Advanced Glycation End Products (AGEs) accumulate in the Reproductive Tract of Men with Diabetes.

Light microscopic studies comparing sperm parameters show little association between diabetes and male fertility. However, with the introduction of new analytical techniques, evidence is now emerging of previously undetectable affects of diabetes on sperm function. Specifically, a recent study has found significantly higher sperm nuclear DNA (nDNA) fragmentation in diabetic men. As advanced glycation end products (AGEs) are important instigators of oxidative stress and cell dysfunction in numerous diabetic complications, we hypothesized that these compounds could also be present in the male reproductive tract. The presence and localization of the most prominent AGE, carboxymethyl-lysine (CML), in the human testis, epididymis and sperm was determined by immunohistochemistry. Parallel ELISA and Western blot analyses were performed to ascertain the amount of CML in seminal plasma and sperm from 13 diabetic and 9 non-diabetic subjects. CML immunoreactivity was found through out the seminiferous epithelium, the nuclei of spermatogonia and spermatocytes, in the basal and principle cells (cytoplasm and nuclei) of the caput epididymis and on most sperm tails, mid pieces and all cytoplasmic droplets. The acrosomal cap, especially the equatorial band, was prominently stained in diabetic samples only. The amount of CML was significantly higher (p = 0.004) in sperm from non diabetic men. Considering the known detrimental actions of AGEs in other organs, the presence, location and quantity of CML, particularly the increased expression found in diabetic men, suggests that these compounds may play a hitherto unrecognized role in male infertility.

Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication.

The recently discovered aging-dependent large accumulation of point mutations in the human fibroblast mtDNA control region raised the question of their occurrence in postmitotic tissues. In the present work, analysis of biopsied or autopsied human skeletal muscle revealed the absence or only minimal presence of those mutations. By contrast, surprisingly, most of 26 individuals 53 to 92 years old, without a known history of neuromuscular disease, exhibited at mtDNA replication control sites in muscle an accumulation of two new point mutations, i.e., A189G and T408A, which were absent or marginally present in 19 individuals younger than 34 years. These two mutations were not found in fibroblasts from 22 subjects 64 to 101 years of age (T408A), or were present only in three subjects in very low amounts (A189G). Furthermore, in several older individuals exhibiting an accumulation in muscle of one or both of these mutations, they were nearly absent in other tissues, whereas the most frequent fibroblast-specific mutation (T414G) was present in skin, but not in muscle. Among eight additional individuals exhibiting partial denervation of their biopsied muscle, four subjects >80 years old had accumulated the two muscle-specific point mutations, which were, conversely, present at only very low levels in four subjects <or =40 years old. The striking tissue specificity of the muscle mtDNA mutations detected here and their mapping at critical sites for mtDNA replication strongly point to the involvement of a specific mutagenic machinery and to the functional relevance of these mutations.

Male Infertility: A Clinical Reflection

The introduction of intracytoplasmic sperm injection (ICSI) has led to an inappropriate decrease in interest in male fertility. It is apparent that light microscopy provides limited information and molecular techniques show that DNA abnormalities need to be considered further. Abnormalities include not only Yq11 deletions but also DNA strand breaks. Increases in advanced glycation end-products in sperm from well controlled diabetics may provide a mechanism for this damage in non-diabetics. In addition, much publicity is given to decreased male fertility: this is NOT confirmed as technical variations and differences in study populations make it difficult to draw conclusions. The generation of stem cell derived germ cells provides hope for men without germ cells but this is currently only experimental.

Feasibility of online collaborative voltage stability control of power systems

This paper presents the results of feasibility study of a novel concept of power system on-line collaborative voltage stability control. The proposal of the on-line collaboration between power system controllers is to enhance their overall performance and efficiency to cope with the increasing operational uncertainty of modern power systems. In the paper, the framework of proposed on-line collaborative voltage stability control is firstly presented, which is based on the deployment of multi-agent systems and real-time communication for on-line collaborative control. Then two of the most important issues in implementing the proposed on-line collaborative voltage stability control are addressed: (1) Error-tolerant communication protocol for fast information exchange among multiple intelligent agents; (2) Deployment of multi-agent systems by using graph theory to implement power system post-emergency control. In the paper, the proposed on-line collaborative voltage stability control is tested in the example 10-machine 39-node New England power system. Results of feasibility study from simulation are given considering the low-probability power system cascading faults.

Damping torque analysis for DC bus implemented damping control

Damping torque analysis is a well-developed technique for understanding and studying power system oscillations. This paper presents the applications of damping torque analysis for DC bus implemented damping control in power transmission networks in two examples. The first example is the investigation of damping effect of shunt VSC (Voltage Source Converter) based FACTS voltage control, i.e., STATCOM (Static Synchronous Compensator) voltage control. It is shown in the paper that STATCOM voltage control mainly contributes synchronous torque and hence has little effect on the damping of power system oscillations. The second example is the damping control implemented by a Battery Energy Storage System (BESS) installed in a power system. Damping torque analysis reveals that when BESS damping control is realized by regulating exchange of active and reactive power between the BESS and power system respectively, BESS damping control exhibits different properties. It is concluded by damping torque analysis that BESS damping control implemented by regulating active power is better with less interaction with BESS voltage control and more robust to variations of power system operating conditions. In the paper, all analytical conclusions obtained are demonstrated by simulation results of example power systems.

Robustness of Damping Control Implemented by Energy Storage Systems Installed in Power Systems

An energy storage system (ESS) installed in a power system can effectively damp power system oscillations through controlling exchange of either active or reactive power between the ESS and power system. This paper investigates the robustness of damping control implemented by the ESS to the variations of power system operating conditions. It proposes a new analytical method based on the well-known equal-area criterion and small-signal stability analysis. By using the proposed method, it is concluded in the paper that damping control implemented by the ESS through controlling its active power exchange with the power system is robust to the changes of power system operating conditions. While if the ESS damping control is realized by controlling its reactive power exchange with the power system, effectiveness of damping control changes with variations of power system operating condition. In the paper, an example power system installed with a battery ESS (BESS) is presented. Simulation results confirm the analytical conclusions made in the paper about the robustness of ESS damping control. Laboratory experiment of a physical power system installed with a 35kJ/7kW SMES (Superconducting Magnetic Energy Storage) was carried out to evaluate theoretical study. Results are given in the paper, which demonstrate that effectiveness of SMES damping control realized through regulating active power is robust to changes of load conditions of the physical power system.

Cochlin in the eye: Functional implications

Aqueous humor is actively produced in the ciliary epithelium of the anterior chamber and has important functions for the eye. Under normal physiological conditions, the inflow and outflow of the aqueous humor are tightly regulated, but in the pathologic state this balance is lost. Aqueous outflow involves structures of the anterior chamber and experiences most resistance at the level of the trabecular meshwork (TM) that acts as a filter. The modulation of the TM structure regulates the filter and its mechanism remains poorly understood. Proteomic analyses have identified cochlin, a protein of poorly understood function, in the glaucomatous TM but not in healthy control TM from human cadaver eyes. The presence of cochlin has subsequently been confirmed by Western and immunohistochemical analyses. Functionally, cochlin undergoes multimerization induced by shear stress and other changes in the microenvironment. Cochlin along with mucopolysaccharide deposits have been found in the TM of glaucoma patients and in the inner ear of subjects affected by the hearing disorder DNFA9, a late onset, progressive disease that also involves alterations in fluid shear regimes. In vitro, cochlin induces aggregation of primary TM cells suggesting a role in cell adhesion, possibly in mechanosensation, and in modulation of the TM filter.

Rates of childhood trauma in a sample of patients with schizophrenia as compared with a sample of patients with non-psychotic psychiatric diagnoses

Despite strong evidence of high rates of childhood and adult trauma in schizophrenia, the area remains under-researched. Our objectives in the study were first, to examine the rates of exposure to childhood, adult and lifetime (child plus adult) trauma in a population with schizophrenia and a population with non-psychotic psychiatric diagnoses and second, to examine the effect of trauma on the symptoms of schizophrenia. Two groups, those with schizophrenia (n = 40), and those with a non-psychotic diagnosis (n = 30), were recruited. Data were collected for demographic, psychiatric and trauma histories for all participants and on psychosocial functioning and psychiatric symptomatology for the patients with schizophrenia. Childhood exposure to trauma was significantly more common in the schizophrenia group (t = 5.196, df = 68, p <0.001, Eta squared = 0.28), with the strongest relationship being childhood physical assault. In the schizophrenia group a history of trauma was significantly related to poor communication skills (r = -0.529, p <0.001) and depressive symptoms (r = 0.443, p = 0.004). Evidence that childhood exposure to trauma is more common in a population with schizophrenia is consistent with other studies and raises the possibility that such trauma is of etiological importance. Further research is required to replicate those findings, to elucidate possible pathways by which the experience of trauma may contribute to the development of schizophrenia, and to explore the relationship between a history of childhood trauma and the experience of depressive symptoms in schizophrenia.

The Voice as Transcursive Inscriber: The Relation of Body and Instrument Understood through the Workings of a Machine

This article examines the relationship of the body with a musical instrument; specifically it looks at the vital threshold conditions that occur during the interplay of voice and instrument. By examining the work ‘IKAS’ (1982) for solo saxophone by German composer Hans-Joachim Hespos, the unusual timbral relationships created between vocal and instrumental sounds are exposed. I argue that this particular work highlights the performer/instrument relation as one marked by Gilles Deleuze’s notion of the workings of a machine and a machine’s relation to a ‘flow’, in particular a machine’s function with view to the break in the flow. By turning towards Deleuze’s concept of the machine, this article offers a slightly different vocabulary for music analysis, one that more easily encompasses certain works of the twentieth century, specifically those that are more timbre- than pitch-based.

Epidermal Langerhans Cells are Dispensable for Humoral and Cell-Mediated Immunity Elicited by Gene Gun Immunization.

Gene gun immunization, i.e., bombardment of skin with DNA-coated particles, is an efficient method for the administration of DNA vaccines. Direct transfection of APC or cross-presentation of exogenous Ag acquired from transfected nonimmune cells enables MHC-I-restricted activation of CD8(+) T cells. Additionally, MHC-II-restricted presentation of exogenous Ag activates CD4(+) Th cells. Being the principal APC in the epidermis, Langerhans cells (LC) seem ideal candidates to accomplish these functions. However, the dependence on LC of gene gun-induced immune reactions has not yet been demonstrated directly. This was primarily hampered by difficulties to discriminate the contributions of LC from those of other dermal dendritic cells. To address this problem, we have used Langerin-diphtheria toxin receptor knockin mice that allow for selective inducible ablation of LC. LC deficiency, even over the entire duration of experiments, did not affect any of the gene gun-induced immune functions examined, including proliferation of CD4(+) and CD8(+) T cells, IFN-gamma secretion by spleen cells, Ab production, CTL activity, and development of protective antitumor immunity.

The challenge of patients’ unmet palliative care needs in the final stages of chronic illness.

Background: There is consensus in the literature that the end of life care for patients with chronic illness is suboptimal, but research on the specific needs of this population is limited. Aim: This study aimed to use a mixed methodology and case study approach to explore the palliative care needs of patients with a non-cancer diagnosis from the perspectives of the patient, their significant other and the clinical team responsible for their care. Patients (n 18) had a diagnosis of either end-stage heart failure, renal failure or respiratory disease. Methods: The Short Form 36 and Hospital and Anxiety and Depression Questionnaire were completed by all patients. Unstructured interviews were (n 35) were conducted separately with each patient and then their significant other. These were followed by a focus group discussion (n 18) with the multiprofessional clinical team. Quantitative data were analysed using simple descriptive statistics and simple descriptive statistics. All qualitative data were taped, transcribed and analysed using Colaizzi’s approach to qualitative analysis. Findings: Deteriorating health status was the central theme derived from this analysis. It led to decreased independence, social isolation and family burden. These problems were mitigated by the limited resources at the individual’s disposal and the availability of support from hospital and community services. Generally resources and support were perceived as lacking. All participants in this study expressed concerns regarding the patients’ future and some patients described feelings of depression or acceptance of the inevitability of imminent death. Conclusion: Patients dying from chronic illness in this study had many concerns and unmet clinical needs. Care teams were frustrated by the lack of resources available to them and admitted they were ill-equipped to provide for the individual’s holistic needs. Some clinicians described difficulty in talking openly with the patient and family regarding the palliative nature of their treatment. An earlier and more effective implementation of the palliative care approach is necessary if the needs of patients in the final stages of chronic illness are to be adequately addressed. Pa

Plasma ion evolution in the wake of a high-intensity ultrashort laser pulse

Experimental investigations of the late-time ion structures formed in the wake of an ultrashort, intense laser pulse propagating in a tenuous plasma have been performed using the proton imaging technique. The pattern found in the wake of the laser pulse shows unexpectedly regular modulations inside a long, finite width channel. On the basis of extensive particle in cell simulations of the plasma evolution in the wake of the pulse, we interpret this pattern as due to ion modulations developed during a two-stream instability excited by the return electric current generated by the wakefield.