Weak Parity

We study the query complexity of Weak Parity: the problem of computing the parity of an n-bit input string, where one only has to succeed on a 1/2+eps fraction of input strings, but must do so with high probability on those inputs where one does succeed. It is well-known that n randomized queries and n/2 quantum queries are needed to compute parity on all inputs. But surprisingly, we give a randomized algorithm for Weak Parity that makes only O(n/log^0.246(1/eps)) queries, as well as a quantum algorithm that makes only O(n/sqrt(log(1/eps))) queries. We also prove a lower bound of Omega(n/log(1/eps)) in both cases; and using extremal combinatorics, prove lower bounds of Omega(log n) in the randomized case and Omega(sqrt(log n)) in the quantum case for any eps>0. We show that improving our lower bounds is intimately related to two longstanding open problems about Boolean functions: the Sensitivity Conjecture, and the relationships between query complexity and polynomial degree.Comment: 18 page

Development and characterization of Brain Targeted Niosomal Formulations of Emtricitabine to treat HIV associated CNS Disorders

Formulations of drug-free niosomes were prepared by four different methods (Thin layer evaporation-vortex, Thin layer evaporation-paddle, Reverse phase evaporation method and Proniosome method) using two surfactants, Span 60 and Span 40 with cholesterol and Solulan C24. Variations were made in the molar ratios and the total concentration of lipid components. Among all the formulations niosomes prepared by TLE-vortex and TLE-paddle methods produced narrow sized niosomal dispersions. It was found that vesicles formulated with Span alone yielded comparatively larger niosomes than those with cholesterol and Solulan added to it. Since, small unilamellar vesicles exhibit prolonged plasma concentrations with more entrapment of aqueous phase compared with that of large unilamellar and multilamellar vesicles, two widely used size reduction methods (sonication and size extrusion) were carried out. Among the two methods of size reduction employed, probe sonication was found to be more satisfactory in reducing the vesicle size by approximately two times than that of size extrusion method for all formulations. The suitability of the drug at different hydration temperatures was evaluated by subjecting the drug solution to 65±50 and 90±50C. The results showed that the drug is stable and can be subjected to such temperatures. Based on the results of mean particle size, formulations containing Span 60 and Span 40 with a total molar concentration of 38mM in the molar ratio of Span:CHL:SOL:NPG as 50:40:10:10 prepared by TLE-vortex and TLE-paddle were selected as the optimized formulations. The NPG drug-free niosomes were prepared by varying the hydration temperatures of 65±50 and 90±50C and the hydration temperature was optimized to 65±50C. IMPACT OF STUDY: Emtricitabine is nucleoside reverse transcriptase inhibitor used in the treatment of HIV patients. The drug is an intermediate CNS penetrating drug. So, the effective concentration of the drug required to reduce the viral load in the CSF of HIV patients is not attained. In this regard, considering the potential benefits of niosomal formulations with glucose analogues for brain-targeted drug delivery, emtricitabine loaded N-palmitoyl glucosamine niosomal formulations were developed and optimized for various formulation parameters. The optimized emtricitabine loaded N-palmitoyl glucosamine niosomal formulation (FTC-NPG-F1B2) with good drug entrapment and stability showed improved CNS penetration as determined by the in vitro blood-brain barrier penetration of emtricitabine from drug loaded NPG niosomes using immobilized artificial membrane phosphatidylcholine column chromatography. Thus, this formulation may be a boon for HIV patients suffering from HIV associated neurocognitive disorders by improving their living during the survival period

2,3-dihydroxybenzoic acid decarboxylase from Aspergillus niger: a novel decarboxylase

2,3-Dihydroxybenzoic acid decarboxylase, the last enzyme in the fungal metabolism of indole to catechol, catalyzes the non-oxidative decarboxylation of 2,3-dihydroxybenzoic acid to catechol. Unlike most other decarboxylases, this enzyme does not require a cofactor, underlining the importance of active-site residues in the reaction mechanism. Earlier studies from this laboratory [Kamath, A. V., Appaji Rao, N. & Vaidyanathan, C. S. (1989) Biochem. Biophys. Res. Commun. 165, 20-261, have shown that the sulfhydryl agent N-ethylmaleimide (MalNEt) inactivated the enzyme by modifying a single class of cysteine residues and that this inactivation was prevented in the presence of salicylate, a substrate analogue. In the present study, this essential cysteine residue has been identified by specific labelling with [14C]- MalNEt using the differential labelling technique. The stoichiometry of incorporation of [I4C]MalNEt was approximately one/subunit of the homotetrameric protein. The peptide bearing this reactive cysteine residue was isolated by tryptic digestion of the differentially labelled enzyme and subsequent reverse-phase chromatography of the peptide mixture. The sequence of the major radioactive peptide that was identified to be the active-site peptide, was LLGLAETCK. A search for sequences similar to this active-site peptide indicated that this sequence was probably unique to the decarboxylase under study. A partial primary structure map constructed from the sequences of peptides derived from enzymic cleavage of the protein using endoproteinase Glu-C and trypsin did not share any significant sequence similarity with sequences reported in the database, again suggesting the uniqueness of the enzyme. This is the first report on the active-site peptide and the partial primary structure of a non-oxidative decarboxylase catalyzing the removal of a carboxyl group from an aromatic nucleus

Recurrence of biased quantum walks on a line

The Polya number of a classical random walk on a regular lattice is known to depend solely on the dimension of the lattice. For one and two dimensions it equals one, meaning unit probability to return to the origin. This result is extremely sensitive to the directional symmetry, any deviation from the equal probability to travel in each direction results in a change of the character of the walk from recurrent to transient. Applying our definition of the Polya number to quantum walks on a line we show that the recurrence character of quantum walks is more stable against bias. We determine the range of parameters for which biased quantum walks remain recurrent. We find that there exist genuine biased quantum walks which are recurrent.Comment: Journal reference added, minor corrections in the tex

Feasibility of utilising address card system for obtaining accurate address of patients under programme conditions

An addresscard, one on which patient's home address is asked to be recorded by a person knowing for sure the patient's address, was investigated for acceptability and efficiency, in two Government hospitals located in semiurban areas and six Primary Health Centres located in rural areas in North Arcot district. In all 394 address-cards were given to the patients from the eight centres, of which 374 were returned with the address filled in, showing an acceptability rate of 95%. In all, 373 Type A letters were then posted to these addresscard addresses in respect of which acknowledgment cards were received back from 306 (82%) patients. For 140 patients, the recorded addresses were found to be the same as on the addresscard and the treatment card: In the remaining 233, there was some difference between the two addresses. Type B letters were then posted to the 233 patients at their treatment card address. No definite information was available regarding the receipt of one or both types of letters in respect of 80 patients; so, an attempt was made to visit these patients in their homes to find out the fate of these letters. Of these, no information could be collected in 9 patients. Out of 224 patients for whom information regarding the receipt of letter was available, 143 (64%) patients received both letters and 16 (7%) received neither Type A nor Type B letter. Twenty one (9%) had probably or definitely not received the Type A letter, but had received the Type B letter. Forty four (20%) had definitely or probably not received the Type B letter, but had received the Type A letter

A study of patients 'lost' from short course chemotherapy under district tuberculosis programme

A study was undertaken in North Arcot and Raichur districts in South India to find out the reasons for patients getting ‘lost’ from short course chemotherapy. There were 545 (40%) patients ‘lost’ from treatment in North Arcot during 14 months and 219 (46%) in Raichur during 72 months. Approximately half of the ‘lost’ patients from both the districts discontinued treatment within two months from the start of treatment. Due to inadequate or incorrect address, 84 (15%) and 26 (13%) patients could not be traced at North Arcot and Raichur, respectively. Reasons could not be elicited from 39 (7%) and 16 (7%) patients, respectively, as they had migrated. Eighty-two (15%) from North Arcot and 33 (15%) from Raichur had died. For 55 (10%) patients from North Arcot and 15 (7%) from Raichur treatment had been changed. Twenty -three (4%) from North Arcot had actually completed their treatment at a different Peripheral Health Institution. Reasons for stopping treatment were obtained from 262 (48%) and 127 (58%) patients, respectively, from the two districts. Abatement of symptoms (19%, 35%), adverse reactions (22%, 13%), outstation trips (22%, 2%), lack of faith in diagnosis and treatment (10%, 27%) and taking private treatment (9%, 32%) were some of the reasons given by the patients Interviewed respectively from these two districts . Some of the patients gave more than one reason

Estimation of burden of tuberculosis in India for the year 2000

Background & objectives: Data on the burden of tuberculosis (TB) in India are vital for programme planners to plan the resource requirements and for monitoring the nation-wide TB control programme. There was a need to revise the earlier estimate on the burden of TB in India based on the increase in population and current epidemiological data. This study estimates the burden of disease for the year 2000 based on recent prevalence of TB and annual risk of tuberculosis infection (ARTI) estimates. Methods: Data on prevalence generated among adults by the Tuberculosis Research Centre (TRC), Chennai, among children by National Tuberculosis Institute (NTI), Bangalore, and the ARTI estimates from the nation-wide sample survey by NTI and TRC were used for the estimation. The prevalence of disease corresponding to 1 per cent ARTI was extrapolated to different parts of the country using the estimates of ARTI and the population in those areas and added together to get the total cases. Abacillary cases that required treatment were estimated from X-ray abnormals. The estimates of bacillary, abacillary and extrapulmonary cases were then combined to get the national burden. Results: The estimated number of bacillary cases was 3.8 million (95% CI: 2.8 - 4.7). The number of abacillary cases was estimated to be 3.9 million and that for extrapulmonary cases was 0.8 million giving a total burden of 8.5 million (95% CI: 6.3-10.4) for 2000. Interpretation & conclusion: The present estimate differs from the earlier estimates because we have included the disease burden of X-ray cases that are likely to breakdown to bacillary cases in a one year period, and extrapulmonary TB cases. The current estimates provided baseline information for advocacy and planning resource allocation for TB control activities. Also, these estimates can be compared with that in future years to measure the long term impact of TB control activities in India

Association of conversion & cure with initial smear grading among new smear positive pulmonary tuberculosis patients treated with Category I regimen

Background & objective: Early diagnosis of tuberculosis (TB) is important for initiating treatment to gain cure. The present investigation was undertaken to study the association of conversion and cure with initial smear grading among pulmonary tuberculosis (TB) patients registered in a directly observed treatment – short course (DOTS) programme in Tiruvallur district, south India. Methods: All new smear positive cases registered from May, 1999 to December, 2002 were analysed for conversion and cure related to initial smear grading. Results: Of the 1463 patients, 1206(82.4%) were converted at the end of the intensive phase and 1109 (75.8%) were declared ‘cured’ after the completion of treatment. The cure rate decreased as the initial smear grading increased and the decrease in trend was statistically significant (P=0.01). Similarly, a significant decrease in conversion rate was also observed with increase in initial smear grading (P<0.001). In multivariate analysis, lower cure rate was significantly associated with patient’s age (AOR=1.5, 95% CI=1.1-2.1), alcoholism (AOR=1.7, 95% CI 1.2- 2.4) and conversion at the end of intensive phase (AOR=3.5, 95% CI= 2.6-4.8). Interpretation & conclusion: Cure and conversion rates were linearly associated with initial smear grading. High default and death rates were responsible for low cure and conversion. The proportion of patients who required extension of treatment and those who had an unfavourable treatment outcome were significantly higher among patients with a 3+ initial smear grading. This reiterates the need to pay more attention in motivating these patients to return to regular treatment and sustained commitment in the control of tuberculosis. There is a need to extend the treatment for one more month in the intensive phase of treatment

Active community surveillance of the impact of different tuberculosis control measures, Tiruvallur, South India, 1968-2001

Background: Tuberculosis is curable, but community surveys documenting epidemiological impact of the WHO-recommended DOTS strategy on tuberculosis prevalence have not been published. We used active community surveillance to compare the impact of DOTS with earlier programmes. Methods: We conducted tuberculosis disease surveys using random cluster sampling of a rural population in South India approximately every 2.5 years from 1968 to 1986, using radiography as a screening tool for sputum examination. In 1999, DOTS was implemented in the area. Prevalence surveys using radiography and symptom screening were conducted at the start of DOTS implementation and after 2.5 years. Results: From 1968 to 1999, culture-positive and smear-positive tuberculosis declined by 2.3 and 2.5% per annum compared with 11.9 and 5.6% after DOTS implementation. The 2.5 year period of DOTS implementation accounted for one-fourth of the decline in prevalence of culture-positive tuberculosis over 33 years. Multivariate analysis showed that prevalence of culture-positive tuberculosis decreased substantially (10.0% per annum, 95% CI: 2.8–16.6%) owing to DOTS after only slight declines related to temporal trends (2.1% annual decline, 95% CI: 1.1–3.2%) and short-course chemotherapy (1.5% annual decline, 95% CI: �9.7% to 11.5%). Under DOTS, the proportion of total cases identified through clinical care increased from 81 to 92%. Conclusions: Following DOTS implementation, prevalence of culture-positive tuberculosis decreased rapidly following a gradual decline for the previous 30 years. In the absence of a large HIV epidemic and with relatively low levels of rifampicin resistance, DOTS was associated with rapid reduction of tuberculosis prevalenc