Modulation of Bax/Bak Dependent Apoptosis by Sirtuin 3 and Mitochondrial Permeability Transition by Sirtuin 4

Mitochondria are dynamic organelles that regulate a myriad of cellular functions, including energy production and metabolic regulation. Mitochondria are also a critical regulator of cell death signaling cascades modulating both apoptotic and necrotic cell death. However, what determines which cell death pathway is activated is still unclear. The mitochondrial/intrinsic pathway of apoptosis is dependent on the activation of pro-apoptotic proteins, Bax and Bak, which induce mitochondrial outer membrane permeabilization (MOMP). Once the integrity of outer mitochondrial membrane (OMM) is compromised, pro-apoptotic intermembrane space proteins like cytochrome c, Smac/Diablo, Omi/HtrA2 and AIF are released into the cytoplasm, which activates the post-mitochondrial phase of apoptosis. In humans, there are seven sirtuins (Sirtl-7), three of which are localized to the mitochondria (Sirt3-5). Sirt3 and Sirt5 have acetyltransferase activity, whereas Sirt4 has ADP-ribosyltransferase activity. Sirt3 is the major deacetylase in the mitochondrial matrix, and regulates various metabolic pathways by modulating the acetylation status of key metabolic enzymes. Although, metabolic regulation by Sirt3 has been studied extensively, the role of Sirt3 in cancer progression and regulation of the apoptotic pathway remains unclear. To sustain their rapid growth, cancer cells have a high glycolytic rate. This is achieved by overexpression of a key glycolytic enzyme, hexokinase II (HKII), which attaches to the OMM. HK.II binding to the OMM transmembrane voltage-dependent anion channel (VDAC) protein renders cancer cells resistant to a variety of cell death stimuli (e.g. DNA damage, oxidative stress and TNFa) by inhibiting activation of Bax/Bak. In this thesis, I present evidence that Sirt3 acts a mitochondrial localized tumor suppressor by modulating the binding of HKII on the OMM. Sirt3 dependent dissociation ofHKII from the OMM increases activation of pro apoptotic protein Bax/Bak in response to pro death stimuli, t-Bid and cisplatin. In contrast to apoptosis, opening of a multiprotein mitochondrial permeability transition pore (MPTP) by oxidative stress or mitochondrial calcium overload leads to necrotic cell death. The constituents of the MPTP, though controversial, consist of cyclophilin-D in the matrix, adenine nucleotide translocator (ANT) in the inner mitochondrial membrane, and VDAC on the OMM. Sirt4-mediated ribosylation of glutamate dehydrogenase-1 (GDH-1) inhibits its activity. In the second part of this thesis, I demonstrate that Sirt4 regulates the induction of the permeability transition by regulating the activity of GDH-1. Down-regulation of Sirt4 inhibits PIP induction by calcium overload and the thiol reactive agent phenylarsine oxide by increasing GDH-1 activity. Similarly, in intact cells, depletion of Sirt4 protected against PIP induction by cytotoxic drugs like INFa and doxorubicin. The evidence presented here demonstrates possible mechanisms by which mitochondria, more specifically, Sirt3 and Sirt4 modulate apoptotic and necrotic cell death, respectively

Fundamentals of MV Motors

TutorialMedium voltage ASDs (MV Adjustable Speed Drives) and motors are widely applied to plant rotating machinery like compressors, pumps, fans, extruders, mills, kilns, etc., ranging from a few horsepower (HP) to tens of thousands of horsepower. Safe, reliable and successful application of these ASDs and motors require a system level approach. The Short Course is an information-packed one-day series of practical sessions covering the selection, specification, and application of industrial MV equipment. The focus for the course will be application topics that can be used right away to specify, evaluate, procure and install a successful MV motor and drive system. The dimensions of the course will be medium voltage (>2.3kV) and motor power ranging from 500 HP thru 100,000 HP. In addition to classroom presentations, attendees are encouraged to bring their own real-world application issues for group discussion

Broadcasting Scenario under Different Protocols in MANET: A Survey

A wireless network enables people to communicate and access applications and information without wires. This provides freedom of movement and the ability to extend applications to different parts of a building, city, or nearly anywhere in the world. Wireless networks allow people to interact with e-mail or browse the Internet from a location that they prefer. Adhoc Networks are self-organizing wireless networks, absent any fixed infrastructure. broadcasting of data through proper channel is essential. Various protocols are designed to avoid the loss of data. In this paper an overview of different broadcast protocols are discussed

Oxygen vacancies tuned carrier localization, magnetic and thermoelectric properties in ultrathin (LaNiO3−δ_{3-\delta})1_1/(LaAlO3_{3})1_1(001) superlattices

Here we explore the effect of oxygen vacancies on electronic, magnetic, and thermoelectric properties in ultrathin (LaNiO$_{3-\delta}$)$_1$/(LaAlO$_{3}$)$_1$(001) superlattices (SLs) using a combination of density functional theory calculations including an on-site Coulomb repulsion term (DFT+$U$) and Boltzmann transport theory within the constant relaxation time approximation. For pristine SLs, we find the stabilization of an antiferromagnetic charge-disproportionated (AFM-CD) ($d^{8}${$\underline L$}$^{2}$)$_{S=0}$($d^{8}$)$_{S=1}$ phase, irrespective of strain. At $\delta$ = 0.125 and 0.25, the interplay of confinement and strain triggers a varying degree of charge disproportionation, resulting in ferrimagnetic insulators. However at $\delta$ = 0.5, an insulating phase emerges with alternating stripes of Ni$^{2+}$ (high-spin) and Ni$^{2+}$ (low-spin) and oxygen vacancies ordered along the [110] direction (S-AFM), resulting in a robust $n$-type in-plane power factor of 12.4~$\mu$W/K$^2$ cm (assuming relaxation time $\tau = 4$~fs), at 300~K. This demonstrates the fine tunability of electronic, magnetic, and thermoelectric properties by oxygen vacancies in ultrathin nickelate superlattices.Comment: 7 pages, 3 figure

Painful finger, diagnosis and surgical management: Clinical puzzle

It is really very difficult to live with a painful finger. Here, we are discussing a case who presented with a complaint of severe lancinating pain in her left index finger for about 7 years. This pain was so distressing to her that she was requesting for the amputation of her finger. Being a reconstructive surgeon, it was really very difficult to fulfill her wish. In the past 7 years, she consulted to several practitioners but did not get relief of her pain. Clinical suspicion of Glomus tumor was made and magnetic resonance imaging was done to confirm the diagnosis. Surgical excision of the swelling was done, and the patient was completely relieved of her pain

EXPERIMENTAL AND COMPUTATIONAL STUDY OF BINDING INTERACTION OF ALKOXY DERIVATIVES OF N-ARYLHYDROXAMIC ACIDS WITH DNA

Objective: Binding affinity towards DNA for small molecules is very important in the development of new therapeutic reagents. Interaction between N-Arylhydroxamic acid derivatives N-p-Tolyl-4-Ethoxybenzohydroxamic acid (p-TEBHA) and N-o- Tolyl-4-Ethoxybenzohydroxamic Acid (o-TEBHA), with calf thymus DNA (CT DNA) were studied by UV–visible absorption, fluorescence,  viscosity measurement and molecular docking. Methods: The absorption and emission spectra of DMSO solution of hydroxamic acid derivatives were studied for their binding activity with calf-thymus DNA by titration with increasing amount hydroxamic acids. Docking was performed by HEX software. Results: Fluorescent spectra showed that CT DNA quenches the emission spectra of p-TEBHA & o-TEBHA with binding constant 1.6 Ñ… 108 M-1 and 4.3 Ñ… 103 M-1 respectively. Competitive study with ethidium bromide (EB) indicates that p-TEBHA can displace the DNA-bound EB suggesting strong competition with EB whereas o-TEBHA does not displace the DNA-bounded Ethidium bromide effectively. UV study of the interaction of the complexes with calf-thymus DNA has shown that the hydroxamic acid derivatives can bind with CT DNA. The docking studies were used to predict the mode of interaction of the drug with DNA. It was observed that as far as binding strength was concerned the computational results complemented the experimental results. Conclusion: Investigated hydroxamic acid derivatives are found to be strong DNA binders and seem to have promising drug like nature

Epidemic of Fear: Cause and Effect

This review attempts to focus on the Epidemic of fear and its causes and effects on the people during the pandemic situation. Primarily the aim was to understand the psychological concept of the origination of fear due to epidemic or pandemic situations. Several theories and researches helped in explaining the underlying roots of the epidemics of fear and the behavioral changes in a person due to this. Through previous researches, a better understanding of the ways to prevent the fear of spreading among us is presented in this paper. Several types of researches and articles were studied that acted as the pillars of this paper reflect on the causes of the epidemic of fear

Multi-Stage Intrusion Detection Approach for Network Security

Nowadays, the massive increment in applications running on a computer and excessive in network services forces to take convenient security policies into an account. Many methods of intrusion detection proposed to provide security in a computer system and network using data mining methods. These methods comprise of the outlier, unsupervised and supervised methods. As we know, each data mining method is not able to find different types of attacks. So, for removing this vulnerability, we are using Multi-Stage Intrusion Detection Method that containing outlier, unsupervised and supervised detection approaches for improving the performance and detection accuracy by reducing the false alarms for detection of known and unknown attacks. We have used NSL-KDD, KDD Corrected and GureKDD dataset in our experiment. We have compared our proposed outlier method GBBK + with GBBK method and our method gives the same result with the less time complexity. The Unsupervised classification algorithm k − point performing the unnecessary comparison of objects iteratively by reducing number of attributes every time up to the threshold that is improved and named as k – point + . Empirically, the proposed scheme compared with existing methods, and the results shows that the proposed method outperform in term of time complexity and detection accuracy

k-Anonymity using Two Level Clustering

Data publising is becoming popular because of its usage and application in many fields. But original data have some sensitive information of individual whose personal privacy can be violated if original data is published . There are some agreements and policies which have to be fulfilled before publishing data . The techniques or protcols which preserve the privacy and retain useful information to apply data mining is nown as it is known as privacy preserving data publishing.k -anonymity is a technique to preserve privacy of individual while publishing data which still have useful information to apply data mining. To achieve k -anonymity local recoding algorithms gives less information loss but their execution time is more compared to global recoding algorithms. Their execution time mostly depends on for each cluster how they find the most suitable cluster to merge it,its linear search takes unnecessary time which can be reduce by find some most suitable cluster without linear search which we applied in our purposed algorithm. In our work, we used clustering at two levels , cluster at outer level contains inner clusters which are most likely to be merged. so to satisfy k value ,inner clusters merge within same outer cluster if still it do not satisfy k -anonymity then they merge with inner clusters of some other outer cluster, which other outer cluster is most suitable can be find without linear search and most of its inner cluster which still unsatisfied k -anonymity can be find without linear search. It this way we have reduced the execution time of our algorithm which it lesser than other efficient local recoding algorithm KACA and TopDown -KACA and other metrics such as distortion and discernibility gives similar resulted value as other local recoding algorithms