331 research outputs found
The tseung kwan o landfill controversy
AnalysisThis article examines the controversy that arose from the Hong Kong Government's plan to extend the South East New Territories Landfill in Tseung Kwan O into the Clear Water Bay Country Park, particularly how the proposed landfill extension led to a confrontation between the government and the legislature. The authors argue that s 14 of the Country Parks Ordinance (Cap 208) imposes an obligation on the Chief Executive to make an order which he is not free to repeal thereafter. This arrangement comports with the overall statutory scheme and purpose of the legislation which features a four-stage process with provisions for public consultation. The controversy calls into question the efficacy of this four-stage process as well as that of the environmental impact assessment regime. The authors suggest that there is a need to consider strengthening the statutory mechanism for public involvement to prevent a repetition of the present controversy. This article also examines the broader issue of the territory's waste management strategy and the need for more environmentally sustainable policies.published_or_final_versio
Reconstruction of phyletic trees by global alignment of multiple metabolic networks
Background: In the last decade, a considerable amount of research has been devoted to investigating the phylogenetic properties of organisms from a systems-level perspective. Most studies have focused on the classification of organisms based on structural comparison and local alignment of metabolic pathways. In contrast, global alignment of multiple metabolic networks complements sequence-based phylogenetic analyses and provides more comprehensive information.
Results: We explored the phylogenetic relationships between microorganisms through global alignment of multiple metabolic networks. The proposed approach integrates sequence homology data with topological information of metabolic networks. In general, compared to recent studies, the resulting trees reflect the living style of organisms as well as classical taxa. Moreover, for phylogenetically closely related organisms, the classification results are consistent with specific metabolic characteristics, such as the light-harvesting systems, fermentation types, and sources of electrons in photosynthesis.
Conclusions: We demonstrate the usefulness of global alignment of multiple metabolic networks to infer phylogenetic relationships between species. In addition, our exhaustive analysis of microbial metabolic pathways reveals differences in metabolic features between phylogenetically closely related organisms. With the ongoing increase in the number of genomic sequences and metabolic annotations, the proposed approach will help identify phenotypic variations that may not be apparent based solely on sequence-based classification.National Institutes of Health (U.S.) (Grant GM081871
The anti-tumor effect of Apo2L/TRAIL on patient pancreatic adenocarcinomas grown as xenografts in SCID mice
BACKGROUND: Apo2L/TRAIL has considerable promise for cancer therapy based on the fact that this member of the tumor necrosis factor family induces apoptosis in the majority of malignant cells, while normal cells are more resistant. Furthermore, in many cells, when Apo2L/TRAIL is combined with chemotherapy, the effect is synergistic. The majority of this work has been carried out using cell lines. Therefore, investigation of how patient tumors respond to Apo2L/TRAIL can validate and/or complement information obtained from cell lines and prove valuable in the design of future clinical trials. METHODS: We have investigated the Apo2L/TRAIL sensitivity of patient derived pancreatic tumors using a patient tumor xenograft/ SCID mouse model. Mice bearing engrafted tumors were treated with Apo2L/TRAIL, gemcitabine or a combination of both therapies. RESULTS: Patient tumors grown as xenografts exhibited a spectrum of sensitivity to Apo2L/TRAIL. Both Apo2L/TRAIL sensitive and resistant pancreatic tumors were found, as well as tumors that showed heterogeneity of response. Changes in apoptotic signaling molecules in a sensitive tumor were analyzed by Western blot following Apo2L/TRAIL treatment; loss of procaspase 8, Bid and procaspase 3 was observed and correlated with inhibition of tumor growth. However, in a tumor that was highly resistant to killing by Apo2L/TRAIL, although there was a partial loss of procaspase 8 and Bid in response to Apo2L/TRAIL treatment, loss of procaspase 3 was negligible. This resistant tumor also expressed a high level of the anti-apoptotic molecule Bcl-X(L )that, in comparison, was not detected in a sensitive tumor. Importantly, in the majority of these tumors, addition of gemcitabine to Apo2L/TRAIL resulted in a greater anti-tumor effect than either therapy used alone. CONCLUSION: These data suggest that in a clinical setting we will see heterogeneity in the response of patients' tumors to Apo2L/TRAIL, including tumors that are highly sensitive as well as those that are resistant. While much more work is needed to understand the molecular basis for this heterogeneity, it is very encouraging, that Apo2L/TRAIL in combination with gemcitabine increased therapeutic efficacy in almost every case and therefore may be a highly effective strategy for controlling human pancreatic cancer validating and expanding upon what has been reported for cell lines
Photometry of Kuiper belt object (486958) Arrokoth from New Horizons LORRI
On January 1st 2019, the New Horizons spacecraft flew by the classical Kuiper belt object (486958) Arrokoth (provisionally designated 2014 MU69), possibly the most primitive object ever explored by a spacecraft. The I/F of Arrokoth is analyzed and fit with a photometric function that is a linear combination of the Lommel-Seeliger (lunar) and Lambert photometric functions. Arrokoth has a geometric albedo of p_v = 0.21_(−0.04)^(+0.05) at a wavelength of 550 nm and ≈0.24 at 610 nm. Arrokoth's geometric albedo is greater than the median but consistent with a distribution of cold classical Kuiper belt objects whose geometric albedos were determined by fitting a thermal model to radiometric observations. Thus, Arrokoth's geometric albedo adds to the orbital and spectral evidence that it is a cold classical Kuiper belt object. Maps of the normal reflectance and hemispherical albedo of Arrokoth are presented. The normal reflectance of Arrokoth's surface varies with location, ranging from ≈0.10–0.40 at 610 nm with an approximately Gaussian distribution. Both Arrokoth's extrema dark and extrema bright surfaces are correlated to topographic depressions. Arrokoth has a bilobate shape and the two lobes have similar normal reflectance distributions: both are approximately Gaussian, peak at ≈0.25 at 610 nm, and range from ≈0.10–0.40, which is consistent with co-formation and co-evolution of the two lobes. The hemispherical albedo of Arrokoth varies substantially with both incidence angle and location, the average hemispherical albedo at 610 nm is 0.063 ± 0.015. The Bond albedo of Arrokoth at 610 nm is 0.062 ± 0.015
Etanercept withdrawal and retreatment in nonradiographic axial spondyloarthritis: results of RE-EMBARK, an open-label phase IV trial
Clinical trial[Abstract] Objective: RE-EMBARK investigated etanercept (ETN) withdrawal and retreatment in patients with nonradiographic axial spondyloarthritis (nr-axSpA) achieving inactive disease.
Methods: Patients received ETN and a background nonsteroidal antiinflammatory drug for 24 weeks in period 1 (P1); those achieving inactive disease (Ankylosing Spondylitis Disease Activity Score [ASDAS] with C-reactive protein [CRP] < 1.3) discontinued ETN for 40 weeks or less (period 2 [P2]). Patients who flared (ASDAS with erythrocyte sedimentation rate [ESR] ≥ 2.1) were retreated for 12 weeks in period 3 (P3). The primary endpoint was the proportion of patients with inactive disease who flared within 40 weeks of ETN withdrawal. Baseline characteristics were analyzed post hoc as predictors of maintenance and regaining of inactive disease, respectively, using univariate logistic and stepwise multivariable logistic regression models.
Results: The proportion of patients experiencing flare following ETN withdrawal (P2) increased from 22.3% (25/112) after 4 weeks to 67% (77/115) after 40 weeks; 74.8% (86/115) experienced flare at any time during P2. Median time to flare was 16.1 weeks. Most patients (54/87, 62.1%) who were retreated with ETN in P3 reachieved inactive disease. Absence of both sacroiliitis detected on magnetic resonance imaging (MRI) and high-sensitivity CRP (hs-CRP) > 3 mg/L at baseline predicted inactive disease maintenance in P2 following ETN withdrawal in multivariable analysis; male sex and age younger than 40 years predicted regaining of inactive disease in P3 after flare/retreatment. There were no unexpected safety signals.
Conclusion: Approximately 25% of patients maintained inactive disease for 40 weeks after discontinuing ETN. Absence of both MRI sacroiliitis and high hs-CRP at baseline predicted response maintenance after ETN withdrawal
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