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Legacy oil and gas wells are a significant source of hydrogen sulphide and methane gas release to the atmosphere. Unanticipated occurrences of gas release in urbanized areas can pose human health risks. Several high hydrogen sulphide-emitting wells have been identified in Norfolk County, Ontario, Canada, based on the remote detection of sulphurous water discharging to the surface along the wellbore. Although oil and gas well records report well status and location, community reports of noxious hydrogen sulphide odours suggest potentially compromised well seals and inaccuracies in their documented location. Given the broad-scale nature of this issue and limitations in site access, a remote-sensing based methodology utilizing satellite and high-resolution aerial photography could support identification of undocumented sulphurous water leaks associated with compromised oil and gas wells and subsequent characterization of hydrological and ecohydrological impacts over time. This study presents a multifaceted approach to identifying sulphurous leaking wells utilizing complimentary remote sensing imagery and image analysis tools within ArcGIS. Southwestern Ontario Orthophotography Project air photos and Sentinel-2 satellite imagery were determined to be the most applicable sources of imagery based on their respective advantages in resolution and revisit time. The application of a normalized difference vegetation index showed that major well leaks could exhibit signs of vegetative scarcity, while minor well leaks may have only a limited impact on vegetation. A band combination utilizing the green and near infrared bands was created to enhance the detection of sulphurous water leaks. Utilizing the identified band combination, a pair of potentially undiscovered leaks were located west of a fluvial river channel. Continued research should attempt to employ an automated approach for discerning additional sulphurous water leaks in the region or at different points in time. Possible techniques may involve the deep learning object and change detection models incorporated in ArcGIS.

Expansion of shale gas extraction has fuelled global concern about the potential impact of fugitive methane on groundwater and climate. Although methane leakage from wells is well documented, the consequences on groundwater remain sparsely studied and are thought by some to be minor. Here we present the results of a 72-day methane gas injection experiment into a shallow, flat-lying sand aquifer. In our experiment, although a significant fraction of methane vented to the atmosphere, an equal portion remained in the groundwater. We find that methane migration in the aquifer was governed by subtle grain-scale bedding that impeded buoyant free-phase gas flow and led to episodic releases of free-phase gas. The result was lateral migration of gas beyond that expected by groundwater advection alone. Methane persisted in the groundwater zone despite active growth of methanotrophic bacteria, although much of the methane that vented into the vadose zone was oxidized. Our findings demonstrate that even small-volume releases of methane gas can cause extensive and persistent free phase and solute plumes emanating from leaks that are detectable only by contaminant hydrogeology monitoring at high resolution.

This study exploits the high‐density zonal sampling at the turnaround latitude of the High Resolution Dynamics Limb Sounder (HIRDLS) in the Southern Hemisphere to investigate the missing drag in chemistry‐climate models near 60°S. Gravity wave (GW) properties including amplitude, zonal wavenumber, vertical wavelength, and momentum flux are estimated with a wave analysis method based on the S‐transform. Monthly means of GW properties compare well with estimates from previous studies. We further investigate the contribution to GW momentum flux above orographic and nonorographic regions and find that while fluxes are much larger locally over orographic regions, the contribution to the zonal mean is roughly 3 times smaller than the contribution over nonorographic regions. We also investigate the relationship with the zonal wind and find that GW momentum flux is highly correlated with the near surface winds over orographic regions. In addition to momentum flux, we also provide estimates of the zonal drag and use these estimates to evaluate the current GW parameterizations and resolved wave forcing in models participating in phase 1 of the Chemistry‐Climate Model Initiative (CCMI‐1). The HIRDLS zonal drag estimates suggest that the CCMI‐1 models have insufficient zonal drag, especially in June, July, and August, and that the majority of the missing drag is over nonorographic regions. Our discussion includes implications for the Brewer‐Dobson Circulation and ozone hole. Atmospheric gravity waves are small‐scale perturbations that are generated by, for example, flow over orography or by nonorographic sources like convection. Theses waves affect the general circulation of the atmosphere and accounting for their effects in models is important. Most models are too coarse to fully resolve all scales of atmospheric gravity waves, and they must account for the missing effects of these waves through parameterizations. Gravity wave parameterizations have been developed and they are adjusted to obtain realistic temperatures and winds in models. Ideally parameterizations would be constrained well by observations, but many observational challenges make it difficult. Biases in the circulation and temperature in climate models, especially in the Southern Hemisphere winter, are usually attributed to deficiencies in current gravity parameterizations. In fact, the phenomenon has been called the “missing drag” in chemistry‐climate models (CCMs). In this study we use satellite measurements of temperature from the High Resolution Dynamics Limb Sounder instrument to estimate the effects of gravity waves near 60° South to determine the sources of the missing drag. The analysis suggests that a large part of the missing drag in CCMs is from nonorographic sources. Gravity wave (GW) momentum fluxes near 60°S are much larger locally over orography, but contribution to zonal mean is larger over nonorographic regionsGW momentum flux in winter upper stratosphere is highly correlated with near surface winds over orographic regionsHigh Resolution Dynamics Limb Sounder zonal drag estimates suggest CCMI‐1 models have insufficient zonal drag and majority of missing drag is over nonorographic regions Gravity wave (GW) momentum fluxes near 60°S are much larger locally over orography, but contribution to zonal mean is larger over nonorographic regions GW momentum flux in winter upper stratosphere is highly correlated with near surface winds over orographic regions High Resolution Dynamics Limb Sounder zonal drag estimates suggest CCMI‐1 models have insufficient zonal drag and majority of missing drag is over nonorographic regions

In many hydrological applications, ground‐wave velocity measurements are increasingly used to map and monitor shallow soil water content. In this study, we propose an automated spectral velocity analysis method to determine the direct ground‐wave (DGW) velocity from common midpoint (CMP) or multi‐offset ground‐penetrating radar (GPR) data. The method introduced in this paper is a variation of the well‐known spectral velocity analysis for seismic and GPR reflection events where velocity spectra are computed using different coherency measures along hyperbolas following the normal moveout model. Here, the unnormalized cross‐correlation is computed between waveforms across data gathers that are corrected with a linear moveout equation using a predefined range of velocities. Peaks in the resulting velocity spectra identify linear events in the GPR data gathers like DGW events and allow for estimating the corresponding velocities. In addition to obtaining a DGW velocity measurement, we propose a robust method to estimate the associated velocity uncertainties based on the width of the peak in the calculated velocity spectrum. Our proposed method is tested on synthetic data examples to evaluate the influence of subsurface velocity, surveying geometry and signal frequency on the accuracy of estimated ground‐wave velocities. In addition, we investigate the influence of such velocity uncertainties on subsequent soil water content estimates using an established petrophysical relationship. Furthermore, we apply our approach to analyse field data, which were collected across a test site in Canada to monitor a wide range of seasonal soil moisture variations. A comparison between our spectral velocity estimates and results derived from manually picked ground‐wave arrivals shows good agreement, which illustrates that our spectral velocity analysis is a feasible tool to analyse DGW arrivals in multi‐offset GPR data gathers in an objective and more automated manner.

Bortezomib induces remissions in 30%-50% of patients with relapsed mantle cell lymphoma (MCL). Conversely, more than half of patients' tumors are intrinsically resistant to bortezomib. The molecular mechanism of resistance has not been defined. We generated a model of bortezomib-adapted subclones of the MCL cell lines JEKO and HBL2 that were 40- to 80-fold less sensitive to bortezomib than the parental cells. Acquisition of bortezomib resistance was gradual and reversible. Bortezomib-adapted subclones showed increased proteasome activity and tolerated lower proteasome capacity than the parental lines. Using gene expression profiling, we discovered that bortezomib resistance was associated with plasmacytic differentiation, including up-regulation of IRF4 and CD38 and expression of CD138. In contrast to plasma cells, plasmacytic MCL cells did not increase immunoglobulin secretion. Intrinsically bortezomib-resistant MCL cell lines and primary tumor cells from MCL patients with inferior clinical response to bortezomib also expressed plasmacytic features. Knockdown of IRF4 was toxic for the subset of MCL cells with plasmacytic differentiation, but only slightly sensitized cells to bortezomib. We conclude that plasmacytic differentiation in the absence of an increased secretory load can enable cells to withstand the stress of proteasome inhibition. Expression of CD38 and IRF4 could serve as markers of bortezomib resistance in MCL. This study has been registered at http://clinicaltrials.gov as NCT00131976.

Bortezomib induces remissions in 30%-50% of patients with relapsed mantle cell lymphoma (MCL). Conversely, more than half of patients' tumors are intrinsically resistant to bortezomib. The molecular mechanism of resistance has not been defined. We generated a model of bortezomib-adapted subclones of the MCL cell lines JEKO and HBL2 that were 40- to 80-fold less sensitive to bortezomib than the parental cells. Acquisition of bortezomib resistance was gradual and reversible. Bortezomib-adapted subclones showed increased proteasome activity and tolerated lower proteasome capacity than the parental lines. Using gene expression profiling, we discovered that bortezomib resistance was associated with plasmacytic differentiation, including up-regulation of IRF4 and CD38 and expression of CD138. In contrast to plasma cells, plasmacytic MCL cells did not increase immunoglobulin secretion. Intrinsically bortezomib-resistant MCL cell lines and primary tumor cells from MCL patients with inferior clinical response to bortezomib also expressed plasmacytic features. Knockdown of IRF4 was toxic for the subset of MCL cells with plasmacytic differentiation, but only slightly sensitized cells to bortezomib. We conclude that plasmacytic differentiation in the absence of an increased secretory load can enable cells to withstand the stress of proteasome inhibition. Expression of CD38 and IRF4 could serve as markers of bortezomib resistance in MCL. This study has been registered at http://clinicaltrials.govas NCT00131976.

The article discusses legal issues related to schools and religion. The author discusses how the Constitution of the United States addresses education in schools. The article examines issues such as student prayer, teaching of Evolution, and student freedom of speech. The author argues that student religious speech should be protected as other forms of speech are.

Opinion. Comments that the issue of parental rights in the face of governmental intervention is not new in the United States. Responsibility of parents in raising children; Equality in upbringing of offsprings; Right to intervene in educational programs which are religiously or morally offensive.

An instrument is described which measures the change in thickness of a rectangular crystal to 0.00025 of a millimeter and the change in length to approximately 0.001 of a millimeter. The instrument is designed to be used with a crystal of dimensions of 17.5×6×4 millimeters, the thickness dimension of 4 millimeters being parallel to the X axis and the length dimension being parallel to the Y axis; thus a strain as small as 0.00005 along Y and a strain as small as 0.00006 along X can be detected. The ratio of the compressional strain along Y to the extensional strain along X was found to be approximately unity over a fairly wide range of values for the strain along Y. This result is an approximate experimental verification of Voigt’s theory of the piezoelectric effect in quartz for static conditions. The device is constructed on a standard Michelson interferometer and a microscope of only medium power is necessary.

Surface ground‐penetrating radar (GPR) techniques have been used by a number of previous researchers to characterize soil moisture content in the vadose zone. However, limited temporal sampling and low resolution near the surface in these studies greatly impedes the quantitative analysis of vertical soil moisture distribution and its associated dynamics within the shallow subsurface. To further examine the capacity of surface GPR, we have undertaken an extensive 26 month field study using concurrent high‐frequency (i.e., 900 MHz) reflection profiling and common‐midpoint (CMP) soundings to quantitatively monitor soil moisture distribution and dynamics within the shallow vadose zone. This unprecedented data set allowed us to assess the concurrent use of these techniques over two contrasting annual cycles of soil conditions. Reflection profiles provided high‐resolution traveltime data between four stratigraphic reflection events while cumulative results of the CMP sounding data set produced precise depth estimates for those reflecting interfaces, which were used to convert interval‐traveltime data into soil moisture. The downward propagation of major infiltration episodes associated with seasonal and transient events are well resolved by the GPR data. The use of CMP soundings permitted the determination of direct ground wave velocities, which provided high‐resolution information along the air‐soil interface. This improved resolution enabled better characterization of short‐duration wetting/drying and freezing/thawing processes, and permitted better evaluation of the nature of the coupling between shallow and deep moisture conditions. The nature of transient infiltration pulses, evapotranspiration episodes, and deep drainage patterns observed in the GPR data series were further examined by comparing them with a vertical soil moisture flow simulation based on the variably saturated model, HYDRUS‐1D. Using laboratory‐derived soil hydraulic property information from soil samples and a number of simplifying assumptions about the upper and lower‐boundary condition, we were able to achieve very good agreement between measured and simulated soil moisture profiles without model calibration; this is a strong indication of the overall quality of the GPR‐derived soil moisture estimates. The only notable difference between simulated values and GPR water content estimates occurred during extended dry soil conditions near the surface. Surface‐GPR yields valuable information of soil moisture dynamicsDirect ground waves provide necessary surface resolutionField results support potential inverse parameter estimation with GPR

Direct ground wave (DGW) measurements obtained with ground‐penetrating radar have been used in a number of previous studies to estimate volumetric water content in the shallow soil zone; however, these studies have generally involved controlled field experiments or measurements collected across limited natural ranges of soil moisture conditions. To further investigate the capacity of this method, we have undertaken an extensive field study using multifrequency (i.e., 225, 450, and 900 MHz) DGW measurements to monitor a complete annual cycle of soil water content variations typical of midlatitude climates at three sites with different soil textures. The use of common‐midpoint surveys allowed us to understand the nature and evolution of the near‐surface electromagnetic wavefields and their impact on DGW moisture predictions. We present the novel characterization of a wide‐range of seasonal moisture dynamics including soil freezing and thawing process using multifrequency DGW measurements for a range of soil textures. These data showed significant temporal variations in both the near‐surface wavefield and multifrequency DGW velocities corresponding to both seasonal and shorter‐term variations in soil conditions. Although all of the measurement sites displayed similar temporal responses, the rate and magnitude of these velocity variations corresponded to varying soil water contents, which were controlled by the soil textural properties. Although there were no observed systematic differences in DGW velocities due to frequency dispersion for the 225–900 MHz range, the DGW measurements obtained using higher‐frequency antennas was less impacted by near‐surface wavefield interference due to their shorter signal pulse duration. DGW velocity measurements combined with an appropriate dielectric mixing formula provided quantitative predictions of soil water content that accurately replicated the soil sample data over the annual cycle of moisture conditions.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Abstract 412

Abstract 287

ROR-1, an orphan receptor tyrosine kinase (RTK) carrying an extracellular WNT binding motif, is highly expressed in many tissues during development. Expression of ROR-1 in lymphoid cells has first been noted in a gene expression profiling study of B-cell chronic lymphocytic leukemia (B-CLL), where ROR-1 was expressed in CLL cells but not in diffuse large B-cell lymphoma or in normal B-cells (Rosenwald, 2001). B-CLL is the most common type of leukemia in western countries and is characterized by an accumulation of mature B lymphocytes in the blood and lymphoid tissues. The prolonged survival of the malignant cells in-vivo is dependent on signals derived from the microenvironment. ROR-1 recently has been implicated in mediating stroma dependent survival signals, with WNT5a being a putative ligand for ROR-1 (Fukuda, 2008). In addition, an RNAi screen identified ROR-1 as a tyrosine kinase with anti-apoptotic effects in Hela cells (MacKeigan, 2005). With this background, we have further examined the role of ROR-1 in the survival of B-cell malignancies. We first characterized ROR-1 surface expression by flow cytometry on various lymphoid cell lines and primary cells. We found ROR-1 was highly expressed in mantle cell lymphoma (MCL) cell lines and moderately expressed in the CLL derived EBV positive cell line MEC-1. In contrast, cell lines derived from other B-cell (BJAB, SUDHL-4) and T-cell (Jurkat) malignancies had no ROR-1 expression. Moreover, ROR-1 was highly expressed in primary MCL cells (n= 5) and in follicular lymphoma (n=1). Comparable levels of expression were also detected in CLL cells independent of IgVH mutation status (IgVH unmutated: n=11; IgVH mutated: n= 8). To investigate whether and how ROR-1 could activate intracellular signaling pathways, we chose a monoclonal antibody to induce ROR-1 activation through receptor dimerization. In response to antibody binding, ROR-1 was tyrosine phosphorylated within minutes in a dose dependent manner in MCL cell lines and in primary CLL and MCL cells. Intriguingly, the MCL cell line UPN-1, bearing high ROR-1 surface expression (specific MFI ratio of 19), showed constitutive ROR-1 phosphorylation that further increased after crosslinking. Several studies on ROR-2, the closest ROR-1 homolog, reported activation of the non-canonical WNT signaling pathway and c-Jun N-terminal kinase (JNK) activation. We therefore investigated whether ROR-1 cross-linking could activate JNK and/or lead to stabilization of beta-catenin, the main mediator of canonical WNT signaling. Indeed, we detected JNK phosphorylation in MCL cell lines and in primary CLL cells, while we could not detect beta-catenin activation. In conclusion, ROR-1 surface expression is high in MCL cell lines and primary cells from CLL, MCL and FL patients. ROR-1 crosslinking leads to ROR-1 phosphorylation in both cell lines and primary cells followed by activation of the non-canonical WNT/JNK pathway. Our findings suggest that ROR-1, which plays important roles in embryonic development and organogenesis, could play an important role in the pathogenesis of low grade lymphomas and B-CLL.

ROR-1, an orphan receptor tyrosine kinase (RTK) carrying an extracellular WNT binding motif, is highly expressed in many tissues during development. Expression of ROR-1 in lymphoid cells has first been noted in a gene expression profiling study of B-cell chronic lymphocytic leukemia (B-CLL), where ROR-1 was expressed in CLL cells but not in diffuse large B-cell lymphoma or in normal B-cells (Rosenwald, 2001). B-CLL is the most common type of leukemia in western countries and is characterized by an accumulation of mature B lymphocytes in the blood and lymphoid tissues. The prolonged survival of the malignant cells in-vivois dependent on signals derived from the microenvironment. ROR-1 recently has been implicated in mediating stroma dependent survival signals, with WNT5a being a putative ligand for ROR-1 (Fukuda, 2008). In addition, an RNAi screen identified ROR-1 as a tyrosine kinase with anti-apoptotic effects in Hela cells (MacKeigan, 2005). With this background, we have further examined the role of ROR-1 in the survival of B-cell malignancies. We first characterized ROR-1 surface expression by flow cytometry on various lymphoid cell lines and primary cells. We found ROR-1 was highly expressed in mantle cell lymphoma (MCL) cell lines and moderately expressed in the CLL derived EBV positive cell line MEC-1. In contrast, cell lines derived from other B-cell (BJAB, SUDHL-4) and T-cell (Jurkat) malignancies had no ROR-1 expression. Moreover, ROR-1 was highly expressed in primary MCL cells (n= 5) and in follicular lymphoma (n=1). Comparable levels of expression were also detected in CLL cells independent of IgVH mutation status (IgVH unmutated: n=11; IgVH mutated: n= 8). To investigate whether and how ROR-1 could activate intracellular signaling pathways, we chose a monoclonal antibody to induce ROR-1 activation through receptor dimerization. In response to antibody binding, ROR-1 was tyrosine phosphorylated within minutes in a dose dependent manner in MCL cell lines and in primary CLL and MCL cells. Intriguingly, the MCL cell line UPN-1, bearing high ROR-1 surface expression (specific MFI ratio of 19), showed constitutive ROR-1 phosphorylation that further increased after crosslinking. Several studies on ROR-2, the closest ROR-1 homolog, reported activation of the non-canonical WNT signaling pathway and c-Jun N-terminal kinase (JNK) activation. We therefore investigated whether ROR-1 cross-linking could activate JNK and/or lead to stabilization of beta-catenin, the main mediator of canonical WNT signaling. Indeed, we detected JNK phosphorylation in MCL cell lines and in primary CLL cells, while we could not detect beta-catenin activation. In conclusion, ROR-1 surface expression is high in MCL cell lines and primary cells from CLL, MCL and FL patients. ROR-1 crosslinking leads to ROR-1 phosphorylation in both cell lines and primary cells followed by activation of the non-canonical WNT/JNK pathway. Our findings suggest that ROR-1, which plays important roles in embryonic development and organogenesis, could play an important role in the pathogenesis of low grade lymphomas and B-CLL.

An instrument is described which measures the change in thickness of a rectangular crystal to 0.00025 of a millimeter and the change in length to approximately 0.001 of a millimeter. The instrument is designed to be used with a crystal of dimensions of 17.5×6×4 millimeters, the thickness dimension of 4 millimeters being parallel to the X axis and the length dimension being parallel to the Y axis; thus a strain as small as 0.00005 along Y and a strain as small as 0.00006 along X can be detected. The ratio of the compressional strain along Y to the extensional strain along X was found to be approximately unity over a fairly wide range of values for the strain along Y. This result is an approximate experimental verification of Voigt’s theory of the piezoelectric effect in quartz for static conditions. The device is constructed on a standard Michelson interferometer and a microscope of only medium power is necessary.