Anand Mehta - Academia.edu (original) (raw)

Papers by Anand Mehta

Research paper thumbnail of Parameterized Kernels for Support Vector Machine Classification

Proceedings of the Second International Conference on Computer Vision Theory and Applications, 2007

Kernel machines (e.g. SVM, KLDA) have shown state-of-the-art performance in several visual classi... more Kernel machines (e.g. SVM, KLDA) have shown state-of-the-art performance in several visual classification tasks. The classification performance of kernel machines greatly depends on the choice of kernels and its parameters. In this paper, we propose a method to search over the space of parameterized kernels using a gradient-based method. Our method effectively learns a non-linear representation of the data useful for classification and simultaneously performs dimensionality reduction. In addition, we introduce a new matrix formulation that simplifies and unifies previous approaches. The effectiveness and robustness of the proposed algorithm is demonstrated in both synthetic and real examples of pedestrian and mouth detection in images.

Research paper thumbnail of MALDI Imaging Mass Spectrometry of N-glycans and Tryptic Peptides from the Same Formalin-Fixed, Paraffin-Embedded Tissue Section

Methods in molecular biology (Clifton, N.J.), Jan 21, 2017

Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a unique a... more Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a unique and well developed tool for probing the protein content of formalin-fixed, paraffin-embedded tissue (FFPE). Integral to this approach is the application of trypsin, and more recently peptide N-glycosidase F, to release tryptic peptides or N-glycans from tissue and report localization of distinct species. This is typically done on serial or adjacent tissue sections, and there is an emerging need to understand the colocalized protein population linked to the exact same regions of N-glycans. Here we describe an approach where N-glycans are first imaged from a tissue section followed by reprocessing of the same tissue section for tryptic peptide MALDI IMS. Strategies for colocalizing peptides to target N-glycans or N-glycan regions are described.

Research paper thumbnail of Diagnosis of liver pathology through assesment of protein glycosylation

Research paper thumbnail of Substance Abuse, HIV-1 and Hepatitis

Current HIV Research, 2012

During the course of human immunodeficiency virus type 1 (HIV-1) disease, the virus has been show... more During the course of human immunodeficiency virus type 1 (HIV-1) disease, the virus has been shown to effectively escape the immune response with the subsequent establishment of latent viral reservoirs in specific cell populations within the peripheral blood (PB) and associated lymphoid tissues, bone marrow (BM), brain, and potentially other end organs. HIV-1, along with hepatitis B and C viruses (HBV and HCV), are known to share similar routes of transmission, including intravenous drug use, blood transfusions, sexual intercourse, and perinatal exposure. Substance abuse, including the use of opioids and cocaine, is a significant risk factor for exposure to HIV-1 and the development of acquired immune deficiency syndrome, as well as HBV and HCV exposure, infection, and disease. Thus, coinfection with HIV-1 and HBV or HCV is common and may be impacted by chronic substance abuse during the course of disease. HIV-1 impacts the natural course of HBV and HCV infection by accelerating the progression of HBV/HCVassociated liver disease toward end-stage cirrhosis and quantitative depletion of the CD4 + T-cell compartment. HBV or HCV coinfection with HIV-1 is also associated with increased mortality when compared to either infection alone. This review focuses on the impact of substance abuse and coinfection with HBV and HCV in the PB, BM, and brain on the HIV-1 pathogenic process as it relates to viral pathogenesis, disease progression, and the associated immune response during the course of this complex interplay. The impact of HIV-1 and substance abuse on hepatitis virusinduced disease is also a focal point.

Research paper thumbnail of Diagnosis of Liver Pathology Through Assessment of Protein Glycosylation

Research paper thumbnail of Imino sugars that are less toxic but more potent as antivirals, in vitro, compared with N-n-nonyl DNJ

Antiviral chemistry & chemotherapy, 2002

Imino sugar glucosidase inhibitors have selective antiviral activity against certain enveloped, m... more Imino sugar glucosidase inhibitors have selective antiviral activity against certain enveloped, mammalian viruses. Deoxynojirimycins (DNJs) modified by N-alkylation to contain a nine carbon atom side chain (N-n-nonyl-deoxynojirimycin; N-nonyl-DNJ, NN-DNJ) were shown to be, for example, at least 20 times more potent in inhibiting hepatitis B virus (HBV) and bovine viral diarrhoea virus (BVDV) in cell based assays than the non-alkylated DNJ. These data suggested that modification of the alkyl side chain could influence antiviral activity. Previous work has focused on varying side chain length. In this report, the influence of side chain branching and cyclization upon toxicity and antiviral activity was explored. Briefly, using a virus secretion assay for HBV and a single step growth (yield reduction) assay for BVDV, 14 different DNJ-based sugars, possessing various N-alkyl substitutions, were tested for antiviral activity. Of the series, N-methoxy-nonyl-DNJ and N-butyl-cyclohexyl DNJ ...

Research paper thumbnail of Host erythrocyte environment influences the localization of exported protein 2, an essential component of the Plasmodium translocon

Eukaryotic Cell, 2015

Malaria parasites replicating inside red blood cells (RBCs) export a large subset of proteins int... more Malaria parasites replicating inside red blood cells (RBCs) export a large subset of proteins into the erythrocyte cytoplasm to facilitate parasite growth and survival. PTEX, the parasite-encoded translocon, mediates protein transport across the parasitophorous vacuolar membrane (PVM) in Plasmodium falciparum -infected erythrocytes. Proteins exported into the erythrocyte cytoplasm have been localized to membranous structures, such as Maurer's clefts, small vesicles, and a tubovesicular network. Comparable studies of protein trafficking in Plasmodium vivax -infected reticulocytes are limited. With Plasmodium yoelii -infected reticulocytes, we identified exported protein 2 (Exp2) in a proteomic screen of proteins putatively transported across the PVM. Immunofluorescence studies showed that P. yoelii Exp2 ( Py Exp2) was primarily localized to the PVM. Unexpectedly, Py Exp2 was also associated with distinct, membrane-bound vesicles in the reticulocyte cytoplasm. This is in contrast ...

Research paper thumbnail of Emphysematous cystitis with clinical subcutaneous emphysema

International Journal of Emergency Medicine, 2011

Emphysematous cystitis (EC) is the presence of intramural gas, with or without luminal gas, withi... more Emphysematous cystitis (EC) is the presence of intramural gas, with or without luminal gas, within the bladder as a result of a primary infection of the lower urinary tract with a gas-producing organism. It is a well-recognised complication of urinary tract infections involving Escherichia coli in diabetic patients. Clinical subcutaneous emphysema is a rare complication of EC that appears to have poor prognosis. Only careful clinical judgement, and a high degree of suspicion, will lead to its early diagnosis and treatment. Here, we report a case of subcutaneous emphysema due to EC based on a clinical diagnosis confirmed using computed tomography (CT).

Research paper thumbnail of Glycosylation and Liver Cancer

Advances in Cancer Research, 2015

Liver cancer is the 5 th most common cancer, but the 2 nd leading cause of cancer death, in the w... more Liver cancer is the 5 th most common cancer, but the 2 nd leading cause of cancer death, in the world, with more than 700,000 fatalities annually. The major etiology of liver cancer is infection with an hepatotropic virus such as hepatitis B virus (HBV) or hepatitis C virus infection (HCV). While chronic viral infection remains the main cause of liver disease and risk of HCC, rates of non-viral associated HCC are occurring at an alarmingly increasing rate. Like many cancers, survival rates are closely associated with time of detection. If HCC is caught early, survival rates can be as high as 50%. Regrettably, most cases of HCC are caught late where survival rates can be as low as 2-7%. Thus, there has been great interest in discovering serum biomarkers that could be used to identify those with HCC. To this end, many groups have examined the N-linked glycans to identify changes that occur with HCC. As the liver secretes the vast majority of proteins into the serum, this has often been a starting point for study. In serum, alterations in core fucosylation, outer-arm fucosylation, increased sialylation and glycan branching have been observed in patients with HCC. Similar findings have been found directly in HCC tissue suggesting that these glycan changes may play a role in tumor formation and development.

Research paper thumbnail of Implementation of single precision floating point multiplier using Karatsuba algorithm

2013 International Conference on Green Computing, Communication and Conservation of Energy (ICGCE), 2013

ABSTRACT This paper presents an efficient floating point multiplier using Karatsuba algorithm. Di... more ABSTRACT This paper presents an efficient floating point multiplier using Karatsuba algorithm. Digital signal processing algorithms and media applications use a large number of multiplications, which is both time and power consuming. We have used IEEE 754 format for binary representation of the floating point numbers. Verilog HDL is used to implement Karatsuba multiplication algorithm which is technology independent pipelined design. This multiplier implements the significant multiplication along with sign bit and exponent computations. Three stage pipelining is being used in the design with the latency of 8 clock cycles. In this design, the mantissa bits are divided into three parts of particular bit width in such a way so that the multiplication can be done using the standard multipliers available in FPGA cyclone II device family and synthesized using Altera-Quartus II.

Research paper thumbnail of Evidence That N-Linked Glycosylation Is Necessary for Hepatitis B Virus Secretion

Virology, 1995

Human hepatitis B virus (HBV) envelopes contain three distinct glycoproteins called L, M, and S H... more Human hepatitis B virus (HBV) envelopes contain three distinct glycoproteins called L, M, and S HBsAg. Each is posttranslationally modified to contain N-linked oligosaccharides. N-linked oligosaccharides, after attachment to a polypeptide backbone, are processed by enzymes within the endoplasmic reticulum (ER). There is uncertainty about what role, if any, these N glycans and their modification in the ER play in the function of the HBV envelope proteins. By treating hepatoblastoma cultures which secrete HBV (HepG 2.2.15 cells) with inhibitors of different steps of the glycosylation and glycan modifying pathway, we provide evidence that glycosylation and the first step in the processing pathway are necessary for virion, but not subviral particle, secretion. That is, using a highly sensitive immunoprecipitation/polymerase chain reaction system, enveloped HBV could not be detected in the medium of HepG2.2.15 cells incubated with tunicamycin. However, HBV subviral particle secretion was not prevented by tunicamycin. Moreover, inhibitors of a-glucosidase I (the first step in the glycan processing pathway) also prevented virion secretion. Inhibitors of mannose trimming (a later step) and glycolipid synthesis, did not prevent virion secretion, defining the limits of the glycosylation requirements in secretion. These results demonstrate a requirement for N-glycosylation and glucosidase processing in the secretion of virions and further distinguish between the requirements for virion and subviral particle secretion.

Research paper thumbnail of An Acidic Motif Retains Vesicular Monoamine Transporter 2 on Large Dense Core Vesicles

Journal of Cell Biology, 2001

The release of biogenic amines from large dense core vesicles (LDCVs) depends on localization of ... more The release of biogenic amines from large dense core vesicles (LDCVs) depends on localization of the vesicular monoamine transporter VMAT2 to LDCVs. We now find that a cluster of acidic residues including two serines phosphorylated by casein kinase 2 is required for the localization of VMAT2 to LDCVs. Deletion of the acidic cluster promotes the removal of VMAT2 from LDCVs during their maturation. The motif thus acts as a signal for retention on LDCVs. In addition, replacement of the serines by glutamate to mimic phosphorylation promotes the removal of VMAT2 from LDCVs, whereas replacement by alanine to prevent phosphorylation decreases removal. Phosphorylation of the acidic cluster thus appears to reduce the localization of VMAT2 to LDCVs by inactivating a retention mechanism.

Research paper thumbnail of The influence of new guidelines on cardiopulmonary resuscitation (CPR) decisions. Five cycles of audit of a clerk proforma which included a resuscitation decision

Resuscitation, 2003

Current guidelines advise discussion with patients before issuing a &... more Current guidelines advise discussion with patients before issuing a 'do not attempt resuscitation' (DNAR) order. We report five audit cycles of cardiopulmonary resuscitation (CPR) documentation after introducing a proforma, the last cycle following the latest guidelines. In first audit data were collected from 75 patient discharges. CPR decisions were documented in 27 (36%). Four subsequent point prevalence audits carried out on all inpatients following proforma introduction showed documentation improved to 102/109 (94%), 135/148 (91%), 131/140 (94%) and 102/119 (86%) in cycles two, three, four and five, respectively. The last three audits also revealed that consultants consistently made more DNAR orders than trainee doctors. However, following the introduction of the latest guidelines the proportion of patients in whom a decision was made, and the percentage of those decisions that were DNAR, fell.

Research paper thumbnail of Peptide histidine methionine (PHM) increases ileostomy output

Regulatory Peptides, 1988

The human vasoactive intestinal peptide (VIP) gene also encodes peptides histidine methionine (PH... more The human vasoactive intestinal peptide (VIP) gene also encodes peptides histidine methionine (PHM) which has substantial sequence homology with VIP. Both are present in nerve fibers in the human ileum and circulate in greatly increased concentrations in patients with the watery diarrhoea syndrome. We have infused PHM (23 pmol/kg/min) into 5 patients with ileostomies to determine the effect of PHM on human ileal output. Plasma PHM levels rose from 22 + 6 to 6013 4-874 pM (mean 4-S.E.M.) during PHM infusions and ileal output rose from 16 ± 3 to 177 4-27 g/30 min (P < 0.0001). PHM infusions also produced a significant fall in the percentage of solid material and a rise in the concentration of chloride in the ileal effluent. Mean plasma PHM concentrations during PHM infusions were equal to the highest levels seen in patients with the watery diarrhoea syndrome, so PHM may contribute to diarrhoea in this condition. Neuronal PHM may exert physiological control over ileal transport of water and electrolytes.

Research paper thumbnail of Altered Functionality of Anti-Bacterial Antibodies in Patients with Chronic Hepatitis C Virus Infection

Research paper thumbnail of Acquired Autoimmune Polyglandular Syndrome, Thymoma, and an AIRE Defect

New England Journal of Medicine, 2010

Research paper thumbnail of GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma

Journal of Hepatology, 2005

Background/Aims: Golgi protein-73 (GP73) is up-regulated in hepatocellular carcinoma (HCC). The a... more Background/Aims: Golgi protein-73 (GP73) is up-regulated in hepatocellular carcinoma (HCC). The aims of this study were to determine if GP73 is detected in the serum, and to establish the sensitivity and specificity of serum GP73 for diagnosing HCC. Methods: Serum GP73 was detected by immunoblots and quantified by densitometric analysis. Results: A total of 352 patients were studied. Serum GP73 levels were significantly higher in patients with HCC compared to those with cirrhosis (P!0.001). GP73 had a sensitivity of 69% and a specificity of 75% at the optimal cutoff point of 10 relative units, with an area under the receiver operating curve of 0.79 vs. 0.61 for AFP (PZ0.001). GP73 levels had significantly higher sensitivity (62%) than AFP (25%) for diagnosing early HCC (P!0.0001). Moreover, GP73 levels were elevated in the serum of 57% (32/56) of individuals with HCC who had serum AFP levels less than 20 ng/ml. Conclusions: Higher levels of GP73 can be found in the serum of patients with HCC than of those without. GP73 was better than AFP for the diagnosis of early HCC. Further validation studies are needed to confirm the role of GP73 in the early detection of HCC.

Research paper thumbnail of Massive Thrombus in Transit Detected by Echocardiography

Journal of Cardiothoracic and Vascular Anesthesia, 2008

extraterrestrial visitors to our planet, the intracardiac “unidentified” object shown here displa... more extraterrestrial visitors to our planet, the intracardiac “unidentified” object shown here displayed a pattern of motion that was inconsistent with any known law of physics and was easily debunked by an alternative viewing perspective. The images reinforce that catheters, cannulae, or pacing electrodes are best examined by using multiple TEE imaging planes in order to definitively exclude imaging artifacts that may otherwise be misidentified as relevant intracardiac structures1,2 or a portent of imminent alien invasion.

Research paper thumbnail of Human Immunodeficiency Virus-Related Microbial Translocation and Progression of Hepatitis C

Gastroenterology, 2008

Background & Aims-HIV-1 infection has been associated with enhanced microbial translocation, and ... more Background & Aims-HIV-1 infection has been associated with enhanced microbial translocation, and microbial translocation is a mechanism through which alcohol and some enteric conditions cause liver disease. We hypothesized that HIV promotes liver disease by enhancing microbial translocation. Methods-We studied human cohorts in which hepatitis C virus (HCV) and HIV outcomes were carefully characterized. Results-HIV-related CD4+ lymphocyte depletion was strongly associated with microbial translocation as indicated by elevated levels of circulating lipopolysaccharide (LPS), LPS binding protein, soluble CD14, fucose-binding lectin (AAL) reactive to IgG specific for the alpha galactose epitope, and suppressed levels of endotoxin-core antibodies (EndoCAb IgM) in HIV-infected subjects compared with the same persons before they had HIV infection and compared with HIVuninfected subjects. The same measures of microbial translocation were strongly associated with HCV-related liver disease progression (cirrhosis), e.g. LPS, odds ratio 19.0 (p = 0.002), AAL, odds ratio 27.8 (p<0.0001); in addition, levels of LPS were elevated prior to recognition of cirrhosis. Conclusions-Microbial translocation may be a fundamental mechanism through which HIV accelerates progression of chronic liver disease.

Research paper thumbnail of α-Glucosidase inhibitors as potential broad based anti-viral agents

FEBS Letters, 1998

N-Linked oligosaccharides play many roles in the fate and functions of glycoproteins. One functio... more N-Linked oligosaccharides play many roles in the fate and functions of glycoproteins. One function is to assist in the folding of proteins by mediating interactions of the lectin-like chaperone proteins calnexin and calreticulin with nascent glycoproteins. These interactions can be prevented by inhibitors of the K K-glucosidases and this causes some proteins to be misfolded and retained within the endoplasmic reticulum. In human immunodeficiency virus (HIV) and hepatitis B virus (HBV) the misfolding of key viral envelope glycoproteins interferes with the viral life cycle. It has been demonstrated in an animal model of chronic HBV that glucosidase inhibitors can alter glycosylation and have anti-viral activity. As the mechanism of action of K K-glucosidase inhibitors is the induction of misfolded or otherwise defective viral glycoproteins, such inhibitors may be useful therapeutics for many viruses, especially those which bud from the endoplasmic reticulum (where protein folding takes place). For example bovine viral diarrhea virus, a pestivirus akin to hepatitis C virus, is also extremely sensitive to glucosidase inhibition.

Research paper thumbnail of Parameterized Kernels for Support Vector Machine Classification

Proceedings of the Second International Conference on Computer Vision Theory and Applications, 2007

Kernel machines (e.g. SVM, KLDA) have shown state-of-the-art performance in several visual classi... more Kernel machines (e.g. SVM, KLDA) have shown state-of-the-art performance in several visual classification tasks. The classification performance of kernel machines greatly depends on the choice of kernels and its parameters. In this paper, we propose a method to search over the space of parameterized kernels using a gradient-based method. Our method effectively learns a non-linear representation of the data useful for classification and simultaneously performs dimensionality reduction. In addition, we introduce a new matrix formulation that simplifies and unifies previous approaches. The effectiveness and robustness of the proposed algorithm is demonstrated in both synthetic and real examples of pedestrian and mouth detection in images.

Research paper thumbnail of MALDI Imaging Mass Spectrometry of N-glycans and Tryptic Peptides from the Same Formalin-Fixed, Paraffin-Embedded Tissue Section

Methods in molecular biology (Clifton, N.J.), Jan 21, 2017

Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a unique a... more Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a unique and well developed tool for probing the protein content of formalin-fixed, paraffin-embedded tissue (FFPE). Integral to this approach is the application of trypsin, and more recently peptide N-glycosidase F, to release tryptic peptides or N-glycans from tissue and report localization of distinct species. This is typically done on serial or adjacent tissue sections, and there is an emerging need to understand the colocalized protein population linked to the exact same regions of N-glycans. Here we describe an approach where N-glycans are first imaged from a tissue section followed by reprocessing of the same tissue section for tryptic peptide MALDI IMS. Strategies for colocalizing peptides to target N-glycans or N-glycan regions are described.

Research paper thumbnail of Diagnosis of liver pathology through assesment of protein glycosylation

Research paper thumbnail of Substance Abuse, HIV-1 and Hepatitis

Current HIV Research, 2012

During the course of human immunodeficiency virus type 1 (HIV-1) disease, the virus has been show... more During the course of human immunodeficiency virus type 1 (HIV-1) disease, the virus has been shown to effectively escape the immune response with the subsequent establishment of latent viral reservoirs in specific cell populations within the peripheral blood (PB) and associated lymphoid tissues, bone marrow (BM), brain, and potentially other end organs. HIV-1, along with hepatitis B and C viruses (HBV and HCV), are known to share similar routes of transmission, including intravenous drug use, blood transfusions, sexual intercourse, and perinatal exposure. Substance abuse, including the use of opioids and cocaine, is a significant risk factor for exposure to HIV-1 and the development of acquired immune deficiency syndrome, as well as HBV and HCV exposure, infection, and disease. Thus, coinfection with HIV-1 and HBV or HCV is common and may be impacted by chronic substance abuse during the course of disease. HIV-1 impacts the natural course of HBV and HCV infection by accelerating the progression of HBV/HCVassociated liver disease toward end-stage cirrhosis and quantitative depletion of the CD4 + T-cell compartment. HBV or HCV coinfection with HIV-1 is also associated with increased mortality when compared to either infection alone. This review focuses on the impact of substance abuse and coinfection with HBV and HCV in the PB, BM, and brain on the HIV-1 pathogenic process as it relates to viral pathogenesis, disease progression, and the associated immune response during the course of this complex interplay. The impact of HIV-1 and substance abuse on hepatitis virusinduced disease is also a focal point.

Research paper thumbnail of Diagnosis of Liver Pathology Through Assessment of Protein Glycosylation

Research paper thumbnail of Imino sugars that are less toxic but more potent as antivirals, in vitro, compared with N-n-nonyl DNJ

Antiviral chemistry & chemotherapy, 2002

Imino sugar glucosidase inhibitors have selective antiviral activity against certain enveloped, m... more Imino sugar glucosidase inhibitors have selective antiviral activity against certain enveloped, mammalian viruses. Deoxynojirimycins (DNJs) modified by N-alkylation to contain a nine carbon atom side chain (N-n-nonyl-deoxynojirimycin; N-nonyl-DNJ, NN-DNJ) were shown to be, for example, at least 20 times more potent in inhibiting hepatitis B virus (HBV) and bovine viral diarrhoea virus (BVDV) in cell based assays than the non-alkylated DNJ. These data suggested that modification of the alkyl side chain could influence antiviral activity. Previous work has focused on varying side chain length. In this report, the influence of side chain branching and cyclization upon toxicity and antiviral activity was explored. Briefly, using a virus secretion assay for HBV and a single step growth (yield reduction) assay for BVDV, 14 different DNJ-based sugars, possessing various N-alkyl substitutions, were tested for antiviral activity. Of the series, N-methoxy-nonyl-DNJ and N-butyl-cyclohexyl DNJ ...

Research paper thumbnail of Host erythrocyte environment influences the localization of exported protein 2, an essential component of the Plasmodium translocon

Eukaryotic Cell, 2015

Malaria parasites replicating inside red blood cells (RBCs) export a large subset of proteins int... more Malaria parasites replicating inside red blood cells (RBCs) export a large subset of proteins into the erythrocyte cytoplasm to facilitate parasite growth and survival. PTEX, the parasite-encoded translocon, mediates protein transport across the parasitophorous vacuolar membrane (PVM) in Plasmodium falciparum -infected erythrocytes. Proteins exported into the erythrocyte cytoplasm have been localized to membranous structures, such as Maurer's clefts, small vesicles, and a tubovesicular network. Comparable studies of protein trafficking in Plasmodium vivax -infected reticulocytes are limited. With Plasmodium yoelii -infected reticulocytes, we identified exported protein 2 (Exp2) in a proteomic screen of proteins putatively transported across the PVM. Immunofluorescence studies showed that P. yoelii Exp2 ( Py Exp2) was primarily localized to the PVM. Unexpectedly, Py Exp2 was also associated with distinct, membrane-bound vesicles in the reticulocyte cytoplasm. This is in contrast ...

Research paper thumbnail of Emphysematous cystitis with clinical subcutaneous emphysema

International Journal of Emergency Medicine, 2011

Emphysematous cystitis (EC) is the presence of intramural gas, with or without luminal gas, withi... more Emphysematous cystitis (EC) is the presence of intramural gas, with or without luminal gas, within the bladder as a result of a primary infection of the lower urinary tract with a gas-producing organism. It is a well-recognised complication of urinary tract infections involving Escherichia coli in diabetic patients. Clinical subcutaneous emphysema is a rare complication of EC that appears to have poor prognosis. Only careful clinical judgement, and a high degree of suspicion, will lead to its early diagnosis and treatment. Here, we report a case of subcutaneous emphysema due to EC based on a clinical diagnosis confirmed using computed tomography (CT).

Research paper thumbnail of Glycosylation and Liver Cancer

Advances in Cancer Research, 2015

Liver cancer is the 5 th most common cancer, but the 2 nd leading cause of cancer death, in the w... more Liver cancer is the 5 th most common cancer, but the 2 nd leading cause of cancer death, in the world, with more than 700,000 fatalities annually. The major etiology of liver cancer is infection with an hepatotropic virus such as hepatitis B virus (HBV) or hepatitis C virus infection (HCV). While chronic viral infection remains the main cause of liver disease and risk of HCC, rates of non-viral associated HCC are occurring at an alarmingly increasing rate. Like many cancers, survival rates are closely associated with time of detection. If HCC is caught early, survival rates can be as high as 50%. Regrettably, most cases of HCC are caught late where survival rates can be as low as 2-7%. Thus, there has been great interest in discovering serum biomarkers that could be used to identify those with HCC. To this end, many groups have examined the N-linked glycans to identify changes that occur with HCC. As the liver secretes the vast majority of proteins into the serum, this has often been a starting point for study. In serum, alterations in core fucosylation, outer-arm fucosylation, increased sialylation and glycan branching have been observed in patients with HCC. Similar findings have been found directly in HCC tissue suggesting that these glycan changes may play a role in tumor formation and development.

Research paper thumbnail of Implementation of single precision floating point multiplier using Karatsuba algorithm

2013 International Conference on Green Computing, Communication and Conservation of Energy (ICGCE), 2013

ABSTRACT This paper presents an efficient floating point multiplier using Karatsuba algorithm. Di... more ABSTRACT This paper presents an efficient floating point multiplier using Karatsuba algorithm. Digital signal processing algorithms and media applications use a large number of multiplications, which is both time and power consuming. We have used IEEE 754 format for binary representation of the floating point numbers. Verilog HDL is used to implement Karatsuba multiplication algorithm which is technology independent pipelined design. This multiplier implements the significant multiplication along with sign bit and exponent computations. Three stage pipelining is being used in the design with the latency of 8 clock cycles. In this design, the mantissa bits are divided into three parts of particular bit width in such a way so that the multiplication can be done using the standard multipliers available in FPGA cyclone II device family and synthesized using Altera-Quartus II.

Research paper thumbnail of Evidence That N-Linked Glycosylation Is Necessary for Hepatitis B Virus Secretion

Virology, 1995

Human hepatitis B virus (HBV) envelopes contain three distinct glycoproteins called L, M, and S H... more Human hepatitis B virus (HBV) envelopes contain three distinct glycoproteins called L, M, and S HBsAg. Each is posttranslationally modified to contain N-linked oligosaccharides. N-linked oligosaccharides, after attachment to a polypeptide backbone, are processed by enzymes within the endoplasmic reticulum (ER). There is uncertainty about what role, if any, these N glycans and their modification in the ER play in the function of the HBV envelope proteins. By treating hepatoblastoma cultures which secrete HBV (HepG 2.2.15 cells) with inhibitors of different steps of the glycosylation and glycan modifying pathway, we provide evidence that glycosylation and the first step in the processing pathway are necessary for virion, but not subviral particle, secretion. That is, using a highly sensitive immunoprecipitation/polymerase chain reaction system, enveloped HBV could not be detected in the medium of HepG2.2.15 cells incubated with tunicamycin. However, HBV subviral particle secretion was not prevented by tunicamycin. Moreover, inhibitors of a-glucosidase I (the first step in the glycan processing pathway) also prevented virion secretion. Inhibitors of mannose trimming (a later step) and glycolipid synthesis, did not prevent virion secretion, defining the limits of the glycosylation requirements in secretion. These results demonstrate a requirement for N-glycosylation and glucosidase processing in the secretion of virions and further distinguish between the requirements for virion and subviral particle secretion.

Research paper thumbnail of An Acidic Motif Retains Vesicular Monoamine Transporter 2 on Large Dense Core Vesicles

Journal of Cell Biology, 2001

The release of biogenic amines from large dense core vesicles (LDCVs) depends on localization of ... more The release of biogenic amines from large dense core vesicles (LDCVs) depends on localization of the vesicular monoamine transporter VMAT2 to LDCVs. We now find that a cluster of acidic residues including two serines phosphorylated by casein kinase 2 is required for the localization of VMAT2 to LDCVs. Deletion of the acidic cluster promotes the removal of VMAT2 from LDCVs during their maturation. The motif thus acts as a signal for retention on LDCVs. In addition, replacement of the serines by glutamate to mimic phosphorylation promotes the removal of VMAT2 from LDCVs, whereas replacement by alanine to prevent phosphorylation decreases removal. Phosphorylation of the acidic cluster thus appears to reduce the localization of VMAT2 to LDCVs by inactivating a retention mechanism.

Research paper thumbnail of The influence of new guidelines on cardiopulmonary resuscitation (CPR) decisions. Five cycles of audit of a clerk proforma which included a resuscitation decision

Resuscitation, 2003

Current guidelines advise discussion with patients before issuing a &amp;amp;amp;amp;amp;amp;... more Current guidelines advise discussion with patients before issuing a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;do not attempt resuscitation&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; (DNAR) order. We report five audit cycles of cardiopulmonary resuscitation (CPR) documentation after introducing a proforma, the last cycle following the latest guidelines. In first audit data were collected from 75 patient discharges. CPR decisions were documented in 27 (36%). Four subsequent point prevalence audits carried out on all inpatients following proforma introduction showed documentation improved to 102/109 (94%), 135/148 (91%), 131/140 (94%) and 102/119 (86%) in cycles two, three, four and five, respectively. The last three audits also revealed that consultants consistently made more DNAR orders than trainee doctors. However, following the introduction of the latest guidelines the proportion of patients in whom a decision was made, and the percentage of those decisions that were DNAR, fell.

Research paper thumbnail of Peptide histidine methionine (PHM) increases ileostomy output

Regulatory Peptides, 1988

The human vasoactive intestinal peptide (VIP) gene also encodes peptides histidine methionine (PH... more The human vasoactive intestinal peptide (VIP) gene also encodes peptides histidine methionine (PHM) which has substantial sequence homology with VIP. Both are present in nerve fibers in the human ileum and circulate in greatly increased concentrations in patients with the watery diarrhoea syndrome. We have infused PHM (23 pmol/kg/min) into 5 patients with ileostomies to determine the effect of PHM on human ileal output. Plasma PHM levels rose from 22 + 6 to 6013 4-874 pM (mean 4-S.E.M.) during PHM infusions and ileal output rose from 16 ± 3 to 177 4-27 g/30 min (P < 0.0001). PHM infusions also produced a significant fall in the percentage of solid material and a rise in the concentration of chloride in the ileal effluent. Mean plasma PHM concentrations during PHM infusions were equal to the highest levels seen in patients with the watery diarrhoea syndrome, so PHM may contribute to diarrhoea in this condition. Neuronal PHM may exert physiological control over ileal transport of water and electrolytes.

Research paper thumbnail of Altered Functionality of Anti-Bacterial Antibodies in Patients with Chronic Hepatitis C Virus Infection

Research paper thumbnail of Acquired Autoimmune Polyglandular Syndrome, Thymoma, and an AIRE Defect

New England Journal of Medicine, 2010

Research paper thumbnail of GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma

Journal of Hepatology, 2005

Background/Aims: Golgi protein-73 (GP73) is up-regulated in hepatocellular carcinoma (HCC). The a... more Background/Aims: Golgi protein-73 (GP73) is up-regulated in hepatocellular carcinoma (HCC). The aims of this study were to determine if GP73 is detected in the serum, and to establish the sensitivity and specificity of serum GP73 for diagnosing HCC. Methods: Serum GP73 was detected by immunoblots and quantified by densitometric analysis. Results: A total of 352 patients were studied. Serum GP73 levels were significantly higher in patients with HCC compared to those with cirrhosis (P!0.001). GP73 had a sensitivity of 69% and a specificity of 75% at the optimal cutoff point of 10 relative units, with an area under the receiver operating curve of 0.79 vs. 0.61 for AFP (PZ0.001). GP73 levels had significantly higher sensitivity (62%) than AFP (25%) for diagnosing early HCC (P!0.0001). Moreover, GP73 levels were elevated in the serum of 57% (32/56) of individuals with HCC who had serum AFP levels less than 20 ng/ml. Conclusions: Higher levels of GP73 can be found in the serum of patients with HCC than of those without. GP73 was better than AFP for the diagnosis of early HCC. Further validation studies are needed to confirm the role of GP73 in the early detection of HCC.

Research paper thumbnail of Massive Thrombus in Transit Detected by Echocardiography

Journal of Cardiothoracic and Vascular Anesthesia, 2008

extraterrestrial visitors to our planet, the intracardiac “unidentified” object shown here displa... more extraterrestrial visitors to our planet, the intracardiac “unidentified” object shown here displayed a pattern of motion that was inconsistent with any known law of physics and was easily debunked by an alternative viewing perspective. The images reinforce that catheters, cannulae, or pacing electrodes are best examined by using multiple TEE imaging planes in order to definitively exclude imaging artifacts that may otherwise be misidentified as relevant intracardiac structures1,2 or a portent of imminent alien invasion.

Research paper thumbnail of Human Immunodeficiency Virus-Related Microbial Translocation and Progression of Hepatitis C

Gastroenterology, 2008

Background & Aims-HIV-1 infection has been associated with enhanced microbial translocation, and ... more Background & Aims-HIV-1 infection has been associated with enhanced microbial translocation, and microbial translocation is a mechanism through which alcohol and some enteric conditions cause liver disease. We hypothesized that HIV promotes liver disease by enhancing microbial translocation. Methods-We studied human cohorts in which hepatitis C virus (HCV) and HIV outcomes were carefully characterized. Results-HIV-related CD4+ lymphocyte depletion was strongly associated with microbial translocation as indicated by elevated levels of circulating lipopolysaccharide (LPS), LPS binding protein, soluble CD14, fucose-binding lectin (AAL) reactive to IgG specific for the alpha galactose epitope, and suppressed levels of endotoxin-core antibodies (EndoCAb IgM) in HIV-infected subjects compared with the same persons before they had HIV infection and compared with HIVuninfected subjects. The same measures of microbial translocation were strongly associated with HCV-related liver disease progression (cirrhosis), e.g. LPS, odds ratio 19.0 (p = 0.002), AAL, odds ratio 27.8 (p<0.0001); in addition, levels of LPS were elevated prior to recognition of cirrhosis. Conclusions-Microbial translocation may be a fundamental mechanism through which HIV accelerates progression of chronic liver disease.

Research paper thumbnail of α-Glucosidase inhibitors as potential broad based anti-viral agents

FEBS Letters, 1998

N-Linked oligosaccharides play many roles in the fate and functions of glycoproteins. One functio... more N-Linked oligosaccharides play many roles in the fate and functions of glycoproteins. One function is to assist in the folding of proteins by mediating interactions of the lectin-like chaperone proteins calnexin and calreticulin with nascent glycoproteins. These interactions can be prevented by inhibitors of the K K-glucosidases and this causes some proteins to be misfolded and retained within the endoplasmic reticulum. In human immunodeficiency virus (HIV) and hepatitis B virus (HBV) the misfolding of key viral envelope glycoproteins interferes with the viral life cycle. It has been demonstrated in an animal model of chronic HBV that glucosidase inhibitors can alter glycosylation and have anti-viral activity. As the mechanism of action of K K-glucosidase inhibitors is the induction of misfolded or otherwise defective viral glycoproteins, such inhibitors may be useful therapeutics for many viruses, especially those which bud from the endoplasmic reticulum (where protein folding takes place). For example bovine viral diarrhea virus, a pestivirus akin to hepatitis C virus, is also extremely sensitive to glucosidase inhibition.