Investigations of aerosol black carbon from a semi-urban site in the Indo-Gangetic Plain region

Long-term (2009-2012) data from ground-based measurements of aerosol black carbon (BC) from a semi-urban site, Pantnagar (29.0 degrees N, 79.5 degrees E, 231 m amsl), in the Indo-Gangetic Plain (IGP) near the Himalayan foothills are analyzed to study the regional characterization. Large variations are seen in BC at both diurnal and seasonal scales, associated with the mesoscale and synoptic meteorological processes, and local/regional anthropogenic activities. BC diurnal variations show two peaks (morning and evening) arising from the combined effects of the atmospheric boundary layer (ABL) dynamics and local emissions. The diurnal amplitudes as well as the rates of diurnal evolution are the highest in winter season, followed by autumn, and the lowest in summer-monsoon. BC exhibits nearly an inverse relation with mixing layer depth in all seasons; being strongest in winter (R-2 = 0.89) and weakest (R-2 = 0.33) in monsoon (July-August). Unlike BC, co-located aerosol optical depths (AOD) and aerosol absorption are highest in spring over IGP, probably due to the presence of higher abundances of aerosols (including dust) above the ABL (in the free troposphere). AOD (500 nm) showed annual peak (>0.6) in May-June, dominated by coarse mode, while fine mode aerosols dominated in late autumn and early winter. Aerosols profiles from CALIPSO show highest values close to the surface in winter/autumn, similar to the feature seen in surface BC, whereas at altitudes > 2 km, the extinction is maximum in spring/summer. WRF-Chem model is used to simulate BC temporal variations and then compared with observed BC. The model captures most of the important features of the diurnal and seasonal variations but significantly underestimated the observed BC levels, suggesting improvements in diurnal and seasonal varying BC emissions apart from the boundary layer processes. (C) 2015 Elsevier Ltd. All rights reserved.

El ácido all trans retinoico reduce in vitro el efecto protumoral de los factores de crecimiento e incrementa la eficacia de la quimioterapia en el rabdomiosarcoma S4MH

257 p.

A questão penitenciária no Rio de Janeiro: os reflexos de políticas de lei e ordem

A Prefeitura do Rio de Janeiro, por meio da Secretaria de Ordem Pública e a operação Choque de Ordem, bem como o Governo do Estado do Rio de Janeiro, atra-vés da Secretaria de Segurança Pública e do projeto UPP, demonstram que é cada vez mais constante no cotidiano carioca a adoção de políticas de lei e ordem. Em tempos de Jornada Mundial da Juventude, Copa do Mundo e Olimpíadas, controlar, vigiar, punir, neutralizar são expressões que se destacam nas políticas de segurança pública. As esta-tísticas oficiais demonstram que a adoção de políticas de lei e ordem provocaram, nos últimos cinco anos, crescimento significativo da população carcerária fluminense, com destaque para as prisões provisórias e para o elevado aumento de adolescentes apreen-didos, o que gerou sérias consequências para a execução penal e contribuiu para o au-mento do déficit de vagas do sistema penitenciário do estado do Rio de Janeiro.

7 种蛇毒小肽对临床分离耐(多) 药结核分枝杆菌的体外活性研究

目的　检测7 种从蛇毒分离的小肽是否对临床分离的耐药性结核分枝杆菌菌株具有活性。方法　放射性方法检测蛇毒 小肽对结核分枝杆菌的最小抑制浓度,细菌存活计数确证放射性方法的结果。结果　7 种蛇毒小肽对耐药性结核分枝杆菌菌 株都有活性。其MIC 值分别为(μg·mL - 1) : Opiophagus hannah 5. 4 , Naja at ra 8. 6 , B ungarus f asciatus 6. 4 , Trimeresurus ste2 jnegri 12. 6 , Protobothrops mucrosquamatus 11. 8 , Protobothrops jerdonii 7 , A gksist rodon halys 4. 2 。结论　这些结果是首次报 道,为进一步设计和开发新来源的抗结核病新药提供了依据。

Prolonged cardiac xenograft survival in guinea pig-to-rat model by a highly active cobra venom factor

A highly active cobra venom factor (CVF) was isolated from the venom of Naja kaouthia by sequential column chromatography. It displays strong anticomplementary activity, and has 1515 U of anti complementary activity per mg protein. A single dose of 0.1 mg/kg CVF given i.v. to rats completely abrogated complement activity for nearly 5 days. Given 0.02 mg/kg of CVF. the complement activity of rats was reduced by more than 96.5% in 6 It. In guinea pig-to-rat heart transplant model, rats treated with a single dose of 0.05 mg/kg CVF had significantly prolonged xenograft survival (56.12 +/- 6.27 h in CVF-treated rats vs. 0.19 +/- 0.07 h in control rats, P < 0.001). (C) 2003 Elsevier Ltd. All rights reserved.

Improved suppression of circulating complement does not block acute vascular rejection of pig-to-rhesus monkey cardiac transplants

At present, acute vascular rejection (AVR) remains a primary obstacle inhibiting long-term graft survival in the pig-to-non-human primate transplant model. The present study was undertaken to determine whether repetitive injection of low dose Yunnan-cobra venom factor (Y-CVF), a potent complement inhibitor derived from the venom of Naja kaouthia can completely abrogate hemolytic complement activity and subsequently improve the results in a pig-to-rhesus monkey heterotopic heart transplant model. Nine adult rhesus monkeys received a heterotopic heart transplant from wild-type pigs and the recipients were allocated into two groups: group 1 (n = 4) received repetitive injection of low dose Y-CVF until the end of the study and group 2 (n = 5) did not receive Y-CVF. All recipients were treated with cyclosporine A (CsA), cyclophosphamide (CyP) and steroids. Repetitive Y-CVF treatment led to very dramatic fall in CH50 and serum C3 levels (CH50 < 3 units/C3 remained undetectable throughout the experiment) and successfully prevented hyperacute rejection (HAR), while three of five animals in group 2 underwent HAR. However, the continuous suppression of circulating complement did not prevent AVR and the grafts in group 1 survived from 8 to 13 days. Despite undetectable C3 in circulating blood, C3 deposition was present in these grafts. The venular thrombosis was the predominant histopathologic feature of AVR. We conclude that repetitive injection of low dose Y-CVF can be used to continuously suppress circulating complement in a very potent manner and successfully prevent HAR. However, this therapy did not inhibit complement deposition in the graft and failed to prevent AVR. These data suggest that using alternative pig donors [i.e. human decay accelerating factor (hDAF)-transgenic] in combination with the systemic use of complement inhibitors may be necessary to further control complement activation and improve survival in pig-to-non-human primate xenotransplant model.

Polycyclic aromatic hydrocarbons (PAHS) (I): Measures of prevention and control

Measures of prevention and control against polycyclic aromatic hydrocarbons (PAHs) focus on an official food control, a code of best practice to reduce PAHs levels by controlling industry and in the development of a chemopreventive strategy. Regulation (EU) 835/2011 establishes maximum levels of PAHs for each food group. In addition, Regulations (EU) 333/2007 and 836/2011 set up the methods of sampling and analysis for its official control. Scientific studies prove that the chemopreventive strategy is effective against these genotoxic compounds effects. Most chemopreventive compounds studied with proven protective effects against PAHs are found in fruit and vegetables.

Global down-regulation of HOX gene expression in PML-RAR alpha(+) acute promyelocytic leukemia identified by small-array real-time PCR

Acute promyelocytic leukemia (APL) is associated with a reciprocal and balanced translocation involving the retinoic acid receptor-alpha (RARalpha). All-trans retinoic acid (ATRA) is used to treat APL and is a potent morphogen that regulates HOX gene expression in embryogenesis and organogenesis. HOX genes are also involved in hematopoiesis and leukemogenesis. Thirty-nine mammalian HOX genes have been identified and classified into 13 paralogous groups clustered on 4 chromosomes. They encode a complex net-Work of transcription regulatory proteins whose precise targets remain poorly understood. The overall function of the network appears to be dictated by gene dosage. To investigate the mechanisms involved in HOX gene regulation in hematopoiesis and leukemogenesis by precise measurement of individual HOX genes, a small-array real-time HOX (SMART-HOX) quantitative polymerase chain reaction (PCR) platform was designed and validated. Application of SMART-HOX to 16 APL bone marrow samples revealed a global down-regulation of 26 HOX genes compared with normal controls. HOX gene expression was also altered during differentiation induced by ATRA in the PML-RARalpha(+) NB4 cell line. PML-RARalpha, fusion proteins have been reported to act as part of a repressor complex during myelold cell differentiation, and a model linking HOX gene expression to this PML-RARalpha repressor complex is now proposed.

Pim2 cooperates with PML-RAR alpha to induce acute myeloid leukemia in a bone marrow transplantation model

Although the potential role of Pim2 as a cooperative oncogene has been well described in lymphoma, its role in leukemia has remained largely unexplored. Here we show that high expression of Pim2 is observed in patients with acute promyelocytic leukemia (APL). To further characterize the cooperative role of Pim2 with promyelocytic leukemia/retinoic acid receptor alpha (PML/RAR alpha), we used a well-established PML-RAR alpha (PR alpha) mouse model. Pim2 coexpression in PR alpha-positive hematopoietic progenitor cells (HPCs) induces leukemia in recipient mice after a short latency. Pim2-PR alpha cells were able to repopulate mice in serial transplantations and to induce disease in all recipients. Neither Pim2 nor PR alpha alone was sufficient to induce leukemia upon transplantation in this model. The disease induced by Pim2 overexpression in PR alpha cells contained a slightly higher fraction of immature myeloid cells, compared with the previously described APL disease induced by PR alpha. However, it also clearly resembled an APL-like phenotype and showed signs of differentiation upon all-trans retinoic acid (ATRA) treatment in vitro. These results support the hypothesis that Pim2, which is also a known target of Flt3-ITD (another gene that cooperates with PML-RAR alpha), cooperates with PR alpha to induce APL-like disease. (Blood. 2010; 115(22): 4507-4516)

FUS expression alters the differentiation response to all-trans retinoic acid in NB4 and NB4R2 cells

The FUS gene is overexpressed in acute myeloid leukaemia (AML) patients and has roles in transcription and mRNA processing. We used ectopic expression of FUS and FUS antisense sequences to assess the effect of modulation of FUS expression in all-trans retinoic acid (ATRA)-sensitive (NB4) and insensitive (NB4R2) human acute promyelocytic (APL) cell lines which express the t(15:17) translocation. Growth, viability and differentiation patterns were maintained, but the expression of the FUS antisense construct in both the cell lines altered the response to ATRA: the previously ATRA-sensitive NB4 cells exhibited resistance; whilst the previously resistant NB4R2 cells showed a differentiation response to treatment.

Assessing the extent to which temporal changes in waterbird community composition are driven by either local, regional or global factors.

1. Lough Neagh and Lough Beg Special Protection Area (SPA, hereafter Lough Neagh) is an important non-estuarine site in Britain and Ireland for overwintering wildfowl. Multivariate analysis of the winter counts showed a state-shift in the waterbird community following winter 2000/2001, mostly due to rapid declines in abundance (46–57% declines in the mean mid-winter January counts between 1993–2000 and 2002–2009) of members of the diving duck guild (pochard Aythya ferina, tufted duck Aythya fuligula and goldeneye Bucephala clangula) and coot (Fulica atra), a submerged macrophyte feeder.
2. Only pochard showed correlations between declines at Lough Neagh and those of overall species flyway population indices to suggest that global changes could contribute to declines at the site. However, indices from the Republic of Ireland showed no overall decline in the rest of Ireland. Tufted duck indices at the site were inversely related to indices in Great Britain. Lough Neagh goldeneye indices were positively correlated with indices in the Republic of Ireland and Great Britain, suggesting that short-stopping could contribute to declines at the site. Coot declines at Lough Neagh did not correlate with trends elsewhere, suggesting local factors involved in the decline.
3. These analyses indicate that although there are potentially different explanations for the dramatic declines in these four waterbird species at this site, the simultaneous nature of the declines across two feeding guilds strongly
suggest that local factors (such as loss of submerged macrophytes and benthic invertebrates) were involved. An assessment of the food supply, local disturbance and other factors at Lough Neagh is required to find an explanation for the observed adverse trends in wintering numbers of the affected species.
4. This study highlights the potential of waterbird community structure to reflect the status of aquatic systems, but confirms the need to establish site-specific factors responsible for the observed changes in abundance of key waterbird species at a site.

Global down-regulation of HOX gene expression in PML-RARalpha + acute promyelocytic leukemia identified by small-array real-time PCR

Acute promyelocytic leukemia (APL) is associated with a reciprocal and balanced translocation involving the retinoic acid receptor-alpha (RARalpha). All-trans retinoic acid (ATRA) is used to treat APL and is a potent morphogen that regulates HOX gene expression in embryogenesis and organogenesis. HOX genes are also involved in hematopoiesis and leukemogenesis. Thirty-nine mammalian HOX genes have been identified and classified into 13 paralogous groups clustered on 4 chromosomes. They encode a complex network of transcription regulatory proteins whose precise targets remain poorly understood. The overall function of the network appears to be dictated by gene dosage. To investigate the mechanisms involved in HOX gene regulation in hematopoiesis and leukemogenesis by precise measurement of individual HOX genes, a small-array real-time HOX (SMART-HOX) quantitative polymerase chain reaction (PCR) platform was designed and validated. Application of SMART-HOX to 16 APL bone marrow samples revealed a global down-regulation of 26 HOX genes compared with normal controls. HOX gene expression was also altered during differentiation induced by ATRA in the PML-RARalpha(+) NB4 cell line. PML-RARalpha fusion proteins have been reported to act as part of a repressor complex during myeloid cell differentiation, and a model linking HOX gene expression to this PML-RARalpha repressor complex is now proposed.

Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes:results of the MRC AML15 trial

Two hundred eighty-five patients, median age 42, with PML-RARa-positive acute promyelocytic leukaemia were randomised to Ara-C-containing 'Medical Research Council (MRC) Chemotherapy'+ATRA (All-trans-retinoic acid) or anthracycline+ATRA (modified 'Spanish') therapy. MRC treatment comprised four courses with ATRA in courses 1-2. Spanish treatment comprised four anthracycline-based courses with ATRA in courses 1-3. In course 3 patients were randomised to gemtuzumab ozogamicin (GO) or not. The Spanish arm received 24-month maintenance. Patients were sequentially molecularly monitored. Quality of life was assessed at baseline, 3, 6, 9, 12, 24 months. Remission rates were similar in both arms (93%): cumulative incidence of haematological relapse (CIHR) was 6% at 5 years; 5 patients relapsed molecularly. Survival post relapse was 80%. There were more deaths in remission in the MRC arm (4% vs 10%: P=0.2). The overall 5-year relapse-free and overall survival was similar between arms (81% vs 82% and 84% vs 83%, respectively). More supportive care and hospitalisation (81.8 vs 63 days, P10 × 10(9)/l) was not prognostic overall, or within treatment arms. Both approaches deliver similar results with minor differences in quality of life. MRC treatment required more hospitalisation. This suggests that additional chemotherapy, Ara-C in particular, is not required.

Forecasting invasions: resource use by mussels informs invasion patterns along the South African coast

Invasive species are often more able to rapidly and efficiently utilise resources than natives, and comparing per capita resource use at different resource densities among invaders and trophically analogous natives could allow for reliable predictions of invasiveness. In South Africa, invasion by the Mediterranean mussel Mytilus galloprovincialis has transformed wave-exposed shores, negatively affecting native mussel species. Currently, South Africa is experiencing a second mussel invasion with the recent detection of the South American Semimytilus algosus. We tested per capita uptake of an algal resource by invading M. galloprovincialis, S. algosus, and the native Aulacomya atra at different algal concentrations and temperatures, representing the west and south coasts of South Africa, to examine whether their per capita resource use could be a predictor of their spread and subsequent invasiveness. Regardless of temperature, M. galloprovincialis was the most efficient consumer, significantly reducing algal cells compared to the other species when the resource was presented in both low and high starting densities. Furthermore, these findings aligned with a greater biomass of M. galloprovincialis on the shore in comparison with the other species. Resource use by the new invader S. algosus was dependent on the density of resource and, although this species was efficient at low algal concentrations at cooler temperatures, this pattern broke down at higher algal densities. This was once more reflected in lower biomass in surveys of this species along the cool west coast. We therefore forecast that S. algosus will be become established along the south coast; however, we also predict that M. galloprovincialis will maintain dominance on these shores.

Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial

BACKGROUND: Acute promyelocytic leukaemia is a chemotherapy-sensitive subgroup of acute myeloid leukaemia characterised by the presence of the PML-RARA fusion transcript. The present standard of care, chemotherapy and all-trans retinoic acid (ATRA), results in a high proportion of patients being cured. In this study, we compare a chemotherapy-free ATRA and arsenic trioxide treatment regimen with the standard chemotherapy-based regimen (ATRA and idarubicin) in both high-risk and low-risk patients with acute promyelocytic leukaemia.

METHODS: In the randomised, controlled, multicentre, AML17 trial, eligible patients (aged ≥16 years) with acute promyelocytic leukaemia, confirmed by the presence of the PML-RARA transcript and without significant cardiac or pulmonary comorbidities or active malignancy, and who were not pregnant or breastfeeding, were enrolled from 81 UK hospitals and randomised 1:1 to receive treatment with ATRA and arsenic trioxide or ATRA and idarubicin. ATRA was given to participants in both groups in a daily divided oral dose of 45 mg/m(2) until remission, or until day 60, and then in a 2 weeks on-2 weeks off schedule. In the ATRA and idarubicin group, idarubicin was given intravenously at 12 mg/m(2) on days 2, 4, 6, and 8 of course 1, and then at 5 mg/m(2) on days 1-4 of course 2; mitoxantrone at 10 mg/m(2) on days 1-4 of course 3, and idarubicin at 12 mg/m(2) on day 1 of the final (fourth) course. In the ATRA and arsenic trioxide group, arsenic trioxide was given intravenously at 0·3 mg/kg on days 1-5 of each course, and at 0·25 mg/kg twice weekly in weeks 2-8 of course 1 and weeks 2-4 of courses 2-5. High-risk patients (those presenting with a white blood cell count >10 × 10(9) cells per L) could receive an initial dose of the immunoconjugate gemtuzumab ozogamicin (6 mg/m(2) intravenously). Neither maintenance treatment nor CNS prophylaxis was given to patients in either group. All patients were monitored by real-time quantitative PCR. Allocation was by central computer minimisation, stratified by age, performance status, and de-novo versus secondary disease. The primary endpoint was quality of life on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 global health status. All analyses are by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN55675535.

FINDINGS: Between May 8, 2009, and Oct 3, 2013, 235 patients were enrolled and randomly assigned to ATRA and idarubicin (n=119) or ATRA and arsenic trioxide (n=116). Participants had a median age of 47 years (range 16-77; IQR 33-58) and included 57 high-risk patients. Quality of life did not differ significantly between the treatment groups (EORTC QLQ-C30 global functioning effect size 2·17 [95% CI -2·79 to 7·12; p=0·39]). Overall, 57 patients in the ATRA and idarubicin group and 40 patients in the ATRA and arsenic trioxide group reported grade 3-4 toxicities. After course 1 of treatment, grade 3-4 alopecia was reported in 23 (23%) of 98 patients in the ATRA and idarubicin group versus 5 (5%) of 95 in the ATRA and arsenic trioxide group, raised liver alanine transaminase in 11 (10%) of 108 versus 27 (25%) of 109, oral toxicity in 22 (19%) of 115 versus one (1%) of 109. After course 2 of treatment, grade 3-4 alopecia was reported in 25 (28%) of 89 patients in the ATRA and idarubicin group versus 2 (3%) of 77 in the ATRA and arsenic trioxide group; no other toxicities reached the 10% level. Patients in the ATRA and arsenic trioxide group had significantly less requirement for most aspects of supportive care than did those in the ATRA and idarubicin group.

INTERPRETATION: ATRA and arsenic trioxide is a feasible treatment in low-risk and high-risk patients with acute promyelocytic leukaemia, with a high cure rate and less relapse than, and survival not different to, ATRA and idarubicin, with a low incidence of liver toxicity. However, no improvement in quality of life was seen.