Long-term Infiltration Research Articles

Abstract B021: Treatment with a novel targeting module, redirecting UniCAR T cells against PSCA, delays subcutaneous tumor growth and prolongs survival of tumor-bearing NSG mice

Abstract Background: The adoptive transfer of T cell engineered with chimeric antigen receptors (CARs) is currently considered a highly promising therapeutic option for treating so far incurable malignant diseases. In order to reduce adverse reactions associated with CAR engineered T cells, a flexible modular universal chimeric antigen receptor (UniCAR) platform is developed, which allows a precise control of CAR T cell reactivity to manage side effects while preserving efficacy. The UniCAR technology splits the signaling and antigen-binding aspects of conventional CARs into two individual components. The UniCAR is structurally similar to second-generation CARs, however the single chain variable fragment (scFv) does not recognize a cell surface antigen but a short peptide motif derived from a human nuclear autoantigen. Antigen-specificity and crosslinking of UniCAR expressing T cells to target cells is provided by a separate targeting module (TM) compromising a scFv, binding to specific cell surface antigens, fused to the aforementioned peptide motif. Thus, T cells engineered to express UniCARs remain inactivated after infusion, since the UniCAR target is not available for binding under physiological conditions. Only in the presence of the TM, antigen specific activation of UniCAR T cells occurs, which allows for a more sophisticated regulation. Methods: We developed a novel radio-immune target module (TM), which consists of an anti-PSCA (prostate stem cell antigen) scFv for redirecting of UniCARs to PSCA expressing tumor cells. Three different tags are fused in a row to the C-Terminus of the scFv to functionalize the molecule for combined immune- and radiotherapy. First, a ten amino acid (aa) long tag mediates the crosslink to T cells genetically modified with the UniCAR. Further downstream, a peptide tag (Rx) for enhanced conjugation of radionuclides and finally, a 6xhistidine (His) tag are located. TM-Rx efficacy was evaluated for target cell killing in-vitro and compared to a TM without Rx-tag. In-vivo efficacy of the TM-Rx was also investigated in a high and low-tumor burden mouse model. Results: Rx-TM and TM equivalently kill PSCA-expressing tumor cells in-vitro in presence of UniCARs in an E:T (Effector:Target) ratio of 1:1 after 24 hours. UniCAR T cell engrafted NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice show no clinical signs of autoimmunity neither in presence nor absence of the TM. One week treatment with TM delays subcutaneous tumor growth and prolongs survival of tumor bearing, UniCAR T cell engrafted NSG mice. Longterm infiltration of tumor tissue by UniCARs could be observed over 16 weeks in the high and low-tumor burden ectopic carcinoma model. Conclusion: The UniCAR technology shows efficacy both in-vitro and in-vivo. Extension of the TM with an additional tag does not impair functionality of the UniCAR platform. Short-treatment prolongs survival of tumor bearing mice but does not lead to cure, therefore combination with other treatment modalities e.g. radiation oncology seems reasonable. Citation Format: Elham Pishali Bejestani, Malte von Bonin, Marc Cartellieri, Armin Ehninger, Mechthild Krause, Michael Baumann, Gerhard Ehninger, Michael Bachmann. Treatment with a novel targeting module, redirecting UniCAR T cells against PSCA, delays subcutaneous tumor growth and prolongs survival of tumor-bearing NSG mice. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B021.

Periradicular infiltration therapy : Clinical indications, technique and results

Minimally invasive procedures have played an emerging role in pain management during recent years. Evaluation of the different types of periradicular infiltration as fundamental procedures in the progressive stepwise concept of pain management. Comparison of the different therapeutic substances. In the mid-term and long-term periradicular infiltration is effective in 60-80 % of patients regarding analgesic and functional aspects. Compliance with the guidelines should help to minimize potentially fatal complications. Periradicular infiltration is of significant importance concerning the treatment of spinal nerve root irritation. Periradicular infiltration is regarded as a safe procedure, especially when supported by computed tomography (CT) scans.

Association between dry eye and inflammatory response mediated by CCR5 and CXCR3 and their ligands

Background Sustained abnormal tear secretion in dry eye patients may lead to ocular surface and lacrimal glands in the state of long-term inflammatory cell infiltration. Lacrimal gland suffers immune attack by lymphoproliferative, and inflammation interferes normal gland secretion, in which chemokines and their receptors on lymphocytes play a key role. Objective This study was to investigate the inflammation mechanism of delayed allergy induced by Th1 cell in the development of dry eye. Methods Sixty eyes of 30 patients with dry eye and matched 30 healthy volunteers were enrolled in Affiliated First Hospital of Xinjiang Medical University from June to December in 2012. SchirmerⅠtest (SⅠt), break up time (BUT) of tear and corneal fluorescence stain (FLS) were performed on the subjects, and conjunctiva epithelial cells were obtained using cytological method of conjunctiva imprinting. Positive cell rates of CC chemokine receptor 5 (CCR5) and CXC chemokine receptor 3 (CXCR3) were detected by flow cytology, and the relative expression levels of regulated upon activation of normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α and MIP-1β, monokine induced by interferon-γ (IFN-γ) (MIG), interferon-γ inducible protein 10 (IP10) and interferon-inducible T-cell α chemoattractant (I-TAC) mRNA were quantitatively assayed by real-time PCR. Differences of the positive rates of CCR5, CXCR3 and lignds were compared between dry eye group and normal control group. Relationship between the positive rates of CCR5, CXCR3 and BUT, SⅠt, FLS scores was analyzed. Results The values of BUT, SⅠt were (2.90±1.37) seconds and (4.00±2.49) mm/5 minutes in the dry eye group, which were significantly lower than (8.56±4.69) seconds and (11.31±5.23) mm/5 minutes in the normal control group (t=3.172, 2.186, both at P 0.05). The positive correlations were seen between the masculine rate of CCR5 with the relative expression of RANTES or MIP-1α mRNA (r=0.473, 0.285, both at P 0.05). In addition, the masculine rate of CXCR3 was positive correlated with the expressions of MIG and IP10 mRNA (r=0.553, 0.314, both at P 0.05). Conclusions Dry eye is probably along with the long-term infiltration of inflammatory cells. The delayed allergy induced by Th1 cells and the nature killed cells is probably the primary cause to xerophthalmia. CCR5, CXCR3 and their ligands might be the regulative targets in the inflammation mechanism of dry eye. Key words: Dry eye; Chemokines; Receptors, chemokines; Conjunctiva/metabolism; Flow cytometry; Real-time PCR; Humans

Allogeneic tendon-derived stem cells promote tendon healing and suppress immunoreactions in hosts: in vivo model.

The medium- to long-term healing effect and infiltration of inflammatory cells, after transplantation of allogeneic tendon-derived stem cell (TDSC) to the rat patellar tendon window wound, were examined. Allogeneic patellar TDSCs derived from a green fluorescent protein rat were used. The outcome of tendon healing and the infiltration of inflammatory cells were examined by histology and immunohistochemistry up to week 16 postinjury. The fate of the transplanted cells was examined by ex vivo fluorescent imaging and immunohistochemistry. Our results showed that the transplantation of allogeneic TDSCs promoted tendon healing with no increased risk of ectopic chondro-ossification up to week 16. A low infiltration of T cells, ED1 macrophages, ED2 macrophages, and mast cells in the window wound was obtained. The transplanted TDSCs were found in the window wound at week 1 and 2, but were absent after week 4 postinjury. In conclusion, allogeneic TDSCs promoted tendon repair in the medium to long term and exhibited weak immunoreactions and anti-inflammatory effects in the hosts after transplantation in a rat model. There was no increased risk of ectopic chondro-ossification after TDSC transplantation. The decrease in the number of transplanted cells with time suggested that allogeneic TDSCs did not promote tendon repair through direct differentiation.

NLRP3 inflammasome activation is required for fibrosis development in NAFLD.

NLR inflammasomes, caspase 1 activation platforms critical for processing key pro-inflammatory cytokines, have been implicated in the development of nonalcoholic fatty liver disease (NAFLD). As the direct role of the NLRP3 inflammasome remains unclear, we tested effects of persistent NLRP3 activation as a contributor to NAFLD development and, in particular, as a modulator of progression from benign hepatic steatosis to steatohepatitis during diet-induced NAFLD. Gain of function tamoxifen-inducible Nlrp3 knock-in mice allowing for in vivo temporal control of NLRP3 activation and loss of function Nlrp3 knockout mice were placed on short-term choline-deficient amino acid-defined (CDAA) diet, to induce isolated hepatic steatosis or long-term CDAA exposure, to induce severe steatohepatitis and fibrosis, respectively. Expression of NLRP3 associated proteins was assessed in liver biopsies of a well-characterized group of patients with the full spectrum of NAFLD. Nlrp3(-/-) mice were protected from long-term feeding CDAA-induced hepatomegaly, liver injury, and infiltration of activated macrophages. More importantly, Nlrp3(-/-) mice showed marked protection from CDAA-induced liver fibrosis. After 4 weeks on CDAA diet, wild-type (WT) animals showed isolated hepatic steatosis while Nlrp3 knock-in mice showed severe liver inflammation, with increased infiltration of activated macrophages and early signs of liver fibrosis. In the liver samples of patients with NAFLD, inflammasome components were significantly increased in those patients with nonalcoholic steatohepatitis (NASH) when compared to those with non-NASH NAFLD with mRNA levels of pro-IL1 beta correlated to levels of COL1A1. Our study uncovers a crucial role for the NLRP3 inflammasome in the development of NAFLD. These findings may lead to novel therapeutic strategies aimed at halting the progression of hepatic steatosis to the more severe forms of this disease. Key message: Mice with NLRP3 inflammasome loss of function are protected from diet-induced steatohepatitis. NLRP3 inflammasome gain of function leads to early and severe onset of diet-induced steatohepatitis in mice. Patients with severe NAFLD exhibit increased levels of NLRP3 inflammasome components and levels of pro-IL1β mRNA correlate with the expression of COL1A1.

Modelling hydrology of a single bioretention system with HYDRUS-1D.

A study was carried out on the effectiveness of bioretention systems to abate stormwater using computer simulation. The hydrologic performance was simulated for two bioretention cells using HYDRUS-1D, and the simulation results were verified by field data of nearly four years. Using the validated model, the optimization of design parameters of rainfall return period, filter media depth and type, and surface area was discussed. And the annual hydrologic performance of bioretention systems was further analyzed under the optimized parameters. The study reveals that bioretention systems with underdrains and impervious boundaries do have some detention capability, while their total water retention capability is extremely limited. Better detention capability is noted for smaller rainfall events, deeper filter media, and design storms with a return period smaller than 2 years, and a cost-effective filter media depth is recommended in bioretention design. Better hydrologic effectiveness is achieved with a higher hydraulic conductivity and ratio of the bioretention surface area to the catchment area, and filter media whose conductivity is between the conductivity of loamy sand and sandy loam, and a surface area of 10% of the catchment area is recommended. In the long-term simulation, both infiltration volume and evapotranspiration are critical for the total rainfall treatment in bioretention systems.

Long-Term Hydraulic Performance of Porous Asphalt Pavements in Northern Sweden

The effect of clogging on the long-term infiltration capacity and porosity of two 18- and 24-year-old porous asphalts was examined by using replicate double-ring infiltrometer tests and analyzing asphalt core samples. Tests were carried out to see if high pressure washing and vacuum cleaning could restore the hydraulic performance. The infiltration capacity of the porous asphalts decreased substan- tially, primarily due to surficial clogging (0.50 � 0.26 in Lulea, Sweden, and 0.22 � 0.12 in Haparanda, Sweden, compared to initially > 290 mmmin −1 ). In Lulea, washing and vacuum cleaning could partially restore the infiltration capacity (3.48 � 3.00 mmmin −1 ), but in Haparanda, no effect was measured. The porosity was constantly between 16 and 18%. The difference of the long-term behavior and effect of cleaning in Lulea and Haparanda is primarily attributable to different street maintenance, age, and winter maintenance (application of fine gravel and/or sand). Although the infiltration capacity in Lulea was far below initial values, the asphalt still has the capacity to infiltrate an intense design rainfall (100 year average return interval, 15 min duration), underlining that porous asphalt can be a resilient feature also under nonfavorable conditions. DOI: 10.1061/(ASCE)IR.1943-4774.0000569. © 2013 American Society of Civil Engineers. CE Database subject headings: Porous media; Asphalt pavements; Clogging; Infiltration; Sweden; Hydraulics. Author keywords: Porous asphalt; Long-term performance; Clogging; High-pressure washing/vacuum cleaning; Infiltration capacity; Porosity.

Bonding implications of heap leach infiltration rates at Nevada mines

One important factor in determining bonding costs for mine reclamation is the steady-state infiltration rate of the heap leach pad(s). The importance of assessing each mine on a case-by-case basis is demonstrated. Long-term infiltration rates were investigated for 19 Nevada heaps: <2% at <1860 m above mean sea level (amsl) and <3% at >1860 m amsl. A common means of reducing steady-state infiltration rate is the application of a vegetative cover. Cover implementation costs can be optimised by mathematical modelling of precipitation flow through the heap. For the proposed Buffalo Valley mine, the post-closure heap equilibrium flux of ∼1 mm/year for a 0.9-, 1.2- or 1.5-m-thick cover was calculated after ∼11, 17, and 23 years, respectively, demonstrating that covers > 0.9 m (adequate for successful revegetation) accrue no incremental reduction in infiltration rate. The infiltration rate for this cover thickness (0.6%) was consistent with heaps at similar elevations.

Effective Vertical Solute Transport in Soils by Artificial Macropore System

AbstractSolute transport is an important factor governing soil environmental processes, such as effective fertilizer application or dispersion areas of remediation chemicals for contaminated soils. Macropores are ubiquitous in soils. In unsaturated conditions, they enhance air intrusion into soils, thus reducing the chances of clogging and surface ponding. However, their structure is hard to maintain, and they tend to collapse during long-term infiltration. In this experiment, macropore fillings were introduced into the pores to maintain their structure. Solute transport experiments were conducted for four soils with no macropores, empty macropores, macropores with paper towel fillings, and macropores with glass fiber fillings. The macropores with fillings worked as water pathways that conducted solutions to the deeper profile without saturation at the surface, thus avoiding clogging. When bio-remediation experiments were conducted using these four soil columns, soil columns with glass fiber fillings main...

Abdominal γ-Radiation Induces an Accumulation of Function-Impaired Regulatory T Cells in the Small Intestine

To assess the frequency and the functional characteristics of one major component of immune tolerance, the CD4(+)FoxP3(+) regulatory T cells (Tregs) in a mouse model of abdominal irradiation. Mice were exposed to a single abdominal dose of γ-radiation (10 Gy). We evaluated small intestine Treg infiltration by Foxp3 immunostaining and the functional suppressive activity of Tregs isolated from mesenteric lymph nodes. Foxp3 immunostaining showed that radiation induced a long-term infiltration of the intestine by Tregs (levels 5.5 times greater than in controls). Co-culture of Tregs from mesenteric lymph nodes with CD4(+) effector cells showed that the Tregs had lost their suppressive function. This loss was associated with a significant decrease in the levels of Foxp3, TGF-β, and CTLA-4 mRNA, all required for optimal Treg function. At Day 90 after irradiation, Tregs regained their suppressive activity as forkhead box P3 (Foxp3), transforming growth factor beta (TGF-β), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression returned to normal. Analysis of the secretory function of mesenteric lymph node Tregs, activated in vitro with anti-CD3/anti-CD28 Abs, showed that this dysfunction was independent of a defect in interleukin-10 secretion. Radiation caused a long-term accumulation of function-impaired Foxp3(+)CD4(+) Tregs in the intestine. Our study provides new insights into how radiation affects the immune tolerance in peripheral tissues.

Properties of modified Nafion® membranes with heavy amount of (3-mercaptopropyl) trimethoxysilane prepared by long-term infiltration

Modified Nafion® membranes with a large amount of (3-mercaptopropyl) trimethoxysilane (MPTS) were fabricated by a long-term infiltration process. MPTS has been known as a strong surface modifier due to its ability to form inorganic phases having a high concentration of sulfonic acid ligands by proper oxidation of thiol-groups. In this work, the long-term infiltration of 3-mercaptopropyltrimethoxysilane (MPTS) monomers into the Nafion® matrix was performed to achieve the goal of reducing methanol crossover without sacrificing proton conductivity. Thiol (-SH) groups of MPTS molecules were converted into sulfonic acid groups by mild oxidation with hydrogen peroxide (H2O2). The fabricated membranes were characterized through microstructure observation, solvent uptake and expansion test, and proton conductivity measurement. The MPTS-derived inorganic phase formed in the ionic cluster pathways and the free volume in the Nafion® matrix could significantly reduce the methanol transfer rate, keeping high proton conductivity due to an increase in sulfonic acid concentration induced from the oxidation of the infiltrated MPTS.

Application of the steady-state principle of constant-head well permeameter to indirect subsurface drip irrigation

Indirect subsurface drip irrigation (ISDI) is a method of increasing the irrigation water use efficiency of drip irrigation without the need to bury irrigation tubes and wet the soil surface. A major problem of ISDI is the mismatch between emitter discharge rate and water-conducting device dimension, which will result in over-filling of application water. In this paper, we propose to use the steady-state principle of constant-head well permeameter (CHWP) to quantify the relationship between emitter discharge rate and water-conducting device dimension for ISDI. CHWP tests and ISDI tests were carried out in a 300 m2 winter wheat fallow to verify its feasibility. The steady-state characteristic of these two methods was also studied using long-term infiltration. Results indicate that the equilibration time (110 min) in the ISDI tests was greater than that in the CHWP tests (30 min). The steady ponded depth in ISDI had a smaller variation than the steady water discharge rate in the CHWP. When using the steady-state principle of CHWP to design ISDI systems, there was significant linear correlation between predicted and measured ponded depth values (R2 = 0.8379). The soil field-saturated hydraulic conductivity calculated by these two tests was approximately equal. These results demonstrate that the steady-state principle of CHWP could be used to select appropriate irrigation systems for ISDI, and ISDI provides another technique to obtain the field-saturated hydraulic conductivity. Key words: Constant-head well permeameter, field-saturated hydraulic conductivity, indirect subsurface drip irrigation, steady-state

New method for monitoring soil water infiltration rates applied to a disc infiltrometer

Summary Disc infiltrometers commonly use low-capacity water-supply reservoirs made of small diameter tubes. This reservoir geometry allows accurate measurements of water levels, but makes it necessary to stop the infiltration measurements to refill the water-supply reservoir when long-term infiltration experiments are conducted. The purpose of this study is to determine if a double Mariotte system provides accurate infiltration rate data from disc infiltrometer. To this end, infiltration rates (Q) is calculated from the head losses (ΔHT) produced by the water flowing along a flexible silicone pipe that connects a high-capacity water-supply reservoir and the disc of the infiltrometer. The method was calibrated in the laboratory using 2- and 3-mm internal diameter (i.d.) and 50- and 100-cm-long silicone pipes by comparing the measured ΔHT with the corresponding theoretical values, for different Q measured from the drop in water level in the water-supply reservoir. This method was next applied to field conditions, where the infiltration rates (at four supply pressure heads in five different soils) measured from the water-level drop in the water-supply reservoir of a double Mariotte disc infiltrometer (using 2- and 3-mm-i.d. and 100-cm-long silicone pipes) were compared with the corresponding values calculated from ΔHT measured in the Mariotte tube. An excellent correlation was found in the laboratory experiment between the calculated and the measured ΔHT (r2 = 0.99), and between Q measured from the water-supply reservoir and that calculated from the measured ΔHT (r2 = 0.99). In the field experiments, excellent correlation was shown between the infiltration rates measured from the water-level drop in the water-supply reservoir and the corresponding values calculated from the ΔHT measured in the Mariotte tube. This correspondence indicated that this method would be a consistent alternative to the standard procedure used in the disc infiltrometry technique.

A serendipitous, long-term infiltration experiment: Water and tritium circulation beneath the CAMBRIC trench at the Nevada Test Site

Underground nuclear weapons testing at the Nevada Test Site introduced numerous radionuclides that may be used subsequently to characterize subsurface hydrologic transport processes in arid climates. In 1965, a unique, 16-year pumping experiment designed to examine radionuclide migration away from the CAMBRIC nuclear test, conducted in the saturated zone beneath Frenchman Flat, Nevada, USA, gave rise to an unintended second experiment involving radionuclide infiltration through the vadose zone, as induced by seepage of pumping effluents beneath an unlined discharge trench. The combined experiments have been reanalyzed using a detailed, three-dimensional numerical model of transient, variably saturated flow and mass transport in a heterogeneous subsurface, tailored specifically for large-scale and efficient calculations. Simulations have been used to estimate tritium travel and residence times in various parts of the system for comparison with observations in wells. Model predictions of mass transport were able to clearly demonstrate radionuclide recycling behavior between the trench and pumping well previously suggested by isotopic age dating information; match travel time estimates for radionuclides moving between the trench, the water table, and monitoring and pumping wells; and provide more realistic ways in which to interpret the pumping well elution curves. Collectively, the results illustrate the utility of integrating detailed numerical modeling with diverse observational data in developing more accurate interpretations of contaminant migration processes.

Evidence for a compositional boundary within the lithospheric mantle beneath the Kalahari craton from S receiver functions

S and P receiver functions from the Southern African Seismic Experiment are analyzed for lithospheric discontinuities beneath the Kalahari craton. Besides the Moho, the most prominent feature is a discontinuous reduction in seismic velocity of about 4.5% at approximately 150 km depth. The discontinuity appears to have a width of about 10 km. Termed the K-discontinuity, this feature is restricted to the northern half of the array, extending from the Zimbabwe craton south to the TML (Thabazimbi–Murchison lineament), and in the west from Botswana to the edge of the Kalahari craton in the east. It spans several Archean sutures and is thus unlikely related to Archean tectonics. It does, however, appear to be related to subsequent magmatic episodes. The strongest anomaly is coincident with the most intense Karoo volcanism, and it extends to the northern edge of the Bushveld intrusion. From mantle xenoliths and xenocrysts, the entire lithosphere in this region appears to have experienced a long-term infiltration of basaltic melt and metasomatic fluids. We propose that the K-discontinuity reflects the influence of this melt/metasomatic infiltration, which has, over time, intruded and refertilized the lithosphere. Based on kimberlites pipes that show obvious signs of melt metasomatism and likely Karoo influence, the observed reduction in seismic velocity is plausibly consistent with the observed major-element and volatile enrichment at 150 km depth in such kimberlites. If this interpretation is correct, then the high-temperature kimberlite nodules that most clearly reflect this perturbation likely represent the general state of the lower lithosphere, rather than only reflecting local mantle properties in the immediate vicinity of the kimberlite eruption.

Uniqueness of Soil Hydraulic Parameters Determined by a Combined Wooding Inverse Approach

Knowledge of soil hydraulic properties is essential for a proper understanding and evaluation of physical and chemical processes within the vadose zone involved in variably saturated water flow and transport of water-dissolved salts and pollutants. Soil hydraulic properties are often expressed using functional relationships between the soil hydraulic conductivity (K), water content (θ), and matric potential Ψ). Our objectives were (i) to combine the Wooding's analytical solution for steady-state infiltration from a circular pond and the inverse determination of parameters from transient infiltration events into a coupled method for the in situ estimation of soil hydraulic properties, and (ii) to develop a simple semiautomatic device for the in situ estimation of the soil hydraulic functions. The experimental method consists of measurements of transient (short-term) and steady-state (long-term) infiltration flow rates from a set of rings having different radii, each positioned sequentially at the same location on the soil surface. A shallow water depth is maintained within a 1- to 2-mm range over the soil surface with an electrode set. The flow rate is determined by continuous weighing of a water reservoir. The flow is monitored and controlled by a laptop computer, which also automatically calculates the soil hydraulic properties from collected data. The coupled method starts with the application of the Wooding's analytical solution to obtain estimates of the soil hydraulic properties using steady-state fluxes. These estimates are then finalized using numerical inversion of the transient data. The coupled method was evaluated using numerically generated data. Unique and fast reproduction of soil hydraulic properties for generated data was obtained. The method's applicability was also tested using field experiments for two soils. The technique was found to be sound and the device simple to operate.

Induction of prolonged infiltration of T lymphocytes and transient T lymphocyte–dependent collagen deposition in mouse lungs following adenoviral gene transfer of CCL18

Levels of CCL18 are elevated in patients with scleroderma lung disease and other fibrotic pulmonary diseases associated with T lymphocyte involvement. We sought to determine whether CCL18 alone can induce pulmonary T lymphocytic infiltration and fibrosis in mouse lungs. An adenovirus vector was constructed and used for CCL18 delivery to mouse lungs in vivo. Immunohistochemical, flow cytometric, and enzyme-linked immunosorbent assay analyses were used to assess the resulting changes. Overexpression of CCL18 led to massive perivascular and peribronchial infiltration of T lymphocytes. Although the expression of CCL18 peaked on day 7, the infiltration persisted up to day 64 after infection. The infiltrates were negative for proliferating cell nuclear antigen and TUNEL, suggesting the role of cell trafficking, rather than proliferation and apoptosis, in the infiltration dynamics. Patchy destruction of the alveolar architecture and collagen accumulation in association with the infiltrates were also noticed. These changes were infiltration-dependent, rather than CCL18-dependent, since treatment with antilymphocyte serum completely abrogated the CCL18-induced changes. The infiltrates consisted almost exclusively of T lymphocytes that were minimally activated, with a minimal increase in the expression of CD69 and no changes in the expression of CD25, Fas, FasL, or CD40L. There was no increase in total pulmonary levels of profibrotic cytokines transforming growth factor beta1 (TGFbeta1) or interleukin-13, although active TGFbeta1 was present locally in association with the infiltrates and areas of distorted alveolar architecture. Prestimulation of primary T lymphocytes with CCL18 in vitro caused an up-regulation of TGFbeta1 and collagen production in T lymphocyte/fibroblast cocultures. CCL18 promotes selective, long-term pulmonary infiltration of T lymphocytes and infiltration-dependent accumulation of collagen through a TGFbeta1-dependent mechanism.

Clogging microstructures in the vadose zone—laboratory and field studies

Long-term water infiltration into porous media, like clastic deposits, causes colmatage (clogging), which is expressed by the decrease of permeability. It is caused by progressive filling of pore spaces with fine particles carried in suspension (mechanical colmatage) and minerals precipitated from water (chemical colmatage or biochemical colmatage, when the process is affected by bacterial activity). Although this material is introduced into the sediment after deposition, it does not destroy the primary framework of it but it only coats grains and fills voids. This process results in some characteristic microstructures that are called ‘clogging microstructures’. The research included: (1) experiments on sands exposed to mechanical colmatage in laboratory conditions, which aimed to describe clogging microstructures and to examine the effects of grain size distribution on the rate and degree of clogging; (2) field and laboratory studies of deposits in which colmatage occurred in natural conditions in the infiltrating water intake ‘Debina’ in Poznan, Poland. The main goal of the research was to identify post-depositional changes that took place in fluvial deposits affected by forced river water infiltration in the Warta River valley. Examples are presented of clogging microstructures formed in deposits affected by colmatage in the laboratory and in natural conditions.

Identification and regional quantification of hydrochemical processes at the contact zone between anoxic groundwater and surface water in poldered floodplains (Oderbruch polder, Germany)

The hydrochemistry in the largest polder of the Oder River, named Oderbruch, is affected by long-term infiltration of water from the Oder into the aquifer below an alluvial loamy top layer of the polder. These exceptional hydraulic conditions are a result of dyke constructions which were built more than 250 a ago. The objective of this investigation is a better understanding and a characterisation of the contact zone between the anaerobic groundwater and the surface water of a vast drainage system. Induced by changing water levels, different hydraulic conditions occur, which strongly influence the hydrochemistry of the shallow aquifer and therefore the natural sink function of the polder area. Field investigations with a hydrochemical and hydraulic characterisation of selected drainage ditch locations show considerable chemical interactions between groundwater and surface water. Depending on the drainage ditch type, which is defined by the hydraulic situation, the redox processes create a chemical gradient combined with a distinct enrichment of Fe and Mn. The source of the high amounts of Fe and Mn in the groundwater are reduced Fe- and Mn-hydroxides from the aquifer sediments. Under exfiltrating conditions interrupted by dry phases, more than 50 g kg −1 Fe and 0.25 g kg −1 Mn have accumulated in the drainage ditch floor sediments since the construction of the drainage ditches 35 a ago. The results show a very effective fixation of trace metals in the drainage ditch sediments under these conditions. Under permanent exfiltration conditions, the enrichment of Fe and Mn is relatively low. The maximum Fe content was 4 g kg −1 sediment and the Mn content reached only 0.4 g kg −1. This is less than 10% of the mobile Fe 2+ and less than 1% of the Mn 2+ which migrates from the aquifer into the surface water.

Development of Long Term Precipitation and Infiltration Records for the Performance Evaluation of a Proposed Regional Tunnel

This chapter describes how long-term precipitation and infiltration records were developed for use in the performance evaluation of a proposed regional drainag…