression pattern, and lower expression of GluN2C subunit has been reported in postmortem brains from schizophrenia patients. We found that loss of GluN2C subunit leads to a shift in cortical excitatory-inhibitory balance towards greater inhibition. Specifically, pyramidal neurons in the medial prefrontal cortex (mPFC) of GluN2C knockout mice have reduced mEPSC frequency and dendritic spine density and a contrasting higher frequency of mIPSCs. In addition a greater number of perisomatic GAD67 puncta was observed suggesting a potential increase in parvalbumin interneuron inputs. At a network level the GluN2C knockout mice were found to have a more robust increase in power of oscillations in response to NMDAR blocker MK- 801. Furthermore, GluN2C heterozygous and knockout mice exhibited abnormalities in cognition and sensorimotor gating. Our results demonstrate that loss of GluN2C subunit leads to cortical excitatoryinhibitory imbalance and abnormal neuronal oscillations associated with neurodevelopmental disorders

STUDY OF ACCESSORY SUPRAORBITAL FORAMEN IN NORTH INDIAN HUMAN SKULL

Objective: This research was aimed at telling the anatomical characteristics of the accessory supraorbital foramen (ASOF) in relation to the main supraorbital foramen (SOF), which is necessary in clinical situations that require regional surgical procedures. Methods: A total dedicated to the presence and location of 72 dry Indian adults of unknown age and sex were investigated. In each skull, the ASOF location was measured on both sides with a Vernier caliper metal case, with the SOF as the reference point. The total number of accessory foramen was also noted. Results: Accessory infraorbital foramens (IOFs) were seen only in 4.16% in our study and all seen were single in number. Half of those accessory foramen were present on medial and rest half were present on superomedial position as compared to the main IOF. Half among present accessory foramens were located at a distance of <2 mm and half were located at a distance of more than 2 mm. The mean location of accessory IOF was at 7.07 mm from main IOF. Conclusion: Knowledge of the anatomical characteristics of ASOF can have major effects on surgical and local anesthetic preparation blockage of the super orbital nerves. Additional guidance for surgeons may be provided with information on the foramens obtained from this study. The surgeons should note this during the nerve block as damage to either branch will lead to sensory impairment and incomplete blocking of the nerve

An Experimental Investigation of the Incipient Drawdown Conditions in Two-Layered Stratified Flow.

An experimental study of stratified fluid flow phenomena for two equal depth, different density stratified liquids in a rectangular channel is presented. Two two fluid combinations were used, a sugar water and fresh water, and fresh water and varsol. The critical value of the determined densimetric Froude number at which the upper fluid began to participate in the flow was obtained and found to be 0.28 as against Huber's (1) predicted value of 2.76. It was concluded that the interfacial mixing and viscous effects are largely responsible for this difference. An attempt to extend Harleman's (7) work was made. The results obtained in present work were in good agreement with Harleman's (7) experimental work. ThesisMaster of Engineering (ME

Self heating Effects in GaN High Electron Mobility Transistor for Different Passivation Material

In this paper effect of self-heating has been studied of AlGaN/GaN high electron mobility transistor (HEMT) for different passivation layers which is promising device for high power at high frequencies. The different passivation layers used are aluminium oxide (Al2O3), silicon nitride (SiN) and silicon dioxide (SiO2). The device GaN HEMT has been simulated and characterised for its thermal behaviour by the distribution of lattice temperature inside the device using device simulation tool ATLAS from SILVACO. The transfer and output characteristics with and without self-heating has been studied for electrical characterisation. The channel temperature for different passivation observed is 448 K, 456 K and 471 K forAl2O3, SiN and SiO2 respectively. The observed different temperatures are due to difference in their thermal conductivity. This channel temperature information is critical to study the reliability of the device at high power levels

A study on body mass index and its correlation with type 2 diabetes

Obesity and increases in body weight are among the most important risk factors for type 2 diabetes mellitus. Obesity contributes to the development of type 2 diabetes mellitus. Body mass index is also known as obesity index. Body mass index is a strong and independent risk factor for being diagnosed in cases of type 2 diabetes mellitus. There is a high risk of type 2 diabetes in those who have a higher body mass index. The present study has been done with the objective of finding correlation between BMI and type 2 diabetes

A study of anionic, cationic and amphoteric collector

Online access for this thesis was created in part with support from the Institute of Museum and Library Services (IMLS) administered by the Nevada State Library, Archives and Public Records through the Library Services and Technology Act (LSTA). To obtain a high quality image or document please contact the DeLaMare Library at https://unr.libanswers.com/ or call: 775-784-6945.Flotation tests for quartz and alumina were carried out using sodium N-coco-B aminopropionate and g-y Dipal mitoyl L—a lecithin as collectors. In some systems, good flotation of a mineral occurs in the surfactant's isoelectric range while in others a mineral is floated over a wide range of pH including the mineral's point of zero charge. Electrophoretic mobility studies indicate a positive adsorption of the amphoteric surfactants on these minerals. The adsorption of amphoteric surfactants may be accounted for partially by electrostatic charge attraction but also there should be some special affinity involved between surfactant's polar group and the mineral surfaces. The amphoteric surfactants seem to be potential selective collectors for some oxide minerals

STUDY OF VERTICAL DISTANCE BETWEEN SUPRAORBITAL FORAMEN AND INFRAORBITAL FORAMEN AMONG NORTH INDIAN HUMAN DRY SKULLS

Objectives: The aim of study was to document the positional distance of supraorbital foramen (SOF) in relation to Infraorbital foramen (IOF), which is necessary for periorbital procedures. Materials and Methods: A total of 72 dry human skulls of unknown age and gender from North India, were studied. In each skull, distance between supraorbital and IOF was measured on both sides using a metal casing Vernier Caliper. Results: The mean distance between inferior wall of SOF and superior wall of IOF was found to be 40.81 (±6.66) mm on the left side and 40.91 (±6.15) mm on the right side. The overall value for both sides was 40.86 (±6.28) mm Conclusion: Precise knowledge about distance between supraorbital and IOF have important bearings on orbital and periorbital procedures. It provides guidance for anesthesiologists and facial surgeons