Equidistribution of Fekete Points on the Sphere

Fekete points are the points that maximize a Vandermonde-type determinant that appears in the polynomial Lagrange interpolation formula. They are well suited points for interpolation formulas and numerical integration. We prove the asymptotic equidistribution of Fekete points in the sphere. The way we proceed is by showing their connection to other arrays of points, the so-called Marcinkiewicz-Zygmund arrays and interpolating arrays, that have been studied recently.

Embankment Quality and Assessment of Moisture Control Implementation, TR-677, 2016

A specification for contractor moisture quality control (QC) in roadway embankment construction has been in use for approximately 10 years in Iowa on about 190 projects. The use of this QC specification and the development of the soils certification program for the Iowa Department of Transportation (DOT) originated from Iowa Highway Research Board (IHRB) embankment quality research projects. Since this research, the Iowa DOT has applied compaction with moisture control on most embankment work under pavements. This study set out to independently evaluate the actual quality of compaction using the current specifications. Results show that Proctor tests conducted by Iowa State University (ISU) using representative material obtained from each test section where field testing was conducted had optimum moisture contents and maximum dry densities that are different from what was selected by the Iowa DOT for QC/quality assurance (QA) testing. Comparisons between the measured and selected values showed a standard error of 2.9 lb/ft3 for maximum dry density and 2.1% for optimum moisture content. The difference in optimum moisture content was as high as 4% and the difference in maximum dry density was as high as 6.5 lb/ft3 . The difference at most test locations, however, were within the allowable variation suggested in AASHTO T 99 for test results between different laboratories. The ISU testing results showed higher rates of data outside of the target limits specified based on the available contractor QC data for cohesive materials. Also, during construction observations, wet fill materials were often observed. Several test points indicated that materials were placed and accepted at wet of the target moisture contents. The statistical analysis results indicate that the results obtained from this study showed improvements over results from previous embankment quality research projects (TR-401 Phases I through III and TR-492) in terms of the percentage of data that fell within the specification limits. Although there was evidence of improvement, QC/QA results are not consistently meeting the target limits/values. Recommendations are provided in this report for Iowa DOT consideration with three proposed options for improvements to the current specifications. Option 1 provides enhancements to current specifications in terms of material-dependent control limits, training, sampling, and process control. Option 2 addresses development of alternative specifications that incorporate dynamic cone penetrometer or light weight deflectometer testing into QC/QA. Option 3 addresses incorporating calibrated intelligent compaction measurements into QC/QA.

CD1d-antibody fusion proteins target iNKT cells to the tumor and trigger long-term therapeutic responses.

Despite the well-established antitumor activity of CD1d-restricted invariant natural killer T lymphocytes (iNKT), their use for cancer therapy has remained challenging. This appears to be due to their strong but short-lived activation followed by long-term anergy after a single administration of the CD1d agonist ligand alpha-galactosylceramide (αGC). As a promising alternative, we obtained sustained mouse iNKT cell responses associated with prolonged antitumor effects through repeated administrations of tumor-targeted recombinant sCD1d-antitumor scFv fusion proteins loaded with αGC. Here, we demonstrate that CD1d fusion proteins bound to tumor cells via the antibody fragment specific for a tumor-associated antigen, efficiently activate human iNKT cell lines leading to potent tumor cell lysis. The importance of CD1d tumor targeting was confirmed in tumor-bearing mice in which only the specific tumor-targeted CD1d fusion protein resulted in tumor inhibition of well-established aggressive tumor grafts. The therapeutic efficacy correlated with the repeated activation of iNKT and natural killer cells marked by their release of TH1 cytokines, despite the up-regulation of the co-inhibitory receptor PD-1. Our results demonstrate the superiority of providing the superagonist αGC loaded on recombinant CD1d proteins and support the use of αGC/sCD1d-antitumor fusion proteins to secure a sustained human and mouse iNKT cell activation, while targeting their cytotoxic activity and cytokine release to the tumor site.

Difficult-to-engage patients: a specific target for time-limited assertive outreach in a Swiss setting.

OBJECTIVE: Assertive community treatment (ACT) failed to develop in Europe, and its efficacy is debated. In Lausanne, Switzerland, ACT focuses on difficult-to-engage patients and aims to facilitate linkage with outpatient care through time-limited interventions. This study aimed to evaluate the applicability and efficiency of time-limited ACT. METHODS: We retrospectively assessed social, clinical, and functional outcomes and motivation for treatment in 75 consecutively seen subjects treated between 2000 and 2002. RESULTS: With 70% of the interventions lasting less than 6 months, we observed significant improvement in most clinical and social problems, in collaboration, in motivation for treatment, and in social network support, despite high baseline levels of clinical and social problems. The number of hospitalizations decreased significantly. CONCLUSIONS: Time-limited ACT is a useful treatment for difficult-to-engage patients with severe clinical and social problems, and it facilitates linkage to care. This narrower target for ACT may facilitate its implementation in Europe.

Target joining of duplicated insertion sequence IS21 is assisted by IstB protein in vitro.

Tandemly repeated insertion sequence IS21, located on a suicide plasmid, promoted replicon fusion with bacteriophage lambda in vitro in the presence of ATP. This reaction was catalyzed in a cell extract containing the 45-kDa IstA protein (cointegrase) and the 30-kDa IstB helper protein of IS21 after both proteins had been overproduced in Escherichia coli. Without IstB, replicon fusion was inefficient and did not produce the 4-bp target duplications typical of IS21.

Profile Following for Inspection of Underwater Structures

We present a seabed profile estimation and following method for close proximity inspection of 3D underwater structures using autonomous underwater vehicles (AUVs). The presented method is used to determine a path allowing the AUV to pass its sensors over all points of the target structure, which is known as coverage path planning. Our profile following method goes beyond traditional seabed following at a safe altitude and exploits hovering capabilities of recent AUV developments. A range sonar is used to incrementally construct a local probabilistic map representation of the environment and estimates of the local profile are obtained via linear regression. Two behavior-based controllers use these estimates to perform horizontal and vertical profile following. We build upon these tools to address coverage path planning for 3D underwater structures using a (potentially inaccurate) prior map and following cross-section profiles of the target structure. The feasibility of the proposed method is demonstrated using the GIRONA 500 AUV both in simulation using synthetic and real-world bathymetric data and in pool trials

Baseline Results of an Acute Ischemic Stroke Registry Including Acute Multimodal Imaging (ASTRAL)

Background: The DEFUSE (n_74) and EPITHET (n_101) studies have in common that a baseline MRI was obtained prior to treatment (tPA in DEFUSE; tPA or placebo in EPITHET) in the 3-6 hour time-window. There were however important methodological differences between the studies. A standardized reanalysis of pooled data was undertaken to determine the effect of these differences on baseline characteristics and study outcomes. Methods: To standardize the studies 1) the DWI and PWI source images were reprocessed and segmented using automated image processing software (RAPID); 2) patients were categorized according to their baseline MRI profile as either Target Mismatch (PWITmax_6/DWI ratio_ 1.8 and an absolute mismatch _15mL), Malignant (DWI or PWITmax_10 lesion _ 100 mL), or No Mismatch. 3) favorable clinical response was defined as NIHSS score of 0-1 or a _8 points improvement on the NIHSSS at day 90. Results: Prior to standardization there was no difference in the proportion of Target Mismatch patients between EPITHET and DEFUSE (54% vs 49%, p_0.6), but the EPITHET study had more patients with the Malignant profile than DEFUSE (35% vs 9%, p_0.01) and fewer patients that had No Mismatch (11% vs 42%, p_0.01). These differences in baseline MRI profiles between EPITHET and DEFUSE were largely eliminated by standardized processing of PWI and DWI images with RAPID software (Target Mismatch 49% vs 48%; Malignant 15% vs 8%; No Mismatch 36% vs 25%; p_NS for all comparisons) Reperfusion was strongly associated with a favorable clinical response in mismatch patients (figure). This relationship was not affected by the standardization procedures (pooled odds ratio of 8.8 based on original data and 6.6 based on standardized data). Conclusion: Standardization of image analyses procedures in acute stroke is important as non-standardized techniques introduce significant variability in DWI and PWI imaging characteristics. Despite methodological differences, the DEFUSE and EPITHET studies show a consistent and robust association between reperfusion and favorable clinical response in Target Mismatch patients regardless of standardization. These data support an RCT of iv tPA in the 3-6 hour time-window for Target Mismatch patients identified using RAPID.

Safety concerns about CCR5 as an antiviral target.

PURPOSE OF REVIEW: Clinical trials of CCR5 antagonists attest to their efficacy and tolerance in HIV treatment. However, there has been debate on their long-term safety because of the role of CCR5 in innate immunity. This review highlights gaps in our understanding of epidemiology of infections that are modulated by CCR5, in particular, in HIV-infected individuals. RECENT FINDINGS: In the mouse model, CCR5 has a role in the response against pathogens as diverse as Toxoplama gondii, West Nile virus, Mycobacterium tuberculosis, herpes simplex virus, Trypanosoma cruzi, Cryptococcus neoformans, Chlamydia trachomatis, Listeria, and plasmodia. In human cohorts, individuals carrying the defective CCR5Delta32 allele present an increased susceptibility to flavivirus (West Nile virus and tickborne encephalitis virus). The selective pressures that led to the spread of loss-of-function CCR5 mutations in humans (CCR5Delta32), and in mangabeys (CCR5Delta24) are not understood. SUMMARY: The recent availability of CCR5 antagonists has raised concern that genetic, biological, or chemical CCR5 knockout, although beneficial against some pathogens (i.e. HIV), could be deleterious for other processes implicated in pathogen response. The consequences of long-term pharmaceutical intervention on CCR5 should be carefully assessed through rigorous postmarketing surveillance.

The need for combination antihypertensive therapy to reach target blood pressures: what has been learned from clinical practice and morbidity-mortality trials?

Pharmacological treatment of hypertension represents a cost-effective way for preventing cardiovascular and renal complications. To benefit maximally from antihypertensive treatment blood pressure (BP) should be brought to below 140/90 mmHg in every hypertensive patient, and even lower (< 130/80 mmHg) if diabetes or renal disease co-exists. Most of the time such targets cannot be reached using monotherapies. This is especially true in patients who exhibit a high cardiovascular risk. The co-administration of two agents acting by different mechanisms considerably increases BP control. Such preparations are not only efficacious, but also well tolerated, and some fixed low-dose combinations have a tolerability profile similar to placebo. This is for instance the case for the preparation containing the angiotensin-converting enzyme inhibitor perindopril (2 mg) and the diuretic indapamide (0.625 mg), a fixed low-dose combination that has recently been shown in controlled interventional trials to be more effective than monotherapies in reducing albuminuria, regressing cardiac hypertrophy and improving macrovascular stiffness. Fixed-dose combinations are becoming more and more popular and are even proposed by current hypertension guidelines as a first-line option to treat hypertensive patients.

Peripheral Nerve Neuropathy is Associated with a Glial Reaction in the Gracile Nucleus Associated with a regulation of the GABA transporter GAT-1

Allodynia (pain in response to normally non painful stimulation) and paresthesia (erroneous sensory experience) are two debilitating symptoms of neuropathic pain. These stem, at least partly, from profound changes in the non-nociceptive sensory pathway that comprises large myelinated neuronal afferents terminating in the gracile and cuneate nuclei. Further than neuronal changes, well admitted evidence indicates that glial cells (especially in the spinal cord) are key actors in neuropathic pain, in particular the possible alteration in astrocytic capacity to reuptake neurotransmitters (glutamate and GABA). Yet, the possibility of such a changed astrocytic scavenging capacity remains unexplored in the dorsal column pathway. The present study was therefore undertaken to assess whether peripheral nerve injury (spared nerve injury model, SNI) could trigger a glial reaction, and especially changes in glutamate and GABA transporters, in the gracile nucleus. SNI surgery was performed on male Sprague-Dawley rats. Seven days after surgery, rats were used for immunofluorescence (fixation and brain slicing), western-blot (fresh brain freezing and protein extraction) or GABA reuptake on synaptosomes. We found that SNI results in a profound glial reaction in the ipsilateral gracile nucleus. This reaction was characterized by an enhanced immunolabelling for microglial marker Iba1 as well as astrocytic protein GFAP (further confirmed by western-blot, p <0.05, n = 7). These changes were not observed in sham animals. Immunofluorescence and western-blot analysis shows that the GABA transporter GAT-1 is upregulated in the ipsilateral gracile nucleus (p <0.001; n = 7), with no detectable change in GAT-3 or glutamate transporters EAAT-1 and EAAT-2. Double immunoflurescence shows that GAT-1 and GFAP colocalize within the same cells. Furthermore, the upregulation of GFAP and GAT-1 were shown to occur all along the rostrocaudal axis of the gracile nucleus. Finally, synaptosomes from ipsilateral gracile nucleus show an increased capacity to reuptake GABA. Together, the data presented herein show that glial cells in the gracile nucleus react to neuropathic lesion, in particular through an upregulation of the GABA transporter GAT-1. Hence, this study points to role of an increased GABA transport in the dorsal column nuclei in neuropathic pain, calling attention to GAT-1 as a putative future pharmacological target to treat allodynia and paresthesia.

Tertiary treatment of pulp and paper mill effluents

Työn tavoitteena oli selvittää mitä käsittelyvaihtoehtoja on olemassa jäteveden puhdistamon tertiäärikäsittelyyn ja miten suuri tarve paperi- ja selluteollisuuden prosessivesien puhdistukseen on. Tarkoituksena oli saada käsitys koko tertiäärikäsittelystä eri näkökulmista. Lopuksi läpikäytiin tertiäärikäsittelymenetelmiä ja etsittiin mahdollisia uusia menetelmiä, joita voitaisiin käyttää jäteveden tertiääripuhdistukseen. Ensimmäisenä työssä on perehdytty jäteveden koostumukseen paperi- ja selluteollisuudessa ja puhdistukseen ilmastetulla aktiivilietemenetelmällä, jotta tertiäärikäsittely ymmärrettäisiin konseptina paremmin. Lisäksi työssä selvitettiin tertiäärikäsittelyn tarvetta ja vaihtoehtoja sen käyttämättä jättämiselle teollisuuden ja muun ympäristöä vahingoittavan toiminnan ympäristönäkökohdat huomioonottaen. Lyhyiden menetelmäesitysten jälkeen kiteytetään tertiäärikäsittelyn ympäristönäkökohdatja vaihtoehdot sen käytölle yhteenvetona, jossa otetaan huomioon myös viranomaisten, yrityksen ja BAT referenssien sisältämä tieto tertiäärikäsittelystä. Työn kokeellinen osa sisältää erään tertiäärikäsittelysovelluksenrakentamisen, koekäytön ja laboratorioanalyysien yhteenvedon. Lisäksi menetelmää verrataan kustannus-tehokkuudeltaan vastaavien menetelmien kanssa. Tarkoituksena oli löytää jäteveden tertiäärikäsittelyyn sopiva laitteisto, jonka toimintaanei sisältyisi kemikaalien annostelua ja sitä käytettäisiin lähinnä jätevedenpuhdistamon ongelmatilanteiden väliaikaiseksi ratkaisuksi. Mahdollisesti se voisi toimia myös jatkuvatoimisesti veden kirkastuksessa. Diplomityössä rakennettu laitteisto, jota käytettiin myös pilot koeajoissa, ei ollut paras mahdollinen laitteisto tertiäärikäsittelyn toteuttamiseksi paperi- ja selluteollisuudessa, mutta kilpailukykyinen muiden laitteistojen kanssa. Laitteiston toimintaperiaate on kuitenkin käyttökelpoinen tietyin varauksin ja sitä voidaan käyttää vedenpuhdistamiseen.

Item master management in the engineer-to-order supply chain

Diplomityöntavoitteena on tutkia, kuinka nimiketiedon hallinnalla voidaan parantaa kustannustehokkuutta projektiohjautuvassa toimitusketjussa. Työn kohdeyritys on Konecranes Oyj:n tytäryhtiö Konecranes Heavy Lifting Oy. Nimiketiedon hallinta liittyy läheisesti tuotetiedon hallintaan. Teoriaosassa käsitellään toimitusketjuympäristön tekijöitä, modulaarisuuden ja asiakaskohtaisuuden ongelmallisuutta sekä informaatiovirran vaikutuksia eri toiminnoissa. Yritysosassa vertaillaan konsernitason kahta liiketoiminta-aluetta strategiavalintojen, tuotteiden modulaarisuuden sekä tilaus-toimitusprosessissa liikkuvan nimikeinformaation perusteella. Diplomityön tuloksena annetaan suuntaviivat; nimikemassan eheytykseen, strategisten nimikkeiden tunnistamiseen ja määrittämiseen, nimikkeiden hallintaan sekä master-datan sijoittamiseen tietojärjestelmäympäristöön.

egr-4, a target of EGFR signaling, is required for the formation of the brian primordial and head regeneration in planarians

During the regeneration of freshwater planarians, polarity and patterning programs play essential roles in determining whether a head or a tail regenerates at anterior or posterior-facing wounds. This decision is made very soon after amputation. The pivotal role of the Wnt/β-catenin and Hh signaling pathways in re-establishing anterior-posterior (AP) polarity has been well documented. However, the mechanisms that control the growth and differentiation of the blastema in accordance with its AP identity are less well understood. Previous studies have described a role of Smed-egfr-3, a planarian epidermal growth factor receptor, in blastema growth and differentiation. Here, we identify Smed-egr-4, a zinc-finger transcription factor belonging to the early growth response gene family, as a putative downstream target of Smed-egfr-3. Smed-egr-4 is mainly expressed in the central nervous system and its silencing inhibits anterior regeneration without affecting the regeneration of posterior regions. Single and combinatorial RNA interference to target different elements of the Wnt/β-catenin pathway, together with expression analysis of brain- and anterior-specific markers, revealed that Smed-egr-4: (1) is expressed in two phases - an early Smed-egfr-3-independent phase and a late Smed-egfr-3-dependent phase; (2) is necessary for the differentiation of the brain primordia in the early stages of regeneration; and (3) that it appears to antagonize the activity of the Wnt/β-catenin pathway to allow head regeneration. These results suggest that a conserved EGFR/egr pathway plays an important role in cell differentiation during planarian regeneration and indicate an association between early brain differentiation and the proper progression of head regeneration.

Prosessijohtamisen soveltaminen energialaitoksen kunnossapidossa

Diplomityössä tarkastellaan prosessijohtamista energialaitoksen kunnossapidossa. Tarkastelun kohteena on Helsingin Energian voimalaitosten kunnossapito. Asioita tarkastellaan kunnossapitoliiketoiminnon näkökulmasta. Työ kertoo tapahtuneista muutoksista, nykyisestä toimintatavasta ja tulevaisuuden kehitystarpeista. Työn lähtökohtana ovat energia-alalla tapahtuneet toimintaympäristön muutokset ja yrityksen organisaation muutos. Yrityksen organisaatio on muutettu funktionaalisesta organisaatiosta liiketoimintopohjaiseksi, joka toi mukanaan sisäisen kaupankäynnin. Kunnossapidon toimittamiseen asiakkaalle sovelletaan prosessijohtamista. Prosessin kehittyminen on hidasta ja vaatii määrätietoista työtä edistyäkseen. Prosessit on kuvattava ja otettava käyttöön, jonka jälkeen voidaan tunnistaa kehityskohteita. Kunnossapitoprosessi ylittää liiketoimintojen välisen rajan, jonka toimivuus on ratkaisevaa prosessin suorituskyvylle. Prosessijohtamisen edistämiseksi on tunnistettu tärkeimmiksi kehityskohteiksi kunnossapitostrategian kehittäminen, rajapinnan selkiyttäminen ja prosessin mittaaminen.