Chemotherapeutic effect of a novel temozolomide analog on nasopharyngeal carcinoma in vitro and in vivo.

BackgroundMany patients with nasopharyngeal carcinoma (NPC) face poor prognosis. Due to its hidden anatomical location, the tumor is usually diagnosed quite late, and despite initially successful treatment with radiation and cisplatin, many patients will relapse and succumb to the disease. New treatment options are urgently needed. We have performed preclinical studies to evaluate the potential NPC therapeutic activity of a newly developed analog of temozolomide (TMZ), an alkylating agent that is the current chemotherapeutic standard of care for patients with malignant glioma.ResultsTMZ was covalently conjugated to the natural monoterpene perillyl alcohol (POH), creating the novel fusion compound NEO212. Its impact on two NPC cell lines was studied through colony formation assays, cell death ELISA, immunoblots, and in vivo testing in tumor-bearing mice. In vitro, NEO212 effectively triggered tumor cell death, and its potency was significantly greater than that of its individual components, TMZ or POH alone. Intriguingly, merely mixing TMZ with POH also was unable to achieve the superior potency of the conjugated compound NEO212. Treatment of NPC cells with NEO212 inactivated the chemoprotective DNA repair protein MGMT (O6-methylguanine methyltransferase), resulting in significant chemosensitization of cells to a second round of drug treatment. When tested in vivo, NEO212 reduced tumor growth in treated animals.ConclusionOur results demonstrate anticancer activity of NEO212 in preclinical NPC models, suggesting that this novel compound should be evaluated further for the treatment of patients with NPC

It Takes a Team to Make It Through: The Role of Social Support for Survival and Self-Care After Allogeneic Hematopoietic Stem Cell Transplant

Background: Social support plays an important role for health outcomes. Support for those living with chronic conditions may be particularly important for their health, and even for their survival. The role of support for the survival of cancer patients after receiving an allogeneic hematopoietic cell transplant (alloHCT) is understudied. To better understand the link between survival and support, as well as different sources and functions of support, we conducted two studies in alloHCT patients. First, we examined whether social support is related to survival (Study 1). Second, we examined who provides which support and which specific support-related functions and tasks are fulfilled by lay caregivers and healthcare professionals (Study 2). Methods: In Study 1, we conducted a retrospective chart review of alloHCT patients (N = 173, 42.8% female, age: M = 49.88) and registered availability of a dedicated lay caregiver and survival. In Study 2, we prospectively followed patients after alloHCT (N = 28, 46.4% female, age: M = 53.97, 46.4% ethnic minority) from the same hospital, partly overlapping from Study 1, who shared their experiences of support from lay caregivers and healthcare providers in semi-structured in-depth interviews 3 to 6 months after their first hospital discharge. Results: Patients with a dedicated caregiver had a higher probability of surviving to 100 days (86.7%) than patients without a caregiver (69.6%), OR = 2.84, p = 0.042. Study 2 demonstrated the importance of post-transplant support due to patients' emotional needs and complex self-care regimen. The role of lay caregivers extended to many areas of patients' daily lives, including support for attending doctor's appointments, managing medications and financial tasks, physical distancing, and maintaining strict dietary requirements. Healthcare providers mainly fulfilled medical needs and provided informational support, while lay caregivers were the main source of emotional and practical support. Conclusion: The findings highlight the importance of studying support from lay caregivers as well as healthcare providers, to better understand how they work together to support patients' adherence to recommended self-care and survival

Development of an End-Use Sector-Based Low-Carbon Indicator System for Cities in China

In 2009, China committed to reducing its carbon dioxide intensity (CO2/unit of gross domestic product, GDP) by 40 to 45 percent by 2020 from a 2005 baseline. In March 2011, China’s 12th Five-Year Plan established a carbon intensity reduction goal of 17% between 2011 and 2015. China’s National Development and Reform Commission (NDRC) then announced the selection of five provinces and eight cities to pilot low carbon development work. Macro-level indicators of low carbon development, such as energy use or CO2 emissions per unit of GDP or per capita may be too aggregated to be meaningful measurements of whether a city or province is truly “low carbon”. Instead, indicators based on energy end-use sectors (industry, residential, commercial, transport) offer a better approach for defining “low carbon” and for taking action to reduce energy-related carbon emissions. This paper presents and tests a methodology for the development of an end-use sectorbased low-carbon indicator system at the city level, providing initial results for an end-use low carbon indicator system based on data available at the municipal levels. The paper consists of a discussion of macro-level indicators that are typically used for inter-city, regional, or intercountry comparisons; the methodology used to develop a more robust low carbon indicator system for China; and the results of this indicator system. The research concludes with a discussion of issues encountered during the development of the end-use sector-based low-carbon indicator, followed by recommendations for future improvement

Direct grafting of tetraaniline via perfluorophenylazide photochemistry to create antifouling, low bio-adhesion surfaces.

Conjugated polyaniline has shown anticorrosive, hydrophilic, antibacterial, pH-responsive, and pseudocapacitive properties making it of interest in many fields. However, in situ grafting of polyaniline without harsh chemical treatments is challenging. In this study, we report a simple, fast, and non-destructive surface modification method for grafting tetraaniline (TANI), the smallest conjugated repeat unit of polyaniline, onto several materials via perfluorophenylazide photochemistry. The new materials are characterized by nuclear magnetic resonance (NMR) and electrospray ionization (ESI) mass spectroscopy. TANI is shown to be covalently bonded to important carbon materials including graphite, carbon nanotubes (CNTs), and reduced graphene oxide (rGO), as confirmed by transmission electron microscopy (TEM). Furthermore, large area modifications on polyethylene terephthalate (PET) films through dip-coating or spray-coating demonstrate the potential applicability in biomedical applications where high transparency, patternability, and low bio-adhesion are needed. Another important application is preventing biofouling in membranes for water purification. Here we report the first oligoaniline grafted water filtration membranes by modifying commercially available polyethersulfone (PES) ultrafiltration (UF) membranes. The modified membranes are hydrophilic as demonstrated by captive bubble experiments and exhibit extraordinarily low bovine serum albumin (BSA) and Escherichia coli adhesions. Superior membrane performance in terms of flux, BSA rejection and flux recovery after biofouling are demonstrated using a cross-flow system and dead-end cells, showing excellent fouling resistance produced by the in situ modification

De novo design of bioactive protein switches.

Allosteric regulation of protein function is widespread in biology, but is challenging for de novo protein design as it requires the explicit design of multiple states with comparable free energies. Here we explore the possibility of designing switchable protein systems de novo, through the modulation of competing inter- and intramolecular interactions. We design a static, five-helix 'cage' with a single interface that can interact either intramolecularly with a terminal 'latch' helix or intermolecularly with a peptide 'key'. Encoded on the latch are functional motifs for binding, degradation or nuclear export that function only when the key displaces the latch from the cage. We describe orthogonal cage-key systems that function in vitro, in yeast and in mammalian cells with up to 40-fold activation of function by key. The ability to design switchable protein functions that are controlled by induced conformational change is a milestone for de novo protein design, and opens up new avenues for synthetic biology and cell engineering

More Filtering on SNP Calling Does Not Remove Evidence of Inter-Nucleus Recombination in Dikaryotic Arbuscular Mycorrhizal Fungi

Evidence for the existence of dikaryote-like strains, low nuclear sequence diversity and inter-nuclear recombination in arbuscular mycorrhizal fungi has been recently reported based on single nucleus sequencing data. Here, we aimed to support evidence of inter-nuclear recombination using an approach that filters SNP calls more conservatively, keeping only positions that are exclusively single copy and homozygous, and with at least five reads supporting a given SNP. This methodology recovers hundreds of putative inter-nucleus recombination events across publicly available sequence data from individual nuclei. Challenges related to the acquisition and analysis of sequence data from individual nuclei are highlighted and discussed, and ways to address these issues in future studies are presented

Impact of Trucking Network Flow on Preferred Biorefinery Locations in the Southern United States

The impact of the trucking transportation network flow was modeled for the southern United States. The study addresses a gap in existing research by applying a Bayesian logistic regression and Geographic Information System (GIS) geospatial analysis to predict biorefinery site locations. A one-way trucking cost assuming a 128.8 km (80-mile) haul distance was estimated by the Biomass Site Assessment model. The median family income, timberland annual growth-to-removal ratio, and transportation delays were significant in determining mill location. Transportation delays that directly impacted the costs of trucking are presented. A logistic model with Bayesian inference was used to identify preferred site locations, and locations not preferential for a mill location. The model predicted that higher probability locations for smaller biomass mills (feedstock capacity, the size of sawmills) were in southern Alabama, southern Georgia, southeast Mississippi, southern Virginia, western Louisiana, western Arkansas, and eastern Texas. The higher probability locations for large capacity mills (feedstock capacity, the size for pulp and paper mills) were in southeastern Alabama, southern Georgia, central North Carolina, and the Mississippi Delta regions

Ozone and Daily Mortality in Shanghai, China

BACKGROUND: Controversy remains regarding the relationship between ambient ozone and mortality worldwide. In mainland China, the largest developing country, there has been no prior study investigating the acute effect of O(3) on death risk. Given the changes in types of air pollution from conventional coal combustion to the mixed coal combustion/motor vehicle emissions in China’s large cities, it is worthwhile to investigate the acute effect of O(3) on mortality outcomes in the country. OBJECTIVES: We conducted a time-series study to investigate the relation between O(3) and daily mortality in Shanghai using 4 years of daily data (2001–2004). METHODS: We used the generalized additive model with penalized splines to analyze mortality, O(3) pollution, and covariate data in warm and cold seasons. We considered daily counts of all-cause mortality and several cause-specific subcategories (respiratory and cardiovascular). We also examined these associations among several subpopulations based on age and sex. RESULTS: O(3) was significantly associated with total and cardiovascular mortality in the cold season but not in the warm season. In the whole-year analysis, an increase of 10 μg/m(3) of 2-day average (lag01) O(3) corresponds to 0.45% [95% confidence interval (CI), 0.16–0.73%], 0.53% (95% CI, 0.10–0.96%), and 0.35% (95% CI, −0.40 to 1.09%) increase of total nonaccidental, cardiovascular, and respiratory mortality, respectively. In the cold season, the estimates increased to 1.38% (95% CI, 0.68–2.07%), 1.53% (95% CI, 0.54–2.52%), and 0.95% (95% CI, −0.71 to 2.60%), respectively. In the warm season, we did not observe significant associations for both total and cause-specific mortality. The results were generally insensitive to model specifications such as lag structure of O(3) concentrations and degree of freedom for time trend. Multipollutant models indicate that the effect of O(3) was not confounded by particulate matter ≤ 10 μm in diameter (PM(10)) or by sulfur dioxide; however, after adding nitrogen dioxide into the model, the association of O(3) with total and cardiovascular mortality became statistically insignificant. CONCLUSIONS: O(3) pollution has stronger health effects in the cold than in the warm season in Shanghai. Our analyses also strengthen the rationale for further limiting levels of O(3) pollution in outdoor air in the city