Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion

Background： The CD38/cyclic ADP-ribose （cADPR） pathway plays a role in various central nervous system diseases and in morphine tolerance, but its role in local anesthetic intoxication is unknown. The aim of this study was to determine the role of the CD38/cADPR pathway in ropivacaine-induced convulsion. Methods： Forty male Sprague-Dawley rats were randomly divided into five groups （n = 8 per group）： sham group, ropivacaine group, ropivacaine＋8-Br-cADPR （5 nmol） group, ropivacaine＋8-Br-cADPR （10 nmol） group, and ropivacaine＋8-Br-cADPR （20 nmol） group （no rats died）. Rats were intracerebroventricularly injected with normal saline or 8-Br-cADPR 30 min before receiving an intraperitoneal injection of ropivacaine. Electroencephalography and convulsion behavior scores were recorded. The hippocampus was harvested from each group and subjected to nicotinamide adenine dinucleotide and cADPR assays, Western blotting analysis, and malondialdehyde （MDA） and superoxide dismutase （SOD） assays. Results： Intraperitoneal injection of ropivacaine （33.8 mg/kg） induced convulsions in rats. CD38 and cADPR levels increased significantly following ropivacaine-induced convulsion （P = 0.031 and 0.020, respectively, compared with the sham group）. Intraventricular injection of 8-Br-cADPR （5, 10, and 20 nmol） significantly prolonged convulsion latency （P = 0.037, 0.034, and 0.000, respectively）, reduced convulsion duration （P = 0.005, 0.005, and 0.005, respectively）, and reduced convulsion behavior scores （P = 0.015, 0.015, and 0.000, respectively）. Intraventricular injection of 8-Br-cADPR （10 nmol） also increased the B-cell lymphoma-2 （Bcl-2）/Bcl-2-associated X protein ratio （P = 0.044） and reduced cleaved Caspase 3/Caspase 3 ratio, inducible nitric oxide synthase, MDAand SOD levels （P = 0.014, 0.044, 0.001, and 0.010, respectively） compared with the ropivacaine group. Conclusions： The CD38/cADPR pathway is activated in ropivacaine-induced convulsion. Inhibiting this pathway alleviates ropivacaine-induced convulsion and protects the brain from apoptosis and oxidative stress.

Structure-activity relationship of cyclic ADP-ribose, an update

Cyclic ADP-ribose (cADPR) is a universal Ca2+ mobilizing second messenger in many different cell types and organisms. cADPR activates Ca2+ release from endo/sarcoplasmic reticulum via ryanodine receptors. In addition, Ca2+ entry secondary to Ca2+ depletion is at least one of the mechanisms in which cADPR triggers Ca2+ inflow, too. Analogues of cADPR have been prepared by chemical and chemo-enzymatic routes. Most of the analogues were analyzed for biological activity in intact or permeabilized Jurkat T cells (a human T-lymphoma cell line). As a systematic approach, analogues were grouped according to alterations in the base, the northern ribose, the southern ribose, the pyrophosphate backbone, or in complex modifications, comprising more than one part of the molecule. Biological activity of the analogues is reviewed, with special emphasis on Jurkat T cells.

Liquefaction susceptibility and deformation characteristics of saturated coral sandy soils subjected to cyclic loadings-a critical review

Coral sandy soils widely exist in coral island reefs and seashores in tropical and subtropical regions.Due to the unique marine depositional environment of coral sandy soils,the engineering characteristics and responses of these soils subjected to monotonic and cyclic loadings have been a subject of intense interest among the geotechnical and earthquake engineering communities.This paper critically reviews the progress of experimental investigations on the undrained behavior of coral sandy soils under monotonic and cyclic loadings over the last three decades.The focus of coverage includes the contractive-dilative behavior,the pattern of excess pore-water pressure(EPWP)generation and the liquefaction mechanism and liquefaction resistance,the small-strain shear modulus and strain-dependent shear modulus and damping,the cyclic softening feature,and the anisotropic characteristics of undrained responses of saturated coral sandy soils.In particular,the advances made in the past decades are reviewed from the following aspects:(1)the characterization of factors that impact the mechanism and patterns of EPWP build-up;(2)the identification of liquefaction triggering in terms of the apparent viscosity and the average flow coefficient;(3)the establishment of the invariable form of strain-based,stress-based,or energy-based EPWP ratio formulas and the unique relationship between the new proxy of liquefaction resistance and the number of cycles required to reach liquefaction;(4)the establishment of the invariable form of the predictive formulas of small strain modulus and strain-dependent shear modulus;and(5)the investigation on the effects of stress-induced anisotropy on liquefaction susceptibility and dynamic deformation characteristics.Insights gained through the critical review of these advances in the past decades offer a perspective for future research to further resolve the fundamental issues concerning the liquefaction mechanism and responses of coral sandy sites subjected to cyclic loadings associated with seismic events in marine environments.

Damage evolution of rock-encased-backfill structure under stepwise cyclic triaxial loading

Rock-encased-backfill(RB)structures are common in underground mining,for example in the cut-andfill and stoping methods.To understand the effects of cyclic excavation and blasting activities on the damage of these RB structures,a series of triaxial stepwise-increasing-amplitude cyclic loading experiments was conducted with cylindrical RB specimens(rock on outside,backfill on inside)with different volume fractions of rock(VF=0.48,0.61,0.73,and 0.84),confining pressures(0,6,9,and 12 MPa),and cyclic loading rates(200,300,400,and 500 N/s).The damage evolution and meso-crack formation during the cyclic tests were analyzed with results from stress-strain hysteresis loops,acoustic emission events,and post-failure X-ray 3D fracture morphology.The results showed significant differences between cyclic and monotonic loadings of RB specimens,particularly with regard to the generation of shear microcracks,the development of stress memory and strain hardening,and the contact forces and associated friction that develops along the rock-backfill interface.One important finding is that as a function of the number of cycles,the elastic strain increases linearly and the dissipated energy increases exponentially.Also,compared with monotonic loading,the cyclic strain hardening characteristics are more sensitive to rising confining pressures during the initial compaction stage.Another finding is that compared with monotonic loading,more shear microcracks are generated during every reloading stage,but these microcracks tend to be dispersed and lessen the likelihood of large shear fracture formation.The transition from elastic to plastic behavior varies depending on the parameters of each test(confinement,volume fraction,and cyclic rate),and an interesting finding was that the transformation to plastic behavior is significantly lower under the conditions of 0.73 rock volume fraction,400 N/s cyclic loading rate,and 9 MPa confinement.All the findings have important practical implications on the ability of backfill to support underground excavations.

Enhancing capacitive deionization performance and cyclic stability of nitrogen-doped activated carbon by the electro-oxidation of anode materials

Electrode materials with high desalination capacity and long-term cyclic stability are the focus of capacitive deionization(CDI) community. Understanding the causes of performance decay in traditional carbons is crucial to design a high-performance material. Based on this, here, nitrogen-doped activated carbon(NAC) was prepared by pyrolyzing the blend of activated carbon powder(ACP) and melamine for the positive electrode of asymmetric CDI. By comparing the indicators changes such as conductivity, salt adsorption capacity, pH, and charge efficiency of the symmetrical ACP-ACP device to the asymmetric ACP-NAC device under different CDI cycles, as well as the changes of the electrochemical properties of anode and cathode materials after long-term operation, the reasons for the decline of the stability of the CDI performance were revealed. It was found that the carboxyl functional groups generated by the electro-oxidation of anode carbon materials make the anode zero-charge potential(E_(pzc)) shift positively,which results in the uneven distribution of potential windows of CDI units and affects the adsorption capacity. Furthermore, by understanding the electron density on C atoms surrounding the N atoms, we attribute the increased cyclic stability to the enhanced negativity of the charge of carbon atoms adjacent to quaternary-N and pyridinic-oxide-N.

Experimental study of the damage characteristics of rocks containing non-penetrating cracks under cyclic loading

The damage evolution process of non-penetrating cracks often causes some unexpected engineering disasters.Gypsum specimens containing non-penetrating crack(s)are used to study the damage evolution and characteristics under cyclic loading.The results show that under cyclic loading,the relationship between the number of non-penetrating crack(s)and the characteristic parameters(cyclic number,peak stress,peak strain,failure stress,and failure strain)of the pre-cracked specimens can be represented by a decreasing linear function.The damage evolution equation is fitted by calibrating the accumulative plastic strain for each cycle,and the damage constitutive equation is proposed by the concept of effective stress.Additionally,non-penetrating cracks are more likely to cause uneven stress distribution,damage accumulation,and local failure of specimen.The local failure can change the stress distribution and relieve the inhibition of non-penetrating crack extension and eventually cause a dramatic destruction of the specimen.Therefore,the evolution process caused by non-penetrating cracks can be regarded as one of the important reasons for inducing rockburst.These results are expected to improve the understanding of the process of spalling formation and rockburst and can be used to analyze the stability of rocks or rock structures.

Mechanical responses of anchoring structure under triaxial cyclic loading

Dynamic load on anchoring structures(AS)within deep roadways can result in cumulative damage and failure.This study develops an experimental device designed to test AS under triaxial loads.The device enables the investigation of the mechanical response,failure mode,instability assessment criteria,and anchorage effect of AS subjected to combined cyclic dynamic-static triaxial stress paths.The results show that the peak bearing strength is positively correlated with the anchoring matrix strength,anchorage length,and edgewise compressive strength.The bearing capacity decreases significantly when the anchorage direction is severely inclined.The free face failure modes are typically transverse cracking,concave fracturing,V-shaped slipping and detachment,and spallation detachment.Besides,when the anchoring matrix strength and the anchorage length decrease while the edgewise compressive strength,loading rate,and anchorage inclination angle increase,the failure intensity rises.Instability is determined by a negative tangent modulus of the displacement-strength curve or the continued deformation increase against the general downward trend.Under cyclic loads,the driving force that breaks the rock mass along the normal vector and the rigidity of the AS are the two factors that determine roadway stability.Finally,a control measure for surrounding rock stability is proposed to reduce the internal driving force via a pressure relief method and improve the rigidity of the AS by full-length anchorage and grouting modification.

Theoretical investigation on axial cyclic performance of monopile in sands using interface constitutive models

Cyclic loads generated by environmental factors,such as winds,waves,and trains,will likely lead to performance degradation in pile foundations,resulting in issues like permanent displacement accumulation and bearing capacity attenuation.This paper presents a semi-analytical solution for predicting the axial cyclic behavior of piles in sands.The solution relies on two enhanced nonlinear load-transfer models considering stress-strain hysteresis and cyclic degradation in the pile-soil interaction.Model parameters are calibrated through cyclic shear tests of the sand-steel interface and laboratory geotechnical testing of sands.A novel aspect involves the meticulous formulation of the shaft loadtransfer function using an interface constitutive model,which inherently inherits the interface model’s advantages,such as capturing hysteresis,hardening,degradation,and particle breakage.The semi-analytical solution is computed numerically using the matrix displacement method,and the calculated values are validated through model tests performed on non-displacement and displacement piles in sands.The results demonstrate that the predicted values show excellent agreement with the measured values for both the static and cyclic responses of piles in sands.The displacement pile response,including factors such as bearing capacity,mobilized shaft resistance,and convergence rate of permanent settlement,exhibit improvements compared to non-displacement piles attributed to the soil squeezing effect.This methodology presents an innovative analytical framework,allowing for integrating cyclic interface models into the theoretical investigation of pile responses.

Effect of NaCl Concentration on the Cumulative Strain and Pore Distribution of Clay under Cyclic Loading

Clay,as the most common soil used for foundationfill,is widely used in various infrastructure projects.The phy-sical and mechanical properties of clay are influenced by the pore solution environment.This study uses a GDS static/dynamic triaxial apparatus and nuclear magnetic resonance experiments to investigate the effects of cyclic loading on clay foundations.Moreover,the development of cumulative strain in clay is analyzed,and afitting model for cumulative plastic strain is introduced by considering factors such as NaCl solution concentration,con-solidation stress ratio,and cycle number.In particular,the effects of the NaCl solution concentration and con-solidation stress ratio on the pore distribution of the test samples before and after cyclic loading are examined,and the relationship between microscopic pore size and macroscopic cumulative strain is obtained accordingly.Our results show that as the consolidation stress ratio grows,an increasing number of large pores in the soil samples are transformed into small pores.As the NaCl solution concentration becomes higher,the number of small pores gradually decreases,while the number of large pores remains unchanged.Cyclic loading causes the disappearance of the large pores in the samples,and the average pore size before cyclic loading is posi-tively correlated with the axial cumulative strain after cyclic loading.The cumulative strain produced by the soil under cyclic loading is inversely proportional to the NaCl solution concentration and consolidation stress ratio.

Numerical Analysis of Fiber Reinforced Polymer-Confined Concrete under Cyclic Compression Using Cohesive Zone Models

This paper examines the mechanical behavior offiber reinforced polymer(FRP)-confined concrete under cyclic compression using the 3D cohesive zone model(CZM).A numerical modeling method was developed,employing zero-thickness cohesive elements to represent the stress-displacement relationship of concrete potential fracture surfaces and FRP-concrete interfaces.Additionally,mixed-mode damage plastic constitutive models were pro-posed for the concrete potential fracture surfaces and FRP-concrete interface,considering interfacial friction.Furthermore,an anisotropic plastic constitutive model was developed for the FRP composite jacket.The CZM model proposed in this study was validated using experimental data from plain concrete and large rupture strain(LRS)FRP-confined concrete subjected to cyclic compression.The simulation results demonstrate that the pro-posed model accurately predicts the mechanical response of both concrete and FRP-confined concrete under cyc-lic compression.Lastly,various parametric studies were conducted to investigate the internal failure mechanism of FRP-confined concrete under cyclic loading to analyze the influence of the inner friction plasticity of different components.

The Effect of Preloading on the Cyclic Liquefaction Strength Measured in the Laboratory

The effect of preloading on the liquefaction cyclic strength was investigated by cyclic shear tests where horizontal shear stress oscillated about a zero mean value on sands with varying fines content and at varying prestress ratios, densities and verticalstresses. Test results showed a marked increase of the cyclic soil strength with the prestress ratio. The effect is more pronounced for the looser specimens. An empirical expression predicting this effect is proposed. This expression is validated from results of a field test.

The Performance of Small Diameter Aluminum Light Support Structures Containing Handholes under Cyclic Fatigue

Aluminum light poles play a pivotal role in modern infrastructure, ensuring proper illumination along highways and in populated areas during nighttime. These poles typically feature handholes near their bases, providing access to electrical wiring for installation and maintenance. While essential for functionality, these handholes introduce a vulnerability to the overall structure, making them a potential failure point. Although prior research and analyses on aluminum light poles have been conducted, the behavior of smaller diameter poles containing handholes remains unexplored. Recognizing this need, a research team at the University of Akron undertook a comprehensive experimental program involving aluminum light poles with handholes containing welded inserts in order to gain a better understanding of their fatigue life, mechanical behavior, and failure mechanisms. The research involved testing seven large-scale aluminum light poles each 8-inch diameter, with two separate handholes. These handholes included a reinforcement that was welded to the poles. Finite Element Analysis (FEA), statistical analysis, and comparison analysis with their large counterparts (10-inch diameter) were used to augment the experimental results. The results revealed two distinct failure modes: progressive crack propagation leading to ultimate failure, and rupture of the pole near the weld initiation/termination site around the handhole. The comparison analysis indicated that the 8-inch diameter specimens exhibited an average fatigue life exceeding that of their 10-inch counterparts by an average of 30.7%. The experimental results were plotted alongside the fatigue detail classifications outlined in the Aluminum Design Manual (ADM), enhancing understanding of the fatigue detail category of the respective poles/handholes.

Investigation of the Micro-Mechanics of an Extruded Precipitation-Strengthened Magnesium Alloy under Cyclic Loading

Precipitation strengthening is a crucial microscopic mechanism for enhancing the strength of magnesium alloys. In order to elucidate the influence of precipitation on the microscopic deformation mechanisms and macroscopic mechanical response of magnesium alloys under cyclic loading conditions, we employed a crystal plasticity model to analyze the stress-strain curves, specific crystal plane diffraction intensities, and the temporal evolution of various microscopic deformation mechanisms and twinning volume fractions for an extruded magnesium alloy, AXM10304, containing coherent precipitates. The research findings indicate that precipitation does not fundamentally alter the microscopic mechanisms of this alloy. However, it hinders twinning during the compression stage, mildly promotes detwinning during the tension stage, and enhances tension secondary hardening by elevating the difficulty of activation of the prismatic slip.

Cyclic ADP-ribose and NAADP:fraternal twin messengers for calcium signaling

The concept advanced by Berridge and colleagues that intracellular Ca2+-stores can be mobilized in an agonist-dependent and messenger(IP3)-mediated manner has put Ca 2+-mobilization at the center stage of signal transduction mechanisms.During the late 1980s,we showed that Ca2+-stores can be mobilized by two other messengers unrelated to inositol trisphosphate(IP 3) and identified them as cyclic ADP-ribose(cADPR),a novel cyclic nucleotide from NAD,and nicotinic acid adenine dinucleotide phosphate(NAADP),a linear metabolite of NADP.Their messenger functions have now been documented in a wide range of systems spanning three biological kingdoms.Accumulated evidence indicates that the target of cADPR is the ryanodine receptor in the sarco/endoplasmic reticulum,while that of NAADP is the two pore channel in endolysosomes. As cADPR and NAADP are structurally and functionally distinct,it is remarkable that they are synthesized by the same enzyme.They are thus fraternal twin messengers.We first identified the Aplysia ADP-ribosyl cyclase as one such enzyme and,through homology,found its mammalian homolog,CD38.Gene knockout in mice confirms the important roles of CD38 in diverse physiological functions from insulin secretion,susceptibility to bacterial infection,to social behavior of mice through modulating neuronal oxytocin secretion.We have elucidated the catalytic mechanisms of the Aplysia cyclase and CD38 to atomic resolution by crystallography and site-directed mutagenesis.This article gives a historical account of the cADPR/NAADP/CD38-signaling pathway and describes current efforts in elucidating the structure and function of its components.

Experimental investigation on shear strength deterioration at the interface between different rock types under cyclic loading

The shear strength deterioration of bedding planes between different rock types induced by cyclic loading is vital to reasonably evaluate the stability of soft and hard interbedded bedding rock slopes under earthquake;however,rare work has been devoted to this subject due to lack of attention.In this study,experimental investigations on shear strength weakening of discontinuities with different joint wall material(DDJM)under cyclic loading were conducted by taking the interface between siltstone and mudstone in the Shaba slope of Yunnan Province,China as research objects.A total of 99 pairs of similar material samples of DDJM(81 pairs)and discontinuities with identical joint wall material(DIJM)(18 pairs)were fabricated by inserting plates,engraved with typical surface morphology obtained by performing three-dimensional laser scanning on natural DDJMs sampled from field,into mold boxes.Cyclic shear tests were conducted on these samples to study their shear strength changes with the cyclic number considering the effects of normal stress,joint surface morphology,shear displacement amplitude and shear rate.The results indicate that the shear stress vs.shear displacement curves under each shear cycle and the peak shear strength vs.cyclic number curves of the studied DDJMs are between those of DIJMs with siltstone and mudstone,while closer to those of DIJMs with mudstone.The peak shear strengths of DDJMs exhibit an initial rapid decline followed by a gradual decrease with the cyclic number and the decrease rate varies from 6%to 55.9%for samples with varied surface morphology under different testing conditions.The normal stress,joint surface morphology,shear displacement amplitude and shear rate collectively influence the shear strength deterioration of DDJM under cyclic shear loading,with the degree of influence being greater for larger normal stress,rougher surface morphology,larger shear displacement amplitude and faster shear rate.

Poly(ADP-ribose) polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain

Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that jimit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially per- oxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly（ADP-ribose） polymerase （PARP） upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neu- ronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the in- volvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.

Multiple facets of poly(ADP-ribose) polymerase-1 in neurological diseases

The highly conserved abundant nuclear protein poly （ADP-ribose） polymerase-1 （PARP-1） is activated by DNA damage. PARP-1 activation is associated in DNA repair, cell death and inflammation. Since oxidative stress induced robust DNA damage and wide spread inflamma- tory responses are common pathologies of various CNS diseases, the attention towards PARP-1 as a therapeutic target has been amplifying. This review highlights the multiple roles of PARP- 1 in neurological diseases and po- tential of PARP- 1 inhibitors to enter clinical translation.

Mechanical response and microscopic damage mechanism of pre-flawed sandstone subjected to monotonic and multilevel cyclic loading:A laboratory-scale investigation

This study aims to investigate the mechanical response and acoustic emission(AE)characteristic of pre-flawed sandstone under both monotonic and multilevel constant-amplitude cyclic loads.Specifically,we explored how coplanar flaw angle and load type impact the strength and deformation behavior and microscopic damage mechanism.Results indicated that being fluctuated before rising with increasing fissure angle under monotonic loading,the peak strength of the specimen first increased slowly and then steeply under cyclic loading.The effect of multilevel cyclic loading on the mechanical parameters was more significant.For a single fatigue stage,the specimen underwent greater deformation in early cycles,which subsequently stabilized.Similar variation pattern was also reflected by AE count/energy/b-value.Crack behaviors were dominated by the fissure angle and load type and medium-scale crack accounted for 74.83%–86.44%of total crack.Compared with monotonic loading,crack distribution of specimen under cyclic loading was more complicated.Meanwhile,a simple model was proposed to describe the damage evolution of sandstone under cyclic loading.Finally,SEM images revealed that the microstructures at the fracture were mainly composed of intergranular fracture,and percentage of transgranular fracture jumped under cyclic loading due to the rapid release of elastic energy caused by high loading rate.

Inhibition of poly(ADP-Ribose)polymerase:A promising strategy targeting pancreatic cancer with BRCAness phenotype

The use of chemotherapeutic regimens for the treatment of pancreatic cancer is still limited because pancreatic cancer is usually diagnosed at an advanced stage as a refractory disease in which symptoms are difficult to recognize in the early stages.Furthermore,at advanced stages,there are important challenges to achieve clinical benefit and symptom resolution,even with the use of an expanded spectrum of anticancer drugs.Recently,a point of reduced susceptibility to conventional chemotherapies by breast cancer susceptibility gene(BRCA)mutations led to a new perspective for overcoming the resistance of pancreatic cancer within the framework of increased genome instability.Poly(ADP-Ribose)polymerase(PARP)-1 is an enzyme that can regulate intrinsic functions,such as response to DNA damage.Therefore,in an environment where germline mutations in BRCAs(BRCAness)inhibit homologous recombination in DNA damage,resulting in a lack of DNA damage response,a key role of PARP-1 for the adaptation of the genome instability could be further emphasized.Here,we summarized the key functional role of PARP-1 in genomic instability of pancreatic cancer with the BRCAness phenotype and listed clinical applications and outcomes of PARP-1 inhibitors to highlight the importance of targeting PARP-1 activity.

Hydraulic and volume change behaviors of compacted highly expansive soil under cyclic wetting and drying

The wide engineered application of compacted expansive soils necessitates understanding their behavior under field conditions.The results of this study demonstrate how seasonal climatic variation and stress and boundary conditions individually or collectively influence the hydraulic and volume change behavior of compacted highly expansive soils.The cyclic wetting and drying(CWD)process was applied for two boundary conditions,i.e.constant stress(CS)and constant volume(CV),and for a wide range of axial stress states.The adopted CWD process affected the hydraulic and volume change behaviors of expansive soils,with the first cycle of wetting and drying being the most effective.The CWD process under CS conditions resulted in shrinkage accumulation and reduction in saturated hydraulic conductivity(k sat).On the other hand,CWD under CV conditions caused a reduction of swell pressure while has almost no impact on k sat.An elastic response to CWD was achieved after the third cycle for saturated hydraulic conductivity(k sat),the third to fourth cycle for the volume change potential under the CV conditions,and the fourth to fifth cycle for the volume change potential under the CS conditions.Finally,both swell pressure(s s)and saturated hydraulic conductivity(k sat)are not fundamental parameters of the expansive soil but rather depend on stress,boundary and wetting conditions.