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ObjectivesPolymorphism in a coding region of deoxyribonuclease I-like III (DNASE1L3), causing amino acid substitution of Arg-206 to Cys (R206C), is a robustly replicated heritable risk factor for SSc and other autoimmune diseases. DNASE1L3 is secreted into the circulation, where it can digest genomic DNA (gDNA) in apoptosis-derived membrane vesicles (AdMVs). We sought to determine the impact of DNASE1L3 R206C on digestion of circulating gDNA in SSc patients and healthy controls (HCs).MethodsThe ability of DNASE1L3 to digest AdMV-associated gDNA was tested in vitro. The effect of R206C substitution on extracellular secretion of DNASE1L3 was determined using a transfected cell line and primary monocyte-derived dendritic cells from SSc patients. Plasma samples from SSc patients and HCs with DNASE1L3 R206C or R206 wild type were compared for their ability to digest AdMV-associated gDNA. The digestion status of endogenous gDNA in plasma samples from 123 SSc patients and 74 HCs was determined by measuring the proportion of relatively long to short gDNA fragments.ResultsThe unique ability of DNASE1L3 to digest AdMV-associated gDNA was confirmed. Extracellular secretion of DNASE1L3 R206C was impaired. Plasma from individuals with DNASE1L3 R206C had reduced ability to digest AdMV-associated gDNA. The ratio of long: short gDNA fragments was increased in plasma from SSc patients with DNASE1L3 R206C, and this ratio correlated inversely with DNase activity.ConclusionOur results confirm that circulating gDNA is a physiological DNASE1L3 substrate and show that its digestion is reduced in SSc patients with the DNASE1L3 R206C variant.

Conventional approaches to quantify alternative splicing are exon-centric and derive a ratio based on relative levels of the isoforms (or isoform groups) that include versus exclude a particular alternative RNA segment. The ratio measurement to study alternative splicing regulation can be confounded when alternative isoforms undergo differential RNA decay, for example, nonsense-mediated mRNA decay (NMD). Isoform-centric quantification is more informative for functional studies of alternative splicing, but challenges remain in distinguishing specific isoforms. Here, we provide a practical guide on addressing the specificity of isoform quantification and describe a simple sensitive method. Quantitative measurement of alternatively spliced RNA isoforms can be used to differentiate splicing regulation from transcriptional control and isoform-specific RNA decay regulation.

The selective adsorption/separation of C2 hydrocarbons has been realized in a "flexible-robust" MOF, Zn2(Atz)2Ox. Owing to the distinctive guest-dependent multistep adsorption behaviors and suitable guest-framework interactions, this MOF shows outstanding separation performance for C2H2/C2H4 mixtures in a wide range of temperature confirmed by a column breakthrough experiment.

Metal–organic frameworks (MOFs) have emerged as one of the most fascinating libraries of porous materials. In spite of their myriad merits, practical application of most MOFs is restricted due to their high preparation cost because of the complicated organic ligands involved. To address this limitation, we propose to use simple and cheap organic precursors to synthesize MOFs with complicated ligands via “one-pot” in situ reactions of these precursors along with the formation of new MOFs. In this work, we have carefully screened several organic reactions, through which target ligands were generated in situ from easily available reactants during the MOF construction. With this “one-pot” approach, the fabrication of a series of novel MOFs by integrating the organic covalent bond and the coordinate bond has thus been realized through the judicious selection of organic reactions, which effectively simplifies the MOF synthesis process and thus reduces the cost.

Luminescence sensing is commonly based on the change of emission intensity, lifetime, and/or quantum yield of luminescent materials. Wavelength-based luminescence sensing has been comparatively rarely documented. Flexible metal–organic frameworks (MOFs) with rich fluorophores are promising sensory materials due to their unique stimuli-responsive luminescence. However, it is still challenging to construct such materials with high hydrolytic stability, which would allow them to be utilized in water systems. Here, we present two isoreticular flexible MOFs synthesized by carbazole-derived ligands, which show high porosity and excellent stability in aqueous solutions with a wide range of pH values. Interestingly, both MOFs show a structural breathing behavior with variation of the guest molecules inside their pores due to the topologically allowed flexibility. With their frameworks breathing, sensitive fluorescence changes in the wavelength of the maximum emission have been observed. Remarkably, the wavelengths of the maximum emission are well dependent on the pH values (1 to 8) of the aqueous solution in a linear relationship, suggesting a new means of accomplishing pH sensing based on emission wavelength instead of intensity. Wavelength-based fluorescence sensing thus offers an alternative way of achieving pH indication, free from some of the drawbacks associated with intensity-based fluorescence sensing, which should be fundamentally important for the development of new pH sensors in environmental and life sciences.

Return Loss in a Helix TWT output circuit vs. frequency is both physically measured and modeled using 3D RF simulation software. The modeled RF circuit extends from helix sever to output waveguide. Comparison of both sets of data show strongly correlated results both in phase and magnitude over a broad frequency range.

Despite progress based on multilocus, phylogenetic studies of the palms (order Arecales, family Arecaceae), uncertainty remains in resolution/support among major clades and for the placement of the palms among the commelinid monocots. Palms and related commelinids represent a classic case of substitution rate heterogeneity that has not been investigated in the genomic era. To address questions of relationships, support and rate variation among palms and commelinid relatives, 39 plastomes representing the palms and related family Dasypogonaceae were generated via genome skimming and integrated within a monocot-wide matrix for phylogenetic and molecular evolutionary analyses. Support was strong for 'deep' relationships among the commelinid orders, among the five palm subfamilies, and among tribes of the subfamily Coryphoideae. Additionally, there was extreme heterogeneity in the plastid substitution rates across the commelinid orders indicated by model based analyses, with c. 22 rate shifts, and significant departure from a global clock. To date, this study represents the most comprehensively sampled matrix of plastomes assembled for monocot angiosperms, providing genome-scale support for phylogenetic relationships of monocot angiosperms, and lays the phylogenetic groundwork for comparative analyses of the drivers and correlates of such drastic differences in substitution rates across a diverse and significant clade.

Purpose: The aim of this retrospective study was to investigate the possible association between peri-implant marginal bone loss and the apicocoronal (vertical) positioning of dental implants placed adjacent to a tooth. Materials and Methods: Dental records at the University of Michigan, School of Dentistry, were screened. To be included in the study, the patient had to have at least one implant in the premolar or molar region, unilaterally or bilaterally, in either arch, with an immediately mesial adjacent tooth. The implant had to have been functionally loaded for at least 3 years after crown insertion, and clear, nondistorted periapical films had to be available. Several landmarks were identified: the cementoenamel junction (CEJ) and crestal bone (CB) of the tooth adjacent to the implant, the implant platform (PL), and the first radiographic implant-bone contact (BL). The following parameters were measured: CEJ-PL, CEJ-CB, CB-PL, horizontal distance between the adjacent tooth and PL (HD), and vertical distance between BL and the first implant thread at the mesial (BL-m) and distal (BL-d) implant surfaces. Results: A total of 139 patients with a mean age of 62.1 ± 9.3 years were included. The mean follow-up period was 4.42 ± 2.5 years. When the implant was placed more than 3 mm apical to the CEJ of the adjacent tooth, significantly greater peri-implant bone loss occurred at the mesial (difference of means = 0.57 mm) and distal (difference of means = 0.83 mm) implant surfaces. Conclusion: In this study population, implants placed in the posterior area with a vertical distance greater than 3 mm from the CEJ of the adjacent tooth displayed more peri-implant bone loss. Further investigation is required to determine whether this increased peri-implant bone loss predisposes a site to peri-implantitis.

With the growth of renewable energy connecting to the grid, there is a demand for distributed and emerging energy storage technologies to be developed. Moreover, the fast demand of Cloud, Big Data, and Intelligent City industries demand that highly energy efficient Internet Data Center (IDC) to be flexible and have on-demand deployment for a sustainable profit business case. In the effort to make the energy storage management system independent of multiple battery technologies adopted, a new Software Defined Energy (SDE) storage technology is developed and applies the IDC operation. The SDE coupled with the IT equipment not only enables a new generation of highly reliable power system in IDC, but also provides the highly efficient IT power consumption solution. In this paper, a 3-layer topology architecture of the SDE solution is proposed, which consists of Energy Router, Micro dc-grid, and Energy Management Policy Server in the cloud based environment. The analytic reliability model of SDE is conducted and presented. The innovative approach is also applicable in the behind the meter, distributed energy storage and management systems for Industry and Community.

Copper(II)-paddlewheel-based metal–organic frameworks (CP-MOFs) represent a unique subclass of MOFs with highly predictable porous structures, facile syntheses, and functional open metal sites. However, the lack of high hydrolytic stability is an obstacle for CP-MOFs in many practical applications. In this work, we report a new CP-MOF, [Cu4(tdhb)] (BUT-155), which is constructed from a judiciously designed carboxylate ligand with high coordination connectivity (octatopic), abundant hydrophobic substituents (six methyl groups), and substituent constrained geometry (tetrahedral backbone), tdhb8– [H8tdhb = 3,3′,5,5′-tetrakis(3,5-dicarboxyphenyl)-2,2′,4,4′,6,6′-hexamethylbiphenyl)]. BUT-155 shows high porosity with a Brunauer–Emmett–Teller surface area of 2070 m2/g. Quite interestingly, this CP-MOF retains its structural integrity after being treated in water for 10 days at room temperature or in boiling water for 24 h. To the best of our knowledge, BUT-155 represents the first CP-MOF that is demonstrated to ...

Summary Frac packing is a completion technique that merges two distinct processes—hydraulic fracturing and gravel packing. The main challenge of a frac-pack completion is the successful creation of high-conductivity fractures with the tip-screenout (TSO) technique and the placement of proppant within those fractures and in the annulus between the screen and wellbore wall. This is further compounded by having to do so in an ultra high-permeability environment, in which high fluid-leakoff rates are evident. From 1997 to 2006, job data from more than 600 frac-packing operations, representing an estimated 5% of the worldwide total, have been compiled into a database. This paper reviews well information and key frac-packing parameters. Also summarized are engineering implementations and challenges, best practices, and lessons learned. Essential frac-pack design parameters that were attained from the step-rate test (SRT) and minifrac test are evaluated. These include bottomhole pressure, rock-closure time, and fracturing-fluid efficiency. Downhole pressure and temperature are also discussed because of their importance to the post-completion efficiency evaluation and fracturing-fluid-optimization phase. Worldwide case histories are provided that demonstrate how to both deploy different frac-packing systems and pack the wellbore during extreme conditions with improved packing efficiency and a higher chance of success.

Coiled Tubing (CT) intervention operations in extended reach wells (more than 10,000 ft in the lateral length) have become quite common in North America. In general, a 2.0″ CT has enough weight to reach the target depth in a 5,000 ft lateral. Therefore, to reach a 10,000 ft lateral, the use of metal-to-metal friction reducer (MFR) or lubricants will be required to work in conjunction with downhole extended reach tools. However, in some interventions, only lubricants can be used, without the downhole extended reach tool.Various lubricants are available in the CT industry. Based on field operations, a typical lubricant could reduce the coefficient of friction (CoF) by about 20%, while a high performance lubricant could reduce the CoF by up to 50%. In order to reach the bottom of a long lateral well, it is imperative that coiled tubing operators are using the most optimal lubricant in correct applications.In this paper, a linear friction apparatus was introduced and used to evaluate the friction reduction performance of 7 lubricants at various concentrations. With a test fixture, both the static and dynamic CoFs were measured. In addition, the performance of the lubricants was also evaluated with the introduction of polyacrylamide (a fluid friction reducer, FR), the salinity, and sand in the fluid system.The test results indicated that only a few lubricants could effectively deliver CT extended reach. In general, the static CoF of the lubricants was 10% to 30% higher than the dynamic friction. An increase in water salinity and the presence of sand in the wellbore had a negative effect on the performance of the lubricant.A higher lubricant concentration resulted in a lower friction coefficient, especially for the high salinity and sand conditions. However, the use of a fluid friction reducer could be detrimental to the lubricant friction performance when the FR concentration is more than 1%.

In this paper, the related properties of graphene were described as the new materials. Through the comparison, the advantages and disadvantages about the preparation methods of graphene were analyzed. According to the present situation of its application, application areas, existing products, etc. of the graphene materials, that Graphene materials are widely used in the future. And the possible environmental pollution risk in the process of development and application are put forward.

The role of adhesion-associated actin-binding proteins in cell migration is not well defined. In mouse fibroblasts we screened for focal adhesion-associated proteins that were isolated with collagen-coated beads and detected by tandem mass spectrometry. We identified flightless I (FliI) as an actin-binding protein in focal adhesion fractions, which was verified by immunoblotting. By confocal microscopy most FliI was distributed throughout the cytosol and in focal adhesions. By sedimentation assays and in vitro binding assays, we found that FliI associates with actin filaments and actin monomers. Assays using purified proteins showed that FliI inhibits actin polymerization and caps but does not sever actin filaments. Cells with FliI knockdown or cells overexpressing FliI migrated more or less rapidly, respectively, than wild-type controls. Compared with controls, cells with FliI knockdown were less adherent than wild-type cells, exhibited reduced numbers of focal adhesions containing activated β1 integrins and vinculin, and exhibited increased incorporation of actin monomers into nascent filaments at focal adhesions. These data indicate that FliI regulates cell migration through its localization to focal adhesions and its ability to cap actin filaments, which collectively affect focal adhesion maturation.

The transcriptional inhibitor Snail is a critical regulator for epithelial–mesenchymal transition (EMT). Although low oxygen induces Snail transcription, thereby stimulating EMT, a direct role of hypoxia-inducible factor (HIF) in this process remains to be demonstrated. Here we show that hypoxia induces the expression of Snail via HIF. In silico analysis identified a potential hypoxia-response element (HRE) close to the minimal promoter of the human and mouse genome of the snail gene. Gel shift assays demonstrated that a specific hypoxia-inducible complex is formed with the putative HRE and that the complex contains HIF proteins. ChIP assays confirmed the interaction of HIF proteins with the putative HRE in vivo. Reporter gene analyses showed that the putative HRE responds to hypoxia in its natural position as well as in front of a heterologous promoter and that the HRE is directly activated by HIF-1α or HIF-2α. HIF knockdown with siRNA at 2% oxygen and overexpression of an oxygen-insensitive HIF (HIF-ΔODD) mutant at 21% oxygen showed that HIF regulates Snail activation and subsequent cell migration. Our findings identify snail as a HIF target gene and provide novel insights into the regulation of snail and hypoxia-induced EMT. Mol Cancer Res; 9(2); 234–45. ©2011 AACR.

Background Monitoring the incidence and severity of disease due to varied pneumococcal (Pn) serotypes (STs) over time is important in assessing the benefit of Pn vaccines. We describe changes in adult IPD after the 2010 introduction of routine infant PCV13 in Ontario, Canada (PCV13 is funded only for immunocompromised adults ≥50 years as of 2015). Methods TIBDN has conducted population-based surveillance for IPD in Toronto/Peel, Canada (pop 4.3M) since 1995. Cases are reported to a central office; one isolate/case is serotyped. Demographic and clinical data are collected by chart review and patient/family physician interview. Results Of 6,275 episodes of adult IPD, 5,674 (90%) have STs and 6,007 (96%) detailed clinical data. Incidence of IPD decreased from 14.2/100,000/year in 1995 to 6.0/100,000/year in 2013–2017). One thousand two hundred and three (19%) adults with IPD were 15–44 years, 1,889 (30%) were 45–64 years, 3,182 (51%) ≥65 years. Figures 1 and 2 show rates over time by ST group and age. In multivariable analyses, there was no difference across vaccine ST groups (nonvaccine type (NVT) vs. PPV23 not PCV vs. PCV13) in patient age, proportion with ICU admission, requirement for mechanical ventilation (MV), death, length of stay (LOS) or diagnosis of meningitis, except that patients with NVT isolates were more likely to require ICU admission (OR 1.5, 95% CI 1.2,2.0), and to have meningitis (OR 1.9, 95% CI 1.1,3.3). Case fatality declined from 25% (480/1,949) 1995–2001 to 19% (148/763) in 2012–2017 (multivariable OR/year 0.98 95% CI 0.97,0.99); requirements for ICU admission (26–31%; OR/year 1.02, 95% CI 1.01,1.03) and MV (OR/year 18–22%; 1.02, 95% CI 1.01–1.03) increased, LOS did not change. From 2013 to 2017, the distribution of vaccine group STs has not changed: 37% PCV13 (383/1,031); 20% PCV20not13 (205); 9% PPV23not 20 (94), 34% NVT (349). NVT strains include over 23 ST, most commonly 23A (72, 21%), 15A (46, 13%), 35B (37,11%), 6C (36, 10%), 23B (20, 8%). Conclusion In our population, with infant but no routine adult PCV13, the incidence of adult IPD appears to have stabilized, with PCV13 ST strains contributing 37% of IPD. Case fatality has decreased; ICU admission increased. Adult vaccination may be required to further reduce PCV13 ST infections. Figure 1: IPD incidence, adults 15–65 years, by ST group, 2006–2017. Infant PCV7 started 2005 and PCV13 in 2010. Figure 1. IPD incidence, adults ≥65 years, by ST group, 2006–2017. Infant PCV7 started 2005 and PCV13 in 2010. Disclosures A. McGeer, Pfizer: Grant Investigator and Scientific Advisor, Research grant and Research support; Merck: Scientific Advisor, Research support; GlaxoSmithKline: Grant Investigator and Scientific Advisor, Research support.

Background Several studies have documented factors predictive of antimicrobial resistance (AMR) in invasive pneumococcal disease(IPD). However, the implementation of routine pediatric PCV programs, antimicrobial stewardship, and increasing immunocompromised in populating might be expected to change such factors. We report on predictive factors for AMR in IPD from 2012 to 2017. Methods TIBDN performs population-based surveillance for IPD in Toronto/Peel (pop 4.5M). IPD cases are reported to a central office and one isolate/case is serotyped and has antimicrobial susceptibility testing performed by broth microdilution to CLSI standards. Results 2459 cases of IPD were identified from January 2012 to December 2017. Overall rates of resistance to penicillin, macrolides, fluoroquinolones, and TMP-SMX were relatively stable over the course were stable over the study. Risk factors for infection with resistant to penicillin at meningitis breakpoints as opposed to penicillin- susceptible pneumococci were current residence at nursing home (odds ratio [OR], 2.30; P < 0.001), immune compromised status (OR, 1.41; P = 0.012), HIV infection (OR 2.13, P = 0.016), history of receiving PPV23 vaccine (OR 1.38; P = 0.007). Infection with TMP-SMX-resistant pneumococci was associated with HIV infection (OR, 3.2; P = 0.001) and current residence in a nursing home (OR 2.4, P = 0.002). Infection with macrolide-resistant isolates was associated with any use of macrolide 3 months prior to infection (OR, 3.24; P < 0.001), or macrolide treatment failure of the current episode (OR, 6.64; P = 0.003). Infection with levofloxacin-resistant pneumococci was associated with current residence in a nursing home (OR, 13.7; P < .001), and fluorquinolone treatment failure of the current episode (OR 49.4, P = 0.0034). Conclusion Previous same class antibiotic exposure remains a major predictive factor for macrolide resistance. History of treatment failure is a predictive factor for macrolide and fluoroquinolone failure. HIV infection and immune compromise are risk factors for IPD infection with penicillin resistant pneumococci. Hospital acquisition of infection is no longer a risk factor for fluoroquinolone resistance. Disclosures All authors: No reported disclosures.

Summary Cleaning fill from wellbores is the most common coiled tubing (CT) application. The process is a function of multiple variables including fluid properties, flow velocities, wellbore geometry and deviation, pipe eccentricity, particle properties, fill penetration rate and wiper trip speed. Removing fill from wells with low bottom hole pressures (BHP) can be challenging especially if wells are completed with smaller diameter production tubulars which significantly reduce circulation flow cross-section and choke flow(1). Such challenges are further compounded by high deviation or horizontal well trajectories especially in large diameter wellbores. A variety of cleanout methods have been developed in the past, often incorporating high circulation rates, special fluids, wiper trips, or reverse circulation to remove solids. Many of these conventional sand cleanout methods often apply excess hydrostatic pressure on the formation, resulting in lost circulation in pressure depleted reservoirs. The conventional solution to overcome excess hydrostatic pressure has been to include nitrogen to reduce fluid density and thus lessen the hydrostatic head; however, sand vacuuming technology using a concentric coiled tubing (CCT) with a downhole jet pump is an alternative technique for removing fill without placing a hydrostatic load on the reservoir. This paper reviews the individual sand cleanout systems and discusses the advantages and limitations related to each method. In recent years, cleaning sand using the wiper trip method has become the preferred technique. However, an appropriate pump rate and reservoir pressure are needed to maintain a proper return flow rate to carry the sands to the surface. For pressure-depleted reservoirs completed with horizontal wells, a sand vacuuming system can be used to efficiently remove the debris without circulating nitrogen and without high pump rates. When the fill cannot be removed from large-diameter deviated wellbores using conventional low-cost cleanout fluids, then fluids with high solids suspension capability (under shear conditions) in conjunction with wiper tripping may be an economical option. The main application for the reverse circulation technique is cleaning sand from large diameter wellbores when the necessary pump rates for conventional "forward" circulation are not achievable. A venturi junk bailer is often used to retrieve larger or heavier material which cannot be circulated out by traditional methods. Field cases are provided, demonstrating how to select the proper cleaning method and how to efficiently remove sand from a wellbore based on both operational and logistical conditions.

Summary Solids cleanouts using coiled tubing (CT) remain a major part of total activity in the CT industry. Because of the multitude of parameters that influence solids transport, it can be very challenging to design and execute solids cleanouts successfully with CT in highly deviated, larger wellbores with 7-in. production tubing, or even larger tubulars, installed. Numerous papers have been written about the development of wiper-trip cleanout technology and associated engineering design tools, but this paper is focused instead on important practical issues that directly impact the effective implementation of wiper-trip technology in the field. This paper presents the results and lessons learned based on a database that was compiled from more than 100 solids cleanout operations using wiper-trip methodologies. Results will be presented showing how the wiper trip cleanout methodology has improved cleanout efficiency and success rate. Examples are presented showing how the effectiveness of cleanout bottom-hole assemblies (BHAs) involving positive-displacement motors (PDMs) and mills has been improved, while simultaneously reducing stress on surface equipment during the operation. Circulation rates higher than specified maximum rates for the PDM are being used without danger of damaging the PDM, while reducing the total volume pumped through the PDM during the cleanout by 80–90%. Larger outer diameter (OD) items in the BHA are kept clean of solids while wiper tripping, reducing the risk of stuck CT and protecting sensitive completion components from undesirable interactions with the PDM/mill BHA. Multiple wiper trips can be performed in one run without the use of drop balls, while having the ability to use selected functions of critical BHA components and full-size drifting of the wellbore for subsequent operations. Field-proven procedures are explained, allowing solids loading in the annulus to be controlled and reduced when necessary, and allowing estimates of solids volumes during the cleanout to be established, on the basis of feedback from the cleanout BHA before any solids have actually reached surface.

High performance X-ray inspection systems are widely used in the PCBA manufacturing process. These include 2DX systems with sub-micron feature recognition that are equipped with 3D micro-CT (Computer Tomography) and Large Board CT 1-2 (also called Partial Angle CT and PCT). The Large Board CT functionality is extremely important in order to be able to perform 3D CT inspection of regions of interest within a large PCBs in a completely non-destructive way and still provide very high resolution and detail. The micro-CT is mostly effective for small samples and not for large PCBAs. In this paper we share our experience for verifying the quality of a potting process using completely nondestructive X-ray methods (2DX and Large Board CT/PCT). The defects we verify for are voiding and incomplete potting curing. Traditionally, the standard way of controlling the potting process has been a destructive sampling (mechanical cross-sectioning) that results in board damage and scrapping. We compared our X-ray inspection results (2DX and PCT) with mechanical cross section results and proved that the non-destructive X-ray techniques provide completely satisfactory testing solution that gives good confidence to our customers. The X-ray inspection provides clear 2D and 3D images of the defects and it is easy to optimize. In addition, the X-ray inspection (2DX and PCT) of potting process resulted in a significant cost savings for our customers. This is due to the fact that the X-ray techniques are completely non-destructive and also much faster, compared to the mechanical cross-sectioning. In addition, using X-ray inspection we can offer 100% testing solution that is not possible using mechanical cross section. Naturally, as a future project, we will be looking to fully automate the X-ray inspection and provide a fully automatic, extremely fast and completely non-destructive solution for PCBA potting process verification.

Background In Ontario a publicly funded PCV7 infant program (3 + 1 schedule), was introduced in 1/2005, PCV10 in 10/2009 and PCV13 in 11/2010 (2 + 1 schedule with catch-up to 35m). TIBDN performs population-based surveillance for invasive pneumococcal disease (IPD) in Toronto/Peel to evaluate program impact. Methods IPD cases are reported to a central office and one isolate/case is serotyped. Demographic/ clinical data are collected by chart review and patient/physician interview. Results From 1/1995–5/2017, 9727 IPD cases have been identified. Among 910 IPD cases since 2015, 109 (12%) were aged

Abstract The transport of solids is often encountered in well drilling, completion, well intervention and production processes. The process is affected by many variables and the complexity of the phenomena presents challenges to the field engineer who is trying to determine how these parameters affect solids-transport even if only one of these variables is changed during an operation. In the early stage, solids-transport studies mainly focused on finding the minimum critical velocity to prevent the formation of a stationary debris bed in the wellbore annulus for conventional rotary drilling with mud fluids. Over the past 10 years, the research and development focus has been on obtaining information related to the prediction of the equilibrium solids concentration profile along the whole well path during tripping in, on the wiper trip speed during tripping out, and on the prediction of the hole-cleaning time. Various correlations and models have been developed that would guide the field engineer to design and optimize the hole cleaning process. However, due to the complexity of the process, a comprehensive and proven model still does not exist at present. In this paper, based on 20 years of research experience, the authors present a critical review of the state of the art of previous approaches to studying the solids transport during both drilling and well interventions. It mainly focuses on theoretical studies. An overview of the experimental study of solids transport is given in a companion paper (Li et al. 2014). The methodology used to develop a model to simulate the hole cleaning process is also discussed. To date, completely satisfactory solids transport software, is still not available for the oil industry. Hopefully, this paper will provide a useful and helpful general guide for future research related to this subject and will aid in a better understanding of the lack of previous studies and what issues should be focused on in future research. Introduction The transport of solids is encountered in various industries which include the mining (Wilson et al. 2006), sedimentation (García, 2008), oil transport, well drilling, well cementing, well completion, and well intervention and production applications. Coal water slurry, iron ore, mineral concentrate, sand removal, limestone or cement kiln feeding in the cement industry, dredging and tailings disposal and heavy bitumen transport are examples of typical slurry hydraulic transport in a pipeline. Figure 1 shows the proppant image which was taken from a downhole camera after a fracturing job in a horizontal wellbore. The sand bed is in the form of dunes that has to be cleaned out the wellbore before the well can start to produce. Otherwise the sands could block the perforations and reduce the production rate. In some cases if the sands are not cleaned out before the production, a high production rate could clean the well. However, once the sand enters the surface lines, it could cause erosion problems for the surface pipeline and other equipment. The cuttings transport in a conventional drilling application involves a drilling period and a hole-cleaning period. In the drilling period, the bit cuts the rock formation and generates the cuttings. As the drilling progresses, the cuttings are transported toward to the surface. Depending on the flow rate and the well deviation angle, cuttings usually form a cuttings bed in the highly deviated section of a wellbore (between 60o and 90o) and form sand dunes between 40o and 60o of the build section. In the vertical wellbore (between 0o and 40o), the particles are usually fully fluidized. Once the drilling is completed, all cuttings should be cleaned out of the hole. The cuttings could be removed out of the hole when the bit remains at the last position (called the stationary circulation hole cleaning mode) or pull the drilling string out of the hole, at the same time the fluid continues to be circulated (called the wiper trip hole cleaning mode). For conventional drilling, the stationary circulation mode is usually applied during the hole-cleaning period since the pump rate is relatively high (annular fluid velocity >1 m/s) and the drill pipe can also be rotated to aid the solids transport.

Abstract Liquid loading is a common production problem in mature gas wells. As the formation pressure decreases and gas flow rate also decreases, the gas kinetic energy is unable to lift the liquid phase completely to the surface. Liquid starts to accumulate at the bottom of the well, which increases the back pressure of the reservoir. This is reflected in a fluctuated production of liquid and gas rates. At the same time, it significantly reduces the production rate and eventually kills the well. Correct prediction of critical gas velocity at which the well starts to load is very important to the operators since they could take appropriate measures to prevent liquid loading and extend the well production life. In the past, most studies on liquid loading focused on vertical wells. Only recently have a few studies been conducted to deal with the liquid loading for deviated and horizontal wells. To date, there are few published studies discussing how to predict the critical gas velocity across a wide deviation angle range. In fact, there are contradictory conclusions made by different researchers. In this paper a database related to the critical gas velocity is compiled with data from published literature. A new model is developed and evaluated with the experimental data. The gaps in the previous studies and modeling are also discussed. Introduction Gas wells often produce water and other condensate. In the early production stage, the gas flow rate is high enough to carry the produced liquids to the surface. As the reservoir pressure is depleted, the produced gas flow rate decreases until the gas reaches a critical condition at which time the liquid loading is initiated. At the inception of liquid loading, the gas flow rate is not enough to carry the liquid completely to the surface and the liquids start to accumulate at the bottom of the well. Then, the back pressure builds up and the increased reservoir pressure will eventually be sufficient to lift the liquid to the surface. Once the liquid slug is pushed out by the gas, the liquid starts to reload the well again and the cycles are repeated again and again until the well is eventually loaded completely and gas production stops. Accurate prediction of liquid loading in the well is very important to the operators since this will allow them to take the necessary measures to void liquid loading and extend the well production life. The most common liquid loading symptoms observed in the field are pressure (or pressure gradient) fluctuations and reduction of gas production. In general, there are two different liquid loading principles proposed in the literature: liquid droplet fall back and liquid film reversal. The liquid droplet mechanism is based on the falling back of liquid droplets while the liquid film concept is related to the partial or full reversal flow of the liquid film.

Purpose: Recently, implantology has shifted its focus from implant placement to periimplant disease early detection, prevention, and treatment. The purpose of this article was to review the current understanding of the biomarkers associated with periimplant diseases. Materials and Methods: A search of PubMed was conducted up to August 2013 with keywords “peri-implantitis” and “biomarkers.” Selected articles addressed the relationship between biomarkers and periimplant mucositis or peri-implantitis. Results: Biomarkers have been shown to possess potential in detecting periimplant diseases. For example, interleukin (IL)-1β levels were shown to be a good marker to detect periimplant mucositis lesions before they progress to peri-implantitis. Matrix metalloproteinase (MMP)-8 levels in periimplant sulcus fluid may be useful for monitoring the progression of periimplant disease. Osteoprotegerin (OPG) and receptor activator of NFκB ligand (RANKL) were found to be significantly higher in peri-implantitis sites compared with healthy implant sites. Conclusion: Biomarkers such as IL-1β, MMP-8, OPG, RANKL, and others have shown promising outcomes in differentiating from periimplant disease to health. However, because of varying results, additional evidence is needed to validate the links reported.

Parasitic organisms exemplify morphological and genomic reduction. Some heterotrophic, parasitic plants harbor drastically reduced and degraded plastid genomes resulting from relaxed selective pressure on photosynthetic function. However, few studies have addressed the initial stages of plastome degradation in groups containing both photosynthetic and nonphotosynthetic species. Corallorhiza is a genus of leafless, heterotrophic orchids that contains both green, photosynthetic species and nongreen, putatively nonphotosynthetic species, and represents an ideal system in which to assess the beginning of the transition to a "minimal plastome." Complete plastomes were generated for nine taxa of Corallorhiza using Illumina paired-end sequencing of genomic DNA to assess the degree of degradation among taxa, and for comparison with a general model of degradation among angiosperms. Quantification of total chlorophyll suggests that nongreen Corallorhiza still produce chlorophyll, but at 10-fold lower concentrations than green congeners. Complete plastomes and partial nuclear rDNA cistrons yielded a fully resolved tree for Corallorhiza, with at least two independent losses of photosynthesis, evidenced by gene deletions and pseudogenes in Co. striata and nongreen Co. maculata. All Corallorhiza show some evidence of degradation in genes of the NAD(P)H dehydrogenase complex. Among genes with open reading frames, photosynthesis-related genes displayed evidence of neutral evolution in nongreen Corallorhiza, whereas genes of the ATP synthase complex displayed some evidence of positive selection in these same groups, though for reasons unknown. Corallorhiza spans the early stages of a general model of plastome degradation and has added critical insight for understanding the process of plastome evolution in heterotrophic angiosperms.

The major differences between conventional rotary drilling and Coiled Tubing drilling are the absence of pipe rotation and the continuous circulation of drilling fluids. In rotary drilling the circulated fluid must be selected to support the cuttings while making a connection. In slide drilling, the circulated fluids can be continuously circulated. This capability greatly aids the use of gasified fluids in underbalanced drilling. In slide drilling, the pipe does not rotate; while in rotary drilling, the pipe rotation enhances the cuttings transport by the agitation effect due to the pipe rotation and vibration. For a typical Coiled Tubing drilling job, the challenge is achieving the circulation rate required to keep the hole clean. Current field practice is to perform frequent wiper trips. The economics of hole cleaning are crucial to the industry and therefore we seek answers to questions such as: What is the change in the cuttings bed height when the fluids flow rates are altered? How long does it take to clean out an existing cuttings bed? Is there a need to remove the cuttings bed fully before resuming drilling? In this study, 600 tests were conducted and a new computer program was developed for the prediction of cuttings transport in the multi-phase system (gas+liquid+cuttings). The sensitivity of cuttings bed height with respect to liquid/gas volume flow rate ratio, in-situ liquid velocity, ROP, inclination angle and circulation fluid properties was conducted. The hole cleaning time with both circulation mode and wiper trip is also discussed. The results from the sensitivity analysis presented in this paper indicate that: i) the fraction of the circulation liquid has a significant impact on the cuttings transport in underbalanced drilling with gasified fluids, ii) among different variables, the in-situ liquid velocity is the most important variable for cuttings transport, iii) the hole cleaning time decreases non-linearly with increasing fluid circulation rate.

The interactions between two key macromolecular species, nucleic acids and proteins, control many important biological processes. There have been limited effective methodologies to study these interactions in real time. In this work, we have applied a newly developed molecular beacon (MB) DNA probe for the analysis of an enzyme, lactate dehydrogenase (LDH), and for the investigation of its properties of binding with single-stranded DNA. Molecular beacons are single-stranded oligonucleotide probes designed to report the presence of specific complementary nucleic acids by fluorescence detection. The interaction between LDH and MB has resulted in a significant fluorescence signal enhancement, which is used for the elucidation of MB/LDH binding properties. The processes of binding between MB and different isoenzymes of LDH have been studied. The results show that the stoichiometry of LDH-5/MB binding is 1:1, and the binding constant is 1.9 x 10(-7) M(-1). We have also studied salt effects, binding sites, temperature effects, pH effects, and the binding specificities for different isoenzymes. Our results demonstrate that MB can be effectively used for sensitive protein quantitation and for efficient protein-DNA interaction studies. MB has a signal transduction mechanism built within the molecule and can thus be used for the development of rapid protein assays and for real-time measurements.

Coiled tubing drilling technology is gaining popularity and momentum as a significant and reliable method of drilling horizontal underbalanced wells. It is quickly moving into new frontiers. To this point, most efforts in the Western Canadian Basin have been focused towards sweet oil reservoirs in the 900–1300 m true vertical depth (TVD) range, however there is an ever-increasing interest in deeper and gas-producing formations. Fig. 1 shows a composite vertical section of the horizontal or directional under-balanced wells drilled with coiled tubing in Canada, and also highlights the aforementioned trend towards oil over gas. Significant design challenges on both conventional and coiled tubing drilling operations are imposed when attempting to drill these formations underbalanced. Coiled tubing is an ideal technology for underbalanced drilling due to its absence of drillstring connections resulting in continuous underbalanced capabilities. This also makes it suitable for sour well drilling and live well intervention without the risk of surface releases of reservoir gas. Through the use of pressure deployment procedures it is possible to complete the drilling operation without need to kill the well, thereby maintaining under-balanced conditions right through to the production phase. The use of coiled tubing also provides a means for continuous wireline communication with downhole steering, logging and pressure recording devices. Coiled tubing drilling rigs currently exist in several different forms and setups, but generally consist of a drilling coil, injector to feed the tubing into or out of the well, (blowout prevention) (BOP) system for well control and return fluid path, and a control cab and power unit. The coiled tubing drilling equipment used to drill the case studies presented later in this paper consisted of either 60.3 or 73.0 mm coiled tubing and injector with a hydraulic power unit with control cabin and accumulator. A coiled tubing hybrid mast unit and substructure complete with V-door and catwalk was used. Pumping equipment included a fluid pumper capable of liquid rates of 0.10–1.5 m3/min, nitrogen pumper capable of 10–120 m3/min, and a nitrogen bulk storage unit of 50,000 m3 capacity. When drilling sour gas formations, a chemical injection pump for corrosion inhibition is typically used.

Based on the properties, structure and application of dendritic polymer, this paper analysed the methods of the preparation of nanoparticles using dendritic polymer, detailed preparation process, technical parameters and application effect about a single metal nanoparticles, bimetallic nanoparticles, sulfide and halide nanoparticles. The influencing factors of the preparation about nanoparticles were discussed, including the molecular algebra, the molar ratio of the metal ions to the dendritic polymer, and so on.

A mechanical packer and abrasive perforator, conveyed by Coiled tubing(CT), grants great flexibility to the design of an annular fracturing treatment. On the downside the solids from a previous fracture treatment, or abrasive perforation cut, can be picked up by the subsequent pad fluid leading to a screen out. This is complicated by the fact that tolerance to solids varies between formations. To avoid this, solids transport during abrasive perforating, fracturing, displacement, and cleaning must be considered. Unique to this analysis is the ability to model the distribution of solids at any point in time, and the subsequent pick up of solids by the clean pad fluid. This leads to an unprecedented job optimization opportunity for reservoirs that can tolerate some solids in the initial pad stage, and risk mitigation for those which can’t. The model considers a transient mass balance for the solids bed and slurry. Non-uniform distribution of solids in the slurry is considered, which means the solids are not transported with the average slurry velocity. A drift flux model relates solids velocity in the slurry to the average slurry velocity. The difference between these is described by two terms. The first term accounts for variation in the cross sectional profiles of liquid velocity and solids concentration. This considers turbulent diffusion, settling velocity, and a liquid velocity profile based on Prandtl mixing length theory. The second term accounts for the interaction of gravity and buoyancy. Experiments to measure cleaning time involved a transparent pipe with a smaller pipe located eccentrically inside and a known amount of solids. Water is then injected through the smaller pipe and circulated in the annulus to clean the solids. The time required to remove all solids from the annulus is measured for a number of deviation angles and flow rates. Simulation results are compared to experimental data at all deviation angles. A field case is presented for a well that initially screened out during the pad after abrasive perforating. Finally a sample simulation details the solids transport for the entire process and a cleanout that was required following a screen out in the fracturing stage. This highlights how the model can be used to predict the axial distribution of solids in coiled tubing and wellbore at any time, for uphill and downhill flows, at all deviation angles.

Frac-packing is a completion technique that merges two distinct processes: Hydraulic fracturing and gravel packing. The main challenge of a frac-pack completion is the successful creation of high conductivity fractures using the tip-screen out technique and placement of proppant within those fractures and the annulus between the screen and wellbore. This is further compounded by having to do so in an ultra high permeability environment, where high fluid leak-off rates are evident. Since 1997, job data from more than 600 frac-packing operations worldwide have been compiled into a database. This paper reviews well information and key frac-packing parameters. Also summarized are engineering implementations and challenges, best practices, and lessons learned. Essential frac-pack design parameters attained from the step-rate-test (SRT) and mini-frac test are evaluated. These include bottom hole pressure, rock closure time and fracturing fluid efficiency. Down hole pressure and temperature are also discussed because of their importance to the post completion efficiency evaluation and fracturing fluid optimization phase. Worldwide case histories are provided demonstrating how to deploy different frac-packing systems and pack the wellbore under extreme conditions with improved packing efficiency and a higher chance of success.

The conventional adaptive resource allocation schemes for Orthogonal Frequency Division Multiple Access (OFDMA) systems cannot guarantee that the peak power of its time-domain modulated signal shall not exceed the transmitter peak power limit. When such a limit is exceeded, the transmitter creates extra in-band and adjacent-band interferences that were not considered by the conventional resource allocation algorithms, and thus invalidate the optimality of resource allocation. We therefore propose a novel optimization strategy in resource allocation under the peak power constraint. An adaptive iterative resource allocation scheme is developed that maximizes the system throughput and does not create any extra in-band and adjacent-band interferences. In addition a joint scheme of resource allocation and peak power reduction is developed for further throughput improvement.

Annular fracturing of multiple zones with coiled tubing (CT) has been practiced for more than a decade. A typical treatment involves sand jetting perforating, cleaning the well, fracturing and isolation. It is economically desirable to perforate, fracture and isolate each interval quickly, allowing all intervals to be treated in the shortest time possible. However, CT lying on the bottom of horizontal wells creates a solids bed during the perforation and fracturing stage, this introduces additional complexities into the reliable execution of the fracturing process. For tight formations, proppant beds have to be completely or partially removed, otherwise the pad can entrain the proppant which creates a high potential for premature screen out. In this paper, a new approach to cleaning the hole between multiple annular fractures is proposed. This hole cleaning process involves circulating the clean fluid through the annulus to the bottom of the wellbore and bringing the sands back to the surface through the CT; at the same time the CT pulls out of the hole (POOH). The sand particles at the top section of the wellbore are swept toward to the end of CT, while the solids near the end of the bottom hole assembly (BHA) are sucked into the CT as it is pulled out of hole. Eventually, all solids are removed with the CT partially pulled through the initial bed section. As a wiper trip to surface is not required, the efficiency of this new process is higher than other cleaning processes. A full scale flow loop was used to simulate the process. Maximum POOH speed and the hole cleaning time were determined under various conditions. Empirical correlations were developed to allow for optimization of the process under the down hole conditions.