THz Bragg structures fabricated with additive manufacturing.

The advancement of THz science and technology is desirable to facilitate the application of THz technologies in many sectors. Specialized THz photonic elements for these applications require desirable absorption and refractive characteristics in the THz regime. THz photonic elements can be created with additive manufacturing, and specifically 3D printing, forgoing the need for complex fabrication procedures and methodologies. Such THz photonic elements include periodic Bragg structures, which are capable of filtering specific THz frequencies. The authors present a THz Bragg structure fabricated with 3D printing via fused filament fabrication. The THz Bragg structure is made from high-impact polystyrene filament material, which is characterized in this paper with THz time-domain spectroscopy. The geometry and theoretical operation of the THz Bragg structure is investigated with finite-difference time-domain electromagnetic simulations. The THz Bragg structure is evaluated using a THz experimental test bed. There is agreement between the theoretical and the experimental filtering placement within the frequency domain for the THz Bragg structure. The capability of tunable frequency filtering of the presented THz Bragg structure, fabricated with 3D printing, is established and facilitates future advancements in applications of THz science and technology.

Leukocyte Tetraspanin CD53 Restrains α3 Integrin Mobilization and Facilitates Cytoskeletal Remodeling and Transmigration in Mice.

The importance of tetraspanin proteins in regulating migration has been demonstrated in many diverse cellular systems. However, the function of the leukocyte-restricted tetraspanin CD53 remains obscure. We therefore hypothesized that CD53 plays a role in regulating leukocyte recruitment and tested this hypothesis by examining responses of CD53-deficient mice to a range of inflammatory stimuli. Deletion of CD53 significantly reduced neutrophil recruitment to the acutely inflamed peritoneal cavity. Intravital microscopy revealed that in response to several inflammatory and chemotactic stimuli, absence of CD53 had only minor effects on leukocyte rolling and adhesion in postcapillary venules. In contrast, Cd53-/- mice showed a defect in leukocyte transmigration induced by TNF, CXCL1 and CCL2, and a reduced capacity for leukocyte retention on the endothelial surface under shear flow. Comparison of adhesion molecule expression in wild-type and Cd53-/- neutrophils revealed no alteration in expression of ß2 integrins, whereas L-selectin was almost completely absent from Cd53-/- neutrophils. In addition, Cd53-/- neutrophils showed defects in activation-induced cytoskeletal remodeling and translocation to the cell periphery, responses necessary for efficient transendothelial migration, as well as increased α3 integrin expression. These alterations were associated with effects on inflammation, so that in Cd53-/- mice, the onset of neutrophil-dependent serum-induced arthritis was delayed. Together, these findings demonstrate a role for tetraspanin CD53 in promotion of neutrophil transendothelial migration and inflammation, associated with CD53-mediated regulation of L-selectin expression, attachment to the endothelial surface, integrin expression and trafficking, and cytoskeletal function.

Prescribing vegetarian or flexitarian diets leads to sustained reduction in meat intake.

Many people agree that reducing the consumption of meat has good ends (e.g., for animal welfare, the environment, and human health). However, the question of which advocacy strategies are most effective in enabling wide-spread meat reduction remains open. We explored this by prescribing four different meat reduction diets to omnivorous participants for a seven-day adherence period, and studied their meat consumption over time. The diets included a Vegetarian diet, and three flexitarian diets (Climatarian - limit beef and lamb consumption; One Step for Animals - eliminate chicken consumption; Reducetarian - reduce all meat consumption). Results showed pronounced differences between groups in meat consumption during the adherence period, where the Vegetarian group ate significantly less meat than the flexitarian groups. All groups decreased their meat intake in the weeks following the adherence period compared to baseline, however, there were no significant group differences in the level of decrease over time. Participants also changed their attitudes toward meat and animals from pre-to post-intervention, and decreases in commitment toward and rationalization of meat-eating partially mediated change in meat intake. These findings reveal that the diet assignments had some impact on participants' meat consumption and attitudes even after the prescribed adherence period had ended. However, the sustained decrease in consumption did not vary depending on what meat reduction strategy was originally used.

Comparison of nonlinear filtering techniques for photonic systems with blackbody radiation.

This work explores a theoretical solution for noise reduction in photonic systems using blackbody radiators. Traditionally, signal noise can be reduced by increasing the integration time during signal acquisition. However, increasing the integration time during signal acquisition will reduce the acquisition speed of the signal. By developing and applying a filter using a model based on the theoretical equations for blackbody radiation, the noise of the signal can be reduced without increasing integration time. In this work, three filters, extended Kalman filter, unscented Kalman filter (UKF), and extended sliding innovation filter (ESIF), are compared for blackbody photonic systems. The filters are tested on a simulated signal from five scenarios, each simulating different experimental conditions. In particular, the nonlinear filters, UKF and ESIF, showed a significant reduction of noise from the simulated signal in each scenario. The results show great promise for photonic systems using blackbody radiators that require post-process for noise reduction.

Psychiatric and psychosocial characteristics of suicide completers: A 13-year comprehensive evaluation of psychiatric case records and postmortem findings.

Currently, there are limited data comparing demographic and clinical characteristics of individuals who died by probable suicide and who did and did not previously attend mental health services (MHSs). This study compared demographic and clinical factors for both groups, in a Western region of Ireland over a 13-year period. Postmortem reports between January 1, 2006 and March 31, 2019 were reviewed for 400 individuals who died by probable suicide. Relevant sociodemographic and clinical data were extracted from individuals' lifetime case notes. One hundred and fifty nine individuals (40%) had attended MHSs at some stage ("attendee"). Hanging was the most common method of suicide (61%), followed by drowning (18%) for both attendees and nonattendees of MHSs, with more violent methods utilized overall by nonattendees (p = 0.028). Sixty-eight percent of individuals who previously attempted hanging subsequently died utilizing this method. A higher proportion of attendees were female compared to nonattendees of MHSs (28.9 vs. 14.5%, p = 0.001). Recurrent depressive disorder (55%) was the most common diagnosed mental health disorder. For individuals with a diagnosis of schizophrenia, 39% had antipsychotic medications detectable in their toxicology reports. In conclusion, the majority of people who died by probable suicide had never had contact with MHSs, and nonattendees overall were more likely to utilize violent methods of suicide. Nonconcordance with psychotropic medications in psychotic patients and previous hanging attempt were highlighted as potential risk factors for death by probable suicide.

Trampoline-related injuries in children: a preliminary biomechanical model of multiple users.

BACKGROUND: The recent popularity of domestic trampolines has seen a corresponding increase in injured children. Most injuries happen on the trampoline mat when there are multiple users present. This study sought to examine and simulate the forces and energy transferred to a child's limbs when trampolining with another person of greater mass. METHODS: The study used a computational biomechanical model. RESULTS: The simulation demonstrated that when two masses bounce out of phase on a trampoline, a transfer of kinetic energy from the larger mass to the smaller mass is likely to occur. It predicted that when an 80 kg adult is on a trampoline with a 25 kg child, the energy transfer is equivalent to the child falling 2.8 m onto a solid surface. Additionally, the rate of loading on the child's bones and ligaments is greater than that on the accompanying adult. CONCLUSIONS: Current guidelines are clear that more than one user on a trampoline at a time is a risk factor for serious injury; however, the majority of injuries happen in this scenario. The model predicted that there are high energy transfers resulting in serious fracture and ligamentous injuries to children and that this could be equated to equivalent fall heights. This provides a clear take-home message, which can be conveyed to parents to reduce the incidence of trampoline-related injuries.

Searching for meaning is associated with costly prosociality.

The study of meaning in life has largely centered on its relationship with personal well-being, while a focus on how meaning is related to enhancing the well-being of others has received less research attention. Although searching for meaning may imply lower personal well-being, we find that meaning-seekers are more motivated to perform costly prosocial actions for the sake of others' well-being, given the perceived meaningfulness of these behaviors. Studies 1-4 (N = 780) show that meaning-seeking correlates with the motivation to engage in a range of costly prosocial behaviors. Meaning-seeking is further shown to be distinct from pursuing happiness in its relationship with costly prosociality (Study 2 & 3) and to share a stronger association with high-cost than low-cost prosociality (Study 3 & 4). Study 5 (N = 370; pre-registered) further shows that the search for meaning is related to costly prosocial behavior in the recent past. While our studies are cross-sectional, the pattern of findings suggests that seeking meaning (rather than happiness) may play an important role in motivating altruistic tendencies.

Insulin increases H2O2-induced pancreatic beta cell death.

Insulin resistance results, in part, from impaired insulin signaling in insulin target tissues. Consequently, increased levels of insulin are necessary to control plasma glucose levels. The effects of elevated insulin levels on pancreatic beta (ß) cell function, however, are unclear. In this study, we investigated the possibility that insulin may influence survival of pancreatic ß cells. Studies were conducted on RINm, RINm5F and Min-6 pancreatic ß-cells. Cell death was induced by treatment with H(2)O(2), and was estimated by measurements of LDH levels, viability assay (Cell-Titer Blue), propidium iodide staining and FACS analysis, and mitochondrial membrane potential (JC-1). In addition, levels of cleaved caspase-3 and caspase activity were determined. Treatment with H(2)O(2) increased cell death; this effect was increased by simultaneous treatment of cells with insulin. Insulin treatment alone caused a slight increase in cell death. Inhibition of caspase-3 reduced the effect of insulin to increase H(2)O(2)-induced cell death. Insulin increased ROS production by pancreatic ß cells and increased the effect of H(2)O(2). These effects were increased by inhibition of IR signaling, indicative of an effect independent of the IR cascade. We conclude that elevated levels of insulin may act to exacerbate cell death induced by H(2)O(2) and, perhaps, other inducers of apoptosis.

Does Mode of Surgical Intervention Based on Oncotype DX Score Influence Disease Recurrence in Early Breast Cancer?

Introduction Routine utilization of multigene assays to inform operative decision-making in early breast cancer (EBC) treatment is yet to be established. In this pilot study, we sought to establish the potential benefits of surgical intervention in EBC based on recurrence risk quantification using the Oncotype DX (ODX) assay. Materials and Methods Consecutive ODX tests performed over a 9-year period from October 2007 to May 2016 were evaluated. Oncotype scores were classified into high (≥31), medium (18-30), or low-risk (0-17) groups. The primary outcome was breast cancer recurrence. Subgroup analysis offered assessment of the recurrence effect of mode of surgical intervention for patient groups as defined by the oncotype score. Results In total 361 patients underwent ODX testing. The mean age and follow-up were 55.25 (± 10.58) years and 38.59 (± 29.1) months, respectively. The majority of patients underwent wide local excision (86.7%) with 8.9 and 4.4% patients having a mastectomy or wide local excision with completion mastectomy, respectively. Fifty-one percent of patients fell into the low risk ODX category with a further 40.2 and 8.5% deemed to be of intermediate and high risk. Five patients (1.38%) had disease recurrence. Comparative analysis of operative groups in each oncotype group revealed no difference in recurrence scores in the low- ( p = 0.84) and high-risk groups ( p = 0.92) with a statistically significant difference identified in the intermediate risk group ( p = 0.002). Conclusion To date we have been unable to definitively identify a role for ODX in guiding surgical approach in EBC. There is, however, a need for larger studies to examine this hypothesis.

Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression.

Tetraspanins regulate key processes in immune cells; however, the function of the leukocyte-restricted tetraspanin CD53 is unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53-/- mice were smaller than those of wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53-/- B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53-/- B cells and reduced stability of L-selectin on Cd53-/- T cells. Further analyses, including on human lymphocytes, showed that CD53 stabilizes L-selectin surface expression and may restrain L-selectin shedding via both ADAM17-dependent and ADAM17-independent mechanisms. The disruption in lymphocyte recirculation in Cd53-/- mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate an essential role for CD53 in lymphocyte trafficking and immunity.

Characterisation of graphene electrodes for microsystems and microfluidic devices.

Fabrication of microsystems is traditionally achieved with photolithography. However, this fabrication technique can be expensive and non-ideal for integration with microfluidic systems. As such, graphene fabrication is explored as an alternative. This graphene fabrication can be achieved with graphite oxide undergoing optical exposure, using optical disc drives, to impose specified patterns and convert to graphene. This work characterises such a graphene fabrication, and provides fabrication, electrical, microfluidic, and scanning electron microscopy (SEM) characterisations. In the fabrication characterisation, a comparison is performed between traditional photolithography fabrication and the new graphene fabrication. (Graphene fabrication details are also provided.) Here, the minimum achievable feature size is identified and graphene fabrication is found to compare favourably with traditional photolithography fabrication. In the electrical characterisation, the resistivity of graphene is measured as a function of fabrication dose in the optical disc drive and saturation effects are noted. In the microfluidic characterisation, the wetting properties of graphene are shown through an investigation of the contact angle of a microdroplet positioned on a surface that is treated with varying fabrication dose. In the SEM characterisation, the observed effects in the previous characterisations are attributed to chemical or physical effects through measurement of SEM energy dispersive X-ray spectra and SEM images, respectively. Overall, graphene fabrication is revealed to be a viable option for development of microsystems and microfluidics.

Vascular proliferations of the breast.

Vascular proliferations of the breast are uncommon but potentially diagnostically challenging lesions. Clinically apparent processes are more likely to be malignant; however, a range of benign entities which must be differentiated from angiosarcoma also exists. This review discusses first, breast lesions of apparent vascular origin, then benign and histologically bland perilobular, cavernous and capillary haemangiomas. Subsequently, more diagnostically challenging, atypical haemangiomas, papillary endothelial hyperplasia, angiomatosis and angiolymphoid hyperplasia with eosinophilia (epithelioid haemangioma) are considered. In addition, lesions with low-grade malignant potential such as haemangiopericytomas and epithelioid haemangioendotheliomas may rarely present in the breast. However, primary angiosarcomas and radiation-associated vascular lesions are reviewed in depth, as these entities are of greatest clinical and pathological significance.

Re-Appraisal of Estrogen Receptor Negative/Progesterone Receptor Positive (ER-/PR+) Breast Cancer Phenotype: True Subtype or Technical Artefact?

Expression of the ER and PR receptors is routinely quantified in breast cancer as a predictive marker of response to hormonal therapy. Accurate determination of ER and PR status is critical to the optimal selection of patients for targeted therapy. The existence of an ER-/PR+ subtype is controversial, with debate centred on whether this represents a true phenotype or a technical artefact on immunohistochemistry (IHC). The aim of this study was to investigate the true incidence and clinico-pathological features of ER-/PR+ breast cancers in a tertiary referral symptomatic breast unit. Clinico-pathological data were collected on invasive breast cancers diagnosed between 1995 and 2005. IHC for ER and PR receptors was repeated on all cases which were ER-/PR+, with the same paraffin block used for the initial diagnostic testing. Concordance between the diagnostic and repeat IHC was determined using validated testing. Complete data, including ER and PR status were available for 697 patients diagnosed during the study period. On diagnostic IHC, the immunophenotype of the breast tumours was: ER+/PR+ in 396 (57%), ER-/PR- in 157 (23%), ER+/PR- in 88 (12%) and ER-/PR+ in 56 (8.6%) patients. On repeat IHC of 48/56 ER-/PR+ tumours 45.8% were ER+/PR+, 6% were ER+/PR- and 43.7% were ER-/PR- None of the cases were confirmed to be ER-/PR+. The ER-/PR+ phenotypic breast cancer is likely to be the result of technical artefact. Prompt reassessment of patients originally assigned to this subtype who re-present with symptoms should be considered to ensure appropriate clinical management.

Neuroblastoma sensitivity to growth inhibition by deferrioxamine: evidence for a block in G1 phase of the cell cycle.

Iron (Fe) is known to be necessary for cellular proliferation. Previous studies have suggested that neuroblastoma cells appear to be relatively sensitive to growth inhibition by a specific Fe chelator, deferrioxamine (DFO), in vitro. Also, DFO has been recently used for the treatment of neuroblastoma patients. In this paper we demonstrate that neuroblastoma cell proliferation in vitro is extremely sensitive to inhibition by DFO as compared to another cell line with almost identical growth kinetics. Neuroblastoma cells treated with DFO adapt appropriately to Fe chelation as measured by marked upregulation of transferrin receptor mRNA, increased functional transferrin receptor, and decreased cellular ferritin concentration. Further studies that quantitated cellular incorporation of 59Fe from added transferrin-59Fe in the presence of DFO indicated that neuroblastoma cells were more sensitive to inhibition of Fe incorporation by the chelator as compared to the other cell line. Neuroblastoma cells treated with DFO showed a consistent arrest in the G1 phase of the cell cycle. For cells taken from the "resting" state this block occurred before the vast majority of cells had entered S or G2-M phases of the cell cycle. Further evidence that neuroblastoma cells were arrested before the G1-S interface was provided when cells inhibited by DFO and released into aphidicolin exhibit arrest at the G1-S interface, whereas release from aphidicolin into DFO resulted in entry into S phase. Also, DFO-treated cells exhibited a decrease in both p34cdc2 immunoreactive protein as well as kinase activity. The results of these latter studies strongly indicate evidence for a Fe requirement for malignant cell proliferation before the onset of DNA synthesis. Our results also provide a basis for further studies that will better define a therapeutic approach to patients with neuroblastoma utilizing DFO treatment.

Protein kinase Calpha and protein kinase Cdelta play opposite roles in the proliferation and apoptosis of glioma cells.

Protein kinase C (PKC) has been implicated in the proliferation and apoptosis of glial tumors, but the role of specific PKC isoforms remains unresolved. Comparing brain tumors differing in degree of malignancy, we found that malignant gliomas expressed higher levels of PKCalpha and lower levels of PKCdelta as compared with low-grade astrocytomas. Consistent with a mechanistic role for these differences, overexpression of PKCalpha in the human U87 glioma cell line resulted in enhanced cell proliferation and decreased glial fibrillary acidic protein (GFAP) expression as compared with controls. Reciprocally, overexpression of PKCdelta inhibited cell proliferation and enhanced GFAP expression. Using PKC chimeras, we found that the regulatory domains of PKCalpha and PKCdelta mediated their effects on cell proliferation and GFAP expression. PKCalpha and delta have been implicated as potential signaling molecules in apoptosis. Therefore, we examined the role of these isoforms in the resistance of glioma cells to apoptotic stimuli. In U87 cells, manipulation of PKCalpha levels had little effect on apoptosis in response to etoposide. In contrast, overexpression of PKCdelta rendered the U87 cells more sensitive to the apoptotic effect of etoposide, and PKCdelta was cleaved in these cells by a caspase-dependent process. Furthermore, the glioma cell line U373, which expresses endogenous PKCdelta, underwent apoptosis in response to etoposide, and the apoptotic response was blocked by the PKCdelta inhibitor rottlerin. Our results suggest that PKCalpha and PKCdelta play opposite roles in the proliferation and apoptosis of glioma cells.

vFLIP protects PC-12 cells from apoptosis induced by Sindbis virus: implications for the role of TNF-alpha.

Sindbis virus (SV) is an alphavirus used as a model for studying the pathogenesis of viral encephalitis. In this study we examined the effects and the mechanisms involved in the apoptosis induced by SV in PC-12 cells, and the role of a vFLIP in this process. Infection of PC-12 cells with a neurovirulent strain of SV, SVNI, induced cell apoptosis. Overexpression of vFLIP encoded by the HHV-8 or treatment with a caspase-8 inhibitor inhibited cell apoptosis. SVNI induced an increase in the expression of tumor necrosis factor alpha (TNF-alpha), and pre-treatment of the cells with an anti-TNF-alpha blocking antibody or with soluble TNF-alpha receptor abrogated the apoptotic effect of SVNI. Moreover, TNF-alpha R1 knockout mice were more resistant to the cytopathic effects of the virus as compared to control animals. Our results indicate that the apoptosis induced by SVNI is mediated by activation of caspase-8, and that TNF-alpha plays an important role in the apoptotic response.

Nerve growth factor regulates TNF-alpha production in mouse macrophages via MAP kinase activation.

In this study, we examined the expression of nerve growth factor (NGF) and its receptors in mouse macrophages and the mechanisms involved in the effect of NGF on tumor necrosis factor (TNF)-alpha production. Macrophages expressed NGF and the NGF receptors TrkA and p75. Treatment of J744 cells or peritoneal macrophages with NGF induced a large increase in the production of TNF-alpha. In addition, NGF induced the secretion of nitric oxide in interferon-gamma-treated J774 cells or lipopolysaccharide-treated peritoneal macrophages. The induction of TNF-alpha production by NGF was blocked by K252a, an inhibitor of the TrkA receptor. NGF induced phosphorylation and activation of extracellular signal-regulated kinase, Erk1/Erk2 and c-Jun amino-terminal kinase, whereas it did not induce phosphorylation of p38 mitogen-activated protein kinase. Inhibition of the MAP kinase-Erk kinase pathway with PD 098059 decreased the secretion of TNF-alpha by NGF. Our results suggest that NGF has an important role in the activation of macrophages during inflammatory responses via activation of mitogen-activated protein kinases.

Characterization of thyroid hormone effects on Na channel synthesis in cultured skeletal myotubes: role of Ca2+.

Thyroid hormones (TH) cause an increase in spontaneous electrical activity of cultured rat skeletal myotubes. This activity is associated with tetrodotoxin (TTX)-sensitive Na channels. In addition, the initial effect of TH on Na-K pump synthesis has been shown to be TTX dependent. Accordingly, we have studied effects of TH on expression of TTX-sensitive Na channels in cultured skeletal muscle. Expression of Na channels was determined by measurements of the binding of [3H]saxitoxin (STX). The frequency and rate of rise of spontaneously occurring action potentials, which are related to the density of TTX-sensitive Na channels, were also determined. TH caused dose-dependent increases in Na channels as well as in action potential frequency and rate of rise. The increases were detectable as early as 12 h after treatment with TH was begun, and levels reached a maximum plateau after 36-48 h. The effects of TH were blocked by inhibitors of protein synthesis. Scatchard analysis showed the channels in TH-treated myotubes to have lower affinity for STX than those in control cells. The effect of TH to up-regulate Na channels was reduced by growth of the cells in elevated external calcium. In contrast, treatment with TTX or verapamil, which lower cytosolic Ca2+, resulted in a marked increase in the effect of TH over that in control myotubes. Thus, TH appears to regulate Na channels in cultured myotubes by two opposing mechanisms; 1) direct stimulation of Na channel synthesis, and 2) indirect decrease in synthesis mediated by an increase in cytosolic Ca2+. The results indicate that TH may play an important role in developmental expression of Na channels in excitable tissue.

Characterization of thyroid hormone effects on Na-K pump and membrane potential of cultured rat skeletal myotubes.

The purpose of this study was to characterize the effects of thyroid hormone on the Na-K pump and resting membrane potential (EM) of rat skeletal myotubes in culture. Myotubes were obtained from fetal (19-21 day) or neonatal rats (1-2 day) by serial trypsinization and maintained in culture for up to 10 days. Cells were treated with T4 or T3 on day 6 or 7, and measurements were made of EM, [3H]ouabain binding, and ouabain-sensitive 86Rb uptake at various times thereafter. Hormone treatment increased the values of all three variables within 24 h, plateau levels being attained by 48-72 h. Cycloheximide and actinomycin D totally blocked the effects of thyroid hormone when added together to the cells, thus suggesting that protein synthesis is necessary for the effects of these hormones. Scatchard analysis showed that the new receptors have lower ouabain affinity than those in control. Blockade of spontaneously occurring action potentials with tetrodotoxin, which blocks voltage-dependent Na channels, or Na/H antiporter with amiloride, abolished the hormone effects seen after 24 h and significantly reduced those obtained after 48 h of hormone treatment. The results demonstrate that thyroid hormone-induced increased amount and activity of the electrogenic Na-K pump in cultured myotubes occurs, at least in part, in response to an initial effect to increase Na influx. Moreover, the findings are consistent with the concept that the Na-K pump plays an important role in regulation of EM in this preparation.