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ARIADNE is a 1-ton (330 kg fiducial mass) dual-phase liquid argon (LAr) time projection chamber (TPC) featuring a novel optical readout. Four electron-multiplying charge-coupled device (EMCCD) cameras are mounted externally, and these capture the secondary scintillation light produced in the holes of a thick electron gas multiplier (THGEM). Track reconstruction using this novel readout approach is demonstrated. Optical readout has the potential to be a cost effective alternative to charge readout in future LArTPCs. In this paper, the technical design of the detector is detailed. Results of mixed particle detection using a secondary beam from the CERN PS (representing the first ever optical images of argon interactions in a dual-phase LArTPC at a beamline) and cosmic muon detection at the University of Liverpool are also presented., 58 pages, 40 figures. Changes from previous version based on pre-publication review: improved quality of various figures, improved clarity of some definitions and reduced longer sentences for better readability, fixed typos and formatting errors

The $K^+\rightarrow \pi^+ \nu \bar \nu$ decay is one of the theoretically cleanest meson decay where to look for indirect effects of new physics complementary to LHC searches. The NA62 experiment at CERN is designed to measure the branching ratio (BR) of this decay with 10\% precision. NA62 has been successfully launched in October 2014, took data in pilot runs in 2014 and 2015 reaching the final designed beam intensity. The NA62 experimental setup is illustrated and quality of data acquired in view of the final measurement is reported. The $K^+\rightarrow \pi^+ \nu \bar \nu$ decay is theoretically one of the cleanest meson decays and so a good place to look for indirect effects of new physics complementary to LHC searches. The NA62 experiment at CERN is designed to measure the branching ratio of this decay with 10\% precision. NA62 was commissioned in October 2014, took data in pilot runs in 2014 and 2015. The NA62 experimental setup is illustrated and data quality is reported. The K+→π+νν‾ decay is theoretically one of the cleanest meson decays and so a good place to look for indirect effects of new physics complementary to LHC searches. The NA62 experiment at CERN is designed to measure the branching ratio of this decay with 10% precision. NA62 was commissioned in October 2014, took data in pilot runs in 2014 and 2015. The NA62 experimental setup is illustrated and data quality is reported.

Colossal two-phase Liquid Argon Time Projection Chambers (LAr TPCs) are a proposed option for future long-baseline neutrino experiments. This study illustrates the feasibility of using an EMCCD camera to capture light induced by single cosmic events in a two-phase LAr TPC employing a THGEM. An Andor iXon Ultra 897 EMCCD camera was externally mounted via a borosilicate glass viewport on the Liverpool two-phase LAr TPC. The camera successfully captured the secondary scintillation light produced at the THGEM holes that had been induced by cosmic events. The light collection capability of the camera for various EMCCD gains was assessed. For a THGEM gain of 64 and an EMCCD gain of 1000, clear images were captured with an average signal-to-noise ratio of 6. Preliminary 3D reconstruction of straight cosmic muon tracks has been performed by combining the camera images, PMT signals and THGEM charge data. Reconstructed cosmic muon tracks were used to determine THGEM gain and to calibrate the intensity levels of the EMCCD image.

Future giant liquid argon (LAr) time projection chambers (TPCs) require a purity of better than 0.1 parts per billion (ppb) to allow the ionised electrons to drift without significant capture by any electronegative impurities. We present a comprehensive study of the effects of electronegative impurity on gaseous and liquid argon scintillation light, an analysis of the efficacy of various purification chemicals, as well as the Liverpool LAr setup, which utilises a novel re-circulation purification system. Of the impurities tested - Air, O_2, H_2O, N_2 and CO_2 in the range of between 0.01 ppm to 1000 ppm - H_2O was found to have the most profound effect on gaseous argon scintillation light, and N_2 was found to have the least. Additionally, a correlation between the slow component decay time and the total energy deposited with 0.01 ppm - 100 ppm O_2 contamination levels in liquid argon has been established. The superiority of molecular sieves over anhydrous complexes at absorbing Ar gas, N_2 gas and H_2O vapour has been quantified using BET isotherm analysis. The efficiency of Cu and P_2O5 at removing O_2 and H_2O impurities from 1 bar N6 argon gas at both room temperature and -130 ^oC was investigated and found to be high. A novel, highly scalable LAr re-circulation system has been developed. The complete system, consisting of a motorised bellows pump operating in liquid and a purification cartridge, were designed and built in-house. The system was operated successfully over many days and achieved a re-circulation rate of 27 litres/hour and high purity.

This paper presents a preliminary study into the use of CCDs to image secondary scintillation light generated by THick Gas Electron Multipliers (THGEMs) in a two phase LAr TPC. A Sony ICX285AL CCD chip was mounted above a double THGEM in the gas phase of a 40 litre two-phase LAr TPC with the majority of the camera electronics positioned externally via a feedthrough. An Am-241 source was mounted on a rotatable motion feedthrough allowing the positioning of the alpha source either inside or outside of the field cage. Developed for and incorporated into the TPC design was a novel high voltage feedthrough featuring LAr insulation. Furthermore, a range of webcams were tested for operation in cryogenics as an internal detector monitoring tool. Of the range of webcams tested the Microsoft HD-3000 (model no:1456) webcam was found to be superior in terms of noise and lowest operating temperature. In ambient temperature and atmospheric pressure 1 ppm pure argon gas, the THGEM gain was approximately 1000 and using a 1 msec exposure the CCD captured single alpha tracks. Successful operation of the CCD camera in two-phase cryogenic mode was also achieved. Using a 10 sec exposure a photograph of secondary scintillation light induced by the Am-241 source in LAr has been captured for the first time., The acronym TGEM was changed to THGEM. Typos in text and figures were corrected. References were added

In this paper we present a successful experimental test of filling a volume of 6 m$^3$ with argon gas, starting from normal ambient air and reducing the impurities content down to few parts per million (ppm) oxygen equivalent. This level of contamination was directly monitored measuring the slow component of the scintillation light of the Ar gas, which is sensitive to {\it all} sources of impurities affecting directly the argon scintillation., Comment: 9 pages, 6 figures, to appear in Proc. 1st International Workshop towards the Giant Liquid Argon Charge Imaging Experiment (GLA2010), Tsukuba, March 2010

The effect of EBV-conversion of two EBV-negative lymphoma lines (Ramos and BJAB) on agarose clonability and tumorigenicity in nude mice was explored. The cloning frequency was increased in all 9 sublines investigated, between 1.1 and 4.9 times compared to the original "parental" lines. Tumorigenicity was increased in one out of 2 BJAB-derived, EBV-positive lines and in 3 of 6 Ramos-derived lines, while it was decreased in 3 others. A strong positive correlation between the number of genomes/cell and the amount of EBNA/cell was detected, and in 7 of 9 converted lines the cloning frequency also correlated to the number of EBV genomes. On the other hand, no relation was established between the number of EBV-genomes/cell, the amount of EBNA/cell and tumorigenicity.

The pronase-enhanced release of 14C-labeled DNA was used to assay cytotoxicity of murine natural killer cells. YAC-1 lymphoma cells were labeled with [14C]thymidine and incubated with increasing numbers of spleen cells from nude mice. At harvest, nuclease-free pronase was used to digest damaged target cells. Increases in cytotoxicity of 5--39% were obtained using optimal conditions. The reaction could be successfully inhibited with unlabeled YAC-1 cells. The degree of cytotoxicity was similar to that detected by 51Cr release, but a longer period of incubation was required.

Summary Bovine adenovirus type 3 (BAV-3), strain WBR-1, quantitatively transforms hamster embryo carcass cells with a maximum efficiency of 4.7 × 104 p.f.u./focus-forming units (f.f.u.). This frequency is significantly inhibited by the presence of 1.8 mm of Ca++. The transformed cells are highly tumourigenic in hamsters and possess T- and tumour-specific transplantation antigens. BAV-3 is one of the most oncogenic of the adenoviruses and an ideal model virus for the study of transformation.

The passive hemagglutination inhibition technique was used to test serologically for the presence of Syrian hamster type C virus antigen(s) (SHCVA) in a wide variety of normal and transformed hamster cells and tissues. SHCVA could not be detected in normal tissues or nonneoplastic tissues of tumor-bearing Syrian hamsters. Normal hamster embryo cells or cells transformed in vitro by simian adenovirus, by chemical alone, or doubly transformed by simian adenovirus and chemical did not contain SHCVA; however, SHCVA was found in a majority of tumors resulting from transplantation of these in vitro-transformed cells. No consistent pattern was observed in the capacity of individual transformed cell lines to produce SHCVA-positive or -negative tumors. When cells of a given transformed line were inoculated at 4 sites on each of 8 hamsters, SHCVA-positive tumors were found not to be randomly distributed but rather to be clustered on a few animals. SHCVA could be detected in only a few primary tumors induced by inoculation of carcinogenic DNA viruses; however, both the incidence and titer of SHCVA were significantly increased in a variety of transplanted tumors. These data suggest that SHCVA may be introduced into transplanted, transformed hamster cell tumors during passage in the host animal. Alternatively, in vivo conditions may allow expression of viral antigens not found under in vitro conditions; however, if this is true, only certain animals appear to be capable of activating SHCVA.

Hamster, rat, and mouse embryo cells were quantitatively transformed by simian adenovirus 7 with maximum efficiencies of 2.1 X 10(5), and 2.5 X 10(5) plaque-forming unit/focus-forming unit, respectively. Bovine adenovirus type 3 did not transform rat or mouse embryo cells, but transformed hamster embryo cells with a maximum efficiency of 3.4 X 10(4) plaque-forming unit/focus-forming unit. All of the transformed cells were tumorigenic in appropriate hosts and possessed viral-specific T-antigen.

Cell lines were established from 2 primary hepatocellular carcinomas (HC's) and 3 sarcomas produced in Syrian golden hamsters inoculated as newborns with chicken embryo lethal orphan (CELO) virus. Cell lines from 2 sarcomas (COT, CMT) and 1 HC (CEHEP) produced CELO virus-specific T-antigen. The antigen was not detected in cells of the third sarcoma line (RCT) until they had undergone more than 34 passages in vitro. Although 5-10% of cells in the second HC line (CILT/2) contained T-antigen during early passages, it was not demonstrable after the fifth subculture. Nevertheless, cells of both HC lines possessed CELO virus tumor-specific transplantation antigen. All 5 cell lines also contained hamster type R particles, and both HC lines had type C and intracytoplasmic type A particles. The percentage of carcinoma cells producing type R particles increased during cultivation in vitro, whereas the number of cells with type A particles decreased. Treatment with dibutyryl cyclic AMP and theophylline enhanced the number of cells producing type C particles in 1 HC line and type R particles in 2 sarcoma lines.

Complement dependent cytotoxicity to malignant melanoma tumor cells was demonstrated in incubations that included rheumatoid factor (RF) positive plasma and normal plasma. Cytotoxicity was not demonstrated to cells from a number of normal tissues. The phenomenon involved coating of tumor cells with immunoglobulins and complement fixation. The activity in RF positive plasma was present in high titer an may not be RF. The activity in normal plasma was present in low titer, was found in plasma from eight out of 11 healthy subjects and may be a naturally occurring antibody. This previously undescribed humoral cytotoxicity system may participate in tumor host interactions, especially after therapy, when the majority of patients become RF seropositive.

Chicken-embryo-lethal-orphan (CELO) virus, Phelps strain, agglutinated erythrocytes at 37 C. The hemagglutinating activity, which is a function of complete and incomplete virus particles, was sensitive to heat but not to pH. The soluble components of the virus were similar in sedimentation characteristics to those obtained from human adenovirus type 1. The effects of chemical and physical agents on CELO hemagglutinin, CELO infectivity, and red-cell receptors suggested that the last were protein in nature and that cell-virus attachment was mediated by amino groups on the virion. The attachment of virus to red blood cells via the penton projection was demonstrated by electron microscopy.

Avian adenoviruses were isolated from 56 of 106 fecal and rectal tissue samples taken from apparently healthy young chickens on 4 farms. Only one isolation was made from the 37 samples from 3- and 4-week-old chicks, while the isolation frequency was 64-100% in groups 5 weeks old and older. The 56 adenovirus isolates were classified into 6 serotypes. Vurses of 3 or 4 types were found on each farm. Avian adeno-associated virus CF antigens were found, using chicken embryos coinfected with an adenovirus helper, in 2 of the 38 adenovirus isolated studied.

Hidden complement-dependent cytotoxins were demonstrated in normal donor sera after removing anti-immunoglobulins that normally block the ability of these immunoglobulin Gs to react with surface antigens on tumor cells. The blocking antibodies had certain properties of anti-idiotypes. Immunoglobulin G from Cohn Fraction II, after removing these anti-immunoglobulins, was cytotoxic for cultured fetal cells and for malignant melanoma, breast, lung, colon, and other tumor cells maintained either in tissue culture or by serial passage in nude mice. The cytotoxins were not adsorbed by extracts from normal lymphoid, liver, skin, or red blood cells. These results suggest that a heterogeneous group of natural antibodies reactive with antigens expressed on a variety of neoplastic and fetal cells circulate in normal donor sera as part of a soluble immune complex, together with a blocking anti-immunoglobulin.

Protection against bovine adenovirus type 3-induced primary or transplantable tumors was studied in hamsters immunized with bovine adenoviruses, human adenovirus type 12 (A-12), simian adenovirus type 7 (SA7), or chicken-embryo-lethal-orphan (CELO) virus. Newborn hamsters inoculated with 2.3 times 10-5 plaqueforming units of bovine adenovirus type 3 were given injections of bovine serotypes 1, 2, or 3 during the latent period of tumor development. No hamsters immunized with type 3 and only 47% of those inoculated with types 1 or 2 developed tumors as compared to a control incidence of 90%. Primary tumors were not prevented when hamsters inoculated at birth with bovine adenovirus type 3 were immunized during the latent period with A-12, SA7, or CELO, even though 10-100 times more infectious virus was used. When adult hamsters were given injections of the bovine adenoviruses on 3 successive weeks and then challenged with graded doses of tumor cells, the three serotypes produced a 20-fold to 200-fold increase in the 50% tumor-producing dose of tumor cells. These studies indicate that bovine adenoviruses types 1, 2, and 3 induce cross-reactive transplantation antigens which, however, do not cross-react with those induced by oncogenic adenoviruses of either avian, simian, or human origin.

Bovine adenoviruses types 1, 2, and 3 were purified and concentrated by polyethylene glycol precipitation and CsCl density-gradient centrifugation. The efficiency of recovery of infective particles was 64 to 80%. The guanine-cytosine contents of DNA of the nononcogenic types 1 and 2 and the highly oncogenic type 3 were found to be 62, 61, and 48%, respectively--a pattern similar to that of nononcogenic and oncogenic human adenoviruses.

Admixed spleen cells from normal animals or from animals given injections of Syrian hamster type C virus significantly potentiated the growth of the transplanted D9 lymphoma of random-bred hamsters. Potentiation was measured by an increase in incidence of tumors, a shortened latent period, and a decreased 50% tumor-producing dose of tumor cells. Intermediate doses of spleen cells (10 to 100 spleen cells per tumor cell) produced the greatest potentiation. Preincubation of admixed spleen and tumor cell suspensions in vitro was unnecessary. Immunization to isoantigens was not responsible for potentiation, since growth of a transplantable carcinoma of inbred hamsters was also facilitated by normal spleen cells. In addition, normal kidney or liver cells increased the incidence of tumors transplanted by a small number of tumor cells. Potentiation did not occur when spleen cells were injected at a site remote from the tumor cells. Since the potentiating cells might act eigher as a physical barrier to host response, or by blocking normal macrophage function, we injected charcoal with tumor cells. Simultaneous treatment with charcoal facilitated the growth of the lymphoma but not that of the carcinoma. Treatment with some doses of charcoal was also effective at distant sites. Although potentiation of tumor growth by cells or charcoal may operate through different mechanisms, these phenomena should be explored in regard to outgrowth of primary tumors, tumor immunity, or enhancement of tumor growth.

Protection against bovine adenovirus type 3-induced primary or transplantable tumors was studied in hamsters immunized with bovine adenoviruses, human adenovirus type 12 (A-12), simian adenovirus type 7 (SA7), or chicken-embryo-lethal-orphan (CELO) virus. Newborn hamsters inoculated with 2.3 times 10-5 plaqueforming units of bovine adenovirus type 3 were given injections of bovine serotypes 1, 2, or 3 during the latent period of tumor development. No hamsters immunized with type 3 and only 47% of those inoculated with types 1 or 2 developed tumors as compared to a control incidence of 90%. Primary tumors were not prevented when hamsters inoculated at birth with bovine adenovirus type 3 were immunized during the latent period with A-12, SA7, or CELO, even though 10-100 times more infectious virus was used. When adult hamsters were given injections of the bovine adenoviruses on 3 successive weeks and then challenged with graded doses of tumor cells, the three serotypes produced a 20-fold to 200-fold increase in the 50% tumor-producing dose of tumor cells. These studies indicate that bovine adenoviruses types 1, 2, and 3 induce cross-reactive transplantation antigens which, however, do not cross-react with those induced by oncogenic adenoviruses of either avian, simian, or human origin.

SummaryIn contrast to tumor bearing hamsters, in which 95% (59 of 62) of the animals in this series developed complement fixing (C-F) antibodies against homologous adenovirus type 12 tumors, only 18% (7 of 40) of the C3Hf/Gs mice bearing adenovirus type 12 transplant tumors developed C-F antibodies against homologous mouse tumors. Only 7% (5 of 69) of the tumor bearing mice developed C-F antibody when tested against adenovirus type 12 hamster tumor antigen. Also, there was no significant correlation in the mouse between tumor size and antibody titer as there was in the hamster. The disparity between the development of antibodies in the mouse and the hamster is not accounted for by absence of antigen in the mouse tumors because most contained antigen as determined by reactivity with positive hamster sera.

SINCE the discovery1 of the herpes-like virus particle (EBV) in cell cultures of Burkitt's lymphoma, the virus has been found in many (but not all) lymphoid cell cultures derived from patients with Burkitt's lymphoma2 and other lymphoid neoplasms3 or infectious mononucleosis4 as well as from normal individuals5. The virus has also been found in some biopsies of Burkitt tumours6. Serological evidence has implicated it as a causal or associated agent in heterophile-positive infectious mononucleosis7, 8, although its relationship to Burkitt's lymphoma is less clear. Antigenic studies suggest a relationship between the herpes-like virus and antigens detected by indirect immunofluorescence (IF) techniques in fixed cells9, surface antigens on viable cells10 and complement-fixing (CF) antigens in extracts of Burkitt cell cultures11.

The group considered that approximately one-third of the earth’s surface is water (± 23° North and South of the equator). In this region solar energy is stored by absorption by the sea and in the latent heat of evaporation. On the average about 0.5 cm per day evaporates from this surface, thus providing about 300 calories per cm to fuel the earth’s weather machinery. It is this key to the weather that is the subject of intense research by the world’s meteorological research laboratories as to how this fuel gets distributed.

© Copyright owned by the author(s). There is a significant R&D effort ongoing in the liquid argon (LAr) time projection chamber (TPC) community. Due to the scintillation and ionisation properties of LAr, coupled with its low cost, it is possible to construct detectors with immense fiducial volume at a modest cost. It is for this reason that LAr TPCs are fast becoming the detector of choice for long baseline neutrino physics experiments. Using LAr TPCs it is possible to provide the large targets required to make direct observation of neutrino interactions a statistically reasonable prospect. Experiments such as the deep underground neutrino experiment (DUNE) are proposing the use of 68,000 tons of liquid argon as the target material of choice shared between four colossal LAr TPCs. In a two-phase TPC the charge amplification process is performed in the gas phase. By performing charge amplification in the gas phase it is possible to achieve much higher gains and hence improved signal-to-noise ratios. ARIADNE is a novel and innovative two-phase LAr TPC pioneering the direct imaging of secondary scintillation light produced during the charge amplification process using a THGEM in the gas phase. Optical readout presents many advantages over current readout technologies such as massive reductions in the number of readout channels, ease of scalability, upgrade, installation and maintenance as well as cost effectiveness.

Chicken-embryo-lethal-orphan (CELO) virus is an avian adenovirus shown to be oncogenic in newborn random bred and inbred hamsters (1). Transformation of human cells by this agent has been reported (2). This virus is ubiquitously present in chickens and market eggs and is therefore considered to be a potential candidate for cancer etiology in man.Virus for the present study was inoculated into 10-day CELO-free embryonated eggs, and crude stocks consisted of 72-hr allantoic fluid harvests. To 80 ml of crude stock was added 0. 8 gm Na-deoxycholate and 4. 0 ml of 0. 25% trypsin, and the mixture incubated at 37 C for 30 min.

A microtechnique for staining preparations of cells grown in vitro for indirect immunofluorescence tests is described. Smaller amounts of materials, as well as less handling of cover slips, greatly facilitates the process.