FBG Strain Monitoring of a Road Structure Reinforced with a Geosynthetic Mattress in Cases of Subsoil Deformation in Mining Activity Areas

This paper presents implementation of purpose-designed optical fibre Bragg grating (FBG) sensors intended for the monitoring of real values of strain in reinforced road structures in areas of mining activity. Two field test stations are described. The first enables analysis of the geogrid on concrete and ground subgrades. The second models the situation of subsoil deformation due to mining activity at different external loads. The paper presents a system of optical fibre sensors of strain and temperature dedicated for the investigated mattress. Laboratory tests were performed to determine the strain characteristic of the FBG sensor-geogrid system with respect to standard load. As a result, it was possible to establish the dependence of the geogrid strain on the forces occurring in it. This may be the basis for the analysis of the mining activity effect on right-of-way structures during precise strain measurements of a geogrid using FBG sensors embedded in it. The analysis of the results of measurements in the aspect of forecasted and actual static and dynamic effects of mining on the stability of a reinforced road structure is of key importance for detailed management of the road investment and for appropriate repair and modernization management of the road structure.     

Fibre Optic FBG Sensors for Monitoring of the Temperature of the Building Envelope

Standard sensors for the measurement and monitoring of temperature in civil structures are liable to mechanical damage and electromagnetic interference. A system of purpose-designed fibre optic FBG sensors offers a more suitable and reliable solution—the sensors can be directly integrated with the load-bearing structure during construction, it is possible to create a network of fibre optic sensors to ensure not only temperature measurements but also measurements of strain and of the moisture content in the building envelope. The paper describes the results of temperature measurements of a building 2-layer wall using optical fibre Bragg grating (FBG) sensors and of a three-layer wall using equivalent classical temperature sensors. The testing results can be transmitted remotely. In the first stage, the sensors were tested in a climatic test chamber to determine their characteristics. The paper describes test results of temperature measurements carried out in the winter season for two multilayer external walls of a building in relation to the environmental conditions recorded at that time, i.e., outdoor temperature, relative humidity, and wind speed. Cases are considered with the biggest difference in the level of the relative humidity of air recorded in the observation period. It is found that there is greater convergence between the theoretical and the real temperature distribution in the wall for high levels (~84%) of the outdoor air relative humidity, whereas at the humidity level of ~49%, the difference between theoretical and real temperature histories is substantial and totals up to 20%. A correction factor is proposed for the theoretical temperature distribution.     

Rapid and specific detection of clinically significant haemoglobinopathies using electrospray mass spectrometry-mass spectrometry

Increasing demand for population screening for the haemoglobinopathies gives rise to a requirement for high throughput systems, which allow for cost effective, rapid, sensitive and specific screening of clinically significant haemoglobins. We have developed a practical and efficient approach using tryptic digestion and electrospray triple quadrupole mass spectrometry-mass spectrometry (MSMS) in multiple reaction monitoring acquisition mode for the identification of the clinically important haemoglobin variants, S, C, DPunjab, OArab, and E. A total of 200 blood samples, comprising 52 haemoglobin AA, 57 AS (sickle cell trait), 44 AC (C trait), 16 SC (SC disease), 14 SS (sickle cell disease), 10 AE (E trait), 2 ADPunjab (DPunjab trait) and 1 each of AOArab (OArab trait), CC (C disease), DPunjabDPunjab (DPunjab disease), OArabOArab (OArab disease), and EE (E disease), have been analysed in parallel with existing phenotype and molecular methods. All haemoglobin variants were correctly identified by MSMS, with no false positives or false negatives. The system detects both heterozygotes and homozygotes and has potential applications in neonatal and antenatal screening.     

The future of continuous glucose monitoring: closed loop

Improvements in accuracy of real-time continuous glucose monitoring facilitate the development of closed-loop systems consisting of a continuous glucose monitor, a control algorithm, and an insulin pump. Closed-loop systems can be divided according to the way meal delivery is handled as "fully closed-loop" or "closed-loop" with meal announcement systems. Depending on the subcutaneous (sc) or intravenous (iv) body interface, three major types of closed-loop systems are recognised, (i) sc sensing and sc delivery system, (ii) the iv sensing and intraperitoneal delivery system, and (iii) the iv glucose sensing and iv insulin delivery system. Given the current research focus, this review centres on the sc-sc closed-loop approach, which has the greatest potential for a near-future commercial exploitation as recognised by the JDRF Artificial Pancreas Project. Other approaches utilising intraperitoneal or intravenous sensing/delivery are also discussed. Closed-loop systems may revolutionise diabetes management but their introduction is likely to be gradual starting from simpler applications such as hypoglycaemia prevention or overnight glucose control progressing to more complex approaches such as 24/7 glucose control. The most important question is what is achievable with existing technologies and when the first generation of closed-loop systems will find its way into clinical practice.     

Differential serodiagnosis of cystic and alveolar echinococcosis using native and recombinant antigens in Japan

Our group at Asahikawa Medical College has established differential serodiagnosis for zoonotic larval cestodiases such as alveolar echinococcosis (AE), cystic echinococcosis (CE) and neurocysticercosis (NCC) using purified specific antigens. In this brief review, we introduce (a) four imported CE cases in Japan, easily identified serologically, (b) most recent advances in serology for differentiation of AE and monitoring of prognosis of AE in Japan. It includes application of affinity purified Em18 and prototype of a recombinant Em18 antigen. Serology using affinity purified Em18 antigens is showing much higher sensitivity for detection of AE cases which are usually undetectable by the ongoing serology for AE authorized in Hokkaido, Japan. As serology for AE, CE or NCC is still not popular in the majority of Asian countries, we expect that this review paper stimulates researchers who are interested in serology or serodiagnosis for these larval cestodiases including AE, CE and NCC.     

Fracture Characterization of Ultra-High Performance Concrete Notched Beams under the Influence of Different Material Factors Based on Acoustic Emission Technique

Acoustic emission (AE) technology is widely used in structural health monitoring. Glass sand (GS) made from waste glass is a promising replacement aggregate for quartz sand (QS) in ultra-high performance concrete (UHPC). This paper addresses the effects of different factors including water-binder ratio, length of basalt fiber (BF) and ratio of GS replacing QS on the fluidity and flexural strength of UHPC notched beam under four-point flexural loads. Meanwhile, the fracture characteristics of UHPC notched beam were characterized through acoustic emission (AE) technique. The results show that water-binder ratio and replacement ratio of GS present a positive correlation with work performance of UHPC, while length of BF exhibits a negative one. The flexural strength of UHPC notched beams can be improved by the decrease of the water-binder ratio and fiber length. The effect of water-binder ratio on flexural strength is the most significant, while the addition of GS presents the minimum one. The fracture characteristics of UHPC notched beams could be favorably characterized by AE parameters. Through the analysis and comparison of the evolution of AE parameters, the differences in fracture properties of UHPC notched beams with different flexural strengths can be realized. Through this study, the fluidity and flexural performance of UHPC produced by replacing QS with GS were demonstrated, which is beneficial to the cleaner production of UHPC. Meanwhile, the AE technique presented great potential for fracture characterization of UHPC notched beam, which also provided a promising method for real-time monitoring of cracking in the diagnosis of UHPC structures.     

Dose titration of repaglinide in patients with inadequately controlled type 2 diabetes

A total of 385 drug-therapy na?ve patients, with inadequately controlled type 2 diabetes, were randomised into a multinational, parallel-group study to compare two strategies for dose titration of the oral hypoglycaemic agent repaglinide. Patients were allocated to either a fasting blood glucose (FBG) monitoring group with titration target 4.4-6.1 mmol/l or to a post-prandial blood glucose (PPBG) monitoring group with titration target 4.4-8.0 mmol/l. An initial titration period of up to 8 weeks was followed by a 12-week treatment period. Glycaemic control and hypoglycaemic outcomes were compared for the respective groups. HbA(1c) decreased significantly more in the FBG monitoring group by a mean of 1.38% compared to the PPBG group by a mean of 1.22% (P=0.03). The glycaemic control targets were met by fewer patients in the FBG group than in the PPBG group (57% versus 86% (P<0.001)) despite a higher mean dose of repaglinide in the FBG group. The within-patient blood glucose variability was significantly lower in the FBG group than in the PPBG group (P<0.001). In conclusion, repaglinide lowered the HbA(1c) effectively and safely in both groups and self-monitored FBG is a suitable parameter for titration of repaglinide. Whether a lower PPBG target might be as good a guide as FBG for titration of repaglinide should be addressed in a future study.     

Smart sensor systems for human health breath monitoring applications

Breath analysis techniques offer a potential revolution in health care diagnostics, especially if these techniques can be brought into standard use in the clinic and at home. The advent of microsensors combined with smart sensor system technology enables a new generation of sensor systems with significantly enhanced capabilities and minimal size, weight and power consumption. This paper discusses the microsensor/smart sensor system approach and provides a summary of efforts to migrate this technology into human health breath monitoring applications. First, the basic capability of this approach to measure exhaled breath associated with exercise physiology is demonstrated. Building from this foundation, the development of a system for a portable asthma home health care system is described. A solid-state nitric oxide (NO) sensor for asthma monitoring has been identified, and efforts are underway to miniaturize this NO sensor technology and integrate it into a smart sensor system. It is concluded that base platform microsensor technology combined with smart sensor systems can address the needs of a range of breath monitoring applications and enable new capabilities for healthcare.     

Fiber-Embedded Metallic Materials: From Sensing towards Nervous Behavior

Embedding of fibers in materials has attracted serious attention from researchers and has become a new research trend. Such material structures are usually termed “smart” or more recently “nervous”. Materials can have the capability of sensing and responding to the surrounding environmental stimulus, in the former, and the capability of feeling multiple structural and external stimuli, while feeding information back to a controller for appropriate real-time action, in the latter. In this paper, embeddable fibers, embedding processes, and behavior of fiber-embedded metallic materials are reviewed. Particular emphasis has been given to embedding fiber Bragg grating (FBG) array sensors and piezo wires, because of their high potential to be used in nervous materials for structural health monitoring. Ultrasonic consolidation and laser-based layered manufacturing processes are discussed in detail because of their high potential to integrate fibers without disruption. In addition, current challenges associated with embedding fibers in metallic materials are highlighted and recommendations for future research work are set.     

M17, a gene specific for germinal center (GC) B cells and a prognostic marker for GC B-cell lymphomas, is dispensable for the GC reaction in mice

In T-cell-dependent antibody responses, antigen-specific B cells undergo a phase of secondary antibody diversification in germinal centers (GCs). Somatic hypermutation (SHM) introduces mutations into the rearranged immunoglobulin (Ig) variable (V) region genes, and class-switch recombination (CSR) alters the Ig heavy (H) chain constant region. Aberrant SHM or CSR is thought to contribute to the development of GC-derived B-cell malignancies. Diffuse large B-cell lymphomas (DLBCLs) are a heterogeneous group of such GC-derived tumors. Based on their gene expression profile, DLBCLs can be divided into activated B-cell-like and GC-like subgroups. The human gene HGAL is predominantly expressed in GCs. It is also part of the gene expression signature of GC-like DLBCL, and its high expression in DLBCL has been associated with a better clinical prognosis. We have generated mice deficient of the HGAL homologue M17 in order to investigate its functional significance. The mutant animals form normal GCs, undergo efficient CSR and SHM, and mount T-cell-dependent antibody responses similar to wild-type controls. Thus, M17 is dispensable for the GC reaction, and its potential function in the pathogenesis of DLBCL remains elusive.     

A target selection of somatic hypermutations is regulated similarly between T and B cells upon activation-induced cytidine deaminase expression

Activation-induced cytidine deaminase (AID) is essential for somatic hypermutations (SHM) and class switch recombination. Overexpression of AID in non-B cells can induce SHM in artificial constructs inserted in various loci in the genome. AID overexpression was thus proposed to introduce mutations in a wide variety of genes with little specificity. We previously showed that AID transgenic mice developed T cell lymphomas in which the variable region beta genes of the T cell receptor and c-myc were mutated as frequently as SHM in activated B cells. To understand the target specificity of SHM in AID-expressing T lymphomas, we sequenced six oncogenes (c-myc, pim1, p53, atm, tgfbr-2, and k-ras) and two genes (cd4 and cd5) that are actively transcribed in T lymphomas. SHM was found only in c-myc, pim1, cd4, and cd5, which share the E47 binding motif in the enhancer/promoter. The rest that are not mutated in B cells were not mutated in AID-induced T lymphomas either, although they are transcribed in T and B cells. Comparison of several features of SHM, including selection of targets and mutation distribution, suggests that the regulatory mechanism of SHM is similar between T and B cells. SHM base specificities in the CD4 and CD5 genes were biased to AT, indicating that the preference of target bases of the mutations generated by overexpression of AID is not always GC bases but variable between target genes.     

Dissociation of in vitro DNA deamination activity and physiological functions of AID mutants

Activation-induced cytidine deaminase (AID) is essential for the DNA cleavage that initiates both somatic hypermutation (SHM) and class switch recombination (CSR) of the Ig gene. Two alternative mechanisms of DNA cleavage by AID have been proposed: RNA editing and DNA deamination. In support of the latter, AID has DNA deamination activity in cell-free systems that is assumed to represent its physiological function. To test this hypothesis, we generated various mouse AID mutants and compared their DNA deamination, CSR, and SHM activities. Here, we compared DNA deamination, CSR, and SHM activities of various AID mutants and found that most of their CSR or SHM activities were disproportionate with their DNA deamination activities. Specifically, we identified a cluster of mutants (H48A, L49A, R50A, and N51A) with low DNA deamination activity but relatively intact CSR activity. Of note is an AID mutant (N51A) that retained CSR function but lost DNA deamination activity. In addition, an APOBEC1 mutation at N57, homologous to N51 of AID, also abolished DNA deamination activity but retained RNA editing activity. These results indicate that DNA deamination activity does not represent the physiological function of AID.     

Primary cutaneous follicle center lymphoma and primary cutaneous large B-cell lymphoma, leg type, are both targeted by aberrant somatic hypermutation but demonstrate differential expression of AID

We assessed primary cutaneous large B-cell lymphoma, leg type (PCLBCL, leg type; n = 13), and primary cutaneous follicle center lymphoma (PCFCL; n = 19) for somatic hypermutation (SHM) of BCL6, and aberrant SHM of MYC, RhoH/TTF, and PAX5. We demonstrate SHM of BCL6 in 8 PCLBCLs (62%), leg type, and 7 PCFCL patients (37%), and aberrant SHM in PAX5, RhoH/TTF, and/or MYC in 7 PCLBCLs (54%), leg type, and 10 PCFCL patients (53%). The majority of mutations consisted of single base-pair substitutions (n = 54) with rare deletions/insertions (n = 4), and displayed molecular features typical of the SHM process. Quantitative real-time PCR and immunohistochemical stainings for activation-induced cytidine deaminase, which is indispensable for SHM, demonstrated significantly higher expression in PCLBCL, leg type. Our results suggest that (aberrant) SHM may contribute to the pathogenesis of PCLBCL, leg type, and PCFCL and is not restricted to diffuse large B-cell lymphomas with an aggressive clinical behavior.     

Swedish registers to examine drug safety and clinical issues in RA

Data from several different monitoring systems are examined. The potential for registers based on data obtained from clinical practice, and linkage of such data to national health and population registers, is discussed. The approach described is a possible prototype for long term surveillance systems needed for the safe introduction of new treatments.     

Long-term oxygen therapy

This article provides an overview of the status of long-term oxygen therapy (LTOT). In the United States, payment cutbacks are occurring as a result of congressionally mandated competitive bidding and capped rental programs. These Medicare programs are discussed. These legislative and regulatory changes may result in reduced patient access to appropriate oxygen-delivery systems that meet medical needs, including optimal ambulation. Prescribing LTOT is addressed in this article, as is the need for adequate patient education. The importance of appropriate monitoring and reassessment is presented. The use of an LTOT collaborative care model is discussed. Although the new intermittent flow oxygen-delivery systems have potential benefits, there is consensus that each patient should be tested on the specific device because of variability in delivery and patient response. Feasible locations for patient education and monitoring are identified.     

Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation

Activation-induced cytidine deaminase (AID) is shown to be essential and sufficient to induce two genetic alterations in the Ig loci: class switch recombination (CSR) and somatic hypermutation (SHM). However, it is still unknown how a single-molecule AID differentially regulates CSR and SHM. Here we identified Spt6 as an AID-interacting protein by yeast two-hybrid screening and immunoprecipitation followed by mass spectrometry. Knockdown of Spt6 resulted in severe reduction of CSR in both the endogenous Ig locus in B cells and an artificial substrate in fibroblast cells. Conversely, knockdown of Spt6 did not reduce but slightly enhanced SHM in an artificial substrate in B cells, indicating that Spt6 is required for AID to induce CSR but not SHM. These results suggest that Spt6 is involved in differential regulation of CSR and SHM by AID.