A microbiological survey of a constructed wetland system supplied by dairy 'dirty water' effluent

A constructed wetland at Greenmount College, Co. Antrim, N. Ireland was built in 2004 to study the treatment of ‘dirty water’ effluent from the Greenmount dairy unit. The effluent has a mean BOD5 of c.1000 mg/L and contains milking parlour wash-water and runoff from silage clamps and yard areas lightly contaminated with cattle manure. The nominal water retention time of this wetland is 100 days. The primary purposes of the wetland are to eliminate organic pollution and eutrophication risk from nitrogen and phosphorus compounds. However the wetland should also effectively remove any zoonotic pathogens present in manure and milk. Accordingly, a 12-month microbiological survey of water in the five ponds of the wetland commenced in August 2007. The aims of the survey are to determine changes, as effluent passes through the wetland system, in a broad range of indicator organisms (faecal coliforms, Escherichia coli, Enterococcus faecalis and Clostridium perfringens) and the occurrence of several pathogens - Salmonella, Campylobacter, Cryptosporidium and Mycobacterium avium subsp. paratuberculosis (Map). The highest indicator organism counts - E. coli and faecal coliforms, 103-104 CFU/ml - are observed in pond 1, and a significant reduction (1-3 log10) in all indicator organisms occurs as water passes through the wetland from pond 1 to pond 5. Hence the wetland is efficient at reducing levels of indicator organisms in the dairy effluent. Salmonella and Campylobacter spp. are being detected intermittently in all the ponds, whilst Cryptosporidium and Map have yet to be detected, and so the ability of the wetland to reduce/eliminate specific pathogens is less clear at present.

Role of versican V0/V1 and CD44 in the regulation of human melanoma cell behaviour

Versican is a hyaluronan-binding, large extracellular matrix chondroitin sulfate proteoglycan whose expression is increased in malignant melanoma. Binding to hyaluronan allows versican to indirectly interact with the hyaluronan cell surface receptor CD44. The aim of this work was to study the effect of silencing the large versican isoforms (V0 and V1) and CD44 in the SK-mel-131 human melanoma cell line. Versican V0/V1 or CD44 silencing caused a decrease in cell proliferation and migration, both in wound healing assays and in Transwell chambers. Versican V0/V1 silencing also caused an increased adhesion to type I collagen, laminin and fibronectin. These results support the proposed role of versican as a proliferative, anti-adhesive and pro-migratory molecule. On the other hand, CD44 silencing caused a decrease in cell adhesion to vitronectin, fibronectin and hyaluronan. CD44 silencing inhibited the binding of a FITC-hyaluronan complex to the cell surface and its internalization into the cytoplasm. Our results indicate that both versican and CD44 play an important role regulating the behavior of malignant melanoma cells.

Investigation of Machining Parameters for Multiple Response Optimization in Microelectrodischarge Milling

This paper investigated the influence of three micro electrodischarge milling process parameters, which were feed rate, capacitance, and voltage. The response variables were average surface roughness (R a ), maximum peak-to-valley roughness height (R y ), tool wear ratio (TWR), and material removal rate (MRR). Statistical models of these output responses were developed using three-level full factorial design of experiment. The developed models were used for multiple-response optimization by desirability function approach to obtain minimum R a , R y , TWR, and maximum MRR. Maximum desirability was found to be 88%. The optimized values of R a , R y , TWR, and MRR were 0.04, 0.34 μm, 0.044, and 0.08 mg min−1, respectively for 4.79 μm s−1 feed rate, 0.1 nF capacitance, and 80 V voltage. Optimized machining parameters were used in verification experiments, where the responses were found very close to the predicted values.

Immunoselection of breast and ovarian cancer cells with trastuzumab and natural killer cells:selective escape of CD44high/CD24low/HER2low breast cancer stem cells

Although trastuzumab (Herceptin) has substantially improved the overall survival of patients with mammary carcinomas, even initially well-responding tumors often become resistant. Because natural killer (NK) cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) is thought to contribute to the therapeutic effects of trastuzumab, we have established a cell culture system to select for ADCC-resistant SK-OV-3 ovarian cancer and MCF7 mammary carcinoma cells. Ovarian cancer cells down-regulated HER2 expression, resulting in a more resistant phenotype. MCF7 breast cancer cells, however, failed to develop resistance in vitro. Instead, treatment with trastuzumab and polyclonal NK cells resulted in the preferential survival of individual sphere-forming cells that displayed a CD44(high)CD24(low) "cancer stem cell-like" phenotype and expressed significantly less HER2 compared with non-stem cells. Likewise, the CD44(high)CD24(low) population was also found to be more immunoresistant in SK-BR3, MDA-MB231, and BT474 breast cancer cell lines. When immunoselected MCF7 cells were then re-expanded, they mostly lost the observed phenotype to regenerate a tumor cell culture that displayed the initial HER2 surface expression and ADCC-susceptibility, but was enriched in CD44(high)CD24(low) cancer stem cells. This translated into increased clonogenicity in vitro and tumorigenicity in vivo. Thus, we provide evidence that the induction of ADCC by trastuzumab and NK cells may spare the actual tumor-initiating cells, which could explain clinical relapse and progress. Moreover, our observation that the "relapsed" in vitro cultures show practically identical HER2 surface expression and susceptibility toward ADCC suggests that the administration of trastuzumab beyond relapse might be considered, especially when combined with an immune-stimulatory treatment that targets the escape variants.

Balls to the wall: How acoustic information from a ball in motion guides interceptive movement in people with Parkinson’s disease

Previous research has shown that Parkinson's disease (PD) patients can increase the speed of their movement when catching a moving ball compared to when reaching for a static ball (Majsak et al., 1998). A recent model proposed by Redgrave et al. (2010) explains this phenomenon with regard to the dichotomic organization of motor loops in the basal ganglia circuitry and the role of sensory micro-circuitries in the control of goal-directed actions. According to this model, external visual information that is relevant to the required movement can induce a switch from a habitual control of movement toward an externally-paced, goal-directed form of guidance, resulting in augmented motor performance (Bienkiewicz et al., 2013). In the current study, we investigated whether continuous acoustic information generated by an object in motion can enhance motor performance in an arm reaching task in a similar way to that observed in the studies of Majsak et al. (1998, 2008). In addition, we explored whether the kinematic aspects of the movement are regulated in accordance with time to arrival information generated by the ball's motion as it reaches the catching zone. A group of 7 idiopathic PD (6 male, 1 female) patients performed a ball-catching task where the acceleration (and hence ball velocity) was manipulated by adjusting the angle of the ramp. The type of sensory information (visual and/or auditory) specifying the ball's arrival at the catching zone was also manipulated. Our results showed that patients with PD demonstrate improved motor performance when reaching for a ball in motion, compared to when stationary. We observed how PD patients can adjust their movement kinematics in accordance with the speed of a moving target, even if vision of the target is occluded and patients have to rely solely on auditory information. We demonstrate that the availability of dynamic temporal information is crucial for eliciting motor improvements in PD. Furthermore, these effects appear independent from the sensory modality through-which the information is conveyed. 

Docking the value of pigmeat? Prevalence and financial implications of welfare lesions in Irish slaughter pigs.

Expansion of the meat inspection process to incorporate animal-based welfare measurements could contribute towards significant improvements in pig (Sus scrofa domesticus) welfare and farm profitability. This study aimed to determine the prevalence of different welfare-related lesions on the carcase and their relationship with carcase condemnations (CC) and carcase weight (CW). The financial implications of losses associated with CC and CW reductions related to the welfare lesions were also estimated. Data on tail lesions, loin bruising and bursitis, CW and condemnation/trimming outcome (and associated weights) were collected for 3,537slaughter pigs (mean [± SEM] carcase weight: 79.2 [± 8.82] kg). Overall, 72.5% of pigs had detectable tail lesions, whilst 16.0 and 44.0% were affected by severe loin bruising and hind limb bursitis, respectively. There were 2.5% of study carcases condemned and a further 3.3% were trimmed. The primary cause of CC was abscessation. While tail lesion severity did not increase the risk of abscessation, it was significantly associated with CC. Male pigs had a higher risk of tail lesions and of CC. The financial loss to producers associated with CC and trimmings was estimated at €1.10 per study pig. CW was reduced by up to 12 kg in cases of severe tail lesions. However, even mild lesions were associated with a significant reduction in CW of 1.2 kg. The value of the loss in potential CW associated with tail lesions was €0.59 per study pig. Combined with losses attributable to CC and trimmings this represented a loss of 43% of the profit margin per pig, at the time of the study, attributable to tail biting. These findings illustrate the magnitude of the impact of tail biting on pig welfare and on profitability of the pig industry. They also emphasise the potential contribution that the inclusion of welfare parameters at meat inspection could make to pig producers in informing herd health and welfare management plans.

The Distribution and Adoption of the Byre-house (Longhouse) in Late Medieval Britain

It has long been recognized that the byre-house or longhouse, in which animals and humans lived in the same building and with direct contact, was a distinctive building plan. Earlier interpretations have seen it as a ubiquitous house type found throughout Britain, but gradually replaced by separate buildings for keeping animals and accommodating humans. More recent work has suggested that it was a regional variant of the common late medieval domestic plan. The use of this building type was restricted to parts of Wales, and northern and western areas of England. It is argued that the introduction of the byre-house occurs mainly in the thirteenth century as part of a wider trend to provide accommodation for livestock during the winter months. The byre-house was a one response to this need, and its adoption was not due to climatic or geographical factors. Instead, it is interpreted as reflecting localized cultural attitudes to the relationship between humans and animals.

The fate of chemoresistance in triple negative breast cancer (TNBC)

Background: Treatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype. 
Scope of Review: How tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease. Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed. 
Major conclusions: Cellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome. 
General Significance: Focusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy

Proportioning variability in the dispensation of hand-mixed dental cements

Objectives: The purpose of this investigation was to determine for dispensed multiples (1 through 4) of powder (P) and liquid (L) in hand-mixed dental cement whether: (1) the mean (P/L) ratio (m/m) and (2) the maximum difference in (P/L) ratio is dependent on the number of multiples dispensed. The Null hypotheses were: (a) mean (P/L) ratio is independent of the number of multiples dispensed and (b) maximum difference in (P/L) ratio is independent of the number of multiples dispensed.
Methods: The materials investigated are listed in the Table. The masses of dispensed aliquots of powder and liquid were measured by a single operator (n=10, for multiples 1 through 4) on a 4-place analytical balance. All measurements were made independently and all possible (P/L) ratios calculated for each sample. The effect of multiple dispensations on (P/L) ratios and maximum (P/L) differences was by one-way ANOVA and linear regression, respectively, with the Tukey post-hoc correction for multiple comparisons.MULTIPLE DISPENSEDDISPENSED MU(x1)(x2)(x3)(x4)Zinc phosphateHeraeus12.271(0.691)a13.051(1.269)b13.215(0.824)b13.118(1.149)bFuji IXGC4.209(0.373)a4.085(0.275)b4.095(0.226)b4.095(0.217)bIRMDentsply7.933(0.767)a7.430(0.451)b7.977(0.729)a8.186(0.929)aKetac-Cem3M Espe9.6206(0.613)a9.714(0.523)a9.298(0.314)b9.321(0.292)bMean (SD) powder/liquid ratio (m/m). Superscript letters represent significances (α = 0.05) within each material
Results: Mean (SD) (P/L) ratios are presented in the Table. Null hypothesis (a) is rejected: either (x1) or (x2) dispensation yields a different (P/L) ratio to (x3) or (x4) (p < 0.05). Null hypothesis (b) is rejected: a negative correlation is observed in max (P/L) ratio difference with dispensed multiple for Ketac Cem (p = 0.029).
Conclusion: For hand-mixed dental cements: (1) more consistent (P/L) ratios may be observed with multiple dispensations of powder & liquid; (2) maximum differences in (P/L) ratio may be negatively correlated with dispensation multiple in some materials.

Labour Law as Human Rights Law: A Critique of the Use of ‘Dignity’ by Freedland and Kountouris

In their recent book, The Legal Construction of Personal Work Relations, Mark Freedland and Nicola Kountouris present an ambitious study of the personal scope of (what they would not want to call) ‘employment’ law. The book does this within a broader argument that calls for the reconceptualization of labour law as a whole, and it is this broader argument on which I shall focus in this chapter. Their aim, in urging us to see labour law through the lens of ‘dignity’ is to bring labour law and human rights law into closer alignment than has sometimes been the case in the past. Increasingly, dignity is seen as providing a, sometimes the, foundation of human rights law, particularly in Europe. I shall suggest that whilst the aim of constructing a new set of foundations for labour law is a worthy and increasingly urgent task, the concepts on which Freedland and Kountouris seek to build their project pose significant difficulties. In particular, their espousal of ‘dignity’ presents problems that must be addressed if their reconceptualization is not to prove a blind alley.

High resolution monitoring of surface morphological change of building limestones in response to simulated salt weathering

A salt weathering simulation using a mix of sodium chloride (5%) and magnesium sulphate (5%) in a salt corrosion cabinet and five granular limestones is described. Progressive surface loss from vertical exposed faces was mapped using a high resolution (sub-millimetre) object scanner (Konica Minolta Vi9i). Patterns of loss are related to surface porosity/permeability measurements obtained using a hand-held gas permeameter. Introduction of this spatial dimension into damage assessment is seen as essential for understanding the initial conditions that allow surface loss to be triggered, and changes in surface characteristics as weathering proceeds which dictate subsequent decay in space and time. Preliminary observations suggest that scanning at this high resolution is particularly valuable in quantifying very subtle trends and distortions that are pre-cursors to material loss, including surface swelling and pore filling.

Mullerian inhibiting substance inhibits breast cancer cell growth through an NFkappa B-mediated pathway

Müllerian inhibiting substance (MIS), a member of the transforming growth factor-beta superfamily, induces regression of the Müllerian duct in male embryos. In this report, we demonstrate MIS type II receptor expression in normal breast tissue and in human breast cancer cell lines, breast fibroadenoma, and ductal adenocarcinomas. MIS inhibited the growth of both estrogen receptor (ER)-positive T47D and ER-negative MDA-MB-231 breast cancer cell lines, suggesting a broader range of target tissues for MIS action. Inhibition of growth was manifested by an increase in the fraction of cells in the G(1) phase of the cell cycle and induction of apoptosis. Treatment of breast cancer cells with MIS activated the NFkappaB pathway and selectively up-regulated the immediate early gene IEX-1S, which, when overexpressed, inhibited breast cancer cell growth. Dominant negative IkappaBalpha expression ablated both MIS-mediated induction of IEX-1S and inhibition of growth, indicating that activation of the NFkappaB signaling pathway was required for these processes. These results identify the NFkappaB-mediated signaling pathway and a target gene for MIS action and suggest a putative role for the MIS ligand and its downstream interactors in the treatment of ER-positive as well as negative breast cancers.

Mullerian inhibiting substance inhibits breast cancer cell growth through an NFκB-mediated pathway

Mullerian inhibiting substance (MIS), a member of the transforming growth factor-β superfamily, induces regression of the Mullerian duct in male embryos. In this report, we demonstrate MIS type II receptor expression in normal breast tissue and in human breast cancer cell lines, breast fibroadenoma, and ductal adenocarcinomas. MIS inhibited the growth of both estrogen receptor (ER)-positive T47D and ER-negative MDA-MB-231 breast cancer cell lines, suggesting a broader range of target tissues for MIS action. Inhibition of growth was manifested by an increase in the fraction of cells in the G₁ phase of the cell cycle and induction of apoptosis. Treatment of breast cancer cells with MIS activated the NFκB pathway and selectively up-regulated the immediate early gene IEX-1S, which, when overexpressed, inhibited breast cancer cell growth. Dominant negative IκBα expression ablated both MIS-mediated induction of IEX-1S and inhibition of growth, indicating that activation of the NFκB signaling pathway was required for these processes. These results identify the NFκB-mediated signaling pathway and a target gene for MIS action and suggest a putative role for the MIS ligand and its downstream interactors in the treatment of ER-positive as well as negative breast cancers.

Rapidly Evolving and Luminous Transients from Pan-STARRS1

In the past decade, several rapidly evolving transients have been discovered whose timescales and luminosities are not easily explained by traditional supernovae (SNe) models. The sample size of these objects has remained small due, at least in part, to the challenges of detecting short timescale transients with traditional survey cadences. Here we present the results from a search within the Pan-STARRS1 Medium Deep Survey (PS1-MDS) for rapidly evolving and luminous transients. We identify 10 new transients with a time above half-maximum (t_1/2) of less than 12 days and -16.5 > M > -20 mag. This increases the number of known events in this region of SN phase space by roughly a factor of three. The median redshift of the PS1-MDS sample is z = 0.275 and they all exploded in star-forming galaxies. In general, the transients possess faster rise than decline timescale and blue colors at maximum light (g_P1-rP1 ≲ -0.2). Best-fit blackbodies reveal photospheric temperatures/radii that expand/cool with time and explosion spectra taken near maximum light are dominated by a blue continuum, consistent with a hot, optically thick, ejecta. We find it difficult to reconcile the short timescale, high peak luminosity (L > 10⁴³erg s^-1), and lack of UV line blanketing observed in many of these transients with an explosion powered mainly by the radioactive decay of ⁵⁶Ni. Rather, we find that many are consistent with either (1) cooling envelope emission from the explosion of a star with a low-mass extended envelope that ejected very little (<0.03 M) radioactive material, or (2) a shock breakout within a dense, optically thick, wind surrounding the progenitor star. After calculating the detection efficiency for objects with rapid timescales in the PS1-MDS we find a volumetric rate of 4800-8000 events yr^-1Gpc^-3(4%-7% of the core-collapse SN rate at z = 0.2).