Biophysical and structural study of intrinsically disordered proteins : investigations on the periplasmic domain of apo OmpA from Acinetobacter baumannii and a new AT-rich DNA-binding domain of human methyl CpG binding protein2

Mushtaq, Ameeq Ui Korea University 2018 국내박사

CD38 plays critical role in thrombin-induced procoagulant activity of platelets

Mushtaq, Mazhar Chonbuk National Univ. 2011 국내박사

Effect of Compressive Stress on the Area-Specific Resistance and Leakage of Planar SOFC with Mica Seals

MUSHTAQ USMAN UST 2014 국내석사

Phlogopite mica has been assessed singly as a sealant material in SOFC applications but the literature lacks the compression effects on the cells’ electrical performance. Thus, in this study, a test-kit is designed to simultaneously investigate and relate the compressive stress effects on the leakage and electrical performance of the SOFC with mica seals. Commercially available mica sheets were used as channel gaskets and insulation in planar 5cm x 5cm anode supported solid oxide fuel cell test kits; Crofer 22 APU sheets with nickel and silver wires and meshes as current collectors to imitate real stack conditions. The kits were mechanically loaded using SUS430 steel manifolds at 208kPa, 268kPa and 327kPa compressive stress and tested at 700, 750, 800oC with 100-500sccm H2 + 3%H2O as fuel and 1250sccm air as oxidant. The fuel-side leakages were measured using a bubble-meter while the area specific resistance (ASR) variation was measured through electrochemical impedance spectroscopy. The measured leakage across the kit compressed at 208kPa was recorded as 0.516, 0.524 and 0.536sccm/cm at 700, 750 and 800oC. While the kit compressed at 268kPa showed a decreasing leakage of 0.490, 0.468 and 0.466sccm/cm at 700, 750 and 800oC. Similarly, the leakage decreased significantly for the kit compressed at 327kPa by 0.469, 0.413 and 0.389sccm/cm at furnace temperatures of 700, 750 and 800oC. The corresponding variation in leakage from 700-800oC was +∆0.02sccm/cm for 208kPa, -∆0.03 and -∆0.08sccm/cm for kits compressed at 268 and 327kPa. The added effect of decrease in ASR was measured to be 454, 441 and 403mΩcm2 at 700oC for kits compressed at 208, 268 and 327kPa. While for same compression, the ASR decreased linearly by 394, 371 and 342 mΩcm2 at 750oC. The decrease in ASR at 800oC was 337, 318 and 303 mΩcm2 for kits at 208, 268 and 327kPa compression. The corresponding change in ASR was -∆51, -∆52 and -∆34 mΩcm2 at 700, 750 and 800oC increasing compressive stress from 208 to 327kPa. The results show both the leakage and ASR decreased by increasing compressive stress on the kits with local and external temperatures. The sealing ability of phlogopite mica improved after 500-1000hours with increased compressive stress at elevated temperature, but the decrease in ASR signifies an undesirable increased mechanical stress on the cell’s surface. Using cell and current collector components led to surface pressure variation on mica generating leak paths. Thus, a parameter optimization through computer simulation would be useful for designing SOFC stacks using mica as a potential sealant and gasket material for the uniform distribution of stress on mica while keeping them well below the fracture strength of the cells.

Radiosynthesis and biological evaluation of SPECT tracers

Mushtaq, Sajid University of Science and Technology 2018 국내박사

Cancer is complex class of diseases with many possible causes. If cancer is not treated at early stages it can grow and can transfer into surrounding healthy tissues and other normal parts of body via lymphatic system or blood stream, and can damage circulatory, nervous and digestive system. The cancer deaths as more on a global scale than hepatitis, malaria, TB, and AIDS combined. Under these circumstances there is a great need of the best diagnosis and treatment procedures to defeat the cancer at early stages. The early diagnosis means successful cancer treatment. The nuclear medicine diagnosis and treatment procedures have great potential for the treatment of cancer as compared with conventional medical procedures. Among many possible applications, molecular imaging made it possible the visualization of human disease in animal models, development of new drugs, efficiency of therapeutic procedure, and the radiation and chemotherapy based treatment of tumors and cancer cells. Molecular imaging extensively used to detect the tumor at early stages so that new therapeutic procedures were applied to treat the tumor. The nuclear imaging using suitable radiotracers and PET or SPECT system have many advantages over other traditional imaging modalities including unlimited depth penetration, high intrinsic sensitivity, and high resolution. In the era of positron emission tomography, the single photon emission computed tomography (SPECT) kept its safe position in the field of nuclear medicine especially in combination with CT. The dual modality imaging procedure using SPECT/CT is still useful in variety of diagnostic procedures in the clinic. The easy availability of advanced SPECT/CT system offers an opportunity to get accurate images within short acquisition time. The SPECT/CT has many advantages as compare with PET and it is a dominating imaging modality in the field ofoncology. It is low cost easily available modality with variety of cheap easily available radioisotopes which can be incorporated into the biomolecules. The SPECT/CT system not only uses for early cancer diagnosis but also in a wide range of chronic medical disorders.The tumor imaging and therapy mostly based upon the specific interaction of over expressed antigens, transporters, enzymes, and receptors on the tumor and the radiolabeled peptides and proteins. The ideal radiopharmaceutical targets its target tissue without harming healthy tissues. The quality and in vivo behavior of radiopharmaceutical based upon the radiolabeling methods. The in vivo stability of radiopharmaceutical also depends upon the radiolabeling strategy. In the design of radiopharmaceutical the choice of appropriate biomolecule (peptide, protein, or antibody), radioisotope and finally strategy to incorporate radioisotope into the biomolecule is the most important task. In this dissertation the radioiodine (125I) and 99mTc have been selected for the synthesis of SPECT based radiotracers. In chapter 2, 3 and 4 new radiolabeling strategies were discussed to incorporate 125I into biomolecules for the synthesis ofcancer targeting biomolecules. In chapter 5 99mTc-labeled imaging agent was synthesized for SPECT based apoptosis imaging. To circumvent the limitation of 99mTc labeled antibodies, antibody mimetic protein (repebody protein) was radiolabeled with 99mTc and initial clearance properties or biological evaluation have been discussed in the chapter 6. All these SPECT based radiopharmaceuticals synthesized in this study, including radioiodinated cRGD peptide, human serum albumin protein, transferrin human protein and 99mTc labeled antibody mimetic protein have their own biological importance which has been discuss in the respective chapters.

(The)nucleation and growth of diamond and non-diamond coatings

Dar, Mushtaq Ahmad Chonbuk National Univ. 2006 국내박사

Characterization of microfabricated tunnel junction device for thermodynamic temperature measurement from electronic noise

Rehman, Mushtaq Ur Chonnam National Univ. 2011 국내박사

(An) Analysis on digital divide structure and pattern across Asia Pacific countries based on multivariate statistical methods

Majid Mushtaq Hankuk University of Foreign Studies Department of 2018 국내석사

Seeing ICT as a catalyst for economic growth, many governments have come up with ways to induce the development of ICT in their strategic plans. Yet, the boom of internet technologies has also resulted in disparities in digital access between certain regions and countries, presenting a threat to leaving these countries behind in the race to global competitiveness. Various attempts have been made to define and analyze the digital divide in various regions of the world, yet until now, there hasn’t been any sort of work done measuring the digital divide structure and pattern on a large scale in the Asia Pacific region. The purpose of this research is to analyze the structure, pattern and dynamics of the digital divide in the Asia-Pacific area. We tackled the measurement of digital divide among 31 countries of this region by means of multivariate statistical methods. Our analysis of digital divide structure and dynamics was focused on 3 objectives. First, we used factor analysis in order to determine a small number of factors that summarize the set of economic, demographic, social and digital development related indicators. Second, we clustered countries using their ICT-related indicators and determined which group of countries can be classified as digital laggards and which ones are digital leaders. Third, we observed short term digital divide evolution by drawing the path movements of these countries between the year 2011 and 2016 which helped us to analyze the evolution of each country by answering the question that whether or not, a country has experience digital improvement in these 5 years. With the help of these multivariate statistical methods, we found out that the digital gap exists in this region and is much wider than the digital gap across the European Union countries. Moreover, of 10 variables in consideration, 2 latent factors were found, namely digital diffusion and cost, and digital infrastructure. On the other hand, cluster analysis grouped these Asia Pacific countries into 5 different clusters sharing similar digital profiles in each cluster. Short term digital evolution shows that countries have been improving in their digital development scores, yet the digital gap is huge between certain clusters. We have also suggested some recommendations for policy makers in these countries to help them narrow the digital gap between their countries and ‘digital leaders’. 전 세계 대부분의 국가들은 경제 성장의 촉매로서 정보통신기술의 개발과 활용을 위한 다양한 관련 정책들을 경제에 적용하였다. 그러나 인터넷 기술의 폭발적인 발전에도 불구하고 특정 지역이나 국가들 간 다양한 형태의 불균형이 발생하였으며, 이는 특정 국가들의 경제 성장이나 산업 경쟁력에서의 차이를 야기하는 결과로 이어 졌다. 따라서 국제 지역간 혹은 국가간 정보 격차에 대한 원인과 구조 그리고 동태적 변화와 해소를 위한 정책 개발에 다양한 연구가 수행되었다. 그러나 아시아, 태평양 지역을 대상으로 한 정보 격차의 구조와 패턴 그리고 정책 연구는 매우 미진한 상황이다. 이에 본 연구는 아시아, 태평양 지역의 정보 격차의 구조, 패턴 그리고 동태적 특성을 분석하여 역내 국가간 정보격차를 해소하기 위한 정책적 대안을 모색하는 것을 목적으로 한다. 아시아, 태평양 지역 31개 국가들을 대상으로 다변량 통계 방법론을 적용하여 정보 격차를 측정하여, 그 구조와 동태적 특성을 분석한다. 구체적으로 우선, 경제적, 인구학적, 사회적 그리고 정보통신기술 관련 다양한 지표들을 대상으로 요인 분석을 수행, 두 개의 요인을 추출하고, 이를 바탕으로 역내 국가간 정보격차의 핵심 원인을 고착한다. 두 번째로는 이러한 두 개의 핵심 요인을 기반으로 31개국에서 정보격차가 유사한 집단들을 구분하는 군집분석을 수행하여 역내 정보격차 구조의 특성을 분석한다. 특히, 요인분석 이전의 다양한 지표를 대상으로 군집분석을 수행하여, 2 요인 기반 군집분석과 비교하여 정보격차 구조의 특성을 고찰한다. 마지막으로 2011년과 2016년의 정보 격차의 구조를 비교하여 정보 격차 해소 과정에 효과를 보이는 국가들의 특성을 파악한다. 이러한 다자간 통계방법론을 통해 이 지역에서 정보 격차가 다양한 형태로 존재한다는 것과 기존 유럽연합국가들을 수행한 연구 결과와 비교하여 격차의 정도가 보다 심각하는 것을 파악하였다. 특히, 요인분석을 통하여 아시아, 태평양 지역의 정보 격차의 핵심 요인으로 디지털 확산 비용과 디지털 인프라를 파악하였다. 또한, 이러한 요인에 근거하여 31개 국가들의 정보격차 구조를 5개의 군집으로 식별할 수 있었으며, 하위 군집과 상위 군집간 정보 격차의 차이가 매우 크다는 사실을 확인하였다. 또한, 동태적 분석에서 하위 군집의 국가들의 정보격차가 개선되는 방향으로 이루어지고 있으나, 여전히 상위 및 하위 군집간 정보 격차는 지속되고 있다. 이러한 연구 결과를 바탕으로 상위 국가군과의 격차를 해소하기 위한 다양한 정책적 방안을 제시하였다. 본 연구결과와 정책적 제언은 향후 아시아, 태평양 지역의 정보 격차의 해소를 위한 좋은 참고 자료로 활용 가능하며, 특히 역내 정보격차의 동태적 변화를 추적하여 정책 실행의 효과 분석의 방법론적 기반으로 활용할 수 있을 것으로 기대된다. 그러나, 현재 정보통신기술의 발전 속도가 매우 빠르고, 또한 다양한 산업과의 융합 발전이 가시화되고 있는 상황에서 기술적, 경제적, 환경적 그리고 수요 변화 요인들을 고려한 보다 확장된 분석 모델이 필요할 것으로 보인다.

Confidence building measures for Indo-Pak nuclear deterrence

Chaudhary Atif Mushtaq 경희대학교 평화복지대학원 2017 국내석사

Since, the bloodstained, partition of subcontinent by British in 1947 both countries, ‘India and Pakistan’, have been involved in wars, territorial conflicts and disputes. Congress and Muslim league were the political parties of Hindu and Muslims respectively. Since congress was against the partition and wanted to see greater India, therefore they did not accept the independence of Pakistan, which put it in security dilemma because of large size, and population of India. And right after one year of independence newly born states get involved in a territorial war in 1948 followed by 1965, 1971 wars. After the defeat in 1971 war from India, Pakistan felt international humiliation and decided to have nuclear weapons in order to counter its four times larger enemy. Both countries successfully entered into nuclear club in 1998. In 1999 a limited territorial war broke out between them which lead both countries to brink of nuclear war, but presence of nuclear arsenals possessed by both states also prevented the full-fledge war and play the role of deterrence. Deterrence played effective role in prevention of war and it proved to be effective but there are limitations of deterrence and both nations paying high price for maintaining this deterrence. The instability in the region may cause the failure of deterrence, which can provoke them to use their nuclear arsenals, which cannot only be devastating for the region but also dangerous for world peace because of their strategic location. Along with deterrence peace and cooperation in the region is unavoidable for entire humanity. In the contemporary situation it’s like utopian to expect them to give up their nuclear armaments but at the same time both countries must focus on institutionalizing CBMs (Confidence building measures) to reduce enmity, bridge the gap of cooperation and interdependence on each other, and gradually aware the people of both countries that peace and cooperation can replace deterrence so that they could put pressure on their governments to make policies accordingly. In a region, with the history of violent conflicts, the importance of CBMs (Confidence building measures), cannot be underestimated, which are very important in reducing tensions, avoiding skirmishes, and pave the way toward peace and prosperity. Both countries, being traditional enemies and nuclear powered states, are in dire need to take measures to limit hostilities and reduce stiffness. The significance of CBMs has increased after entry of both countries into nuclear group. Military and Non-military CBMs in the region, with true spirit, are unavoidable for lasting peace and stability in the region. Though it is very hard to expect major output but at slightest CBMs between them can help in structuring an essential level of confidence among them for lasting peace and cooperation in the region and prevention of limited territorial war like ‘Kargil Crisis’ when both countries put their forces on borders and risk of nuclear war was evident. However, history of CBMs in South Asia is not inspiring because of some major impediments and confines, but still their importance cannot be ignored.

Biophysical and structural study of Intrinsically Disordered Proteins : Investigations on the periplasmic domain of apo OmpA from Acinetobacter baumannii and a new AT-rich DNA-binding domain of human methyl CpG binding protein2

AMEEQ UL MUSHTAQ 고려대학교 대학원 2018 국내박사

In this thesis solution nuclear magnetic resonance (NMR) and other biophysical methods were used to investigate the structure and dynamics of Intrinsically Disordered Proteins (IDPs), periplasmic domain of apo OmpA from Acinetobacter baumannii and a new AT-rich DNA binding domain of human methyl CpG binding protein2 (MeCP2). 1) The first part of thesis investigates the folding of apo OmpA periplasmic domain from Acinetobacter baumannii (AbOmpA-PD) in vitro using biophysical methods. AbOmpA-PD binds to diaminopimelate (DAP) and anchors the outer membrane to the peptidoglycan layer in the cell wall. Although the crystal structure of AbOmpA-PD with its ligands has been reported, the mechanism of ligand-mediated folding of AbOmpA remains elusive. Here, we report that in vitro refolded apo AbOmpA-PD in the absence of ligand exists as a mixture of two partially folded forms in solution: mostly unfolded (apo-state I) and holo-like (apo-state II) states. Binding of the DAP or glycine ligand induced complete folding of AbOmpA-PD. The apo-state I was highly flexible and contained some secondary structural elements, whereas the apo-state II closely resembled the holo-state in terms of both structure and backbone dynamics, except for the ligand-binding region. 15N-relaxation-dispersion analyses for apo-state II revealed substantial motion on a millisecond time scale of residues in the H3 helix near the ligand-binding site, with this motion disappearing upon ligand binding. These results provide an insight into the ligand-mediated folding mechanism of AbOmpA-PD in solution. 2) The second part of thesis investigates the binding, structure and dynamics of an intrinsically disordered AT-rich DNA binding motif from the transcription repression domain (TRD) of human MeCP2. MeCP2 is a chromatin associated protein which is highly expressed in brain and relevant with Rett syndrome (RTT). There are so-called AT-hook motifs in MeCP2 which can bind with AT-rich DNA, suggesting a role in chromatin binding. Here, we report the identification and characterization of another AT-rich DNA binding motif (residues 295 to 313) from the C-terminal transcription repression domain of MeCP2 by NMR and isothermal calorimetry (ITC). This motif shows a micromolar affinity to AT-rich DNA, and it binds to the minor groove of DNA like AT-hook motif. Together with the previous studies, our results provide an insight into a critical role of this motif in chromatin structure and function. SUMMARY (IN KOREAN) 본 논문에서는 논문에서는 논문에서는 논문에서는 논문에서는 Intrinsically Disordered Protein (IDP)의 구조 및 운동성을 연구하기 연구하기 연구하기 연구하기 위 하여 , human MeCP2의 양전하클러스터 양전하클러스터 양전하클러스터 양전하클러스터 양전하클러스터 양전하클러스터 양전하클러스터 펩타이드 (BCP)와 Acinetobacter baumannii OmpA 의 periplasmic domain (AbOmpA-PD) 을 nuclear magnetic resonance (NMR)로 분 석하였다 석하였다 석하였다 석하였다 . 1) 논문 첫 부분은 NMR 및 생물물리학적 방법들을 이용해서 AbOmpA-PD의 folding상태를 조사했다. AbOmpA-PD는 diaminopimelate (DAP) 과의 상호작용을 통해 세포벽의 peptidoglycan 층에 결합한다. AbOmpA-PD와 그것의 리간드의 결정구조가 발표되었음에도 불구하고AbOmpA-PD의 리간드 매게 접힘의 메커니즘은 여전히 규명되어지지 않았다. 이 연구에서, 리간드가 없는 AbOmpA-PD는 용액상태에서 두 종류의 부분적으로 접힌 folding 중간체가 혼합하여 존재 한다는 것을 발견했다: 대부분 접히지 않은 상태 (apo-state I)와 리간드와 결합된 holo-단백질과 유사한 구조를 갖는 상태(apo-state II) 이다. DAP나 글리신 리간드의 결합은 AbOmpA-PD단백질의 접힘을 유도했다. apo-state I 은 매우 유연하고 약간의 이차구조 요소를 포함하는 반면에, apo-state II 는 리간드 결합부위를 제외 하고 holo-state 상태와 유사한 구조와 backbone dynamics를 가지고 있다. apo-state II에 대한 15N-relaxation-dispersion 분석을 통하여, 리간드 결합부위 주변의 H3 helix가 밀리 세컨드 시간 단위의 움직임을 하고 있음을 발견하였다. 이러한 운동성은 리간드가 결합하면 대부분 사라지게 된다. 이러한 결과들은 용액 상태 에서 partially folding 된 119 AbOmpA-PD가 리간드 결합에 의하여 folding 이 되는 메커니즘에 관한 정보를 제공한다. 2) 논문의 두 번째 부분은 인간 MeCP2의 transcription repression domain (TRD)에 존재하는 양전하 클러스터 펩타이드 (BCP) 가 AT-rich DNA에 결합할 떄의 구조 변화 및 운동성에 대하여 연구하였다. 이 펩타이드는 본질적으로 random 한 구조를 갖지만, AT-rich DNA에 결합하면 extended conformation을 갖게 된다. MeCP2는 뇌에서 많이 발현되고 Rett syndrome (RTT)와 관련있는 크로마틴 구조 관련 단백질이다. MeCP2에는 3개의 AT-hook motif 가 AT-rich DNA 결합도메인으로 알려져 있는데, 이번 연구를 통하여, 네번째 AT-hook 유사 도메인으로서 양전하 클러스터 펩타이드 (BCP)를 발견하고, 이 펩타이드의 AT-rich DNA 결합을 확인하였다. 이 펩타이드도 기존의 AT-hook motif 와 유사한 결합능으로 DNA에 결합하고, 또한 DNA의 minor groove에 결합하는 것을 NMR 실험을 통해 확인할 수 있었다. 이러한 면에서 BCP는 기존의 AT-hook 과 함께 크로마틴 구조 형성에 중요한 역할을 할 것으로 예측된다. 위의 두가지 두가지 두가지 연구 결과로부터 결과로부터 결과로부터 결과로부터 결과로부터 본 저자는 저자는 저자는 NMR 을 활용한 IDP의 구조 및 운 동성을 분석하 고, 구조생물학적 구조생물학적 구조생물학적 구조생물학적 구조생물학적 구조생물학적 의미를 제시하였다 제시하였다 제시하였다 제시하였다 제시하였다 .

Fault Tolerance in Distributed Systems

Mushtaq, Aisha ProQuest Dissertations & Theses University of Cali 2022 해외박사(DDOD)

Modern datacenter applications need to provide resiliency to mask failures. These applications widely use techniques like Replicated State Machines to provide fault tolerance. Replicated State Machines typically rely on consensus protocols to provide availability and consistency. These applications also require high throughput and low latency from the underlying consensus protocols. Furthermore, in an effort to further reduce latency experienced by clients, we are seeing the emergence of edge computing; storage and computational resources are placed in between the clients and servers in datacenters (typically closer to the client). This placement provides many benefits: lower-latency responses to clients, lower bandwidth demands on the backbone and increased privacy. Stateful applications running on the edge pose a problem of losing state when an edge node fails.This dissertation looks at fault tolerance for datacenters and edge computing. First, RingWorld looks at datacenter fault tolerance for highly available lock services. RingWorld adapts ring-based consensus protocols to leverage programmable switches and datacenter topology. This allows RingWorld to provide higher throughput and comparable latency to existing lock services. Second, to provide fault tolerance for edge computing, CESSNA provides a mechanism to recover from edge failures for strongly stateful applications that ensures correctness and good performance. To do this, CESSNA defines the consistency guarantee for correctness in the face of edge failures, and recovers from failures by adapting techniques like log-replay.