6,993 research outputs found
A high resolution silicon-on-glass Z Axis Gyroscope Operating at Atmospheric Pressure
No full textThis paper describes a high-resolution silicon-on-glass z axis gyroscope operating at atmospheric pressure. The mechanical structure is designed in such a way that it exhibits low cross coupling between drive and sense mode of less than 0.5% simulated using finite-element method and 1.35% verified by experimental measurements. Due to a symmetrically designed structure, the specified bandwidth can be maintained despite of fabrication imperfections. The fabrication process flow is based on a combination of silicon on glass bonding and deep reactive ion etching which results in a large proof mass and capacitances. A closed loop self-oscillation drive interface is used to resonate the gyroscope in the drive mode, which reaches steady-state after 150 ms. Using area-varying capacitors, large quality factors of 217 and 97 for drive and sense mode, respectively, were achieved operating at atmospheric pressure. A low drive voltage, with a 1 Vpeak-peak AC drive amplitude and 10 V DC bias was used to excite the drive mode. The measured scale factor was 10.7 mV/º/s in a range of ±300 º/s with a R2-nonlinearity of 0.12%. The noise equivalent angular rate is 0.0015 º/s/Hz1/2 (=5.4 º/h/Hz1/2) in a 50 Hz bandwidth. The measured SNR was 34 dB at an angular rate input signal with an amplitude of 12.5 º/ s and a frequency of 10 Hz. Without any active temperature control, zero bias stability of 1 was achieved for long-term measurements over six hours and 0.3 º/s for short-term measurements over 120 seconds (1-σ)
Steric disruption of EGFR oligomerization overcomes therapy resistance in non-small cell lung cancer
No full textAcquired drug resistance mutations in epidermal growth factor receptor (EGFR) present a substantial clinical challenge in treating non-small cell lung cancer (NSCLC). While EGFR oligomerization plays a pivotal role in modulating receptor signaling, its relationship with resistance mutations remains unclear. Here, we investigated the real-time link between oligomerization of oncogenic and resistant EGFR mutants and downstream signaling using a fluorescent protein-based proximity probe and signaling reporter in living cells. We found that EGFR mutants resistant to tyrosine kinase inhibitors (TKIs) exhibited higher oligomerization than did wild-type EGFR with or without EGF. The efficacy of TKIs and allosteric drugs inversely correlated with receptor oligomerization. Furthermore, sterically disrupting EGFR oligomerization by genetically fusing a bulky protein to resistant mutants overcame resistance and suppressed proliferation. Moreover, extracellular application of bulky EGFR binders suppressed resistant mutants by disrupting oligomerization. These findings highlight steric disruption of EGFR oligomerization as a promising strategy for overcoming therapy resistance in NSCLC and introduce a versatile screening platform for developing competitive and allosteric inhibitors.
Philosophy A to Z: Essays for café philosophy
No full textA collection of essays and other texts of popular philosophy written by best-selling author, Michael Picard, MSc PhD, the MIT-trained philosopher who has facilitated hundreds of Cafe Philosophy dialogues with the public, for which the entries in this accidental lexicon were composed. Intended to stimulate readers' thoughts prior to public participatory philosophy sessions, Picard's writing invites the reader on a tour de force of the philosophical dimensions of contemporary life.
This anti-dictionary explodes the meanings of philosophically-intriguing concepts as it defines and un-defines them. Written by MIT-trained philosopher and author of best-selling This is not a Book (2007), this unique alphabetical collection of provocative essays and other texts tease and treat the reader to fresh and foreign perspectives on dozens of philosophy topics of interest to thinking public and critical seekers anywhere. At times playful or profound, alternately skeptical and reverential, the entries in this philosophical lexicon push paradox and pull for pluralism, spanning the vast range of philosophy, ancient and modern, East and West, social and spiritual, moral and metaphysical, and yet more. This book is for people yearning to explore have fun gaining new perspectives and thinking for themselves, and ready to have their minds ignited by the curious, all-consuming questioning spirit of philosophy. -- From publisher description.bookPublished
Jewish feminist writers of the 20th century
No full textThe voice of the Jewish American Feminism writer were to be kept silenced by their male counterparts. The voices of Jewish Feminist writer such as Grace Paley, Cynthia Ozick, Amy Bloom, and Tillie Olsen and their contributions to a concept of womanhood, their unique style of literature, through the astute use of metaphor, language, symbolism, and characterization. This exemplifies their "Jewishness" as the paramount agent of change.M.A.Includes bibliographical referencesby Michael J. Zer
Enantioselective Total Synthesis of Lycoposerramine‑Z Using Chiral Phosphoric Acid Catalyzed Intramolecular Michael Addition
No full textA new
enantioselective total synthesis of phlegmarine-type Lycopodium alkaloid lycoposerramine-Z (1) has
been accomplished, using one-pot chemoselective sequential additions
of two different Grignard reagents to the bis-Weinreb-amide intermediate
and an efficient construction of the fully fuctionalized cyclohexanone
intermediate with a chiral phosphoric acid catalyzed enantioselective
intramolecular Michael addition
Stereoselective synthesis of enamino ketones through an aza-Michael/hydrolysis cascade reaction
No full textHighly functionalized (Z)-β-enamino ketones have been prepared from readily available 3,4-dihydroisoquinoline imines and ynones through an aza-Michael/hydrolysis cascade reaction.</p
O (nieco zapomnianym) mistrzu fantastyki. Sprawozdanie z konferencji Niekończący się Michael Ende – sylwetka, sygnatura, strategie fantastyczne (Kraków, 8 listopada 2019 roku)
No full textNiniejszy tekst jest sprawozdaniem z konferencji Niekończący się Michael Ende – sylwetka, syg-natura, strategie fantastyczne, która odbyła się 8 listopada 2019 roku w Krakowie. Autorka przedstawia w nim wyznaczone przez organizatorów cele, z których najważniejszym wydaje się przypomnienie postaci oraz twórczości tego wybitnego, a jednocześnie nieco zapomnianego nad Wisłą klasyka literatury fantastycznej. Najwięcej uwagi poświęca przebiegowi konferencji, krótko omawiając wszystkie wygłoszone podczas sesji referaty. Zwraca uwagę na interdyscyplinarny charakter spotkania, wskazując ponadto możliwe kierunki poszerzenia refleksji dotyczącej twórczości niemieckiego pisarza wyznaczane przez przywoływaną literaturę przedmiotu.The text summarizes the conference “The NeverEnding Michael Ende – profile, signature, fantasy strategies”, which took place on 8 November 2019 in Kraków. The author describes the organizers’ objectives, among which the main aim was to remind attendees of the profile and work of Michael Ende – a remarkable fantasy writer who is nowadays somewhat forgotten in Poland. The paper focuses in particular on the course of the conference, briefly summing up all the presentations and emphasizing the interdisciplinary nature of the meeting. Based on the critical studies and further source literature, the author indicates some potential ways in which the reception of Ende’s work could develop
PhyloCSF: a comparative genomics method to distinguish protein-coding and non-coding regions
No full textAs high-throughput transcriptome sequencing provides evidence for novel transcripts in many species, there is a renewed need for accurate methods to classify small genomic regions as protein-coding or non-coding. We present PhyloCSF, a novel comparative genomics method that analyzes a multi-species nucleotide sequence alignment to determine whether it is likely to represent a conserved protein-coding region, based on a formal statistical comparison of phylogenetic codon models. We show that PhyloCSF's classification performance in 12-species _Drosophila_ genome alignments exceeds all other methods we compared in a previous study, and we provide a software implementation for use by the community. We anticipate that this method will be widely applicable as the transcriptomes of many additional species, tissues, and subcellular compartments are sequenced, particularly in the context of ENCODE and modENCODE
Statistical analysis of "Plasmodium falciparum" infection dynamics
No full textMalaria is one of the major contributors to the global burden of disease. Worldwide, there were an estimated number of 200 million malaria cases in the year 2008, with a vast majority (85%) of those being in the African Region. This has lead to an estimated number of up to one million deaths, with a similar majority (89%) happening in the African region. There are several parasite species causing malaria, but most deaths are caused by Plasmodium falciparum. Malaria remains a major challenge for scientific research: constantly the parasite evolves resistance against existing drugs, and ever new substances to cure malaria need to be found. Creating a vaccine against Plasmodium falciparum proves exceptionally difficult, because the parasite has found ways to escape the human immune response. How exactly, is poorly understood. In addition, many countries affected by the disease suffer from poverty and ineffective health infrastructure. In the 1950’s the final eradication of malaria was envisioned by the WHO: the newly discovered insecticide DDT showed very promising results in reducing the malaria burden by killing the Anopheles mosquitoes, through which malaria is transmitted, and mathematical models of malaria transmission predicted that eradication of the disease would be possible. Despite great successes in the Caribbean, parts of Asia and South-Central America, and elimination in Europe and North America during the following decades, the efforts did not succeed in tropical Africa and many parts of Asia. After that failure, malaria was a “neglected” disease for a long period. Only since recent times malaria is again high on the global health agenda. Now, the enormous progress in the life sciences during the last decades provides new tools to better understand the parasite’s natural history, and perhaps will reveal new ways of attacking it. One factor which limited the understanding of the epidemiology of the parasite was that microscopy as diagnostic tool is not able to distinguish multiple concurrent infections within one human host: people in endemic areas often harbour several infecting clones in parallel. DNA-based methods make use of genetic loci of which many different variants exist in the parasite population, e.g. merozoite surface protein 2 (msp2), to distinguish co-infecting clones. This thesis develops statistical models to analyse such data on the presence of (mostly) msp2 genotypes. In particular, data from a longitudinal study in Navrongo, Northern Ghana is used in all chapters except chapter 6, where data from Papua New Guinea is analysed. A major challenge in the analysis of this type of data is the phenomenon of imperfect detection: the parasite hides in the deep blood vessels by attaching to the capillary walls, and it can therefore not be always detected in the peripheral blood. The three parameters which are estimated by our statistical models from time-series on presence or absence of genotypes are i) the force of infection (the number of infections acquired per person and year), ii) the duration of infection for one parasite clone, and iii) the detectability (the probability of detecting a parasite, given it is present). Previous statistical methods for the analysis of longitudinal genotyping data were restricted to exponential distributions of infection duration: this means that a constant rate (per time) is assumed at which infections are cleared. The reason for this was mathematical simplicity: the age structure of the infection population within a host can be neglected because the clearance rate is constant and does not depend on the age of an infection. In other words, the same mathematical model as for radioactive decay was used. Biologically, this is a very unrealistic assumption, and to understand more about within-host dynamics of P. falciparum or immunity against it one would like to distinguish between young and old infections. This thesis develops an extension to previous statistical analysis methods and makes use of parametric survival distributions to describe infection clearance and how it depends on the age of an infection. In addition to the age of infection, the effect of host age on infection clearance is investigated: older persons have experienced more infections and are therefore more immune. Changes in infection clearance with host age can therefore be interpreted as effects of immunity. An difference between the distribution of infection durations in the Ghanaian dataset compared to artificial infections4 emerged: a large proportion of infections in the Ghanaian population are cleared quickly after inoculation. It is the first time this could be measured from field data, and the result was confirmed using a different statistical method and study design. The difference between artificial infections and the field data cannot be attributed to acquired immunity in the Ghanaian population because all age groups show a similar abundance of very short infection durations. An interaction between the multiple infections within one host in Northern Ghana appears to be the most likely explanation. The implications of this finding for our understanding of the within-host processes in falciparum malaria are discussed
Stereoselective synthesis of fluoroalkenes via (Z)-2-fluoroalkenyliodonium salts
No full textStereoselective synthesis of fluoroalkenes is described. (Z)-2-Fluoro-1-alkenyl(phenyl)iodonium tetrafluoroborates (1) were synthesized stereoselectively in good yields by Michael-type addition of HF to 1-alkynyl(phenyl)iodonium tetrafluoroborates (2) with a commercially available HF reagent, hydrofluoric acid or Et3N–3HF. Pd-catalyzed cross-coupling reactions using 1 gave (Z)-2-fluoro-1-alkene derivatives in moderate yields. The treatment of 1 with KI in the presence of a catalytic amount of CuI gave (Z)-2-fluoro-1-iodo-1-alkenes (3). Pd-catalyzed cross-coupling reactions of 3 gave better results than that of 1, and a variety of (Z)-2-fluoro-1-alkene derivatives were synthesized in good yields
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