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DBIA Updates BIM Resource | Facility Executive - Creating Intelligent Buildings
This new resource details how design-build teams can make the greatest use of a technology that is transforming the A/E/C industry.
DBIA Updates BIM Resource
The Design-Build Institute of America (DBIA) has released the latest revision to the Design-Build Manual of Practice, "BIM and Design-Build Project Delivery." Developed by DBIA's BIM Committee, a group of practitioners representing the full spectrum of design and construction disciplines, the chapter details how design-build teams can make the greatest use of a technology that is transforming the A/E/C industry.
At its core, BIM is a visualization tool, a detailed database, and a communication aid to enhance collaboration of the project team. These attributes have particular significance for design-build projects, because they augment and support a project delivery method that is already fundamentally collaborative. Because design-build is an integrated approach that delivers design and construction services under one contract with a single point of responsibility, design-build team members, as well as owners, are able to leverage BIM capabilities more completely and throughout the entire design and construction process.
This new resource illustrates how BIM can be used to add value to a project from very beginning. As early as the pre-proposal phase, owners can take advantage of BIM as a cost-effective means of visualizing what they want to build. There are many dimensions and uses of BIM that can further the design-build process, including integral cost comparison, energy analysis, and even 4D scheduling.
A first step in applying BIM to the virtual design and construction (VDC) of a design-build project is for the team to define the project's BIM objectives and deliverables. In addition to project examples, "BIM and Design-Build Project Delivery" also includes a BIM Checklist and Guide for Design-Build that can be used by both owners and design-build team members as they make virtual design and construction a reality on their next project.
The DBIA Design-Build Manual of Practice (MOP) contains basic definitions, narrative instructions, procedural guidance, sample formats, and best practices recommendations as well as risk management guidelines, licensure data, and regulatory and legal information. As the only organization that defines, teaches, and promotes best practices in design-build, DBIA is committed to keeping the MOP a relevant and up-to-date handbook of design-build project delivery. DBIA provides the MOP free of charge to members.
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My husband and I started snowboarding in the winter of 2010 and fell in love with peek n peak. It is a great place to learn without being intimidated. The s...
I think when you're talking about PKNPK, you've got think in relative terms, meaning yeah, it's not the biggest place on earth, but for the area that it's i...
This place rocks! The skiing is awesome and not far from Ohio, the grooming rocks corduroy all the way. Plenty of trail and slopes. I had a great spill and ...
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text: Columbus by SNOWMINE published on 2013-10-21T19:39:53Z PRE-ORDER DIALECTS NOW AT: WWW.SNOWMINE.COM Single from upcoming full length "Dialects" "Dialects" release: 2.4.14 Mixed and Engineered by Jake Aron and Yale Yng Wong Mastered by Chris Gehringer Lyrics: Late last night I lost track of time And I know I was waiting for the sun to rise These summer days they keep stretching on As our friends in and out of town and tide. We spent our nights Hoping for nice things. We should have known we don't need nice things What's that don't know your way back home You wanna know why? All this time when you read my mind You read my mind All those thoughts that I knew you'd find I hid between the lines. We could dress for anywhere else It's been a long, long time since your kingdom fell. And I can hear something over these engines It sounds like us in the backseat of your car Sounds like our mysteries in skin Just to steal away again. All this time when you read my mind You read my mind All those thoughts that I knew you'd find I hid between the lines. All this time when you read my mind You read my mind Those countries where we could have been I left them all behind. Why would you bother the hurt your among? When all that you needed was here all along? All this time when you read my mind You read my mind All those thoughts that I knew you'd find I hid between the lines. All this time when you read my mind You read my mind Those countries where we could have been We left them all behind. Genre Indie Comment by anett.m. neat☆ 2016/05/15 15:11:45 +0000 Comment by foxx_16 *scReam* 2016/04/29 03:08:55 +0000 Comment by Bdog Music @ayydy: hell yeah 2016/04/04 18:12:21 +0000 Comment by MARY amazing!!! 2016/04/01 16:06:09 +0000 Comment by Ayydy Best song in existence 2016/03/12 17:52:22 +0000 Comment by Dmita34 Boom! 2015/12/09 17:37:08 +0000 Comment by Mustardmind this is luscious. 2015/11/05 04:04:06 +0000 Comment by Muhd Faizel i like the intro.. 2015/03/10 10:21:45 +0000 Comment by Rahma Darries Interesting and really awesome too :D 2014/11/02 07:22:08 +0000 Comment by A.krisztin very good work. 2014/10/05 09:21:25 +0000 Comment by Vrolly spettacolare 2014/07/02 10:39:09 +0000 Comment by dripw slay queen 2014/07/02 08:25:18 +0000 Comment by Stories High When you want to favourite a song you have already favourited. 2014/07/01 13:07:40 +0000 Comment by Stories High Another beautiful track. 2014/06/20 11:27:25 +0000 Comment by The Cinematic Shuffle Cool song guys, loving your style and vibe. My 6 year old is loving it as well... 2014/06/16 18:52:18 +0000 Comment by Kurt Adams I fucking love the chorus 2014/06/15 23:02:29 +0000 Comment by AwakeFM such a nice sound 2014/06/14 15:50:00 +0000 Comment by AcidHawk Kind of unsettling fir me in the beginning 2014/06/07 01:58:27 +0000 Comment by Gabriel Coelho 31 orgasmos 2014/05/27 17:41:30 +0000 Comment by HolyMoly33 Taking a train to India. 2014/05/26 15:47:57 +0000 Comment by Patrick Egdorf Where can I buy this song or your CDs? I love this... 2014/05/24 21:44:15 +0000 Comment by Royal Hayze Productions this song takes me to the best place in the world 2014/05/24 07:31:04 +0000 Comment by pauline_hrd love !! 2014/05/23 19:45:19 +0000 Comment by Amel Dabboussi Vibrant song ! 2014/05/17 21:29:01 +0000 Comment by JOHNNY WHAT fave 2014/05/16 22:26:13 +0000 Comment by user391358233 completely in love 2014/05/12 04:54:44 +0000 Comment by Sylvie Munoz yes!!!!!!!!!!!!!!!!!!! 2014/05/01 15:21:20 +0000 Comment by Marianna Giannini magica 2014/04/29 11:17:58 +0000 Comment by MICHELE MAFFEI So fresh, really great 2014/04/18 20:52:32 +0000 Comment by Fineanddandy1 lovely voice! 2014/04/14 21:46:07 +0000


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Barska 20-60x60mm Spotter SV Spotting Scope with Soft-Sided Case
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Nanoparticles are an essential component in the emerging field of nanomedical imaging and therapy. When deployed in vivo, these materials are typically protected from the immune system by polyethylene glycol (PEG). A wide variety of strategies to coat and characterize nanoparticles with PEG has established important trends on PEG size, shape, density, loading level, molecular weight, charge and purification. Strategies to incorporate targeting ligands are also prevalent. This article presents a background to investigators new to stealth nanoparticles, and suggests some key considerations needed prior to designing a nanoparticle PEGylation protocol and characterizing the performance features of the product.
Nanoparticles (NPs) are synthetic materials with dimensions from one to hundreds of nanometers, and remarkable applications in biomedicine due to the unique way in which they interact with matter [1,2]. There are currently more than 35 US FDA-approved NPs often incorporating polyethylene glycol (PEG), with a larger number in preclinical studies for both imaging and therapy (Figure 1A) [1,3–9]. NPs have large payloads, stability, avidity, signal enhancement and the capacity for multiple, simultaneous applications owing to their unique size and high surface area:volume ratio [10]. While they are bigger than molecules and many proteins, yet smaller than cells, they behave differently to other therapies and imaging agents, affecting their in vivo applications. For example, in cancer tissue, NPs not only extravasate from the leaky tumor vasculature to a higher degree than healthy tissue, but also remain in the area by the enhanced permeability and retention (EPR) effect [11]. NPs lodged in the tumor can then perform signaling and/or therapy [10].
Despite these advantages, some fundamental challenges hamper NP deployment to the clinic. These include uptake by the reticuloendothelial system (RES), in which NPs are rapidly shuttled out of circulation to the liver, spleen or bone marrow, and nonspecific binding of NPs to nontargeted or nondiseased areas. Concerns about NP toxicity often arise because of this RES accumulation. Aggregation can lead to NP entrapment in the liver, lungs or elsewhere due to capillary occlusion [12].
The addition of PEG to the NP surface (PEGylation) can reduce many of these challenges (Figure 1B). PEG is a coiled polymer of repeating ethylene ether units with dynamic conformations (Figure 1C). In both drug-delivery and imaging applications, the addition of PEG to NPs reduces RES uptake and increases circulation time versus uncoated counterparts [13]. Aggregation decreases owing to passivated surfaces, and association with nontargeted serum and tissue proteins is diminished, resulting in so-called `stealth' behavior. The PEG chains reduce the charge-based contact typical of proteins and small-molecule interactions. Solubility in buffer and serum increases due to the hydrophilic ethylene glycol repeats and the EPR effect is modulated due to NP size changes via addition of a PEG coat [14,15]. Due to these attributes, PEGylated NPs generally accumulate in the liver a half to a third of the amount of non-PEGylated NPs and demonstrate higher tumor accumulation versus background [16]. PEG is inexpensive, versatile and FDA approved for many applications [12].
This article summarizes PEG utilization in NP systems. Rather than a comprehensive review, it is an introduction to the many factors that need consideration in a PEGylation protocol. Emphasis will be given to the selection of proper PEG type, methods to quantify the amount of PEG per NP, and the effect these variables have on in vivo behavior. Attention is given to NPs deployed for imaging and drug-delivery applications. Excellent reviews on protein and peptide PEGylation exist in the literature [17].
All NPs contain at least two fundamental spatial components: the core and the corona that interact with the environment or solvent. While core/shell, core/multishell systems add further complexity, for example [18], all still possess an area in which NP interfaces with the solvent (Figure 1B). PEG chains modify this interface layer and increase circulation time. Circulation half-time (t½) describes blood pool residence and is the period over which the concentration of circulating NPs remains above 50% of the injected dose, analogous to a drug's half-life [19]. NP efficacy requires sufficient t½ to not only reach the target, but also remain in the affected area (at concentrations sufficiently above background tissue) long enough for image capture or drug delivery. The RES system prevents site-specific accumulation because it removes the NPs from circulation, acting as a competitor to the intended target site [20]. In addition, the NPs must clear from the non-targeted area to produce imaging contrast or dosing efficiency.
The ideal t½ is dependent on application. In imaging, 2–6 h is optimal for injection, accumulation at targeted site, clearance from nontargeted areas and data collection. The ideal circulation time for therapeutic NPs is longer (days) to allow repeated exposure to affected area. Unfortunately, this can also expose healthy organ systems to the drug and is the motivation for targeted NPs, as such systems preferentially accumulate in the diseased area.
Approaches to measuring t½ vary with NP type. When labeled with radionuclides, γ counting of either specific organ systems or blood aliquots determines NP circulation time. One limitation is dissociation of radionuclide from NPs; however, radioactivity measurements may always be carried out noninvasively [21]. Measurement of t½ via fluorescence, Raman, inductively coupled plasma or chromatography/mass spectrometry is very specific to the NP, but requires sequential sampling of the blood pool.
The RES is an immune system component, utilizing circulating macrophages and monocytes, liver Kupffer cells and spleen and other lymphatic vessels to remove foreign material, such as bacteria and viruses, from the body [20]. Figure 2 illustrates how opsonin proteins associate with foreign bodies and coat its surface [22]. As bacteria and viruses have the same negative surface charge as phagocytic cells, opsonins are critical to reducing the charge repulsion between the two systems [13]. Next, phagocytic cells engulf the material and transport it to the liver or spleen for degradation and excretion (Figure 2 A3–A4). Additional phagocytic macrophages are permanently located in the liver. Known as Kupffer cells, these cells serve as a major filter for many types of NPs and are a major interference with long t½ [23]. The PEG polymer on a NP surface increases t½ by reducing this opsonization process (Figure 2B2), thus preventing recognition by monocytes and macrophages, allowing the NPs to remain in the blood pool [13,22]. Hydrophobic particles are also more vulnerable to the RES and hydrophilic PEG reduces these complications [22].
In addition to NP–RES interactions, poor t½ can also result from NP–NP interactions (i.e., aggregation). NPs aggregate primarily because the attraction between particles is stronger than the attraction for solvent [13,24]. NPs with a high surface energy have a greater tendency to aggregate as described by the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory [25,26]. For spherical NPs, the interaction potential is related to the electrostatic repulsive potential and the van der Waals attraction potential [26]. PEG decreases the surface energy of NPs and minimizes van der Waals attraction [27–29].
Aggregation can be induced by solvents of high (>100 mM) ionic strength (shielding of solvent from NP), highly concentrated solutions of NPs (less distance between the NPs), time from synthesis, or NP preparations with a very neutral (~±5 mV) zeta potential [30]. PEG decreases the amount of attraction between NPs by increasing the steric distance between them and increasing hydrophilicity via ether repeats forming hydrogen bonds with solvent. Other benefits to PEGylation include modifying the size of the particle. The reduced renal filtration of particles larger than 10 nm increases t½; however, at too large a size (>100 nm), liver uptake increases and EPR extravasation may decrease [31]. PEG modifies the NP flexibility and the NP can become `softer' after PEGylation than the underlying material, influencing extravasation.
Prior to NP applications, PEG was used as a nontoxic, water-soluble dispersant/stabilizer. Also known as Carboxwax®, it is present in health and beauty aids, including laxatives, toothpastes and eye drops, and is an excipient in tablet formulations [32]. PEG stabilizes organ and blood donations.
Early work with PEGylated NPs stemmed mostly from drug delivery [16,33–36]. One of the first reports on PEGylation was described by Davis and Abuchowski [37,38], where they covalently attached methoxy-PEGs (mPEGs) of 1900 and 5000 Da to bovine serum albumin and to liver catalase. Later, acrylic microspheres functionalized with PEG-modified human serum albumin increased t½ in vivo [39]. Li and colleagues found that 75-nm latex particles remained in rat circulation 40-times longer (half-life 20 min vs 13 h) when coated than uncoated with PEG larger than 5000 kDa [33]. Klibanov and Huang found that incorporation of dioleoyl N-(monomethoxy polyethyleneglycol succinyl) phosphotidylethanolamine (PEG-PE) into posphatidylcholine:cholesterol liposomes (1:1) increased t½ from 30 min to 5 h without increasing leakage of the liposome interior [35]. In the mid-1990s, Doxil® (liposomal delivery vehicle for doxorubicin) and oncospar (PEG-l-asparaginase) became the first FDA-approved NP therapeutics [40]. Doxil increases doxorubicin bioavailability nearly 90-fold at 1 week from injection of PEGylated liposomes versus free drug [41]. The use of PEG on the doxorubicin carrier yields a drug half-life of 72 h with circulation half-life of 36 h [42,43]. Later, Abraxane® was introduced as an albumin-functionalized NP for delivery of taxane without cremphor to enhance drug efficiency [44].
The PEG monomer and the basic structure of the polymer are shown in Figure 1C. Most PEG molecules contain the following components: one end (designated R1) attaches to the NP surface, while the other distal terminal group (R2) interacts with the solvent. Any number (n) of ethylene glycol repeats connect R1 and R2. PEG is also described as polyethylene oxide, especially when referring to longer PEG repeats or mPEG [45]. Below the major factors affecting the behavior of PEG–NP constructs are considered, in light of increased t½.
The type of NP to be PEGylated remains the most important factor for stability and t½. It is most affected by the NP size, charge and composition. For example, ganglioside liposomes have a size-dependent distribution (<70 nm accumulate in liver and >200 nm in spleen), while identical liposomes of phosphatidylserine showed size-independent liver accumulation [46]. In the case of NPs with positive surface charges and sizes above 100 nm, the NPs are still rapidly cleared from the circulation in the face of even the most careful PEGylation strategies [31,47]. PEG types appropriate for a liposome NP may fail when deployed to solid, metallic NPs as liposomal NPs better mimic naturally circulating entities (i.e., cells) and, thus, may not require as stringent of a PEGylation protocol. NP composition is the most important consideration when selecting a PEG conjugation approach.
In imaging, one of the first NP applications was superparamagnetic iron oxide (SPIO) and reports of this material in nanomaterial form date from the 1960s [48,49] and had become routine by the 1990s [50]. PEGylation or dextran coating of SPIO and ultrasmall SPIO (USPIO) lengthens t½ by up to 200 min and improves image quality [51–53]. Targeted SPIO allows molecular imaging via MRI, generally impossible without exogenous contrast agents [54]. Gold NPs were first used as immunogold for transmission electron microscopy contrast in the 1970s, but are now also used for computed tomography and radiograph contrast [55,56]. Many applications of PEGylated gold NPs and nanorods have since been reported [57–62]. A fundamental challenge of gold NPs for CT is low sensitivity. High amounts are needed to achieve contrast. Silica NPs have applications in MRI as gadolinium containers or to protect inner imaging cores [63,64]. NPs deployed to molecular imaging include quantum dots (QDs) for optical reporting [65–67], carbon nanotubes and gold nanorods for photoacoustic imaging and gold surface-enhanced Raman scattering NPs [68–70]. Both QDs and carbon nanotubes suffer from toxicity concerns [71]. Some NPs are multimodal – that is, they report signal through more than one method (e.g., fluorescence and MRI) [72,73].
In therapeutic applications, the NP scaffold stabilizes the payload (~104–105 copies of drug molecules per NP [74,75]), allowing a metered release of drug, reducing toxicity and side effects, and increasing patient compliance [31]. Hydrophobic drugs are protected by the NP interior [15]. Rather than the solid metallic NPs used in imaging, most therapeutic drug-carrying NPs are in the form of liposomes or lipid-based complexes, as well as polymeric micelles or biodegradable polymer/drug composites [76–78]. One of the most common substrate is a blend of poly(lactic-co-glycolic acid) (PLGA) and PEG, (PLGA–PEG). However, there are many other PEGylated polymers for making drug-containing NPs, including polylactic acid [79], poly(hexadecylcyanoacrylate) (PHDCA) [21], polycaprolactone [80], chitosan [81] and poly(sebacic acid) [82]. RNA interference (RNAi) via NPs or PEGylated cationic polymers and lipids are reported [3,5,83,84]. Metallic NPs are also used in tandem with infrared heating for therapy; nanoshells and nanorods are the most common examples [85]. Other NP types detailed in Table 1 include silica, phosphors (NaYF4) and QDs [86,87].
Larger PEG chains contain more monomer repeats, n, (Table 1). Although some reports list the number of monomers in the polymer (e.g., PEG40 would be 40 ethylene glycol repeats), the most common way of reporting the size/length of the PEG chain is the molecular weight, with the weight average molar mass (Mw) being the most common [88]. Some common PEG Mw values include 2000, 3400, 5000, 10,000 and 20,000 Da (i.e., PEG20K). The Mw of a given PEG can be roughly translated into n monomers by dividing Mw by 44, which is the approximate molecular weight of one ethylene glycol monomer moiety or residue.
Larger PEG chains (n = 103–104) are bigger molecules, and the thickness of a grafted PEG layer on the NP surface correlates with polymer conformation. Polymer conformation can be described in terms of the Flory radius (F) according to Equation 1, where n is the number of monomers per polymer chain and α is the length of one monomer in Angstroms (α = 3.5 Å for PEG) [89,90]. The F of some typical PEG Mw are plotted in Figure 3B. There are two main conformations that PEG chains can acquire depending on grafting density. If the surface density is low (i.e., the distance D, between the attachment points of polymer to a surface is larger than F), polymer chains will acquire a `mushroom' conformation (Figure 4A). In this conformation, a polymer chain occupies roughly a half sphere with a radius comparable to the Flory radius. For increased grafting densities (D < F), a polymer will acquire a `brush' regime, with long, thin bristles of PEG extending from the NP surface (Figure 4B) [89,90]. The number of repeating units required to transition from mushroom to brush arrangement is highly dependent on the type of PEG and NP [91]. Pastor and coworkers report that mushroom conformation becomes brush-like when the distance between individual PEG molecules on the surface nears F [45]. NPs with brush PEG generally have longer circulation times as the denser coatings better shield the NPs from the RES [92]. These two different PEG orientations illustrate the wide diversity in PEG footprints in Table 1 and explain footprints smaller than F detailed in Table 2. The PEG footprint in Table 2 is the average space occupied by one PEG on the surface and is not related to F. It is the effective distance between graft sites and is determined by dividing NP surface area by number of PEG ligands. When only the distal R1 occupies NP area, the footprint may be smaller than F.
In general, smaller therapeutic materials use larger PEGs [17]. Oligos and small molecules may be coated with PEG 20,000–50,000 to prevent excretion by the kidneys and maintain a high blood pool concentration for longer periods of time (by enhancing recirculation). Larger NPs in the 50–100-nm range are frequently coated with smaller lengths of PEG (3400–10,000) because further increases in hydrodynamic radius could shorten t½ [12]. Kidney excretion of unconjugated PEG decreases as a function of molecular weight, but liver uptake increases [12]. Mori and Huang, in 1991, reported that liposome circulation time with PEG5000 is significantly longer (7 h) than PEG2000 or PEG750 (~1 h) [93]. Some reports indicate that larger Mw PEGs produce longer t½ on QDs [94–96]. The larger a PEG, the fewer copy numbers can be loaded onto a NP in mushroom conformation.
Important exceptions to the general structure shown in Figure 1C include star PEG, branch PEG and comb PEG [97]. Branch PEGs have one to three pendent PEG units deviating from a central backbone annealed to the NP surface, while star PEGs have several branches emanating from a central point. Branch PEGs result in carbon nanotubes with t½ values of 21 h [98]. NPs with blended PEG chains (two different PEG types on the same NP) are also common and typically involve a high-density short PEG (Mw = 2 kDa) for stealth and a lower density, longer (Mw = 5 kDa; ratio 1:5) PEG for attaching targeting ligands and preventing loop formation in the longer components [99].
The terminal end of the polymer indicated as R2 in Figure 1C influences in vivo behavior. Whitesides compared PEG with different terminal groups and identified that a PEG methoxy or alcohol terminus reduced nonspecific binding of the model proteins lysosyme and fibrinogen to self-assembled monolayers of alkane thiol repeats by orders of magnitude compared with non-PEGylated or alternative terminus [100,101]. mPEG is so ubiquitous that it is often implied when an investigator mentions PEG. Nevertheless, a broad range of PEG types are commercially available, including halo, azido, sulfo and thiol derivatives [102].
As the cell surface is negative, coating NPs with a negative charge (thiol or carboxyl) causes fewer phagocytotic events than positive charges (amine) [31]. Others have studied simple hydroxyl for reducing nonspecific binding [103]. Termini other than methoxy are most commonly used to localize a succimide-, maleimide- or alkyne-reactive group on the end of the PEG to facilitate later binding of a secondary targeting ligand via amine, thiol or click chemistry, respectively [104]. One problem is steric crowding. At coating densities below the brush threshold, the reactive site can sometimes be hidden deep inside the mushroom coil, which prevents secondary linkage (see `Ligands' section).
After selection of the proper PEG, the next consideration is annealing it to the NP surface. Both covalent and noncovalent approaches are used. For solid NPs, such as gold, thiol binding is the classic approach where a sulfhydryl-capped PEG chain adheres to the gold surface [105]. To increase stability, the Mattoussi group and others have deployed multidentate ligands (e.g., dihydrolipoic acid) for more robust PEG stabilization than simple thiols [106]. Silica NP surfaces are generally capped with an organosilane such as amino- or mercapto-trimethoxysilane for routine bioconjugation [104].
A commonly used approach for noncovalent PEGylation is coating the hydrophobic NP surface with lipid-PEG conjugates. For example, PEGylated phospholipids with linear or branched PEG chains bind to the hydrophobic surface of single-walled carbon nanotubes in such a way that hydrophilic PEG groups are facing the aqueous exterior and provide the nanotubes with hydrophilic PEG corona [107,108]. Other techniques prepare hydrophobic polymeric NPs [109], oleic acid-coated magnetic NPs [110] or QDs [111] coated with PEGylated lipids. The hydrophobic interactions between lipids and NPs anchor the PEG chain. For the liposomal preparations, it is also feasible to simply include PEGylated lipids into the lipid mixture [112], or incubate non-PEGylated lipid nanopcapsules with aqueous micellar solution of PEGylated lipids [113]. Regardless of immobilization chemistry, purification of the PEG-NP conjugate is carried out via repeated centrifugation and washing steps, filtration, dialysis or by separation methods, such as size-exclusion or ion-exchange chromatography.
Dynamic light scattering offers three important characteristics of the final PEGylated NP: NP size, zeta potential and size distribution [114]. The zeta descriptor measures the electrostatic potential that exists between the shear plane of a NP and the solvent, and provides information on the colloidal stability of the NP. It is dependent on the solvent, salt type and concentration, and pH. High charge differences (>±10 mV) lead to greater interparticle repulsion. The zeta potential also offers information on the surface coating. Thiols and carboxyls have negative values while amines have positive charge. Sizing via dynamic light scattering suffers from poor reproducibility, yet it is quick and can be used to monitor the sequential size increases that occur during PEGylation and bioconjugation. The size distribution can be used to measure the homogeneity of the final product. Although size increases offer evidence for NP PEGylation and may discriminate between brush and mushroom PEG configurations [115], it cannot answer the specific loading level (i.e., the number of PEG units bound per NP).
Unfortunately, this measurement is only studied casually with many reports simply using NP surface area, PEG size and an assumption of complete saturation to determine loading levels. Another suboptimal alternative is to measure the PEG concentration before and after incubation with the NPs, remove the NPs by filtration or centrifugation and suggest that the difference in solution-phase PEG is immobilized on the NPs. While many of the PEGs are attached, a large number are also nonspecifically bound. This technique often overestimates the loading level by orders of magnitude and is especially difficult when large excess of PEG is used as the measurement of slight differences.
Different types of analytical chemistry solutions for measuring the PEG:NP ratio are detailed in Table 2, and report three different metrics for PEG loading levels (PEG:NP ratio, pmol of PEG/cm2 and PEG footprint) [116]. While footprints (the area of NP surface occupied by each PEG molecule) smaller than F may be counterintuitive, the very dense brush coatings created result in the small footprint and describe a situation in which only the terminal end of the PEG occupies space on the NP surface. While Raman analysis offers very detailed information on loading and conformation, it is beyond the scope of routine laboratories [91]. Thermogravimetric analysis measures change in weight as a function of temperature increase (PEG loss) and is reported for this purpose, but also requires specialized equipment [117]. For the routine user, NMR is used to detect the ethylene protons at 3.65 parts per million, but is not quantitative [118,119]. We, and others, have successfully used fluorescent analogs of the PEG to model the binding densities possible at different loading levels [120,121]. This approach may not be appropriate for gold NPs because of quenching. Other possible methods include surface plasmon resonance (mostly for flat surfaces), size-exclusion chromatography, gels and colorimetric approaches that utilize a reactive R2 [116,122,123]. Gas or liquid chromatography could also be used to not only remove loosely bound PEG, but also offer indirect quantitative information on the NP's PEG loading [124].
Perhaps the most important characterization metric is t½, which is measured by injecting a known amount of NPs into an animal subject and serially collecting blood to monitor the amount of NP in circulation. Approaches to measuring the NP concentration include γ counting, elemental analysis, and mass spectrometry. Some representative t½ values for PEGylated nanomaterials are presented in Table 3. With the proper matching of PEG to NP, long t½ values are achieved. Circulation times near 120 h have been reported for PEGylated xyotax (paclitaxel encapsulated in a biodegradable polyglutamate polymer; also known as OPAXIO) in humans [77,125].
The ideal PEG R2 reduces nonspecific protein absorption, increases hydrophilicity, prevents NP aggregation and facilitates ligand binding for targeted NPs. Compared with the passive targeting via the EPR effect, targeted NPs combine a recognition element with the PEGylated particle for increased accumulation at the site of interest [126–128]. Ligands can increase the tumor accumulation caused by the EPR effect and targeted NPs offer site-specific accumulation, followed by release of a therapeutic not restricted to the vasculature. Ligand types include antibodies [129], small peptides or molecules [128,130–132], lectins [133], aptamers [134], engineered proteins [135] and protein fragments [136]. As NPs leave the vasculature to a lesser degree than small molecules, they are especially useful for targeting markers of angiogenesis [131]. Recent work has shown NPs to be effective vehicles of RNAi outside the vasculature [5]. Both the VEGF and αvβ3 integrins have been imaged via PEGylated NPs to assess tumor vascularization [137]. Without PEGylation, the NPs would have decreased opportunity to interface with vascular targets. Importantly, the use of such ligands (while increasing NP specificity), can also come at the expense of NP performance. As these targeting molecules have exposed charged regions, they can compromise the integrity of the stealth coat and increase RES uptake. The mPEGs, which offer the least nonspecific binding, have no bioconjugation activity, and must be modified or replaced with less stealthy options.
One solution is to use PEGs with reactive ends, although this may increase nonspecific binding (Figure 5A & Table 4). Another approach is blended PEGs, in which one type offers stealth character, while another offers binding capacity [99]. A further option is to anneal the ligand to the NP surface via the same surface reactive sites as the PEG molecules, and coat the remaining sites with PEG, as shown in Figure 5B [138]. One challenge of this approach is steric hindrance of the ligand binding sites by PEG. An additional challenge is quantifying the number of ligands present on the NP, which is important for avidity amplification measurements. Similar approaches to PEG quantification are used; however, since ligands generally have more reactive sites than PEG they can be fluorescently tagged and this reporter used for ligand:NP ratios for all NPs except those that quench fluorescence (i.e., gold NPs).
Targeting of some lipid-based nanocarriers can also be achieved by inserting peptide-lipid conjugates into the outer layer of a parent PEGylated liposome [139]. Alternatively, receptor-targeted nanocomplexes can be prepared by mixing PEGylated cationic liposomes with peptide and drug (plasmid DNA) at precise mixing ratios [140]. Using a mixture of PEGylated, non-PEGylated polymers, as well as polymer–PEG–ligand conjugates during NP preparation, allows for single-step surface functionalization of polymeric NPs [141].
Despite these achievements, a number of limitations and challenges still hamper complete deployment of PEG [12]. Although PEG toxicity is low, it does occur with frequency inversely proportional to molecular weight, especially after oral ingestion. Toxicity after intravenous injection is more likely owing to the NP than the PEG corona. Immunogenicity has also been reported, but generally less so than the immunogenicity of the NP [142]. Furthermore, repeated injections of PEGylated material show markedly decreased t½. This `accelerated blood clearance' (or ABC effect), is thought to be a result of increased splenic production of IgM [143]. While the resistance of PEG to serum degradation is useful from a stability standpoint, NPs and coatings that safely biodegrade in vivo after a defined time point are desirable. A final challenge of PEG is degradation by light, heat or sheer stress, which can result in fragmentation of the PEG and diminish cloaking ability [12].
Alternatives to PEG include natural products, PEG hybrids, and next-generation polymers. Chitons, dextran and other saccharide-containing products have been used to deliver doxorubicin [144,145]. PLGA/PEG copolymer, and polyvinyl pyrrolidone have also shown promise at maintaining long t½ [146,147]. Dendrimers offer both a scaffold for NP synthesis and also a stabilizing sheath [148]. Poly amino acids have a biodegradable structure, but less stealth capacity. Coatings and NPs that better mimic the body's innate stealthing of circulating materials, such as lipids, are increasingly reported [149]. These particles may offer even better shielding and can have site-selective biodegradation. Other researchers report micelles and liposomes that detach the PEG coat to facilitate endosomal escape upon entering the cell [150,151]. Alternatively, cell or bacteria have been deployed as a `Trojan Horse' to deliver NPs [152,153]. Additional NPs are responsive to pH as tumors are usually acidic relative to the rest of the body (pH ~7.4) [154,155]. Langer and others have designed NPs from a triblock copolymer of poly(ethylene oxide) and poly(propylene oxide) and poly(β-amino ester), which degrade and release their therapeutic payload at pH less than 6.5 [156].
The use of PEG and similar stabilizers on NP surfaces will undoubtedly continue. It is unclear how emerging materials will complement PEG's role as the gold-standard cloaking agent. NPs that transition from passive targeting via the EPR effect to NPs that are truly selective for a molecular phenotype will likely require PEG or equivalent to promote circulation time and inhibit removal by the liver and spleen. Strategies to combine the signaling or therapeutic benefits of NPs with effective in vivo delivery remain one of the primary challenges in nanomedicine.
Financial & competing interests disclosure This work was supported by funding from NCI ICMIC P50CA114747 (SSG), NCI CCNE-T U54 U54CA151459, NIBIB BRP 5-RO1-EBB000312 (SSG), NCI U01 EDRN CA152737, Doris Duke Foundation, Canary Foundation, Ben and Catherine Ivy Foundation, Sir Peter Michael Foundation. JV Jokerst is grateful for SMIS fellowship support (R25 CA118681). RN Zare and T Lobovkina acknowledge the National Science Foundation under CBET-0827806. T Lobovkina is the recipient of the Knut and Alice Wallenberg Foundation, Sweden.
No writing assistance was utilized in the production of this manuscript.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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Crazy Substitute Teachers
Enjoy, NG4.05 / 5.00 1,551 Views
Vacuum Salesman
This dude and his Megazord vacuum cleaner3.98 / 5.00 2,441 Views
Markiplier Animated | Mark Of The Survey Corps
This took far too long to make...3.91 / 5.00 4,051 Views
It was awesone, however...
I think it was really awesome, however even me that knows warcraft and some expressions like r0fl or something like that didnt got all the jokes. Besides that, a really cool video.
10 out of 10 think it was the longest flash i ever seen ,it was really nice
it looked good and the story was good keep up the good work :D
I really enjoy these, i get it because i hate dota i would be luck duck.. .Haha, anyways please make more of these animations.
"L2P Noobs" "Touche" Haha awesome
Sanya, multik mowniy, pohoze ti ego o4en' dolgo delal :-) ! Zal 4to russkaya fraza tolko odna i ta maternaya :-D . A est' Russkaya versiya multika?
I've been playing DotA for 6 years now ... i've never watched a clip that was so funny as this one xDD ... so real ... so true
PS: If anyone wants to play DotA with me :D >. Find me on Garena as account


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A South Jersey builder will be one of a select group of contractors eligible to help about 3,500 New Jersey homeowners eligible for federal funding to rebuild properties damaged or destroyed by Hurricane Sandy.
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|"John Golubenko" <goluben...@columbiafunds.com>
|RE: Where to set the JAVA_HOME?
|Mon, 12 Feb 2001 17:33:01 GMT
in /etc/profile add line set JAVA_HOME=/path/to/jdk; export JAVA_HOME on windows set %JAVA_HOME%=c:/jdk i believe, but i dont remember. -----Original Message----- From: firstname.lastname@example.com [mailto:firstname.lastname@example.com] Sent: Monday, February 12, 2001 9:16 AM To: email@example.com Subject: Where to set the JAVA_HOME? Hi: Where do you set the JAVA HOME in tomcat? I looked all over the place for this including the .conf file? Thanks, Stefan NOTICE: This communication may contain confidential or other privileged information. If you are not the intended recipient, or believe that you have received this communication in error, please do not print, copy, retransmit, disseminate, or otherwise use the information. Also, please indicate to the sender that you have received this email in error, and delete the copy you received. Any communication that does not relate to official Columbia business is that of the sender and is neither given nor endorsed by Columbia. Thank you.
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I'm having a minor headache with the TalkBack screen reader service when reading phone numbers in a WebView, and I can't seem to find a solution. This is a snippet of some html code that I am reading into the WebView:

Call 1-800-QUIT-NOW(1-800-784-8669) for phone support

The screen reader reads this as "Call one to eight hundred quit now one to eight hundred link". Is there a way to force it/signal to read it differently? I need it to be read in a more natural format, i.e. "One Eight Hundred".


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Search results
Did you mean: canons
Create the page "Canna" on this wiki! See also the search results found.
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The Idaho State University-Meridian Accelerated Nursing undergraduate degree is offered to individuals who have a bachelor's degree in another discipline and wish to make a career change. This program is three semesters in length and admits 30 students every summer semester. Classes are taught on the Meridian campus through three formats: online, interactive telecommunication, and face to face. Clinical experiences are offered in the simulation lab and at a variety of off- campus settings, including community hospitals, community health facilities, service agencies, and schools.
The Accelerated Program provides learning opportunities for undergraduate students in a variety of classroom and clinical settings to prepare students to take the National Council Licensure Examination Registered Nurse (NCLEX-RN) to secure licensure as a professional nurse.
The Importance of a Bachelor's Degree in Nursing
The Bachelor of Science degree in Nursing is a critical first step for a career in professional nursing. The American Association of Colleges of Nursing (AACN), the national voice for baccalaureate and graduate nursing programs, recognizes the BS degree in nursing as the minimum educational requirement for a professional nursing practice. Recommendations by AACN state that education has a significant impact on the knowledge and competencies of the nurse clinician.
Nurses with BS degrees are well-prepared to meet the demands placed on today's nurse. Bachelor of Science nurses are prized for their skills in critical thinking, leadership, case management, and health promotion, and for their ability to practice across a variety of inpatient and outpatient settings. Nurse executives, federal agencies, the military, leading nursing organizations, health care foundations, community hospitals, and minority nurse advocacy groups all recognize the unique value that baccalaureate-prepared nurses bring to the practice setting. Following the nursing curriculum prepares students to become professional registered nurses and includes the following essential components of all baccalaureate nursing programs: a liberal education, professional values, core competencies, core knowledge, and role development.
Online Application
The applicant is required to apply to Idaho State University and to the School of Nursing.
Apply to ISU
*There is a $50.00 application fee to Idaho State University. Apply as Transfer Undergraduate/ Nursing Pre-major.
For more information and to apply to the School of Nursing Accelerated program, please click here http://elearning.isu.edu/community/.
Professional Fee for Nursing BSN = $890 per semester.
In addition to ISU tuition and fees, a professional fee is assessed for all undergraduate and graduate students in the School of Nursing. Professional fees for the nursing programs are used to support faculty salaries, instruction support services, durable & disposable equipment and supplies, faculty and staff program travel, capital equipment and a reserve for maintenance and purchase of major capital items.
Costs for tuition and general fees at
ISU are listed on the Cost of Attendance Page
The School of Nursing annually awards approximately $42,000 in scholarships.
See Idaho State University scholarship information
Application and Admission Requirements
The student must apply to and meet all requirements for admission to Idaho State University. In addition to the general requirements of Idaho State University, the student must comply with the following:
- Earned Bachelor of Science (B.S.) or Bachelor of Arts (B.A.) from a regionally accredited college or university.
- Mandatory attendance at the orientation for the Accelerated Nursing Program to be held on the ISU-Meridian campus following admission.
There are two deadlines each applicant must meet.
- All prospective applicants are required to meet with a School of Nursing advisor to determine eligibility for the Accelerated BS Nursing program. A. The deadline for meeting with the advisor is no later than 5pm on 1/29/16.
B. Printed copies of specific documents are required for the meeting with the advisor to determine application eligibility. The documents required include the following:
i. Transcripts showing completion of prior Bachelors degree
ii. Transcripts showing completion of and grades for all Set A courses
iii. Completed and approved petitions as required for Sets A and B
iv. Transcripts showing either grades for or registration of all Set B courses
v. TEAS V exam results
vi. Application Instructions packet
B. Please see the Application Instructions for more details on the application and admission process.
C. The application instructions, electronic application, and fee payment are available in Moodle ISU Community at http://elearning.isu.edu/community/ until February 26, 2016.
D. If the prospective applicant does not already have an account in Moodle ISU Community        (elearning.isu.edu/community), the applicant will need to create an account to access the application as        well as upload the required documents for the application process.
E. The prospective applicant must meet with a School of Nursing adviser to complete the Advising        Certification Form. The prospective applicant will be given access to complete the application and upload        required documents only after the Advising Certification Form is uploaded in their Moodle account.
For more details regarding prerequisites and application information please see Accelerated Program information.
School of Nursing course petition form
Selection Process for the Accelerated Nursing Program Summer 2016 Admission Cycle
Acceptance decisions will be made by early April 2016.
Applicant selection is based upon:
- Prerequisite GPA - The GPA is ranked based upon the calculation of grades from the prerequisite courses
(Set A).
- Test of Essential Academic Skills (TEAS V) - The score of the TEAS V is ranked.
Program Information
Please see the Accelerated Baccalaureate Course Plan for upper division nursing courses.
Review tuition, fees and costs:
*Idaho State University and School of Nursing costs related to attendance.
*The fees for the nursing program are $890.00 per semester (program consists of 3 semesters: Summer, Fall, Spring).
If you have questions after looking through the School of Nursing website, please see the Frequently Asked Questions document for more information.
More Information
Questions related to this degree program should be addressed to:
Abbey Hirt, BA, M.Ed
Academic Advisor
Idaho State University School of Nursing
Division of Health Sciences
Abbey Hirt
208.282.4481 (Office)


text:
Do-it-yourself projects and plans for anyone who can swing a hammer.
By Heidi Hunt
DIY, question to readers
Purchasing the materials for a DIY project can involve making a number of decisions. For instance, if you're building a backyard deck, you can choose from a range of materials that are inexpensive, but may last for only a couple of years, to expensive composite wood that can last a decade or more.
Decks can be constructed from high-end composite lumber, soft pine, durable cedar or redwood, or inexpensive slab lumber from a local sawmill. And the wood doesn't have to be new; you might find it at a Habitat for Humanity ReStore or tear down an old building for the lumber. Each type of wood has advantages and disadvantages — price and durability are the key factors to weigh in your decision.
When you're deciding on the materials for an outdoor wooden project, are you more apt to be swayed by cost or durability? Share your experiences in the comments section, below.
Ask the Builder
The Hardware Aisle
Popular Mechanics
Steve Maxwell
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Check out our guide on what to see, do and eat in Singapore!
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Click any word in a definition or example to find the entry for that word
90% of the time, speakers of English use just 7,500 words in speech and writing. These words appear in red, and are graded with stars. One-star words are frequent, two-star words are more frequent, and three-star words are the most frequent.
The thesaurus of synonyms and related words is fully integrated into the dictionary. Click on the thesaurus category heading under the button in an entry to see the synonyms and related words for that meaning.more
Vegetables should be stored in a cool dry place.
The chicken was overcooked and dry.
All they gave me was some dry bread (=with no butter or anything else on it).
This is the British English definition of dry. View American English definition of dry.
Change your default dictionary to American English.
in competitive cycling, the illegal use of motors on bikes in order to gain advantage over other ridersBuzzWord Article
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be reversed; be as if it had never happenedadd a word
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text:
Women's Soccer
Stats (HTML)
Stats (PDF)
2015 Media Guide
Soccer A-Z Game Day Guide
Stats (PDF)
Gameday Information
Transforming Ath Campus
Media Guide
2016 Quick Facts
Prospect Questionnaire
Game Day Hospitality
2015 ACC Championship
In the Pros
Courtesy: Shane Lardinois
Freshman Toni Payne
Duke Takes Down Maryland, 2-1, on the Road
Courtesy: Duke Sports Information
BDN+ Premium Content
Related Links
Box Score: Duke 2, Maryland 1
Duke Overall Statistics
Box Score: Duke 2, Maryland 1
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COLLEGE PARK, Md. –
In the middle of a four-match road trip, the Duke women's soccer team traveled to College Park, Md., on Sunday and netted a key ACC victory with a 2-1 clipping of Maryland at Ludwig Field. The win for the Blue Devils was the first since Sept. 12 at home versus Miami.
"I am very proud of how this team responded," commented head coach
Robbie Church
. "We had a tough game last Sunday up at Boston College. We gave the kids a couple of days off and we came back to practice and you could see us get better and better during the week. We thought it was the best week we have had offensively during the week in a long time. The kids were all committed and did a great job getting their selves ready for the game. It was a huge game, like the rest of them are."
The win for the Blue Devils gives Duke a much-needed three points in the ACC standings as the Blue Devils own a 5-6-3 overall and 2-4-2 league mark. Maryland drops to 7-7-0, 3-5-0.
Maryland opened the match taking three out of the first four shots, before Duke featured attempts by senior
Laura Weinberg
and junior
Kelly Cobb
, which went wide and were saved by Terrapin goalkeeper Rachelle Beanlands. Maryland responded with five straight shots, but three were saved by redshirt junior goalkeeper
Meghan Thomas
of the Blue Devils. Thomas, who is out of Castle Rock, Colo., was making her third collegiate start and the first appearance since Aug. 30.
Duke freshman
Toni Payne
then made a great run down the right side of the pitch into the Maryland 18. A pair of Terrapin defenders closed in on her, but Payne was able to get off an arching shot that looked at first to be heading harmlessly wide of the net, but the ball curled into the upper left corner to give Duke a 1-0 lead in the 34th minute. Payne, who is a native of Birmingham, Ala., registered her second collegiate goal for the Blue Devils.
Toni Payne
scored an unbelievable goal, which was a solo run down the right hand side of the pitch," said Church. "The bench couldn't see if it was a goal because it had no angle. It was great for her because she has had so many turns and runs lately that it was great for her to net one and for us to get the 1-0 lead."
At the end of the first half, Duke held a 1-0 lead, but trailed 8-6 in the shot category.
The Blue Devils took advantage of a corner kick in the 55th minute. Senior
Mollie Pathman
sent the corner kick from the right corner to the back post where senior defender
Natasha Anasi
headed it back into the center of the six. That's where Cobb was able to find it amidst a jumble of players and nudge the ball into the Maryland net for a 2-0 Duke lead. A native of Chugiak, Alaska, Cobb posted her team-best fourth goal of the season, 17th of her career and seventh career game-winner.
Maryland had an opportunity to trim the lead back to a goal in the 59th minute as Aubrey Baker played a cross into the Blue Devils' 18 for Hayley Brock, but her effort was stopped by Thomas, who finished the match with a career-high nine saves in 90 minutes.
The Terrapins got on the board in the 69th minute to make it a one-goal game once again. Baker had some space on the left side of the 18 and drilled a shot that look like it was heading for the right corner of the net, but Thomas used all of her 6-foot-2 frame to stretch out and make the save. But Thomas couldn't control the ball upon impact with the ground and it bounced away from her just enough for Cory Ryan to slide in and finish into the left side of the net.
"Even when they scored a goal nobody panicked," said Church. "We dropped our line a little bit deeper, dropped some players back and I thought we managed the game out well at the end. It was a really good win in a lot of different areas. Most important we get the three points, climbing back towards .500, which makes us NCAA eligible, but we still have a long way to go."
For the match, Duke was outshot 16-9 with the Blue Devils being led by Cobb and Weinberg with three shots each.
"Meghan did a great job in goal," said Church. "She was confident back there and wanted the challenge. I thought she did a really good job in goal, communicated well, and kicked the ball well. Unfortunately, the shutout got away a little bit but that is what happens. She played really well and was a major factor in us winning the game."
The Blue Devils will next travel to Clemson, S.C., on Thursday, Oct. 17 for a 7:00 p.m., match at Clemson. The contest will be aired live on ESPN3.
DWS Freshman Spotlight: Mackenzie Coles
DWS Freshman Spotlight: Lexi Magliarditi
DWS Freshman Spotlight: Ella Stevens
DWS Freshman Spotlight: Mackenzie Coles
The First Golden Blue Devil
Mullins Duke Stats
Eight Blue Devils Named to IWLCA Academic Honor Roll
IWLCA Academic Honor Roll
DWB Kicks Off Unique Initiative with Duke Children's
All for the Kids Flier
DWS Freshman Spotlight: Lexi Magliarditi
Inaugural ACE Class Checks in from China
Inaugural ACE Program Class Announced
Rubenstein-Bing Student-Athlete Civic Engagement (ACE) Program
WS Miller Draws Inspiration from Ice Skating...
WSOC - Final Day in China
WSOC vs Beijing Normal University
WSOC - BFSU Cultural Activity
WSOC vs. Beijing Normal University
Women's Soccer Travels to the Great Wall
WSOC Arrives in China
WS Blue Devils Prepare for China Trip
WS Miller Draws Inspiration from Ice Skating
WSOC - Final Day in China
WSOC vs Beijing Normal University
WSOC - BFSU Cultural Activity
WS Duke Tours Forbidden City & Square
DWS Freshman Spotlight: Emma Carlson
DWS Freshman Spotlight: Brooke Heinsohn
DWS Freshman Spotlight: Mia Gyau
Four Blue Devils Receive TeamSnap All-America
No. 4 Rated Class
MORE Women's Soccer
Stats (PDF)
Gameday Information
Transforming Ath Campus
Media Guide
2016 Quick Facts
Prospect Questionnaire
Game Day Hospitality
2015 ACC Championship
In the Pros


text:
Bryan Shaw need to start being used in low leverage situations for the Cleveland Indians
The Cleveland Indians can no longer allow 28-year old righty reliever Bryan Shaw to work out his kinks pitching late in close games. He needs to pitch earlier in games in lower leverage situations until he can get back on the right track. Shaw has pitched in 29 games (0 starts) for the Tribe so far this year and he is 0-2 with a 5.18 ERA and a 1.44 WHIP. One of those losses came last night against the Angels in Anaheim. He has given up 26 hits (6 homers) and 9 walks while whiffing 25 batters in his first 24 1/3 innings this year, so he has been getting hit extremely hard so far in 2016. 31-year old righty Dan Otero (1-0, 1 save, 0.73 ERA and 1.01 WHIP), 28-year old righty Zach McAllister (2-2, 3.38 ERA and 1.45 WHIP) or 29-year old righty Tommy Hunter (2-1 with a 3.46 ERA and a 1.15 WHIP) should get shots to pitch later in games over Shaw for right now.


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Every article posted on CodeProject has a discussion board associated with it. This page allows you to casually browse through the last 200 messages posted, plus view all postings in the General forums.
Re: Great stuff ... [^]
by miscwriter at 12-Jun-03 4:47
Fun With Templates: Part 1 (Article)


text:
Shai Levi is Assistant Professor at Tel Aviv University; Benjamin Segal is Associate Professor at Fordham University; and Dan Segal is Associate Professor of Accounting at the Interdisciplinary Center Herzliya. This post is based on a recent paper by Professors Levi, Segal, and Segal.
Financial reports should provide useful information to both shareholders and creditors, according to U.S. accounting principles. However, directors of corporations have fiduciary duties toward equity holders only. In our paper, Does Fiduciary Duty to Creditors Reduce Debt-Covenant Avoidance Behavior?, we examine whether this slant in corporate governance biases financial reports in favor of equity investors. In particular, we examine whether the likelihood that firms manipulate their reporting to circumvent debt covenants is higher when directors owe fiduciary duties only to equity holders, rather than when they owe fiduciary duties also to creditors. Debt covenants set limits on leverage and performance, and act as a tripwire allowing creditors to take timely actions to reduce bankruptcy risk and costs. When managers manipulate financial reports to circumvent these debt covenants, they transfer wealth from creditors to shareholders.


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Goldman Sachs to lose two top forex prop traders
A spokesperson at Goldman Sachs said the two, both in their 40s, are retiring and have no immediate plans to undertake further employment. However, RiskNews' sister publication FX Week understands that Siva-Jothy, who is moving to Italy from London, is in the planning stages of establishing a hedge fund. The pair will be replaced by Driss Ben Brahim, who was previously a London-based trader in the interest rates product group.
The Goldman Sachs spokesperson said the departures were unconnected to any losses there may have been on the prop trading desk, and pointed to the strong overall thrid quarter returns for the fixed income, currency and commodity division of the business in which the prop desk operates.
A source formerly employed by the bank pointed out that the incentive for partners such as Siva-Jothy and Grant to remain had diminished since the third and final IPO payment was made in June.
More on People
7 days in 60 seconds
Repo, MVA and securitisation
The week on Risk.net, July 8–14, 2016Receive this by email


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- Miss Florida 2017 stripped of crown days after win - US Weekly
- Lindsay Lohan steps out amid relationship drama - TMZ
- Was Taylor Swift snubbed by the VMAs? - Gossip Cop
- Rachel Platten sings "Fight Song" with lots of stars - Just Jared Jr
- Farrah Abraham sizzles in a revealing bikini - Radar
- New pics from the Clooneys' Italian summer - Lainey Gossip
- Fox News snubs major DNC moment - The Hollywood Reporter
01 December 2012 at 2:25 AM
Hilary Duff: It's Beginning To Look Like Christmas!
About this photo set: Hilary Duff loads her adorable baby boy Luca in her SUV on Thursday (November 29) in Los Angeles. The 25-year-old actress and her 8-month-old son stopped by the… Read More Here
Photo #: 2766270
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text:
I have the Amazon-sold Vivere Double Hammock that I bought to use inside. (...
Type: Posts; User: ka8yiu
I have the Amazon-sold Vivere Double Hammock that I bought to use inside. (...
"Liquid apple pie." Love it.
Is this North of Orlando? I am new to Florida and I need a new car hanging campground.
If you ordered your whoopsies from whoopiesljngs.com, then look at their single line tarp ridgeline, which uses a knotbone on one end and figure 9 on the other. I have two of them, one on my HH Hex,...
I recall seeing something about using the campfire ashes to clean your dishes and have done that a few times. I can see how you can use the same method for your hands.
I think my G'friend is starting to catch on. The pic says it all.59650
I too have the HH Hex and I got the Single Line Tarp Ridge Line from whoopieslings.com. No regrets!
Just my recommendation.
^^^^^^ On for last two posts. Auxier Ridge area is where I've spent most of my time hiking. Nice loops for day hikes.
I've yet to camp in the gorge, though. I usually stay in Koomer Ridge...
I too made a PLUQ as a test for making one for outdoor use and I use it on my indoor hammock. The loft in it was real poor, so it worked great for indoor use.
What are some of the methods being used tie the tarp ridgelines on the stands?
I'm in, too.
Tnx. It will be for outdoor use, so I'm thinking I will keep the tripod legs a little longer for a wider stance and longer horizontal support.
OK, I have been reading through the thread and it is long! I have not found the answer, so I will ask it:
Has anyone determined any minimum/maximum ranges on any parts of the stand?
I have a...
Setup, dinner followed immediately by rain. Nap time, re-stoke the fire and watch it burn. Nite-nite with some more rain, but dry as a bone. (First time using the Hennessy Hex.)
Oh, I'm going. My only reluctance is 14+ hours I worked at the rained out NASCAR race yesterday. I'm beat.
All the more reason to go!!!
I am considering heading to Red River Gorge to my favorite campground this afternoon. We have 40-50% chances of isolated and scattered t-storms today/tonight/tomorrow. But, the cool WX is an...
I received mine in the mail yesterday and immediately hung my hammock in the garage to put them on. Very nice. I am pleased with the item and a very accommodating person to deal with.
I had a similar issue with an SE call, W4K, one year. I won't do it again.
Good luck
Not a full-time hanger, but I have the exact same setup you have. Consider keeping it and just changing the hammock to something different. I used the stand last week in my backyard with my Hennessy...
USAF 1984-1990 - Security Forces/K-9
The comforter is covering the horizontal beam, in case the setup failed.
Wait, I think I read your question wrong: The stand is one piece, I believe like a Vario stand. It is free standing and quite stable.
The end posts only.
This is my indoor stand and it was the right length for my HH. The rain fly was just a bit long, but I made it work.
I was playing with a way to hang in the backyard. It seemed to work.
Curiously awaiting a KY response. I do know the manager at at one park (Fort Boonesborough) told me it was OK.
Does the AFLAC duck hang?
I have two snugpak sleeping bags. They compress down very well and I've never been cold in them.
^What they said!
HR, if you see a big white Ky state truck that says safe patrol, honk and wave!
We were only hiking in for a quick day trip but looks like we are going to pass. Maybe again this year.
Where's the like button? Oh, this isn't Facebook!
Nice story.
Keep in mind the hang in Red River Gorge March 22-24. WX permitting, even consider coming out for a day hike and check out some other gear setups.
Welcome from Lex. You made a good choice!
I got mine today:
What diameter pole works best? I recall she sells different ones.
...Should be "I made it halfway up the staircase." Fat-fingering the iPhone keyboard.
I was checking out the area today. Why not: WX was great!
Inside it halfway up the staircase and decided I wanted to find the other way in! We went to Princess Arch and that's the way I'm coming...
I bought a moisture absorber at a gun store to put in my gun safe. When the color changes, it needs to be recharged. You do this by placing it in the oven for a time (instructions included.)
Good luck.
There is also a good Forest Service campground if you want to car camp and not do the primitive. It is called Koomer Ridge. My favorite! Lots of trees and many of the sites are somewhat...
Mine was mailed yesterday!
Silent, there is no additional charge for the customization. She was very nice and accommodating.
If I/we hike in for a quick visit Saturday, I guess I can park at Gladie to free up a closer spot for overnighters.
I'm beginning to wonder of the parking area will have enough room!
Lexington, KY? Red River Gorge. About 45 minutes East of Lexington.
A group trip is coming up March 22-24.
Planning on walking in on Saturday for a quick visit. Hoping to find you as I've never been on that trail or at the staircase.
I need my G'friend to see some setups to sell her on it.
She sells different flag pole diameters. Which one have some of you found is the best option?
Thank goodness my G'friend got a flat tire tonight. I'd made 3 or 4 purchases tonight up until that call! She might have saved me some money!
I may be way off base here, but if you look at just the nylon hammock part of the HH, from the gathered ends where the suspension is attached, it has a 30* look to it. I think the ridge line and...
What is the best cordage to use for the ridgeline?
...I might just bring the g'friend. I just need to clarify that if I show up with her. Not the same!
Thanks. I was debating bringing the dog.


text:
Saint Emma, also known as Emma of Lesum, or Emma of Stiepel, lived in the city that is Bremen today. She is the first female inhabitant of the city to be known by name. Emma lived in the ... continue reading
This holy priest was born in 1698 at the village of Voltaggio in the diocese of Genoa and was one of the four children of an excellent and highly respected couple. When he ws ten a nobleman ... continue reading
St. Genevieve was born about the year 422, at Nanterre near Paris. She was seven years old when St. Germain of Auxerre came to her native village on his way to great Britain to combat the ... continue reading
St Pantaleon came from Nicomedia, near the Black Sea, in Asia. He was such a famous doctor that the Emperor himself chose him for his own doctor. Pantaleon was a Christian, but the bad influence from ... continue readingMore Saint of the Day
Few details are known of St. Christina but she lived during the third century and was the daughter of a rich and powerful magistrate believed to have been named Urbain. He was deep in the practices of heathenism and had a number of golden idols, which he distributed ... continue readingMore Female Saints
Saint Michael the Archangel isn't a saint, but rather he is an angel, and the leader of all angels and of the army of God. This is what the title "Archangel" means, that he is above all the others in rank. St. Michael has four main responsibilities or offices, as we ... continue reading
Francis was a young nobleman at the court of the King of Spain. He became a Duke when he was only thirty-three and lived a happy, peaceful life with his wife Eleanor and their eight children. But unlike so many other powerful nobles, Francis was a perfect Christian ... continue reading
Artaldus (also called Arthaud) was born in the castle of Sothonod in Savoy. At the age of eighteen, he went to the court of Duke Amadeus III, but a year or two after, he became a Carthusian at Portes. After many years, being a priest and an experienced and holy ... continue reading
By Deacon Keith Fournier
This great defender of the faith insisted on the central claim of Christianity: God can be known and loved-indeed, that is why He came into our midst in the person of His Son; so that through a relationship with Jesus Christ, man could participate in the very ... continue readingMore Christian Saints & Heroes


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I am looking for documentation on color. I need to know the hex values for a list of common named colors, and what hue they belong to. I would also like to know what the cutoff points are (in hex) between different hues. For example At which point does a light blue become just blue? Now I know technically each color has exactly one value, but I am looking for ranges of approximate color.
Also, please note I am colorblind. So when I look at a page that says the color is 'Myrtle' I have no idea if that color is red, brown, orange, or green.