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"Ganapathy, V"
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Steam generators and waste heat boilers : for process and plant engineers
This title focuses on the thermal design and performance aspects of steam generators, HRSGs and fire tube, water tube waste heat boilers including air heaters, and condensing economizers. Over 120 real-life problems are fully worked out which will help plant engineers in evaluating new boilers or making modifications to existing boiler components without assistance from boiler suppliers. The book examines recent trends and developments in boiler design and technology and presents novel ideas for improving boiler efficiency and lowering gas pressure drop.
Book
Anteroposterior stability: A determinant of gait dysfunction and falls in spinocerebellar ataxia
Background: Establishing an association between gait variability and direction specific balance indices may help in identifying the risk of falls in patients with spinocerebellar ataxia (SCA) which may help in developing an appropriate intervention. This study is intended to identify the association between balance and gait parameters especially gait variability in these patients. Methods: Patients with genetically confirmed SCA (n = 24) as well as controls (n = 24) who met the study criteria were recruited. Gait was assessed using the GAITRite system and balance was assessed using dynamic posturography (Biodex) to record direction-specific dynamic balance indices. Disease severity was assessed using international cooperative ataxia rating scale (ICARS). Results: The mean age of the SCA group (38.83 ± 13.03 years) and the control group (36.38 ± 9.09 years) were comparable. The age of onset of illness was 32 ± 10.62 years and duration of 5.67 ± 3.62 years. The mean ICARS was 45.10 ± 16.75. There was a significant difference in the overall balance index (OBI), anterior-posterior index (API), medial/lateral index (MLI) between SCA patients (4.56 ± 2.09, 3.49 ± 1.88, 2.94 ± 1.32) and the controls (2.72 ± 1.25, 2.08 ± 0.85, 1.85 ± 0.97). However, correlation was observed only between gait stability and balance parameters in API direction. Conclusions: There was an increased anteroposterior oriented balance deficit in patients with SCA, which was significantly correlating with the gait parameters. The balance training intervention may focus on improving anteroposterior direction to prevent falls and improving walking efficiency.
Journal Article
RCAD/Ufl1, a Ufm1 E3 ligase, is essential for hematopoietic stem cell function and murine hematopoiesis
The Ufm1 conjugation system is a novel ubiquitin-like modification system, consisting of Ufm1, Uba5 (E1), Ufc1 (E2) and poorly characterized E3 ligase(s). RCAD/Ufl1 (also known as KIAA0776, NLBP and Maxer) was reported to function as a Ufm1 E3 ligase in ufmylation (Ufm1-mediated conjugation) of DDRGK1 and ASC1 proteins. It has also been implicated in estrogen receptor signaling, unfolded protein response (UPR) and neurodegeneration, yet its physiological function remains completely unknown. In this study, we report that RCAD/Ufl1 is essential for embryonic development, hematopoietic stem cell (HSC) survival and erythroid differentiation. Both germ-line and somatic deletion of RCAD/Ufl1 impaired hematopoietic development, resulting in severe anemia, cytopenia and ultimately animal death. Depletion of RCAD/Ufl1 caused elevated endoplasmic reticulum stress and evoked UPR in bone marrow cells. In addition, loss of RCAD/Ufl1 blocked autophagic degradation, increased mitochondrial mass and reactive oxygen species, and led to DNA damage response, p53 activation and enhanced cell death of HSCs. Collectively, our study provides the first genetic evidence for the indispensable role of RCAD/Ufl1 in murine hematopoiesis and development. The finding of RCAD/Ufl1 as a key regulator of cellular stress response sheds a light into the role of a novel protein network including RCAD/Ufl1 and its associated proteins in regulating cellular homeostasis.
Journal Article
Role of SLC5A8, a plasma membrane transporter and a tumor suppressor, in the antitumor activity of dichloroacetate
There has been growing interest among the public and scientists in dichloroacetate (DCA) as a potential anticancer drug. Credible evidence exists for the antitumor activity of this compound, but high concentrations are needed for significant therapeutic effect. Unfortunately, these high concentrations produce detrimental side effects involving the nervous system, thereby precluding its use for cancer treatment. The mechanistic basis of the compound's antitumor activity is its ability to activate the pyruvate dehydrogenase complex through inhibition of pyruvate dehydrogenase kinase. As the compound inhibits the kinase at micromolar concentrations, it is not known why therapeutically prohibitive high doses are needed for suppression of tumor growth. We hypothesized that lack of effective mechanisms for the entry of DCA into tumor cells may underlie this phenomenon. Here we show that SLC5A8 transports DCA very effectively with high affinity. This transporter is expressed in normal cells, but expression is silenced in tumor cells by epigenetic mechanisms. The lack of the transporter makes tumor cells resistant to the antitumor activity of DCA. However, if the transporter is expressed in tumor cells ectopically, the cells become sensitive to the drug at low concentrations. This is evident in breast cancer cells, colon cancer cells and prostate cancer cells. Normal cells, which constitutively express the transporter, are however not affected by the compound, indicating tumor cell-selective therapeutic activity. The mechanism of the compound's antitumor activity still remains its ability to inhibit pyruvate dehydrogenase kinase and force mitochondrial oxidation of pyruvate. As silencing of SLC5A8 in tumors involves DNA methylation and its expression can be induced by treatment with DNA methylation inhibitors, our findings suggest that combining DCA with a DNA methylation inhibitor would offer a means to reduce the doses of DCA to avoid detrimental effects associated with high doses but without compromising antitumor activity.
Journal Article
Wnt inhibitory factor 1 suppresses cancer stemness and induces cellular senescence
Hyperactivation of the Wingless-type (Wnt)/
β
-catenin pathway promotes tumor initiation, tumor growth and metastasis in various tissues. Although there is evidence for the involvement of Wnt/
β
-catenin pathway activation in salivary gland tumors, the precise mechanisms are unknown. Here we report for the first time that downregulation of the Wnt inhibitory factor 1 (WIF1) is a widespread event in salivary gland carcinoma ex-pleomorphic adenoma (CaExPA). We also show that WIF1 downregulation occurs in the CaExPA precursor lesion pleomorphic adenoma (PA) and indicates a higher risk of progression from benign to malignant tumor. Our results demonstrate that diverse mechanisms including
WIF1
promoter hypermethylation and loss of heterozygosity contribute to WIF1 downregulation in human salivary gland tumors. In accordance with a crucial role in suppressing salivary gland tumor progression, WIF1 re-expression in salivary gland tumor cells inhibited cell proliferation, induced more differentiated phenotype and promoted cellular senescence, possibly through upregulation of tumor-suppressor genes, such as
p53
and
p21
. Most importantly, WIF1 significantly diminished the number of salivary gland cancer stem cells and the anchorage-independent cell growth. Consistent with this observation, WIF1 caused a reduction in the expression of pluripotency and stemness markers (
OCT4
and c-
MYC
), as well as adult stem cell self-renewal and multi-lineage differentiation markers, such as
WNT3A
,
TCF4
, c-
KIT
and
MYB
. Furthermore, WIF1 significantly increased the expression of microRNAs
pri-let-7a
and
pri-miR-200c
, negative regulators of stemness and cancer progression. In addition, we show that WIF1 functions as a positive regulator of
miR-200c
, leading to downregulation of
BMI1
,
ZEB1
and
ZEB2
, with a consequent increase in downstream targets such as E-cadherin. Our study emphasizes the prognostic and therapeutic potential of WIF1 in human salivary gland CaExPA. Moreover, our findings demonstrate a novel mechanism by which WIF1 regulates cancer stemness and senescence, which might have major implications in the field of cancer biology.
Journal Article
Regenerative chatter control in turning process using constrained viscoelastic vibration absorber
This paper focuses on utilization of viscoelastic material to control regenerative chatter in turning process. Self-induced vibrations can lead to the condition called regenerative chatter which produces violent relative vibrations between cutting tool and workpiece and reduces tool life and productivity. The regenerative chatter in turning processes can be controlled by maximizing negative real part of the frequency response function of cutting tool structure. In order to achieve this, a constrained viscoelastic vibration absorber (CVVA) is used. A CVVA consists of a viscoelastic material, such as natural rubber, which is sandwiched between two similar or dissimilar metallic layers. The CVVA is used as a cantilever beam whose fundamental natural frequency is tuned to the natural frequency of the dominant mode of cutting tool/tool holder. The optimum stiffness and damping coefficient of the CVVA are found using a numerical optimization technique and these optimal values are used to find the dimensions of CVVA. The resulting natural frequency of CVVA is verified using finite element simulation software ANSYS. The effectiveness of CVVA in controlling regenerative chatter in a compact CNC lathe is also analysed by constructing stability lobes which are plots of depth of cut vs spindle speed.
Journal Article
Power Quality Improvement Using Multi-Level Inverter Based DVR and DSTATCOM Using Neuro-Fuzzy Controller
STATCOM is one of the shunt type FACTS controllers which can supply reactive power and improve bus voltage. STATCOM, a controlling device used on alternating current transmission networks, has advantages like transient free switching and smooth variation of reactive power. This paper proposes a cascaded multilevel inverter type DSTATCOM and DVR to compensate voltage sag in utilities in power distribution network. The proposed DSTATCOM is implemented using multilevel topology with isolated dc energy storage and reduced number of switches. A DVR injects a voltage in series with the system voltage and a D-STATCOM implant a current into the system to correct the voltage sag, swell and interruption. The phase shifter PWM technique is described to generate firing pulse to cascaded inverter. The proposed neuro-fuzzy controller follow itself to the sag and provides effective means of mitigation. The voltage sag with the minimum harmonic at the efficacy end. The proposed technique is simulated using MATLAB/Simulink.
Journal Article