Pressure management in water distribution systems through PRVs optimal placement and settings.

Optimal pressure management is a standard strategy for water loss minimization in water distribution systems (WDS). A pragmatic solution to regulating water pressures and leakage is introducing pressure-reducing valves (PRVs). This paper presents a valve positioning algorithm for optimally deciding the positions and setpoints of PRVs in a WDS. The algorithm derives the hydraulic solution of a WDS as a directed graph, established on the flow directions, using EPANET 2.2 and develops the downstream network supplied by water flowing out of every pipe in the network by applying the depth-first search method. The algorithm later recognizes the pipes leading to the most extended downstream networks, with pressures above the minimum required service pressure, and prioritizes them as the ideal locations for PRV placement. In this way, the proposed algorithm overcomes the limitations of the state-of-the-art in realistically conceptualizing the leakage reduction for optimally positioning the PRVs in WDS. Four studies with varying complexities were selected to demonstrate the algorithm's applicability for deriving pressure management solutions. The solution time for PRV positioning was in seconds for the first three networks and several minutes for the extensive fourth case study. The results corroborate the algorithm's ability to pinpoint the critical nodes with the most increased potential for downstream pressure control and for maintaining the pressure at the least required service pressure level through optimally allocating the PRVs, with acceptable setpoint values, within the pipe network.

Flexible decision-making framework for developing operation protocol for water distribution systems.

Past water distribution systems (WDS) management studies derived operation protocols to maximize WDS reliability by using residual chlorine as the sole surrogate parameter for water quality reliability. Albeit the advancement in mechanistic modeling to examine the WDS water quality, emerging water quality parameters of concern are not yet involved in solving WDS management problems. This paper attempts to overcome this limitation by developing a flexible decision-making framework -integrating EPANET-C, a mechanistic modeling tool for WDS water quality, with Analytic Hierarchy Process (AHP), a multi-criteria decision-making method - to rank the possible water quality parameter-based operating alternatives (organic matter and residual chlorine levels at the source points) for WDS. The uncertainty analysis was incorporated into the mechanistic modeling using the Monte Carlo method to realize insufficient knowledge about the complex biological and physicochemical interactions inside WDS. Six cases, each ranking the alternatives diversely, were applied to reflect the expert judgment impressions on the AHP outcomes. The consistency of the proposed decision-making framework was verified by deriving the operation protocol for two test networks by making trade-offs between the multiple and conflicting microbiological, chemical, and organoleptic quality criteria. The disinfection by-products formation control and taste and odor problems control emerged as the most critical water quality criteria determining the WDS performance under the operating alternatives examined. Altogether, the obtained results suggested the practicality of adopting a flexible operation protocol to maintain the water quality benchmarks over various plausible WDS performance scenarios, ranging from worst to best.

Making waves: Applying systems biology principles in water distribution systems engineering.

The complexity of modeling water quality variations in water distribution systems (WDS), studied for decades, stems from multiple constraints and variables involved and the complexity of the system behavior. The conventional macroscale-based WDS water quality models are founded on continuum mechanics. In attempts to provide a broad picture of the multi-species interactions, these models overlook the stochasticity corresponding to the reaction mechanisms within the WDS domain. Furthermore, owing to the black-box type modeling adopted in simulating the multi-species interactions, the existing state-of-the-art models have limitations in representing intermediates and/or by-products formation. Accordingly, they remain ineffective in describing the water chemistry-stoichiometric interactions within the WDS domain. Only a radically new modeling approach could overcome the limitations of the macroscale-based approaches and enables analyzing the stochastic WDS mechanisms by keeping the true nature of the system behavior. Stimulated by the metabolic network modeling principles in systems biology, this article outlines the prospect of developing an innovative 'water'bolic network modeling approach to provide a new outlook to the existing WDS water quality modeling research.

Model-based investigation of the formation, transmission, and health risk of perfluorooctanoic acid, a member of PFASs group, in drinking water distribution systems.

Recent studies identified fluoroalkyl amides (FAs) transformation to perfluorooctanoic acid (PFOA) during disinfection as an indirect source of PFASs contamination of drinking water. This paper discerns the position of water disinfection systems (WDSs) as a PFOA exposure pathway. A new mechanistic model incorporating the derived knowledge about the zwitterionic/cationic FAs transformation to PFOA with the unsteady-state hydraulic characteristics of WDSs was developed. The simulation outputs from model application to a WDS from the USA established the significant role of delivery via distribution network in the PFOA formation in drinking water. PFOA exposure risk assessment studies predicted >95% of the system nodes to be at high risk when the existing stringent health-based guideline values are adopted. The 1 to 3 years and 4 to 8 years old age groups were found susceptible to PFOA exposure through drinking water beyond the tolerable limit of 3 ng/kg/day. The model predicted that reducing the chlorine dose from 2±0.2 to 1±0.1 mg/L at the treatment units drops the share of 1 to 3 years old and 4 to 8 years old consumers falling to PFOA exposure from 4.32 to 0.45% and 0.32 to <0.01%, respectively. Besides, 24.9% more, including ∼x223C10% of the consumers of 1 to 3 years old age group, were found exposed to PFOA risks when the organic loading of water was reduced by 60%.

Effect of malachite green toxicity on non target soil organisms.

Although malachite green (MG), is banned in Europe and US for its carcinogenic and teratogenic effect, the dye being cheap, is persistently used in various countries for fish farming, silk, dye, leather and textile industries. Current research, however, fails to elucidate adequate knowledge concerning the effects of MG in our ecosystem. In the present investigation, for the first time, an attempt has been made to study the effects of MG on soil biota by testing Bacillus subtilis, Azotobacter chroococcum, Saccharomyces cerevisiae, Penicillium roqueforti, Eisenia fetida and seeds of three crop plants of different families. Various tests were conducted for determining cytotoxicity, genotoxicity, acute toxicity, morphological and germination effect. Our data confirmed MG toxicity on fungi and bacteria (gram positive and gram negative organisms) showing elevated level of ROS. Genotoxicity caused in the microorganisms was detected by DNA polymorphism and fragmentation. Also, scanning electron microscopy data suggests that the inhibitory effect of MG to these beneficial microbes in the ecosystem might be due to pore formation in the cell and its eventual disruption. Filter paper and artificial soil test conducted on earthworms demonstrated a LC 50 of 2.6 mg cm(-2) and 1.45 mg kg(-1) respectively with severe morphological damage. However, seed germination of Mung bean, Wheat and Mustard was found to be unaffected in presence of MG up to 100 mL(-1) concentration. Thus, understanding MG toxicity in non target soil organisms and emphasis on its toxicological effects would potentially explicate its role as an environmental contaminant.

Role of reentry of in vivo alloMHC peptide-activated T cells into the adult thymus in acquired systemic tolerance.

BACKGROUND: T cell recognition of alloMHC peptide presented by self dendritic cells via the indirect pathway of allorecognition in the thymus induces T cell tolerance. Most recently we have shown that the i.v. administration of immunodominant Wistar Furth MHC class I (RT1.Au) peptide 5- (P5) pulsed myeloid or lymphoid dendritic cells induces operational tolerance to a fully MHC-mismatched cardiac allograft. This finding led us to hypothesize that circulation of peripheral P5-activated T cells to the thymus plays an important role in the induction of acquired tolerance. METHODS: We used the adoptive transfer of 111Indium-oxine- (111In-oxine) labeled P5-pulsed syngeneic dendritic cells and in vivo P5-activated syngeneic T cells to study the role of their circulation to the thymus in the induction of transplantation tolerance. RESULTS: Intravenously administered 111In-oxine-labeled naïve DC actively migrated to and localized in the liver and spleen but did not enter the lymph nodes, bone marrow, and thymus. In vitro peptide-pulsed dendritic cells had a similar pattern of tissue localization except for a modest number of myeloid but not lymphoid DC entering the thymus. The demonstration that adoptive transfer of in vivo peptide-primed T cells induces permanent graft survival in antilymphocyte serum transiently immunosuppressed syngeneic secondary hosts led us to examine the traffic of in vivo activated T cells. Whereas naïve syngeneic T cells preferentially homed to the peripheral lymphoid organs, they did not reenter the thymus. In contrast, in vivo peptide-activated peripheral T cells migrated to and accumulated in the thymus, thus confirming that reentry of T cells to the thymus is restricted to in vivo activated T cells. Although antilymphocyte serum immunosuppression significantly reduced circulation of primed T cells to the thymus, it did not completely abolish it, as seen with gamma-irradiated primed T cells. CONCLUSION: These findings provide the first formal evidence directly linking reentry of in vivo alloMHC peptide-activated T cells to the thymus with the induction and possibly maintenance of acquired antigen-specific tolerance. Our results suggest that the thymus is open to a two-way traffic with the periphery and may function as a repository of immunological memory.

Mechanisms of acquired thymic tolerance: induction of transplant tolerance by adoptive transfer of in vivo allomhc peptide activated syngeneic T cells.

BACKGROUND: Our most recent observation that i.v. injection of Wistar-Furth (WF) major histocompatibility complex Class I peptide 5 (P5)-pulsed self-myeloid or lymphoid dendritic cells (DC) induces transplantation tolerance suggests that adoptive transfer of in vivo allopeptide-primed host T cells might induce acquired tolerance through their interaction with thymic DC. METHODS: To examine this hypothesis, host myeloid DC cultured in rat granulocyte/macrophage colony stimulating factor and interleukin 4 were pulsed in vitro with P5 and injected intravenously into syngeneic ACI rats. The T cells primed to P5 via the indirect pathway of allorecognition were harvested 7 days later and administered by either intravenously or intrathymically into syngeneic ACI recipients of WF cardiac allografts. RESULTS: Syngeneic T cells obtained from the spleen of P5-primed rats had a high mixed lymphocyte reaction proliferative response to P5 presented by self-DC. I.v. administration of 2x107 P5-primed alloreactive purified host splenic T cells alone on day -7 significantly (P<0.001) prolonged cardiac allograft survival from 10.5+/-1.0 days to 18.6+/-1.8 days in the WF-to-ACI rat combination. I.v. injection of P5-activated host T cells combined with 0.5 ml antilymphocyte serum (ALS)-transient immunosuppression on day -7 led to 100% donor-specific permanent graft survival (>200 days). Thymectomy before i.v. injection of P5-activated syngeneic T cells led to acute graft rejection, suggesting that the homing of in vivo activated T cells to the host thymus might play a role in the induction of tolerance. To further define the role of the recipient thymus in this model, we examined the effects of intrathymic (i.t.) injection of P5-primed alloreactive T cells on graft survival and found that i.t. administration of the P5-primed T cells on day -7 alone significantly prolonged graft survival (15.0+/-0.7 days) and when combined with 0.5 ml ALS led to donor-specific permanent graft survival. The long-term unresponsive recipients permanently (>100 days) accepted second-set donor-specific cardiac allografts but not third-party (Lewis) grafts. CONCLUSIONS: These findings demonstrate that the adoptive transfer of splenic T cells primed to an indirectly presented donor peptide induces transplantation tolerance in a transiently immunosuppressed secondary syngeneic recipient. Our data suggest that the interaction of thymic DC with activated peripheral T cells induces alloantigen (Ag)-specific T-cell tolerance by either inactivation or deletion of alloreactive T cells in the thymus. This observation provides the first formal evidence that the interaction between thymic DC and activated peripheral T cells that continuously circulate through the thymus plays an important role in the induction and maintenance of Ag-specific tolerance.

Indirect allorecognition in acquired thymic tolerance: induction of donor-specific permanent acceptance of rat islets by adoptive transfer of allopeptide-pulsed host myeloid and thymic dendritic cells.

Pancreatic islet transplantation remains a promising approach to the treatment of type 1 diabetes. Unfortunately, graft failure continues to occur because of immunologic rejection, despite the use of potent immunosuppressive agents. It is therefore reasoned that induction of peripheral tolerance by the use of self-dendritic cells (DCs) as a vehicle to deliver specific target antigens to self-T-cells without ex vivo manipulation of the recipient is an attractive strategy in the treatment of type 1 diabetes. The finding that intrathymic inoculation of an immunodominant WF major histocompatibility complex (MHC) Class I (RT1.A(u)) peptide five (P5) or P5-pulsed host myeloid DCs induces acquired thymic tolerance raises the possibility that adoptive transfer of allopeptide-primed host myeloid or lymphoid DCs might induce transplant tolerance. To address this hypothesis, we studied the effects of intravenous transfer of in vitro P5-pulsed syngeneic myeloid DCs or in vivo P5-primed syngeneic lymphoid (thymic) DCs on islet survival in the WF-to-ACI rat combination. In vivo primed thymic DCs isolated from ACI rats given intrathymic inoculation of P5 for 2 days were capable of in vitro restimulation of in vivo P5-primed T-cells (memory cells). In the first series of studies, we showed that intravenous-like intrathymic-inoculation of in vitro P5-pulsed host myeloid DCs induced donor-specific permanent acceptance of islets in recipients transiently immunosuppressed with antilymphocyte serum (ALS). We next examined whether thymic DCs isolated from animals that had been previously intrathymically inoculated with P5 could induce T-cell tolerance. The results showed that intravenous adoptive transfer of in vivo P5-primed thymic DCs led to donor-specific permanent acceptance of islets in recipients transiently immunosuppressed with ALS. This finding suggested that the thymic DCs take up and present P5 to developing T-cells to induce T-cell tolerance, thus providing evidence of a direct link between indirect allorecognition and acquired thymic tolerance. The second series of studies examined the mechanisms involved in this model by exploring whether in vivo generation of peptide-specific alloreactive peripheral T-cells by intravenous inoculation of P5-pulsed self-DCs was responsible for the induction of T-cell tolerance. Intrathymic inoculation of splenic T-cells obtained from syngeneic ACI rats primed with intravenous injection of P5-pulsed DCs with a high in vitro proliferative response to P5 in the context of self-MHC induced donor-specific permanent acceptance of islets from WF donors. In addition, the clinically relevant model of intravenous injection of P5-activated T-cells combined with transient ALS immunosuppression similarly induced transplant tolerance, which was then abrogated by thymectomy of the recipient before intravenous injection of the activated T-cells. These data raise the possibility that circulation of peptide-activated T-cells to the host thymus plays a role in the induction and possibly the maintenance of T-cell tolerance in this model. Our findings suggest that intravenous administration of genetically engineered host DCs expressing alloMHC peptides might have therapeutic potential in clinical islet transplantation for the treatment of autoimmune diabetes.

Clinical and morphological variants of cutaneous tuberculosis and its relation to Mycobacterium species.

Cutaneous tuberculosis forms a small proportion of extrapulmonary tuberculosis. The incidence of cutaneous tuberculosis has fallen from 2% to 0.15% in India whereas it is rare in developed countries. The present study is an attempt at finding out the Mycobacterium species associated with cutaneous tuberculosis. A total of 51 cases of clinically suspected cutaneous tuberculosis were studied over a period of 18 months from July 1997 to December 1998. Of these, 32 (62.75%) were Scrofuloderma cases, 12 (23.52%) cases of Lupus vulgaris and 7 (13.73%) were Tuberculosis verrucosa cutis (TBVC) cases. Twenty nine mycobacterial isolates from 51 specimens gave an isolation rate of 56.86%. These were subjected to a battery of biochemical tests for identification to species level. Twenty six out of 29 isolates were identified as Mycobacterium tuberculosis, two were identified as Mycobacterium Scrofulaceum and one Mycobacterium avium complex was isolated. Sixteen Mycobacterial isolates were recovered from Scrofuloderma cases, 9 were isolated from Lupus vulgaris and 4 from TBVC cases. The three atypical mycobacterial isolates were recovered from Scrofuloderma cases. Though Mycobacterium tuberculosis was the most common isolate, Mycobacterium scrofulaceum and Mycobacterium avium complex were also isolated in the present study.

Induction of transplant tolerance with immunodominant allopeptide-pulsed host lymphoid and myeloid dendritic cells.

We have studied the effects of adoptive transfer of host thymic dendritic cells pulsed with immunodominant WF Class I peptide 5 (residues 93-109) on cardiac allograft survival in the WF-to-ACI rat combination. Our results showed that, whereas intrathymic inoculation of WF peptide 5-pulsed ACI thymic dendritic cells alone on day -7 did not prolong graft survival, similar treatment combined with 0.5 mL antilymphocyte serum (ALS) led to 100% permanent acceptance (> 200d) of donor-specific cardiac allografts. Extension of our study to systemic administration of peptide 5-pulsed host thymic dendritic cells confirmed that intravenous injection of peptide 5-pulsed self thymic dendritic cells combined with ALS transient immunosuppression resulted in 100% permanent donor-specific graft survival (> 200d). These results were reproducible in a clinically relevant model using intravenous injection of peptide-pulsed host myeloid dendritic cells. In contrast, thymectomy prior to adoptive transfer of peptide-pulsed host dendritic cells resulted in acute graft rejection at times equivalent to rejection in thymectomized controls. The long-term unresponsive recipients challenged with second-set grafts accepted permanently (> 100d) donor-type (WF) but not third party (Lewis) cardiac allografts. This study suggests that intravenous administration of genetically engineered dendritic cells expressing donor MHC molecules has the potential of inducing transplant tolerance.

Loss of consciousness following spinal anaesthesia for caesarean section.

A healthy parturient under spinal anaesthesia for Caesarean section lost consciousness for an hour, 20 min after the intrathecal injection of 2 ml of 0.5% heavy bupivacaine. The patient was haemodynamically stable before losing consciousness. The differential diagnosis is discussed.