BUSINESS STRATEGY: USING SHIFT LEFT PRINCIPLES TO MANAGE IT PROJECTS EFFECTIVELY

Customer satisfaction is seen as a key differentiator in a competitive market place. As per Gartner 2012 report, only 75%-80% of IT projects are successful. Customer Satisfaction should be part of the business strategy. As a project manager, the associated project parameters should be pro-actively managed and the project outcome needs to be predicted. There is lot of focus on the end state and in minimizing defect leakage as much as possible. Focus should be to pro-actively manage and shift left in the life cycle. Identify the problem upfront in the project cycle and not wait for lessons to be learnt and take re-active steps. This paper gives the practical applicability of shift left techniques and illustrates use of predictive model in a project to predict system testing defects thus helping to reduce residual defect

TECHNOLOGY ADOPTION USING MEDICAL IMAGE PROCESSING TOOLS IN GLOBAL HEALTH SECTOR DEVELOPMENT

Medical Imaging is a major development in the field of medicine for past 100 years. The tool helps the physicians not only to detect the diseases but also the intensity of the disease can be captured. The paper discusses about the prevailing health system and insurance schemes, the treatment facilities for disease like cancer. The availability of medical imaging tools like x-ray, mammogram, ultrasound, CT and MRI scans and its innovations for the public health diagnosis the diseases in various methods with the aid of modern machines and techniques. The techniques vary in terms of cost, methodology in detecting the diseases and even the accuracy. The people could not continue the treatment because of high cost and sometimes scarcity of medicines. As the treatment are costlier irrespective of various classes of people approach the social security organizations and because of continuous usage the equipments worn out. Though these tools are considered as boon in the field of medical imaging each has its own drawback. The result of the paper states that the physicians can detect the early stage of disease with the aid of these tools and can come up with treatment that will avoid serious health issues or sometimes death. Also the government of concern country is responsible for all the public and seek opportunity for developing health sector often

A H2AX–CARP-1 Interaction Regulates Apoptosis Signaling Following DNA Damage

Cell Cycle and Apoptosis Regulatory Protein (CARP-1/CCAR1) is a peri-nuclear phosphoprotein that regulates apoptosis via chemotherapeutic Adriamycin (doxorubicin) and a novel class of CARP-1 functional mimetic (CFM) compounds. Although Adriamycin causes DNA damage, data from Comet assays revealed that CFM-4.16 also induced DNA damage. Phosphorylation of histone 2AX (γH2AX) protein is involved in regulating DNA damage repair and apoptosis signaling. Adriamycin or CFM-4.16 treatments inhibited cell growth and caused elevated CARP-1 and γH2AX in human breast (HBC) and cervical cancer (HeLa) cells. In fact, a robust nuclear or peri-nuclear co-localization of CARP-1 and γH2AX occurred in cells undergoing apoptosis. Knock-down of CARP-1 diminished γH2AX, their co-localization, and apoptosis in CFM-4.16- or Adriamycin-treated cells. We found that CARP-1 directly binds with H2AX, and H2AX interacted with CARP-1, but not CARP-1 (Δ600–652) mutant. Moreover, cells expressing CARP-1 (Δ600–652) mutant were resistant to apoptosis, and had diminished levels of γH2AX, when compared with cells expressing wild-type CARP-1. Mutagenesis studies revealed that H2AX residues 1–35 harbored a CARP-1-binding epitope, while CARP-1 amino acids 636–650 contained an H2AX-interacting epitope. Surface plasmon resonance studies revealed that CARP-1 (636–650) peptide bound with H2AX (1–35) peptide with a dissociation constant (Kd) of 127 nM. Cells expressing enhanced GFP (EGFP)-tagged H2AX (1–35) peptide or EGFP-tagged CARP-1 (636–650) peptide were resistant to inhibition by Adriamycin or CFM-4.16. Treatment of cells with transactivator of transcription (TAT)-tagged CARP-1 (636–650) peptide resulted in a moderate, statistically significant abrogation of Adriamycin-induced growth inhibition of cancer cells. Our studies provide evidence for requirement of CARP-1 interaction with H2AX in apoptosis signaling by Adriamycin and CFM compounds

Phosphorylation of cell cycle and apoptosis regulatory protein-1 by stress activated protein kinase P38γ is a novel mechanism of apoptosis signaling by genotoxic chemotherapy

CARP-1, a perinuclear phospho-protein, regulates cell survival and apoptosis signaling induced by genotoxic drugs. However, kinase(s) phosphorylating CARP-1 and down-stream signal transduction events remain unclear. Here we find that CARP-1 Serine (S)626 and Threonine (T)627 substitution to Alanines (AA) inhibits genotoxic drug-induced apoptosis. CARP-1 T627 is followed by a Proline (P), and this TP motif is conserved in vertebrates. Based on these findings, we generated affinity-purified, anti-phospho-CARP-1 T627 rabbit polyclonal antibodies, and utilized them to elucidate chemotherapy-activated, CARP-1-dependent cell growth signaling mechanisms. Our kinase profiling studies revealed that MAPKs/SAPKs phosphorylated CARP-1 T627. We then UV cross-linked protein extracts from Adriamycin-treated HeLa cervical cancer cells with a CARP-1 (614–638) peptide, and conducted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses of the peptide-bound protein complexes. This experiment revealed SAPK p38γ interaction with CARP-1 (614–638) peptide. Our studies further established that SAPK p38γ, but not other MAPKs, phosphorylates CARP-1 T627 in cancer cells treated with genotoxic drugs. Loss of p38γ abrogates CARP-1 T627 phosphorylation, and results in enhanced survival of breast cancer cells by genotoxic drugs. CARP-1 T627 phosphorylation was also noted in breast tumors from patients treated with radiation or endocrine therapies. We conclude that genotoxic drugs activate p38γ-dependent CARP-1 T627 phosphorylation to inhibit cell growth

Using a Prediction Model to Manage Cyber Security Threats

Cyber-attacks are an important issue faced by all organizations. Securing information systems is critical. Organizations should be able to understand the ecosystem and predict attacks. Predicting attacks quantitatively should be part of risk management. The cost impact due to worms, viruses, or other malicious software is significant. This paper proposes a mathematical model to predict the impact of an attack based on significant factors that influence cyber security. This model also considers the environmental information required. It is generalized and can be customized to the needs of the individual organization

<span style="font-variant: small-caps">A H2AX–CARP-1 </span>Interaction Regulates Apoptosis Signaling Following DNA Damage

Cell Cycle and Apoptosis Regulatory Protein (CARP-1/CCAR1) is a peri-nuclear phosphoprotein that regulates apoptosis via chemotherapeutic Adriamycin (doxorubicin) and a novel class of CARP-1 functional mimetic (CFM) compounds. Although Adriamycin causes DNA damage, data from Comet assays revealed that CFM-4.16 also induced DNA damage. Phosphorylation of histone 2AX (&#947;H2AX) protein is involved in regulating DNA damage repair and apoptosis signaling. Adriamycin or CFM-4.16 treatments inhibited cell growth and caused elevated CARP-1 and &#947;H2AX in human breast (HBC) and cervical cancer (HeLa) cells. In fact, a robust nuclear or peri-nuclear co-localization of CARP-1 and &#947;H2AX occurred in cells undergoing apoptosis. Knock-down of CARP-1 diminished &#947;H2AX, their co-localization, and apoptosis in CFM-4.16- or Adriamycin-treated cells. We found that CARP-1 directly binds with H2AX, and H2AX interacted with CARP-1, but not CARP-1 (&#916;600&#8315;652) mutant. Moreover, cells expressing CARP-1 (&#916;600&#8315;652) mutant were resistant to apoptosis, and had diminished levels of &#947;H2AX, when compared with cells expressing wild-type CARP-1. Mutagenesis studies revealed that H2AX residues 1&#8315;35 harbored a CARP-1-binding epitope, while CARP-1 amino acids 636&#8315;650 contained an H2AX-interacting epitope. Surface plasmon resonance studies revealed that CARP-1 (636&#8315;650) peptide bound with H2AX (1&#8315;35) peptide with a dissociation constant (Kd) of 127 nM. Cells expressing enhanced GFP (EGFP)-tagged H2AX (1&#8315;35) peptide or EGFP-tagged CARP-1 (636&#8315;650) peptide were resistant to inhibition by Adriamycin or CFM-4.16. Treatment of cells with transactivator of transcription (TAT)-tagged CARP-1 (636&#8315;650) peptide resulted in a moderate, statistically significant abrogation of Adriamycin-induced growth inhibition of cancer cells. Our studies provide evidence for requirement of CARP-1 interaction with H2AX in apoptosis signaling by Adriamycin and CFM compounds

The Expanding Role of Cancer Stem Cell Marker ALDH1A3 in Cancer and Beyond

Aldehyde dehydrogenase 1A3 (ALDH1A3) is one of 19 ALDH enzymes expressed in humans, and it is critical in the production of hormone receptor ligand retinoic acid (RA). We review the role of ALDH1A3 in normal physiology, its identification as a cancer stem cell marker, and its modes of action in cancer and other diseases. ALDH1A3 is often over-expressed in cancer and promotes tumor growth, metastasis, and chemoresistance by altering gene expression, cell signaling pathways, and glycometabolism. The increased levels of ALDH1A3 in cancer occur due to genetic amplification, epigenetic modifications, post-transcriptional regulation, and post-translational modification. Finally, we review the potential of targeting ALDH1A3, with both general ALDH inhibitors and small molecules specifically designed to inhibit ALDH1A3 activity