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Neisseria gonorrhoeae is an urgent threat to public health in the United States and around the world. Many of the current classes of antibiotics to treat N. gonorrhoeae infection are quickly becoming obsolete due to increased rates of resistance. Thus, there is a critical need for alternative antimicrobial targets and new chemical entities. Our team has repurposed the FDA-approved carbonic anhydrase inhibitor scaffold of acetazolamide to target N. gonorrhoeae and the bacteria's essential carbonic anhydrase, NgCA. This study established both structure-activity and structure-property relationships that contribute to both antimicrobial activity and NgCA activity. This ultimately led to molecules 20 and 23, which displayed minimum inhibitory concentration values as low as 0.25 μg/mL equating to an 8- to 16-fold improvement in antigonococcal activity compared to acetazolamide. These analogues were determined to be bacteriostatic against the pathogen and likely on-target against NgCA. Additionally, they did not exhibit any detrimental effects in cellular toxicity assays against both a human endocervical (End1/E6E7) cell line or colorectal adenocarcinoma cell line (Caco-2) at concentrations up to 128 μg/mL. Taken together, this study presents a class of antigonococcal agents with the potential to be advanced for further evaluation in N. gonorrhoeae infection models.

Introduction/Background* According to current guidelines fertility-sparing treatment (FST) in cervical cancer patients should follow the same principles as in patients without fertility preservation. The literature from the last years, however, show a trend towards less-radical procedures. Although oncological outcomes are reported to be equal or better than in non-FST, published groups are small, mostly single institutional, inclusion criteria vary, and treatment is not uniform. The aim of this study was to collect retrospective data from multiple institutions across several countries on oncological and reproductive outcomes after FST. Methodology Included were cervical cancer patients between 18–40 years with stages ≥ IA1+LVSI, who underwent any type of FST and completed follow-up of at least 6 months. Patients were eligible irrespective of neoadjuvant chemotherapy, histotype or tumour grade. Result(s)* Altogether 733 patients from 44 centers in 13 countries were eligible for analyses. Median follow-up of the whole cohort was 6 years (1.2–14.5). More than half of the cases had stage IB1 (54.2%; 397/733). Mean age of patients was 32 years and two thirds were nulliparous (484/733). Most common surgical procedure was conization (48%). Repeated cervical surgery was performed in 161 patients (21.9%), most frequently re-conization (57.8%). Less than half of the patients (49.2%; 361/733) attempted to conceive after treatment. Out of them, 138 (38.2%) got pregnant and 100 (27.7%) successfully delivered. Pre-cancer recurrence was diagnosed in 22 (3%) patients, 51 (7%) patients had cancer recurrence and 19 (2.6%) died of disease. Three times higher risk of recurrence was observed in tumours ≥ 2 cm in comparison to smaller tumours (19.4% vs. 5.7%; p Conclusion* Data from the real life practice showed that FST in cervical cancer patients is safe in patients with HPV related tumours smaller than 2 cm. In such tumours conization represents sufficient procedure with satisfactory pregnancy outcomes. Surprisingly less than half of patients attempt to conceive after treatment.

Neisseria gonorrhoeae is an urgent threat to public health in the United States and around the world. Many of the current classes of antibiotics to treat N. gonorrhoeae infection are quickly becoming obsolete due to increased rates of resistance. Thus, there is a critical need for alternative antimicrobial targets and new chemical entities. Our team has repurposed the FDA-approved carbonic anhydrase inhibitor scaffold of acetazolamide to target N. gonorrhoeae and the bacteria’s essential carbonic anhydrase, NgCA. This study established both structure-activity and structure-property relationships that contribute to both antimicrobial activity and NgCA activity. This ultimately led to molecules 20 and 23, which displayed minimum inhibitory concentration values as low as 0.25 μg/mL equating to an 8- to 16-fold improvement in anti-gonococcal activity compared to acetazolamide. These analogs were determined to be bacteriostatic against the pathogen and likely on-target against NgCA. Additionally, they did not exhibit any detrimental effects in cellular toxicity assays against both a human endocervical (End1/E6E7) cell line or colorectal adenocarcinoma cell line (Caco-2) at concentrations up to 128 μg/mL. Taken together, this study presents a class of anti-gonococcal agents with the potential to be advanced for further evaluation in N. gonorrhoeae infection models.

Environmental disturbances seem to be increasing in frequency and impact, yet we have little understanding of the belowground impacts of these events. Soil fauna, while widely acknowledged to be important drivers of biogeochemical function, soil structure and sustainability, and trophic interactions, are understudied compared to other belowground organisms such as archaea, bacteria, and fungi. In this review we summarize the current state of knowledge of soil fauna as it relates to and is influenced by various disturbances. We focus our review on three main natural and anthropogenic disturbance types: 1) natural disturbances, including damage from wind and flooding; 2) invasive species, including above and belowground flora and fauna; and 3) climate change impacts on the atmosphere and temperature. We do not address the impacts of wildfires, forestry, agricultural practices, mining, or human-caused pollution, as these topics have all been covered in other works. We highlight knowledge gaps and suggest future avenues of research, with hope that the importance of soil fauna and their influences on ecosystems will be given greater emphasis in future research.

Programmable control of the inductive electric field enables advanced operations of reversed-field pinch (RFP) plasmas in the Madison Symmetric Torus (MST) device and further develops the technical basis for ohmically heated fusion RFP plasmas. MST’s poloidal and toroidal magnetic fields (B p and B t) can be sourced by programmable power supplies (PPSs) based on integrated-gate bipolar transistors (IGBT). In order to provide real-time simultaneous control of both B p and B t circuits, a time-independent integrated model is developed. The actuators considered for the control are the B p and B t primary currents produced by the PPSs. The control system goal will be tracking two particular demand quantities that can be measured at the plasma surface (r = a): the plasma current, I p ∼ B p(a), and the RFP reversal parameter, F ∼ B t(a)/Φ, where Φ is the toroidal flux in the plasma. The edge safety factor, q(a) ∝ B t (a), tends to track F but not identically. To understand the responses of I p and F to the actuators and to enable systematic design of control algorithms, dedicated experiments are run in which the actuators are modulated, and a linearized dynamic data-driven model is generated using a system identification method. We perform a series of initial real-time experiments to test the designed feedback controllers and validate the derived model predictions. The feedback controllers show systematic improvements over simpler feedforward controllers.

Osteosarcomas are sarcomas of the bone, derived from osteoblasts or their precursors, with a high propensity to metastasize. Osteosarcoma is associated with massive genomic instability, making it problematic to identify driver genes using human tumors or prototypical mouse models, many of which involve loss of Trp53 function. To identify the genes driving osteosarcoma development and metastasis, we performed a Sleeping Beauty (SB) transposon-based forward genetic screen in mice with and without somatic loss of Trp53. Common insertion site (CIS) analysis of 119 primary tumors and 134 metastatic nodules identified 232 sites associated with osteosarcoma development and 43 sites associated with metastasis, respectively. Analysis of CIS-associated genes identified numerous known and new osteosarcoma-associated genes enriched in the ErbB, PI3K-AKT-mTOR and MAPK signaling pathways. Lastly, we identified several oncogenes involved in axon guidance, including Sema4d and Sema6d, which we functionally validated as oncogenes in human osteosarcoma.

The new Poloidal Field Programmable Power Supply will expand the capabilities of the MST reversed-field pinch experiment. The supply, based on IGBT H-bridges, will generate an arbitrary waveform up to +/− 2700 V at currents up to +/− 85 kA to drive the transformer which produces MST's poloidal field. Additional modules can be added, without other modification, to expand the output current to 115 kA, yielding over 300 MVA.

Confinement in the reversed field pinch (RFP) has been shown to increase strongly with current profile control. The MST RFP can operate in two regimes: the standard regime with a naturally occurring current density profile, robust reconnection and dynamo activity; and the improved confinement regime with strong reduction in reconnection, dynamo and transport. New results in standard plasmas include the observation of a strong two-fluid Hall effect in reconnection and dynamo, the determination that the m = 0 edge resonant mode is nonlinearly driven, and the determination that tearing modes can lock to the wall via eddy currents in the shell. New results in improved confinement plasmas include observations that such plasmas are essentially dynamo-free, contain several isolated magnetic islands (as opposed to a stochastic field) and contain reduced high frequency turbulence. Auxiliary current drive and heating is now critical to RFP research. In MST, a programme to apply auxiliary systems to the RFP is underway and progress has accrued in several techniques, including lower hybrid and electron Bernstein wave injection, ac helicity injection current drive, pellet injection and neutral beam injection.

Energy confinement comparable with tokamak quality is achieved in the Madison Symmetric Torus (MST) reversed field pinch (RFP) at a high beta and low toroidal magnetic field. Magnetic fluctuations normally present in the RFP are reduced via parallel current drive in the outer region of the plasma. In response, the electron temperature nearly triples and beta doubles. The confinement time increases ten-fold (to ~10 ms), which is comparable with L- and H-mode scaling values for a tokamak with the same plasma current, density, heating power, size and shape. Runaway electron confinement is evidenced by a 100-fold increase in hard x-ray bremsstrahlung. Fokker–Planck modelling of the x-ray energy spectrum reveals that the high energy electron diffusion is independent of the parallel velocity, uncharacteristic of magnetic transport and more like that for electrostatic turbulence. The high core electron temperature correlates strongly with a broadband reduction of resonant modes at mid-radius where the stochasticity is normally most intense. To extend profile control and add auxiliary heating, rf current drive and neutral beam heating are in development. Low power lower-hybrid and electron Bernstein wave injection experiments are underway. Dc current sustainment via ac helicity injection (sinusoidal inductive loop voltages) is also being tested. Low power neutral beam injection shows that fast ions are well-confined, even in the presence of relatively large magnetic fluctuations.

Recent technological developments make a laser Thomson scattering diagnostic, operating in the incoherent electron scattering regime, a good candidate to accomplish measurements of fast electron dynamics (i.e., fast equilibrium changes, turbulence, and electron fluctuations) in high temperature plasmas. Pulse repetition rates for current generation Thomson scattering diagnostics have been limited to about 100 Hz, with the possible exception of “burst” modes in which multiple laser systems provide a limited sequence of closely spaced pulses. To overcome this limitation in laser capability, we propose that recent advances in compact, high power, diode-pumped solid state lasers be applied to a fast Thomson scattering diagnostic for fusion research. To illustrate the possibilities, we present an overview of a diagnostic system designed for the Madison Symmetry Torus reversed field pinch. The operational goal for this single-laser system is to measure Te, ne, and pe with a measurement rate of at least 10 kHz...

A pulse-burst laser system has been built for Thomson scattering on NSTX-U, and is currently being integrated into the NSTX-U Thomson scattering diagnostic system. The laser will be operated in three distinct modes. The base mode is continuous 30 Hz rep rate, and is the standard operating mode of the laser. The base mode will be interrupted to produce a "slow burst" (specified 1 kHz rep rate for 50 ms) or a "fast burst" (specified 10 kHz rep rate for 5 ms). The combination of base mode→ interruption→ burst mode is new and has not been implemented on any previous pulse-burst laser system. Laser pulsing is halted for a set period (~ 1 minute) following a burst to allow the YAG rods to cool; this type of operation is called a heat-capacity laser. The laser is Nd:YAG operated at 1064 nm, q-switched to produce ≥ 1.5 J pulses with ~ 20 ns FWHM. It is flashlamp pumped, with dual-rod oscillator (9 mm) and dual-rod amplifier (12 mm). Variable pulsewidth drive of the flashlamps is accomplished by IGBT (insulated gate bipolar transistor) switching of electrolytic capacitor banks. Direct control of the laser Pockels cell drive enables optimal pulse energy extraction. The laser system has demonstrated compliance with all specifications, and is capable of exceeding design specifications by significant margins, e.g., higher rep rates for longer burst periods. Burst operation of this laser system will be used to capture fast time evolution of the electron temperature and density profiles during events such as ELMs, the L-H transition, and various MHD modes.

Mineral inclusions, present in aqueous atmospheric salt droplets, regulate crystallization when relative humidity decreases by providing a surface for heterogeneous nucleation and thus reducing the critical supersaturation. Although laboratory studies have quantified these processes to some extent, the diverse atmospheric mineralogy presents more chemical systems than practically feasible for direct study. Structure--activity relationships are necessary. To that end, in the present work the interactions of ammonium sulfate with corundum, hematite, mullite, rutile, anatase, and baddeleyite were studied by diffuse reflectance fourier transform infrared spectroscopy (DRIFTS) and by epitaxial modeling. The spectroscopic results show that shifts in sulfate peak positions due to chemisorption are not a correlative indicator of the efficacy of heterogeneous nucleation. In contrast, epitaxial modeling results of unreconstructed surfaces explain the sequence of critical supersaturations for constant particle size. If validated by further work, this computer modeling method would provide an important structure--activity tool for the estimation of heterogeneous nucleation properties of the atmospheric mineralogy.

The mechanisms involved in cloud formation affect the resulting cloud radiative properties. Therefore, accurate cloud formation models and related global warming models require freezing data for ammonium sulfate particles, a major constituent of upper tropospheric clouds. Homogeneous ice nucleation in aqueous ammonium sulfate particles has been studied by several laboratory groups; however, there is significant disagreement in the reported data. In the present work, the ice freezing temperatures are measured by sending (NH 4 ) 2 SO 4 particles, generated by vapor condensation, through a temperature-controlled flow cell, where ice formation is detected with infrared spectroscopy. To determine possible explanations for disparate results among several laboratories, the experimental methods used in this study are closely examined. Experiments are performed to preclude artifacts, and experimental conditions are varied to develop a complete understanding of processes involved in particle freezing. All experiments produce consistent results. Mass transfer calculations for the aerosol flow tube technique employed in the current study suggest that one frozen particle in 10 4 to 10 6 may scavenge sufficient water vapor from surrounding supercooled aqueous particles such that a single ice particle accumulates enough mass to yield a positive freezing event in the infrared spectrum. This result appears to partially explain the confusing and conflicting results coming from several laboratories employing different experimental methods to observe homogeneous ice nucleation in ammonium sulfate. Six lower limit J (cm -3 s -1 ) values are determined as 1.1 1 x 10 6 (233 ± 1 K, x=0.013±0.001), 1.1 × 10 6 (231 ± 1 K, x=0.029±0.004), 1.7 × 10 6 (227±1 K, x=0.066±0.015), 2.8 × 10 6 (226±1 K, x=0.071±0.018), 8.4 × 10 6 (224±1 K, x=0.097 ±0.034), and 8.4 x 10 8 (221 ± 1 K, x = 0.153 ±0.076), where the associated temperatures and solute mole fraction aqueous compositions (x) are noted in parentheses.

MS/MS has been used to sequence peptides and small proteins for a number of years. This method allows one to isolate the peptide of interest, which makes it possible to analyze impure samples and unseparated mixtures, such as protein digests. Collision-induced dissociation (CID) of the selected peptide ion generates the product ions that provide sequence information. However, often the MS/MS spectrum does not provide adequate information for complete sequence determination. The quadrupole ion trap has the capability to do multiple stages of mass spectrometry, MSn, which can increase the information available to determine the peptide sequence. A regular and predictable dissociation pattern for peptides further simplifies this analysis. By forming predominantly one type of ion, ambiguity is removed as to whether the ion is N- or C-terminal. This pattern can also be advantageous in that ion intensity remains concentrated for the next stage of MS/MS. In this work, a method to take advantage of the MSn capabilities of the quadrupole ion trap by controlling the dissociation pathways is explored. Dissociation is altered by acetylating the N-terminus of the peptide. MSn of a variety of acetylated peptides is used to determine the effects of the identity of the C-terminal residue and the length of the peptide on the dissociation pathways observed.

One mechanism of cirrus cloud formation is homogeneous ice nucleation within ammoniated sulfuric acid particles. An important constraint on ice formation is the (NH4)2SO4-H2SO4-H2O phase diagram. In the completed laboratory work, the NH4HSO4-H2O phase diagram is determined over the domain relevant to the troposphere. The H2O vapor pressures of aqueous NH4HSO4 solutions are measured from −30 to 25°C, and the compositions of the aqueous phase in equilibrium with a solid phase (i.e., ice or letovicite) are determined at several temperatures. Below 25°C and above 42 wt% NH4HSO4(aq), the first solid to form from supersaturated NH4HSO4(aq) is (NH4)3H(SO4)2(S), not NH4HSO4(s). Supercooling of nearly 20 K is required to initiate letovicite formation for 100 mL samples. The results of this study are in good agreement with the calculations of Clegg et al. [1998].

The far-infrared laser interferometer on the Madison Symmetric Torus has recently been upgraded to allow simultaneous interferometry and polarimetry measurements. Centered around a heterodyne laser system that operates at λ≃432 μm, the diagnostic has a frequency response of 1 kHz for the polarimeter and up to 1 MHz for the interferometer. The distribution of laser power through the 11 chord system is managed with wire mesh beamsplitters. Concurrent with the system upgrade to polarimetry, a detailed study of the effect of the wire mesh beamsplitters on beam polarization was conducted. The study shows that the mesh characteristics must be included to extract the polarimetry phase measurement from the raw data. The modifications to the data analysis as well as preliminary five chord polarimetry profile data are presented.

Growth under elevated [CO 2 ] promoted spring frost damage in field grown seedlings of snow gum (Eucalyptus pauciflora Sieb. ex Spreng.), one of the most frost tolerant of eucalypts. Freezing began in the leaf midvein, consistent with it being a major site of frost damage under field conditions. The average ice nucleation temperature was higher in leaves grown under elevated [CO 2 ] (- 5.7 °C versus - 4.3 °C), consistent with the greater incidence of frost damage in these leaves (34% versus 68% of leaves damaged). These results have major implications for agriculture, forestry and vegetation dynamics, as an increase in frost susceptibility may reduce potential gains in productivity from CO 2 fertilization and may affect predictions of vegetation change based on increasing temperature.

The protein catabolic state of cirrhosis is associated with severe growth hormone (GH) resistance, with low levels of insulin-like growth factor (IGF)-I and its major binding protein (IGFBP)-3. The aim of this study was to conduct a randomized, double-blind, placebo-controlled pilot study of GH therapy in 20 cirrhotic patients to assess the reversibility of GH resistance and subsequent impact on protein economy and safety.Patients were treated with GH (0.25 IU/kg body wt) or placebo for 7 days. Serum levels of GH, IGF-I, IGFBP-3, and insulin were measured by radioimmunoassay and 24-hour urinary nitrogen by the Kjeldahl technique.IGF-I levels increased only in the GH-treated group (mean, 69.2 +/- SE 7.0 to 170.6 +/- 48.8 ng/mL; P0.05) together with IGFBP-3 (1.65 +/- 0.3 to 2.94 +/- 0.6 mg/L; P0.005). Cumulative nitrogen balance similarly improved only in the GH group (2.87-24.16 g; P0.05). No significant side effects of GH were observed.GH therapy can overcome the GH resistance of cirrhosis. The resulting improvement in nitrogen economy and possible influences on clinical outcomes will need to be confirmed in controlled studies of longer duration.

The Thomson scattering diagnostic on MST records both equilibrium and fluctuating electron temperature with a range capability of 10 eV-5 keV. Standard operation with two modified commercial Nd:YAG lasers allows measurements at rates of 1 kHz-25 kHz. Several subsystems of the diagnostic are being improved. The power supplies for the avalanche photodiode detectors (APDs) that record the scattered light are being replaced to improve usability, reliability, and maintainability. Each of the 144 APDs will have an individual rack mounted switching supply, with bias voltage adjustable to match the APD. Long-wavelength filters (1140 nm center, 80 nm bandwidth) have been added to the polychromators to improve capability to resolve non-Maxwellian distributions and to enable directed electron flow measurements. A supercontinuum (SC) pulsed white light source has replaced the tungsten halogen lamp previously used for spectral calibration of the polychromators. The SC source combines substantial brightness produced in nanosecond pulses with a spectrum that covers the entire range of the polychromators.

Physical Science Laboratory’s new generation of spherical grating monochromators incorporates a laser interferometer to control scan angle and an in-vacuum absolute angle reference, as well as other improvements. The design accommodates up to six gratings which can be moved axially (under motor control, with encoder position readback) at any scan angle. The gratings are cooled by means of spring-loaded clamps which conduct heat to a water-cooled plate. The instruments feature hollow roller bearings on the scan axis to minimize bearing runout, and a pseudosine-bar drive for precise control of grating angle. The interferometer angle-measuring optics are mounted inside the vacuum chamber and measure the angle between the grating scan axis and the instrument’s granite base. The laser interferometer measures the grating angle with a resolution of approximately 0.02 arcsec over the entire scan range of 40°. To provide a reference for the interferometer angle measurement, we have built an in-vacuum optical refer...

Pore size distribution and the interconnectivity of cement paste pores have a strong influence on permeability. A computer network model has been developed to simulate flow through the pore microstructure cement paste. Network models have been successfully applied to predicting permeabilities of geological materials including rocks and soils but have not been specifically developed in the area of cement and concrete. The network model presented in this paper is used to obtain further insight into how pore size distributions of cement paste microstructures influences permeability. The model accounts for variations in pore microstructure by using a two-dimensional network of tubes with different log-normal size distributions.

Two types of fast bolometers are described for the plasma energy transport study in the Madison symmetric torus plasma confinement device. Both types use pyrocrystals of LiTaO3 or LiNbO3 as the sensors. One type is used for measurements of the radiated heat losses and is situated at the vacuum shell inner surface. Another type is insertable in the plasma and measures the plasma particle heat flux. The frequency response of the bolometers is measured to be in the 150–200 kHz range. The range of the measured power fluxes is 0.1 W/cm2–10 kW/cm2 and can be adjusted by changing the size of the entrance aperture. The lower limit is determined by the amplifier noise and the frequency bandwidth, the higher limit by destruction of the bolometer sensor.

One may view dry eye conditions as a group of diseases in which the ocular surface is adversely affected. Tear film instability invariably leads to some degree of cellular surface damage over the cornea and conjunctiva. In turn, ocular epitheliopathy may adversely affect tear film stability. The clinical presentation of the disease may not yield a clue as to its etiology. In recent years considerable progress was made both in the diagnosis and the treatment of the disease and promising studies are planned or are underway. The diagnostic techniques can be divided into four groups. The first is concerned with the clinical presentation. The second is concerned with the bulk properties of the aqueous tears including dynamic characteristics, composition, and colligative properties. The third is tear-film related and includes the film break-up time, evaporation rate, and lipid abnormality. The fourth is concerned with the ocular surface and includes vital staining, impression cytology, and surface microscopy. The most promising attempts are being made in the second group by attempting to elucidate the role of enzyme and enzyme activator activity and inhibitor contents as well as the tear protein profiles and correlating them with the specific disease states. The treatment modalities belong to three major groups aside from surgical intervention; the supplementation, preservation, and the stimulation of tears. The modern version of tear supplementation is expected to include the topical use of efficacious aqueous formulations that typically contain film stabilizing polymers, nutrients, and/or--in the future--biochemically active ingredients such as enzyme activators and inhibitors.

Water plays an important role in life processes, although the specifics are not always known. In the past 25 years, major progress has been made in vision science by applying the principles and techniques of interface science to tear film physiology and pathophysiology, to novel surgical techniques, and to contact lens wear. In this paper, the role and structure of the preocular tear film are discussed, as well as the factors affecting its stability. This double-layered fluid film plays an important role not only in vision and the health of the exposed ocular tissues, but also in deciding contact lens tolerance and functioning. The little-known, misunderstood, and often misdiagnosed dry eye syndrome that is effected by the compromised stability of the tear film is also discussed. A newly recognized role of water as a bioabhesive in ocular tissue adhesion and its failure in terms of disjoining pressure and weak boundary layer are examined in the vision-threatening and painful adhesion failure of corneal ep...

Ion temperatures have been measured in the Madison Symmetric Torus (MST) [Dexter et al., Fusion Technol. 19, 131 (1991)] reversed‐field pinch (RFP) with a five channel charge exchange analyzer. The characteristic anomalously high ion temperature of RFP discharges has been observed in the MST. The ion heating expected from ion–electron collisions is calculated and shown to be too small to explain the measured ion temperatures. The charge exchange determined ion temperature is also compared to measurements of the thermally broadened Cv 227.1 nm line. The ion temperature, Ti≊250 eV for I=360 kA, increases by more than 100% during discrete dynamo bursts in MST discharges. Magnetic field fluctuations in the range 0.5–5 MHz were also measured during the dynamo bursts. Structure in the fluctuation frequency spectrum at the ion cyclotron frequency suggests that the mechanism of ion heating involves the dissipation of dynamo fluctuations at ion cyclotron frequencies.

Slip casting and filter pressing are ceramic forming processes which can be affected by the migration of fine particles during filtration. Fine particles can be carried along with the filtrate and deposited within the ceramic compact and /or filter medium, thereby clogging and reducing the permeabilities of the porous media. This in turn affects the growth rate as well as the porosity of the compact. Evidence of clogging of the ceramic compact and filter medium was obtained by (1) SEM analysis of the compact and filter media, (2) surface area measurements of cross sections of compacts, and (3) measurements of the thickness of compacts as a function of casting time.

Plasminogen activator (uPA) activities were determined in the tears of rabbits following mechanical (scraping) or chemical (n-heptanol) debridement and alkali burn of the central part of the corneal epithelium. All three types of injury enhanced the plasminogen activator activities in the tears. The increase in uPA activity was highest in alkali burn, lowest for n-heptanol debridement. Scraping yielded an intermediate increase in uPA activity. The maximum value in activator activity was reached at 5 hours for mechanical injury and at 24 hours for chemical injuries. uPA activity values returned to the normal range by the time of re-epithelialization for mechanical scraping and 1-3 days following re-epithelialization for heptanol debridement and alkali burn. A trend was observed between uPA activity level and the size of the wound but the correlation was not pronounced (R = 0.538).

Results obtained on the Madison Symmetric Torus (MST) reversed‐field pinch [Fusion Technol. 19, 131 (1991)] after installation of the design poloidal field winding are presented. Values of βθe0≡2μ0ne0Te0/B2θ(a)∼12% are achieved in low‐current (I=220 kA) operation; here, ne0 and Te0 are central electron density and temperature, and Bθ(a) is the poloidal magnetic field at the plasma edge. An observed decrease in βθe0 with increasing plasma current may be due to inadequate fueling, enhanced wall interaction, and the growth of a radial field error at the vertical cut in the shell at high current. Energy confinement time varies little with plasma current, lying in the range of 0.5–1.0 msec. Strong discrete dynamo activity is present, characterized by the coupling of m=1, n=5–7 modes leading to an m=0, n=0 crash (m and n are poloidal and toroidal mode numbers). The m=0 crash generates toroidal flux and produces a small (2.5%) increase in plasma current.

" N-EYE wettability is one of the key factors that determines the clinical success of any contact lens. However, when compared with lens design and oxygen permeability, wettability remains somewhat of a 'Cinderalla' property, principally because of the lack of available in vivo measurement techniques and difficulty of interpreting the results. It is important for a contact lens to remain wetted, i.e., to retain a coherent tear film over its surface, in order to provide an optically smooth surface and thereby maintain visual acuity. Additionally, the tears act as a lubricating layer between the lens and the eyelids and so contribute to ocular comfort. More controversially, the film may be said to lower the tendency for lens spoilation by maintaining the lenstear interface in a hydrophilic state. In this state, the lens presents a less favourable interface for adsorption of hydrophobic components, such as the ocular lipids. The latter point is supported by the concept of contact angle hysteresis, in which the surfaces of hydrogel materials appear to be more hydrophilic in aqueous than in non-aqueous environments. ~ The presence of a contact lens within the eye will undoubtedly compromise the ability of the tears to maintain a coherent film over the ocular surface. It is, therefore, necessary to determine the stability of the tear film in subjects prior to lens fitting in order to assess their likely suitability for lens wear. This is normally achieved by measuring the tear film breakup time (BUT). BUT has traditionally been measured by staining the tears with fluorescein and visualising the dyed film with cobalt blue light. The dye is usually applied by placing a drop of saline onto a fluorescein-impregnated paper strip, removing any excess liquid, and gently touching the conjunctival surface with the resultant drop of fluorescein solution. Alternatively, a drop of 1 or 2% fluorescein solution can be placed directly into the lower fornix. Both techniques are invasive. In the former, the paper strip often makes contact with the ocular surface and may cause a degree of reflex tearing. While in the latter, the 7~1 volume of native tear fluid is swamped with 20-30~1 of fiuorescein solution. Both the fluorescein solution

The multipoint Thomson scattering diagnostic on the Madison Symmetric Torus (MST) is now fully operational with 21 spatial points, which cover the entire minor radius. Four full electron temperature profiles can be obtained during each MST discharge, with a variable delay between each profile. This system overcomes challenges that arise from the unique machine design, location, and plasma characteristics of MST. The machine design limits the maximum porthole diameter to 11.4 cm, requiring a compact, re-entrant, seven element lens for scattered light collection. Limited space near MST necessitates a long beam path for the two Nd:YAG lasers requiring a remote beam line adjustment system to suppress drift in the beam position due to thermal expansion of the building. Due to the remote location of the laser head, substantial design effort was put into the creation of a set of safety interlocks for the laser system. The dynamic nature of MST plasmas and the wide range of operating space require a versatile scattered light detection system consisting of filter polychromators with temperature controlled avalanche photodiode detectors. We also implement an insertable integrating sphere, which travels along the laser beam path through the vacuum vessel, for the alignment of both the fiber optics and the lasers.

A new custom-built duo spectrometer has been commissioned for fast localized Doppler measurements of plasma ions in the Madison Symmetric Torus. The instrument combines very high optical throughput (transmission efficiency of 6% and etendue of 0.80 mm(2) sr divided into two simultaneous measurements) with good resolution (lambda/Deltalambda=5600). The design is a double grating variant of the Czerny-Turner layout and has been carefully optimized for fast (100 kHz) measurements of the C VI line at 343.4 nm. The instrument is currently being applied for high speed charge exchange recombination spectroscopy measurements.

In the general area of confinement improvement and concept advancement, recent results in the Madison Symmetric Torus (MST) reversed-field pinch (RFP) include good confinement of both thermal and large-orbit ions and near doubling of total beta to 26% with deuterium pellet injection. Current profile control enables MST to reduce stochastic transport and achieve tokamak-like confinement. In standard RFP operation, substantial MHD tearing mode activity results in stochastic transport and an energy confinement time of about 1 ms in MST. Application of inductive current profile control reduces MHD activity and accompanying stochasticity, improving confinement by about a factor of ten. Previous work concentrated on electron confinement in improved-confinement RFP operation. Recent work confirms that ions are also well confined, and that high beta and improved confinement can be achieved simultaneously. PACS numbers: 52.55.Hc, 52.55.Dy (Some figures in this article are in colour only in the electronic version)

To aid in diagnosis of 3D equilibria in the Madison Symmetric Torus, it has become necessary to control the orientation of the equilibria. In reversed field pinch experiments a transition to a 3D equilibrium is common with sufficiently large plasma current (and Lundquist number). Diagnosis of this state is hampered by the fact that the helical structure is stationary but with an orientation that varies shot-to-shot. A resonant magnetic perturbation (RMP) technique has been developed to vary controllably the orientation of the 3D equilibria and optimized to minimize the plasma wall interaction due to its use. Application of an RMP now allows alignment of the structure with key diagnostics, including Thomson scattering and an interferometer-polarimeter.

The SUMOylation pathway modulates the activity of many cellular proteins and plays an important role in cellular stress protection. We identified the SUMO E2 ligase Ubc9 to be critical for KRAS-driven transformation in colorectal cancer cells. Ubc9 knockdown severely impairs clonogenic and anchorage-independent growth of KRAS mutant cells in vitro and attenuates tumor growth in xenograft models. Ubc9 mutant studies indicate that Ubc9 enzymatic activity is required for KRAS-driven transformation, thus Ubc9 inhibitor could be potentially useful in this setting. SILAC mass-spectrometry reveals that the SUMOylation of multiple proteins are elevated in KRAS mutant cells. Over-expression of some of these SUMO target proteins partially rescued transformation growth of KRAS mutant cells upon Ubc9 depletion. Our findings suggest a model where the SUMO pathway is required for relieving the oncogenic stress associated with KRAS transformation to maintain cell viability. Citation Format: Bing Yu, Steve Swatkoski, Alesia Holly, Liam Changwoo Lee, Valentin Giroux, Chih-Shia Lee, Joseph Carver, Chad Creighton, David K. Ann, William Douglas Figg, Marjan Gucek, Ji Luo. A critical role of the SUMO pathway in KRAS-driven oncogenesis. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B29. doi: 10.1158/1557-3125.RASONC14-B29

We have constructed a simple, low-cost charge-coupled device (CCD) spectrometer capable of both high resolution (Δλ⩽0.015 nm) and large bandpass (110 nm with Δλ∼0.3 nm). These two modes of operation provide two broad areas of capability for plasma spectroscopy. The first major application is measurement of emission line broadening; the second is emission line surveys from the ultraviolet to the near infrared. Measurements have been made on a low-temperature plasma produced by a miniature electrostatic plasma source and the high-temperature plasma in the Madison Symmetric Torus reversed-field pinch. The spectrometer is a modified Jarrell–Ash 0.5 m Ebert–Fastie monochromator. Light is coupled into the entrance slit with a fused silica fiber optic bundle. The exposure time (2 ms minimum) is controlled by a fast electro-mechanical shutter. The exit plane detector is a compact and robust CCD detector developed for amateur astronomy by Santa Barbara Instrument Group. The CCD detector is controlled and read out ...