Background: The beneficial metabolic effects of the PPARγ agonist rosiglitazone (Rosi) are associated with anti-inflammatory changes in adipose tissue macrophages (ATMs) . One study aim was to characterize the in vivo Rosi-induced phenotypic switch of ATMs using a variety of macrophage markers, including the lipid-associated macrophage markers CD9 and Trem2. As a second aim, since ATM-derived exosomes can exert insulin-sensitizing or desensitizing effects dependent on ATM cell context, we assessed the effects of ATM exosomes from Rosi-treated obese mice on in vitro insulin actions.
 Research Design and Method: ATMs were isolated from 4 months HFD/obese mice treated for the last month with Rosi (60 mg/kg HFD) compared to HFD or chow-fed controls. Among CD11b+F4/80+ or CD64+ macrophages, we identified pro-inflammatory ("M1-like" CD11c+ and/or CD9+) , anti-inflammatory ("M2-like" CD11c-CD206+) and lipid-associated (CD9+ and/or Trem2+) ATMs by flow cytometry. Bone marrow-derived macrophages (BMDMs) were treated in vitro with µM Rosi for 24h. 3T3-L1 adipocytes, L6 myotubes, and primary hepatocytes were cultured 24h with exosomes isolated from ATMs of Rosi treated obese mice or in vitro Rosi treated BMDMs and then assessed for insulin sensitivity.
 Results: Rosi treatment reduced adipose tissue inflammation, as seen by reduced numbers of pro-inflammatory ("M1-like") ATMs and increased the Trem2 signature in "M2-like" ATMs. Importantly, Rosi directly induced Trem2 expression in vitro in BMDMs. Additionally, exosomes isolated from Rosi-treated obese mice or M1 BMDMs increased glucose uptake and insulin signalling (pAKT) in adipocytes and myotubes and reduced glucose production in hepatocytes compared to control exosomes.
 Conclusion: Our data indicate that Trem2 is a PPARγ target gene. Since exosomes from Rosi treated ATMs or BMDMs enhance cellular insulin action, this could provide a new explanation for the well-known insulin-sensitizing effects of PPARγ agonists.

 T.V.Rohm: None. F.C.G.Reis: None. R.Isaac: None. M.Paszek: None. G.Bandyopadhyay: None. J.M.Olefsky: None.

 Swiss National Science Foundation (SNF) Early Postdoc.Mobility grant (to T.R.) .


Influence analysis is an important problem in social network analysis due to its impact on viral marketing and targeted advertisements. Most of the existing influence analysis methods determine the influencers in a static network with an influence propagation model based on pre-defined edge propagation probabilities. However, none of these models can be queried to find influencers in both context and time-sensitive fashion from a streaming social data. In this paper, we propose an approach to maintain real-time influence scores of users in a social stream using a topic and time-sensitive approach, while the network and topic is constantly evolving over time. We show that our approach is efficient in terms of online maintenance and effective in terms various types of real-time context- and time-sensitive queries. We evaluate our results on both social and collaborative network data sets.


The morphology of the lactose fermenting organism, Kluyveromyces marxianus var. marxianus NRRLy2415 was studied in batch and continuous culture. The morphology of the organism was observed to vary significantly from a budding yeastlike form to a branched pseudohyphal form depending on the operating conditions. The following morphological classes were deemed important for the complete description of culture morphology: yeast, elongated yeast, filament, double yeast, double elongated yeast, double filament and pseudohyphae.

Image analysis was used to implement the classification system, due to its objectivity in measurement of visual phenomena. The protocol developed was also capable of measuring geometric properties of the cell population including volume, length and width for all cells and hyphal growth unit length for pseudohyphae.

The predominant morphology observed for the organism in fully aerobic batch culture was yeast-like. When the agitation rate was decreased, an increased heterogeneity in the morphology was observed, w ith the generation o f more elongated yeast and filamentous forms. This was attributed to partial oxygen limitation in the fermentations.

In chemostat culture, the morphology observed was predominantly pseudohyphal. This morphological form was found to dominate over a large range of dilution rates (0 .1-0 .45 h ']) and substrate feed concentrations (5 to 20 g /L lactose). At both extrema of dilution rates a reversion to a yeastlike morphology was observed. The mycelial morphology was attributed to substrate limitation and was demonstrated to be of ecological advantage under substrate limited conditions.

Kinetic modelling of substrate metabolism was undertaken for continuous and batch culture results. It was demonstrated that, the stoichiometry of the metabolic pathways studied was identical under all operating conditions. This is significant, as the morphology of the organism varies significantly from batch to continuous culture.

A population model was developed which was capable of describing the distributions of cell geometric parameters based on summed lognormal distributions of selected morphological classes.

The ultrastructure of pseudohyphae was examined. This study demonstrated significant differences in methods of formation between pseudohyphae and true hyphae and highlighted key issues that need to be addressed if successful modeling of such grow this to be undertaken.


The essay explores an 1851 incident of violence among black Bostonians centering on conflicts about the merits of school desegregation. The episode reveals differing concepts of and approaches to citizenship in the African-American community, tensions that were exacerbated by abolitionist activity, Revolutionary memory, and the Fugitive Slave Law.


This week we have the pleasure of hearing Dr. Robert Wachter's speech at the 2017 University of Pennsylvania School of Medicine Commencement, titled "Talk to the Radiologist." Robert M. Wachter, M.D. is Professor and current Chair of the Department of Medicine at the University of California, San Francisco. He is also former President of the Society of Hospital Medicine and former Chair of the American Board of Internal Medicine. Having coined the term "hospitalist" in 1996, he is often considered the "father" of the hospitalist field, the fastest growing specialty in the history of modern medicine. Dr. Wachter is the author of 250 articles and 6 books. In the safety and quality arenas, he edits the U.S. government's leading website on patient safety and has written two books on the subject, including Internal Bleeding and Understanding Patient Safety, the world's best selling safety primer. In 2004, he received the nation's top honor in patient safety the John M. Eisenberg Award. In 2016, Modern Healthcare magazine ranked him as the fourth most influential physician-executive in the U.S., his ninth consecutive year in the top 50 (he was #1 on the list in 2015). He has additionally served on the healthcare advisory boards of several companies, including Google. His 2015 book, The Digital Doctor: Hope, Hype and Harm at the Dawn of Medicine's Computer Age, is a New York Times science bestseller. He recently chaired a blue ribbon commission advising England's National Health Service on its digital strategy. We all have people in our lives that we credit with influencing our decision to become physicians. For Dr. Wachter, it was his father who played a significant role in this decision-making.  His father held a fascination with the medical profession. He went so far as to wear a garage door opener on his belt in imitation of a physician's pager. Altogether, his father's intrigue with medicine, as well as his unexpected and emergent cancer diagnosis, guided Dr. Wachter toward a career in medicine. He states: "The experience taught me many things. How terrifying illness is for patients and family members. How doctors aren't necessarily too great at prognosticating. And how important human-to-human contact is in medicine – not just between doctors and patients, but also among members of the care team." "Medicine is changing."  Dr. Wachter conveys this message throughout the speech.  In particular, he focuses on the technological surge that is making its way through medicine.  He calls it "widespread digitization."  Is this change for better or for worse?  He does not explicitly answer this question.  Instead, he encourages us to take these technologies and apply them creatively, namely in a manner that will improve our ability to care for patients.  He implores caution, however, as he reminds us that we signed up for this career to treat patients, not diseases. "As the work becomes digitized and the software gets better, we will spend more of our time interacting with our digital tools, and less interacting with  each other, and with our patients. This is natural, and –assuming the tools are any good – it might even be OK. After all, computers will hold much of the information, and they will be where we develop and implement many of our diagnostic and treatment plans. But, there is a huge danger from hunkering down in our digital caves. You can never fully understand a consultant's thinking by reading her note. You can  never place a complex radiology finding in context without speaking to the radiologist. You can never allay the anxiety of a sick patient's spouse by sending a text message. And you can never comfort a dying patient without sitting at the bedside and holding his hand." Indeed, technology will allow us to push the bounds of diagnostic and treatment capabilities.  In this regard I remain optimistic, though Dr. Wachter's words have reminded me that at the end of the day, technology is a tool.  Tools supplement –not replace— our creativity, compassion, and ability to connect with others. Dr Wachter concludes with a call to action:  "We have the opportunity today to do more for our patients than ever before. And you have the knowledge, skills, values, and habits of mind to thrive in this changing world. You are the ones who will reinvent the work to deliver for our patients. And you will figure out how to balance our new digital capabilities with the enduring truth that medicine is, and must remain, the most human of professions. Thank you for the honor of speaking to you today. Congratulations to each and every one of you. "


We present optical follow-up imaging obtained with the Katzman Automatic Imaging Telescope, Las Cumbres Observatory Global Telescope Network, Nickel Telescope, Swope Telescope, and Thacher Telescope of the LIGO/Virgo gravitational wave (GW) signal from the neutron star–black hole (NSBH) merger GW190814. We searched the GW190814 localization region (19 deg2 for the 90th percentile best localization), covering a total of 51 deg2 and 94.6% of the two-dimensional localization region. Analyzing the properties of 189 transients that we consider as candidate counterparts to the NSBH merger, including their localizations, discovery times from merger, optical spectra, likely host galaxy redshifts, and photometric evolution, we conclude that none of these objects are likely to be associated with GW190814. Based on this finding, we consider the likely optical properties of an electromagnetic counterpart to GW190814, including possible kilonovae and short gamma-ray burst afterglows. Using the joint limits from our follow-up imaging, we conclude that a counterpart with an r-band decline rate of 0.68 mag day−1, similar to the kilonova AT 2017gfo, could peak at an absolute magnitude of at most −17.8 mag (50% confidence). Our data are not constraining for "red" kilonovae and rule out "blue" kilonovae with M > 0.5 M ⊙ (30% confidence). We strongly rule out all known types of short gamma-ray burst afterglows with viewing angles <17° assuming an initial jet opening angle of ∼5.°2 and explosion energies and circumburst densities similar to afterglows explored in the literature. Finally, we explore the possibility that GW190814 merged in the disk of an active galactic nucleus, of which we find four in the localization region, but we do not find any candidate counterparts among these sources.


The light source of a photometer may induce chemical reactions in photosensitive reactive systems. Diode-array spectrophotometers are particularly suitable for producing such phenomena. This paper provides an overview on how this equipment can be used as a photoreactor. The principles of various techniques to control the intensity and spectral region of the illuminating light are discussed in detail. It will be shown that the quantum yields of various photochemically induced redox reactions can be determined by exploiting specific features of diode-array spectrophotometers. Kinetic coupling between primary photo-chemical and secondary thermally activated reaction steps are utilized to explore intimate details of composite redox reactions. Key aspects of the method applied are demonstrated via the photoreactions of 2,6-dichloro-1,4-benzoquinone (DCQ), the photoinduced autoxidation of S(IV) and a photochemically activated redox reaction of the chlorate ion.


The purpose of this study was to evaluate the efficacy of the radical scavenger IAC (bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl) decantionate) in alleviating behavioral deficits and reducing amyloid-β (Aβ) accumulation in an Alzheimer's disease (AD) transgenic Tg2576 mouse model. Daily treatment with IAC (3-30 mg/kg, i.p.) was started at the age of 6 months and continued until the mice were 13 months old. At the age of 9 months and again at 12 months, the mice were tested in open field and water maze tests. At the age of 13 months, the mice were sacrificed and the brains processed for immunohistochemistry. Mortality was significantly reduced in all IAC-treated groups. In addition, IAC treatment improved the water maze hidden platform training performance but had no effect on motor activity in the open field or water maze swim speed in transgenic mice. Lastly, IAC treatment (10 mg/kg) significantly reduced the cortical Aβ plaque burden. In vitro, IAC is able to increase the number of neurites and neurite branches in cultured cortical primary neurons. In conclusion, IAC slowed down the development of the AD-like phenotype in Tg2576 mice and accelerated neurite growth in cultured neurons.


Due to its high incidence and poor prognosis, gastric cancer is an important health problem worldwide. The liver is the most frequent site of metastases. Advanced cancer in the setting of liver dysfunction poses a dilemma for physicians, as many cancer chemotherapeutic agents undergo hepatic metabolism. This paper reports the case of a patient with liver failure due to liver metastases of gastric cancer. The initial liver function tests showed an elevation of transaminases (aspartate amino transferase 180 IU/l, alanine aminotransferase 110 UI/l), hyperbilirubinemia (total bilirubin at 24 mg/dl), alkaline phosphatase at 1127 UI/l and elevation of tumor markers (carcinoembryonic antigen >1000 ng/ml and CA19,9 at 180 UI/l). We initiated capecitabine/cisplatin based combination chemotherapy. Our data supports the safety and feasibility of cisplatin-capecitabine regimen in patients with severe liver dysfunction secondary to liver metastases of gastric cancer.


Background: Lower extremity peripheral nerve blocks (PNBs) have been traditionally less employed compared to other forms of regional anesthesia. The advent of peripheral nerve stimulator and ultrasonography, complications associated with neuraxial anesthesia, and improved rehabilitation with PNBs has led to renewed interest in lower limb blocks. Lumbar plexus block can be given by anterior (Winnie's "3 in 1" block) and posterior (psoas compartment block) approaches. Subjects and Methods: In this randomized, observer-blinded study, we compared these techniques in two groups of patients (Group A [n = 30] and Group P [n = 30]) undergoing lower limb surgeries using nerve locator. They were supplemented with sciatic nerve block by Labat's approach. The primary objective was to compare the onset of sensory and motor blockade. Secondary objectives included the duration of sensory and motor blockade, sparing of nerves and complications if any. The onset of sensory analgesia was assessed by visual analog scale <3 and motor blockage by modified Bromage scale. For data analysis, t-test and Chi-square test were applied. Results: In Group A, onset of sensory block was 4.816 ± 0.932 min, and in Group P, 17.167 ± 2.364 min. In Group A, the onset of motor action was 7.833 ± 1.227 min, and in Group P, 22.8 ± 4.42 min. The duration of motor block was 5.6 ± 1.07 h in group A and 5.88 ± 0.90 h in Group P. The duration of sensory block was found to be 8.18 ± 1.32 h in Group A and 8.18 ± 0.88 h in Group P. Conclusion: Winnie's 3-in-1 block is associated with rapid onset of sensory and motor block but is associated with sparing of lateral femoral cutaneous nerve and obturator nerve causing inadequate analgesia and tourniquet pain needing additional block or sedation compared to psoas compartment block which provides denser block.


Over the past decade, faster CT scan times, thinner collimation, and the development of multirow detectors, coupled with the increasing capability of computers to process large amounts of data in short periods of time, have lead to an expansion in the ability to create diagnostically useful two-dimensional (2D) and threedimensional (3D) images within the thorax. Applications within the thorax include, but are not limited to, evaluation of pulmonary and systemic vasculature, evaluation of the tracheobronchial tree, and delineation of diffuse lung disease. Pulmonary nodule volume and growth can be more accurately predicted, and represents an improvement in the evaluation of the solitary pulmonary nodule. Multiplanar images increase our understanding of thoracic anatomy and can help to guide bronchoscopic procedures. Because there are strengths and weaknesses to all the reconstruction algorithms, the utility of any given technique is dependent on the clinical question to be answered. For instance, although maximum intensity projection imaging (MIP) is helpful in the evaluation of micronodular lung disease, it is of little value in the diagnosis of aortic dissection. As the ability to generate faster and more precise multidimensional images grow, the demand for such imaging is likely to increase. In this review, the authors discuss the various reconstruction techniques available, followed by a discussion of the clinical applications.


OBJECT
Although the development and prevalence of cerebral vasospasm (CV) has been extensively investigated in adults, little data exist on the development of CV in children. The authors hypothesized that even though children have highly vasoreactive arteries, because of a robust cerebral collateral blood flow, they rarely develop symptomatic CV.

METHODS
The authors retrospectively reviewed their university hospital's neurointerventional database for children (that is, patients ≤ 18 years) who were examined or treated for aneurysmal or traumatic subarachnoid hemorrhage (SAH) during the period 1990-2013. Images from digital subtraction angiography (DSA) were analyzed for the extent of CV and collateralization of the cerebral circulation. Results from transcranial Doppler (TCD) ultrasonography were correlated with those from DSA. Cerebral vasospasm on TCD ultrasonography was defined according to criteria developed for adults. Clinical outcomes of CV were assessed with the pediatric modified Rankin Scale (mRS).

RESULTS
Among 37 children (21 boys and 16 girls ranging in age from 8 months to 18 years) showing symptoms of an aneurysmal SAH (comprising 32 aneurysms and 5 traumatic pseudoaneurysms), 17 (46%) had CV confirmed by DSA; CV was mild in 21% of these children, moderate in 50%, and severe in 29%. Only 3 children exhibited symptomatic CV, all of whom had poor collateralization of cerebral vessels. Among the 14 asymptomatic children, 10 (71%) showed some degree of vessel collateralization. Among 16 children for whom TCD data were available that could be correlated with the DSA findings, 13 (81%) had CV according to TCD criteria. The sensitivity and specificity of TCD ultrasonography for diagnosing CV were 95% and 59%, respectively. The time to CV onset detected by TCD ultrasonography was 5 ± 3 days (range 2-10 days). Twenty-five (68%) of the children had good long-term outcomes (that is, had mRS scores of 0-2).

CONCLUSIONS
Children have a relatively high incidence of angiographically detectable, moderate-to-severe CV. Children rarely develop symptomatic CV and have good long-term outcomes, perhaps due to robust cerebral collateral blood flow. Criteria developed for detecting CV with TCD ultrasonography in adults overestimate the prevalence of CV in children. Larger studies are needed to define TCD ultrasonography-based CV criteria for children.


This paper discusses potential issues with inter-group processes which may be exacerbated through outsourcing contracts. Conflict in group processes can adversely affect performance of individuals, teams and organisations. We use a multiple case study approach carrying out semi-structured interviews with 40 staff from 14 outsourced contracts which had been transferred into 6 outsourcing organisations. A number of in and out group categorisations were used. These included disparaging categories for the out-group (e.g. 'robots' or 'suits'), and discussions of (un)professional behaviour linked to these categories – often indicating high levels of contempt. Implications for practice are highlighted.


Email and email security have been the main topics of this master thesis. The thesis considers how an organization works with email security and security culture, the email specifications, threat agents, vulnerabilities and attacks distributed via email. Several technological security features are standard in email systems nowadays. Technological evolution and development give better solutions for filtering and rejecting malicious email. However, new vulnerabilities are exploited and new attacks take place. Some email containing malware, phishing, or scam will probably get through to end-users' inboxes. The only truly effective protection found is to promote email security and make email users aware of the potential threats. Today there are no good solutions for dealing with email that have passed these technical security measures. As a part of the organizations work to improve security culture, a functionality for users to report suspicious emails has been developed. This enables users to directly report suspicious emails to IT security personnel by a simple click of a button. However, as of now, it us up to the IT security personnel to manually perform analysis on the reported emails. This takes time, and the amount of reported emails increases every week. To improve email security and reduce time spent on manual analysis there is potential for handling such email in a smarter way. One solution is to automate the process of analysing the suspicious emails reported. This automation tool could help IT security personnel reduce risks and provide information to other users so that measures could be taken to stop malicious email. Results from data analyses and hypotheses testing show that it would be beneficial with better information to the users, and to implement some added functionality to the reporting of suspicious emails. This would better achieve the intention of having users report suspicious email as a part of the email security work. An automated system for extracting and parsing reported emails can be used for alerting users and informing system administrators. Further, with few modifications, this system could be used with data from the reported emails to proactively block or filter future emails before they reach end-users' inboxes.


A set of 11 measurements on 40 species of placental (Order Carnivora) and marsupial (Order Dasyurida) carnivores is analysed by means of correspondence analysis. Dasyurida have long mandibles and tooth rows, large muscle attachment areas on the mandible, long moment arms of the temporalis and masseter, and a low occiput and short temporal fossa. Skull shape is uniform in Dasyurida, with about the same variability as in a family of Carnivora. The temporalis of Dasyurida is relatively small, but this may be compensated for by the more rounded shape and longer moment arm. The Tasmanian tiger, Thylacinus cynocephalus, is more similar in skull shape to the red fox, Vulpes vulpes, than to the placental wolf, Canis lupus. The M5 of Dasyurida occupies the same geometric position as the MI in Carnivora, providing a possible explanation for the greater variability in cheek teeth in Carnivora. The Tasmanian devil, Sarcophilus harrisii, is similar to the Hyaenidae in having a shorter distance between the ultimate sectorial molar and the condyle. It is suggested that this is an adaptation to cracking open bones, as this mandible geometry brings the main bone-cracking teeth closer to the region of greatest muscle force.


Design research today is characterized by its focus on technological innovation, especially digital innovation, and on collaborations between university researchers and private or public sector organizations to address practical concerns. In tandem with this direction, funding bodies encourage and often stipulate cross-disciplinary partnerships and look favourably upon projects that contribute to 'real world' impact. These widespread practices, however, can be problematic. They tend to endorse, rather than disinterestedly critique, the dominant paradigm, which despite its many material and practical benefits, is highly destructive of the natural environment, deeply inequitable and socially divisive and, on an individual level, associated with a sense of meaninglessness. Also, such intimate involvement of funding bodies in the positioning of academic inquiry can seriously compromise vitally important elements of scholarship, not least critical distance and academic freedom. Despite the difficulties of doing so within this trenchantly instrumental climate, some take a different path, pursuing design studies that critique narrowly framed technological and economic interpretations of progress; business-focused academic research; and the prioritization of 'impact' over curiosity-based inquiry. It is a path that offers opportunities for design to address some of the more significant concerns of our age. Over time, such work may be capable of fostering changes in understanding and contributing to what we might term meaningful innovation. Because of their diverse and emergent areas of focus these areas of design research have a variety of labels including critical design, speculative design, and propositional design. To contextualize these countervailing directions, this chapter begins with a discussion of the role and nature of design practice in academia. An overview of the historical developments that set the agenda for design in the twentieth century, which still dominates the field in the twenty-first, allows us to better understand the contribution of these new directions in advancing the discipline. The works of several designers are discussed, including examples from the author's own academic design practice. These illustrate the kinds of issues being addressed, the relationship between theory and practice, and the roles of creativity, subjectivity, rhetoric and polemic in design research.


Fowler-Stephens orchiopexy is the most common method of treating high-positioned undescended testes. Its success rate has been reported to be as high as 50-70% based on palpation or in a few circumstances on biopsy. Although it is convenient to evaluate testicular function by palpation and/or biopsy, this method is very subjective and is not scientific enough. To determine testicular function more precisely and objectively, we performed the Fowler-Stephens orchiopexy on Sprague-Dawley rats and observed the morphological and biochemical changes, including assays of LDH, SDH and the testosterone level. In our morphological study, with the use of Fowler-Stephens orchiopexy, only 17% (3/18) of the rat tests could be salvaged. The others revealed either necrosis or fibrosis. Testicular LDH, checked at the 4th postoperative week, revealed 0.62 +/- 0.04 U/mg which was statistically different (p less than 0.05) from that of the control group and the hemicastrated group (0.77 +/- 0.05 U/mg and 0.76 +/- 0.07 U/mg, respectively). The SDH obtained from the testes also revealed significant differences between the study group and the control and hemicastrated groups. Values obtained were 2.67 +/- 0.15 mU/mg, 3.77 +/- 0.4 mU/mg and 3.77 +/- 0.33 mU/mg, respectively (p less than 0.05). Using electrophoresis, 3 out of 18 rats had typical X bands, which is the classical picture of a normal mature testis. In contrast, the others showed faint X bands at the 2nd postoperative week, which subsequently faded thereafter. During testicular ischemia, the Leydig cells are more resistant than the Sertoli cells and the germinal cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Building a research framework for a Parallel Hydraulic Hybrid (PHH) Prototype with Hydraulic Regenerative Braking and Launch Assist (HRB/HLA) System for small and medium sized vehicles has been attempted. The objective of this work is to capture lost Kinetic Energy during braking and store that captured energy in a pressurized accumulator to be used again to assist accleration. The experimental implementation and validation of the Regenerative Braking System concept for light vehicles has been done using a go-kart powered by a single cylinder Honda engine to demonstrate energy savings in a real life braking scenario. A light weight test system accommodating all the Hydraulic Breaking System components mounted at the rear of the go-kart has been successfully built and tested.


Shipping lines generally offer their clients two main value propositions: port- to-port and door-to-door transport. In addition, some shipping lines offer a third value proposition in the form of transport up to inland terminals (ILTs). This third value proposition combines maritime and inland transport and is offered to two types of customers: shippers and forwarders. These two customer groups have different positions in the supply chain. It is therefore expected that shippers and forwarders have different attitudes towards the intermodal value proposition and the service offering of shipping lines in general. In this article we analyse how shippers and forwarders assess the value propositions of shipping through a survey among shippers and forwarders in the Netherlands. We found that shippers and forwarders differ in what they find important in the service offering of shipping lines, that they differ in the share of value propositions they source from the shipping lines and that for both shippers and forwarders the value proposition centred around an ILT is of added value.


Introduction:Telemedicine is the need of the hour to keep pace with developments in the healthcare industry. Easy and better access to facilities facilitates customer retention. Online consultations facilitate hassle free patient-doctor communication, in sharp contrast with the common sight of long waiting queues for doctors. Objective: To develop and analyse the efficacy of a web portal for an assisted reproduction center at a tertiary care hospital in South India.Method:This study was conducted between November 2017 and April 2018. An initial study was conducted to analyse the need for online consultations at this center. Based on this study and considering the future requirements of e consultation in Kasturba hospital, a web portal was developed. Upon the completion and implementation of the web portal, patients who registered for the web portal services were administered a feedback questionnaire on the efficacy of the web portal. This questionnaire had to be filled out by the patients when they logged out of their web portal account. The questionnaire responses were analysed to assess the acceptance level of patients to online consultation and the working efficiency of the web portal.Results:Patients who registered with the web portal found it user friendly. They found it easy to access all information on the portal. The positive feedback and suggestions from patients suggest that the patient portal was wilfully accepted by them.


Technological changes in tax administration especially VAT have also changed the way tax authorities around the world implement e-invoice tax, one of which is Australia. The Ministry of Finance of the Directorate General of Tax (DGT) Indonesia responded to this in 2013 by creating a VAT administrative technology system called the Electronic Tax Invoice (e-Faktur). This study aims to determine the administration of Indonesian e-Faktur by looking at the Australian e-invoice as a benchmark and to find out the problems of e-Faktur in Indonesia after implementation. This research method is a qualitative method with techniques in the form of literature studies and in-depth interviews with informants. The results of this study are that the e-Faktur of the system in Indonesia is different from the understanding of the existing e-invoicing in the literature and the Australian state. Australian e-invoicing system neglects sending data in the form of digital data (PDF) and sending via email. E-Faktur was found to still have problems after its application such as access which was always problematic because of the network, the insecurity of VAT data, and the costs that still arise due to the application e-Faktur such as the still printing of documents and inefficiency. The conclusion from this study is that there are still fundamental differences between the administration of Indonesian and Australian e-invoice.


This study describes the premises underlying Voremetur, a project conducted in the context of higher education. It hypothesises the need to support a competence education method adapted to new educational formulas (from e- to m-learning), new educational challenges (e-science, big data) and the convergent competences now characterised as info-communication literacy, which has favoured the transition from edu-communication to multiliteracy. Such competences should be organised into competence programmes, where the assessment of the beneficial results for learners and the university should be included as an essential element. The article discusses an assessment model for new literacies, including its conceptual framework, ideal evaluation tools and conversion into an ad hoc questionnaire. Lastly, the paper describes model application to a target group and analyses the results most relevant to information behaviour.


Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal bone marrow disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and potential for malignant transformation. Lower/intermediate-risk MDSs are associated with longer survival and high red blood cell (RBC) transfusion requirements resulting in secondary iron overload. Recent data suggest that markers of iron overload portend a relatively poor prognosis, and retrospective analysis demonstrates that iron chelation therapy is associated with prolonged survival in transfusion-dependent MDS patients. New data provide concrete evidence of iron's adverse effects on erythroid precursors in vitro and in vivo. Renewed interest in the iron field was heralded by the discovery of hepcidin, the main serum peptide hormone negative regulator of body iron. Evidence from β-thalassemia suggests that regulation of hepcidin by erythropoiesis dominates regulation by iron. Because iron overload develops in some MDS patients who do not require RBC transfusions, the suppressive effect of ineffective erythropoiesis on hepcidin may also play a role in iron overload. We anticipate that additional novel tools for measuring iron overload and a molecular-mechanism-driven description of MDS subtypes will provide a deeper understanding of how iron metabolism and erythropoiesis intersect in MDSs and improve clinical management of this patient population.


We show that in a reactor disappearance oscillation experiment the sensitivity to the mixing parameter can be substantially improved for (1− 5 · 10) eV 2 mass parameter range which includes both the LSND and the atmospheric neutrino oscillation regions. The objectives are: to search for the sterile neutrinos and to get a better understanding of the atmospheric neutrino oscillation mechanism. The parameters of the underground (600 m.w.e.) Krasnoyarsk reactor and data from the CHOOZ reactor oscillation experiment are used to estimate the effect and background rates.


Convolutional neural networks (CNNs) have become an established part of numerous safety-critical computer vision applications, including human robot interactions and automated driving. Real-world implementations will need to guarantee their robustness against hardware soft errors corrupting the underlying platform memory. Based on the previously observed efficacy of activation clipping techniques, we build a prototypical safety case for classifier CNNs by demonstrating that range supervision represents a highly reliable fault detector and mitigator with respect to relevant bit flips, adopting an eight-exponent floating point data representation. We further explore novel, non-uniform range restriction methods that effectively suppress the probability of silent data corruptions and uncorrectable errors. As a safety-relevant end-to-end use case, we showcase the benefit of our approach in a vehicle classification scenario, using ResNet-50 and the traffic camera data set MIOVision. The quantitative evidence provided in this work can be leveraged to inspire further and possibly more complex CNN safety arguments.


Demand for less skilled workers decreased dramatically in the US and in other developed countries over the past two decades. WE argue that pervasive skill-biased technological change, rather than increased trade with the development world, is the principal culprit. The pervasiveness of this technological change is important for two reasons. Firstly, it is an immediate and testable implication of technological change. Secondly, under standard assumptions, the more pervasive the skill-biased technological, the greater the increase in the embodied supply of less skilled workers and the greater the increase in the embodied supply if less skilled workers and the greater the increases in the embodied supply of less skilled workers and the greater the depressing effect on their relative wages through world goods prices. In contrast, in the Heckscher-Ohlin model with small open economies the skill-bias of local technological changes does not affect wages. Thus, pervasiveness deals with a major criticism of skill-biased technological as a cause. Testing the implications of pervasive, skill-biased technological change, we find strong supporting evidence. Firstly, across the OECD, most industries have increased the proportion of skilled workers employed, despite rising or stable relative wages. Secondly, increases in demand for skills were concentrated in the same manufacturing industries in different developed countries.


Chimpanzee research should not be banned, but its scientific necessity is very limited. Research on chimpanzees is contentious, expensive, and of increasingly limited necessity. Over the past 10 years, there have been only 110 projects involving chimpanzees sponsored by the National Institutes of Health. Close to half of these projects were used for hepatitis research; the remaining studies were in fields including comparative genomics, neuroscience and behavioral research, and infectious diseases such as respiratory syncytial virus (RSV). NIH requested that the Institute of Medicine (IOM) and National Research Council convene an expert committee to assess the current and future scientific necessity of chimpanzee use as a research model in publicly funded biomedical and behavioral research. The committee developed a set of uniform principles around what constitutes necessary use of chimpanzees, because of the lack of existing criteria (1).


A method for the robust position control of brushless DC (BLDC) motors is presented. The linear quadratic controller plus load torque observer is used to obtain an approximately linearized robust BLDC motor system for an AC servo, using the field-orientation method. The gains are obtained systematically from a discrete state space analysis. The robustness is obtained without affecting the overall system response. The load disturbance is detected by a zero-observer of the unknown and inaccessible input, and is feedforward compensated without requiring noisy current information. The overall system is controlled using a microprocessor, and the performance of each control algorithm is compared with both the simulation and the experimental results for two types of machines, a BLDC motor and a brushless direct drive (BLDD) motor. >


Zenia is beautiful, smart and greedy, by turns manipulative and vulnerable, needy and ruthless; a man's dream and a woman"s nightmare. She is also dead. Just to make sure Tony, Roz andd Charis are there for the funeral. But five years on, as the three women share an indulgent, sisterly lunch, the unthinkable happens; 'with waves of ill will flowing out of her like cosmic radiation', Zenia is back...


Identified factors associated with parenting stress among the parents of low birth weight children participating in a prospective longitudinal study. The child's developmental status and the quality of the infant-parent relationship contrib-uted to early childhood parenting stress beyond the contribution of neonatal medical risk, which was a significant predictor until the concurrent measure of child developmental status was entered in the regression analysis. Results are consistent with a model of processes underlying the experiences of parents of medically vulnerable infants presented by the Goldberg and Marcovitch (1986) model. Replication of these findings among parents of specific subgroups of low birth weight children represents a direction for future research.


How could a vulnerability that has been known and understood since 1998 still be included in the Top 10 list of vulnerabilities from the Open Web Application Security Project (OWASP) from 2010 to 2017? The issues are well known and understood, as are the mitigation and fix actions to harden database vulnerabilities. Database vulnerabilities remain persistent because of the proliferation of databases in many aspects of data storage and web applications, where the perceived value of the information in the database is high and the attack mechanism is easy. There are actually several database vulnerabilities, depending on the database employment, which expands the targets and, thus, the vulnerabilities. Individual databases holding organizational data have vulnerabilities, as do web application databases— with web application SQL injection being the most well-known vulnerability. The different database vulnerabilities and attacks can be analyzed through the differentiation between information security and cybersecurity vulnerabilities to better understand the taxonomy and operational semantics for targeted mitigation. The root cause of database vulnerabilities remains poor design and coding. Ultimately, there are multiple SQL injection attack detection methodologies being researched, but prevention through proper design and coding is the best defense. Thus, while a defense in depth is required, when implementing a database solution one of the most important aspects is creating and implementing a robust functional database vulnerability test plan within the request for proposal to ensure that the root cause is mitigated.


This study is a corpus assisted investigation into blues lyrics. Using Wmatrix, an online statistical analysis tool, 795 different blues songs from 35 different male blues artists have been analysed quantitatively for information pertaining to key domains, words and parts of speech. This data has provided the basis for further, qualitative analysis of lyrics with reference being made to ideas already established in other studies of the blues and to linguistic theories about narrative, discourse and metaphor. The thesis seeks to define the linguistic features of blues lyrics at different historical points and attempts to interpret them in the light of the social and political conditions of their times. In doing so, it examines the role of blues lyrics within the African-American community as a whole and investigates the extent to which they established a sense of black identity and were part of a linguistic sub-culture. Further to the exploration of the genre as a whole, the dissertation includes a study into the work of an individual artist, Robert Johnson, with the aim of testing the extent to which he is representative of the blues form in general.


Young people represent a significant asset in economic terms alone; they can contribute to productivity, increased consumption, and income taxes. But youth are also an important asset for social change and innovation. Arab youth see themselves as change agents, with young women as likely to be key to future progress as young men. Young people constitute well over half of Middle East and North Africa's (MENA's) population. Over 30 percent of MENA's population, 100 million individuals were between 15 and 29 years of age in 2007. This can be a demographic opportunity if countries had a majority of youth enter their productive peak while the elderly population still remains small. These windows of opportunity will remain open in MENA for nearly 10 years. In Iraq, Yemen and West Bank and Gaza, the window will be open beyond 2050.


Cardiac myosin binding protein C (cMyBPC) phosphorylation is essential for normal cardiac function. Although PKC was reported to phosphorylate cMyBPC in vitro, the relevant PKC isoforms and functions of PKC-mediated cMyBPC phosphorylation are unknown. We recently reported that a transgenic mouse model with cardiac-specific overexpression of PKCepsilon (PKCepsilon TG) displayed enhanced sarcomeric protein phosphorylation and dilated cardiomyopathy. In the present study, we have investigated cMyBPC phosphorylation in PKCepsilon TG mice. Western blotting and two-dimensional gel electrophoresis demonstrated a significant increase in cMyBPC serine (Ser) phosphorylation in 12-month-old TG mice compared to wild type (WT). In vitro PKCepsilon treatment of myofibrils increased the level of cMyBPC Ser phosphorylation in WT mice to that in TG mice, whereas treatment of TG myofibrils with PKCepsilon showed only a minimal increase in cMyBPC Ser phosphorylation. Three peptide motifs of cMyBPC were identified as the potential PKCepsilon consensus sites including a 100% matched motif at Ser302 and two nearly matched motifs at Ser811 and Ser1203. We treated synthetic peptides corresponding to the sequences of these three motifs with PKCepsilon and determined phosphorylation by mass spectrometry and ELISA assay. PKCepsilon induced phosphorylation at the Ser302 site but not at the Ser811 or Ser1203 sites. A S302A point mutation in the Ser302 peptide abolished the PKCepsilon-dependent phosphorylation. Taken together, our data show that the Ser302 on mouse cMyBPC is a likely PKCepsilon phosphorylation site both in vivo and in vitro and may contribute to the dilated cardiomyopathy associated with increased PKCepsilon activity.


Abstract Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis.


Antisocial Personality Disorder, APD, is characterized by manipulation and disregard for the emotions of others, and individuals suffering from this disorder often display behaviors that cause them to end up in the criminal justice system. The disorder prevents these individuals from learning from their mistakes, leading them to commit multiple crimes over their lifetime. Persons with APD can be diagnosed by psychiatrists and psychologists using psychological assessment tools meant to measure the attributes related to the disorder. However, the psychological tools available today are not entirely reliable or well validated and the instruments are not always useful in various situations. Neuroscientists have developed three brain theories that aim to identify the underlying mechanisms causing the symptoms of the disorder, which could lead to additional methods for diagnosis of APD in the legal setting. The first theory, called the Septo-Hippocampal theory, suggests that a dysfunction in the hippocampus causes the symptoms of APD. The second theory, the Amygdaloid theory, suggests that APD is actually caused by a dysfunction in the amygdala. The third theory, Connectivity theory, suggests that there is dysfunction in the connections between the hippocampus and amygdala that results in APD. The emergence of these theories opens the possibility of using Magnetic Resonance Imaging (MRI) or functional MRI (fMRI) technology as a diagnostic tool for APD. However, none of these theories can adequately explain the occurrence of all cases of APD, suggesting that the dysfunction could be anywhere within the brain system(s) that include the septal nuclei, hippocampus, amygdala, and/or other limbic structures. MRI and fMRI scans may prove to be useless in diagnosing this disorder.


In this paper I use a unique and rich data set on prices and promotions from major US supermarkets to examine the nature of National Brand and Private Label interaction. Private labels are priced and promoted competitively with NBs, in a manner suggesting that retails are careful not to lose private label market share during times of national brand promotions. The price margin between the two types of products continues to fall in US supermarkets, and the major determinants of the price differences between the two are promotional frequency and market concentration.


A recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major determinant of virulence. Elimination of SARS-CoV E protein PBM by using reverse genetics caused a reduction in the deleterious exacerbation of the immune response triggered during infection with the parental virus and virus attenuation. Cellular protein syntenin was identified to bind the E protein PBM during SARS-CoV infection by using three complementary strategies, yeast two-hybrid, reciprocal coimmunoprecipitation and confocal microscopy assays. Syntenin redistributed from the nucleus to the cell cytoplasm during infection with viruses containing the E protein PBM, activating p38 MAPK and leading to the overexpression of inflammatory cytokines. Silencing of syntenin using siRNAs led to a decrease in p38 MAPK activation in SARS-CoV infected cells, further reinforcing their functional relationship. Active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM as compared with the parental virus, leading to a decreased expression of inflammatory cytokines and to virus attenuation. Interestingly, administration of a p38 MAPK inhibitor led to an increase in mice survival after infection with SARS-CoV, confirming the relevance of this pathway in SARS-CoV virulence. Therefore, the E protein PBM is a virulence domain that activates immunopathology most likely by using syntenin as a mediator of p38 MAPK induced inflammation.


Nine obese female patients were placed on a liquid formula diet containing 320 kcal (1.34 MJ), 31 g protein, 44 g carbohydrate, 1.5 g fat, vitamins and essential minerals for a period of four weeks under metabolic-ward conditions. The diet was tolerated well in all patients and mean weight loss was 2.49 kg per week during the four-week period. Basal serum prolactin levels were normal (2.9 +/- 0.6 ng/ml) and did not show any change during this period. In six patients a TRH test was performed before and during caloric restriction. The maximal increment of PRL after TRH was significantly lowered during dietary treatment: 53.2 +/- 16.2 vs. 32.3 +/- 11.6 ng/ml; mean +/- s.e.m.; P less than 0.025). No change was observed in the serum TSH responset to TRH before and during caloric restriction. Dietary restriction suppresses prolactin synthesis and secretion as measured in response to TRH in obese female patients.


Transduction for lactose-fermenting ability between the lactose-positive lysogen Streptococcus lactis LM0221 and plasmid-cured, prophage-cured, lactose-negative S. lactis LM2301 resulted in the appearance of lactose-positive transductants surrounded by a zone of clearing in the lactose-negative cell lawn. By using plaque assay procedures, the zones were shown to contain bacteriophage particles, and both spontaneous release and UV induction of prophage from these transductants were demonstrated. The DNA hybridization confirmed that LM2301 did not contain the prophage in its chromosome and that the zone-producing transductant KZ1 was relysogenized by the temperate bacteriophage. Further, a 4.35 Kb EcoRI digestion fragment appeared to contain the DNA sequences for integration into the chromosome and may provide a means for stabilizing cloned DNA by effecting chromosomal insertion in LM2301 derivatives. The selection of zone-producing lactose-positive transductants of LM2301 provided a means for detecting strains relysogenized by the temperate phage induced from LM0221.


Logging information about the activities that placed in a computer is essential for understanding its behavior. In Homeland Security, the reliability of the computers used in their activities is of paramount importance. However, attackers can delete logs to hide evidence of their activities. Additionally, various problems may result in logs being lost. These problems decrease the dependability of Homeland Security. To address these problems, we previously proposed a secure logging scheme using a virtual machine monitor (VMM). The scheme collects logs and isolates them from the monitored OS. However, the scheme cannot store them automatically. Thus, logs in memory are lost when the computer is shutdown. Further, if the logs are not stored, it is impossible to detect incidents of tampering by comparing the logs of the monitored OS with those of the logging OS. To address these additional problems, this paper proposes a log-storing module and a tamper detection scheme. The log-storing module automatically stores logs collected by the logging module, and tamper detection is realized by comparing these stored log files with those of the monitored OS. We implemented the log-storing module and realized the tamper detection scheme. Evaluations reveal the effectiveness of the tamper detection scheme.


UNU/WIDER was established in 1984 and started work in Helsinki in 1985. The principal purpose of the Institute is to help identify and meet the need for policy-oriented socioeconomic research on pressing global economic problems, particularly those impacting most directly on the developing countries. Its work is carried out by staff researchers and visiting scholars in Helsinki and through networks of collaborating institutions and scholars around the world. The views expressed in this publication are those of the author(s). Publication Joes not imply endorsement by the Institute or the United Nations University of any of the views expressed.


Tumor necrosis factor (TNF), a potent polypeptide mediator released by activated monocytes and macrophages, has a number of proinflammatory effects on endothelial cells. TNF is cytotoxic to tumor cells in vivo and in vitro, but TNF-induced toxicity to endothelial cells is less well established. We now report that cycloheximide (CHX), an inhibitor of protein synthesis, renders endothelial cells highly susceptible to TNF-induced lysis. TNF alone did not change the overall rate of protein synthesis by endothelial cells, whereas the addition of CHX completely abolished protein synthesis. Endothelial cells incubated in TNF alone in high concentrations (up to 1,000 U/ml) showed minimal rounding up and release of 51Cr. Likewise, CHX alone (5 micrograms/ml) had no significant effect on endothelial cell morphology and release of 51Cr. However, incubation of endothelial cells in both CHX and TNF caused injury in a dose-dependent manner. Morphological evidence of cell retraction, rounding, and detachment began within 2 h, but specific 51Cr release did not begin to rise until after 4 h. These changes were not observed when endothelial cells were incubated with TNF/CHX at 4 degrees C. The combination of TNF/CHX was lethal to all endothelial cells tested (bovine pulmonary artery, human umbilical vein, and human aorta), with human aortic cells showing the most pronounced changes. We conclude that healthy endothelial cells are resistant to TNF-induced lysis, but inhibition of their ability to make protein renders them highly susceptible.


Case Study - The Triassic Formation of the Hassi R'mel Field (Algeria). In the sedimentary recordings, clays, if inherited can give a fundamental a reliable and fundamental indication on the continental contributions. The examples studied come from central sahara wells of various basins. The triassic shale sandstone formation of the central sahara is about 200 meters thick, made of two series of the shale sandstone separated by volcanic rocks. The clay fraction was studied by using diffractometer and the following results were obtained: - from the point of view of the clay fraction constitution a) in oued mya basin the principal minerals are illite, chlorite and mixed layers; b) on the other hand in the berkine basin, there is an association of illite, chlorite mixed layers and kaolinite -from the point of view of the characteristic of clay: during the interpretation of the diffractogramms and by superimposing them we remark that: the intensity of illite peak (I001) and chlorite peak (I002) vary considerably with the depth. The peak variation does not occur at the random. In fact, as observed the intensity of the illite peak (I001) decrease from the bottom to the top in a metric level or profile. Thus, it was observed that at the bottom of the profile, illite shows a high intensity (I001) peak, with a good cristallinity, and as one goes up in the profile(i.e.a decrease in the depth) the peak intensity becomes weaker and sometimes, nothing can be noticed on the diffractogramm. The explanation of the loss of the intensity is not due to the reduction in the partiules but to the worse cristalline organisation of the crystalline system. Indeed the climate which characterized the triassic period is arid or semi arid, he is marked by alternation of wet and dry period. The state of the clay fraction, which depends of the source of the sedimentary material that is homogenous in the sedimentary environment system. In period of dryness, the evaporation is intense, concentrates the solutions which become more agressive and start to initially deteriorate the sedimentary unit with the contatc water sediment then penetrates in the sedimentary unit according to its permeability. This proves that the substance analysed is amorphous by XRD, revealing thus a high weathering of the clay fraction. This decrease in the intensity of the I001 peak of illite from the bottom to the top of the level is spectacular. This phenomenon is observed both in the clay fraction content in the sand and shale samples. The repetition of this phenomenon in the space et time and at the regional scale shows the regularity of the climate.This evolution of the clay fraction is similar to the present day pedogenetic one. Thus, degradations or tranformations by degradations seem to be an overall mechanism in the meteoric alteration and pedogenetic process. This permits us to define sections in the sequence called genetic sequences.


An adequate description of economic dynamics requires the introduction of a monetary system including default penalties and expectations in a society whose economy utilizes money and credit. This essay notes and discusses several of the factors involved in the use of money and credit in a process oriented economy. It links these observations with the general equilibrium treatment of the same underlying economy and formulates a government guidance game where the government sets several key parameters in a monetary economy sufficient to select a unique equilibrium. Low information and error correction are noted. The links to the first and second welfare theorems of GE are also considered as is the setting of the price level.


This work experimentally and numerically investigates the heat transfer in uncompressed/compressed metal foams. Experiments were conducted to obtain the thermal characteristics of a rectangular channel filled with aluminum foams using air as the fluid medium. The experimental data reveal that the uncompressed sample has a larger Nusselt number (Nu) than the compressed sample. The 0.93 porosity sample has the largest average Nu followed by the 0.7 porosity sample; the 0.8 porosity sample has the worst average Nu. The experimental data concerning the 0.93 porosity samples (uncompressed samples) were consistent with the numerical predictions obtained using the model for high-porosity metal foam, reported elsewhere. Finally, a numerical model to simulate flow and heat transfer characteristics in compressed metal foams is presented and the interstitial heat transfer coefficient and dispersion conductivity were semi-empirically determined.


To observe the therapeutic effect on acne treated with blood-letting puncture, cupping and Chinese-drug facemask. Thirty-two patients with acne were treated with above-mentioned therapeutic method. Cure,improvement and ineffectiveness were respectively found in 24, 7 and 1 case, with a curative rate of 75.0% and a total effective rate of 96.8%. The combination of blood-letting puncture, cupping and external application of Chinese-drug facemask is effective in treating acne.


Collections and "collecting" are keywords that have in recent years been reintroduced into the focus of library considerations – not least under the influence of the all-embracing present trend of "digitalization", but also because of the attention currently being paid to the cultural heritage, its preservation and presentation. Against this background, the retrospective consolidation of existing collections and the continuation of collecting traditions continue to be pursued by German regional libraries in particular. This book adheres to the goal of publicizing the special collections handed down in the regional libraries as a source for research projects. However, the volume's attention is directed towards those segments within the libraries' inventories that one does not necessarily expect, that are sometimes considered curios, and sometimes even constitute a distinction of uniqueness. The collections presented in this volume embrace a great variety of subjects, ranging from collections of miscellanies pertaining to theater, dance and ballet, of New Year's wishes and leaflets issued by funfair operators, of death sentences, wall newspapers and numismatics to collections of socialist and anarchist literature of the 19th century, writings and memorabilia concerning the German South Sea and China missions of the early 20th century to the history of shorthand.


Results obtained from an animal test system for epidermal cytotoxic drugs prompted the topical use of 1% cycloheximide in the treatment of histologically confirmed superficial basal cell carcinomata of the skin. Excellent clinical clearing of lesions has been demonstrated and this has been confirmed by post treatment biopsies. Preliminary findings in solar keratoses and intraepidermal carcinomata of the skin are also reported.


This article argues that the normative promise of recognition theory in International Relations has become increasingly inadequate to the cross-cutting and intersecting issues characteristic of a globalised and fragmented world. Engaging in critical readings of cosmopolitan forms of recognition theory, the critique of sovereignty and Markell's influential critique of recognition theory, I suggest that the increasing ontological specificity of recognition theory in IR has come at the expense of its ability to develop links between different areas of international politics. The result is a failure to deal with recognition's simultaneity, or the co-existence of analytically distinct and internally coherent recognition orders that is characteristic of the international. Building on this insight, I argue that a more historically-sensitive and materialist approach to recognition can be grounded in the concept of multiplicity. By opening recognition up to processes of interaction, and not merely reproduction, multiplicity frames the international more clearly as a historical presupposition, rather than a limit, of recognition. Furthermore, placing recognition struggles within the state, international institutions or transnational movements in relation to each other ensures that IR can contribute to the further development of recognition theory by situating recognition struggles at the intersection of different moral geographies.


Linda is a language for programming parallel applications whose most notable feature is a distributed shared memory called tuple space. While suitable for a wide variety of programs, one shortcoming of the language as commonly defined and implemented is a lack of support for writing programs that can tolerate failures in the underlying computing platform. This paper describes FT-Linda, a version of Linda that addresses this problem by providing two major enhancements that facilitate the writing of fault-tolerant applications: stable tuple spaces and atomic execution of tuple space operations. The former is a type of stable storage in which tuple values are guaranteed to persist across failures, while the latter allows collections of tuple operations to be executed in an all-or-nothing fashion despite failures and concurrency. The design of these enhancements is presented in detail and illustrated by examples drawn from both the Linda and fault-tolerance domains. An implementation of FT-Linda for a network of workstations is also described. The design is based on replicating the contents of stable tuple spaces to provide failure resilience and then updating the copies using atomic multicast. This strategy allows an efficient implementation in which only a single multicast message is needed for each atomic collection of tuple space operations. >


This paper presents an approach called generic view concept which facilitates the creation and visualization of role-based, task-oriented views on service-oriented architectures. Those views enhance the understanding from the technical and functional point of view, and thus reduce the inherent complexity arising during the creation, use and maintenance of service-oriented architectures. The unique aspect of the generic view concept is that it does not constrain stakeholders to a set of predefined views. In order to examine the usefulness of generic views in real world scenarios, a prototype has been implemented applying 3D visualization techniques.


The cultivated strawberry, Fragaria ×ananassa, originated in France approximately 270 years ago via hybridization between two wild species introduced from North and South America. Both the cultivated strawberry and its parental species are octoploids with 2n=8x=56 chromosomes. In the recent publication of the genome of the cultivated strawberry, the authors present a novel phylogenetic hypothesis, proposing that each of the four subgenomes originated from a different 2n=2x=14 diploid progenitor. They further suggest that the hexaploid species Fragaria moschata was a direct ancestor of the strawberries. We reanalyzed the four octoploid subgenomes in a phylogenomic context, and found that only two extant diploids were progenitors, a result that is consistent with several previous studies. We also conducted a phylogenetic analysis of genetic linkage-mapped loci in the hexaploid F. moschata, and resolved its origin as independent of the octoploids. We identified assumptions in their tree-searching algorithm that prevented it from accepting extinct or unsampled progenitors, and we argue that this is a critical weakness of their approach. Correctly identifying their diploid progenitors is important for understanding and predicting the responses of polyploid plants to climate change and associated environmental stress.


To study the general trade practices, to suggest the ways and means for marketing of goat. Instead of studying all markets, four markets as per geographical distribution of districts were selected viz., Latur, Renapur, Murud and Nalegaon goat markets Majority of 38.33 per cent small and 31.63 per cent medium land holders were involved in the sale and purchase of goats. Osmanabadi breed with 83.33 per cent black colour of goats were preferred by sellers and buyers mostly local market Latur. Mainly adult goats, 60.00 per cent were sold and 73.33 per cent purchased by farmers in selected markets of Latur district. Majority of farmers from Latur district adopted 50.00 per cent broker method followed by 46.63 per cent direct method for marketing of goats. Availability of fodder, drinking water, goat shed was not properly available in the markets. Major reasons for sale of goats were 45.00 per cent fodder problem, 26.67 per cent financial problem.


The Escherichia coli K-12 gene coding for the nucleoid-associated protein HNS was cloned together with 5.6 kb of downstream DNA in the vector pACYC184. The cloned DNA complemented a mutation in the osmZ locus of E. coli, which codes for HNS. However, the multicopy plasmid harboring the cloned sequence was found to be mutagenic and to produce at high frequency mutations that mapped to the E. coli cya gene, which codes for adenylate cyclase. Acquisition of the cya mutations was independent of RecA. These mutations were phenotypically suppressed by providing the cells with exogenous cyclic AMP and were complemented in trans by a plasmid carrying an active copy of the cya gene. A deletion analysis of the cloned sequences showed that DNA downstream of the gene coding for HNS was also required for the mutagenic effect of cya and had a role in regulating the expression of the osmZ-dependent proU locus. These sequences appear to contain at least two genetically active regions.


We report the activity and toxicity of intrathecal melphalan in the treatment of human neoplastic meningitis in the subarachnoid space of athymic nude rats. Animals received injections via chronic indwelling subarachnoid catheters with 5 x 10(5) or 5 x 10(6) TE-671 human rhabdomyosarcoma cells or 5 x 10(6) D-54 MG human glioma cells and were treated with melphalan on days 8, 5, or 5, respectively. Melphalan toxicity in nontumor-bearing rats was assessed at single doses of a 2.0, 3.0, 4.0, or 5.0 mM solution, with clinical and histological evidence of neurotoxicity observed at the 4.0 and 5.0 mM levels. Multiple-dose toxicity studies using a dosing schedule of twice a week for two weeks with a 0.25, 0.5, 0.75, 1.0, 1.5, or 2 mM solution revealed dose-dependent clinical and histological evidence for toxicity at all dosages. Treatment of TE-671 with a single dose of 2.0 mM intrathecal melphalan produced an increase in median survival of 442% compared with saline controls (P < 0.003). Comparison of a single dose of 1.0 or 2.0 mM melphalan with a multiple dose regimen at 0.25 or 0.5 mM melphalan in the treatment of TE-671 revealed increases in median survival of 50% for 1.0 mM, 57% for 2.0 mM, 79% for 0.5 mM, and 111% for 0.25 mM concentrations. Comparison of a single dose of 1 mM melphalan with multiple doses of 0.25 mM melphalan in the treatment of D-54 MG revealed an increase in median survival of 475+% for each of the regimens. Intrathecal melphalan may be an important new addition in the treatment of neoplastic meningitis and is currently being evaluated clinically in a Phase 1 trial.


American soft drink consumption (SDC) has increased since the 1960's surpassing all other kinds of beverage consumption. In recent years, the scientific literature has suggested that SDC has been linked to the rising epidemic of obesity in children and adolescents. However, there is lack of information in scientific literature on the effects of SDC on body fat (BF%) in young females. The purpose of this study was to determine the association between SDC and BF% in young women, ages 16–24 years. Sixty-six females were asked to complete a 3-day food record, food frequency questionnaire, and an assessment BF% by dual-energy x-ray absorptiometry (DXA). Overall, participants consumed 29.44 ± 44.68 fl oz/day of soft drinks. There were significant positive associations between SDC and BF% (r = 0.24, p < 0.05). Due to the large standard deviation in SDC, secondary analysis compared moderate SDC (MSDC: < 32 fl oz/day) to high SDC (HSDC: ≥ 32 fl oz/day). Results suggested HSCD had significantly greater BF% than MSDC. Therefore, limiting the consumption of soft drinks is suggested in order to maintain a healthy BF%.


Abstract #6014 Backround:
 Sphingolipids do not only have structural roles for the cell membrane, but also act as effector molecules and second messengers in signal transduction with links to cancer initiation, progression and treatment response. Knowledge of sphingolipid9s impact on breast cancer and its prognosis is limited to in vitro data. Clinical data is rare but needed.
 Material and Methods: We analyzed gene expression of 43 proteins from the sphingolipid pathways in different subtypes of breast cancer using microarray data of 1269 tumor samples (test set n=171; validation sets n=1098). Kaplan Meier analysis of disease free survival was performed to examine the prognostic value of different markers. In addition immunohistochemistry was done to determine whether the genes of the sphingolipid rheostat are expressed in cancer or stroma cells of the tumor.
 Results: Significant relationships of several genes of the sphingolipid metabolism with clinical parameters were obtained. Sphingosine kinase 1 (SPHK1), ceramide galactosyltransferase (UGT8), and Ganglioside GD3-Synthase (ST8SIA1) displayed higher expression among ER negative tumors. In contrast, glucosylceramidesynthase (GCS), dihydroceramidesynthases (LASS4, LASS 6) and acid ceramidase (ASAH1) were higher expressed in ER positive samples. Survival analysis revealed a significant worse outcome of patients with high SPHK1 expression. LASS 6 and GCS gene expression had no prognostic impact when the estrogen receptor status was taken into account in multivariate analyses. Immunohistochemistry identified the carcinoma cells as the major source of SPHK1 expression in the tumor.
 Conclusions: These studies of a large cohort of clinical breast cancer samples reveal that sphingolipids do play a role in breast cancer. Enzymes of the sphingolipid metabolism have impact on the prognosis of breast cancer patients and targeting the sphingolipid rheostat can open new treatment options. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6014.


The Sevy is typically fine crystalline to microcrystalline tan and gray dolomite which weathers with a distinctive very light gray surface. It occurs in beds from a few inches to 2 feet thick and is usually finely laminated. Sedimentary breccias, and soft-sediment deformations are common. Floating quartz sand grains occur throughout the formation but are usually concentrated near the top. Carbonate sand grains are associated with the quartz grains. The lithogenic unit is remarkable in being recognizable through an area of 100,000 square miles in California, Nevada, Utah, and Idaho. Its average thickness is 500 feet. Throughout most of its extent, which corresponds with the Cordilleran miogeosyncline, the Sevy overlies Silurian dolomite and is overlain by middle Devonian dolomite. It is proposed that the Sevy originated as a primary evaporitic dolomite with redeposited dolomite debris and was formed on extensive mud flats at or near sea-level. These flats were periodically flooded by the issue of streams from the east, and depressions on the flats were filled with water. Marine invasions from the sea on the west were blocked or impeded by the possible existence of a barrier inherited from a Silurian barrier-reef trend in central Nevada. The quartz sand is believed to have been derived from the erosion of middle Ordovician sandstones along the eastern margin of the depositional area. Streams carried the sand to the edge of the mud flats. Later, the sand grains were probably blown across the periodically emergent flats and entrapped in shallow pools or areas of unhardened sediment.


Understanding the phase transformation in glass and the morphology of related nanostructure after femtosecond laser irradiation is of great importance for fabricating functional optics, in which glass crystallization is involved to obtain nonlinear optical properties. We report on the crystallization inside lithium niobium silicate glass induced by fs laser irradiation. Energy-dispersive X-ray spectroscopy coupled to scanning transmission electron microscopy (STEM/EDS) and transmission electron microscopy confirm a nanoscale phase separation whereby LiNbO3 crystals are embedded in lamella-shaped frames of amorphous SiO2. The obtained nanostructure may have applications in fabricating second-order nonlinear optical devices.


In the intellectual property arena, policymakers and commentators have advanced different proposals to combat the COVID-19 pandemic. One pathbreaking proposal that has become highly controversial calls for a waiver of more than thirty provisions in the WTO TRIPS Agreement, covering copyrights, industrial designs, patents, and the protection of undisclosed information. Even after more than a year since the release of the initial proposal in October 2020, policymakers and commentators remain deeply divided. To help put the ongoing debate in the right perspective and to advance scholarship that helps address the present pandemic while preparing for future pandemics, this article draws on political scientist Robert Putnam's seminal work to explain why it is important to understand the international negotiation and domestic implementation of the waiver as a two-level game. The failure to win in any one of these levels will result in the non-implementation of the waiver in the relevant country—be it the United States or one of the instrument's proponents or co-sponsors. This article briefly recounts the strengths and weaknesses of the waiver proposal. It then identifies the negotiation and implementation challenges confronting efforts to operationalize the instrument in individual nations. Drawing on Putnam's work, this article calls into question the likelihood of quick worldwide implementation of the waiver to combat COVID-19. In view of these challenges, this article offers a novel alternative proposal that would facilitate the deferral of intellectual property rights in pandemic times. Aiming to "split the difference" between the proponents and opponents of the waiver, the proposal draws support from prior precedents involving temporal adjustments to intellectual property rights. The article further explores the strengths and limitations of the deferral proposal.


Modern public law, according to Martin Loughlin's Foundations of Public Law, depends upon the autonomy of the political realm. This is explained on the basis of an orthodox secularisation thesis of modernity, the autonomy of the political emerging through its successful separation from the theological. But when viewed in relation to the economic (the material realm), the autonomy of political ordering looks more fragile, subject to the continuing struggle between democracy and capitalism. The concrete features of this struggle are explored by way of a stylised diachronic overview of the transformation of the Western European state and regional state-system in the twentieth century, first with the interwar breakdown of political order, then with postwar reconstruction in the project of European integration. In the recent Euro-crisis phase it again enters a critical period. All of this, however, escapes the lens of a purely political jurisprudence.


Max is a helix-loop-helix zipper protein that associates in vitro with Myc family proteins to form a sequence-specific DNA-binding complex. We show here, by means of a coimmunoprecipitation assay with anti-Myc and anti-Max antibodies, that Myc and Max are associated in vivo and essentially all of the newly synthesized Myc can be detected in a complex with Max. This complex possesses specific DNA-binding activity for CACGTG-containing oligonucleotides. Although Max itself is a highly stable protein, Myc is rapidly degraded during or after its association with Max. In vivo Max is shown to be a nuclear protein phosphorylated by casein kinase II, and alternatively spliced forms of Max are expressed in cells. Furthermore, the levels of Max expression are equivalent in quiescent, mitogen-stimulated, and cycling cells. We conclude that the highly regulated rate of Myc biosynthesis is likely to be a limiting step in the formation of Myc:Max complexes.


This thesis explores reconstruction of natural sounding speech from whispers. As a broad research class, the generation of normally phonated speech from whispers can be useful in several types of application from different scientific fields ranging from communications to biomedical engineering. The primary focus of the thesis and current work is therefore to investigate appropriate solutions and algorithms for regenerating natural phonated speech from whispers. Interestingly, unlike other speech processing fields, many aspects of such reconstruction, in spite of the useful applications, have not yet been resolved by researchers. In particular, the outcome of this research will find at least two immediate applications which have different forms but similar solutions: a) reconstructing natural speech for laryngectomy patients, b) restoring natural pitched speech in a cell phone/telephone communication when one party talks in a whispering mode for privacy or security reasons. This thesis presents a solution for the conversion of whispers to fullyphonated speech through the modification of the CELP codec. We also present a novel method for spectral enhancement and formant smoothing during the reconstruction process, using a probability mass-density function to identify reliable formant trajectories in whispers, and apply spectral modifications accordingly. The method relies upon the observation that, whilst the pitch generation mechanism of patients with larynx damage is typically unusable, the remaining components of the speech production apparatus may be largely unaffected. The approach outlined here allows patients to regain their ability to speak (simply by whispering into an external prosthesis), yielding a more natural sounding voice than alternative solutions. Since whispered speech can be identified as the core input of the system, the acoustic features of whispers also need to be considered. Despite the everyday nature of whispering, and its undoubted usefulness in vocal communications, whispers have received relatively little research effort to date, apart from some studies analysing the main whispered vowels and some quite general estimations of whispered speech characteristics. In particular, a classic vowel space determination has been lacking for whispers. For voiced speech, this type of information has played an important role in the development and testing of recognition and processing theories over the past few decades, and can be expected to be equally useful for whispermode communications and recognition systems. This thesis also aims to redress the shortfall by presenting a vowel formant space for whispered speech, and comparing the results with corresponding phonated samples. To my parents: Sedigh & Naser for their unconditional kindness and support


B83 Tamoxifen is a selective estrogen receptor modulator (SERM), a class of drugs that mimic or counteract the estrogenic effects. Tamoxifen is also a common chemotherapeutic treatment for ER-positive breast cancer. However, difficulty with some mental functions after chemotherapy, often referred to as "chemo brain" is a common side-effect (i.e. problems include memory and learning, attention and concentration, language and judging spaces and layout when moving about). Therefore, determination of any neuromodulatory events associated with treatment is necessary. . A characteristic that distinguishes SERMs from receptor agonists and antagonists is that their action is different for various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogenic action via activation of estrogen receptor (ER) sub-types ER alpha and/or ER beta. (Ohmichi et al. , 2005) D2 - like dopamine receptors participate directly or indirectly with many of the problems associated with chemo brain. Therefore, this study begins to understand the underlying mechanisms that may lead to gene expression changes in the brain during chemotherapy. Treatment of the human neuroblastoma cell line, SH-SY5Y with, 17beta - estradiol (E2), Tamoxifen (Tam) and the GlaxoSmithKline SERM, GSK653580A (GSK SERM; a gift from Dave Jones of GlaxoSmithKline, RTP, NC) for 24 hours. Analysis of isolated total RNA via real-time polymerase chain reaction indicated the following changes in gene expression pattern of D2-like dopamine and ER receptor sub-types: 1) at 10 -9 M, E2 represses gene expression for D 2 dopamine, D 4 dopamine and both ER sub-types; 2) Tam causes significant increases in the gene expression of the D 2 dopamine receptor sub-type but no significant changes occurred for D 4 dopamine, ER alpha or ER beta receptors; and 3) while GSK-SERM caused increases in ER beta gene expression, but minimal dose-dependent response of D2 dopamine receptor, D4 dopamine receptor or ER alpha receptor subtypes. With all treatments, D3 dopamine receptor was undetected. Therefore, these results suggest that SERMs differentially affect gene expression in the brain.


Many energy conversion, sensing, and microelectronic applications based on ferroic materials are determined by the domain structure evolution under applied stimuli. New hyperspectral, multidimensional spectroscopic techniques now probe dynamic responses at relevant length and time scales to provide an understanding of how these nanoscale domain structures impact macroscopic properties. Such approaches, however, remain limited in use because of the difficulties that exist in extracting and visualizing scientific insights from these complex datasets. Using multidimensional band‐excitation scanning probe spectroscopy and adapting tools from both computer vision and machine learning, an automated workflow is developed to featurize, detect, and classify signatures of ferroelectric/ferroelastic switching processes in complex ferroelectric domain structures. This approach enables the identification and nanoscale visualization of varied modes of response and a pathway to statistically meaningful quantification of the differences between those modes. Among other things, the importance of domain geometry is spatially visualized for enhancing nanoscale electromechanical energy conversion.


SCCharts is a visual language proposed in 2012 for specifying safety-critical reactive systems. We present the results of the first medium sized SCCharts case-study. The case-study was conducted in the context of the railway project performed by students at the Kiel University in the summer term 2014. The railway project is a regularly occurring student training project that teaches principles of concurrent cyber-physical systems on a complex live model railway demonstrator. This report presents details of the first medium size SCCharts models created during the project. We explain what additional language extensions to SCCharts were necessary and how they were implemented. To handle performance issues that arose while developing the controller, compiler enhancements became necessary and are evaluated here. Furthermore, the participants completed a survey at the end of the project to confirm the goals that the SCCharts language and our SCCharts tool chain are suitable to build complex controllers. In the survey, the participants compared both, the SCCharts language and our SCCharts tools, with other modeling and classical programming languages and tools.


This research project involved the collection of data from pupils with Emotional and Behavioural Difficulties (EBD), who were not attending a mainstream school, in order to gain an improved understanding of their behaviour. The factors and processes that they perceived as having influenced their behaviour were explored and analysed from a broad theoretical base. Data were collected through taped interviews with the pupils and analysed both within individual cases in order to better understand individual pupil's experiences, and also across cases in order to highlight common experience and perception. The results revealed that EBD pupils perceive a wide range of factors and processes within the school system, wider social systems and their own individual selves, as significant in influencing their behaviour, and they are often able to describe the nature of and motives for their behaviours in some detail. It is hoped that this research will contribute to the current theoretical debates concerning the behaviour of EBD pupils, and in addition that it will encourage professionals to value and respect the pupils' own perspective, to improve techniques and strategies for obtaining these perspectives, and to use them to ensure appropriate and successful support or provision for these pupils.


This paper reports on design and fabrication aspects of a new microelectromechanical series switch for switching dc and RF signals. The switch consists of a flexible S-shaped film with the switching contact, rolling between a top and a bottom electrode in electrostatic touch-mode actuation. This design allows a low actuation voltage independent of the contact distance in the off-state. With a large contact distance, large overlapping switching contact areas are possible by obtaining a high off-state isolation. The RF transmission line and the MEMS part of the switch are fabricated on separate wafers, allowing an implementation of the switch with different RF substrates. The final assembly is done on device level for the first prototypes, even though the design provides the possibility of an assembly by full wafer bonding, leading to a near-hermetic package integrated switch. The measured prototype actuation voltages are 12 V to open and 15.8 V to close the contacts, with a resistance of 275 m/spl Omega/ of each contact at an estimated contact force of 102 /spl mu/N. The measured RF isolation with a contact distance of 14.2 /spl mu/m is better than -45 dB up to 2 GHz and -30 dB at 15 GHz, at a large nominal switching contact area of 3500 /spl mu/m/sup 2/.


Given the fact that the concept of "classroom management" and its connotations as well as its relation to effective teaching, despite decades of world-wide research, remain rather undefined, or, at least, not fully described, different educational systems and teachers around the world try hard to develop a wide variety of classroom management theories and strategies, since they obviously consider it as being significantly related to effective teaching. Effective classroom management reflects teachers' multifaceted high-ranked ability to, inter alia, establish and maintain within their classrooms acceptable rules of productive teacher-to-student and student-to-student communication, to motivate students to work cooperatively, and to fruitfully implement best teaching strategies according to their students' individualized learning needs. Moreover, it presupposes teachers' ability to create a learning context where students' disruptive attitudes are prevented or addressed and misbehavior is reduced while positive expected learning outcomes are achieved, and the students' cognitive, social and affective development is continuously facilitated and sustained. Finally, it is based on teachers' ability to set clearly defined and agreed—between teacher and students—codes of communication, to produce measurable learning outcomes that fulfill students' and their parents' expectations, and to take full advantage of their students' features, classroom features, and local space features in order to develop their own professional features. It is, thus, evident why successful classroom management is considered by teachers, parents, students, and researchers to be tightly linked to teachers' professional competence and effectiveness.
 Moreover, teachers who successfully implement classroom management are reported to create in time a regulatory framework for communication within the classroom through the establishment and adoption of rules and consequences. They also tend to safeguard the quality of communication with their students, and to develop their professional authority profile. They succeed in that by strengthening their willingness to meet students' learning requirements, needs, and interests, by using effectively verbal and non-verbal communication to encourage learning and, above all, by controlling and managing their institutionalized power.
 International research over the past years has shown that the implementation of learner-centered innovative teaching strategies on the basis of flexible differentiated teaching focused on students' personal values, abilities and potential, the establishment of student-to-student shared responsibility and of a student-to-teacher commitment contract, the development of a dynamic interplay between students during group work, the respect for diversity, and the reinforcing of students' self-regulation all highly contribute to the creation of a fruitful in-class learning environment. In such an environment students feel secure and accepted, teachers manage the classroom successfully and are considered to be competent and effective professionals.


It was experimentally established that the destruction of mitochondria due to a reduction of ATP production and to their compensatory hyperfunction under energy defecit is underlying some disorders in the myocardial metabolism caused by 2,4-DNP intoxication. Energy deficit results in K+ metabolism disorders and the related acetylcholine synthesis which predisopses the changes in the cardiac function and still further increases the myocardial requirements of energy. The bio-energy disorders develop in a vicious circle manner, and when the intoxication increases, it inevitably results in energy depletion and cardiac arrest.


Once a retrovirus infects a eukaryotic cell and integrates within chromosomal DNA, it becomes part of its genome and can be activated/transcribed/translated to produce viral proteins and/or new viral particles. Over the years, some of these retroviruses may lose their pathogenicity and become adapted to the new host. Under these conditions, retroviruses can paradoxically ameliorate the functional portfolio of the infected cell, thus potentially increasing its functionality and/or chances of survival in a difficult environment. Individuals whose cells are infected by retroviruses have acquired, in the last millions of years, innovative functions that, once transmitted to the new generation through germinal cells, have become essential for their homeostasis, or even for their survival. This is the case of some endogenous retroviruses, whose products are mandatory for the proper vascularization of human placenta. To our knowledge, there are no natural means able to selectively eliminate retroviral genes from an infected cell or an individual. Therefore, the chances of getting naturally cured by retroviruses, once infection is set and viral genomes are spread into the body, are minimal or absent. HIV is a retrovirus that behaves as all other retroviruses that interacted with humans in the past millennia. Its fate is to remain forever within the infected body. For these reasons, the chances of getting rid of HIV infection and being biologically cured (that is, eliminating all viral genomes from the body) are very limited if we consider current knowledge, biotechnology and available medical tools (yet it cannot be fully excluded in very peculiar cases). The option offered by the so‐called "functional cure" is different. In this case, medical manipulation may create conditions whereby viral genomes, decreased in number and function by proper therapies/vaccines, are no longer able to harm the host for an indefinite period of time. Patients do remain infected, but viral replicative cycles are absent, and progression of the disease is interrupted. This latter clinical approach may be suitable, and this is where clinical research is directing its efforts. If achievable, infected persons should cope with the virus and keep it under control for decades, without support of chronic antiviral therapy. In conclusion, the proper knowledge of the biological characteristics of HIV helps in selecting the best strategies aimed at obtaining the maximum achievable clinical result.