I am on ArcGIS Desktop 10.2. I have a line feature class of a stream network. I also have a point feature class along the main stream (line) where a catchment enters that stream. I have dissolved my whole streams layer into one line feature and want to split this feature at the points.
However, when I use the Split Line At Point tool, the lines that don't have a point splitting them are still being split at the intersection of two streams.
Why did this line not stay as one feature with the other lines on that side of the splitting node and how can I prevent this from happening?
Multi-part lines constructed with tools like Dissolve or Merge do not necessarily order the parts that touch at branches in a sequential order that would keep the parts together. So the line parts on the same physical side of a branch can be on opposite sides of the part sequence internal to the line. Parts are always traversed sequentially by tools. This makes sense for such complex multi-part lines, since once it reaches an end point of a part that touches no other line how can it know which line part to put next? It has no idea what branches may split and which won't, of if one part will have to split into two or more parts when points occur inside a line part, so there is no way to do that organization in advance. Anyway, the polyline parts are never organized in advance by "sides" of an infinite set of unknowable points that could split the line up, and the tool makes no attempt to do tracings while the splits are occurring. Therefore all branches break apart with this tool.
To get branches organized into parts you would need to write your own tool. The easiest process I can think of is to do the splits as usual, that way you will be working with the full set of lines, including new segments that split at places other than the branches. Then buffer the split points by a small distance (say a centimeter or one-half foot). Next calculate the ObjectID of the original lines after the split into a new long field and then make a copy of the split lines. Erase the portions of all copied split lines that fall inside of the split point buffers. Now buffer the copied and trimmed lines by an even smaller distance (say 1/2 centimeter or 1/4 foot). Dissolve the line buffers into single part polygons. Next spatial join the trimmed lines to the single-part dissolved buffers keeping the line shapes. This will associate the buffer ObjectID to the line set that falls within it and they will not cross the split points. Now you can select each line set by that buffer FID, relate them back to the original lines that were not trimmed and Merge/Dissolve each set of lines. Python could do the iterations more elegantly than ModelBuilder, so learn Python.
The rule of geoprocessing is always make complex items the last things you work with. Always work with the simplest items (single line parts) first and then add complexity at each stage of your script in an order that each stage is handled efficiently. Also each additional level of complexity should only be introduced into the process when the simpler objects cannot help move the process forward to the ultimate goal.
Network organizations have historically met expanding network requirements by building solid network infrastructures and working reactively to handle individual service issues. When an outage occurred, the organization would build new processes, management capabilities, or infrastructure that to prevent a particular outage from occurring again. However, due to a higher change rate and increasing availability requirements, we now need an improved model to proactively prevent unplanned downtime and quickly repair the network. Many service-provider and enterprise organizations have attempted to better define the level of service required to achieve business goals.
Critical Success Factors
Critical success factors for SLAs are used to define key elements for successfully building obtainable service levels and for maintaining SLAs. To qualify as a critical success factor, a process or process step must improve the quality of the SLA and benefit network availability in general. The critical success factor should also be measurable so the organization can determine how successful it has been relative to the defined procedure.
Performance indicators provide the mechanism by which an organization measures critical success factors. You typically review these on a monthly basis to ensure that service-level definitions or SLAs are working well. The network operations group and the necessary tools groups can perform the following metrics.
Note: For organizations without SLAs, we recommend you perform service-level definitions and service-level reviews in addition to metrics.
Performance indicators include:
Documented service-level definition or SLA that includes availability, performance, reactive service response time, problem resolution goals, and problem escalation.
Monthly networking service-level review meeting to review service-level compliance and implement improvements.
Performance indicator metrics, including availability, performance, service response time by priority, time to resolve by priority, and other measurable SLA parameters.
Service-level Management Process Flow
The high-level process flow for service-level management contains two major groups:
Click on the objects in the following diagram to view the details for that step.
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Reflections: Community Embeddedness
In this reflection, the notion of “community embeddedness” is introduced as a concept that is integral to participatory mapping with refugees. Becoming embedded in the community was a necessary part to conducting my research. I first use my case study to reflect on applying embeddedness I then draw from those reflections to initiate theorizing embeddedness. Next, I describe how embeddedness then gave way to innovation with two other elements—technologies and modalities of communication, and social networks— that are necessary for advancing the research.
Embedding in Community
Applying community embeddedness. In this case study, my ‘embeddedness’ was not sought out rather, community embeddedness was emergent. The engagement started with me working with the Bhutanese community for about a year as an intern for a resettlement agency over a decade ago. My work went beyond casework with the agency and was more along the lines of community practice, as I learned about the community’s organizations that were run by and for refugees. I got to know several leaders and community members through a research project and a refugee leadership training program that I helped to initiate and organize together with the community. Those projects constituted not work, but involvement. I shared many cups of chai with refugee leaders as they talked about and organized the programs, and conversations that ranged from philosophy and Walmart to U.S. politics and Bhutanese exile. I continued to work and engage with the community for the next five years, attending events, consulting with their organizations, and having long walks and conversations with leaders. In these conversations, I exchanged and discussed ideas with leaders, instead of just receiving or gaining ideas. I was not there to become embedded in order to do research one day, I just realized that I felt embedded.
Participatory mapping with refugee communities—a population that is considered hard to reach—came forth and then developed out of discussions and interactions with community members going back five years prior to beginning this study. Over the subsequent five years, it continued to be suggested by various people in different cities and states, confirming relevance as well as scale. Furthermore, when it came time to recruit participants, most of those who were approached agreed because the issue resonated with them.
My embeddedness with communities was a primary element that emerged as important. This embeddedness helped determine not only the feasibility of project implementation, but it also opened up possibilities that may not otherwise have been available.
Theorizing community embeddedness. Embeddedness was central to the research process, not only procedurally, to connect with communities in order to implement the study, but also substantively, to inform research questions and gain a sense of what was possible. Embeddedness in a research context pertains to epistemology, or ways of knowing ( Kesby, 2000 ). When applied to community research, embeddedness can be defined as similar to community engagement, but more holistic and more ethnographic. When researchers embed themselves in communities, their relationships with community members and leaders are deeper and longer-lasting, and the researchers’ knowledge of the community is historical and systems-based rather than issue-specific.
Because the issues that refugees face are dynamic, complex, and often not well understood, it is necessary to get the research questions right. Embedding oneself as a researcher with the community is thus a critical early phase for initiating research issues. Communities, including those of refugees, become invested in research only to the extent that the research questions and aims are in line with their community priorities and needs. Trust and meaningful engagement with the community are key in this type of community-based, participatory, and action-oriented research, and these elements take on added salience with refugee communities who are often vulnerable, marginalized, and unfamiliar with research processes. Therefore, these trust-based meaning-centered relationships need to be established at the outset of the research, when the topics of focus are first being identified.
Furthermore, as detailed above through my case study, researchers may gain a different set of procedural options or possibilities for research from being embedded with and knowing the community. The feasibility of data collection methods and recruitment for research that is top-down or researcher-driven is typically assessed by talking with community members. However, as illustrated in my case study, it is embeddedness that can allow for meaningful, generative research questions and innovative research designs to be formulated in the first place and then take shape.
Considering Technology and Modalities of Communications
Embeddedness then led to knowing about technology and modalities of communication in data collection and the research processes. For this project, Facebook Messenger and texting were the primary technologies used to communicate and collect data. In the early stages, email was used to communicate with leaders more formally, but I oftentimes did not receive replies. I then tried Facebook Messenger and texting, and those media garnered responses more often and more quickly than emails. Participating in research requires time and effort from community members, and using tools and media that they already use daily makes participation easier.
Establishing Social Networks
A third element pertains to establishing social networks. Community mapping with refugees simply entails knowing the right people, and this happens only with embeddedness within the community. As researcher, I had done years of work with Bhutanese community leaders, starting with the very first cohorts in 2009. My long-established relationship with a very well-respected community leader translated into not only credibility for the research project but credibility for me personally as a researcher. Social network was crucial: starting with the first informant, state by state and city by city, every community contact was strengthened with each informant who participated.
Thin Film Growth
Lattice Structure Characterization
High-resolution XRD measurements were performed using a Rigaku Smartlab and a PANalytical X'Pert XRD. Atomic-scale imaging of SLs was performed on a spherical aberration-corrected scanning transmission electron microscope (STEM ARM200CF, JEOL) operating at 200 kV. To detect the β-dependency of octahedral distortions in SRO layers, the annular bright-field (ABF) imaging mode was employed along with the high-angle annular dark-field (HAADF) imaging mode. The incident electron probe angle was set to 23 mrad, giving rise to a probe size of 0.78 Å. The ABF and HAADF signals were simultaneously collected over detector angle ranges of 7.5–17 and 70–175 mrad, respectively. Cross-sectional thin samples for STEM analysis were prepared using a dual-beam focused ion beam system (FIB, FEI Helios Nano Lab 450) subsequently, low-energy Ar ion milling at 700 V (Fischione Model 1040, Nanomill) was carried out for 15 min to remove surface layers damaged owing to heavy Ga ion beam milling in the FIB system.
Temperature-(M(T)) and magnetic field-dependent magnetization (M(H)) were measured using a Magnetic Property Measurement System (MPMS, Quantum Design). The measurements were performed at a range of 300–2 K under 100 Oe of the magnetic field along the out-of-plane direction of the thin films. M(H) curves were obtained at 5 K with a magnetic field along the out-of-plane direction.
Ru L3-edge XAS was performed at the 16A1 beamline of the Taiwan Light Source in the fluorescence yield mode at room temperature, whereas Ti L2,3-edge XAS was performed in the 2A beamline of the Pohang Light Source in the total electron yield mode at room temperature. The probing depth of Ru L-edge XAS was approximately a micron, far exceeding the total thickness of the SLs, whereas that corresponding to Ti L-edge XAS was in the order of 10 nm. To obtain the polarization-dependent data, the samples were either set in a beam-normal geometry (Ix,y) or rotated by 70° [(cos 2 70° × Ix,y) + (sin 2 70° × Iz)].
XLD Simulation and Peak Assignment
To enable a clear peak assignment, we simulated the XLD spectrum for a hypothetical orthorhombic SRO model using a charge transfer multiplets calculation code, CTM4XAS. [ 48 ] In the model, the atomic multiplets of d 4 many-body states under crystal fields of D4h point symmetry were considered in the scheme of configuration interactions with charge transferred states. All the values of the parameters (for instance, crystal field splitting energies, 10Dq, Ds, and Dt, the transfer matrix, and the charge transfer energy) were adopted from reference, [ 49 ] except for the values of the Slater integrals, which were reduced to ≈50% of the atomic values to account for the itinerant nature of the d electrons in SRO. In the ground state (d 4 S = 1), the first unoccupied orbital state was dxz,yz. Thus, the lowest energy feature in the XLD spectrum for orthorhombic SRO should appear as a dip for dxz,yz. A peak for dxy, a dip for dz2, and a peak for dx2-y2 should follow in the order of increasing energy. Meanwhile, in the case of tetragonal SRO, the first dip for dxz,yz (≈2838.5 eV) apparently disappeared, and the peak for dxy (≈2839.5 eV) increased in intensity because of the slight increase (decrease) in the number of electrons at the dxz,yz (dxy) orbital, which is consistent with the scheme shown in Figure 4a.
The first-principles DFT calculations were performed using generalized gradient approximation (GGA) [ 50 ] and the projector-augmented wave method with a plane-wave basis, [ 51 ] as implemented in the Vienna ab-initio simulation package (VASP) code. [ 52 ] For the Brillouin-zone integration, we used a kinetic energy cutoff of 500 eV and Γ-centered 8 × 8 × 8 k-point meshes. For the DOS calculations, we considered orthorhombic Pbnm (Glazer notation, a − a − c + ), and tetragonal P4/mmm (a 0 a 0 c 0 ) structures composed of 20 atoms, and their in-plane lattice parameter was fixed to be 2 a STO . To consider on-site Coulomb interactions, a Hubbard U of 1.6 eV was applied to the Ru-d orbital for all calculations. [ 53 ] The calculations were converged in energy to 10 −6 eV cell −1 , and the structures were allowed to fully relax until the forces reduced below 10 −3 eV Å −1 .
According to Collins and Lacroix (1997), the QTC VIEW seabed classification system is primarily influenced by bottom roughness and the density difference between the sediment surface and the overlying water. Collins and Galloway (1998), working in an area of the inner harbour of Vancouver, Canada, showed that the acoustic diversity measured by the QTC VIEW system successfully captured a high variety of seabed types, based on sediment grain size and the presence/absence of shell debris. Hamilton
How Trailer Maintenance Works
That trailer of yours has definitely seen better days. Look at it over there are those weeds growing around its tires? Wait, is it missing a tire? Face it, buddy: Your trailer is falling apart.
You loved it once. You got it as a present for your birthday years back, and you thought it was the shiniest, coolest, most practical thing you'd ever seen. Now, it sits like a depressed, neglected hulk in the driveway. You and your trailer need to spend some quality time together again.
Sure, you could take it to a specialist. There are plenty of business owners making a good living by maintaining other people's trailers. But what better way to pass a pleasant afternoon than getting your trailer back up to snuff? It's going to take a little bit of elbow grease and some time, but with our advice you'll have your trailer back into road-ready condition.
In this article, we'll look at ways to keep your trailer maintained. You'll learn about what to use when washing it. We'll teach you what parts to keep lubricated and how to do it. We'll also cover maintaining the tires and inspecting the lighting system. In no time, you'll be able to get your trailer back in shape. Read the next page to get started.
For starters, we'll give that old trailer a nice washing. It's a good idea to keep your trailer clean, especially if you have an enclosed trailer. Often, these trailers are given an auto finish with several coats of paint and sealant. As such, you should wash these trailers with warm water, using soap that's specially formulated to take it easy on auto finishes. If you don't have a trailer with an automotive-grade finish, soapy fresh water will suffice. Use a regular hose to rinse off high-powered pressure washers can damage the finish and degrade the trailer body. Be sure to spend time cleaning the reflective plates and lights to let them shine. Don't forget to rinse off the undercarriage, as road dust can accumulate and degrade moving parts.
If you have a boat trailer, you must wash it after every use, especially if you use it around salt water. Salt water can accelerate corrosion, so be sure to pay extra attention to the wheels, suspension and brakes. Salt water can collect on these parts and evaporate, leaving a salt residue that can wreak havoc on metal.
Look for rusted parts and areas as you wash. Sand away any patches you find with sandpaper or steel wool. After you've finished washing and the trailer has dried, touch up the areas with rust-proof paint. Once the paint dries, apply a healthy coat of wax on your trailer's painted metal parts. You should do this even if your trailer didn't require any touching-up. Keeping your trailer waxed sounds a bit over the top for all but the nicest models, but it protects metal parts from the elements and prevents rusting.
As you're washing, you may realize you're facing a challenge: Trailers can be awfully tall. Not to worry, there are plenty of tools on the market to help you get every square inch of that trailer clean. Telescoping wash brushes and chamois can make your life a lot easier. Of course, there's also something to be said for a sturdy, non-slip step ladder with good tread on each step.
The old trailer looks nice and shiny now, doesn't she? Unfortunately, it's time now to get down and dirty. Read the next page to learn about keeping your trailer properly greased and lubricated.
Keeping Trailer Parts Greased
Dirt is your trailer's biggest enemy. Once particles of dirt and dust get into your trailer's moving parts, it can cause friction and break down. Keeping your trailer's parts greased can help keep joints and axels moving smoothly. Before you take it back onto the road, do a little greasing first.
Pretty much any part of your trailer that's designed to move in some form or fashion or comes in contact with other parts should be kept lubricated to prevent corrosion and friction. Features like a winch, ball hitch, springs and tongue jack all require lubrication and you should keep them greased throughout the year. It's a good idea to make lubricating your trailer's moving parts an important part of your routine before each long trip.
It's important to keep all moving parts lubricated. One of the most important parts are the wheel bearings, the cylindrical rings that connect the wheel to the axle and allow for the wheel's free rotation. Since the wheels are extremely important to your trailer's ability to function well, it's important to maintain your wheel bearings. And since the wheel bearings and axles are a metal-on-metal combination, it's important to keep them well greased to prevent friction and potential wheel damage.
The wheel bearings are packed with inner bearings that allow the wheel bearings to move as a whole. Part of any trailer maintenance should include cleaning and greasing the wheel bearings for each wheel. We've included an in-depth guide to properly cleaning your wheel bearings on the Lots More Information page, but here's a quick run down of what you can expect. It may sound like a pain, but, again, it's extremely important to maintain your wheel bearings.
You'll first have to remove your tire and any hardware holding your wheel in place on your axle. You'll find your wheel bearing on the wheel hub, and it should be easily removed after removing the hardware holding it in place. You'll want to soak the wheel bearing in gasoline to loosen grime and old grease. Remove the old seal, then the inner bearing. Thoroughly clean the inner bearing and the wheel bearing as a whole.
After the parts are completely dry, replace the inner bearing and seal the wheel bearing. Gently add grease to prevent breaking the seal, and wipe off any excess grease. Now's also a good time to grease the axle. After you reinstall the wheel bearings and the wheel, move on to the next one.
Since the function your trailer performs is based largely on its tires, it's a good idea to keep your trailer tires well maintained. In many cases, especially with large trailers, the added weight the tires support even when stationary can cause trailer tires to wear out significantly faster than the tires on your coach vehicle.
If your trailer's been sitting around unused for a while, it's a good bet the tires could use inflating. Using your trailer often can obviously lead to loss of air pressure, but tires also lose pressure when not in use. All tires leak air over time, and so keeping an eye on your air pressure is essential to keeping your trailer properly maintained.
The reason for maintaining proper air pressure in your tires is simple: Taking a trailer fully loaded out on the open road with under inflated tires is extremely dangerous. The friction created when the rubber meets the road can cause degradation of your tires. This situation can lead to a blow out, which is the last thing you want to happen to a trailer hitched to your car and traveling at high speeds. Even if a blow out doesn't occur, improperly inflated tires flatten under the strain of an overly heavy load. This can create another dangerous situation, one where swaying of the trailer can occur.
Before inflating your tires, check the manufacturer's suggested pounds per square inch (psi) of inflation. It should be listed in the owner's manual for your trailer. You should also note if your trailer's tires call for a high psi when carrying heavy loads. If so, be sure to observe this when you inflate your trailer tires.
Before every trip, check your trailer tires for wear. It's recommended that you replace your trailer tires every three to five years. When replacing tires, make sure the ones you purchase match the ones you already have, if you're not buying a complete set. It's a good idea to shell out the extra cash to replace all of your trailer tires at once, as even good tires are worn to some extent and the addition of a new, unworn tire can lead to handling difficulty when towing. Some manufacturers make tires that are specially designed for trailers. Bias ply tires are stiffer than the radial tires found on most cars and trucks. This stiffness helps to protect against sway, since the tires don't give from side to side as much as more pliable auto tires can. When you store your trailer, drape tarps over them to protect against sun damage, which can cause cracking and splitting.
Okay, you've gone ahead and spent the money to replace your trailer's tires. You've got them properly inflated and you're good to go. Your trailer's almost back to mint condition. Read the next page about checking your trailer's light systems.
Spatial reasoning about multimedia document for a profile based adaptation
The continuous evolution of smart devices has led to serious limitations in multimedia applications. The multimedia graphic design and animation and the increased use of rich and complex multimedia content on the web or other media have all created a need to diversify the accessibility of the content. Therefore several techniques are used today to design a universally accessible content. The main techniques that are still used to maintain accessibility is to create two parallel streams of design and development of the same content. Thus, the continuous evolution will certainly lead to create other streams. For this, the automatic reasoning on multimedia to allow a computer to modify the design according to different variables, devices capabilities, user status and context to provide personalized adapted content. In this paper, we propose an abstract document model called XMS short for XML Multimedia Specification it describes the composition of an original multimedia document and can be extended to any document type. We present how we may use spatial information present in this document to adapt and modify the original document. We mainly focus on the spatial aspect of a web document, a combination of RCC8, qualitative distances, and directions are used to describe the layout of a set of objects. The level of granularity of the definition of the objects defines the level of details that will be processed by our PROLOG based inference system, simplified versions of algorithms from the inference system and how it works on the spatial dimension of the document are shown. In the end samples of how spatial relations manipulation algorithms work are illustrated.
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Assay validation and HTS parameters
In the present study, we first used various concentrations of androgen receptor protein preparation in the HA androgen receptor-binding assay and the optimal protein concentration was determined as 60 mg L 𢄡 (1:30 of the stock solution), which allowed the assay to possess a specific binding window of 2000𠂜.p.m. ( Figure 2a ). Under the above optimized assay condition, the IC50 value for the natural androgen receptor ligand, DHT, was measured to be approximately 4 n M ( Figure 2b ). When maximal binding (MB DMSO) and nonspecific binding (1 μ M DHT) were assessed, the assay displayed a signal-to-background ratio of 5. Coefficient of variation (CV) values were 5.4% for MB and 7.9% for nonspecific binding, respectively. The Z′ factor, which estimates the suitability to HTS, was calculated to be 0.75 ( Figure 2c ).
High-throughput screening assay validation. (a) Specific-binding (CPMMB𢄬PMNSB) of dihydrotestosterone (DHT) with different amounts of androgen receptor. Serial titration of androgen receptor protein was made to determine the optimal protein concentration. (b) Androgen receptor-binding characteristics of DHT measured by the hydroxyapatite (HA) assay with optimal assay conditions, from which IC50 value was calculated (n=3, mean±s.e.mean). (c) Z′ factor determination. Assays were performed at the optimized conditions and 56 replicates of specific and background signals were studied. Lines indicate means and meansଓ × s.d. of the 56 data points.
Of the 16 samples initially screened, 130 ‘hits' (0.81%) showed greater than 85% competitive inhibition on DHT binding to androgen receptor (AR). Secondary (single compound per well) screening confirmed that 14 of the above ‘hits' displayed consistent inhibitory effects with IC50 values between 150 and 3000 n M ( Table 1 ). Of these, compound SH00000725 ( Figure 1a 4) was chosen for further chemistry development due to its consistent AR antagonist activities in the CV-1 cell assay.
The androgen receptor binding IC50 values of the confirmed ‘hits'
|Compound||IC50 (n M )||Compound||IC50 (n M )|
Forty-nine analogues were designed and synthesized based on the core structure of the initial hit SH00000725 (4). Screening results of these compounds are illustrated in Table 2 showing androgen receptor-binding affinities (IC50 values) and their agonist effects in transfected CV-1 and MDA-MB-453 cells. Nine analogues demonstrated better binding potencies than dihydrotestosterone. Clearly, the best results so far are indicated for R 1 =haloaromatic, R 2 =phenyl or one of its isosteres and between R 3 and R 4 , and R 3 substitution with an electronegative group (NO2 for example). In addition, as seen in Table 2 , CNOH substitutes for the keto moiety did not significantly alter activities. Among the compounds in Table 2 , a number of them were selected for further biological evaluation based on the general criteria described below.
Structuretivity relationship at the substitutions of R 1 , R 2 , R 3 and R 4
Transcriptional activities on AR
Thirty analogues of compound 4 shown in Table 2 possessed androgen receptor-binding activity (IC50) of less than 200 n M and/or weak or no agonist activity (efficacy 㱀%) in CV-1 or MDA-MB-453 cell assays. This suggested that they may be acting as antagonists. All of them, including compounds that displayed special structural interest such as the enantiomeric pair 22 and 23 and the diastereomeric pair 11 and 12, were subsequently tested in the antagonist mode with both cell lines and the results are presented in Table 3 . DHT was used as the standard steroidal androgen receptor agonist and Casodex as a standard non-steroidal androgen receptor antagonist. Some of these compounds, while exhibiting weak agonist effects, demonstrated reasonable antagonistic effects indicating that subtle changes in the structure could switch between agonist and antagonist activities. For example, changing the R 3 group in compound 7 from NO2 to CN in compound 8 resulted in the total loss of agonist activity in CV-1 cells. For compounds such as 13, 23, 24, 28, 45 and 46, there was considerable variation in their agonist activities between these two cell lines ( Table 2 ), but some (compounds 13, 23 and 24) displayed noticeable antagonist activities in MDA-MB-453 cells. Of the 30 analogues, eight showed comparable potency to that of benchmark, Casodex. Among these, compound 21 was chosen for further characterization due to its weak agonist (12% efficacy) and moderate antagonist activities (82% inhibition) in MDA-MB-453 cells. As this class of analogues can exist as enantiomers, compound 21 was separated into its D and L isomers and evaluated independently. Nearly all the androgen receptor-modulating activity and binding resided in the dextrorotatory compound (23) whereas the laevorotatory isomer (22) possessed weak or little effect depending on the cell type studied ( Figures 3a and b Tables 2 and and3 3 ).
Different bioactivities of compound 21 and its enantiomers. (a) CV-1 cells co-transfected with androgen receptor (pSVAR0) and a luciferase reporter gene plasmid (MMTV-Luc) were treated with various concentrations of dihydrotestosterone (DHT), compounds 22 or 23 in the agonist mode. (b) Experiment was performed as above in the antagonist mode, except that DHT (2 n M ) was added 30 min after the addition of compound 22 or Casodex. (c) LNCaP cells were seeded onto 96-well plates and incubated overnight. Different concentrations of DHT and test compounds (10 μ M ) were added to the cells and incubated for 6 days. Data (mean±s.e.mean) are representative of three independent experiments.
Antagonist activities of compounds in CV-1 co-transfection and MDA-MB-453 reporter assays
|Antagonist activity in CV-1 a||Antagonist activity in MDA-453 b|
|Compound||IC50 (n M )||Max. inhibit. (%)||IC50 (n M )||Max. inhibit. (%)|
Inhibition of androgen receptor-mediated cell proliferation
SC3 cell is a mouse mammary cell line that responds well to androgens with increased growth (Minesita and Yamaguchi, 1965). PC3 cell is a human prostate cancer cell line that lacks measurable androgen receptors and can serve as a control for specificity and potential cytotoxicity (Venkateswaran et al., 2002). Table 4 demonstrates that compounds 21 and 26 behaved as androgen receptor antagonists with full efficacy in SC3 cells whereas their effects on PC3 cell proliferation were very weak with greatly reduced efficacy, indicating little or no toxicity. Compound 26 was selected in this assay as, although structurally similar to all the analogues, it lacked biological activity in transfection assays and could serve as a general cytotoxicity control. Figure 3c depicts the effects of compound 21 and Casodex on androgen-induced proliferation in LNCaP cells. Like DHT, compound 21 significantly increased proliferation of these cells but to a lesser extent (data not shown). In the presence of varying concentrations of DHT, compound 21, like Casodex, was able to markedly block the effect of DHT (Pπ.05 or 0.01) indicating that it is acting as a partial AR antagonist in this assay. The effect of compound 21 on the expression of prostate-specific antigen in LNCaP cells was also investigated: the compound induced prostate-specific antigen expression when DHT was absent but it significantly reduced prostate-specific antigen levels in the presence of DHT (Supplementary information 2).
Bioactivities in SC3 and PC3 cell proliferation assays
|SC3 antagonist mode a||PC3 cytotoxicity b|
|Compound||IC50 (μ M )||Inhibition (%)||IC50 (μ M )||Inhibition (%)|
Crossreactivity with other nuclear receptors
The crossreactivity of compound 21 with related nuclear receptors was assessed using human progesterone, oestrogen, glucocorticoid and mineralocorticoid receptor-binding and co-transfection assays. Although weak crossreactivity was detected with progesterone (180.4 n M ) and glucocorticoid (531.7 n M ) receptor-binding assays, at concentrations up to 10 μ M , no agonist or antagonist activity was observed for compound 21 except against androgen receptors in the CV-1 co-transfection assays. This result suggests that 3-(phenylamino)-propan-1-one analogues were highly selective for androgen receptors and were at least to 86-fold more potent on androgen receptors than any other nuclear receptor in receptor-binding assays.
Suppression of androgen actions in vivo
Compound 21 was subsequently tested in castrated immature male rats for its ability to inhibit prostate, seminal vesicles and levator ani growth induced by exogenous testosterone. In the castrated control group, there was a significant drop in dry weights of all test tissues compared to the sham group. In the presence of exogenous testosterone, there was a marked increase in the weight of these three tissues as would be expected. Casodex (25 mg kg 𢄡 ) inhibited this return towards normality as did the two doses (100 and 200 mg kg 𢄡 ) of compound 21. However, the compound was not as potent as Casodex ( Figure 4 ). In contrast, compound 26, which possesses neither AR agonist nor antagonist properties in CV-1 and MDA-MB-453 cells, was inactive in this model (data not shown).
Effects of compound 21 on ventral prostate, seminal vesicles and levator muscle (dry weight) in castrated immature rats. Three-week-old male Spraguewley rats were castrated and allowed to recover for 6 weeks. Rats were randomly divided into six groups (n𪟨 per group): sham-operated group received vehicle alone (Sham) castrated group received vehicle alone (Ctrl) castrated animals received s.c. testosterone alone (T) castrated animals received s.c. testosterone and an oral dose of Casodex (T⯊sodex) castrated animals received s.c. testosterone and i.p. compound 21 (100 or 200 mg T⬡). The dry weights (corrected for the body weight of each individual animal) of prostate, seminal vesicles and levator ani were recorded following 10 days of treatment. * Pπ.05 and ** Pπ.01 compared to testosterone-treated group (T). Data shown are mean±s.e.mean.
You can do this as follows on SQL Server 2008 or greater:
You can also do the less verbose:
Whatever you do, do not use - to subtract dates, because the operation is not atomic, and you will on occasion get indeterminate results due to race conditions between the system datetime and the local datetime being checked at different times (i.e., non-atomically).
Please note that this answer does not take DST into account. If you want to include a DST adjustment, please also see the following SO question:
I didn't find any of these example helpful in getting a datetime stored as UTC to a datetime in a specified timezone (NOT the timezone of the server because Azure SQL databases run as UTC). This is how I handled it. It's not elegant but it's simple and gives you the right answer without maintaining other tables:
If your local date time is say Eastern Standard Time and you want to convert from UTC to that, then in Azure SQL and SQL Server 2016 and above, you can do:
The full list of timezone names can be found with:
And yes, the timezones are badly named - even though it is Eastern Standard Time , daylight savings is taken into account.
If you need a conversion other than your server's location, here is a function that allows you to pass a standard offset and accounts for US Daylight Savings Times:
Using new SQL Server 2016 opportunities:
But clr procedure works in 5 times faster :'-(
Pay attention that Offset for one TimeZone can change to winter or summer time. For example
You can't just add constant offset.
If enabling CLR on your database is an option as well as using the sql server's timezone, it can be written in .Net quite easily.
A UTC datetime value goes in and the local datetime value relative to the server comes out. Null values return null.
There is no simple way to do this in a correct AND generic way.
First of all it must be understood that the offset depends on the date in question, the Time Zone AND DST. GetDate()-GetUTCDate only gives you the offset today at the server's TZ, which is not relevant.
I have seen only two working solution and I have search a lot.
1) A custom SQL function with a a couple of tables of base data such as Time Zones and DST rules per TZ. Working but not very elegant. I can't post it since I don't own the code.