cssi/SciSciGPT-SciSciNet huggingface dataset:
Synthesis of β and γ‐fluorenylmethyl esters of respectively Nα‐Boc‐L‐aspartic acid and Nα‐Boc‐L‐glutamic acid

The orthogonal synthesis of N alpha-Boc-L-aspartic acid-gamma-fluorenylmethyl ester and N alpha-Boc-L-glutamic acid-delta-fluorenylmethyl ester is reported. This is a four-step synthesis that relies on the selective esterification of the side-chain carboxyl groups on N alpha-CBZ-L-aspartic acid and N alpha-CBZ-L-glutamic acid. Such selectivity is accomplished by initially protecting the alpha-carboxyl group through the formation of the corresponding 5-oxo-4-oxazolidinone ring. Following side-chain esterification, the alpha-carboxyl and alpha-amino groups are deprotected with acidolysis. Finally, the alpha-amino group is reprotected with the t-butyl-oxycarbonyl (Boc) group. Thus aspartic acid and glutamic acid have their side-chain carboxyl groups protected with the base-labile fluorenylmethyl ester (OFm) and their alpha-amino groups protected with the acid-labile Boc group. These residues, when used in conjunction with N alpha-Boc-N epsilon-Fmoc-L-lysine, are important in the formation of side-chain to side-chain cyclizations, via an amide bridge, during solid-phase peptide synthesis.
The objectionable act as a mechanism for testing the coercive power of the hypnotic state.

Abstract Two experiments were carried out to determine the extent to which hypnotic Ss and simulators would perform two tasks that might be objectionable, but not antisocial, criminal or illegal. Fourteen percent of the hypnotizable Ss and 16% of the simulators declined to cut an American flag in half. Thirty-three percent of the hypnotizable Ss and 20% of the simulators refused to mutilate a Bible. Overall, 19.7% of the Ss in the two experiments did not carry out one or both of the requested tasks. None of the differences between hypnotizable subjects and simulators in compliance rates is statistically significant. It is concluded first, that the objectionable task appears suitable for research into the coercive power of hypnosis and second, that hypnosis probably cannot be used generally to coerce behavior.
Activation of peripheral mitochondrial benzodiazepine receptors in the hippocampus stimulates allopregnanolone synthesis and produces anxiolytic-like effects in the rat

Rationale and objectives: Stimulation of the mitochondrial benzodiazepine receptor (MBR) in the brain activates the synthesis of neurosteroids that can act as positive modulators of the GABAA receptor complex. Allopregnanolone is a potent anxiolytic, anticonvulsant, sedative and hypnotic GABAergic neurosteroid. The anxiolytic-like effects of FGIN 1-27, an MBR agonist, were determined after microinjection into the dorsal hippocampus. Methods: Behavior in the elevated plus-maze was assessed in adult male rats after bilateral injections of 0, 1.25, 2.5, or 5 µg FGIN 1-27. The behavioral effects of FGIN 1-27 were also determined in animals receiving intrahippocampal co-administration of 20 ng picrotoxin, 5 µg flumazenil, or 200 ng PK 11195. The effects of FGIN 1-27 on behavior in the elevated plus-maze and shock-probe burying test were measured in animals pretreated systemically with 10 mg/kg 4-MA, a 5α-reductase inhibitor. Hippocampal and blood plasma levels of allopregnanolone were measured in separate groups of animals pretreated with 4-MA and receiving an intrahippocampal injection of FGIN 1-27. Results: Intrahippocampal injections of FGIN 1-27 produced anxiolytic-like effects in the plus-maze and in the shock-probe burying test. Hippocampal and blood levels of allopregnanolone were also increased by FGIN 1-27. The anxiolytic-like effects of FGIN 1-27 were attenuated by PK 11195 and were blocked by picrotoxin and 4-MA pretreatment, but remained unaffected by flumazenil pretreatment. The neurosteroidogenic effect of FGIN 1-27 was also eliminated by 4-MA. Conclusion: Activation of the MBR in the hippocampus leads to the synthesis of allopregnanolone, an anxiolytic neurosteroid that potentiates GABAA receptor function.
Pelvic floor: anatomy and function

The pelvic floor is a dome-shaped striated muscular sheet that encloses the bladder, uterus, and rectum, and, together with the anal sphincters, has an important role in regulating storage and evacuation of urine and stool. This article reviews the anatomy, nerve supply, pharmacology, and functions of the anal sphincters and the pelvic floor. The internal and external anal sphincters are primarily responsible for maintaining faecal continence at rest and when continence is threatened, respectively. Defecation is a somato-visceral reflex regulated by dual nerve supply (i.e. somatic and autonomic) to the anorectum. The net effects of sympathetic and cholinergic stimulation are to increase and reduce anal resting pressure, respectively. Faecal incontinence and functional defecatory disorders may result from structural changes and/or functional disturbances in the mechanisms of faecal continence and defecation.
Introduction: Regions and Regionalism in India

This introduction outlines some major ways in which regions and regionalism have been defined. It provides a brief overview of the contents of this special edition of India Review.
Mild and severe Hunter syndrome (MPS II) within the same sibships.

X-linked Hunter syndrome (MPS II) is presently thought to exist in two clinically and genetically distinct forms, mild and severe, which are biochemically indistinguishable. However, two sibships have been studied in which both mildly and severely affected children are present. Therefore, genetic counseling for families with MPS II should be reconsidered to take into account the possibility of heterogeneity within a family in terms of the degree of psychornotor retardation and potential longevity.
Models for medical diagnosis.

The great variety of ills that man is heir to and the tremendous number of symptoms associated with such diseases make the task of medical diagnosis more speculative than scientific. There is an expanding interest in the possibilities of using computers to help make medical diagnoses more quickly and accurately, but here again, the vastness of the task complicates the establishment of a general quantitative diagnostic procedure. Suggested here are models which simplify this procedure into a sequence of decision processes of manageable size for a statistical approach. Perhaps automatic data processing can make an initial inroad into the area of medical diagnosis through the accumulation and continuous revision of base rates appropriate to the various levels in the diagnostic decision process.
Mid-infrared quantum cascade lasers

The design flexibility of quantum cascade lasers has enabled their expansion into mid-infrared wavelengths of 3–25 μm. This Review focuses on the two major areas of recent improvement: power and power efficiency, and spectral performance.
Molecular modeling suggests conformational scaffolds specifically targeting five subtypes of somatostatin receptors.

Several analogs of somatostatin with conformational constraints in their peptide backbones have been modeled to determine energetically feasible conformations. Comparison of low-energy backbone structures of these peptides suggested unique conformations of the central Phe/AlaiD-Trpi+1-Lysi+2-Thri+3 fragment characteristic for specific interactions of somatostatin with each of the five distinct subtypes of somatostatin receptors (SSTRs). The conformations obtained were in good agreement with experimental data obtained earlier by NMR measurements and/or X-ray crystallography. The results help rationalize experimental observations on the specificity of binding of various somatostatin analogs with different subtypes of the SSTRs. They also serve as templates for the design of conformationally constrained non-peptide scaffolds that effectively and selectively interact with different subtypes of SSTRs. Such scaffolds can be convenient carriers of radiolabels and near-infrared labels in specific agents for imaging tumors expressing different SSTR subtypes.
Gut feelings about diabetes

Studies of patients going into diabetes remission after gastric bypass surgery have demonstrated the important role of the gut in glucose control. The improvement of type 2 diabetes after gastric bypass surgery occurs via weight dependent and weight independent mechanisms. The rapid improvement of glucose levels within days after the surgery, in relation to change of meal pattern, rapid nutrient transit, enhanced incretin release and improved incretin effect on insulin secretion, suggest mechanisms independent of weight loss. Alternatively, insulin sensitivity improves over time as a function of weight loss. The role of bile acids and microbiome in the metabolic improvement after bariatric surgery remains to be determined. While most patients after bariatric surgery experienced sustained weight loss and improved metabolism, small scale studies have shown weight regain and diabetes relapse, the mechanisms of which remain unknown.
Interaction of the Influenza A Virus Nucleocapsid Protein with the Viral RNA Polymerase Potentiates Unprimed Viral RNA Replication

The influenza A virus polymerase transcribes and replicates the eight virion RNA (vRNA) segments. Transcription is initiated with capped RNA primers excised from cellular pre-mRNAs by the intrinsic endonuclease of the viral polymerase. Viral RNA replication occurs in two steps: first a full-length copy of vRNA is made, termed cRNA, and then this cRNA is copied to produce vRNA. The synthesis of cRNAs and vRNAs is initiated without a primer, in contrast to the initiation of viral mRNA synthesis, and requires the viral nucleocapsid protein (NP). The mechanism of unprimed viral RNA replication is poorly understood. To elucidate this mechanism, we used purified recombinant influenza virus polymerase complexes and NP to establish an in vitro system that catalyzes the unprimed synthesis of cRNA and vRNA using 50-nucleotide-long RNA templates. The purified viral polymerase and NP are sufficient for catalyzing this RNA synthesis without a primer, suggesting that host cell factors are not required. We used this purified in vitro replication system to demonstrate that the RNA-binding activity of NP is not required for the unprimed synthesis of cRNA and vRNA. This result rules out two models that postulate that the RNA-binding activity of NP mediates the switch from capped RNA-primed transcription to unprimed viral RNA replication. Because we showed that NP lacking RNA-binding activity binds directly to the viral polymerase, it is likely that a direct interaction between NP and the viral polymerase results in a modification of the polymerase in favor of unprimed initiation.
The pharmacokinetic evaluation of mirabegron as an overactive bladder therapy option

Introduction: Mirabegron is a new once-daily, oral treatment for management of overactive bladder (OAB) that is approved in USA, EU and Japan. It activates β3 adrenoceptor to facilitate bladder filling and reduce mean micturition frequency with better safety profile than current treatment of antimuscarinic drugs. Areas covered: The following article reviews the information available from published randomized trials on the metabolism and pharmacokinetics mirabegron. The reader will gain better insight into the variability in plasma exposure of mirabegron due to various causes. Propensity for drug interactions with mirabegron is low as its clearance involves multiple metabolic and excretory pathways. Mirabegron is generally well tolerated, but its pharmacokinetics is altered by dose and gender with implications for cardiovascular toxicity. Expert opinion: Mirabegron is a first-in-class of β3 adrenoceptor agonists that could offer an alternative to antimuscarinics for OAB patients. The marketed dose of 50 mg...
Viewing urban decay from the sky: A multi-scale analysis of residential vacancy in a shrinking U.S. city

Abstract Demographic shifts result in not only urban sprawl but also urban decay. Although urban vacant land is a sign of economic decline, it is beneficial to the improvement of urban ecology since it provides a variety of critical ecosystem services. It is unclear how socioeconomic/ecological drivers collectively affect the emergence and dynamics of vacant land within the urban context of population decrease and economic decline in different shrinking cities. To address this issue, this research performed comprehensive analyses to examine and quantify the impacts of social processes, economic conditions, urban ecological and spatial proximity factors on residential vacant land at both the block group level and the parcel level through incorporating high spatial resolution multispectral aerial photographs and GIS datasets. Results indicate three major conclusions. First, the mean lot NDVI is found to be a consistently effective measurement of residential landscape management behaviors at both levels, which is significantly and positively related to residential vacancy. Second, proximity factors indirectly and partially characterize a number of socioeconomic variables. Third, a ratio index called neighborhood vacancy prevalence was proposed to capture the neighborhood blight effect, and a potentially optimal neighborhood size was obtained among different neighborhood radii. By considering different categories of variables, residential vacancy can be explained and modeled adequately at both the aggregate and fine levels. Urban planners, geographers and social scientists could benefit from the explanatory and predictive model at the fine scale to yield the most updated parcel data with acceptable estimation accuracy for various practical applications.
Convex Combinations of Planar Harmonic Mappings Realized Through Convolutions with Half-Strip Mappings

Recent investigations into what geometric properties are preserved under the convolution of two planar harmonic mappings on the open unit disk $${\mathbb {D}}$$ have typically involved half-plane and strip mappings. These results rely on having a convolution that is locally univalent and sense-preserving on $${\mathbb {D}}$$ , and thus, much focus has been on trying to satisfy this condition. We introduce a family of right half-strip harmonic mappings, $$\Psi _c : {\mathbb {D}}\rightarrow {\mathbb {C}}$$ , $$c>0$$ , and consider the convolution $$\Psi _c * f$$ for a harmonic mapping $$f = h +\overline{g}: {\mathbb {D}}\rightarrow {\mathbb {C}}$$ . We prove it is sufficient for $$h \pm g$$ to be starlike for $$\Psi _c *f$$ to be locally univalent and sense-preserving. Moreover, $$\Psi _c * f$$ decomposes into a convex combination of two harmonic mappings, one of which is f itself. This decomposition is key in addressing mapping properties of the convolution, and from it, we produce a family of convex octagonal harmonic mappings as well some other families of convex harmonic mappings. Additionally, motivated by the construction of $$\Psi _c$$ , we introduce a generalized harmonic Bernardi integral operator. We demonstrate convolution preserving properties and a weak subordination relationship for this extended operator.
Lessons from the History of Bank Examination and Supervision in the United States, 1863-2008

The history of American banking provides five distinct regulatory/supervisory regimes that cast light on the difficulties of constructing a regime that will guarantee the efficiency as well as the safety and soundness of the system. A basic taxonomy of regulation and supervision is provided to identify the key elements and rationale of each regime. Mark-to-market and prompt closure of insolvent institutions produced the lowest cost to depositors, shareholders and taxpayers, whereas discretion and forbearance created the banking cataclysms of the 1980s and 2000s.
Efficient Computation of Hartree-Fock Exchange Using Recursive Subspace Bisection.

We use a recursive subspace bisection approach introduced in Phys. Rev. Lett.2009, 102, 166406 to accelerate the computation of the Hartree–Fock exchange operator in plane-wave pseudopotential electronic structure calculations. Recursive subspace bisection allows for an unbiased localization of orbitals in domains of varying size and a truncation of orbitals that preserves accuracy in a controlled manner. This representation is used to accelerate the computation of the Hartree–Fock exchange operator, which in turn makes first-principles molecular dynamics simulations based on hybrid density functionals feasible for larger systems than previously possible. We describe a parallel implementation of the method and a load balancing algorithm. The efficiency and accuracy of this approach are demonstrated in electronic structure calculations of a chloride ion solvated in liquid water and calculations of the vacancy formation energy in a 512-atom silicon crystal using the PBE0 hybrid exchange-correlation functional.
Imaging brain phospholipase A2 activation in awake rats in response to the 5-HT2A/2C agonist (+/-)2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI).

Imaging Brain Phospholipase A 2 Activation in Awake Rats in Response to the 5-HT 2A/2C Agonist (±)2,5-Dimethoxy-4-Iodophenyl-2-Aminopropane (DOI)
Role of the mevalonate pathway of isoprenoid synthesis in IL-8 generation by activated monocytic cells.

The highly regulated enzyme HMG-CoA reductase generates mevalonate, the precursor of a complex series of isoprenoids that posttranslationally modify (isoprenylate) certain proteins (e.g., the low-molecular-weight GTP-binding proteins) or that are incorporated into cholesterol and other end products. We recently reported that isoprenoids are required for NADPH oxidase activity in granulocytes via LMW GTP-binding protein isoprenylation. In this study, we evaluated the effects of isoprenoid depletion on the expression of proinflammatory genes in human monocytic THP-1 cells. We selected conditions under which pretreatment for 24 h with isoprenoid synthesis inhibitors (HMG-CoA reductase inhibitor lovastatin or compactin at 10 microM) did not compromise cell viability but markedly suppressed H2O2 generation. Under these conditions interleukin-8 (IL-8) production was attenuated (by 50-90%) in response to lipopolysaccharide, granulocyte-macrophage colony-stimulating factor, and phorbol myristate acetate. Coincubation of reductase inhibitor-treated cells with mevalonate prevented the attenuation of IL-8 production by reductase inhibitors. The effects of isoprenoid depletion on cytokine production were selective: IL-1 beta generation was not inhibited but the production of IL-6 and IL-8 was concomitantly suppressed. IL-8 induction was suppressed at least in part through attenuation of the increase in mRNA in stimulated cells. We conclude that isoprenoid generation through the mevalonate pathway is a requirement for IL-8 induction by activated monocytic cells in vitro. Isoprenylation inhibitors have the potential to alter monocyte proinflammatory function.
Increasing the efficiency and flexibility of capital funding for public and private hospitals.

This paper outlines the recent history of capital funding in the health sector in Australia. It focuses on the trends in capital expenditures and the roles of the public and private sectors. The demand for future capital funding will depend upon a number of factors, including the state of the current capital stock and uncertain future impacts of technology and changes in patient demands. Because of these uncertainties, capital funding for the future must be flexible to meet any changes in operations and demand. The paper highlights the possible use of joint ventures between various public and private organisations, based on the principles of competition and cooperation. (author abstract)
Status of vaccines for porcine epidemic diarrhea virus in the United States and Canada

In 2013, porcine epidemic diarrhea virus (PEDV) emerged in the United States as a rapidly spreading epidemic causing dramatic death losses in suckling piglets. Neonatal piglets are most vulnerable to clinical disease and their only protection is passive immunity from their dam. At the end of the third year of the PEDV outbreak, most US sow herds have been infected and many are entering into an endemic disease with much less, but still chronic losses. This endemic state and the occasional naive herd that breaks with PEDV demonstrate a need to immunize sows to protect piglets. Stimulating PEDV immunity in the sow using safe and efficacious vaccines is the best course of action; however, conducting such studies to develop sow vaccines is very costly and logistically difficult. This manuscript reviews the status of PEDV vaccines available in the United States and Canada, and describes an experiment evaluating the potential use of young pigs as a surrogate model to evaluate potential sow vaccines.
Nano-Mechanical Response of Red Blood Cells

In their physiological function, red blood cells (RBCs) need to undergo large deformations in order to pass through capillaries and small vessels. In several pathological conditions, including diabetes mellitus and Alzheimer’s disease, this extreme deformability appears to be deeply impaired and an increase in the RBCs stiffness is usually detected.
Family Workshops in Residential Treatment

For some time, purposeful integration of the family into adolescent residential treatment has been correlated with positive and long-lasting outcomes for those treated in these settings. Family workshops are a key aspect of family integration attempts and provide a unique opportunity to create second-order change in the family system. However, conducting family workshops requires the clinician to confront unique challenges, and many clinicians feel unprepared to develop and facilitate family workshops. This chapter attempts to prepare clinicians for this type of work by first reviewing relevant literature on family workshops and adolescent treatment. Second, by drawing on family systems theory and the author’s experiences as a therapist in two residential treatment centers, a structure for family workshops (i.e., preparation, reunion, and separation phases) and sample interventions are proposed. Finally, special considerations when delivering family workshops, such as the timing of the workshop and typical family and group dynamics, are discussed.
Monoclonal Gammopathy of Undetermined Significance (MGUS) Follow-up Practice Patterns in the US: Frequency of Visits, Types of Tests and Concordance with Clinical Practice Guidelines

Background: The optimal follow-up of MGUS patients, including frequency of visits and type of tests to order, is unknown because there are no evidence-based data available for guidance. Nevertheless, there are currently 4 clinical practice guidelines that are based on expert-consensus: UK-Nordic (2009), International Myeloma Working Group (IMWG; 2010), International Expert Consensus (IEC; 2010) and European Myeloma Network (EMN; 2014). Most guidelines recommend annual follow-up with laboratory tests until life expectancy becomes limited. How MGUS patients are followed in the US and whether clinical practice guidelines are being followed remain largely unknown. Methods: We conducted a retrospective analysis of adult (age >18 years) patients from 2006-2012 using theOptum Labs Data Warehouse,a large database including administrative claims information on >150 million privately insured and Medicare Advantage enrollees throughout the US. We identified patients with an incident diagnosis of MGUS (ICD9: 273.1) who had enrollment periods of>1 year pre- and>2 years post-diagnosis in order to exclude patients with a prior history or subsequent diagnosis of lymphoplasmacytic malignancy. We determined the overall outpatient follow-up practice patterns (visits or tests performed for MGUS), their variations over time and by geo-demographic subgroups, and concordance with current clinical practice guidelines Results: There were 10,349 MGUS patients who met the study criteria. The mean interval per MGUS follow-up visit was 13.1 months. The distribution of patients by mean interval between visits was: q 24 months (46.8%). There was a significant trend towards a higher proportion of patients being followed q 24 months compared to their counterparts (P Conclusions: In the US, the MGUS follow-up practice patterns varied demographically and geographically. Only half of the patients were followed according to current guideline recommendations. A large proportion of patients with limited life expectancy continued to undergo close follow-ups. Disclosures No relevant conflicts of interest to declare.
Gene Editing with Helper-Dependent Adenovirus Can Efficiently Introduce Multiple Changes Simultaneously over a Large Genomic Region.

Helper-dependent adenoviral vectors (HDAds) possess long homology arms that mediate high-efficiency gene editing. These long homology arms may permit simultaneous introduction of multiple modifications into a large genomic region or may permit a single HDAd to correct many different individual mutations spread widely across a gene. We investigated this important potential using an HDAd bearing 13 genetic markers in the region of homology to the target CFTR locus in human iPSCs and found that all markers can be simultaneously introduced into the target locus, with the two farthest markers being 22.2 kb apart. We found that genetic markers closer to the HDAd's selectable marker are more efficiency introduced into the target locus; a marker located 208 bp from the selectable marker was introduced with 100% efficiency. However, even markers 11 kb from the selectable marker were introduced at a relatively high frequency of 21.7%. Our study also revealed extensive heteroduplex DNA formation of up to 10 kb with no bias toward vector or chromosomal repair. However, mismatches escape repair at a frequency of up to 15%, leading to a genetically mixed colony and emphasizing the need for caution, especially if the donor and target sequences are not 100% homologous.
A deep vision landmark framework for robot navigation

Robot navigation requires specific techniques for guiding a mobile robot to a desired destination. In general, a desired path is required in an environment described by different terrain and a set of distinct objects, such as obstacles and particular landmarks. In this paper, a new approach for autonomous navigation is presented using machine learning techniques such as Convolutional Neural Network to identify markers or objects from images and Robot Operating System and Object Position Discovery system to orient to the marker, calculate the distance and navigate towards these markers using depth camera.
Citrullination Following Traumatic Brain Injury: A Mechanism for Ongoing Pathology Through Protein Modification

Traumatic brain injury (TBI) is a major public health issue in the USA, with over 1.7 million cases per year. At least 5.3 million Americans currently live with ongoing disability due to TBI (Walker and Tesco 2013). The long-term consequences of TBI can be complex and progressive: 10–15% of individuals diagnosed with mild TBI continue to suffer from persistent symptoms, while as many as 50% of patients with moderate TBI experience long-term dysfunction (Bales et al. 2009; Walker and Tesco 2013). In addition to the post-injury development of cognitive deficits in attention, memory, and executive function (Bales et al. 2009), a chronic inflammatory state can persist in the brain for months, and even years, following TBI (Opii et al. 2007; Piao et al. 2013). Despite the prevalence of these chronic dysfunctions following TBI, elucidating the mechanisms that underlie these symptoms has proven challenging. It is understood that the post-injury processes of TBI involve a primary and a secondary phase of injury. Primary injury occurs during the initial insult, resulting from the displacement of the physical structures within the brain. Secondary injury occurs over time and involves an interdependent series of cellular dysfunctions that persist long after injury (Giza and Hovda 2001; Nilsson et al. 1996; Park et al. 2008; Walker and Tesco 2013; Werner and Engelhard 2007). Currently, it is not well understood how the acute mechanical injury of TBI, and subsequent secondary injury processes, can result in serious long-term dysfunctions that can persist for years.
Are Joint Surgeons Being Adequately Compensated for Single-Component versus Double-Component Revision TKA? An Analysis of Relative Value Units.

Relative value units (RVUs) are used for ensuring that physicians are appropriately reimbursed based on case complexity. While past research has elucidated that surgeons are reimbursed at a higher rate for primary total knee arthroplasty (TKA) versus revision TKA, no study has explored differences in reimbursements between single-component and double-component revisions, considering a double-component revision is likely to require more effort/skill as compared with single-component revision. The 2015 to 2016 American College of Surgeons National Surgical Quality Improvement Program files were queried using Current Procedural Terminology (CPT) codes for single-component revision TKA (CPT-27486) and double-component revision TKA (CPT-27487). A total of 1,962 single-component and 4,184 double component revisions were performed during this period. Total RVUs, RVU/min, and dollar amount/min were calculated for each case. The mean RVU was 21.12 and 27.11 for single-component and double-component revision TKAs, respectively. A statistically significant difference was noted in mean operative time (single component = 100.44 vs. double component = 144.29; p < 0.001) between the two groups. Single-component revision had a significantly higher mean RVU/min (0.267) versus double-component revision (0.223). The reimbursement amounts calculated for single-component versus double-component revisions were per minute ($9.58/min vs. $8.00/min), per case ($962.22 vs. $1,154.32), and per day ($5,773.32 vs. $4,617.28) with a projected annualized cost difference of $184,966. Orthopaedic surgeons are reimbursed at a higher rate for single-component revision TKAs as compared with double-component revision TKAs, despite the higher complexity and longer operative times required in the latter. The study highlights the need for a change in the RVUs for either double-component or single-component revision to ensure reimbursement per unit time is adequate for performing a complex case such as double-component revision TKA.
Electrostatic equilibria of non-neutral plasmas confined in a Penning trap with axially varying magnetic field

A procedure for computing the electrostatic equilibria of non-neutral plasmas in a Penning trap with a nonuniform magnetic field by solving Poisson's equation using an iterative method is described. Plasma equilibria in a model Penning trap with high and low field regions are computed. The plasma is assumed to follow the Boltzmann density distribution along magnetic field lines. Correspondence with previous investigations examining similar configurations analytically and using particle-in-cell simulations is found. The relationship between the plasma density in low and high field regions is examined for various plasma temperatures, densities, magnetic mirror ratios, and plasma and electrode radii. An analytical description of the radial density profile in the high field region is developed and compared with the computed equilibria. A concept is described for cooling a positron plasma with laser-cooled ions trapped axially within a high magnetic field region, while antiprotons are trapped axially separated from the laser-cooled ions within a low field region, and the positron plasma extends to both regions.
CD62E-Positive Endothelial Microparticle-Neutrophil Conjugates, a Novel Marker of Prothrombotic and Inflammatory Disorders.

Background: In vitro studies have shown that endothelial-cell derived microparticles (EMP) can bind and activate leukocytes. It is unknown whether EMP binding to leukocytes regulates leukocyte activation in vivo. In this study, we examined the correlation between EMP binding to neutrophils (EMP-neutrophil conjugates) and neutrophil activation in various clinical conditions. Methods: We studied a total of 251 venous blood samples from 221 subjects with several prothrombotic and inflammatory conditions, including acute venous thromboembolism (n=25), atrial fibrillation (n=48), metabolic syndrome (n=37), congestive heart failure (n=44), early sepsis (n=35), late sepsis (n=30), as well as normal controls (n=32). Using flow cytometry, we measured leukocyte expression of activation marker CD11b and 2 different populations of EMP-neutrophil conjugates. Bitmapping by forward- and side-scatter gating was used to identify neutrophils; EMP62E+-neutrophil conjugates and EMP54+-neutrophil conjugates were measured based on the detection of E-selectin (CD62E) or CD54, respectively, co-expressed with CD45 in neutrophils. Neutrophil nitric oxide (NO) levels were measured by flow cytometry after loading neutrophils with the membrane permeable NO-selective fluorescent indicator DAF-DA. Results: Levels of EMP62E+-neutrophil conjugates consistently and significantly correlated with CD11b expression. This finding was present in patients with acute venous thromboembolism (r=0.46; p=0.02), atrial fibrillation (r=0.42; p=0.003), metabolic syndrome (r=0.56; p 0.05). EMP62E+-neutrophil conjugates correlated with NO levels in neutrophils in patients with congestive heart failure (r=0.48; p=0.001) and atrial fibrillation (r=0.33; p=0.02), but no correlation was seen in other disease states. Conclusions: EMP62E+-neutrophil conjugates strongly correlate with neutrophil activation in normal adults, as well as in multiple pro-inflammatory and pro-thrombotic disease states. EMP62E+-neutrophil conjugates may serve as a marker of prothrombotic and inflammatory states. Our results combined with prior in vitro studies suggest that EMP62E+ binding to neutrophils is an important and “universal” determining factor for neutrophil activation in vivo in humans. In contrast, binding of EMP54+ to neutrophils does not seem to regulate neutrophil activation. These findings also support the concept that different species of endothelial microparticles have different biologic functions. EMP binding to neutrophils seems to affect NO production in only some disease states.
Atomic Force Microscopy: Fundamental Concepts and Laboratory Investigations

This book focuses primarily on the atomic force microscope and serves as a reference for students, postdocs, and researchers using atomic force microscopes for the first time. In addition, this book can serve as the primary text for a semester-long introductory course in atomic force microscopy. There are a few algebra-based mathematical relationships included in the book that describe the mechanical properties, behaviors, and intermolecular forces associated with probes used in atomic force microscopy. Relevant figures, tables, and illustrations also appear in each chapter in an effort to provide additional information and points of interest. This book includes suggested laboratory investigations that provide opportunities to explore the versatility of the atomic force microscope. These laboratory exercises include opportunities for experimenters to explore force curves, surface roughness, friction loops, conductivity imaging, and phase imaging.
Mitogenesis and retinal pigment epithelial cell antigen expression in the rat after krypton laser photocoagulation.

PURPOSE Polypeptide growth factors, such as the acidic and basic fibroblast growth factors (aFGF and bFGF), may be important in the pathogenesis of subretinal neovascularization. The authors studied the relationship of aFGF and bFGF expression to retinal pigment epithelial (RPE) cell and choriocapillary endothelial cell proliferation in krypton-laser-treated regions of the retina, RPE, and choroid of a model of subretinal neovascularization in the pigmented rat they developed. METHODS Multiple krypton laser burns were applied to the posterior poles of the eyes of pigmented rats according to a protocol described for producing subretinal neovascularization in these animals. At intervals up to 80 days after treatment, the retinas, RPE, and choroid of these animals were examined by [3H]-thymidine autoradiography and electron microscopic immunocytochemistry, using antibodies to aFGF, bFGF, cytoplasmic retinaldehyde-binding protein, opsin, and various basement membrane macromolecules. RESULTS Nuclear radiolabeling became evident in these layers when the label was injected as late as 75 days after photocoagulation, but the number of labeled nuclei was greatest when isotope was injected 2-5 days after laser treatment. Although there were labeled nuclei in the retina, RPE, and choroid, the frequency of labeling as a fraction of the total number of nuclei appeared to be greatest in the RPE and choriocapillaris. Non-laser-damaged RPE cells were immunocytochemically strongly positive for cytoplasmic retinaldehyde-binding protein, but were negative for aFGF and bFGF. After laser treatment, many RPE cells lost their cytoplasmic retinaldehyde-binding protein positivity but stained strongly for aFGF and bFGF within intracellular structures of variable shape and homogeneous appearance. Although these structures had an appearance suggestive of basement membrane, they did not stain with antibodies to collagens type IV or V, to laminin, or to heparan sulfate proteoglycan core protein. They also did not stain with an antibody to the N-terminal peptide of opsin. Choriocapillary endothelial cells were unreactive with antibodies to aFGF, bFGF, or cytoplasmic retinaldehyde-binding protein either before or after laser treatment. FGF-positive RPE cells persisted for the 80-day duration of the experiment. CONCLUSIONS Because the presence of FGF-positive RPE cells coincides temporally with increased nuclear thymidine labeling in the RPE and choriocapillaris, aFGF and/or bFGF may be at least partly responsible for initiating the process of cell proliferation and subretinal neovascularization in these animals.
Heartbeat: When should patients consider implantable cardiac defibrillator deactivation?

The use of implantable cardiac defibrillators (ICDs) has dramatically improved outcomes for patients with many types of heart disease. Yet, the patient with an ICD faces a difficult decision near the end of life—should the ICD be deactivated and, if so, when? Evidence to support a specific approach to this clinical dilemma is not amenable to standard research approaches because the outcomes are qualitative, not quantitative. Thus, carefully designed and implemented qualitative research studies are needed to inform clinical practice. In this issue of Heart , Stoevelaar and colleagues1 performed a focus group study using a constant comparative method for analysis of transcriptions from group sessions with 41 participants. Patients reported that few physicians discussed deactivation of ICDs. Patients also expressed a desire for more information about deactivation and advance care planning, depending on disease stage and patient preferences. The online version of this article also features a helpful video abstract. In the accompanying editorial, Steiner2, Bernacki and Kirkpatrick suggest a tiered approach to discussing the patient’s experience with their ICD, their understanding of the options for advance care planning and the possibility of ICD deactivation (figure 1). They conclude: ‘The heterogeneity of patients’ views on ICD therapy at the end of life presented in this manuscript supports the need for more open communication and ongoing education on this topic for both patients and providers. Patients look to their clinicians for guidance with end-of-life decision-making, and it is the …
The evidence landscape in precision medicine

Precision medicine is beginning to make an impact on the treatment of different diseases, but there are still challenges that must be overcome, such as the complexity of interventions, the need for marker validation, and the level of evidence necessary to demonstrate effectiveness. In this Perspective, we describe how evidence landscapes can help to address these challenges.
Towards an Envelope of Design Solutions for Combined/Intensified Reaction/Separation Systems

In this work, we develop an envelope of design solutions for combined intensified reaction/separation systems. The attainable region-based continuous flow stirred tank reactor equivalence principle...
Performance regression detection in DevOps

Performance is an important aspect of software quality. The goals of performance are typically defined by setting upper and lower bounds for response time and throughput of a system and physical level measurements such as CPU, memory and I/O. To meet such performance goals, several performance-related activities are needed in development (Dev) and operations (Ops). In fact, large software system failures are often due to performance issues rather than functional bugs. One of the most important performance issues is performance regression. Although performance regressions are not all bugs, they often have a direct impact on users' experience of the system. The process of detection of performance regressions in development and operations is faced with challenges. First, the detection of performance regression is conducted after the fact, i.e., after the system is built and deployed in the field or dedicated performance testing environments. Large amounts of resources are required to detect, locate, understand and fix performance regressions at such a late stage in the development cycle. Second, even we can detect a performance regression, it is extremely hard to fix it because other changes are applied to the system after the introduction of the regression. These challenges call for further in-depth analyses of the performance regression. In this dissertation, to avoid performance regression slipping into operation, we first perform an exploratory study on the source code changes that introduce performance regressions in order to understand root-causes of performance regression in the source code level. Second, we propose an approach that automatically predicts whether a test would manifest performance regressions in a code commit. To assist practitioners to analyze system performance with operational data, we propose an approach to recovering field-representative workload that can be used to detect performance regression. We also propose that using execution logs generated by unit tests to predict performance regression in load tests.
Developing an Epidemiological Model to Study Spread of Toxicity on YouTube.

The increased global salience of social media has fueled the propagation of various forms of toxicity. As digital technologies and interactive websites proliferate, cyberspace has become a venue through which toxic users torment their victims. Numerous platforms are trying to combat this phenomenon by training computational methods that are capable of automatically recognizing these toxic contents and removing them from the user-generated text on their platforms. However, given the immensity and speed of content posted on online platforms, identifying and deterring these behaviors at scale remains challenging. Aiming to address this challenge, in this paper, we describe a novel approach to understand and explain the spread of toxicity on YouTube by using well-known epidemic models. Our underlying hypothesis is that the spread of toxicity on YouTube is comparable to the spread of disease. Since mathematical epidemiology has been widely studied, being able to express the spread of toxicity as an epidemic model will enable us to use a wide range of tools and techniques that have been proven to be analytically rich and operationally useful. We leveraged the YouTubeTracker application to extract comments on YouTube. We then employed Google’s Perspective API to assign a toxicity score to each comment. The results of our analysis show that our approach can be fruitfully combined with other strategies to moderate the spread of toxicity on online platforms.
An Unusual Case of Urothelial Cell Carcinoma With Metastasis to the Pancreas

Metastasis to the pancreas is far less common than primary pancreatic tumors. Bladder cancer metastasis involving the pancreas is rarely reported. Here, we report a case of metastasis to the pancreas of urothelial cell origin, diagnosed via upper endoscopic ultrasound-guided fine-needle aspiration and biopsy, and coupled with immunostaining. A high index of suspicion must be maintained for atypical metastatic locations of urothelial cell carcinoma, especially to the pancreas.
Modernity and Bourgeois Life: Society, Politics, and Culture in England, France and Germany since 1750

Preface 1. Introduction: ends and means Part I. Contours of Modernity: 2. Precocious integration: England 3. Monarchical centralization, privilege, and conflict: France 4. Localism, state-building, and burgerliche gesellschaft: Germany 5. Modern industry, class, and party politics in nineteenth-century England 6. France and bourgeois France: from teleocracy to autonomy 7. One special path: modern industry, politics, and bourgeois life in Germany Part II. Calculations and Lifeworlds: 8. Time, money, capital 9. Men and women 10. Bourgeois morals: from Victorianism to modern sexuality 11. Jews as bourgeois and network people Part III. A Culture of Means: 12. Public places, private spaces 13. Bourgeois and others 14. Bourgeois life and the avant-garde 15. Conclusion.
High temperature SAW gas sensor on langasite

Novel Surface Acoustic Wave (SAW) devices using the new langasite (LGS) family of crystals have been designed, fabricated, and tested for high temperature (up to 750/spl deg/C) gas sensor applications. The devices were fabricated using platinum (Pt) and palladium (Pd) thin film technology and were mounted in a high temperature sealed stainless steel chamber for gas testing. The high temperature SAW sensors have been exposed to temperatures from 250/spl deg/C to 750/spl deg/C and cycled more than ten times in that temperature range over periods from two to six weeks. Gas sensing of C/sub 2/H/sub 4/ in N/sub 2/ and H/sub 2/ in N/sub 2/ with baselines of O/sub 2/ and N/sub 2/ on the LGS SAW devices has been performed from 250/spl deg/C to 550/spl deg/C and is reported for the first time in this paper.
Microfluidic Wound Bandage: Localized Oxygen Modulation of Collagen Maturation

Restoring tissue oxygenation has the potential to improve poorly healing wounds with impaired microvasculature. Compared to more established wound therapy using hyperbaric oxygen chambers, topical oxygen therapy has lower cost and better patient comfort, although topical devices have provided inconsistent results. To provide controlled topical oxygen while minimizing moisture loss, a major issue for topical oxygen, we’ve devised a novel wound bandage based on microfluidic diffusion delivery of oxygen. In addition to modulating oxygen from 0–100% in 60s rise time, the microfluidic oxygen bandage provides a conformal seal around the wound. When 100% oxygen is delivered, it penetrates wound tissues as measured in agar phantom and in vivo wounds. Using this microfluidic bandage, we applied the oxygen modulation to 8 mm excisional wounds prepared on diabetic mice. Treatment with the microfluidic bandage demonstrated improved collagen maturity in the wound bed, although only marginal differences were observed in total collagen, microvasculature, and external closure rates. Our results show that proper topical oxygen can improve wound parameters underneath the surface. Because of the ease of fabrication, the oxygen bandage represents an economical yet practical method for oxygen wound research.