Genome-wide association study in two cohorts from a multi-generational mouse advanced intercross line highlights the difficulty of replication due to study-specific heterogeneity

There has been extensive discussion of the Replication Crisis in many fields, including genome-wide association studies

Would transcranial direct current stimulation (tDCS) enhance the effects of working memory training in older adults with mild neurocognitive disorder due to Alzheimer’s disease: study protocol for a randomized controlled trial

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Granulin-epithelin precursor is an oncofetal protein defining hepatic cancer stem cells

Background and Aims: Increasing evidence has suggested that hepatocellular carcinoma (HCC) might originate from a distinct subpopulation called cancer stem cells (CSCs), which are responsible for the limited efficacy of conventional therapies. We have previously demonstrated that granulin-epithelin precursor (GEP), a pluripotent growth factor, is upregulated in HCC but not in the adjacent non-tumor, and that GEP is a potential therapeutic target for HCC. Here, we characterized its expression pattern and stem cell properties in fetal and cancerous livers. Methods: Protein expression of GEP in fetal and adult livers was examined in human and mouse models by immunohistochemical staining and flow cytometry. Liver cancer cell lines, isolated based on their GEP and/or ATP-dependent binding cassette (ABC) drug transporter ABCB5 expression, were evaluated for hepatic CSC properties in terms of colony formation, chemoresistance and tumorigenicity. Results: We demonstrated that GEP was a hepatic oncofetal protein that expressed in the fetal livers, but not in the normal adult livers. Importantly, GEP+ fetal liver cells co-expressed the embryonic stem (ES) cell-related signaling molecules including β-catenin, Oct4, Nanog, Sox2 and DLK1, and also hepatic CSC-markers CD133, EpCAM and ABCB5. Phenotypic characterization in HCC clinical specimens and cell lines revealed that GEP+ cancer cells co-expressed these stem cell markers similarly as the GEP+ fetal liver cells. Furthermore, GEP was shown to regulate the expression of ES cell-related signaling molecules β-catenin, Oct4, Nanog, and Sox2. Isolated GEP high cancer cells showed enhanced colony formation ability and chemoresistance when compared with the GEP low counterparts. Co-expression of GEP and ABCB5 better defined the CSC populations with enhanced tumorigenic ability in immunocompromised mice. Conclusions: Our findings demonstrate that GEP is a hepatic oncofetal protein regulating ES cell-related signaling molecules. Co-expression of GEP and ABCB5 further enriches a subpopulation with enhanced CSC properties. The current data provide new insight into the therapeutic strategy. © 2011 Cheung et al.published_or_final_versio

Cognitive Function in Patients Undergoing Arthroplasty: The Implications for Informed Consent

Obtaining informed consent for an operation is a fundamental daily interaction between orthopaedic surgeon and patient. It is based on a patient's capacity to understand and retain information about the proposed procedure, the potential consequences of having it, and the alternative options available. We used validated tests of memory on 59 patients undergoing lower limb arthroplasty to assess how well they learned and recalled information about their planned procedure. All patients showed an ability to learn new material; however, younger age and higher educational achievement correlated with better performance. These results have serious implications for orthopaedic surgeons discussing planned procedures. They identify groups of patients who may require enhanced methods of communicating the objectives, risks, and alternatives to surgery. Further research is necessary to assess interventions to improve communication prior to surgery

Identification and characterization of tropomyosin 3 associated with granulin-epithelin precursor in human hepatocellular carcinoma

Background and Aim: Granulin-epithelin precursor (GEP) has previously been reported to control cancer growth, invasion, chemo-resistance, and served as novel therapeutic target for cancer treatment. However, the nature and characteristics of GEP interacting partner remain unclear. The present study aims to identify and characterize the novel predominant interacting partner of GEP using co-immunoprecipitation and mass spectrometry. Methods and Results: Specific anti-GEP monoclonal antibody was used to capture GEP and its interacting partner from the protein extract of the liver cancer cells Hep3B. The precipitated proteins were analyzed by SDS-PAGE, followed by mass spectrometry and the protein identity was demonstrated to be tropomyosin 3 (TPM3). The interaction has been validated in additional cell models using anti-TPM3 antibody and immunoblot to confirm GEP as the interacting partner. GEP and TPM3 expressions were then examined by real-time quantitative RT-PCR in clinical samples, and their transcript levels were significantly correlated. Elevated TPM3 levels were observed in liver cancer compared with the adjacent non-tumorous liver, and patients with elevated TPM3 levels were shown to have poor recurrence-free survival. Protein expression of GEP and TPM3 was observed only in the cytoplasm of liver cancer cells by immunohistochemical staining. Conclusions: TPM3 is an interacting partner of GEP and may play an important role in hepatocarcinogenesis. © 2012 Lam et al.published_or_final_versio

Inherent noise can facilitate coherence in collective swarm motion

Among the most striking aspects of the movement of many animal groups are their sudden coherent changes in direction. Recent observations of locusts and starlings have shown that this directional switching is an intrinsic property of their motion. Similar direction switches are seen in self-propelled particle and other models of group motion. Comprehending the factors that determine such switches is key to understanding the movement of these groups. Here, we adopt a coarse-grained approach to the study of directional switching in a self-propelled particle model assuming an underlying one-dimensional Fokker–Planck equation for the mean velocity of the particles. We continue with this assumption in analyzing experimental data on locusts and use a similar systematic Fokker–Planck equation coefficient estimation approach to extract the relevant information for the assumed Fokker–Planck equation underlying that experimental data. In the experiment itself the motion of groups of 5 to 100 locust nymphs was investigated in a homogeneous laboratory environment, helping us to establish the intrinsic dynamics of locust marching bands. We determine the mean time between direction switches as a function of group density for the experimental data and the self-propelled particle model. This systematic approach allows us to identify key differences between the experimental data and the model, revealing that individual locusts appear to increase the randomness of their movements in response to a loss of alignment by the group. We give a quantitative description of how locusts use noise to maintain swarm alignment. We discuss further how properties of individual animal behavior, inferred by using the Fokker–Planck equation coefficient estimation approach, can be implemented in the self-propelled particle model to replicate qualitatively the group level dynamics seen in the experimental data

Enhanced performance in polymer photovoltaic cells with chloroform treated indium tin oxide anode modification

Enhanced performance of a poly(3-hexylthiophene):(6,6)-phenyl C61 butyric acid methyl ester bulk heterojunction polymer photovoltaic cell is reported by modifying the indium tin oxide (ITO) anode with chloroform solution. Instead of the traditional UV-ozone treatment, the optimized chloroform modification on ITO anode can result in an enhancement in the power conversion efficiency of an identical device, originating from an increase in the photocurrent with negligible change in the open-circuit voltage. The performance enhancement is attributed to the work function modification of the ITO substrate through the surface incorporation of the chlorine, and thus improved charge collection efficiency. © 2011 American Institute of Physics

A phase 1 dose-escalating study of pegylated recombinant human arginase 1 (Peg-rhArg1) in patients with advanced hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) cells are auxotrophic for arginine, depletion of which leads to tumour regression. The current study evaluated safety, pharmacokinetics (PK)/ pharmacodynamics (PD) parameters, and potential anti-tumor activity of pegylated recombinant human arginase 1 (peg-rhArg1) in advanced HCC patients. Methods Eligibility criteria included advanced HCC with measurable lesions, Child-Pugh A or B, and adequate organ function. Initial single IV bolus was followed by weekly doses of peg-rhArgI escalated from 500 U/kg to 2500 U/kg in a 3 + 3 design. Results Fifteen patients were enrolled at weekly doses of 500 U/kg (n = 3), 1000 U/kg (n = 3), 1600 U/kg (n = 3) and 2500 U/kg (n = 6). The median age was 57 years (33-74); 87% were hepatitis B carriers and 47% had prior systemic treatment. The most commonly reported drug-related non-haematological adverse events (AEs) were diarrhea (13.3%), abdominal discomfort (6.7%) and nausea (6.7%). No drug-related haematological AEs were seen. Only 1 of the six patients that received 2500U/kg peg-rhArg1 experienced DLT (grade 4 bilirubin elevation) and thus the maximum tolerated dose was 2500 U/kg. PK and PD analysis indicated that peg-rhArg1 was efficacious in inducing arginine depletion in a dose-dependent manner. Adequate arginine depletion dose was achieved in the 1,600-2,500 U/kg range and therefore the optimal biological dose was at 1600 U/kg, which was chosen as the recommended dose. The best response was stable disease for >8 weeks in 26.7% of the enrolled patients. Conclusion Peg-rhArg1 has manageable safety profile and preliminary evidence of activity in advanced HCC patients.published_or_final_versio

Surface plasmon-enhanced electroluminescence in organic light-emitting diodes incorporating Au nanoparticles

Surface plasmon-enhanced electroluminescence (EL) in an organic light-emitting diode is demonstrated by incorporating the synthesized Au nanoparticles (NPs) in the hole injection layer of poly(3,4-ethylene dioxythiophene):polystyrene sulfonic acid. An increase of ∼25% in the EL intensity and efficiency are achieved for devices with Au NPs, whereas the spectral and electrical properties remain almost identical to the control device. Time-resolved photoluminescence spectroscopy reveals that the EL enhancement is ascribed to the increase in spontaneous emission rate due to the plasmonic near-field effect induced by Au NPs. © 2012 American Institute of Physics