Vikas Yadav - Academia.edu (original) (raw)
Papers by Vikas Yadav
Active queue management disciplines such as RED and its extensions (CHOKe, FRED, BRED) have been ... more Active queue management disciplines such as RED and its extensions (CHOKe, FRED, BRED) have been widely studied as mechanisms for providing congestion avoidance, differentiated services and fairness between different traffic classes. With the emergence of new applications with diverse QoS requirements over the Internet, the need for mechanisms that provide differentiated services has become increasingly important. We propose Selective Fair Early Detection (SFED), a rate control based queue management discipline which ensures a fair bandwidth allocation amongst competing flows even in the presence of nonadaptive traffic. We show that SFED can be used to partition bandwidth in proportion to pre-assigned weights and is well-suited for allocation of bandwidth to aggregate flows as required in the differentiated services framework. We study and compare SFED with other well known queue management disciplines and show that SFED ensures fair allocation of bandwidth across a much wider range of buffer sizes at a bottleneck router. We then propose a more efficient version of SFED using randomization that has an O(1) average time complexity, and, is therefore scalable.
Active queue management disciplines such as RED and its extensions (CHOKe, FRED, BRED) have been ... more Active queue management disciplines such as RED and its extensions (CHOKe, FRED, BRED) have been widely studied as mechanisms for providing congestion avoidance, differentiated services and fairness between different traffic classes. With the emergence of new applications with diverse QoS requirements over the Internet, the need for mechanisms that provide differentiated services has become increasingly important. We propose Selective Fair Early Detection (SFED), a rate control based queue management discipline which ensures a fair bandwidth allocation amongst competing flows even in the presence of nonadaptive traffic. We show that SFED can be used to partition bandwidth in proportion to pre-assigned weights and is well-suited for allocation of bandwidth to aggregate flows as required in the differentiated services framework. We study and compare SFED with other well known queue management disciplines and show that SFED ensures fair allocation of bandwidth across a much wider range of buffer sizes at a bottleneck router. We then propose a more efficient version of SFED using randomization that has an O(1) average time complexity, and, is therefore scalable.
Journal of Biosciences, 2002
Sleep and wakefulness are instinctive behaviours that are present across the animal species. Rapi... more Sleep and wakefulness are instinctive behaviours that are present across the animal species. Rapid eye movement (REM) sleep is a unique biological phenomenon expressed during sleep. It evolved about 300 million years ago and is noticed in the more evolved animal species. Although it has been objectively identified in its present characteristic form about half a century ago, the mechanics of how REM is generated, and what happens upon its loss are not known. Nevertheless, extensive research has shown that norepinephrine plays a crucial role in its regulation. The present knowledge that has been reviewed in this manuscript suggests that neurons in the brain stem are responsible for controlling this state and presence of excess norepinephrine in the brain does not allow its generation. Furthermore, REM sleep loss increases levels of norepinephrine in the brain that affects several factors including an increase in Na-K ATPase activity. It has been argued that such increased norepinephrine is ultimately responsible for REM sleep deprivation, associated disturbances in at least some of the physiological conditions leading to alteration in behavioural expression and settling into pathological conditions.
Pharmacology Biochemistry and Behavior, 2001
Sleep-wakefulness and body temperature are two circadian rhythmic biological phenomena. The role ... more Sleep-wakefulness and body temperature are two circadian rhythmic biological phenomena. The role of GABAergic inputs in the medial preoptico-anterior hypothalamus (mPOAH) on simultaneous regulation of those phenomena was investigated in freely moving normally behaving rats. The GABA-A receptors were blocked by microinjecting picrotoxin, and the effects on electrophysiological parameters signifying sleep-wakefulness, rectal temperature and brain temperature were recorded simultaneously. The results suggest that, normally, GABA in the medial preoptic area acts through GABA-A receptor that induces sleep and prevents an excessive rise in body temperature. However, the results do not allow us to comment on the cause and effect relationship, if any, between changes in sleep-wakefulness and body temperature. The changes in brain and rectal temperatures showed a positive correlation, however, the former varied within a narrower range than that of the latter.
Biochemical Pharmacology, 2005
b i o c h e m i c a l p h a r m a c o l o g y 7 1 ( 2 0 0 5 ) 6 9 -7 3 (M.H. el Kouni). a v a i l... more b i o c h e m i c a l p h a r m a c o l o g y 7 1 ( 2 0 0 5 ) 6 9 -7 3 (M.H. el Kouni). a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / b i o c h e m p h a r m 0006-2952/$ -see front matter #
Journal of Medicinal Chemistry, 2005
(-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4-yl)thymine (DOT) is the first thymidine kinase-acti... more (-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4-yl)thymine (DOT) is the first thymidine kinase-activated nucleoside that is significantly active against all of the clinically significant NRTI-resistant HIV-1 mutants, including AZT (D67N/K70R/T215Y/K219Q), Tenofovir (K65R), and Lamivudine (M184V). To understand the molecular mechanism of drug resistance and the antiviral activity of DOT against drug-resistant RTs, molecular modeling studies of DOT-TP complexed with the wild-type (WT) and mutated RT were conducted. The key reason for this interesting antiviral activity profile is the presence of a dioxolane ring.
Journal of Medicinal Chemistry, 2004
Bioorganic & Medicinal Chemistry Letters, 2004
Molecular modeling studies of adefovir diphosphate with the wild type and the mutant HBV polymera... more Molecular modeling studies of adefovir diphosphate with the wild type and the mutant HBV polymerase-DNA complex demonstrated that the increase in adefovir sensitivity toward HBV polymerase mutants (rtL180M, rtM204V/I, rtL180M-M204V/I) is a result of increased van der Waals interaction and is supplemented by the decreased affinity of natural substrate toward the mutant HBV polymerase. In the case of rtN236T mutant, loss of two hydrogen bonds accompanied by significant decrease in electrostatic interactions is observed, which explains the observed decrease in drug sensitivity and binding affinity of adefovir diphosphate toward the rtN236T mutant HBV polymerase.
Journal of Medicinal Chemistry, 2006
Various D- and L-thietanose nucleosides were synthesized from D- and L-xylose. The four-membered ... more Various D- and L-thietanose nucleosides were synthesized from D- and L-xylose. The four-membered thietane ring was efficiently synthesized by the cyclization of 1-thioacetyl-3-mesylate (4/38) under basic conditions. Condensation with various heterocyclic bases was conducted via Pummerer-type rearrangement to afford various nucleoside derivatives. Among the synthesized nucleosides, D-uridine (23), D-cytidine (24), D-5-fluorocytidine (25), and L-cytidine (52) analogues showed moderate anti-HIV activity, with EC50 = 6.9, 1.3, 5.8, and 14.1 microM, respectively. However, these four nucleoside analogues are cytotoxic in peripheral blood mononuclear and CEM cells. The other nucleosides are neither active nor cytotoxic. Interestingly, the oxetanocin A analogue 33 was not active. Comparison of the minimized reverse transcriptases (RTs) complexed with the corresponding triphosphates of the cytidine analogue 24 and the adenosine analogue 33 by molecular modeling studies showed that there is no difference in the binding mode of the triphosphate of the cytidine analogue 24 to the active site of HIV-1 RT from that of the triphosphate of the adenosine analogue 33. Modeling studies on the initial monophosphorylation step by deoxycytidine kinase showed that the catalytic efficiency of phosphorylation through a nucleophilic attack of the 4'-hydroxyl group of thietanose on the gamma-phosphate of ATP is diminished in the case of L-cytidine analogue (52) due to the increased distance between the 4'-hydroxyl group and the gamma-phosphate.
Biochemical Pharmacology, 2005
Toxoplasma gondii adenosine kinase (EC.2.7.1.20) is the major route of adenosine metabolism in th... more Toxoplasma gondii adenosine kinase (EC.2.7.1.20) is the major route of adenosine metabolism in this parasite. The enzyme is significantly more active than any other enzyme of the purine salvage in T. gondii and has been established as a potential chemotherapeutic target for the treatment of toxoplasmosis. Certain 6-substituted purine nucleosides act as subversive substrates of T. gondii, but not the human, adenosine kinase. Therefore, these compounds are preferentially metabolized to their respective nucleotides and become selectively toxic against the parasites but not their host. Herein, we report the testing of newly synthesized 6-benzylthioinosine analogues with various substituents on the phenyl ring of their benzyl group as subversive substrates of T. gondii adenosine kinases. The binding affinity of these compounds to T. gondii adenosine kinase and their efficacy as antitoxoplasmic agents varied depending on the nature and position of the various substituents on the phenyl ring of their benzyl group. p-Cyano-6-benzylthioinosine and 2,4-dichloro-6-benzylthioinosine were the best ligands. In general, analogues with substitution at the para position of the phenyl ring were better ligands than those with the same substitutions at the meta or ortho position. The better binding of the para-substituted analogues is attributed to the combined effect of hydrophobic as well as van der Waals interactions. The 6-benzylthioinosine analogues were devoid of host-toxicity but all showed selective anti-toxoplasmic effect in cell culture and animal models. These results further confirm that toxoplasma adenosine kinase is an excellent target for chemotherapy and that 6-substituted purine nucleosides are potential selective antitoxoplasmic agents # Abbreviations: FBS, fetal bovine serum; HPMC, hydroxypropylmethylcellulose; MTT, microculture tetrazolium test; PBS, phosphate buffered saline * Corresponding author. Tel.: +1 205 934 1132; fax: +1 205 934 8240.
Active queue management disciplines such as RED and its extensions (CHOKe, FRED, BRED) have been ... more Active queue management disciplines such as RED and its extensions (CHOKe, FRED, BRED) have been widely studied as mechanisms for providing congestion avoidance, differentiated services and fairness between different traffic classes. With the emergence of new applications with diverse QoS requirements over the Internet, the need for mechanisms that provide differentiated services has become increasingly important. We propose Selective Fair Early Detection (SFED), a rate control based queue management discipline which ensures a fair bandwidth allocation amongst competing flows even in the presence of nonadaptive traffic. We show that SFED can be used to partition bandwidth in proportion to pre-assigned weights and is well-suited for allocation of bandwidth to aggregate flows as required in the differentiated services framework. We study and compare SFED with other well known queue management disciplines and show that SFED ensures fair allocation of bandwidth across a much wider range of buffer sizes at a bottleneck router. We then propose a more efficient version of SFED using randomization that has an O(1) average time complexity, and, is therefore scalable.
Active queue management disciplines such as RED and its extensions (CHOKe, FRED, BRED) have been ... more Active queue management disciplines such as RED and its extensions (CHOKe, FRED, BRED) have been widely studied as mechanisms for providing congestion avoidance, differentiated services and fairness between different traffic classes. With the emergence of new applications with diverse QoS requirements over the Internet, the need for mechanisms that provide differentiated services has become increasingly important. We propose Selective Fair Early Detection (SFED), a rate control based queue management discipline which ensures a fair bandwidth allocation amongst competing flows even in the presence of nonadaptive traffic. We show that SFED can be used to partition bandwidth in proportion to pre-assigned weights and is well-suited for allocation of bandwidth to aggregate flows as required in the differentiated services framework. We study and compare SFED with other well known queue management disciplines and show that SFED ensures fair allocation of bandwidth across a much wider range of buffer sizes at a bottleneck router. We then propose a more efficient version of SFED using randomization that has an O(1) average time complexity, and, is therefore scalable.
Journal of Biosciences, 2002
Sleep and wakefulness are instinctive behaviours that are present across the animal species. Rapi... more Sleep and wakefulness are instinctive behaviours that are present across the animal species. Rapid eye movement (REM) sleep is a unique biological phenomenon expressed during sleep. It evolved about 300 million years ago and is noticed in the more evolved animal species. Although it has been objectively identified in its present characteristic form about half a century ago, the mechanics of how REM is generated, and what happens upon its loss are not known. Nevertheless, extensive research has shown that norepinephrine plays a crucial role in its regulation. The present knowledge that has been reviewed in this manuscript suggests that neurons in the brain stem are responsible for controlling this state and presence of excess norepinephrine in the brain does not allow its generation. Furthermore, REM sleep loss increases levels of norepinephrine in the brain that affects several factors including an increase in Na-K ATPase activity. It has been argued that such increased norepinephrine is ultimately responsible for REM sleep deprivation, associated disturbances in at least some of the physiological conditions leading to alteration in behavioural expression and settling into pathological conditions.
Pharmacology Biochemistry and Behavior, 2001
Sleep-wakefulness and body temperature are two circadian rhythmic biological phenomena. The role ... more Sleep-wakefulness and body temperature are two circadian rhythmic biological phenomena. The role of GABAergic inputs in the medial preoptico-anterior hypothalamus (mPOAH) on simultaneous regulation of those phenomena was investigated in freely moving normally behaving rats. The GABA-A receptors were blocked by microinjecting picrotoxin, and the effects on electrophysiological parameters signifying sleep-wakefulness, rectal temperature and brain temperature were recorded simultaneously. The results suggest that, normally, GABA in the medial preoptic area acts through GABA-A receptor that induces sleep and prevents an excessive rise in body temperature. However, the results do not allow us to comment on the cause and effect relationship, if any, between changes in sleep-wakefulness and body temperature. The changes in brain and rectal temperatures showed a positive correlation, however, the former varied within a narrower range than that of the latter.
Biochemical Pharmacology, 2005
b i o c h e m i c a l p h a r m a c o l o g y 7 1 ( 2 0 0 5 ) 6 9 -7 3 (M.H. el Kouni). a v a i l... more b i o c h e m i c a l p h a r m a c o l o g y 7 1 ( 2 0 0 5 ) 6 9 -7 3 (M.H. el Kouni). a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / b i o c h e m p h a r m 0006-2952/$ -see front matter #
Journal of Medicinal Chemistry, 2005
(-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4-yl)thymine (DOT) is the first thymidine kinase-acti... more (-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4-yl)thymine (DOT) is the first thymidine kinase-activated nucleoside that is significantly active against all of the clinically significant NRTI-resistant HIV-1 mutants, including AZT (D67N/K70R/T215Y/K219Q), Tenofovir (K65R), and Lamivudine (M184V). To understand the molecular mechanism of drug resistance and the antiviral activity of DOT against drug-resistant RTs, molecular modeling studies of DOT-TP complexed with the wild-type (WT) and mutated RT were conducted. The key reason for this interesting antiviral activity profile is the presence of a dioxolane ring.
Journal of Medicinal Chemistry, 2004
Bioorganic & Medicinal Chemistry Letters, 2004
Molecular modeling studies of adefovir diphosphate with the wild type and the mutant HBV polymera... more Molecular modeling studies of adefovir diphosphate with the wild type and the mutant HBV polymerase-DNA complex demonstrated that the increase in adefovir sensitivity toward HBV polymerase mutants (rtL180M, rtM204V/I, rtL180M-M204V/I) is a result of increased van der Waals interaction and is supplemented by the decreased affinity of natural substrate toward the mutant HBV polymerase. In the case of rtN236T mutant, loss of two hydrogen bonds accompanied by significant decrease in electrostatic interactions is observed, which explains the observed decrease in drug sensitivity and binding affinity of adefovir diphosphate toward the rtN236T mutant HBV polymerase.
Journal of Medicinal Chemistry, 2006
Various D- and L-thietanose nucleosides were synthesized from D- and L-xylose. The four-membered ... more Various D- and L-thietanose nucleosides were synthesized from D- and L-xylose. The four-membered thietane ring was efficiently synthesized by the cyclization of 1-thioacetyl-3-mesylate (4/38) under basic conditions. Condensation with various heterocyclic bases was conducted via Pummerer-type rearrangement to afford various nucleoside derivatives. Among the synthesized nucleosides, D-uridine (23), D-cytidine (24), D-5-fluorocytidine (25), and L-cytidine (52) analogues showed moderate anti-HIV activity, with EC50 = 6.9, 1.3, 5.8, and 14.1 microM, respectively. However, these four nucleoside analogues are cytotoxic in peripheral blood mononuclear and CEM cells. The other nucleosides are neither active nor cytotoxic. Interestingly, the oxetanocin A analogue 33 was not active. Comparison of the minimized reverse transcriptases (RTs) complexed with the corresponding triphosphates of the cytidine analogue 24 and the adenosine analogue 33 by molecular modeling studies showed that there is no difference in the binding mode of the triphosphate of the cytidine analogue 24 to the active site of HIV-1 RT from that of the triphosphate of the adenosine analogue 33. Modeling studies on the initial monophosphorylation step by deoxycytidine kinase showed that the catalytic efficiency of phosphorylation through a nucleophilic attack of the 4'-hydroxyl group of thietanose on the gamma-phosphate of ATP is diminished in the case of L-cytidine analogue (52) due to the increased distance between the 4'-hydroxyl group and the gamma-phosphate.
Biochemical Pharmacology, 2005
Toxoplasma gondii adenosine kinase (EC.2.7.1.20) is the major route of adenosine metabolism in th... more Toxoplasma gondii adenosine kinase (EC.2.7.1.20) is the major route of adenosine metabolism in this parasite. The enzyme is significantly more active than any other enzyme of the purine salvage in T. gondii and has been established as a potential chemotherapeutic target for the treatment of toxoplasmosis. Certain 6-substituted purine nucleosides act as subversive substrates of T. gondii, but not the human, adenosine kinase. Therefore, these compounds are preferentially metabolized to their respective nucleotides and become selectively toxic against the parasites but not their host. Herein, we report the testing of newly synthesized 6-benzylthioinosine analogues with various substituents on the phenyl ring of their benzyl group as subversive substrates of T. gondii adenosine kinases. The binding affinity of these compounds to T. gondii adenosine kinase and their efficacy as antitoxoplasmic agents varied depending on the nature and position of the various substituents on the phenyl ring of their benzyl group. p-Cyano-6-benzylthioinosine and 2,4-dichloro-6-benzylthioinosine were the best ligands. In general, analogues with substitution at the para position of the phenyl ring were better ligands than those with the same substitutions at the meta or ortho position. The better binding of the para-substituted analogues is attributed to the combined effect of hydrophobic as well as van der Waals interactions. The 6-benzylthioinosine analogues were devoid of host-toxicity but all showed selective anti-toxoplasmic effect in cell culture and animal models. These results further confirm that toxoplasma adenosine kinase is an excellent target for chemotherapy and that 6-substituted purine nucleosides are potential selective antitoxoplasmic agents # Abbreviations: FBS, fetal bovine serum; HPMC, hydroxypropylmethylcellulose; MTT, microculture tetrazolium test; PBS, phosphate buffered saline * Corresponding author. Tel.: +1 205 934 1132; fax: +1 205 934 8240.