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Purpose To determine the risk for infection in trigger finger release surgery after preoperative corticosteroid injection. Methods We retrospectively evaluated all patients undergoing trigger finger release by 16 surgeons over a 2-year period. Data collected included demographic information, medical comorbidities, trigger finger(s) operated on, presence of a prior corticosteroid injection, date of most recent corticosteroid injection, postoperative signs of infection, and need for surgery owing to deep infection. Superficial infection was defined per Centers for Disease Control criteria. Deep infection was defined as the need for surgery related to a surgical site infection. Results In this cohort of 2,480 fingers in 1,857 patients undergoing trigger release surgery, 53 (2.1%) developed an infection (41 superficial [1.7%] and 12 deep [0.5%]). Before surgery, 1,137 fingers had no corticosteroid injection. These patients developed 1 deep (0.1%) and 17 superficial (1.5%) infections. In contrast, 1,343 fingers had been given a corticosteroid injection before surgery. These patients developed 11 deep (0.8%) and 24 superficial (1.8%) infections. Median time from corticosteroid injection to trigger release surgery was shorter for fingers that developed a deep infection (63 days) compared with those that developed no infection (183 days). The risk for developing a deep infection in patients who were operated on within 90 days of an injection (8 infections in 395 fingers) was increased compared with patients who were operated on greater than 90 days after an injection (3 infections in 948 fingers). Conclusions Preoperative corticosteroid injections are associated with a small but statistically significantly increased rate of deep infection after trigger finger release surgery. The risk for postoperative deep infection seems to be time dependent and greater when injections are performed within 90 days of surgery, especially in the 31- to 90-day postinjection period. Type of study/level of evidence Therapeutic IV.

Purpose: Thumb basal joint arthritis is a common degenerative condition of the hand that is often managed with thumb basal joint arthroplasty (BJA). This procedure generally results in a high level of patient satisfaction; however, the rate and cause of early unplanned reoperation after thumb BJA are not well-understood. Therefore, we performed a review to better understand the rate and cause of early reoperation. Methods: A retrospective review of all thumb BJA cases performed at a single private academic center between 2014 and 2016 yielded 637 patients and 686 primary thumb BJAs with a minimum 1-year follow-up (mean, 2.4 years). Data collection included patient demographics, surgical technique and type of thumb BJA performed, time to reoperation, reason for early reoperation (within 2 years), and type of reoperation. Results: Of 686 patients undergoing thumb BJAs, 10 had unplanned early reoperation (1.5%). Mean duration between the index procedure and reoperation was 5.2 months (range, 0.5–14.3 months). Of the 10 unplanned early reoperations, 4 thumbs in 4 patients required revision arthroplasties owing to persistent pain. Time to reoperation for revision arthroplasty was 9.6 months (range, 3.9–14.3 months). Three of 10 reoperations resulted from early infection, 2 from unplanned early removal of symptomatic K-wires, and one from radial sensory neuritis. Conclusions: In this series of nearly 700 consecutive cases, we identified an unexpected early reoperation rate of 1.5%, with only a 0.6% reoperation rate specifically for painful subsidence requiring a revision arthroplasty. Mean time to revision was 9.6 months. These rates are lower than those published previously and should be considered by patients and surgeons when planning thumb BJA. Type of study/level of evidence: Prognostic IV. Key words: Basal joint arthroplasty, Reoperation, Revision, Thumb, Trapeziometacarpal arthritis

We consider the exterior Dirichlet problem for the heterogeneous Helmholtz equation, i.e. the equation ∇ ⋅ ( A ∇ u ) + k 2 n u = − f where both A and n are functions of position. We prove new a priori bounds on the solution under conditions on A, n, and the domain that ensure nontrapping of rays; the novelty is that these bounds are explicit in k, A, n, and geometric parameters of the domain. We then show that these a priori bounds hold when A and n are L ∞ and satisfy certain monotonicity conditions, and thereby obtain new results both about the well-posedness of such problems and about the resonances of acoustic transmission problems (i.e. A and n discontinuous) where the transmission interfaces are only assumed to be C 0 and star-shaped; the novelty of this latter result is that until recently the only known results about resonances of acoustic transmission problems were for C ∞ convex interfaces with strictly positive curvature.

This article reviews and develops a perspective for the meaning of authenticity in the context of quality assessment of botanical materials and the challenges associated with discerning adulterations vs. contaminations vs. impurities. Authentic botanicals are by definition non-adulterated, a mutually exclusive relationship that is confirmed through the application of a multilayered set of analytical methods designed to validate the (chemo) taxonomic identity of a botanical and certify that it is devoid of any adulteration. In practice, the ever-increasing sophistication in the process of intentional adulteration, as well as the growing number of botanicals entering the market, altogether necessitate a constant adaptation and reinforcement of authentication methods with new approaches, especially new technologies. This article summarizes the set of analytical methods - classical and contemporary – that can be employed in the authentication of botanicals. Particular emphasis is placed on the application of untargeted metabolomics and chemometrics. An NMR-based untargeted metabolomic model is proposed as a rapid, systematic, and complementary screening for the discrimination of authentic vs. potentially adulterated botanicals. Such analytical model can help advance the evaluation of botanical integrity in natural product research.

In this paper we outline the stakeholder-led approaches in the development of biological data products to support effective conservation, management and policy development. The requirements of a broad range of stakeholders and iterative, structured processes framed the development of tools, models and maps that support the FAIR (Findable, Accessible, Interoperable, Reusable) data principles. By structuring the resultant data products around the emerging biological Essential Ocean Variables, and through the engagement with a broad range of end-users, the EMODnet (European Marine Observation and Data Network) Biology project has delivered a suite of demonstration data products. These products are presented in the European Atlas of Marine Life, an online resource demonstrating the value of open marine biodiversity data and help to answer fundamental and policy-driven questions related to managing the natural and anthropogenic impacts in European waters.

Tumoricidal neural stem cells (NSCs) are an emerging therapy to combat glioblastoma (GBM). This therapy employs genetically engineered NSCs that secrete tumoricidal agents to seek out and kill tumor foci remaining after GBM surgical resection. Biomaterial scaffolds have previously been utilized to deliver NSCs to the resection cavity. Here, we investigated the impact of scaffold degradation rate on NSC persistence in the brain resection cavity. Composite acetalated dextran (Ace-DEX) gelatin electrospun scaffolds were fabricated with two distinct degradation profiles created by changing the ratio of cyclic to acyclic acetal coverage of Ace-DEX. In vitro, fast degrading scaffolds were fully degraded by one week, whereas slow degrading scaffolds had a half-life of >56 days. The scaffolds also retained distinct degradation profiles in vivo. Two different NSC lines readily adhered to and remained viable on Ace-DEX gelatin scaffolds, in vitro. Therapeutic NSCs secreting tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) had the same TRAIL output as tissue culture treated polystyrene (TCPS) when seeded on both scaffolds. Furthermore, secreted TRAIL was found to be highly potent against the human derived GBM cell line, GBM8, in vitro. Firefly luciferase expressing NSCs were seeded on scaffolds, implanted in a surgical resection cavity and their persistence in the brain was monitored by bioluminescent imaging (BLI). NSC loaded scaffolds were compared to a direct injection (DI) of NSCs in suspension, which is the current clinical approach to NSC therapy for GBM. Fast and slow degrading scaffolds enhanced NSC implantation efficiency 2.87 and 3.08-fold over DI, respectively. Interestingly, scaffold degradation profile did not significantly impact NSC persistence. However, persistence and long-term survival of NSCs was significantly greater for both scaffolds compared to DI, with scaffold implanted NSCs still detected by BLI at day 120 in most mice. Overall, these results highlight the benefit of utilizing a scaffold for application of tumoricidal NSC therapy for GBM.

Febuxostat prevents gout attacks by lowering serum urate. Aspects of the pharmacokinetic-pharmacodynamic relationship of febuxostat concentrations to urate in gout patients need further elucidation. In order to undertake these studies, the assay methodology for febuxostat has been enhanced and validated to meet FDA standards. An HPLC method with fluorescence-detection has been modified to increase sensitivity, reduce complexity, shorten the sample preparation process and improve the inter-day coefficient of variation of the lowest quality control sample (0.03 μg/L). Protein in plasma samples (200 μL) is now precipitated with acetonitrile (400 μL) containing the internal standard (2-naphthoic acid). The supernatant is analysed at excitation and emission wavelengths of 320 and 380 nm, respectively as in the previous method. A Luna C18 column (Phenomenex, Australia) at 40 °C with mobile phase of glacial acetic acid (0.032%) in acetonitrile:water (60:40, v:v), an injection volume of 10 μL and a flow rate of 1.5 mL/min is employed. Analysis time is 8 min. Calibration curves in drug-free plasma range from 0.005 to 10.00 μg/mL. Data points are fitted using linear regression with a weighting factor of 1/concentration. The inter-day accuracy and imprecision of the quality control samples (0.0075, 0.015, 3.00 and 9.80 μg/mL) is 90–115% and ≤ 14.5%, respectively.

Trapeziectomy with suture-button suspensionplasty is a surgical treatment option for thumb carpometacarpal osteoarthritis refractory to nonsurgical management. We describe the cases of 3 patients who presented with index metacarpal fracture, in the absence of traumatic injury, over 4 months after trapeziectomy with suture-button suspensionplasty. All 3 fractures demonstrated the same pattern: short oblique/spiral, oriented proximal radial to distal ulnar with the distal end in the vicinity of the index metacarpal button, presumably after the orientation of the metacarpal drill hole. Two of the fractures were treated with surgical fixation. Fracture healing was obtained in all cases. Two of the 3 patients remained symptomatic with thumb pain, but decided against revision treatment for the carpometacarpal osteoarthritis. The third underwent restabilization of the suture button at the time of fracture fixation. Although uncommon, index metacarpal fracture after trapeziectomy with suture-button suspensionplasty can present without trauma several months after surgery.

Allogeneic islet cell transplantation is a promising treatment for human type 1 diabetes. Currently, human islets are transplanted via intra-portal infusions. While successful, it leads to significant early islet attrition from instant blood-mediated inflammatory reaction. An extra-hepatic site was established by transplanting islet-loaded microporous poly(lactide-co-glycolide) (PLG) scaffolds into the epididymal fat pad in syngeneic islet transplant models. This study examined this technology in allogeneic islet transplantation and determined whether transplant tolerance could be effectively induced to protect PLG scaffold transplanted allogeneic islets. The efficacy of an established tolerance induction strategy using donor splenocytes treated with ethylcarbodiimide(ECDI) was tested. ECDI-fixed donor splenocytes were infused 7 days before and 1 day after islet transplantation. Immediate normoglycemia was restored, and treated mice maintained indefinite normoglycemia whereas untreated mice rejected islet grafts within 20 days of transplantation. Interestingly, efficacy of tolerance induction was superior in PLG scaffold compared with intra-portal transplanted islets. Protection of PLG scaffold islet allografts was associated with several mechanisms of immune regulation. In summary, PLG scaffolds can serve as an alternative delivery system for islet transplantation that does not impair tolerance induction. This approach of combining tolerance induction with scaffold islet transplantation has potential therapeutic implications for human islet transplantation.

Human group IIA-secreted phospholipase A(2) (sPLA(2)-IIA) is an important regulator of cytokine-mediated inflammatory responses in both in vitro and in vivo models of rheumatoid arthritis (RA). However, treatment of RA patients with sPLA(2)-IIA inhibitors shows only transient benefit. Using an activity-impaired sPLA(2)-IIA mutant protein (H48Q), we show that up-regulation of TNF-dependent PGE(2) production and cyclooxygenase-2 (COX-2) induction by exogenous sPLA(2)-IIA in RA fibroblast-like synoviocytes (FLSs) is independent of its enzyme function. Selective cytosolic phospholipase A(2)-α (cPLA(2)-α) inhibitors abrogate TNF/sPLA(2)-IIA-mediated PGE(2) production without affecting COX-2 levels, indicating arachidonic acid (AA) flux to COX-2 occurs exclusively through TNF-mediated activation of cPLA(2)-α. Nonetheless, exogenous sPLA(2)-IIA, but not H48Q, stimulates both AA mobilization from FLSs and microparticle-derived AA release that is not used for COX-2-dependent PGE(2) production. sPLA(2)-IIA-mediated AA production is inhibited by pharmacological blockade of sPLA(2)-IIA but not cPLA(2)-α. Exogenous H48Q alone, like sPLA(2)-IIA, increases COX-2 protein levels without inducing PGE(2) production. Unlike TNF, sPLA(2)-IIA alone does not rapidly mobilize NF-κB or activate phosphorylation of p38 MAPK, two key regulators of COX-2 protein expression, but does activate the ERK1/2 pathway. Thus, sPLA(2)-IIA regulates AA flux through the cPLA(2)-α/COX-2 pathway in RA FLSs by up-regulating steady state levels of these biosynthetic enzymes through an indirect mechanism, rather than direct provision of substrate to the pathway. Inhibitors that have been optimized for their potency in enzyme activity inhibition alone may not adequately block the activity-independent function of sPLA(2)-IIA.

The heme peroxidase enzyme myeloperoxidase (MPO) is released by activated neutrophils and monocytes, where it uses hydrogen peroxide (H(2)O(2)) to catalyze the production of the potent oxidants hypochlorous acid (HOCl), hypobromous acid (HOBr) and hypothiocyanous acid (HOSCN) from halide and pseudohalide (SCN(-)) ions. These oxidants have been implicated as key mediators of tissue damage in many human inflammatory diseases including atherosclerosis, asthma, rheumatoid arthritis, cystic fibrosis and some cancers. It is shown here that acetaminophen (paracetamol), a phenol-based drug with analgesic and antipyretic actions, is an efficient inhibitor of HOCl and HOBr generation by isolated MPO-H(2)O(2)-halide systems. With physiological halide concentrations, acetaminophen concentrations required for 50% inhibition of oxidant formation (IC(50)) were 77+/-6microM (100mMCl(-)) and 92+/-2microM (100mMCl(-) plus 100microMBr(-)), as measured by trapping of oxidants with taurine. The IC(50) for inhibition of HOCl generation by human neutrophils was ca. 100microM. These values are lower than the maximal therapeutic plasma concentrations of acetaminophen (< or =150microM) resulting from typical dosing regimes. Acetaminophen did not diminish superoxide generation by neutrophils, as measured by lucigenin-dependent chemiluminescence. Inhibition of HOCl production was associated with the generation of fluorescent acetaminophen oxidation products, consistent with acetaminophen acting as a competitive substrate of MPO. Inhibition by acetaminophen was maintained in the presence of heparan sulfate and extracellular matrix, materials implicated in the sequestration of MPO at sites of inflammation in vivo. Overall, these data indicate that acetaminophen may be an important modulator of MPO activity in vivo.

The University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements Research began in 1999 with an emphasis on botanical dietary supplements for women’s health. We have concentrated on plants that may improve women’s health, especially to reduce hot flashes in menopausal women, alleviate the symptoms of premenstrual syndrome, and reduce persistent urinary tract infections. The primary focus of this article is to describe the operation of our center, from acquiring and identifying botanicals to isolating and identifying active constituents, to elucidating their mechanisms of action, and to conducting phase I and phase II clinical studies. Black cohosh (Actaea racemosa; syn Cimicifuga racemosa) has been used as a model to illustrate the steps involved in taking this plant from the field to clinical trials. Bioassays are described that were necessary to elucidate the pertinent biological studies of plant extracts and their mechanisms of action. We conclude that this type of research can only be successful with the use of a multidisciplinary approach.

Antibacterial properties of secreted phospholipases A2 (PLA2) have emerged gradually. Group (G) IIA PLA2 is the most potent among mammalian secreted (s) PLA2s against Gram-positive bacteria, but additional antibacterial compounds, e.g. the bactericidal/permeability-increasing protein, are needed to kill Gram-negative bacteria. The mechanisms of binding to the bacterial surface and the killing of bacteria by sPLA2s are based on the positive charge of the PLA2 protein and its phospholipolytic enzymatic activity, respectively. The concentration of GIIA PLA2 is highly elevated in serum of patients with bacterial sepsis, and overexpression of GIIA PLA(2) protects transgenic mice against experimental Gram-positive infection. The synthesis and secretion of GIIA PLA2 are stimulated by the cytokines TNF-alpha, IL-1 and IL-6. Secreted PLA2s may be potentially useful new endogenous antibiotics to combat infections including those caused by antibiotic-resistant bacteria such as methicillin-resistant staphylococci and vancomysin-resistant enterococci.

Mortality from prostate cancer is a result of progression of cancer cells to become androgen-refractory and metastatic. Eicosanoid products of the cyclooxygenase (COX) and lipoxygenase (LOX) pathways are important mediators of the proliferation of prostate cancer cells in culture and regulate tumour vascularisation and metastasis in animal models. Pharmacological agents that block either COX or LOX products effectively reduce the size of prostate cancer xenografts. Recently, phospholipase A(2) (PLA(2)) enzymes, which regulate the provision of arachidonic acid to both COX- and LOX-derived eicosanoids, are found to also regulate the growth of prostate cancer cells and tumours, with one enzyme, secreted PLA(2)-IIA, being increased in prostate cancer tissues. Annexin A1 and A2, known inhibitors of cytosolic phospholipase A(2)-alpha activity, are absent in prostate cancer tissues. We propose that PLA(2) enzyme function is dysregulated by aberrant up regulation of secreted enzymes and downregulation of endogenous inhibitors of cytosolic phospholipase A(2) activity in prostate cancer and that this dysregulation contributes to the pathogenesis of prostate cancer. Thus, in addition to COX and LOX enzymes, PLA(2) enzymes represent important targets for the treatment of prostate cancer.

The ability of the mixture of α-linked glucose oligomers in corn syrup to function as intrafiber components of paper is statistically assessed at the 95% confidence level for two degrees of refining (257 and 402 mL CSF) of never-dried commercial softwood and hardwood/softwood pulps. Independent of the extent of refining, the replacement of the beaten fibers by corn syrup at about the 6% level does not result in a statistically significant deterioration (two-sided t -test, p = 0.05) of the ISO brightness or of the tensile, tear, burst or surface strength values of the resultant papers. The economic potential of such fiber replacement is discussed. As paper additives, the mixed α-oligomers (corn syrup), glucose and lactose perform indistinguishably.

Experiments are presented, which correlate molecular displacement with the multi-exponential T2 relaxation times of water flowing and diffusing through an alginate bead pack. Three systems were studied comprising beads of 3, 1 or < mm in diameter. T2-resolved propagators were obtained through a combined pulsed gradient stimulated echo (PGSTE) and Carr-Purcell-Meiboom-Gill (CPMG) experiment. Fourier transformation with respect to q produces a propagator for each echo in the CPMG train. Inverse Laplace transformation of the CPMG decays for each point (Z) in the propagator produced a two-dimensional propagator. Analysis of these two-dimensional propagators provided insight into the transport and exchange behaviour of water flowing through this system. This experiment has been simulated in a model bead structure and the resulting T2 relaxation time behaviour and T2-resolved propagators were found to be in good agreement with the experimental data. We also present a theoretical analysis of the response to the combined PGSTE/CPMG sequence in the simple model case of Pouseille flow in a cylindrical capillary, where diffusion to a surface sink is assumed to be the dominant relaxation mechanism.

In this work we describe, implement and analyse in detail a high-order fully discrete spectral algorithm for solving the Helmholtz equation exterior to a bounded (sound-soft, sound-hard or absorbing) obstacle in three space dimensions, with Dirichlet, Neumann or Robin (impedance) boundary conditions. Our algorithm may be thought of as a discrete Glerkin method, but it is also equivalent to a Nystrom method after a simple transformation. We test our algorithm with extensive computational experiments on a variety of three-dimensional smooth and non-smooth obstacles with conical singularities. Our tests include the computation of scattered and far fields induced by incident plane waves. Our method is shown to be very accurate for scattering from surfaces which are globally parameterised by spherical coordinates, and tests show that it performs very much better than several ,of the well-established fast algorithms for obstacle sattering on a range of such surfaces, even some which are non-smooth. Further, we prove superalgebraic convergence of the scattered and far fields obtained using our algorithm in the case of smooth scatterers.

The DOUG (domain decomposition on unstructured grids) package was first developed from 1996-1998 as a parallel solver for scalar elliptic PDEs discretised with finite elements. In this paper we describe its extension to unsymmetric elliptic systems of PDEs, highlighting software design and parallelisation issues. As an application we discuss the performance of the extended package applied to the incompressible Navier-Stokes equations, discretised with mixed finite elements. In particular we focus on discontinuous pressure elements, which are important in many practical applications. We also indicate briefly the application of this solver to Navier-Stokes stability assessment.

The amount of muscle that should be retained on the free fibula during harvest is unresolved. Muscle is used to protect the periosteum, but by harvesting a large muscle cuff, the recipient and donor site morbidity increases. A retrospective review of 47 free fibula flaps performed between January 1997 and March 2002 was undertaken. There was an average follow-up of 15 months. The dissection method used for all cases was a muscle sparing technique where the peroneal vessels were skeletonised anteromedially. Only a very thin rim of muscle (1-2 mm) was left attached to the fibula. The recipient and donor vessels were flushed with heparin saline solution intra-operatively and a Dextran 40 infusion was used for four days post-operatively in all cases. Of the 47 flaps, 39 were used for mandible reconstruction, six for maxillary reconstruction and two for long bone reconstruction following trauma. The average age was 47.7 years (range 13-82) and two-thirds (28/43) of the patients were male. There was one post-operative death. The overall failure rate was 10.9% (5/46). Two flaps were lost as a result of arterial thrombosis, one from venous thrombosis, one from sepsis and in one case the cause could not be determined. There were 2 (4.3%) recipient site haematomas. It is suggested that the low recipient site haematoma rate in this series may be related to the limited muscle bulk transferred with the flap. Harvesting less muscle also enables easier insetting and folding of skin flap, and reduces the donor site problems of haematoma and weakness of the foot. The blood supply to the fibula does not appear to be compromised.

The purpose of the study was to determine whether there are chemosensory and neuropsychological changes that predate the onset of Alzheimer's disease in individuals at enhanced risk of developing the condition. To study this question, a unique sample of individuals (n = 33) was studied who were genetically at-risk for AD by virtue of documented multigenerational evidence of the disease (so-called multiplex families). The performance of at-risk individuals was evaluated on various smell, taste, and neuropsychological measures at baseline and 18 months later. Their performance was compared to a control group (n = 32) that was matched in age, gender, education, and race. At baseline the at-risk group performed worse than the control group on the chemosensory measures of phenethyl alcohol smell detection, smell memory, and taste memory, and on a memory measure involving recall of narrative information (Logical Memory I from the Wechsler Memory Scale- Revised). Across both sessions, the at-risk group had lower smell memory scores than the control group. At-risk status was not significantly associated with APOE status. The results of this and other studies suggest that individuals who are genetically at risk for developing AD may perform more poorly on memory and smell measures compared to those not at risk. This effect may be separate from one known genetic risk factor of AD, APOE, and supports that multiple genes are likely responsible for the disease and its associated memory and other neurocognitive symptoms.

Systematic research on delusional disorder (DD) is limited. The goal of this study was to assess DD patients in the following areas: sensory capacities, decision-making style, and complex reasoning. Ten DD patients and 10 matched normal controls completed the following (1) smell, taste, and vision testing; (2) a probabilistic inference test in which subjects made probability decisions; and (3) a gambling task assessing complex reasoning. No significant difference was found between DD subjects and normals for taste acuity, olfactory acuity, or olfactory discrimination. No difference in visual acuity was noted, but sample size was limited. In addition, DD subjects required significantly less data to make probability decisions than normal controls. Despite using less data, DD subjects were as certain as controls regarding the accuracy of their decisions. As for complex reasoning, DD subjects performed as well as normal controls, but tended to surmise the purpose of the task sooner than normals, a difference that approached significance. In conclusion, these results suggest no differences between DD and normal subjects regarding olfaction, taste, and vision. The reasoning studies suggest that DD subjects may have a “cognitive set” that predisposes them to make conclusions with significantly less data than normals. Further, the study suggests that this reasoning difference generalizes to events outside the DD subjects' delusional realm and can be evoked in an experimental environment.

The central inclusive jet cross section has been measured using a successive-combination algorithm for reconstruction of jets. The measurement uses 87.3 pb^{-1} of data collected with the D0 detector at the Fermilab Tevatron ppbar Collider during 1994-1995. The cross section, reported as a function of transverse momentum (pT>60 GeV) in the central region of pseudorapidity (|\eta

A search is reported for a neutral Higgs boson in the decay channel H→Zγ, Z→ℓ +ℓ - (ℓ = e, μ), using 4.5 fb-1 of pp collisions at s=7 TeV and 20.3 fb-1 of pp collisions at s=8 TeV, recorded by the ATLAS detector at the CERN Large Hadron Collider. The observed distribution of the invariant mass of the three final-state particles, mℓℓγ, is consistent with the Standard Model hypothesis in the investigated mass range of 120-150 GeV. For a Higgs boson with a mass of 125.5 GeV, the observed upper limit at the 95% confidence level is 11 times the Standard Model expectation. Upper limits are set on the cross section times branching ratio of a neutral Higgs boson with mass in the range 120-150 GeV between 0.13 and 0.5 pb for s=8 TeV at 95% confidence level.

We report on a measurement of the ratio of the differential cross sections for W and Z boson production as a function of transverse momentum in proton-antiproton collisions at sqrt(s) = 1.8 TeV. This measurement uses data recorded by the D0 detector at the Fermilab Tevatron in 1994-1995. It represents the first investigation of a proposal that ratios between W and Z observables can be calculated reliably using perturbative QCD, even when the individual observables are not. Using the ratio of differential cross sections reduces both experimental and theoretical uncertainties, and can therefore provide smaller overall uncertainties in the measured mass and width of the W boson than current methods used at hadron colliders., Comment: 10 pages, 2 figures, to be published in Physics Letters B

Pulsed-field-gradient NMR measurements of the one-dimensional probability-density distribution P Δ ( X ) for diffusive displacements of water molecules in times Δ in a water-wet sandstone, saturated with a mixture of dodecane and brine, are presented for water saturations S w ≤ 0.32. The distributions show a distinctive shape which is attributed to the distribution of the aqueous phase in thin, locally curved and effectively two-dimensional layers on the pore surface. The data are reproduced well by a simple model in which diffusion is restricted to the surfaces of an isotropic array of infinite planes, with an effective diffusion coefficient D 2 ( Δ ) which shows a systematic dependence on Δ . This is suggested to arise, in the main, from local curvature of the pore surface.

Measurements are presented which correlate the displacements, X(Delta), determined by PGSE NMR, with the multi-mode transverse 1H NMR relaxation of water flowing through a glass bead pack, for which the dominant relaxation mechanism is diffusion through inhomogeneous internal magnetic fields. Analytical solution for the joint amplitude A[X(Delta), T(2k)] for the case of laminar flow in a circular pipe, with a diffusion-to-surface mechanism, shows that, for other than the lowest mode (k = 0), the contributions to the observed relaxation for a given X(Delta) may involve negative as well as positive amplitudes. The experimental measurements are shown to agree with this general conclusion, showing clear evidence of the presence of relaxation modes with negative amplitude at larger values of X(Delta). It is shown that in these, or similar measurements, which provide a spatially-resolved view of surface-mediated relaxation, allowance must be made for fitting with both positive and negative amplitudes.

We present a survey of numerical methods (based on piecewise polynomial approximation) for integral equations of Mellin type, including examples arising in boundary integral methods for partial differential equations on polygonal domains.

Self-diffusion in water, occupying 25% of the pore space within a random packing of 100 μm diameter glass beads, is characterised using pulsed field gradient spin echo (PGSE) NMR to determine the joint probability, P Δ (X, Y) of displacements X and Y in time Δ. It is demonstrated that the detailed features exhibited by the correlation distribution C Δ (X, Y)[=P Δ (X, Y)−P Δ (X)P Δ (Y)] reflect the anisotropic microscopic structures of the water phase despite the overall isotropy of the sample. It is suggested that this will allow detailed structural characterisation of restricting environments, such as porous solids, via the diffusion and flow of contained fluids.

In this paper we describe a fast parallel method for solving highly ill-conditioned saddle-point systems arising from mixed finite element simulations of stochastic partial differential equations (PDEs) modelling flow in heterogeneous media. Each realisation of these stochastic PDEs requires the solution of the linear first-order velocity–pressure system comprising Darcy's law coupled with an incompressibility constraint. The chief difficulty is that the permeability may be highly variable, especially when the statistical model has a large variance and a small correlation length. For reasonable accuracy, the discretisation has to be extremely fine. We solve these problems by first reducing the saddle-point formulation to a symmetric positive definite (SPD) problem using a suitable basis for the space of divergence-free velocities. The reduced problem is solved using parallel conjugate gradients preconditioned with an algebraically determined additive Schwarz domain decomposition preconditioner. The result is a solver which exhibits a good degree of robustness with respect to the mesh size as well as to the variance and to physically relevant values of the correlation length of the underlying permeability field. Numerical experiments exhibit almost optimal levels of parallel efficiency. The domain decomposition solver (DOUG, http://www.maths.bath.ac.uk/~parsoft ) used here not only is applicable to this problem but can be used to solve general unstructured finite element systems on a wide range of parallel architectures.

The low density lipoprotein (LDL) receptor is a transmembrane glycoprotein performing "receptor-mediated endocytosis" of cholesterol-rich lipoproteins. At the N terminus, the LDL receptor has modular cysteine-rich repeats in both the ligand binding domain and the epidermal growth factor (EGF) precursor homology domain. Each repeat contains six disulfide-bonded cysteine residues, and this structural motif has also been found in many other proteins. The bovine LDL receptor has been purified and reconstituted into egg yolk phosphatidylcholine vesicle bilayers. Using gel electrophoresis and cryoelectron microscopy (cryoEM), the ability of the reconstituted LDL receptor to bind its ligand LDL has been demonstrated. After reduction of the disulfide-bonds in the N-terminal domain of the receptor, the reduced LDL receptor was visualized using cryoEM; reduced LDL receptors showed images with a diffuse density region at the distal end of the extracellular domain. Gold labeling of the reduced cysteine residues was achieved with monomaleimido-Nanogold, and the bound Nanogold was visualized in cryoEM images of the reduced, gold-labeled receptor. Multiple gold particles were observed in the diffuse density region at the distal end of the receptor. Thus, the location of the ligand binding domain of the LDL receptor has been determined, and a model is suggested for the arrangement of the seven cysteine-rich repeats of the ligand binding domain and two EGF-like cysteine-rich repeats of the EGF precursor homology domain.

The low density lipoprotein (LDL) receptor is a key protein for maintaining cellular cholesterol homeostasis by binding cholesterol-rich lipoproteins through their apoB and apoE apoproteins. The LDL receptor is a transmembrane glycoprotein of M(r) approximately 115 kDa; based on its primary sequence, five distinct structural domains have been identified (Yamamoto, T., Davis, C. G., Brown, M. S., Schneider, W. J., Casey, M. L., Goldstein, J. L., and Russell, D. W. (1984) Cell 39, 27-38). As a first step toward providing a structural description of the intact LDL receptor, the receptor has been purified from bovine adrenal cortices, reconstituted into unilamellar egg yolk phosphatidylcholine vesicles, and imaged using cryoelectron microscopy (cryoEM). CryoEM has the advantage of providing images of the reconstituted LDL receptor in its frozen, fully hydrated state. LDL receptor molecules were visualized as elongated, stick-like projections from the vesicle surface with maximum dimensions approximately 120-A length by approximately 45-A width. In some of the images, a short arm (or arms) was visible at the distal end of the stick-like projections. The LDL receptor was labeled via accessible free cysteine residues, probably including that corresponding to Cys-431 of the known full-length sequence of the human LDL receptor. The accessible cysteine was demonstrated using a maleimide-biotin.streptavidin conjugate and confirmed by labeling with monomaleimido-Nanogold. Images obtained by cryoEM showed that the extracellular stick-like domain of the reconstituted LDL receptor was labeled by Nanogold. This combined cryoEM-Nanogold labeling study has provided the first low resolution structural images of the reconstituted, full-length bovine LDL receptor.

Medications used to treat cardiovascular diseases such as congestive heart failure, high blood pressure, and arrhythmia, are prescribed extensively in Western countries. However, taste complaints are common side effects of many of these cardiovascular medications. Although clinical observations are helpful in determining potential taste problems from a medication, experimental studies are necessary to obtain quantitative data on taste. In the studies performed here, nine cardiovascular medications (labetalol HCl, captopril, diltiazem HCl, enalapril maleate, hydrochlorothiazide, propranolol HCl, mexiletine HCl, procainamide HCl, and propafenone HCl) were applied to the tongue in human volunteers to measure the direct effect of these drugs on taste receptors. The medications were applied topically to the tongue surface of both young and elderly subjects to mimic the situation in which the drug is secreted into the saliva. Detection thresholds ranged from 0.048 mM (propafenone) to 0.438 mM (procainamide). The detection thresholds of healthy elderly subjects did not significantly differ from young controls. The compounds tested had a predominantly bitter taste with other qualities as well. In addition, topical application of the medications to the tongue affected the taste of one or more taste stimuli, with medications differing in the pattern of taste effects exhibited. The mechanism of taste effects is not fully known, but the results of this study suggest one route may be due to medications' effect on peripheral taste receptors.

Differential scanning calorimetry (DSC) and x-ray diffraction have been used to study the structural and thermal properties of totally synthetic D-erythro-N-palmitoyl-lactosyl-C(18)-sphingosine (C16:0-LacCer). Over the temperature range 0-90 degrees C, fully hydrated C16:0-LacCer shows complex thermal transitions characteristic of polymorphic behavior of exclusively bilayer phases. On heating at 5 degrees C/min, hydrated C16:0-LacCer undergoes a complex two-peak endothermic transition with maxima at 69 degrees C and 74 degrees C and a total enthalpy of 14.6 kcal/mol C16:0-LacCer. At a slower heating rate (1.5 degrees C/min), two endothermic transitions are observed at 66 degrees C and 78 degrees C. After cooling to 0 degrees C, the subsequent heating run shows three overlapping endothermic transitions at 66 degrees C, 69 degrees C, and 71.5 degrees C, followed by a chain-melting endothermic transition at 78 degrees C. Two thermal protocols were used to completely convert C16:0-LacCer to its stable, high melting temperature (78 degrees C) form. As revealed by x-ray diffraction, over the temperature range 20-78 degrees C this stable phase exhibits a bilayer structure, periodicity d approximately 65 A with an ordered chain packing mode. At the phase transition (78 degrees C) chain melting occurs, and C16:0-LacCer converts to a liquid crystalline bilayer (L(alpha)) phase of reduced periodicity d approximately 59 A. On cooling from the L(alpha) phase, C16:0-LacCer converts to metastable bilayer phases undergoing transitions at 66-72 degrees C. These studies allow comparisons to be made with the behavior of the corresponding C16:0-Cer (. J. Lipid Res. 36:1936-1944) and C16:0-GluCer and C16:0-GalCer (. J. Lipid Res. 40:839-849). Our systematic studies are aimed at understanding the role of oligosaccharide complexity in regulating glycosphingolipid structure and properties.

Aged homozygous apolipoprotein E gene-deficient (apoE -/-) mice have been proposed as an experimental model for the role of human apoE isoforms in Alzheimer's disease (AD). However, results from different laboratories have been in conflict regarding the presence or absence of neurodegeneration in these mice. Moreover, despite apoE being the major lipid trafficking molecule in the central nervous system, there has been no investigation of brain lipid levels in apoE -/- mice. Here we have examined male and female apoE -/- and control mice aged 10 to 12 months, testing the hypothesis that lack of apoE leads to some of the neuropathological changes seen in AD. Our results failed to demonstrate significant neurodegeneration, histopathological changes, or reduction in cerebral cortical synaptophysin in apoE -/- mice. However, we did observe a significant reduction in cerebral cortical phospholipids and their constituent fatty acids, as well as elevated lipid peroxidation products, in apoE -/- mice compared to apoE +/+ mice with the same genetic background. Our results suggest that the brains of aged apoE -/- mice display some of the lipid abnormalities associated with AD; however, these changes alone, at the magnitudes achieved in the apoE -/- mice, do not directly lead to the major neurodegenerative changes of AD.

Taste and smell dysfunction has been documented in patients with both acute and chronic liver disease. The purpose of this study was to determine if chemosensory function is improved after restoration of hepatic function with liver transplantation. Nine subjects (seven women and two men) with end-stage liver disease participated in the study. Taste and smell detection and recognition thresholds were determined before and after transplantation. A significant improvement in detection of the taste of sodium chloride and the odor of phenethyl alcohol was found after transplantation. These findings may have clinical significance in food choices and nutritional status of these patients.

We report on a search for the rare decay K_L -> pi^0 nu nubar in the KTeV experiment at Fermilab. We searched for two-photon events whose kinematics were consistent with an isolated pi^0 coming from the decay K_L -> pi^0 nu nubar. One candidate event was observed, which was consistent with the expected level of background. An upper limit on the branching ratio was determined to be B(K_L -> pi^0 nu nubar) < 1.6E-6 at the 90% confidence level.

There is considerable evidence that the anti-rheumatic gold complexes are activated by their conversion to aurocyanide. In order to understand the mechanism of production of aurocyanide, we investigated the involvement of myeloperoxidase in the reaction. This haem enzyme of neutrophils and monocytes uses hydrogen peroxide to oxidise chloride and thiocyanate to hypochlorous acid and hypothiocyanite, respectively. When aurothiomalate (10 μM) was incubated with thiocyanate (200 μM), hydrogen peroxide (100 μM) and myeloperoxidase (20 nM), it was transformed to a product that was spectrally identical to authentic aurocyanide. Aurothiomalate was quantitatively converted to aurocyanide in about 10 min at pH 6.0 and in 40 min at pH 7.4. Aurocyanide formation occurred after myeloperoxidase had used all the hydrogen peroxide available to produce hypothiocyanite. Thus, the cyanide must have formed from the slow decomposition of hypothiocyanite. The rate of aurocyanide production was increased in the presence of 100 mM chloride, which indicates that hypochlorous acid accelerates the formation of cyanide. Hypochlorous acid (100 to 400 μM) reacted non-enzymatically with thiocyanate (200 μM) and aurothiomalate (10 μM) to produce aurocyanide. Thus, aurocyanide is produced by two processes, involving both the formation of hypothiocyanite and hypochlorous acid. Aurocyanide is an effective inhibitor of the respiratory burst of neutrophils and monocytes and the proliferation of lymphocytes. Therefore, aurothiomalate may attenuate inflammation by acting as a pro-drug which is reliant on neutrophils and monocytes to produce hypothiocyanite. When the hypothiocyanite decays to hydrogen cyanide, the pro-drug is converted to aurocyanide which then suppresses further oxidant production by these inflammatory cells.

Dopamine (DA) and related catechols may contribute to selective degeneration of dopaminergic neurons in the substantia nigra in Parkinson's disease. To investigate whether DA induces apoptosis of dopaminergic neurons, we characterized the effects of various concentrations of exogenous DA on a substantia nigra/neuroblastoma hybrid cell line (MES 23.5 or MES). The hybrid MES cells were maintained in the presence of 50 microM glutamate in logarithmic growth on poly-D-lysine-precoated T-75 flasks and plated either onto petri dishes with glass coverslips for morphological studies or onto 6-well plates for quantification of apoptosis by flow cytometry. The results showed that DA exposure (0.5-20 microM) induced time- and dose-dependent apoptotic cell death of MES cells. To further analyze the mechanism responsible for DA-mediated apoptosis, we repeated the experiments at 20 microM DA in the presence or absence of 40 microM nomifensine, a DA re-uptake inhibitor, and 25 microM 2-amino-5-phosphonopentanoic acid (AP5), an N-methyl-D-aspartate (NMDA) receptor antagonist. The data indicate that both compounds significantly prevented DA-induced apoptosis of MES cells and that combination of AP5 and nomifensine provided greater protection against DA toxicity than AP5 alone. These results suggest for the first time that DA-induced apoptosis in dopaminergic neurons is partially attributable to increased vulnerability of these cells to non-toxic levels of excitatory amino acids, i.e., secondary excitotoxicity.

An improved synthesis of (η5-C5Me5)Re(CO)2(H)2 has been devised (yield 88%) via (η5-C5Me5)Re CO)3 and (η5-C5Me5)-Re(CO)2(Br)2. An X-ray crystallographic determination has shown that the hydrido ligands occupy trans positions, in confirmation of IR and NMR measurements. The properties and reactions of trans-(η5-C5Me5)Re(CO)2(H)2 and related compounds (η5-C5Me5)Re-(CO)2(X)(Y) (X  H, Me; Y  H, Me, Cl) are described. The solution photoctemistry of trans-(η5-C5Me5)Re CO2(H)2) in cyclohexane at 298 K and in liquid xenon at 200 K, including studies under D2, indicate that the primary photoproduct is the cis isomer and that trans to cis interconversion, which can be reversed thermally, is an intramolecular process. Photochemical studies of (η5-C5Me5)Re-(CO)2N2) in liquid Xe under H2 and D2 pressures at 200 K gave cis-(η5-C5Me5)Re(CO)2 and cis-(η5-C5Me5)Re(CO)2(D)2, respectively. Matrix isolation studies at about 12 K, including 13CO labelling, confirmed that the photoisomerisation process is an intramolecular process since no ejected CO is observed and no 13CO uptake occurred. subsequent photolysis affords H2 and CO ejection yielding (η5-C5Me5)Re(CO)2 and (η5-C5Me5)Re(CO)(H)2, respectively. In N2 and CO matrices the subsequent photolysis also yielded (η5-C5Me5)Re(CO)2(N2) and (η5-C5Me5)Re(CO)3 but in CH4 matrices there was no evidence of CH photoactivation to yield (η5-C5Me5)Re(CO)2(CH3)(H). Reversals from cis to trans could not be observed for gas matrices but was observed at near ambient temperatures for the cis isomer produced at about 12 K in Nujol mull media.