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Very-high Energy (VHE) gamma-ray astroparticle physics is a relatively young field, and observations over the past decade have surprisingly revealed almost two hundred VHE emitters which appear to act as cosmic particle accelerators. These sources are an important component of the Universe, influencing the evolution of stars and galaxies. At the same time, they also act as a probe of physics in the most extreme environments known - such as in supernova explosions, and around or after the merging of black holes and neutron stars. However, the existing experiments have provided exciting glimpses, but often falling short of supplying the full answer. A deeper understanding of the TeV sky requires a significant improvement in sensitivity at TeV energies, a wider energy coverage from tens of GeV to hundreds of TeV and a much better angular and energy resolution with respect to the currently running facilities. The next generation gamma-ray observatory, the Cherenkov Telescope Array Observatory (CTAO), is the answer to this need. In this talk I will present this upcoming observatory from its design to the construction, and its potential science exploitation. CTAO will allow the entire astronomical community to explore a new discovery space that will likely lead to paradigm-changing breakthroughs. In particular, CTA has an unprecedented sensitivity to short (sub-minute) timescale phenomena, placing it as a key instrument in the future of multi-messenger and multi-wavelength time domain astronomy. I will conclude the talk presenting the first scientific results obtained by the LST-1, the prototype of one CTAO telescope type - the Large-Sized Telescope, that is currently under commission., PoS: Proceedings of Science, 395, ISSN:1824-8039, Proceedings of 37th International Cosmic Ray Conference (ICRC2021)

More efficient agricultural water use sounds uncontroversial. Due to increased agricultural efficiency, about 300,000 acre-feet1 of water per year is made available and is being reallocated from the Imperial Irrigation District to Los Angeles, San Diego and Coachella. This increase in efficiency and transfer of conserved water, however, is predicted to cause a suite of environmental and public health harms as the region’s agricultural sump (the Salton Sea) shrinks. Southern Californian water politics are famously messy, contentious and high stakes. The State struggles with the need to increase its use efficiency and decrease its overall use of its allocation of Colorado River water that supplies Californian south coast cities and inland agriculture. Local, State and federal parties involved in these water allocation decisions conflict over how to mitigate the externalities as there is no clear assignment of liabilities. This case study uses historical documents and recent policy elite interviews to construct a broad understanding of the nature of the dilemma. By engaging with this case, readers will better understand the relative positions of the rural water supplier and the urban water users in the largest water transfer in US history, and understand that increasing use efficiency in one arena—agriculture—does not always work out best for the environment.

We present the first observation by the Telescope Array Surface Detector (TASD) of the effect of thunderstorms on the development of cosmic ray single count rate intensity over a 700 km$^{2}$ area. Observations of variations in the secondary low-energy cosmic ray counting rate, using the TASD, allow us to study the electric field inside thunderstorms, on a large scale, as it progresses on top of the 700 km$^{2}$ detector, without dealing with the limitation of narrow exposure in time and space using balloons and aircraft detectors. In this work, variations in the cosmic ray intensity (single count rate) using the TASD, were studied and found to be on average at the $\sim(0.5-1)\%$ and up to 2\% level. These observations were found to be both in excess and in deficit. They were also found to be correlated with lightning in addition to thunderstorms. These variations lasted for tens of minutes; their footprint on the ground ranged from 6 to 24 km in diameter and moved in the same direction as the thunderstorm. With the use of simple electric field models inside the cloud and between cloud to ground, the observed variations in the cosmic ray single count rate were recreated using CORSIKA simulations. Depending on the electric field model used and the direction of the electric field in that model, the electric field magnitude that reproduces the observed low-energy cosmic ray single count rate variations was found to be approximately between 0.2-0.4 GV. This in turn allows us to get a reasonable insight on the electric field and its effect on cosmic ray air showers inside thunderstorms.

In federations such as the United States, governments at various levels are experimenting with new watershed governance arrangements to protect water quality for both ecosystem health and human consumption. Such arrangements may bring previously uncooperative governments together to credibly commit to resource protection under the auspices of new and intricate formal institutions. Given the risks of cooperation, theory indicates that a robust arrangement will contain means of holding governing actors accountable to each other. This paper examines a purportedly successful case, the New York City watershed governance arrangement, to identify how safeguards against intergovernmental opportunism promote lasting cooperation. Using the qualitative method of process tracing, this paper finds that the New York City watershed governance arrangement uses structural, judicial, and popular safeguards against opportunistic behaviors by governing actors that might threaten the resource or the arrangement. The results indicate that such safeguards are present and interact with other safeguards and rule institutions at the state and federal level to maintain compliance.

In 1997, an unlikely group of governments, nonprofit organizations, and interest groups signed a Memorandum of Agreement (MOA) to share governance of the adjacent Catskill and Delaware watersheds i...

In 1997, New York City and a group of smaller municipalities in the Catskills region of New York came to agree upon a novel and complex means of protecting water quality in the City's upstate reservoirs. The Memorandum of Agreement they authored tied previously uncooperating governments to a new shared goal: preserve the ecological integrity of the Catskill and Delaware watersheds so that the City could avoid chemically filtering its municipal water. The agreement represents a policy experiment in reaction to a stark choice. The U.S. Environmental Protection Agency's 1986 Surface Water Treatment Rule mandated that the City either filter its surface water supply or maintain a watershed control program to ensure the long-term protection of water quality in its source watersheds. The City decided to pursue a watershed control program in lieu of the more expensive filtration. The choice has led to a governing arrangement that has theoretical implications for how to simultaneously secure ecosystem services, promote rural livelihoods, and produce the critical public good of potable water to millions of people. The policy solution displays how cooperative institutions may provide low-cost and low-tech solutions to environmental dilemmas to protect ecosystem services. However, over time, governing entities have faced challenges that raise questions about the durability of the arrangement. This case study explores those challenges to better elucidate the possibilities and pitfalls of watershed governance to secure ecosystem services.

Monitoring and enforcement have been recognized as keys for sustainable common pool resource governance. With a couple of notable exceptions, however, scholars have not examined how they are deployed when governments are the primary actors devising such agreements and where multiple public goods are provided for – an important level of governance to understand. We explore the design of monitoring and enforcement safeguards that governments adopt to limit opportunism and support compliance in a complex governing arrangement, the New York City Watersheds Memorandum of Agreement. The agreement defines how New York City and a group of watershed jurisdictions jointly manage a shared natural resource. Furthermore, we test how the design of such safeguards vary depending on the type of public good they cover, illuminating how “federal” safeguards may work at the sub-state level, and, ultimately, the particular form of polycentric governance being used. The results indicate that concerns for water quality as well as potential for opportunistic behavior drive institutional design considerations. Monitoring and sanctioning authority for water quality is dominated by state and federal actors, which hold New York City to account, while watershed jurisdictions are held responsible by regional actors for administration of economic development goods.

Evidence for a large-scale supergalactic cosmic-ray multiplet (arrival directions correlated with energy) structure is reported for ultra-high-energy cosmic-ray (UHECR) energies above 1019 eV using 7 years of data from the Telescope Array (TA) surface detector and updated to 10 years. Previous energy–position correlation studies have made assumptions regarding magnetic field shapes and strength, and UHECR composition. Here the assumption tested is that, because the supergalactic plane is a fit to the average matter density of the local large-scale structure, UHECR sources and intervening extragalactic magnetic fields are correlated with this plane. This supergalactic deflection hypothesis is tested by the entire field-of-view (FOV) behavior of the strength of intermediate-scale energy–angle correlations. These multiplets are measured in spherical cap section bins (wedges) of the FOV to account for coherent and random magnetic fields. The structure found is consistent with supergalactic deflection, the previously published energy spectrum anisotropy results of the TA (the Hotspot and Coldspot), and toy-model simulations of a supergalactic magnetic sheet. The seven year data posttrial significance of this supergalactic structure of multiplets appearing by chance, on an isotropic sky, is found by Monte Carlo simulation to be 4.2σ. The 10 years of data posttrial significance is 4.1σ. Furthermore, the starburst galaxy M82 is shown to be a possible source of the TA Hotspot, and an estimate of the supergalactic magnetic field using UHECR measurements is presented.

Retained fetal membranes (RFM) is a common post-partum problem in mares for which the treatment is highly variable. The aim of this study was (i) to investigate the different treatments used by equine practitioners for RFM and (ii) to determine if there is a difference between treatments used by reproductive specialists and general equine practitioners. Information regarding treatment of RFM was sought from veterinary practitioners via a survey and this was compared to recommendations in the current literature. The survey was sent out to equine veterinarians and mixed practitioners with a high equine case load. Most treatments of RFM were in line with current recommendations, while some obsolete practices are still routinely performed by a small number of practitioners. Treatment recommendations for RFM have changed over the last few decades, but there are no universally accepted guidelines. The vast variety of treatments reported by practitioners in the present survey reflect this lack of guidance. More extensive research is needed in this area to establish evidence-based, uniformly agreed upon protocols.

On 9 January 2014 (Day 0) a mare from a stud farm in the Waikato region presented with urinary incontinence without pyrexia. Over the following 33 days 15 mares were clinically affected with neurological signs. All but one mare had a foal at foot. The most commonly observed clinical signs were hind limb paresis and ataxia. In some cases recumbency occurred very early in the course of disease and seven mares were subject to euthanasia for humane reasons.Equid herpesvirus (EHV) type 1 was detected using PCR in various tissues collected post mortem from two mares with neurological signs. DNA sequencing data from the DNA polymerase gene of the virus showed a nucleotide transition at position 2254, a mutation encoding amino acid D752 that is highly associated with the neuropathogenic genotype of EHV-1. In total 12/15 mares were confirmed positive for EHV-1 on PCR. Results from a virus neutralisation test and ELISA on paired serum samples, and PCR on whole blood and nasal swabs, indicated that of four paddocks in a high-risk area where a cluster of cases had occurred, 20/21 (95%) horses were likely to have been exposed or were confirmed infected with EHV-1. Subsequent to the outbreak two mares aborted, one at 9 months and one at 10 months of gestation. The cause of abortion was confirmed as EHV-1 with the same genotype as that involved in the outbreak.Equine herpesvirus myeloencephalopathy.The outbreak described shows the considerable impact that can occur in outbreaks of equine herpesvirus myeloencephalopathy in New Zealand. Early biosecurity controls not only reduced the effect on the farm but mitigated the potential for the virus to spread to other horse enterprises.

The Telescope Array experiment studies ultra high energy cosmic rays using a hybrid detector. Fluorescence telescopes measure the longitudinal development of the extensive air shower generated when a primary cosmic ray particle interacts with the atmosphere. Meanwhile, scintillator detectors measure the lateral distribution of secondary shower particles that hit the ground. The Middle Drum (MD) fluorescence telescope station consists of 14 telescopes from the High Resolution Fly’s Eye (HiRes) experiment, providing a direct link back to the HiRes measurements. Using the scintillator detector data in conjunction with the telescope data improves the geometrical reconstruction of the showers significantly, and hence, provides a more accurate reconstruction of the energy of the primary particle. The Middle Drum hybrid spectrum is presented and compared to that measured by the Middle Drum station in monocular mode. Further, the hybrid data establishes a link between the Middle Drum data and the surface array. A comparison between the Middle Drum hybrid energy spectrum and scintillator Surface Detector (SD) spectrum is also shown.

Proteus mirabilis is a common cause of catheter-associated urinary tract infections and frequently leads to blockage of catheters due to crystalline biofilm formation. Scanning electron microscopy (SEM) has proven to be a valuable tool in the study of these unusual biofilms, but entails laborious sample preparation that can introduce artefacts, undermining the investigation of biofilm development. In contrast, environmental scanning electron microscopy (ESEM) permits imaging of unprocessed, fully hydrated samples, which may provide much insight into the development of P. mirabilis biofilms. Here, we evaluate the utility of ESEM for the study of P. mirabilis crystalline biofilms in situ, on urinary catheters. In doing so, we compare this to commonly used conventional SEM approaches for sample preparation and imaging. Overall, ESEM provided excellent resolution of biofilms formed on urinary catheters and revealed structures not observed in standard SEM imaging or previously described in other studies of these biofilms. In addition, we show that energy-dispersive X-ray spectroscopy (EDS) may be employed in conjunction with ESEM to provide information regarding the elemental composition of crystalline structures and demonstrate the potential for ESEM in combination with EDS to constitute a useful tool in exploring the mechanisms underpinning crystalline biofilm formation.

We study the anisotropy of Ultra-High Energy Cosmic Ray (UHECR) events collected by the Telescope Array (TA) detector in the first 40 months of operation. Following earlier studies, we examine event sets with energy thresholds of 10 EeV, 40 EeV, and 57 EeV. We find that the distributions of the events in right ascension and declination are compatible with an isotropic distribution in all three sets. We then compare with previously reported clustering of the UHECR events at small angular scales. No significant clustering is found in the TA data. We then check the events with E>57 EeV for correlations with nearby active galactic nuclei. No significant correlation is found. Finally, we examine all three sets for correlations with the large-scale structure of the Universe. We find that the two higher-energy sets are compatible with both an isotropic distribution and the hypothesis that UHECR sources follow the matter distribution of the Universe (the LSS hypothesis), while the event set with E>10 EeV is compatible with isotropy and is not compatible with the LSS hypothesis at 95% CL unless large deflection angles are also assumed. We show that accounting for UHECR deflections in a realistic model of the Galactic magnetic field can make this set compatible with the LSS hypothesis., 10 pages, 9 figures

The significance of infection with Equid herpesvirus 2 (EHV-2) remains unresolved, mainly due to its widespread distribution, and frequent isolation of the virus not only from diseased animals, but also from clinically normal horses. It has been suggested that EHV-2 exerts its effects on the host indirectly, through predisposition to secondary infections. The aim of this study was to determine kinetics of EHV-2 infection among foals and to investigate the role that EHV-2 may play in development of Rhodococcus equi pneumonia on one farm. Serial blood samples were collected from 43 foals over a period of 10 months. Viral load of EHV-2 in blood was determined using quantitative realtime PCR assay. All but 2 foals were positive for EHV-2 on at least one occasion. The majority (88%) of foals became infected with EHV-2 within the first 2 months of life. Once infected, most foals (86%) remained positive for EHV-2 on all subsequent samplings. The load of EHV-2 varied between individual foals and between different sampling times for each foal. There was a significant difference in EHV-2 load between samples collected from healthy foals and foals suspected of R. equi pneumonia only for 2-month-old foals, but not for foals of other ages. The results of this study extend our knowledge of EHV-2 epidemiology among foals.

Despite the high prevalence of primary uterine inertia in whelping bitches, the underlying pathogenesis remains unclear. The objectives were to i) determine serum concentrations of total calcium, ionized calcium (iCa), parathyroid hormone (PTH), and blood pH in normally whelping bitches throughout the peri-parturient period; and ii) investigate relationships among iCa, PTH, and acid-base status, and the role that they and oxytocin may have in the underlying pathogenesis of canine uterine inertia. Bitches were randomly selected from a population of German Shepherd Dog bitches with a history of uncomplicated parturition (Group 1; n=10), and from a population of Labrador bitches with a clinical history of an increased incidence of uterine inertia and stillbirths (Group 2; n=20). Jugular blood samples were collected daily from -4 d to the onset of whelping (t=0 h), and then every 4h until the last pup was born. Overall, bitches from Group 2 had higher mean+/-SEM serum concentrations of PTH (4.72+/-2.45 pmol/L, P

Bacteriophages were first used successfully to treat bacterial infections a decade before penicillin was discovered. However, the excitement that greeted those initial successes was short-lived, as a lack of understanding of basic phage biology subsequently led to a catalogue of clinical failures. As a consequence, bacteriophage therapy was largely abandoned in the West in favour of the newly emerging antibiotics. Now, as the problem of antibiotic resistance becomes ever more acute, a number of scientists and clinicians are looking again at bacteriophages as a therapeutic option in the treatment of bacterial infections. The chances of success second time round would appear to be much better given our current extensive knowledge of bacteriophage biology following their important role in underpinning the advances in molecular biology. We also have available to us the experience of nearly 80 years of clinical usage in the countries of the former Soviet Union and Eastern Europe as well as a political climate that encourages sharing of that knowledge. This review outlines those features of bacteriophages that contribute to their utility in therapy and explores the potential for their re-introduction into Western medicine. An abundance of clinical evidence is available in the Soviet literature but much of this is technically flawed and a more realistic appraisal of the clinical value of phages can be obtained from animal studies conducted in the West. As interest in bacteriophages increases, a number of companies throughout the world have begun investing in phage technology and this has led to novel approaches to therapy, some of which will be discussed.

BACKGROUND. The aim of this study was to examine p16INK4a protein expression in ThinPrep (Cytyc Corporation, Marlborough, Mass) cervical specimens by using the CINtec p16INK4a Cytology Kit (Dako, Glostrup, Denmark). The ability of this assay to accurately identify underlying high-grade lesions was assessed by using follow-up biopsies and comparing these results with Hybrid Capture 2 (Digene, Gaithersburg, Md) high-risk HPV (hc2) results. METHODS. Three hundred ninety-eight residual ThinPrep samples were collected, and histological follow-up data were retrieved for abnormal cytology specimens. After preparation of a Papanicolaou-stained slide, a second slide was processed in preparation for p16INK4a immunostaining. High-risk human papillomavirus testing (hc2) was also performed. RESULTS. Of the 163 cytologically abnormal samples, 6-month biopsy follow-up data were available for 45% of the specimens. At initial blinded evaluation, 21 of the 26 cases with cervical intraepithelial neoplasia (CIN) II/III follow-up were positive for p16INK4a, yielding an overall diagnostic sensitivity of 81%; 29 of the 47 cases diagnosed as CIN I or less were p16INK4a negative, yielding a diagnostic specificity of 62%. In comparison, the hc2 test results indicated a diagnostic sensitivity of 100% with a diagnostic specificity of 15%. After review of selected cases with CIN II/III follow-up, 25 of 26 slides were deemed to be positive for p16INK4a, increasing the diagnostic sensitivity to 96%. CONCLUSIONS. The CINtec p16INK4a Cytology Kit, in combination with ThinPrep cervical samples, allowed clear evaluation of p16INK4a protein overexpression. Diagnostic specificity of the CINtec p16INK4a assay was significantly improved relative to hc2. To increase p16INK4a immunostaining in abnormal cells, a modified kit version with improved staining performance has been developed and is currently being evaluated. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.

Placentitis is cited as one of the leading causes of abortion in mares worldwide (Tengelsen et al. 1997; Smith et al. 2003; Laugier et al. 2011). Placentitis may also result in the delivery of weak...

There is widespread consensus among environmental scientists that a holistic understanding of how natural resources are managed effectively at different scales requires a solid grasp on the functioning of governance institutions that link human users to the biophysical world in which they are embedded. Societies exist within complex social-ecological systems, in which the social and ecological components are tightly connected in systematic, but often hard to understand, ways. Institutions are, in essence, the lubricant that mediates the relationship between the two components; without the right institutions in place, no human society can tackle environmental problems successfully. Needless to say, the variation of societies and ecological systems around the world is vast and rich, which makes the study of institutional diversity and its effect on the management of natural resources both fascinating and daunting. From the rules to manage small-scale indigenous fisheries to the treaties to tackle global climate change, humans craft and enforce institutions to avoid “tragedies of the commons” that result when the prevalence of individual interests leads to the mismanagement (and sometimes sheer complete destruction) of resources that are open to multiple users. This article serves as an introductory guide for scholars and students with an interest in understanding how social scientists have researched institutions and their role in constraining human behavior in search of sustainable uses of natural resources. Sections cover research focusing on the definition, creation, development, evolution, and performance of institutions, as well as the operation of institutions at different scales and in different topic areas.

The comparison of copolymers containing sulfobetaine or phosphobetaine moieties for use as potential biocompatible coatings has been investigated. Two statistical copolymers were produced by a free radical polymerisation technique, one based on a sulfobetaine and the other on a phosphobetaine, both with a silyl group component to allow thermal crosslinking after coating. PMMA and glass discs were dip-coated with the polymers and their properties were compared to the uncoated controls. Bacterial adhesion to these coated materials was assessed using Staphylococcus epidermidis, Staphylococcus aureus and Pseudomonas aeruginosa. Human macrophages and granulocytes were used to assess the adhesion and activation of inflammatory cells whilst mouse 3T3 fibroblast cells were used to assess the propensity for the materials to support fibroblast cell adhesion. In all cases the polymer coatings reduced cell adhesion with respect to the base materials. The phosphobetaine-based copolymer coatings were shown to be markedly superior to the sulfobetaine-based copolymer coatings.

Aims: To examine the effect on the leakage of low molecular weight cytoplasmic constituents from Staphylococcus aureus using phenolics singly and in combination, and to see if the observations could be modelled using a non-linear dose response. Methods and Results: The rate of potassium, phosphate and adenosine triphosphate leakage was examined in the presence of chlorocresol and m-cresol. Individually, leakage was observed only at long contact times or high concentrations. Combined at these ineffective concentrations, the cytoplasmic pool of all constituents studied was released within minutes. Both chlorocresol and m-cresol were shown to have non-linear dose responses. A rate model for the combinations, which takes account of these non-linear responses, accurately predicted the observations. Conclusions: Antimicrobials, which when used alone exhibit a non-linear dose response, will also give a non-linear dose response in combination. The simple linear-additive model ignores the concept of the dilution coefficient and will always describe the phenomenon of synergy for combinations where one or more of the components has a dilution coefficient greater than one. This has been borne out by examination of the purported prime lesion of chlorocresol and m-cresol, alone and in combination. Significance and Impact of the Study: Studies aimed at producing synergistic mixtures of antimicrobials, which ignore the non-linear additive effect, may waste valuable research effort looking for a physiological explanation for an apparent synergy, where none, in-fact, exists. Patents granted on the basis of analyses using the linear-additive model for combinations of compounds with non-linear dose responses may no longer be supportable.

The aim of this study was to investigate in vitro adhesion of clinically relevant bacteria to standard HEMA and novel biomimetic soft contact lenses (SCL) using bioluminescent ATP assay and image analysis. Unworn SCL were incubated with Pseudomonas aeruginosa, Staphylococcus epidermidis or Serratia marcescens suspended in sterile phosphate buffered saline (PBS). The level of bacterial adhesion after 1, 2, 4, 6 and 18h, was assessed using both image analysis and a bioluminescent ATP assay. Species differences in the overall level of adhesion to the different types of lens were observed using both measurement techniques. Generally bacterial adhesion was shown to peak at 4-6 h, then decline to a much lower level by 18 h. After 4 h, adhesion of all species of bacteria to the biomimetic SCL (omafilcon A) was found to be significantly lower than to the standard HEMA SCL (polymacon) (p0.05. Student's t-test, n = 4). Both these techniques demonstrated that novel biomimetic SCL materials exhibit significantly lower bacterial adhesion in vitro compared to standard HEMA SCL materials. SCL manufactured with these novel biomimetic materials may reduce the risk of infection.

Parkin is an intracellular protein that plays a significant role in the etiopathogenesis of autosomal recessive juvenile parkinsonism. Using immunoblot methods, we found Parkin isoforms varying from 54 to 58 kDa in rat, mouse, bird, frog and fruit-fly brains. Immunocytochemical studies carried out in rats, mice and birds demonstrated multiple cell types bearing the phenotype for Parkin throughout telencephalic, diencephalic, mesencephalic and metencephalic brain structures. While in some instances Parkin-containing neurons tended to be grouped into clusters, the majority of these labeled nerve cells were widely scattered throughout the neuraxis. The topographical distribution and organizational pattern of Parkin within major functional brain circuits was comparable in both rats and mice. However, the subcellular localization of Parkin was found to vary significantly as a function of antibody reactivity. A consistent cytoplasmic labeling for Parkin was observed in rodent tissue incubated with a polyclonal antibody raised against the human Parkin protein and having an identical amino-acid sequence with that of the rat. In contrast, rodent tissue alternately incubated with a polyclonal antibody raised against a different region of the same human Parkin protein but having 10 mismatched amino-acid sequence changes with those of the rat and mouse, resulted in nuclear labeling for Parkin in rat but not mouse neurons. This difference in epitope recognition, however, was reversed when mouse brain tissue was heated at 80 degrees C, apparently unmasking target epitopes against which the antisera were directed. Collectively, these results show a high degree of conservation in the cellular identity of Parkin in animals as different as drosophilids and mammals and points to the possibility that the biochemical specificities of Parkin, including analogous functional roles, may have been conserved during the course of evolution.

A series of in vitro assays for determining the biocompatibility of ocular biomaterials have been developed and used to assess the differences in performance of omafilcon A, etafilcon A and nelfilcon A contact lens materials. The assays assessed bacterial attachment, macrophage adhesion, granulocyte adhesion and activation, epithelial cell adhesion and corneal cell contact damage. Overall, omafilcon A was found to be more biocompatible than the other materials although there was no significant difference between the epithelial cell adhesion and granulocyte adhesion and activation on any of the hydrogels. Etailcon A performed less well compared to nelfilcon A and omafilcon A with respect macrophage adhesion and bacterial adhesion. The results indicate that these biological assays can be successfully applied for the testing of contact lens materials and may be particularly useful in the in vitro screening of new extended wear contact lens materials where cell adhesion and activation may have a greater influence on clinical performance.

General developmental patterns of mean electroencephalogram (EEG) coherence, computed from 16 scalp locations, were separately determined for 224 girls and 284 boys ranging in age from 2 months to 161/2 years. Principal components analysis of mean coherence developmental trajectories demonstrated gender-specific patterns and timing differences in the onset of synchronized-asynchronized oscillations. No brain region in either sex had a maturational plateau period. Differences in gender-specific rhythms were statistically significant in brain regions paired with frontal and temporal cortices. From birth to age 6 years, girls exhibited synchronized EEG coherence peaks in cortical regions known to be associated primarily with concurrent discrimination, language processing, fine motor skills, and social cognition. During this same early period, boys exhibited synchronized EEG coherence peaks in cortical regions known to be associated primarily with spatial-visual discrimination and executive planning related t...

Cell-surface hydrophobicity is different for Staphylococcus epidermidis cells grown under different environmental conditions; this might influence attachment and colonization of surfaces. Although a wide variety of techniques has been employed to measure bacterial surface hydrophobicity, including contact angle determinations, adherence to hydrocarbons, hydrophobic-interaction chromatography and salt aggregation, many of these either require large numbers of cells or do not yield comparable quantitative data. This study describes a novel, quantitative method for the determination of bacterial surface tension on the basis of image analysis of cell-cell interactions. S. epidermidis (strains 900 and 901) were suspended in different concentrations of propanol of known surface tension and examined by bright-field microscopy linked via a charge-couple device (CCD) camera to an image analyser. Frames were chosen randomly and the data recorded as a ratio of count/percentage coverage for each frame. The results showed that for strains 900 and 901 this ratio was maximum at surface tensions of 67 and 61 mN m−1 respectively. At these values of minimal interaction the surface tension of the liquid was equal to the bacterial cell surface tension. The results were in close agreement with those obtained from contact angles. The advantage of surface tension measurements is that, irrespective of the method used, the results generated are quantitative values and are therefore directly comparable. The method reported is reliable, reproducible and is of particular value because the number of cells required is, typically, at least two orders of magnitude lower than is required for commonly used alternative methods.

Cordyceps militaris has been previously shown to invert the chirality of ( r )-2-phenylpropionic acid to its antipode in the absence of any other biotransformation. To investigate the mechanism of this unusual biotransformation. ( r , s )-[2- 2 H 1 ]-2-phenylpropionic acid, ( r , s )-[2- 2 H,3,3,3- 2 H 3 ]-2-phenylpropionic acid, and ( r , s )-[3,3,3- 2 H 3 ]-2-phenylpropionic acid were synthesized and incubated with C. militaris . NMR spectroscopy showed that deuterium exchange of the α-methine proton occurred during the inversion process but there was no exchange of the β-methyl protons. There were no significant differences in the rates of chiral inversion of the three deuterated derivatives and the undeuterated compound, and with all the compounds attaining 84% enantiomeric excess of the ( s )-enantiomer after 48 h incubation. The deuterium exchange is not therefore the rate limiting process in this biotransformation. The recovery profiles demonstrated that there was rapid metabolism of the β-methyl deuterated derivatives which did not occur for the undeuterated 2-phenylpropionic acid or the derivative which was only deuterated at the α-carbon. These studies clearly illustrate that C. militaris is a useful in vitro model of the chiral inversion of 2-arylpropionic acid derivatives in mammalian systems.

The fungus Cordyceps militaris has been previously shown to be capable of inverting the chirality of 2-phenylpropionic acid from its (R)-enantiomer to its (S)-antipode. The structure of this compound is similar to the 2-arylpropionic acid non-steroidal anti-inflammatory drugs, which have also been reported to undergo a similar chiral inversion process in mammals and man. We report here an investigation into the substrate specificity of the enzyme system present in C. militaris using pure enantiomers and racemates of ibuprofen and ketoprofen and racemates of indoprofen, suprofen, flurbiprofen, and fenoprofen and the structurally related compounds 2-phenylbutyric acid and 2-phenoxypropionic acid as substrates, using optimised incubation conditions developed for the inversion of 2-phenylpropionic acid. The results demonstrated that C. militaris is capable of inverting the chirality of all the compounds investigated, which suggests that the active sites of the enzymes are very flexible with regard to the molecular dimensions of the substrate molecule and the spatial occupation of the groups surrounding the chiral centre. Metabolism of all the substrates was observed but the rate of metabolism varied extensively depending on the substrate. Achiral HPLC analysis was used to detect any potential metabolites and the results suggested that the site of the metabolism appeared to be at the aliphatic side groups only, with the aromatic ring being left intact in all cases. These results suggest that C. militaris could be a valuable tool in the investigation of the prospective metabolic fates of new 2-arylpropionic acids during their development. Chirality 10:528–534, 1998. © 1998 Wiley-Liss, Inc.

Microtubule-dependent motors of the kinesin superfamily have undergone structural and functional diversification during evolution and play crucial roles in cell division and intracellular transport. Degenerate oligonucleotides homologous to highly conserved regions of sequence within the motor domain were used in a polymerase chain reaction to isolate five new members (KIF3C, KIFC2, KIFC3, KIFC4, and KIF22) of the kinesin superfamily from a mouse brain cDNA library. Northern analysis showed that KIF3C and KIFC2 are expressed mainly in neural tissues, that KIFC4 and KIF22 are expressed primarily in proliferative tissues and cell lines, and that KIFC3 is apparently ubiquitous. To elucidate the organization of genes encoding kinesin-like motors in the mouse genome and to explore the potential associations of these genes with classical mouse mutations or human genetic diseases, these new genes as well as genes encoding the previously reported KIF3A and KIF3B motors were mapped to mouse chromosomes by using an interspecific backcross panel of DNAs from The Jackson Laboratory. The data indicate that the gene KIFC4 is present in three copies in the mouse genome on chromosomes 13 (KIFC4A), 10 (KIFC4B), and 17 (KIFC4C). The gene KIF22 is present in two copies on chromosomes 7 (KIF22A) and 1 (KIF22B). The genes KIF3A, KIF3B, KIF3C, KIFC2, and KIFC3 are each single loci and map to chromosomes 11, 2, 12, 15, and 8, respectively.

Previous studies have demonstrated that Verticillium lecanii might be used as a microbial model of the inversion of 2-arylpropionic acids in man. This paper describes the optimization of the inversion process in respect of culture medium, pH, cell density and substrate concentration. The study demonstrates that optimum inversion occurs in Sørensen's phosphate buffer at pH 5.5. The extent and rate of inversion were also shown to be dependent on substrate concentration and cell density. This study will form the basis of the development of a microbial model of the metabolism of 2-arylpropionic acids which might be suitable for the in-vitro screening of new compounds in this class.

Previous investigations have described the development of nongrowing suspension of Verticillium lecanii as a microbial model of the mammalian chiral inversion of the 2-arylpropionic acids (2-APAs). Mechanistic studies in mammals have shown that inversion involves loss of the α-methine proton but retention of the original atoms at the β-methyl position, and a mechanism has been proposed involving enzymatic epimerisation of acyl-CoA thioester derivatives of the substrate. Inversion of the 2-APAs by V. lecanii exhibits extensive intersubstrate variation in the presence, rate, extent, and direction of inversion, which are different from those observed in mammalian systems, possibly indicating differences in the mechanism of inversion between mammalian and microbial cells. This study involved the investigation of proton/deuterium exchange by 1H-nuclear magnetic resonance following incubation of deuterated derivatives of 2-phenylpropionic acid (2-PPA), a model compound, in cell suspensions of V. lecanii and incubation of undeuterated 2-PPA in cell suspensions containing D2O. The results indicated that the inversion of 2-PPA by V. lecanii also involved exchange of the α-methine proton but complete retention on the original atoms at the β-methyl position. No kinetic deuterium isotope effect was observed, indicating that loss of the α-methine proton is not the rate-limiting step of the inversion process. This suggests that the observed differences between microbial and mammalian systems probably involve the stereoselective acyl-CoA thioester formation step and not the subsequent epimerisation of the resultant diastereomers. Chirality 9:254–260, 1997. © 1997 Wiley-Liss, Inc.

We search for correlations between positions of extragalactic objects and arrival directions of Ultra-High Energy Cosmic Rays (UHECRs) with primary energy $E \ge 40$ EeV as observed by the surface detector array of the Telescope Array (TA) experiment during the first 40 months of operation. We examined several public astronomical object catalogs, including the Veron-Cetty and Veron catalog of active galactic nuclei. We counted the number of TA events correlated with objects in each catalog as a function of three parameters: the maximum angular separation between a TA event and an object, the minimum energy of the events, and the maximum redshift of the objects. We determine combinations of these parameters which maximize the correlations, and calculate the chance probabilities of having the same levels of correlations from an isotropic distribution of UHECR arrival directions. No statistically significant correlations are found when penalties for scanning over the above parameters and for searching in several catalogs are taken into account.

Preservative efficacy tests were performed in triplicate on each of three batches of three formulated nasal spray preparations to assess the inter- and intra-batch variation in preservative performance which typically results from these procedures, and to assess the relative importance of factors influencing preservative performance in nasal products. Tests were conducted using procedures conforming, as far as possible, to both the European and the US pharmacopoeias and the results interpreted using the performance criteria of both. Despite the adoption of practices designed to maximize reproducibility, a marked variation in the degree of microbial inactivation was observed, both within and between batches of product. A preservative system comprising benzalkonium chloride and phenylethyl alcohol was found to be far superior to combinations of either benzalkonium chloride plus disodium edetate or potassium sorbate plus disodium edetate, both of which failed to satisfy the EP performance criteria on a number of occasions. Proposals are made for the adoption of inactivation criteria which incorporate realistic error limits reflecting the inherent problems of reproducibility of the viable counting procedures involved.

Racemic ibuprofen has previously been shown to undergo metabolism by Verticillium lecanii to yield (S)-2-[4-(2-hydroxy-2-methylpropyl)phenyl] propionic acid which is enriched in the (S)-enantiomer. However, it had not been possible to elucidate whether ibuprofen or the metabolite was inverted. This paper describes the incubation of ibuprofen in non-growing cultures of V. lecanii, the results of which indicate that racemic ibuprofen is converted into a 70 : 30 (S : R) enantiomeric mixture after 6 d incubation in the absence of any metabolism. This suggests that V. lecanii could be a useful model for the investigation of the mechanism of mammalian chiral inversion of iburprofen.

Y.-F. HUNG, M.J. THOMASON, W. RHYS-WILLIAMS, A.W. LLOYD AND G.W. HANLON. 1996. Fifty-nine microbial cultures were screened for their ability to carry out the chiral inversion of (R,S) and (R)-2-phenylpropionic acid under both growing and non-growing conditions. While a number of these micro-organisms metabolized the substrate, only Verticillium lecanii IMI 68689 and Cordyceps militaris CBS 128.25 were able to invert the (R)-enantiomer to its (S)-antipode with no other biotransformation occurring. The rate of inversion was faster for C. militaris but in both cases the reaction was independent of growth and reached an equilibrium after 5 d incubation. Evidence suggests that the (R) to (S) inversion is inhibited in the presence of excess (S)-enantiomer which may account for the equilibrium enantiomeric ratios (S:R) of 90:10 and 70:30 for C. militaris and V. lecanii, respectively. Optimization studies revealed that the fastest rates of reaction for C. militaris were found at lower substrate concentrations (100 μg ml-1) whilst the greatest yield of (S)-2-PPA was obtained at 250 μg ml-1. Optimum inversion was found to occur using Sorensen's phosphate buffer at pH 5.5. These results may have implications for the use of micro-organisms in the production of pure enantiomers from racemic mixtures and, in addition, provide an in vitro model system for the study of a unique and interesting biotransformation.

The objectives of this trial were to determine the effects of 0.5 mg estradiol benzoate administered intramuscularly 24 h after the removal of progesterone-containing intravaginal devices on the occurrence and timing of estrus, synchronized pregnancy rate and synchronized conception rate in dairy heifers. A clinical trial was conducted involving 750 dairy heifers in 13 herds. Within each herd heifers were randomly allocated to 1 of 2 estrus synchronization treatments. All heifers received a CIDR-B progesterone-containing intravaginal device containing a 10 mg estradiol benzoate capsule for 12 d. Twenty-four hours after CIDR-B removal one group received 0.5 mg, im estradiol benzoate while the other group received an intramuscular injection of a placebo. Estrus detection was performed at 48 and 72 h after intravaginal device removal, and heifers detected in estrus at those times were inseminated. Administration of estradiol benzoate 24 h after removal of CIDR-B devices significantly increased the number of heifers exhibiting estrus within the observation period (96.1 vs 90.5%; P0.01). It also altered the onset of estrus so that significantly more heifers were in estrus (86.6 vs 72.3%; P0.01) and conceived (47.1 vs 37.5%; P0.05) by 48 h after CIDR-B device removal. The synchronized conception rate was unaffected by treatment. The distribution of estrus was such that fixed-time insemination after estrus synchronization with this treatment program may be recommended.