159 research outputs found
Ad hominem attacks on scientists are just as likely to undermine public faith in research as legitimate empirical critiques
Media coverage attacking the character and trustworthiness of a scientist can diminish public faith in the research findings of that scientist. Ralph M. Barnes, Heather M. Johnston, Noah MacKenzie, Stephanie J. Tobin and Chelsea M. Taglang have investigated the degree to which such attacks do undermine trust in that scientist's research, and the relative impact of various types of ad hominem attacks. Perhaps surprisingly, purely ad hominem attacks, such as accusations of a financial conflict of interest, for example, prove just as effective in undermining public faith in research findings as direct criticism of the empirical foundations of a science claim
Best Practices of International Student Assessment: the Arcadia University International MBA Case Study
Assessment is always challenging. Whether we are administrators of programs, teaching faculty, staff, graduate or undergraduate students, and the practice of assessment evokes fears of judgment, fears of public failure, and most significantly, fears of change. Because of this, we often assess with a hesitant hand, gingerly prodding the successes and challenges at all levels of our institutions, hoping that—in this moment, at least—we are achieving the goals which we claim that we’re achieving and are doing so with integrity and a clear understanding of student needs
Real-time Video Alignment and Fusion Using Feature Detection on FPGA
Video fusion functions as a way to combine the important or useful parts of two or more sequences of images. The scenario presented is the use of Laplacian fusion to produce a single video composed of the fields of view of two cameras whose areas of focus differ substantially. This is not a useful real-time strategy unless the fields can be aligned. This thesis presents a system for detecting features using an FPGA implementation of SURF (Speeded-Up Robust Features), and aligning video streams by applying a transform generated from the key features.M.S., Computer Engineering -- Drexel University, 201
C(sp3)-H activation énantiospécifique catalysée par des nanoparticules de ruthénium : application au marquage isotopique de molécules d’intérêt biologique.
Isotopic labeling with deuterium and tritium is extensively used in chemistry, biology and pharmaceutical research.Numerous methods of labeling by isotopic exchange allow high isotopic enrichments but generally require harsh conditions (high temperatures, acidity). As a consequence, a general, regioselective and smooth labeling method that might be applicable to a wide diversity of substrates remains to develop. In the first part of this thesis, we demonstrated that the use of ruthenium nanoparticles, synthesized by Pr. Bruno Chaudret’s team (INSA Toulouse), allowed the mild (2 bar of deuterium gas at 55°C), effective and selective H/D exchange reaction of a large variety of nitrogen-containing compounds, such as pyridines, indoles and primary, secondary and tertiary alkyl amines. The usefulness and the efficiency of this novel methodology was demonstrated by the deuteration of eight nitrogen-containing molecules of biological interest without altering their chemical and stereochemical properties. However, the conservation of the original stereochemistry of an activated chiral C-H center remains a major issue. We studied the reactivity of RuNP@PVP on different categories of nitrogen-containing substrates (amines, aminoacids and peptides) in water or in organic solvents. Our results showed that C-H activation of chiral carbons C(sp3) took place efficiently, selectively and, in all cases, with total retention of configuration. The wide range of applications of this procedure was demonstrated by the labeling of three chiral amines, fourteen aminoacids, three aromatic aminoesters and four peptides. Moreover, our collaboration with Pr. Romuald Poteau’s team (INSA Toulouse) led to the identification of two mechanisms by ab initio simulation in agreement with our experimental results: the σ-bond metathesis mechanism and the oxidative addition mechanism. These two mechanisms imply two vicinal ruthenium atoms leading to the formation an original dimetallacycle key-intermediate with four centers.The second part of this thesis deals with the development of a new method for the determination of the conformation and the relative arrangement of auto-assembled small molecules. It is based on the synergy between labeling chemistry, tritium solid-state NMR and molecular modeling. We focused on the diphenylalanine dipeptide (Phe-Phe) which forms either crystals or self-assembled nanotubes depending on the solvent. If the crystalline atomic structure of Phe-Phe has been solved, the structure of the self-assembled nanotubes of Phe-Phe is still unknown. Three Phe-Phe dipeptides ditritiated on aromatic positions, determined with the help of molecular modeling by Dr. Yves Boulard (CEA Saclay), were synthesized. Tritium solid-state NMR allowed Dr. Thibault Charpentier (CEA Saclay) to measure, on crystallized samples, three inter-tritiums distances very close to the reference distances. This technique also revealed a possible orientational disorder on an aromatic cycle of crystallized Phe-Phe. Ab initio modeling led us to set a double labeling Caryl and Cα on Phe-Phe with ruthenium nanoparticles. Deuteration with RuNP@PVP are very promising and supplementary studies are in progress to perform tritium labeling. We expect to set a new tool of structural study to determine atomic structures of small molecules integrated in supramolecular complexes (nanotubes, amyloid peptides or membranes).Le marquage isotopique par le deutérium et le tritium est largement utilisé en chimie, en biologie ainsi qu’en recherche pharmaceutique.De nombreuses méthodes de marquage par échange isotopique permettent d’atteindre des enrichissements isotopiques élevés, mais elles requièrent généralement l’utilisation de conditions drastiques (température élevée, acidité). Ainsi, une méthode générale de marquage, régiosélective et douce, applicable à une grande variété de substrats, reste encore à développer. Dans le premier volet de cette thèse, nous avons montré que des nanoparticules de ruthénium (RuNP@PVP), synthétisées par l’équipe du Pr. Bruno Chaudret (INSA Toulouse), catalysaient avec une grande efficacité la réaction d’échange H/D sur des amines, des pyridines et des indoles par C‒H activation, sous 2 bars de D2 à 55 °C. L’application à la deutération de huit molécules azotées d'intérêt biologique a montré que la réaction était efficace sans pour autant altérer l’intégrité chimique ou stéréochimique des composés. Cependant, le respect de la stéréochimie originelle d’un centre chiral C‒H activé demeurait un problème majeur. Nous avons donc entrepris l’étude de la réactivité des RuNP@PVP sur différentes classes de substrats azotés chiraux (amines, aminoacides et peptides) dans l’eau ou dans des solvants organiques. Nos résultats ont montré sans ambiguïté que la C-H activation des carbones C(sp3) chiraux s’effectuait efficacement, sélectivement et dans tous les cas avec une rétention totale de configuration. La large gamme d’application de cette procédure a été démontrée par le marquage de 3 amines chirales, 14 aminoacides naturels, 3 aminoesters aromatiques et 4 peptides. D’autre part, notre collaboration avec l’équipe du Pr. Romuald Poteau (INSA Toulouse) a permis d’identifier deux mécanismes réactionnels par simulation ab initio en parfait accord avec nos résultats expérimentaux : le mécanisme par métathèse de liaison σ et le mécanisme d’addition oxydante. Ces deux mécanismes impliquent deux atomes de ruthénium voisins agissant ensemble pour conduire à la formation d’un intermédiaire-clé original dimétallacycle à quatre centres.Le second volet de cette thèse est consacré au développement d’une nouvelle méthode de détermination de la conformation et de l’arrangement relatif de petites molécules auto-assemblées. Elle repose sur la synergie entre chimie de marquage, RMN du tritium à l’état solide et modélisation moléculaire. Nous nous sommes plus particulièrement intéressés au dipeptide diphénylalanine (Phe-Phe) qui, selon le solvant utilisé, peut former des cristaux (structure résolue) ou s’auto-assembler en nanotubes dont la structure atomique reste inconnue. Trois dipeptides Phe-Phe ditritiés sur des positions aromatiques, définies à l’aide de la modélisation moléculaire par le Dr. Yves Boulard (CEA Saclay), ont été synthétisés. La RMN du tritium à l’état solide a permis au Dr. Thibault Charpentier (CEA Saclay) de mesurer, sur des échantillons cristallisés, trois distances inter-tritiums très proches des distances de référence. Cette technique a également mis en évidence un éventuel désordre d’orientation d’un cycle aromatique de Phe-Phe cristallisé. Une modélisation ab initio nous a également incités à entreprendre un double marquage Caryl et Cα de Phe-Phe, ce dernier utilisant les nanoparticules de ruthénium. Les essais de marquage au deutérium avec RuNP@PVP sont très encourageants et des études complémentaires sont en cours dans notre laboratoire pour parvenir au marquage au tritium. Ainsi, nous espérons mettre au point un nouvel outil d’étude structurale permettant d’accéder à la structure atomique de petites molécules intégrées dans des ensembles supramoléculaires complexes (nanotubes, peptides amyloïdes ou membranaires)
Business Process Intelligence für mittelständische Unternehmen: Anforderungen, Konzepte und Systeme
Ein Trend, der zunehmend auch in mittelständischen Unternehmen Einzug gefunden hat, ist der Einsatz von Business Intelligence (BI). Es hat sich jedoch gezeigt, dass BI ohne die Berücksichtigung der zugrunde liegenden Geschäftsprozesse an Aussagekraft verliert. Diese Problematik kann durch den Einsatz von Business Process Intelligence (BPI) gelöst werden. BPI berücksichtigt die zugrunde liegenden Geschäftsprozesse und eröffnet neue Analysemöglichkeiten. Auch Business Process Management (BPM) spielt in mittelständischen Unternehmen eine zunehmend wichtigere Rolle. Viele Softwarehersteller haben auf diese Trends reagiert und bieten BPM- und BI-Erweiterungen für ihre Software-Systeme an. Dadurch ist die Grundlage geschaffen, um auch in mittelständischen Unternehmen BPI durchführen zu können. Die vorliegende Arbeit beschäftigt sich mit der Frage, ob BPI im Mittelstand eine Rolle spielen kann und ob mit den am Markt befindlichen Software-Systemen eine Durchführung von BPI möglich ist. Da es sich bei den Software-Systemen für den Mittelstand um ein sehr heterogenes Feld handelt, wird sich in dieser Arbeit auf Enterprise Ressource Planning (ERP)-Systeme als gemeinsame Schnittmenge fokusiert. Das Ziel der Arbeit ist es, eine Systematik aufzubauen, um Unternehmen des Mittelstands im Bezug auf ihre Organisationsstruktur und eingesetzten Software-Systeme zu klassifizieren. Auf dieser Basis sollen anschließend die Anforderungen mittelständischer Unternehmen an BPI erhoben werden. Zusätzlich wird ein Evaluationsprozess entwickelt, um ERP-Systeme auf ihre Eignung für BPI im Mittelstand zu untersuchen. Die Evaluation wird anschließend exemplarisch an zwei ERP-Systemen durchgeführt und ihre Eignung für BPI im Mittelstand festgestellt. Abschließend werden mögliche BPI-Konzepte für den Mittelstand diskutiert
Domesticated dogs’ (Canis familiaris) use of the solidity principle
Shannon M. A. Kundey, Chelsea Taglang, Ayelet Baruch, and Rebecca German, Department of Psychology, Hood College; Andres De Los Reyes, Comprehensive Assessment and Intervention Program, Department of Psychology, University of Maryland at College Park. We would like to thank Jessica Arbuthnot, Rebecca Allen, Ariel Coshun, Erica Royer, Sherry McClurkin, Sabrina Molina, and Robin Reutten for their assistance in data collection and
participant recruitment for this study.Organisms must often make predictions about
the trajectories of moving objects. However, often these objects become hidden. To later locate such objects, the organism must maintain a representation of the object in
memory and generate an expectation about where it will later appear. We explored adult dogs’ knowledge and use of the solidity principle (that one solid object cannot pass through another solid object) by evaluating search behavior. Subjects watched as a treat rolled down an inclined
tube into a box. The box either did or did not contain a solid wall dividing it in half. To find the treat, subjects had to
modify their search behavior based on the presence or absence of the wall, which either did or did not block the treat’s trajectory. Dogs correctly searched the near location when the barrier was present and the far location when the barrier was absent. They displayed this behavior from the
first trial, as well as performed correctly when trial types were intermingled. These results suggest that dogs direct their searches in accordance with the solidity principle
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Combined inhibition of de novo glutathione and nucleotide biosynthesis is synthetically lethal in glioblastoma
Understanding the mechanisms by which oncogenic events alter metabolism will help identify metabolic weaknesses that can be targeted for therapy. Telomerase reverse transcriptase (TERT) is essential for telomere maintenance in most cancers. Here, we show that TERT acts via the transcription factor forkhead box O1 (FOXO1) to upregulate glutamate-cysteine ligase (GCLC), the rate-limiting enzyme for de novo biosynthesis of glutathione (GSH, reduced) in multiple cancer models, including glioblastoma (GBM). Genetic ablation of GCLC or pharmacological inhibition using buthionine sulfoximine (BSO) reduces GSH synthesis from [U-13C]-glutamine in GBMs. However, GCLC inhibition drives de novo pyrimidine nucleotide biosynthesis by upregulating the glutamine-utilizing enzymes glutaminase (GLS) and carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotatase (CAD) in an MYC-driven manner. Combining BSO with the glutamine antagonist JHU-083 is synthetically lethal in vitro and in vivo and significantly extends the survival of mice bearing intracranial GBM xenografts. Collectively, our studies advance our understanding of oncogene-induced metabolic vulnerabilities in GBMs
Hyperpolarized δ-[1- 13C]gluconolactone imaging visualizes response to TERT or GABPB1 targeting therapy for glioblastoma
TERT promoter mutations are a hallmark of glioblastoma (GBM). Accordingly, TERT and GABPB1, a subunit of the upstream mutant TERT promoter transcription factor GABP, are being considered as promising therapeutic targets in GBM. We recently reported that the expression of TERT or GABP1 modulates flux via the pentose phosphate pathway (PPP). Here, we investigated whether 13C magnetic resonance spectroscopy (MRS) of hyperpolarized (HP) δ- [1-13C]gluconolactone can serve to image the reduction in PPP flux following TERT or GABPB1 silencing. We investigated two different human GBM cell lines stably expressing shRNAs targeting TERT or GABPB1, as well as doxycycline-inducible shTERT or shGABPB1cells. MRS studies were performed on live cells and in vivo tumors, and dynamic sets of 13C MR spectra were acquired following injection of HP δ-[1-13C]gluconolactone. HP 6-phosphogluconolactone (6PG), the product of δ-[1-13C]gluconolactone via the PPP, was significantly reduced in TERT or GABPB1-silenced cells or tumors compared to controls in all our models. Furthermore, a positive correlation between TERT expression and 6PG levels was observed. Our data indicate that HP δ-[1-13C]gluconolactone, an imaging tool with translational potential, could serve to monitor TERT expression and its silencing with therapies that target either TERT or GABPB1 in mutant TERT promoter GBM patients
Domesticated dogs (Canis familiaris) react to what others can and cannot hear
Corresponding author at: Hood College, Department of Psychology, 401 Rosemont Avenue, Room ROS 27, Frederick, MD 21701,
USA. Tel.: +1 301 696 3877. E-mail address: [email protected] (S.M.A. Kundey).Recent research suggests some nonhuman primates (e.g., chimpanzees, rhesus macaques)
consider what others hear when acting in competitive situations. We explored whether
dogs living in private homes or sourced from an animal shelter would show this same
predilection. Following an inhibition task where dogs (Canis familiaris) were commanded
not to take a treat left on a plate by a human, we presented subjects with the opportunity to take food from one of two containers. These containers were located within the proximity of a human gatekeeper who was either looking straight ahead or not looking at the time of choice. One container was silent when food was inserted or removed while the other was noisy. Among pet dogs (20 total; 10 in each condition) randomly assigned to the Looking or Not Looking condition, four subjects approached the silent container in the Looking condition (binomial test: P = 0.8) while 10 approached the silent container in the Not Looking condition (binomial test: P = 0.004). We compared pet dogs’ pattern of performance
between conditions using a chi-square test for independence, which indicated that dogs significantly preferred the silent container only in the Not Looking condition (Chi-square [1] = 8.8, P = 0.003). This outcome suggests dogs preferentially attempted to retrieve food silently only when silence was germane to obtaining food unobserved by the human gatekeeper.
Interestingly, dogs sourced from a local animal shelter evidenced similar outcomes.
Among shelter dogs (20 total; 10 in each condition) randomly assigned to the Looking or Not Looking condition, four subjects approached the silent container in the Looking condition (binomial test: P = 0.8) while nine approached the silent container in the Not Looking condition (binomial test: P = 0.02).We compared shelter dogs’ pattern of performance between conditions using a chi-square test for independence, which indicated that dogs significantly
preferred the silent container only in the Not Looking condition (Chi-square [1] = 5.5, P = 0.02). This result suggests shelter dogs, like pet dogs, preferentially tried to retrieve food silently only if silence was relevant to obtaining food unobserved by a human gatekeeper. This result conflicts with other recent data suggesting that shelter dogs perform more poorly than pet dogs in tasks involving human social cues
3066 consecutive Gamma Nails. 12 years experience at a single centre
<p>Abstract</p> <p>Background</p> <p>Fixation of trochanteric hip fractures using the Gamma Nail has been performed since 1988 and is today well established and wide-spread. However, a number of reports have raised serious concerns about the implant's complication rate. The main focus has been the increased risk of a subsequent femoral shaft fracture and some authors have argued against its use despite other obvious advantages, when this implant is employed.</p> <p>Through access to a uniquely large patient data base available, which is available for analysis of trochanteric fractures; we have been able to evaluate the performance of the Gamma Nail over a twelve year period.</p> <p>Methods</p> <p>3066 consecutive patients were treated for trochanteric fractures using Gamma Nails between 1990 and 2002 at the Centre de Traumatologie et de l'Orthopedie (CTO), Strasbourg, France. These patients were retrospectively analysed. Information on epidemiological data, intra- and postoperative complications and patients' outcome was retrieved from patient notes. All available radiographs were assessed by a single reviewer (AJB).</p> <p>Results</p> <p>The results showed a low complication rate with the use of the Gamma Nail. There were 137 (4.5%) intraoperative fracture-related complications. Moreover 189 (6.2%) complications were detected postoperatively and during follow-up. Cut-out of the lag screw from the femoral head was the most frequent mechanical complication (57 patients, 1.85%), whereas a postoperative femoral shaft fracture occurred in 19 patients (0.6%). Other complications, such as infection, delayed healing/non-union, avascular femoral head necrosis and distal locking problems occurred in 113 patients (3.7%).</p> <p>Conclusions</p> <p>The use of the Gamma Nail in trochanteric hip fractures is a safe method with a low complication rate. In particular, a low rate of femoral shaft fractures was reported. The low complication rate reported in this series can probably be explained by strict adherence to a proper surgical technique.</p
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