Effects of post anaerobic digestion thermal hydrolysis on dewaterability and moisture distribution in digestates.

Organic waste fractions such as sewage sludge, food waste and manure can be stabilized by anaerobic digestion (AD) to produce renewable energy in the form of biogas. Following AD, the digested solid fraction (digestate) is usually dewatered to reduce the volume before transportation. Post-AD treatments such as the Post-AD thermal hydrolysis process (Post-AD THP) have been developed to improve the dewatering, but the mode of action is not well understood. In this study, samples from 32 commercial full-scale plants were used to assess the impact of Post-AD THP on a broad range of raw materials. Maximum dewatered cake solids after Post-AD THP was predicted by thermogravimetric analysis (TGA). Post-AD THP changed the moisture distribution of the samples by increasing the free water fraction. A consistent improvement in predicted dewatered cake solids was achieved across the 32 samples tested, on average increasing the dry solids concentration by 87%. A full-scale trial showed that dewatering Post-AD THP digestate at 80 °C improved dewatered cake solids above the predictions by TGA at 35 °C. In conclusion, dewatered cake solids were significantly improved by Post-AD THP, reducing the volume of dewatered cake for disposal.

Surface Toll-like receptor 3 expression in metastatic intestinal epithelial cells induces inflammatory cytokine production and promotes invasiveness.

Toll-like receptors (TLRs) are innate immune receptors for sensing microbial molecules and damage-associated molecular patterns released from host cells. Double-stranded RNA and the synthetic analog polyinosinic:polycytidylic acid (poly(I:C)) bind and activate TLR3. This stimulation leads to recruitment of the adaptor molecule TRIF (Toll/IL-1 resistance (TIR) domain-containing adapter-inducing interferon ß) and activation of the transcription factors nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3), classically inducing IFNß production. Here we report that, unlike non-metastatic intestinal epithelial cells (IECs), metastatic IECs express TLR3 and that TLR3 promotes invasiveness of these cells. In response to poly(I:C) addition, the metastatic IECs also induced the chemokine CXCL10 in a TLR3-, TRIF-, and IRF3-dependent manner but failed to produce IFNß. This was in contrast to healthy and non-metastatic IECs, which did not respond to poly(I:C) stimulation. Endolysosomal acidification and the endosomal transporter protein UNC93B1 was required for poly(I:C)-induced CXCL10 production. However, TLR3-induced CXCL10 was triggered by immobilized poly(I:C), was only modestly affected by inhibition of endocytosis, and could be blocked with an anti-TLR3 antibody, indicating that TLR3 can still signal from the cell surface of these cells. Furthermore, plasma membrane fractions from metastatic IECs contained both full-length and cleaved TLR3, demonstrating surface expression of both forms of TLR3. Our results imply that metastatic IECs express surface TLR3, allowing it to sense extracellular stimuli that trigger chemokine responses and promote invasiveness in these cells. We conclude that altered TLR3 expression and localization may have implications for cancer progression.

Microscopic Investigation into the Electric Field Effect on Proximity-Induced Magnetism in Pt.

Electric field effects on magnetism in metals have attracted widespread attention, but the microscopic mechanism is still controversial. We experimentally show the relevancy between the electric field effect on magnetism and on the electronic structure in Pt in a ferromagnetic state using element-specific measurements: x-ray magnetic circular dichroism (XMCD) and x-ray absorption spectroscopy (XAS). Electric fields are applied to the surface of ultrathin metallic Pt, in which a magnetic moment is induced by the ferromagnetic proximity effect resulting from a Co underlayer. XMCD and XAS measurements performed under the application of electric fields reveal that both the spin and orbital magnetic moments of Pt atoms are electrically modulated, which can be explained not only by the electric-field-induced shift of the Fermi level but also by the change in the orbital hybridizations.

Modulated function of multidrug resistance-associated proteins in cisplatin-induced acute renal failure rats.

The effect of cisplatin-induced acute renal failure (ARF) on the function and expression of multidrug resistanceassociated proteins (MRPs) was evaluated in rats. Rats received an intraperitoneal injection of cisplatin (9 mg/kg), and the induction of ARF state with high plasma concentrations of indoxyl sulfate and creatinine was observed 72 h after cisplatin treatment. The function of MRPs in the liver, kidney and brain was evaluated by measuring the tissue accumulation and biliary excretion of 2,4-dintrophenyl-S-glutathione (DNP-SG), a substrate for MRPs, after administration of 1-chloro-2,4-dintrobenzene (CDNB), a precursor of DNP-SG, in rats. The levels of MRP1-4 expression were evaluated by Western blot analysis. Effect of ARF plasma components on MRP function was also examined by using calcein acetoxymethyl ester (calcein-AM) in HepG2 cells. In ARF rats (72 h after cisplatin treatment), the accumulation of DNP-SG in the liver, kidney and brain was significantly higher than those in control and cisplatin-treated rats (1 h after treatment). In ARF rats, intrinsic biliary excretion clearance of DNP-SG, estimated by dividing the biliary excretion rate of DNP-SG with the liver concentration, was also significantly reduced, though the expression levels of MRP1-4 in the liver remained unchanged. ARF rat plasma (5%) significantly increased the accumulation of calcein, a MRP substrate, in HepG2 cells after application of calcein-AM. In conclusion, MRP function was found to be suppressed not only in the kidney but also in the liver and brain in cisplatin-induced ARF rats, possibly due to the accumulation of some MRP substrates/inhibitors in plasma.

Role of multifunctional transcription factor TFII-I and putative tumour suppressor DBC1 in cell cycle and DNA double strand damage repair.

BACKGROUND: In multicellular organisms, precise control of cell cycle and the maintenance of genomic stability are crucial to prevent chromosomal alterations. The accurate function of the DNA damage pathway is maintained by DNA repair mechanisms including homologous recombination (HR). Herein, we show that both TFII-I and DBC1 mediate cellular mechanisms of cell-cycle regulation and DNA double strand damage repair. METHODS: Regulation of cell cycle by TFII-I and DBC1 was investigated using Trypan blue dye exclusion test, luciferase assay, and flow cytometry analysis. We also analysed the role of TFII-I and DBC1 in DNA double strand damage repair after irradiation by immunofluorescence study, clonogenicity assay, and HR assay. RESULTS: Flow cytometry analysis revealed a novel function that siRNA-mediated knockdown of endogenous DBC1 resulted in G2/M phase arrest. We also have shown that both endogenous TFII-I and DBC1 activate DNA repair mechanisms after irradiation because irradiation-induced foci formation of TFII-I-γH2AX was observed, and the depletion of endogenous TFII-I or DBC1 resulted in the inhibition of normal HR efficiency. CONCLUSION: These results reveal novel mechanisms by which TFII-I and DBC1 can modulate cellular fate by affecting cell-cycle control as well as HR pathway.

Vegetarian diets and incidence of diabetes in the Adventist Health Study-2.

AIM: To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. METHODS AND RESULTS: Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093-1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236-0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503-0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312-0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249-0.740; OR 0.684, 95% CI 0.542-0.862; OR 0.501, 95% CI 0.303-0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110-0.842; OR 0.472, 95% CI 0.270-0.825). These associations were strengthened when BMI was removed from the analyses. CONCLUSION: Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.

Relationship of vitamin D levels to blood pressure in a biethnic population.

BACKGROUND AND AIMS: Accumulating epidemiological and clinical studies have suggested that vitamin D insufficiency may be associated with hypertension. Blacks tend to have lower vitamin D levels than Whites, but it is unclear whether this difference explains the higher blood pressure (BP) observed in Blacks in a population with healthy lifestyle practices. METHODS AND RESULTS: We examined cross-sectional data in the Adventist Health Study-2 (AHS-2), a cohort of non-smoking, mostly non-drinking men and women following a range of diets from vegan to non-vegetarian. Each participant provided dietary, demographic, lifestyle and medical history data. Measurements of weight, height, waist circumference, percent body fat and blood pressure and fasting blood samples were obtained from a randomly selected non-diabetic sample of 284 Blacks and 284 Whites aged 30-95 years. Multiple regression analyses were used to assess independent relationships between blood pressure and 25(OH)D levels. Levels of 25(OH)D were inversely associated with systolic BP in Whites after control for age, gender, BMI, and use of BP-lowering medications (ß-coefficient -0.23 [95% CI, -0.43, -0.03; p = 0.02]). This relationship was not seen in Blacks (ß-coefficient 0.08 [95% CI, -0.14, 0.30; p = 0.4]). Results were similar when controlling for waist circumference or percentage body fat instead of BMI. No relationship between serum 25(OH)D and diastolic BP was seen. CONCLUSION: Systolic BP is inversely associated with 25(OH)D levels in Whites but not in Blacks. Vitamin D may not be a major contributor to the White-Black differential in BP.

High-density lipoprotein cholesterol subfractions and lecithin: cholesterol acyltransferase activity in collegiate soccer players.

Many of the published data on the lipid profile of athletes is based on studies of endurance athletes. The data on soccer players are rare. The purpose of this study was to examine serum high-density lipoprotein cholesterol subfractions and lecithin:cholesterol acyltransferase activity in collegiate soccer players. 31 well-trained male collegiate soccer players were divided into 2 groups: 16 defenders and 15 offenders. They were compared with 16 sedentary controls. Dietary information was obtained with a food frequency questionnaire. The subjects were all non-smokers and were not taking any drug known to affect the lipid and lipoprotein metabolism. The offenders had significantly higher high-density lipoprotein cholesterol, high-density lipoprotein2 cholesterol, and apolipoprotein A-I than the defenders and controls, whereas the defenders had the significantly higher high-density lipoprotein2 cholesterol than the controls. Both groups of athletes had significantly higher lecithin:cholesterol acyltransferase activity than the controls. The results indicate that favorable lipid and lipoprotein profile could be obtained by vigorous soccer training.

Workplace oral health promotion activities among community-aged care workers: A qualitative exploration.

BACKGROUND: The workplace is an ideal-and priority-setting for health promotion activities. Developing and implementing workplace health promotion interventions, including oral health promotion activities, can help create health-supporting workplace environments. OBJECTIVE: To pilot workplace oral health promotion activities among staff working in the aged care sector, report their impact and explore participants' views on the factors that contribute to participation and effectiveness. METHODS: This study comprised three phases: (i) the development and face validation of the resources, (ii) a 3-h educational session and (iii) five interview sessions with participants 4-6 weeks following the education session. The recorded interviews were transcribed verbatim and analysed thematically. RESULTS: Eleven community-aged care workforce were invited to five feedback sessions. Ten participants were female and ranged in age from 18 to 64. All participants gave favourable comments about the content and delivery of the training session and accompanying resources. The participants felt that the benefits of WOHP include improved staff knowledge, awareness and oral care routine, the ability to share (and put into practice) the gained knowledge and information with their dependants, a lower risk of having poor oral health that adversely affects their well-being and work tasks, and potentially beneficial impacts on the organization's staff roster. Their attendance in the WOHP was facilitated by being paid to attend and scheduling the sessions during work time. Future WOHP suggestions include the possibility of a one-stop dental check-up at the workplace or staff dental care discounts from local dental practitioners and combining oral health with other health promotion activities. CONCLUSIONS: Planning and implementing WOHP was deemed acceptable and feasible in this study context and successfully achieved short-term impacts among community-aged care workers. Appropriate times and locations, organizational arrangements and a variety of delivery options contributed to successful programme planning and implementation.

Microfocus x-ray imaging of traceable pointlike (22)Na sources for quality control.

PURPOSE: The purpose of this study is to propose a microfocus x-ray imaging technique for observing the internal structure of small radioactive sources and evaluating geometrical errors quantitatively, and to apply this technique to traceable pointlike (22)Na sources, which were designed for positron emission tomography calibration, for the purpose of quality control of the pointlike sources. METHODS: A microfocus x-ray imaging system with a focus size of 0.001 mm was used to obtain projection x-ray images and x-ray CT images of five pointlike source samples, which were manufactured during 2009-2012. The obtained projection and tomographic images were used to observe the internal structure and evaluate geometrical errors quantitatively. Monte Carlo simulation was used to evaluate the effect of possible geometrical errors on the intensity and uniformity of 0.511 MeV annihilation photon pairs emitted from the sources. RESULTS: Geometrical errors were evaluated with sufficient precision using projection x-ray images. CT images were used for observing the internal structure intuitively. As a result, four of the five examined samples were within the tolerance to maintain the total uncertainty below ±0.5%, given the source radioactivity; however, one sample was found to be defective. CONCLUSIONS: This quality control procedure is crucial and offers an important basis for using the pointlike (22)Na source as a basic calibration tool. The microfocus x-ray imaging approach is a promising technique for visual and quantitative evaluation of the internal geometry of small radioactive sources.

[Is emergency aortic root replacement combined with arch replacement safe?].

BACKGROUND: Aortic root replacement (ARR) combined with aortic arch replacement (AAR) is an invasive procedure even in elective cases. Nevertheless, such combined operations are often mandatory in acute type A aortic dissection. We examined whether emergency operation might have further incremental risks compared with elective surgery in this type of operations. METHODS: Forty-six cases of ARR combined with AAR were divided into 2 groups, the emergency (EM) group and the elective (EL) group. The EM group consisted of 10 cases of acute type A aortic dissection, whereas the EL group of 36:23 of chronic aortic dissection and 13 of true aneurysm. RESULTS: There were no statistical differences between the 2 groups in the durations of aortic crossclamp, selective cerebral perfusion and cardiopulmonary bypass. The incidences in the EM and EL groups were as follows:in-hospital death; 0 vs 3( 8%), respiratory failure; 4 (40%) vs 14 (39%), renal failure; 0 vs 6 (17%), IABP requirement; 1 (10%) vs 3 (8%), and cerebral infarction; 0 vs 1 (3%), respectively. CONCLUSION: Early surgical results of emergency ARR combined with AAR were almost equal to those in elective surgery.

Mass-resolved ion measurement by particle counting analysis for characterizing relativistic ion beams driven by lasers.

Particle counting analysis is a possible way to characterize GeV-scale, multi-species ions produced in laser-driven experiments. We present a multi-layered scintillation detector to differentiate multi-species ions of different masses and energies. The proposed detector concept offers potential advantages over conventional diagnostics in terms of (1) high sensitivity to GeV ions, (2) realtime analysis, and (3) the ability to differentiate ions with the same charge-to-mass ratio. A novel choice of multiple scintillators with different ion stopping powers results in a significant difference in energy deposition between the scintillators, allowing accurate particle identification in the GeV range. Here, we report a successful demonstration of particle identification for heavy ions, performed at the Heavy Ion Medical Accelerator in Chiba. In the experiment, the proposed detector setup showed the ability to differentiate particles with similar atomic numbers, such as C6+ and O8+ ions, and provided an excellent energy resolution of 0.41%-1.2% (including relativistic effect, 0.51%--1.6%).

Robustness of large-area suspended graphene under interaction with intense laser.

Graphene is known as an atomically thin, transparent, highly electrically and thermally conductive, light-weight, and the strongest 2D material. We investigate disruptive application of graphene as a target of laser-driven ion acceleration. We develop large-area suspended graphene (LSG) and by transferring graphene layer by layer we control the thickness with precision down to a single atomic layer. Direct irradiations of the LSG targets generate MeV protons and carbons from sub-relativistic to relativistic laser intensities from low contrast to high contrast conditions without plasma mirror, evidently showing the durability of graphene.

Multifunctional transcription factor TFII-I is an activator of BRCA1 function.

BACKGROUND: The TFII-I is a multifunctional transcriptional factor known to bind specifically to several DNA sequence elements and to mediate growth factor signalling. A microdeletion at the chromosomal location 7q11.23 encoding TFII-I and the related family of transcription factors may result in the onset of Williams-Beuren syndrome, an autosomal dominant genetic disorder characterised by a unique cognitive profile, diabetes, hypertension, anxiety, and craniofacial defects. Hereditary breast and ovarian cancer susceptibility gene product BRCA1 has been shown to serve as a positive regulator of SIRT1 expression by binding to the promoter region of SIRT1, but cross talk between BRCA1 and TFII-I has not been investigated to date. METHODS: A physical interaction between TFII-I and BRCA1 was explored. To determine pathophysiological function of TFII-I, its role as a transcriptional cofactor for BRCA1 was investigated. RESULTS: We found a physical interaction between the carboxyl terminus of TFII-I and the carboxyl terminus of BRCA1, also known as the BRCT domain. Endogenous TFII-I and BRCA1 form a complex in nuclei of intact cells and formation of irradiation-induced nuclear foci was observed. We also showed that the expression of TFII-I stimulates the transcriptional activation function of BRCT by a transient expression assay. The expression of TFII-I also enhanced the transcriptional activation of the SIRT1 promoter mediated by full-length BRCA1. CONCLUSION: These results revealed the intrinsic mechanism that TFII-I may modulate the cellular functions of BRCA1, and provide important implications to understand the development of breast cancer.

Synthesis of an azadioxa-planar triphenylborane and investigation of its structural and photophysical properties.

We report here the first successful synthesis of planar triphenylborane 1 with the phenyl groups bridged by oxygen and nitrogen atoms via double nucleophilic aromatic substitution reaction. The hetero atom-bridged 1 has excellent planarity. Its structural and photophysical properties are tunable by altering the bridging atoms.

Effect of inulin-type fructans on appetite in patients with type 2 diabetes: a randomised controlled crossover trial.

The aim of the study was to investigate the effect of prebiotic fibres on appetite-regulating hormones, subjective feeling of appetite and energy intake in subjects with type 2 diabetes. Data presented are secondary outcomes of a study investigating the effect of prebiotics on glucagon-like peptide-1 and glycaemic regulation. We conducted a randomised and placebo-controlled crossover trial to evaluate the effects of 16 g/d of inulin-type fructans or a control supplement (maltodextrin) for 6 weeks in randomised order, with a 4-week washout period in-between, on appetite in thirty-five men and women with type 2 diabetes. Data were collected at visits before and after each treatment: plasma concentration of the satiety-related peptides ghrelin and peptide YY (PYY) were assessed during a standardised mixed meal. The subjective sensation of appetite was evaluated in response to an ad libitum lunch by rating the visual analogue scale. Twenty-nine individuals (twelve women) were included in the analyses. Compared to control treatment, the prebiotics did not affect ghrelin (P =0⋅71) or the ratings of hunger (P = 0⋅62), satiety (P = 0⋅56), fullness (P = 0⋅73) or prospective food consumption (P = 0⋅98). Energy intake also did not differ between the treatments. However, the response of PYY increased significantly after the control treatment with mean (sem) 11⋅1 (4⋅3) pg/ml when compared to the prebiotics -0⋅3 (4⋅3) pg/ml (P = 0⋅013). We observed no effect of inulin-type fructans on appetite hormones, subjective feeling of appetite or energy intake in patients with type 2 diabetes.

Identification of DBC1 as a transcriptional repressor for BRCA1.

BACKGROUND: DBC1/KIAA1967 (deleted in breast cancer 1) is a putative tumour-suppressor gene cloned from a heterozygously deleted region in breast cancer specimens. Caspase-dependent processing of DBC1 promotes apoptosis, and depletion of endogenous DBC1 negatively regulates p53-dependent apoptosis through its specific inhibition of SIRT1. Hereditary breast and ovarian cancer susceptibility gene product BRCA1, by binding to the promoter region of SIRT1, is a positive regulator of SIRT1 expression. METHODS: A physical interaction between DBC1 and BRCA1 was investigated both in vivo and in vitro. To determine the pathophysiological significance of DBC1, its role as a transcriptional factor was studied. RESULTS: We found a physical interaction between the amino terminus of DBC1 and the carboxyl terminus of BRCA1, also known as the BRCT domain. Endogenous DBC1 and BRCA1 form a complex in the nucleus of intact cells, which is exported to the cytoplasm during ultraviolet-induced apoptosis. We also showed that the expression of DBC1 represses the transcriptional activation function of BRCT by a transient expression assay. The expression of DBC1 also inhibits the transactivation of the SIRT1 promoter mediated by full-length BRCA1. CONCLUSION: These results revealed that DBC1 may modulate the cellular functions of BRCA1 and have important implications in the understanding of carcinogenesis in breast tissue.

Cerebrospinal fluid metabolite and nigrostriatal dopaminergic function in Parkinson's disease.

OBJECTIVES: To evaluate the association between cerebrospinal fluid (CSF) homovanillic acid (HVA) concentrations and nigrostriatal dopaminergic function assessed by positron emission tomography (PET) imaging with carbon-11-labeled 2beta-carbomethoxy-3beta-(4-fluorophenyl)-tropane ((11)C-CFT), which can measure the dopamine transporter (DAT) density, in Parkinson's disease (PD). METHODS: (11)C-CFT PET scans and CSF examinations were performed on 21 patients with PD, and six patients with non-parkinsonian syndromes (NPS) as a control group. RESULTS: In the PD group, CSF HVA concentrations were significantly correlated with the striatal uptake of (11)C-CFT (r = 0.76, P < 0.01). However, in the NPS group, two indices were within the normal range. CONCLUSIONS: In PD, CSF HVA concentrations correlate with nigrostriatal dopaminergic function. Therefore, CSF HVA concentrations may be an additional surrogate marker for estimating the remaining nigrostriatal dopaminergic function in case that DAT imaging is unavailable.

Quantification of soluble recalcitrant compounds in commercial thermal hydrolysis digestates.

Solid residues such as primary sludge (PS), waste activated sludge (WAS), and food waste (FW) can be stabilized through anaerobic digestion (AD). Application of the thermal hydrolysis process (THP) prior to AD results in several benefits in AD and dewatering. However, soluble recalcitrant compounds associated with Maillard reactions have been identified after THP which can impact downstream processes and water discharge limits. In this study, the soluble colloidal chemical oxygen demand, color, ultraviolet absorbance at 254 nm and dissolved organic nitrogen in seven full-scale THP facilities were quantified and compared. The THP substrate influenced the concentration of soluble melanoidin-associated compounds in the digestates. THP implementation in five water resource recovery facilities (WRRFs) was modeled and found to give a 3-8 mg/L increase on the water effluent COD concentration depending on the PS/WAS ratio. The results provide novel information useful in planning new WRRFs and optimization of existing facilities. PRACTITIONER POINTS: High amounts of WAS in substrate resulted in higher concentrations of CODsc, color and dissolved organic nitrogen in the digestate. Food waste treated at 145°C showed equal or lower concentrations of all components compared with sludge operated at 165°C. Installation of THP will increase the COD concentration in the water effluent of a water resource recovery facility. The characteristics of the THP substrate are important to consider in cost/benefit analysis when planning the installation of THP.

The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas.

BACKGROUND: The phosphatidylinositol 3'-kinase (PI3K)-AKT pathway is activated in many human cancers and plays a key role in cell proliferation and survival. A mutation (E17K) in the pleckstrin homology domain of the AKT1 results in constitutive AKT1 activation by means of localisation to the plasma membrane. The AKT1 (E17K) mutation has been reported in some tumour types (breast, colorectal, ovarian and lung cancers), and it is of interest which tumour types other than those possess the E17K mutation. METHODS: We analysed the presence of the AKT1 (E17K) mutation in 89 endometrial cancer tissue specimens and in 12 endometrial cancer cell lines by PCR and direct sequencing. RESULTS: We detected two AKT1 (E17K) mutations in the tissue samples (2 out of 89) and no mutations in the cell lines. These two AKT1 mutant tumours do not possess any mutations in PIK3CA, PTEN and K-Ras. INTERPRETATION: Our results and earlier reports suggest that AKT1 mutations might be mutually exclusive with other PI3K-AKT-activating alterations, although PIK3CA mutations frequently coexist with other alterations (such as HER2, K-Ras and PTEN) in several types of tumours.