Activity-Based Recommendations for Demand Response in Smart Sustainable Buildings

The energy consumption of private households amounts to approximately 30% of the total global energy consumption, causing a large share of the CO2 emissions through energy production. An intelligent demand response via load shifting increases the energy efficiency of residential buildings by nudging residents to change their energy consumption behavior. This paper introduces an activity prediction-based framework for the utility-based context-aware multi-agent recommendation system that generates an activity shifting schedule for a 24-hour time horizon to either focus on CO2 emissions or energy cost savings. In particular, we design and implement an Activity Agent that uses hourly energy consumption data. It does not require further sensorial data or activity labels which reduces implementation costs and the need for extensive user input. Moreover, the system enhances the utility option of saving energy costs by saving CO2 emissions and provides the possibility to focus on both dimensions. The empirical results show that while setting the focus on CO2 emissions savings, the system provides an average of 12% of emissions savings and 7% of cost savings. When focusing on energy cost savings, 20% of energy costs and 6% of emissions savings are possible for the studied households in case of accepting all recommendations. Recommending an activity schedule, the system uses the same terms residents describe their domestic life. Therefore, recommendations can be more easily integrated into daily life supporting the acceptance of the system in a long-term perspective

MPTP-induced degeneration: interference with glutamatergic toxicity

Parkinson's disease (PD) is characterised by the progressive degeneration of nigrostriatal dopamine (DA) neurons resulting in the major symptoms of akinesia and rigidity. Although the primary cause of PD is still not known some features make this disorder a model for neurodegenerative diseases in general. It has been known for some time that symptomatic PD can be attributed to insults with symptoms occurring many years later such as post-encephalitic PD or PD following manganese poisoning. More recently, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) has been identified as a neurotoxin selective for melanin-containing dopaminergic neurons in humans and non-human primates. The specificity of this neurotoxin and the striking clinical similarities to idiopathic PD, seen in primates, make MPTP-induced parkinsonism the most useful animal model of a neurological disease. There are numerous theoretical possibilities to interfere with both MPTP-induced neurotoxicity and the symptomatology of PD. In recent years excitatory amino acids have gained considerable interest since they can cause excitotoxic lesion of neurons under a number of pathological conditions (Olney et al., 1989; Choi, 1988). Here we summarise the present data and provide new experimental evidence indicating that MPTP-induced degeneration of dopaminergic neurons does involve glutamate-mediated toxicity. It is concluded that glutamate-mediated excitotoxicity results in the destruction of DAergic somata in the substantia nigra. Non-competitive or competitive NMDA antagonists protect nigral neurons from MPTP-induced degeneration whereas their striatal terminals still seem to degenerate

Terguride stimulates locomotor activity at 2 months but not 10 months after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets

The mixed dopamine (DA) agonist/antagonist terguride acts as a DA antagonist on normosensitive receptors but shows DA agonistic properties at supersensitive DA receptors. Such a compound could offer an alternative to the treatment of Parkinson's disease with indirect or direct DA agonists. The present study compares the actions of terguride, 4-12 mg/kg i.p., in naive common marmosets with its effects in animals rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2 months or 10 months previously, in order to test its antiparkinsonian efficacy. Terguride reduced locomotor activity in naive common marmosets, similar to its effects in rodents and in line with the DA antagonistic activity of the compound. In marmosets treated with MPTP 2 months previously and exhibiting pronounced behavioural motor deficits, terguride stimulated locomotor activity, showing DA agonistic properties under these conditions. In contrast, the locomotor activity of animals that had recovered from MPTP treatment 10 months previously was not altered by terguride. It is concluded that terguride has anti-akinetic efficacy in this primate model of Parkinson's disease. In addition, terguride offers a unique opportunity to differentiate, pharmacologically, the extent of dopaminergic recovery from MPTP treatment in this primate species

Analysis of the accuracy of the implantation of orthodontic mini implants using different insertion guides after digital position planning

Einleitung: Orthodontische Mini Implantate (OMI) dienen seit Jahrzehnten der temporären skelettalen Verankerung während kieferorthopädischer Behandlungen. Der anteriore Gaumen wird in den letzten Jahren vornehmlich als Insertionsregion genutzt. Mit zunehmender Digitalisierung ist seit kurzem ein komplett digitaler Workflow zur Planung und Insertion der OMI möglich. Dieser umfasst eine exakte präoperative Planung der korrekten Implantatposition bis hin zur Insertion der OMI mittels 3D-gedruckter Schiene. Hierzu liegen bisher nur wenige wissenschaftlich fundierte Untersuchungen vor. In dieser Arbeit werden die Genauigkeit und Reproduzierbarkeit der Insertion von digital geplanten OMI untersucht. Material und Methoden: Die Untersuchung wurde an 17 individuellen 3D-gedruckten OK-Modellen mit knochenähnlichen Eigenschaften durchgeführt. Zur digitalen Planung wurde mit der Software TADmatch ein Fernröntgenseitenbild (FRS) und ein digitales Oberkiefer-Modell miteinander überlagert. Jeweils zwei parallel zueinanderstehende Schrauben wurden damit im Gaumen virtuell geplant. Die Insertion der Schrauben erfolgte über vier verschiedene Methoden: Freihand, mittels einer Silikon , einer Tiefzieh und einer gedruckten 3D Übertragungsschiene. Die Schraubenposition in den Modellen wurde durch einen Intraoralscanner erfasst. Anschließend wurde das gescannte Modell mit dem Planungsmodell überlagert. Die Abweichungen der Schraubenposition wurden am Schraubenkopf, der -spitze sowie über die -achsen bestimmt. Zur statistischen Auswertung wurde der t-Test, der ANOVA-Test sowie der Likelihood Ratio Test verwendet. Das Signifikanzniveau wurde auf α = 5% festgelegt. Ergebnisse: An der Schraubenspitze variierten die Abweichungen im Mittelwert zwischen 1.14 mm und 1.78 mm. Die geringsten Abweichungen erbrachte die 3D-Schieneninsertion, die größten die Freihandinsertion. Bei der Schraubenkopfposition variierten die Mittelwerte zwischen 0.82 mm und 1.56 mm. Die kleinsten Werte wurden mit der 3D-Schienenmethode erzielt. Aber auch die anderen Übertragungsschienen zeigten im Vergleich zur Freihandinsertion signifikant geringere Abweichungen. Signifikant präzisere Streuungswerte lieferte im Schraubenkopfbereich die 3D-gedruckte Schiene gegenüber allen anderen Insertionstechniken. Bei der Winkelabweichung der Schraubenachsen zeigten alle verwendeten Übertragungsschienen signifikant richtigere und präzisere Werte, verglichen mit der Freihandinsertion. Die Werte divergierten zwischen 2.73° und 8.88°. Schlussfolgerung: Die mit TADmatch geplanten und 3D-gedruckten Insertionsschienen erweisen sich als ein zuverlässiges Hilfsmittel zur Platzierung von OMI. Sie erlauben im Vergleich zu den anderen untersuchten Verfahren eine richtigere, präzisere und reproduzierbarere Übertragung der geplanten Schraubenposition auf das Insertionsmodell. Durch alle getesteten Insertionsschablonen werden Winkelabweichungen verringert. Die manuelle Freihandinsertion ist am wenigsten genau.Introduction: Orthodontic Mini Implants (OMI) have been used for decades for temporary skeletal anchorage during orthodontic treatments. The anterior palate has been primarily used as an insertion region in recent years. With increasing digitalization, a completely digital workflow for planning and insertion of OMI has recently become possible. This includes exact preoperative planning of the correct implant position up to the insertion of the OMI by means of a 3D-printed splint. To date, only a few scientifically based studies are available on this subject. In this study, the accuracy and reproducibility of the insertion of digitally planned OMI are investigated. Material and Methods: The study was performed on 17 individual 3D-printed maxillary models with bone-like characteristics. For digital planning, a lateral radiograph (FRS) and a digital model of the maxilla were superimposed using TADmatch software. Two parallel screws were planned virtually in the palate. The screws were inserted using four different methods: Freehand, using a silicone-, a vacuum-formed- and a printed 3D transfer splint. The screw position in the models was charted by an intraoral scanner. Afterwards the scanned model was superimposed on the planning model. The deviations of the screw positions were determined at the screw head, tip, and axes. The t-test, ANOVA test, and likelihood ratio test were used for statistical analysis. The significance level was set at α = 5%. Results: At the screw tip the mean deviations varied between 1.14 mm and 1.78 mm. The 3D splint insertion yielded the smallest deviations, and the freehand insertion yielded the largest. For the screw head position the mean values varied between 0.82 mm and 1.56 mm. The smallest values were observed with the 3D splint method. However, the other transfer splints also showed significantly smaller deviations compared to freehand insertion. Significantly more precise scatter values were provided in the screw head area by the 3D-printed splint compared to all other insertion techniques. For the angular deviation of the screw axes, all transfer splints used showed significantly more accurate and precise values compared to freehand insertion. The values diverged between 2.73° and 8.88°. Conclusion: The insertion splints designed and 3D-printed with TADmatch prove to be a reliable tool for OMI placement. They allow a more accurate, precise and reproducible transfer of the planned screw position to the insertion model compared to the other methods tested. Angular deviations are reduced by all insertion templates tested. Manual freehand insertion is the least accurate and precise

The competitive NMDA antagonist CPP protects substantia nigra neurons from MPTP-induced degeneration in primates

Degeneration of nigrostriatal dopaminergic neurons is the primary histopathological feature of Parkinson's disease. The neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces a neurological syndrome in man and non-human primates very similar to idiopathic Parkinson's disease by selectively destroying dopaminergic nigrostriatal neurons. This gives rise to the hypothesis that Parkinson's disease may be caused by endogenous or environmental toxins. Endogenous excitatory amino acids (EAAs) such as L-glutamate could be involved in neurodegenerative disorders including Parkinson's disease. We report in this study that the competitive NMDA antagonist CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) protects nigral tyrosine hydroxylase (TH) positive neurons from degeneration induced by systemic treatment with MPTP in common marmosets. This indicates that EAAs are involved in the pathophysiological cascade of MPTP-induced neuronal cell death and that EAA antagonists may offer a neuroprotective therapy for Parkinson's disease

A Production-oriented Approach in Electromagnetic Forming of Metal Sheets

parts per unit. Especially demands of modern lightweight design seem to be hard to satisfy by stretching conventional production methods. Thus, it is necessary to find new approaches. Adapting electromagnetic forming technology for the automotive industry would gain additional benefits like - less surface damaging owing to contact-less forming, - the possibility of achieving smaller radii, - focusing on low volume production through minimizing investment costs, and - more manufacturing flexibility. An approach to start qualifying this technology under the aspect of production engineering has been attempted by establishing a high speed forming project. The Volkswagen AG, Siemens AG, H&T ProduktionsTechnologie GmbH together with Fraunhofer Institute of Machine Tools and Forming Technology started activities focusing on - clarifying the fields of research and development which are not resolved to date, - developing necessary equipment, and - a systematic research on the according technology. The analysis of available equipments brought up a number of questions with respect to production engineering requirements. It resulted in a 100 kJ pulse power generator. One of the core components to define the quality of the forming process of flat parts is the flat coil. A coil design is selected to transfer a maximum of stored energy into the sheet metal. A selection of basic and applied experiments had the aim to know the limits of the technique. The paper introduces some representative results of the project. It touches the challenges related to the process of bringing this technology to productio

Enzastaurin inhibits ABCB1-mediated drug efflux independently of effects on protein kinase C signalling and the cellular p53 status

The PKCβ inhibitor enzastaurin was tested in parental neuroblastoma and rhabdomyosarcoma cell lines, their vincristine-resistant sub-lines, primary neuroblastoma cells, ABCB1-transduced, ABCG2-transduced, and p53-depleted cells. Enzastaurin IC50s ranged from 3.3 to 9.5 μM in cell lines and primary cells independently of the ABCB1, ABCG2, or p53 status. Enzastaurin 0.3125 μM interfered with ABCB1-mediated drug transport. PKCα and PKCβ may phosphorylate and activate ABCB1 under the control of p53. However, enzastaurin exerted similar effects on ABCB1 in the presence or absence of functional p53. Also, enzastaurin inhibited PKC signalling only in concentrations ≥ 1.25 μM. The investigated cell lines did not express PKCβ. PKCα depletion reduced PKC signalling but did not affect ABCB1 activity. Intracellular levels of the fluorescent ABCB1 substrate rhodamine 123 rapidly decreased after wash-out of extracellular enzastaurin, and enzastaurin induced ABCB1 ATPase activity resembling the ABCB1 substrate verapamil. Computational docking experiments detected a direct interaction of enzastaurin and ABCB1. These data suggest that enzastaurin directly interferes with ABCB1 function. Enzastaurin further inhibited ABCG2-mediated drug transport but by a different mechanism since it reduced ABCG2 ATPase activity. These findings are important for the further development of therapies combining enzastaurin with ABC transporter substrates

A Novel Reading Scheme for Assessing the Extent of Radiographic Abnormalities and Its Association with Disease Severity in Sputum Smear-Positive Tuberculosis: An Observational Study in Hyderabad/India.

Existing reading schemes for chest X-ray (CXR) used to grade the extent of disease severity at diagnosis in patients with pulmonary tuberculosis (PTB) are often based on numerical scores that summate specific radiographic features. However, since PTB is known to exhibit a wide heterogeneity in pathology, certain features might be differentially associated with clinical parameters of disease severity.We aimed to grade disease severity in PTB patients at diagnosis and after completion of DOTS treatment by developing a reading scheme based on five different radiographic manifestations and analyze their association with the clinical parameters of systemic involvement and infectivity.141 HIV-negative adults with newly diagnosed sputum smear-positive PTB were enrolled in a prospective observational study in Hyderabad, India. The presence and extent on CXRs of five radiographic manifestations, i.e., lung involvement, alveolar infiltration, cavitation, lymphadenopathy and pleural effusion, were classified using the new reading scheme by using a four-quadrant approach. We evaluated the inter-reader reliability of each manifestation, and its association with BMI and sputum smear positivity at diagnosis. The presence and extent of these radiographic manifestations were further compared with CXRs on completion of DOTS treatment.At diagnosis, an average lung area of 51.7% +/- 23.3% was affected by radiographic abnormalities. 94% of the patients had alveolar infiltrates, with 89.4% located in the upper quadrants, suggesting post primary PTB and in 34.8% of patients cavities were found. We further showed that the extent of affected lung area was a negative predictor of BMI (β value -0.035, p 0.019). No significant association of BMI with any of the other CXR features was found. The extent of alveolar infiltrates, along with the presence of cavitation, were strongly associated with sputum smear positivity. The microbiological cure rate in our cohort after 6 months of DOTS treatment was 95%. The extent of the affected lung area in these patients decreased from 56.0% +/- 21.5% to 31.0 +/- 20% and a decrease was also observed in the extent of alveolar infiltrates from 98.4% to 25.8% in at least one quadrant, presence of cavities from 34.8% to 1.6%, lymphadenopathy from 46.8% to 16.1%, and pleural effusion from 19.4% to 6.5%.We established a new assessment scheme for grading disease severity in PTB by specifically considering five radiographic manifestations which were differently associated with the BMI and sputum smear positivity, changed to a different extent after 6 months of treatment and exhibited an excellent agreement between radiologists. Our results suggest that this reading scheme might contribute to the estimation of disease severity with respect to differences in disease pathology. Further studies are needed to determine a correlation with short and long-term pulmonary function impairment and whether there would be any benefit in lengthening or modulating therapy based on this CXR severity assessment

An Observational Study in Hyderabad/India

Background Existing reading schemes for chest X-ray (CXR) used to grade the extent of disease severity at diagnosis in patients with pulmonary tuberculosis (PTB) are often based on numerical scores that summate specific radiographic features. However, since PTB is known to exhibit a wide heterogeneity in pathology, certain features might be differentially associated with clinical parameters of disease severity. Objective We aimed to grade disease severity in PTB patients at diagnosis and after completion of DOTS treatment by developing a reading scheme based on five different radiographic manifestations and analyze their association with the clinical parameters of systemic involvement and infectivity. Methods 141 HIV-negative adults with newly diagnosed sputum smear-positive PTB were enrolled in a prospective observational study in Hyderabad, India. The presence and extent on CXRs of five radiographic manifestations, i.e., lung involvement, alveolar infiltration, cavitation, lymphadenopathy and pleural effusion, were classified using the new reading scheme by using a four-quadrant approach. We evaluated the inter-reader reliability of each manifestation, and its association with BMI and sputum smear positivity at diagnosis. The presence and extent of these radiographic manifestations were further compared with CXRs on completion of DOTS treatment. Results At diagnosis, an average lung area of 51.7% +/- 23.3% was affected by radiographic abnormalities. 94% of the patients had alveolar infiltrates, with 89.4% located in the upper quadrants, suggesting post primary PTB and in 34.8% of patients cavities were found. We further showed that the extent of affected lung area was a negative predictor of BMI (β value -0.035, p 0.019). No significant association of BMI with any of the other CXR features was found. The extent of alveolar infiltrates, along with the presence of cavitation, were strongly associated with sputum smear positivity. The microbiological cure rate in our cohort after 6 months of DOTS treatment was 95%. The extent of the affected lung area in these patients decreased from 56.0% +/- 21.5% to 31.0 +/- 20% and a decrease was also observed in the extent of alveolar infiltrates from 98.4% to 25.8% in at least one quadrant, presence of cavities from 34.8% to 1.6%, lymphadenopathy from 46.8% to 16.1%, and pleural effusion from 19.4% to 6.5%. Conclusions We established a new assessment scheme for grading disease severity in PTB by specifically considering five radiographic manifestations which were differently associated with the BMI and sputum smear positivity, changed to a different extent after 6 months of treatment and exhibited an excellent agreement between radiologists. Our results suggest that this reading scheme might contribute to the estimation of disease severity with respect to differences in disease pathology. Further studies are needed to determine a correlation with short and long-term pulmonary function impairment and whether there would be any benefit in lengthening or modulating therapy based on this CXR severity assessment