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HESS J0632+057 belongs to a rare subclass of binary systems which emits gamma-rays above 100 GeV. It stands out for its distinctive high-energy light curve, which features a sharp ``primary'' peak and broader ``secondary'' peak. We present the results of contemporaneous observations by NuSTAR and VERITAS during the secondary peak between Dec. 2019 and Feb. 2020, when the orbital phase ($\phi$) is between 0.55 and 0.75. NuSTAR detected X-ray spectral evolution, while VERITAS detected TeV emission. We fit a leptonic wind-collision model to the multi-wavelength spectra data obtained over the four NuSTAR and VERITAS observations, constraining the pulsar spin-down luminosity and the magnetization parameter at the shock. Despite long-term monitoring of the source from Oct. 2019 to Mar. 2020, the MDM observatory did not detect significant variation in H$\alpha$ and H$\beta$ line equivalent widths, an expected signature of Be-disk interaction with the pulsar. Furthermore, fitting folded Swift-XRT light curve data with an intra-binary shock model constrained the orbital parameters, suggesting two orbital phases (at $\phi_D = 0.13$ and 0.37) where the pulsar crosses the Be-disk, as well as phases for the periastron ($\phi_0 = 0.30$) and inferior conjunction ($\phi_{\text{IFC}} = 0.75$). The broad-band X-ray spectra with Swift-XRT and NuSTAR allowed us to measure a higher neutral hydrogen column density at one of the predicted disk-passing phases., Comment: 21 pages, 9 figures, accepted to ApJ

Objective -To study the acquisition of tobacco and the development of cigarette brand selection among youth. To com pare four methods of measuring brand preference among underage smokers. Design - Individual interviews were con ducted with youths to elicit their past and present experiences with tobacco. Setting - A high school and public places in Massachusetts, USA. Subjects-A convenience sample of 721 youths, aged 10-17 years. Results - Friends were the source of the subject's first cigarette in 69 % of cases. Fifty per cent of the subjects were smoking three or fewer cigarettes per day when they first purchased tobacco. The first brand smoked was the first regular brand chosen in 67 % of cases, and 51 % of smokers were still smoking the same brand as their first cigarette. Ultra-low tar and generic brands were unpopular among youths. Questions concerning the favourite brand, brand usually pur chased, last brand smoked, and friend's favourite brand produced very similar brand preference results for full-priced brands. However, only the question con cerning the last brand smoked seemed to assess the use of generic brands accu rately.

Endotoxin-responsive (C3H/HeN) and -hyporesponsive (C3H/HeJ) murine B lymphocytes purified by adherence to anti-immunoglobulin ("antibody panning") possess identical gangliosides but different ganglioside surface accessibilities. We investigated the distribution and surface accessibility of gangliosides of B lymphocytes purified by adherence to plastic ("plastic panning") or by subtraction of non-B-lymphocyte components. As with antibody panning, there were no entirely new or absent gangliosides in plastic-panned or subtraction-purified B lymphocytes of each strain. However, striking changes in relative expression of five gangliosides were detected with each purification protocol. Moreover, five gangliosides of antibody-panned and plastic-panned B lymphocytes but only two gangliosides of subtraction-purified B lymphocytes were inaccessible to surface labeling. Unlike the situation for antibody-panned B lymphocytes, no interstrain (HeN vs. HeJ) surface accessibility differences existed in gangliosides of plastic-panned or subtraction-purified cells. Exposure of subtraction-purified B lymphocytes to anti-immunoglobulin failed to elicit changes in ganglioside expression. Murine B lymphocytes have distinct protocol-dependent differences in glycolipid phenotype which likely denote individual subpopulations.

Interleukin-12 (IL-12) is a key regulator of cell-mediated immunity that has therapeutic potential in cancer and infectious disease. In a previous Phase 1 dose escalation study of a single test dose of recombinant human IL-12 (rhIL-12) followed 14 days later by cycles of five consecutive daily intravenous injections every 3 weeks, we showed that a dose level up to 500 ng/kg could be administered with acceptable levels of safety. Based on these results, a Phase 2 study was conducted. In the Phase 2 study, however, administration of rhIL-12 at this same dose level resulted in severe toxicities with some patients unable to tolerate more than two successive doses. Of the 17 patients receiving rhIL-12 in the Phase 2 study, 12 patients were hospitalized and two patients died. A thorough scientific investigation to determine the cause of this unexpected toxicity failed to identify any difference in the drug products used or the patient populations enrolled in the Phase 1 and Phase 2 studies that could have accounted for the profound difference in toxicity. The focus of the investigation therefore shifted to the schedule of rhIL-12 administration. We determined that a single injection of rhIL-12 2 weeks before consecutive dosing included in the Phase 1 study, but not in the schedule of administration in the Phase 2 study, has a profound abrogating effect on IL-12-induced interferon-gamma (IFN-gamma) production and toxicity. This observation of schedule-dependent toxicity of IL-12 has been verified in mice, as well as nonhuman primates. In this regard, a single injection of IL-12 before consecutive daily dosing protected mice and cynomolgus monkeys from acute toxicity including mortality and was associated with an attenuated IFN-gamma response. Because of this unique biologic response, careful attention to the schedule of administration is required to assure safe and effective clinical development of this highly promising cytokine.

L-697,661 is a human immunodeficiency virus type 1 (HIV-1)-specific nonnucleoside reverse transcriptase (RT) inhibitor. Its tolerability and activity in combination with zidovudine were evaluated in a 48-week double-blind study. One hundred nineteen zidovudine-naive HIV-1-infected patients with CD4 cell counts of 200-500/mm 3 received either combination therapy, L-697,661 alone, or zidovudine alone. Activity was assessed by CD4 cell count changes. Selection for L-697,661-resistant virus was monitored by susceptibility testing of RT expressed by circulating viral RNA. Therapy was generally well tolerated. All groups receiving zidovudine exhibited transient increases in CD4 cell counts, while the L-697,661 monotherapy group showed a significant decline and yielded RT >100-fold resistant to L-697,661 and associated with substitutions at RT residue 181. The RT from patients receiving combination therapy was maximally 15-fold less susceptible to L-697,661. Hence, cotreatment with zidovudine prevents selection of HIV-1 variants that are highly resistant to L-697,661 in patients naive to both compounds

Immobilized antigen-antibody complexes are able to inhibit the mitogenic response of murine spleen cells to the B-cell mitogen 8-bromo-3',5'-cyclic guanosine monophosphoric acid. This this inhibition is dependent on intact Fc fragments in the immobilized complexes. Soluble complexes do not mediate this inhibition. When lipopolysaccharide (lps) activation of B cells was studied, it was found that the mitogenic response was inhibited at all times tested between 2 and 7 days of culture. Also, the LPS-induced mitogenesis of nude spleen cells was inhibited by immobilized complexes, indicating that suppressor T cells probably play no significant role in the inhibition. Immobilized complexes inhibit polyclonal antibody responses in a serum-free system and in the presence of normal mouse serum, but are unable to inhibit in the presence of fetal calf serum (FCS). If nu/nu spleen cells are used, however, the FCS does not block the ability of the complexes to inhibit the polyclonal response. It is suggested that that antigen-antibody complexes under appropriate conditions may bind to B lymphocytes via their Fc receptors and trigger a central "off" signal which blocks proliferation and consequently antibody production.

Mouse spleen cells, cultured on surfaces coated with antigen-antibody complexes, are inhibited from responding to the B-cell mitogens, lipopolysaccharide, lipid A, Pneumococcal polysaccharide SIII, and poly I:C. The response to the T-cell mitogen, concanavalin A, is also substantially inhibited by immobilized antigen-antibody complexes, but specific inhibition of the response to phytohemagglutinin is minimal. Control experiments showed that immobilized complexes prepared from IgG F(ab')2 fragments and IgA antibodies (both of which fail to bind to Fc receptors when complexed to antigen) did not show significant inhibitory activity when compared with the inhibition observed with complexes prepared from whole IgG. Suspensions of antigen-antibody complexes prepared from the same antigen and intact IgG antibody did not inhibit mitogenesis. None of the mitogens used could be demonstrated to compete with the binding of aggregated immunoglobulin to the B-cell Fc receptor. It appears that the interaction of Fc receptor-bearing lymphocytes and/or macrophages with immobilized complexes prevents lymphocyte activation by mitogens. It is suggested that the mechanism(s) involved may be relevant to antibody feedback control of the humoral immune response.

A simple, effective method is needed for growing obligate anaerobes in the clinical laboratory. This report describes a pre-reduced anaerobic bottle that can be taken to the bedside for direct inoculation, provides a flat agar surface for evaluation of number and morphology of colonies, and can be incubated in conventional bacteriological incubators. Each anaerobic culture set consisted of two bottles containing brain heart infusion agar and CO 2 . Gentamicin sulfate (50 μg/ml) was added to one of these to inhibit facultative enteric bacilli. Comparison of the anaerobic bottles with an identical aerobic bottle which was also routinely inoculated permitted early identification of anaerobic colonies. Representative species of most anaerobic genera of proven pathogenicity for man have been isolated from this system during 10 months of routine use.

MK-0366, a new derivative of nalidixic acid, was tested against 250 urinary pathogens including Escherichia coli, Serratia marcescens, and Pseudomonas aeruginosa. This new agent was more active than any of the other antibiotics tested, which included carbenicillin, ampicillin, cephalexin, tetracycline, trimethoprim, trimethoprim-sulfamethoxazole, and nalidixic acid. Gentamicin-resistant P. aeruginosa were highly sensitive to MK-0366, with a 90% minimal inhibitory concentration of 0.8 microgram/ml. Serratia strains were the most resistant organisms, with a 90% minimal inhibitory concentration of 3.1 micrograms/ml. These results suggest that clinical trials should be designed to investigate the clinical usefulness of this new drug in urinary infections.

Whole isolated rat glomeruli (WG) were incubated with bacterial collagenase to separate epithelial cells (EC) from the cores of glomerular tufts (GC), which consisted of mesangial and endothelial cells, as demonstrated by electron microscopy. Lysates of WG, EC, and GC and of renal tubules were prepared by hypo-osmotic shock and freeze-thawing. Activities of the following acidic lysosomal hydrolases were measured: acid phosphatase, beta-glucuronidase, cathepsin-D, non-specific esterase, and aryl sulfatases A and B. The glomerular cell preparations showed activities of all studied enzymes. GC had higher activities than EC, save for nonspecific esterase. Studies of the recovery of acid phosphatase and beta-glucuronidase revealed that approximately 2/3 of the hydrolase activities present in WG was still measureable after collagenase treatment and that the bulk of this was found in the GC lysates. These findings demonstrate that the rat glomerulus and its cell components have considerable biochemical activities of acidic hydrolytic enzymes. These appear to be most prominent in the combined mesangial and endothelial cells of the GC components.

The cell walls of gram-negative bacteria contain several biologically active components, including lipopolysaccharide (LPS), lipoprotein, and protein 1. The effects of these individual components and a synthetic analog of lipoprotein, TPP, on several activation parameters of glomerular mesangial cells (MC) were examined. Prostaglandin secretion, synthesis of the autogrowth factor, mesangial interleukin-1 (IL-1), and new synthesis of cellular proteins were assessed as markers of MC activation. All bacterial cell wall components evaluated were active in varying degrees as stimulants of prostaglandin secretion. In general, PGE was the predominant product. TPP and protein 1 also induced substantial secretion of thromboxane. Each cell-wall component was effective in stimulating mesangial IL-1 secretion. The activation of MC was associated with the enhanced synthesis of many cellular proteins in addition to IL-1. Stimulation by these bacterial components was dependent on the state of the mesangial cell cycle, because nonproliferating cells did not respond to these factors. Activation of MC by gram-negative bacterial cell wall components, with release of vasoactive prostaglandins and peptide mitogens, may be responsible for some of the glomerular hemodynamic alterations and cellular proliferative events associated with sepsis or chronic bacterial infection.

Neptunium-237(V) nitrate was administered by gavage to groups of fed or fasted adult and 5-day-old rats. Some groups also received the oxidants quinhydrone or ferric iron, and others received the reducing agent ferrous iron. Adult mice received ferric or ferrous iron and 235Np. When the adult rats were killed at 7 days after gavage, measurements showed that, compared with rats that were fed, a 24-hr fast caused a fivefold increase in 237Np absorption and retention. Both quinhydrone and ferric iron caused an even greater increase in absorption in both fed and fasted rats. Ferrous iron, on the other hand, decreased absorption in fasted rats to values lower than those obtained in fed rats. Similar results were obtained in mice treated with 235Np and either ferric or ferrous iron. The highest absorption obtained after gavage of ferric iron to fasted rats and mice was about two orders of magnitude higher than the value obtained in animals that were fed before gavage. The effects of ferric and ferrous iron on neptunium absorption by neonatal rats were similar to their effects on adult animals but of lesser magnitude. These results are consistent with the hypothesis that Np(V), when given in small mass quantities to fed animals, is reduced in the gastrointestinal tract to Np(IV), which is less well absorbed than Np(V).

A potential role for glycolipid gangliosides to act as immunomodulating agents has been suggested. Most studies have employed brain gangliosides. We have systematically investigated highly purified murine brain gangliosides for their ability to modulate lymphocyte activation. All sialic acid classes of ganglioside inhibited lipopolysaccharide (LPS)-induced antibody secretion and all polysialated gangliosides inhibited LPS-induced DNA synthesis. Monosialated gangliosides had no effect on DNA synthesis induced by LPS. 8-BrcGMP-induced DNA synthesis was also inhibited, suggesting that a negative signal was delivered to B lymphocytes by co-cultivation with exogenous gangliosides. The lack of specificity with respect to sialic acid class observed in these studies suggests that further investigation of an immunomodulatory role for gangliosides focus on endogenous lymphocyte gangliosides.

The results of the research described indicate that the compound Pu(NO/sub 3/)/sub 4/.XH/sub 2/O is a viable material for consideration as a solid shipping form. It meets the criteria set forth to define a suitable solid form of plutonium. Several plutonium compounds were considered for study as a shipping form before selecting Pu(NO/sub 3/)/sub 4/.XH/sub 2/O as having the most desirable characteristics. It is reasonably easy to prepare on a kilogram scale with relatively simple equipment using vacuum evaporation techniques. Plutonium nitrate does begin to thermally decompose at about 100/sup 0/C; however, proper equipment design and instrumentation can overcome this problem. Although Pu(NO/sub 3/)/sub 4/.XH/sub 2/O does produce some radiolytic gases, such as oxygen and nitrogen, an explosive mixture is not produced as only minor amounts of hydrogen are formed except during extended storage. Excessive pressurization in the shipping mode should not be a problem if the transport container is not closed for protracted periods of time. However, some form of thermal insulation would be required to prevent decomposition of the compound and to preclude over-pressurization during a fire. Plutonium nitrate has been found to be completely soluble in nitric acid even after storage for extended periods of time. Aftermore » the equivalent of 25 years of storage time of first-cycle reactor-grade plutonium from a radiation damage standpoint, Pu(NO/sub 3/)/sub 4/.XH/sub 2/O prepared from 85 percent /sup 238/Pu was found to be completely soluble in 4M HNO/sub 3/. Plutonium nitrate was also found to be soluble in water, but it rapidly converted to plutonium polymer.« less

Absorption and retention of plutonium were determined in mice after intragastric administration of either 6 X 10(-4) or 1.5 mg/kg in bicarbonate, citrate, or nitrate media. At the higher concentration, absorption of the citrate was greater than that of the nitrate; at the lower concentration, chemical form was not an important factor in absorption. Concentration and chemical form had much less influence on absorption by the neonatal (versus the adult) rat. The transfer factor (f1) for neonates was between one and two orders of magnitude higher than for adults. Absorption and retention of neptunium were determined in rats and/or mice after intragastric administration at doses ranging from 2.2 X 10(-7) to 43 mg/kg in nitrate solutions of pH 1.5. At the higher concentrations, absorption was 1.5 to 2.7%. For lower concentrations, absorption was 25 to 65 times less. In contrast to results obtained in adult animals, absorption of neptunium by neonates decreased with increasing dose. The data obtained in adult animals suggest that the f1 factor recommended by the ICRP for plutonium should be increased by a factor of 10, but the neptunium f1 factor, in contrast, should be decreased by a factor of 10.

Fifty-three clinical isolates of Klebsiella and fifty-one clinical isolates of Pseudomonas aeruginosa, twenty-six of which were carbenicillin-(CARB) resistant, were tested for susceptibility to mezlocillin (MEZ), azlocillin (AZL), and piperacillin (PIP), both alone and in combination with tobramycin (TOB) using the microtiter broth diluent method and an inoculum density of 10(6) CFU/ml. The Klebsiella were highly resistant to TOB, MEZ, and PIP (MIC90: 8, greater than 256, greater than 128 micrograms/ml, respectively). Synergy was demonstrated in 53 percent (PIP/TOB) and 51 percent (MEZ/TOB). An indifferent response was observed in 47 percent (PIP/TOB) and 49 percent MEZ/TOB of the Klebsiella. PIP, MEZ, and AZL in combination with TOB showed synergism against CARB-resistant Pseudomonas in less than 10 percent of the strains tested. Synergy could be demonstrated against CARB-susceptible Pseudomonas with the combinations PIP/TOB, AZL/TOB, and MEZ/TOB in 12 percent, 12 percent, and 24 percent, respectively, of the twenty-five strains tested. Indifferent effects were observed in 84 percent, 88 percent, and 76 percent, respectively, of these same CARB-susceptible strains. These data suggest that there is no significant difference in the incidence of synergy with these new penicillins and tobramycin against either Pseudomonas or Klebsiella.

A detailed experimental study has shown absorption of plutenium(IV) from 7 M HNO/sub 3/ solutions by strongbase (quaternary amine) anion exchange resins to be a very powerful and versatile processing method for plutonium. The simple expedient of operating at 50 to 60 deg C relieves most of the objections of former anion exchange processes for plutonium in that it permits adequate processing rates and efficiency to be obtained with four per cent cross-linked resins. Commercially available strong-base anion exchange resins Dowex-1, X-4 (50 to 100 mesh), among 50 to 100 mesh resins, and Permutit SK (20 to 50 mesh), among 20 to 50 mesh resins, are markedly superior for most process applications. The anion exchange process consists of an absorption or loading step in which plutonium is absorbed out of a feed solution by the resin, washing step in which impurities are removed by washing the plutonium-laden resin with an appropriate wash solution, and an elution step in which plutonium is stripped off the resin in an appropriate aqueous solution The effects of the pertinent variables in each of these steps have been studied in some detail, yielding informatlon which can be readily extrapolated to new processing applications. (auth)

Neptunium-237(V) nitrate was administered by gavage to groups of fed or fasted adult and 5-day-old rats. Some groups also received the oxidants quinhydrone or ferric iron, and others received the reducing agent ferrous iron. Adult mice received ferric or ferrous iron and 235Np. When the adult rats were killed at 7 days after gavage, measurements showed that, compared with rats that were fed, a 24-hr fast caused a fivefold increase in 237Np absorption and retention. Both quinhydrone and ferric iron caused an even greater increase in absorption in both fed and fasted rats. Ferrous iron, on the other hand, decreased absorption in fasted rats to values lower than those obtained in fed rats. Similar results were obtained in mice treated with 235Np and either ferric or ferrous iron. The highest absorption obtained after gavage of ferric iron to fasted rats and mice was about two orders of magnitude higher than the value obtained in animals that were fed before gavage. The effects of ferric and ferrous iron on neptunium absorption by neonatal rats were similar to their effects on adult animals but of lesser magnitude. These results are consistent with the hypothesis that Np(V), when given in small mass quantities to fed animals, is reduced in the gastrointestinal tract to Np(IV), which is less well absorbed than Np(V).

A study was made of the effect of oxidation state on gastrointestinal absorption of plutonium using solutions that contained, or did not contain, a strong oxidant and animals that were or were not fasted. There was no appreciable difference in the absorption of intragastrically injected /sup 238/Pu(IV) and /sup 238/Pu(VI) by either rats or guinea pigs allowed food ad libitum and injected. To determine if the conditions used by Weeks et al., (Radiat. Res. 4, 339-347, 1956) were responsible for the increased gut absorption of /sup 239/Pu(VI), relative to Pu(IV), both fasted and unfasted rats were gavaged with acid solutions of /sup 239/Pu(VI) nitrate, in the presence or absence of the holding oxidant (K/sub 2/Cr/sub 2/O/sub 7/). The results indicated that the combination of dichromate and fasting increased absorption about 26-fold.

There is a widespread belief that the adjective “Irish” is a general synonym for “unique”. The foundation for this belief is nowhere stronger than in the field of demography. During the past century, while the populations of the countries of Western Europe and of the British Dominions have been rising, that of the twenty-six counties which now constitute the Irish Republic has fallen from 6,529,000 in 1841 to 2,961,000 in 1951. As compared with these other countries, the Irish Republic has the lowest marriage rate, the highest age at marriage, the highest fertility rate and the highest emigration rate. A Commission on Emigration and other Population Problems was appointed in April, 1948, to examine, inter alia, the social and economic effects of the birth, death, emigration and marriage rates, and to investigate the causes and consequences of the present level and trend of population. Its Report, a limited stencilled edition of which appeared last autumn, provides an exhaustive statistical review...