Maintenance Of Reservoir Research Articles

The impact of sex on HIV immunopathogenesis and therapeutic interventions.

Globally, the majority of people living with HIV are women or girls, but they have been a minority of participants in clinical trials and observational studies of HIV. Despite this underrepresentation, differences in the pathogenesis of HIV have been observed between men and women, with contributions from both gender- and sex-based factors. These include differences in the risk of HIV acquisition, in viral load set point and immune activation in responses to viremia, and differences in HIV reservoir maintenance. These differences obligate adequate study in both males and females in order to optimize treatments, but also provide a powerful leverage point for delineating the mechanisms of HIV pathogenesis. The shifts in exposure to sex steroid hormones across a lifespan introduce additional complexity, which again can be used to focus on either genetic or hormonal influences as the driver of an outcome. In this Review, we discuss consistent and reproducible differences by sex across the spectrum of HIV, from acquisition through pathogenesis, treatment, and cure, and explore potential mechanisms and gaps in knowledge.

Hydrocarbon accumulation and orderly distribution of whole petroleum system in marine carbonate rocks of Sichuan Basin, SW China

Based on the situation and progress of marine oil/gas exploration in the Sichuan Basin, SW China, the whole petroleum system is divided for marine carbonate rocks of the basin according to the combinations of hydrocarbon accumulation elements, especially the source rock. The hydrocarbon accumulation characteristics of each whole petroleum system are analyzed, the patterns of integrated conventional and unconventional hydrocarbon accumulation are summarized, and the favorable exploration targets are proposed. Under the control of multiple extensional-convergent tectonic cycles, the marine carbonate rocks of the Sichuan Basin contain three sets of regional source rocks and three sets of regional cap rocks, and can be divided into the Cambrian, Silurian and Permian whole petroleum systems. These whole petroleum systems present mainly independent hydrocarbon accumulation, containing natural gas of affinity individually. Locally, large fault zones run through multiple whole petroleum systems, forming a fault-controlled complex whole petroleum system. The hydrocarbon accumulation sequence of continental shelf facies shale gas accumulation, marginal platform facies-controlled gas reservoirs, and intra-platform fault- and facies-controlled gas reservoirs is common in the whole petroleum system, with a stereoscopic accumulation and orderly distribution pattern. High-quality source rock is fundamental to the formation of large gas fields, and natural gas in a whole petroleum system is generally enriched near and within the source rocks. The development and maintenance of large-scale reservoirs are essential for natural gas enrichment, multiple sources, oil and gas transformation, and dynamic adjustment are the characteristics of marine petroleum accumulation, and good preservation conditions are critical to natural gas accumulation. Large-scale marginal-platform reef-bank facies zones, deep shale gas, and large-scale lithological complexes related to source-connected faults are future marine hydrocarbon exploration targets in the Sichuan Basin.

CGAS-STING-TBK1 Signaling Promotes Valproic Acid-Responsive Human Cytomegalovirus Immediate-Early Transcription during Infection of Incompletely Differentiated Myeloid Cells.

Repression of human cytomegalovirus (HCMV) immediate-early (IE) gene expression is a key regulatory step in the establishment and maintenance of latent reservoirs. Viral IE transcription and protein accumulation can be elevated during latency by treatment with histone deacetylase inhibitors such as valproic acid (VPA), rendering infected cells visible to adaptive immune responses. However, the latency-associated viral protein UL138 inhibits the ability of VPA to enhance IE gene expression during infection of incompletely differentiated myeloid cells that support latency. UL138 also limits the accumulation of IFNβ transcripts by inhibiting the cGAS-STING-TBK1 DNA-sensing pathway. Here, we show that, in the absence of UL138, the cGAS-STING-TBK1 pathway promotes both IFNβ accumulation and VPA-responsive IE gene expression in incompletely differentiated myeloid cells. Inactivation of this pathway by either genetic or pharmacological inhibition phenocopied UL138 expression and reduced VPA-responsive IE transcript and protein accumulation. This work reveals a link between cytoplasmic pathogen sensing and epigenetic control of viral lytic phase transcription and suggests that manipulation of pattern recognition receptor signaling pathways could aid in the refinement of MIEP regulatory strategies to target latent viral reservoirs.

Longevity and Potential Mechanisms of Fenpropathrin Resistance in Asian Citrus Psyllid, Diaphorina citri Kuwayama

The stability of resistance to fenpropathrin was assessed using five populations of Diaphorina citri with varying initial resistances ranging from fully susceptible (SS) to fully resistant (RR). Furthermore, we quantified the relative expression of voltage-gated sodium channel (VGSC) genes in crosses of field-selected and laboratory-susceptible D. citri lines after eight months without insecticide selection. We found that resistance to fenpropathrin remained elevated up to eight months after exposure to fenpropathrin. A real-time quantitative PCR analysis using the susceptible baseline population revealed that levels of VGSC gene expression were significantly higher in the RS75 cross and the RR100 fully resistant line eight months after their last fenpropathrin exposure. Our results suggest that while fenpropathrin resistance is likely unstable under field conditions when interbreeding with susceptible individuals is possible, resistance can remain stable for at least 8 months if those populations are isolated. Further, insecticide rotation and the maintenance of susceptible reservoirs of individuals should mitigate fenpropathrin resistance in D. citri over time. The development of a VGSC gene biomarker may be a useful tool for monitoring pyrethroid resistance in D. citri going forward.

MATHEMATICAL MODEL OF A LARGE RESERVOIR, ESTABLISHING AND FINDING ITS MAIN ENERGY CHARACTERISTICS

Water plays an important role in the normal life of a person as a member of society. The presence or absence of fresh water reserves is one of the most important economic and social factors for the successful existence and development of any country in modern conditions. It is difficult to overestimate the importance of having large fresh water reserves for every sector of the economy. Ukraine has one of the largest such reserves in the world. Over time, as established by research and forecasts, the value and cost of fresh water will only increase. Therefore, preserving, protecting, properly utilizing and maintaining large, man-made water reservoirs is an important and always relevant task for the people of Ukraine. This strategy seems especially important in the current state of full-scale military aggression by the neighboring enemy. Thus, it seems reasonable to care about the preservation and proper use of fresh water in the context of the current geopolitical conflict. Water resources indeed play a critical role in all areas of the economy and daily life. Fresh water supplies are essential for agriculture, industry, drinking water for the population, as well as for energy and other industries. Ukraine, as a country with large freshwater reserves, has the opportunity to use this resource to ensure sustainable development and reduce dependence on imports. Water reservoirs can also play a strategic role in the face of possible threats and military conflicts. The storage and maintenance of water reservoirs is a necessary precautionary measure in case of any possible threats to infrastructure and access to fresh water. It is also important to develop and implement strategies for water conservation and efficient use to guarantee long-term resilience and sustainability in the water supply sector. The context of armed conflict can pose additional challenges to water management. It is therefore important to have contingency plans in place and to ensure the safety of water bodies in such circumstances. The development and improvement of water supply systems, as well as the implementation of effective water management strategies, will contribute to the sustainable development and conservation of an important natural resource, which is fresh water. Taking into account the sufficient importance and relevance of all these issues, in the following studies, a certain mathematical model of a large modern reservoir is proposed and investigated in the form of such a volumetric geometric structure as a spatially horizontally oriented elliptical half cylinder with the corresponding parameters that correspond to the specific dimensions of a real reservoir, such as the length, width and depth of filling such a structure with water.It is believed that the height (depth) of the filling can change, and this fact is essentially the most important factor in the corresponding change in the current volume of stored water and the potential energy of the accumulated liquid.The main results of this work are the possibility of determining the value of the current volume and the accumulated potential energy of such a reservoir. The paper presents a geometric view of the model of such a structure, formulas and their results for finding the values of the mentioned energy characteristics of a reservoir of the corresponding geometry, draws conclusions, points out the advantages and possible disadvantages of the given mathematical model, and provides opportunities for the future creation of an alternative mathematical more adequate model of a modern reservoir in the form of a horizontally oriented elliptical half cone.

Multiple treatments with human embryonic stem cell-derived mesenchymal progenitor cells preserved the fertility and ovarian function of perimenopausal mice undergoing natural aging

ObjectivesCurrently, no approved stem cell-based therapies for preserving ovarian function during aging. To solve this problem, we developed a long-term treatment for human embryonic stem cell-derived mesenchymal progenitor cells (hESC-MPCs). We investigated whether the cells retained their ability to resist ovarian aging, which leads to delayed reproductive senescence.Materials and methodsIn a middle-aged female model undergoing natural aging, we analyzed whether hESC-MPCs benefit the long-term maintenance of reproductive fecundity and ovarian reservoirs and how their transplantation regulates ovarian function.ResultsThe number of primordial follicles and mice with regular estrous cycles were increased in perimenopausal mice who underwent multiple introductions of hESC-MPCs compared to age-matched controls. The estradiol levels in the hESC-MPCs group were restored to those in the young and adult groups. Embryonic development and live birth rates were higher in the hESC-MPC group than in the control group, suggesting that hESC-MPCs delayed ovarian senescence. In addition to their direct effects on the ovary, multiple-treatments with hESC-MPCs reduced ovarian fibrosis by downregulating inflammation and fibrosis-related genes via the suppression of myeloid-derived suppressor cells (MDSCs) produced in the bone marrow.ConclusionsMultiple introductions of hESC-MPCs could be a useful approach to prevent female reproductive senescence and that these cells are promising sources for cell therapy to postpone the ovarian aging and retain fecundity in perimenopausal women.

Numerical simulation of a nonlinear diffusion type equation in a two phase media with linear porosity and permeability model

Predicting and understanding the behavior of pressure is important in reservoir maintenance and evaluation. This work studies the behavior of fluid pressure in a reservoir by numerical simulation of the pressure diffusion type equation in a two phase media with a linear porosity and permeability model. Because the porosity and permeability are pressure dependent, the resulting diffusion type equation is nonlinear and is solved using a backward-forward finite difference method. The simulation code was ran using a constant porosity and permeability model and a linear porosity and permeability model. The results from the linear porosity and permeability model was compared to that of the constant porosity and permeability model. In both cases the pressure gradient was greatest at the wellbore and decreases as the radial distances away from the wellbore increases. The pressure in both cases also decreased with time. However, at each location and time the pressure drop was lower in the linear porosity and permeability model than with the constant porosity and permeability. The backward-forward finite difference method proved to be useful in solving numerically the nonlinear diffusion type equation. This work can be applied in the oil and gas industry to predict pressure behavior in reservoirs and make investment decisions, production and maintenance decision.

Operation And Maintenance Of Cengklik Reservoir In Supporting Integrated Water Resources Management

The management of the Cengklik Reservoir area which currently still has the main function as an irrigation facility with an area of 1,578 ha is still in the feasible category to be developed as a means of tourism and sustainable aquaculture. The development of the Cengklik Reservoir area in 2022 has entered the stage of developing supporting infrastructure such as a jogging track area, reservoir guardrails, arrangement of fish cage cultivation areas, and other infrastructure developments. This must also be balanced with a good pattern of management of operation and maintenance (OP) activities in the form of documents prepared by referring to the Reservoir Operation and Maintenance (OP) Guidelines. The method used in this research is simulation and evaluation on hydrological analysis using a flood design of 476.40 m3/s and an average flood water level of +142.64 m. The data used to measure the management of water resources in the Cengklik Reservoir is based on data hydrology, inflow, and outflow of the Cengklik Reservoir from 2010-2021 based on observations from the Bengawan Solo River Basin Center (BBWS). According to the evaluation results with measured parameters, it was found that the pattern of operation and maintenance of the Cengklik Reservoir is in the feasible category with the need for funding for the operation and maintenance of the reservoir of IDR 474,397,817.00 So that the integrated water resources development that has been carried out in the Cengklik Reservoir can be replicated in the reservoir others throughout Indonesia.

AKT signaling modulates latent viral reservoir viability in HIV-1-infected blood–brain barrier pericytes

Despite antiretroviral therapy (ART), chronic forms of HIV-associated neurocognitive disorders (HAND) affect an estimated 50% of individuals living with HIV, greatly impacting their quality of life. The prevailing theory of HAND progression posits that chronic inflammation arising from the activation of latent viral reservoirs leads to progressive damage in the central nervous system (CNS). Recent evidence indicates that blood-brain barrier (BBB) pericytes are capable of active HIV-1 infection; however, their latent infection has not been defined. Given their location and function, BBB pericytes are poised to be a key viral reservoir in the development of HAND. We present the first transcriptional analysis of uninfected, active, and latent human BBB pericytes, revealing distinct transcriptional phenotypes. In addition, we demonstrate that latent infection of BBB pericytes relies on AKT signaling for reservoir survival. These findings provide insight into the state of reservoir maintenance in the CNS during HIV-1 infection and provide novel targets for reservoir clearance.

Analyzing Downstream Flooding Effects Due to Small-Scale Reservoir Destruction Using Flow-R

The frequency of abnormal weather patterns owing to climate change and the aging of reservoirs are contributing to an increase in dam failures, particularly of small-scale agricultural reservoirs. Dam collapses can lead to significant human and material damage downstream, even in the case of small-scale reservoirs. Therefore, alongside systematic maintenance of aging reservoirs, establishing emergency response plans for dam failures is imperative. However, application of existing dam failure models requires a substantial amount of time and resources, making it challenging to implement for small-scale reservoirs. In this study, the Flow-R model, which can estimate downstream damage areas using only digital topographic maps, was employed to calculate the extent of downstream damage resulting from the collapse of small-scale reservoirs. Five scenarios were analyzed based on the extent of reservoir destruction (ranging from 10% to 100%). The results revealed that the inundation area varied depending on the topography downstream of the reservoir. This study proposes an affordable and straightforward method for estimating damage downstream of reservoirs, even when limited data are available regarding the reservoirs. Thus, this study can be utilized in the development of emergency response plans for small-scale agricultural reservoirs.

Host infection and disease-induced mortality modify species contributions to the environmental reservoir.

Environmental pathogen reservoirs exist for many globally important diseases and can fuel epidemics, influence pathogen evolution, and increase the threat of host extinction. Species composition can be an important factor that shapes reservoir dynamics and ultimately determines the outcome of a disease outbreak. However, disease-induced mortality can change species communities, indicating that species responsible for environmental reservoir maintenance may change over time. Here we examine the reservoir dynamics of Pseudogymnoascus destructans, the fungal pathogen that causes white-nose syndrome in bats. We quantified changes in pathogen shedding, infection prevalence and intensity, host abundance, and the subsequent propagule pressure imposed by each species over time. We find that highly shedding species are important during pathogen invasion, but contribute less over time to environmental contamination as they also suffer the greatest declines. Less infected species remain more abundant, resulting in equivalent or higher propagule pressure. More broadly, we demonstrate that high infection intensity and subsequent mortality during disease progression can reduce the contributions of high-shedding species to long-term pathogen maintenance.

Community Group Participation in Maintenance of Cengklik Reservoir as a Water Resources Conservation Area

Reservoirs are water resources that function for the needs of the community. Reservoir maintenance is carried out to maintain the conservation of water resources and inhibit sedimentation. This study aims to determine the participation of the Ngudi Tirto Lestari community group in Sobokerto Village in maintaining the Cengklik reservoir. This research uses the theory of community participation according to Keith Davis with 3 indicators: individual mental and emotional involvement, motivation to contribute, and individual responsibility. The method used is qualitative with a descriptive approach. Data collection is done by observation, interview, and literature study. The results of the study are Community Group Participation in maintaining the Cengklik reservoir as a water resource conservation area in Sobokerto Village is quite good. In individual mental and emotional involvement, community groups are aware of social activities and the important benefits of maintaining the Cengklik reservoir. The encouragement of contribution motivation, community groups received encouragement from the Sobokerto Village government and PT Pertamina Patra Niaga Adi Soemarmo through socialization and training activities regarding reservoir maintenance. However, there is still a lack of responsibility for reservoir maintenance caused by the collision of other individual activities, so it is necessary to hold bounding between members.

Modifying water use practices to eliminate Pseudomonas aeruginosa bloodstream infections in the neonatal intensive care unit

Objective: To describe the strategies implemented at a tertiary-care healthcare center neopnatal intensive care unit (NICU) to control and assure prevention of subsequent central-line bloodstream infections (CLABSIs) with Pseudomonas aeruginosa after 4 cases of CLABSI with this organism were detected. Methods: During the months of September 2020 to February 2021, 4 cases of CLABSI with Pseudomonas aeruginosa were reported in our NICU in patients meeting criteria for extremely low birthweight (ELBW) infants. All patients were treated according to IDSA guidelines for management of bloodstream infections. To avoid the appearance of new events and to improve existing policies, we implemented a stepwise approach by reviewing routine disinfection and/or cleaning procedures of isolettes: (1) liners for bath basins were applied, (2) sterile water was provided for bathing newborns, (3) we ensured timely biomed preventive maintenance of water reservoirs for patient care equipment (nebulizers, isolettes and fluid warmers), and (4) we implemented the installment of point-of-care filters for tap water. Results: Measures were implemented from February 2021 to July 2021. During the following year from July 2021 to June 2022, no CLBSIs related to Pseudomonas aeruginosa were reported in our NICU in patients meeting criteria for ELBW infants. Conclusions: Recognition of CLABSI from organisms from water resources is important to implementing focused prevention strategies targeting water resources and water utilization practices. In our institution, these interventions yielded complete resolution, with no new infection events.Disclosure: None

Evaluation of Archival HIV DNA in Brain and Lymphoid Tissues.

HIV reservoirs persist in anatomic compartments despite antiretroviral therapy (ART). Characterizing archival HIV DNA in the central nervous system (CNS) and other tissues is crucial to inform cure strategies. We evaluated paired autopsy brain-frontal cortex (FC), occipital cortex (OCC), and basal ganglia (BG)-and peripheral lymphoid tissues from 63 people with HIV. Participants passed away while virally suppressed on ART at the last visit and without evidence of CNS opportunistic disease. We quantified total HIV DNA in all participants and obtained full-length HIV-envelope (FL HIV-env) sequences from a subset of 14 participants. We detected HIV DNA (gag) in most brain (65.1%) and all lymphoid tissues. Lymphoid tissues had higher HIV DNA levels than the brain (P < 0.01). Levels of HIV gag between BG and FC were similar (P > 0.2), while OCC had the lowest levels (P = 0.01). Females had higher HIV DNA levels in tissues than males (gag, P = 0.03; 2-LTR, P = 0.05), suggesting possible sex-associated mechanisms for HIV reservoir persistence. Most FL HIV-env sequences (n = 143) were intact, while 42 were defective. Clonal sequences were found in 8 out of 14 participants, and 1 participant had clonal defective sequences in the brain and spleen, suggestive of cell migration. From 10 donors with paired brain and lymphoid sequences, we observed evidence of compartmentalized sequences in 2 donors. Our data further the idea that the brain is a site for archival HIV DNA during ART where compartmentalized provirus may occur in a subset of people. Future studies assessing FL HIV-provirus and replication competence are needed to further evaluate the HIV reservoirs in tissues. IMPORTANCE HIV infection of the brain is associated with adverse neuropsychiatric outcomes, despite efficient antiretroviral treatment. HIV may persist in reservoirs in the brain and other tissues, which can seed virus replication if treatment is interrupted, representing a major challenge to cure HIV. We evaluated reservoirs and genetic features in postmortem brain and lymphoid tissues from people with HIV who passed away during suppressed HIV replication. We found a differential distribution of HIV reservoirs across brain regions which was lower than that in lymphoid tissues. We observed that most HIV reservoirs in tissues had intact envelope sequences, suggesting they could potentially generate replicative viruses. We found that women had higher HIV reservoir levels in brain and lymphoid tissues than men, suggesting possible sex-based mechanisms of maintenance of HIV reservoirs in tissues, warranting further investigation. Characterizing the archival HIV DNA in tissues is important to inform future HIV cure strategies.

Assessment of sediment yield and deposition in a dry reservoir using field observations, RUSLE and remote sensing: Wadi Assarin, Oman

Soil erosion, sediment yield, and sediment transport associated with flash flooding in arid regions result in reservoir storage losses, decreased infiltration, high evaporation rates, and degradation of downstream channels. However, the lack of observational data from wadi systems and an empirical formula to compute sediment yield has hindered reservoir trapping evaluation, maintenance, and management. Therefore, this research aimed to estimate the annual soil loss in the upstream catchment area of a reservoir based on the Revised Universal Soil Loss Equation (RUSLE) with a remote sensing dataset. The sediment trapped in the Assarin Dam reservoir in Oman was estimated by coupling unmanned aerial vehicle (UAV) surveys with photogrammetry analysis to assess the reservoir siltation. Among the previous sediment trapping events, seven sets of field observation data were collected to investigate the relationship between soil loss at the catchment scale and sediment deposition volumes in the reservoir. The RUSLE method was applied to estimate soil erosion using independent factors such as rainfall erosivity, soil erodibility, topography, cover management and conservation practices. A remote sensing dataset and geographic information system (GIS) environments were used to analyse the quantitative and spatial distribution of the RUSLE parameters. Two drone surveys were conducted over the reservoir before and after a flash flood. The trapped sediment volume was estimated to be approximately 9,075 m3 (11,343 ton) per event, representing approximately 1.26 % of the total reservoir capacity. This computed volume was validated using measurements from monitored sediment scale bars sited throughout the Assarin Dam reservoir, yielding an accuracy of 79 %. From the RUSLE results, the annual soil erosion was estimated to be 196,599 ton/ha yr−1, of which approximately 5.8 % was trapped in the reservoir. Spatial-temporal variability in the rainfall patterns and the corresponding runoff discharges led to high sediment delivery at the outlet of the basin. After analysing available data from previous field surveys in Oman, a new formula for estimating the sediment yield in Wadi Assarin was developed. The results of this research, which represent the first of their type in the Middle East and North Africa (MENA) region, can support reservoir management practices and show that UAV-based photogrammetry is suitable for measuring trapped sediment volumes.

Characterization of the Viral Reservoirs Among HIV-1 Non-B Vertically Infected Adolescents Receiving Antiretroviral Therapy: Protocol for an Observational and Comparative Study in Cameroon.

Antiretroviral therapy (ART) can bring HIV-1 levels in blood plasma to the undetectable level and allow a near-normal life expectancy for HIV-infected individuals. Unfortunately, ART is not curative and must be taken for life, because within a few weeks of treatment cessation, HIV viremia rebounds in most patients except for rare elite or posttreatment controllers of viremia. The primary source of this rebound is the highly stable reservoir of latent yet replication-competent HIV-1 proviruses integrated into the genomic DNA of the resting memory cluster of differentiation 4 (CD4+) T cells. To achieve a cure for HIV, understanding the cell reservoir environment is of paramount importance. The size and nature of the viral reservoir might vary according to the timing of therapy, therapeutic response, ART duration, and immune response. The mechanisms of reservoir maintenance generally depend on the levels/type of immune recognition; in addition, the dynamics of viral persistence are different between pediatric and adult populations. This difference could become more evident as children grow toward adolescence. We aim to characterize the HIV reservoirs and their variability as per the virological and immunological profiles of HIV-1 non-B vertically infected adolescents receiving ART in Cameroon during the Adolescents' Viral Reservoirs study to provide accurate and reliable data for HIV cure research. This study will involve HIV-1 non-B vertically infected adolescents selected from an existing cohort in our institution. Blood samples will be collected for analyzing immunological/virological profiles, including CD4/CD8 count, plasma viral load, immune activation/inflammatory markers, genotyping, and quantification of HIV-1 viral reservoirs. We will equally recruit an age-matched group of HIV-negative adolescents as control for immunological profiling. This study received funding in November 2021 and was approved by the national institutional review board in December 2021. Sample collection will start in November 2022, and the study will last for 18 months. The HIV-1 sequences generated will provide information on the circulating HIV-1 subtypes to guide the selection of the most appropriate ART for the participants. The levels of immune biomarkers will help determine the immune profile and help identify factors driving persistent immune activation/inflammation in HIV-infected adolescents compared to those in HIV-uninfected adolescents. Analysis of the virological and immunological parameters in addition to the HIV-1 reservoir size will shed light on the characteristics of the viral reservoir in adolescents with HIV-1 non-B infection. Our findings will help in advancing the knowledge on HIV reservoirs, in terms of size and genetic variability in adolescents living with HIV. Such evidence will also help in understanding the effects of ART timing and duration on the size of the reservoirs among adolescents living with HIV-a unique population from whom the findings generated will largely contribute to designing functional cure strategies. PRR1-10.2196/41473.

Analysis of flood frequency using plotting position methods and Gumbel’s method: Vaigai River basin, Southern India

&lt;p&gt;Estimation of annual peak flood flow has considerable financial influence, as this can pave numerous ways for water resources planning, design of hydraulic structures, and sustainable management of these valuable resources at an optimum benefit. Six standard plotting position methods coupled with Linear Log-regression Model (LLM) are employed for the Return Period (RP) of 15, 20, 25, 30, 60, and 1000 years to forecast peak flood flow magnitudes and for this daily annual peak flood flow data for the periods of 24 years were used to illustrate the proposed methods. Another method, Gumbel's Analytical Approach (GAA), is also used to forecast the peak flood flow magnitude for the same RP, and it was taken as the benchmark to compare all the six methods of plotting position. The degree of accuracy of the plotting position is based on the coefficient of determination R2. The R2 values for Adamowski, Hazen, Beard, Chegodajev, Tukey, and Benard, are 0.9073, 0.9284, 0.9119, 0.9111, 0.9135, and 0.9111, respectively. Out of the six-plotting position methods, Hazen method predicted a very closer value in comparison with GAA. It is advantageous to have the additional method to forecast peak flood flow for longer RP. The achieved result assuredly facilitates effective planning, regulation, and maintenance of huge reservoirs across the frequent occurrence of floods in river basin areas, considering safety and particularly downstream inhabited areas to save loss of human life, animals, damages to properties, and an impair of cultivated crops.&lt;/p&gt;&#x0D;

Prime, shock and kill: BCL-2 inhibition for HIV cure.

While modern HIV therapy can effectively suppress viral replication, the persistence of the latent reservoir posits the greatest hurdle to complete cure. The "shock and kill" strategy is under investigation for HIV therapy, aiming to reactivate latent HIV, and subsequently eliminate it through anti-retroviral therapy and host immune function. However, thus far, studies have yielded suboptimal results, stemming from a combination of ineffective latency reversal and poor immune clearance. Concomitantly, studies have now revealed the importance of the BCL-2 anti-apoptotic protein as a critical mediator of infected cell survival, reservoir maintenance and immune evasion in HIV. Furthermore, BCL-2 inhibitors are now recognized for their anti-HIV effects in pre-clinical studies. This minireview aims to examine the intersection of BCL-2 inhibition and current shock and kill efforts, hoping to inform future studies which may ultimately yield a cure for HIV.

Ecology and distribution of Leptospira spp., reservoir hosts and environmental interaction in Sri Lanka, with identification of a new strain.

Leptospirosis is a neglected zoonotic disease and one of the leading causes of zoonotic morbidity and mortality, particularly in resource-poor settings. Sri Lanka has one of the highest disease burdens worldwide, with occasional endemic leptospirosis outbreaks (2008, 2011). Rodents are considered the main wildlife reservoir, but due to a scarcity of studies it is unclear which particular species contributes to bacterial transmission and reservoir maintenance in this multi-host multi-parasite system. Several rodent species act as agricultural pests both in rice fields and in food storage facilities. To unravel the interactions among the small mammal communities, pathogenic Leptospira spp. and human transmission pathways, we collected animals from smallholder food storage facilities, where contact between humans and small mammals is most likely, and screened kidney tissue samples for Leptospira spp. using PCR. Samples were collected in three climatic zones along a rainfall gradient. Pathogenic Leptospira spp. were detected in small mammal communities in 37 (74%) out of 50 sampled farms and 61 (12%) out of 500 collected individuals were infected. The small mammal community was comprised of Rattus rattus (87.6%), Suncus shrews (8.8%), Bandicota spp. (2.8%) and Mus booduga (0.8%). Three pathogenic Leptospira spp. were identified, L. borgpetersenii (n = 34), L. interrogans (n = 15), and L. kirschneri (n = 1). Suncus shrews were commonly infected (32%), followed by B. indica (23%) and R. rattus (10%). L. borgpetersenii strains similar to strains previously extracted from human clinal samples in Sri Lanka were detected in R. rattus and Suncus shrews. L. interrogans was observed in R. rattus only. A single L. kirschneri infection was found in M. booduga. The presence of human pathogenic Leptospira species in an agricultural pest rodent (R. rattus) and in commensal shrews (Suncus) calls for management of these species in commensal settings. Further investigation of the interplay between pathogen and reservoir population dynamics, overlap in geographic range and the extent of spill-over to humans in and around rural settlements is required to identify optimal management approaches.

Escherichia coli 0157:H7 virulence factors and the ruminant reservoir.

This review updates recent findings about Escherichia coli O157:H7 virulence factors and its bovine reservoir. This Shiga toxin (Stx)-producing E. coli belongs to the Enterohemorrhagic E. coli (EHEC) pathotype causing hemorrhagic colitis. Its low infectious dose makes it an efficient, severe, foodborne pathogen. Although EHEC remains in the intestine, Stx can translocate systemically and is cytotoxic to microvascular endothelial cells, especially in the kidney and brain. Disease can progress to life-threatening hemolytic uremic syndrome (HUS) with hemolytic anemia, acute kidney failure, and thrombocytopenia. Young children, the immunocompromised, and the elderly are at the highest risk for HUS. Healthy ruminants are the major reservoir of EHEC and cattle are the primary source of human exposure. Advances in understanding E. coli O157:H7 pathogenesis include molecular mechanisms of virulence, bacterial adherence, type three secretion effectors, intestinal microbiome, inflammation, and reservoir maintenance. Many aspects of E. coli O157:H7 disease remain unclear and include the role of the human and bovine intestinal microbiomes in infection. Therapeutic strategies involve controlling inflammatory responses and/or intestinal barrier function. Finally, elimination/reduction of E. coli O157:H7 in cattle using CRISPR-engineered conjugative bacterial plasmids and/or on-farm management likely hold solutions to reduce infections and increase food safety/security.