Oxidative Heck desymmetrisation of 2,2-disubstituted cyclopentene-1,3-diones

Oxidative Heck couplings have been successfully developed for 2,2-disubstituted cyclopentene-1,3-diones. The direct coupling onto the 2,2-disubstituted cyclopentene-1,3-dione core provides a novel expedient way of enantioselectively desymmetrising all-carbon quaternary centres

Preclinical efficacy of hK2 targeted [177Lu]hu11B6 for prostate cancer theranostics

Androgen ablating drugs increase life expectancy in men with metastatic prostate cancer, but resistance inevitably develops. In a majority of these recurrent tumors, the androgen axis is reactivated in the form of increased androgen receptor (AR) expression. Targeting proteins that are expressed as a down-stream effect of AR activity is a promising rationale for management of this disease. The humanized IgG1 antibody hu11B6 internalizes into prostate and prostate cancer (PCa) cells by binding to the catalytic cleft of human kallikrein 2 (hK2), a prostate specific enzyme governed by the AR-pathway. In a previous study, hu11B6 conjugated with Actinium-225 (225Ac), a high linear energy transfer (LET) radionuclide, was shown to generate an AR-upregulation driven feed-forward mechanism that is believed to enhance therapeutic efficacy. We assessed the efficacy of hu11B6 labeled with a low LET beta-emitter, Lutetium-177 (177Lu) and investigated whether similar tumor killing and AR-enhancement is produced. Moreover, single-photon emission computed tomography (SPECT) imaging of 177Lu is quantitatively accurate and can be used to perform treatment planning. [177Lu]hu11B6 therefore has significant potential as a theranostic agent. Materials and Methods: Subcutaneous PCa xenografts (LNCaP s.c.) were grown in male mice. Biokinetics at 4-336 h post injection and uptake as a function of the amount of hu11B6 injected at 72 h were studied. Over a 30 to 120-day treatment period the therapeutic efficacy of different activities of [177Lu]hu11B6 were assessed by volumetric tumor measurements, blood cell counts, molecular analysis of the tumor as well as SPECT/CT imaging. Organ specific mean absorbed doses were calculated, using a MIRD-scheme, based on biokinetic data and rodent specific S-factors from a modified MOBY phantom. Tumor tissues of treated xenografts were immunohistochemically (IHC) stained for Ki-67 (proliferation) and AR, SA-β-gal activity (senescence) and analyzed by digital autoradiography (DAR). Results: Organ-to-blood and tumor-to-blood ratios were independent of hu11B6 specific activity except for the highest amount of antibody (150 µg). Tumor accumulation of [177Lu]hu11B6 peaked at 168 h with a specific uptake of 29 ± 9.1 percent injected activity per gram (%IA/g) and low accumulation in normal organs except in the submandibular gland (15 ± 4.5 %IA/g), attributed to a cross-reaction with mice kallikreins in this organ, was seen. However, SPECT imaging with therapeutic amounts of [177Lu]hu11B6 revealed no peak in tumor accumulation at 7 d, probably due to cellular retention of 177Lu and decreasing tumor volumes. For [177Lu]hu11B6 treated mice, tumor decrements of up to 4/5 of the initial tumor volume and reversible myelotoxicity with a nadir at 12 d were observed after a single injection. Tumor volume reduction correlated with injected activity and the absorbed dose. IHC revealed retained expression of AR throughout treatment and that Ki-67 staining reached a nadir at 9-14 d which coincided with high SA- β-gal activity (14 d). Quantification of nuclei staining showed that Ki-67 expression correlated negatively with activity uptake. AR expression levels in cells surviving therapy compared to previous timepoints and to controls at 30 d were significantly increased (p = 0.017). Conclusions: This study shows that hu11B6 labeled with the low LET beta-emitting radionuclide 177Lu can deliver therapeutic absorbed doses to prostate cancer xenografts with transient hematological side-effects. The tumor response correlated with the absorbed dose both on a macro and a small scale dosimetric level. Analysis of AR staining showed that AR protein levels increased late in the study suggesting a therapeutic mechanism, a feed forward mechanism coupled to AR driven response to DNA damage or clonal lineage selection, similar to that reported in high LET alpha-particle therapy using 225Ac labeled hu11B6, however emerging at a later timepoint

Sites of Biosynthesis of Outer and Inner Membrane Proteins of Neurospora crassa Mitochondria

Outer and inner membranes of Neurospora crassa mitochondria were separated by the combined swelling, shrinking, sonication procedure. Membranes were characterized by electron microscopy and by marker enzyme activities. A red carotenoid pigment was found to be concentrated in the outer membrane. The inner mitochondrial membrane was resolved into about 20 protein bands on polyacrylamide gel electrophoresis, whereas the outer membrane shows essentially one single protein band. Only negligible incorporation of radioactive amino acids occurs into outer membrane when isolated mitochondria are synthesizing polypeptide chains. In agreement with this observation labeling of outer membrane protein is almost entirely blocked, when whole Neurospora cells are incubated with radioactive amino acids in the presence of cycloheximide, an inhibitor of cytoplasmic protein synthesis. Finally, the essential electrophoretic protein band from outer membrane does not become labeled when mitochondria are incubated with radioactive amino acids either in vitro or in vivo in the presence of cycloheximide. It is concluded that the vast majority, if not all, of the outer membrane protein is synthesized by the cytoplasmic system and that polypeptide chains formed by the mitochondrial ribosomes are integrated into the inner mitochondrial membrane

Support for graphicacy: a review of textbooks available to accounting students

This Teaching Note reports on the support available in textbooks for graphicacy that will help students understand the complexities of graphical displays. Graphical displays play a significant role in financial reporting, and studies have found evidence of measurement distortion and selection bias. To understand the complexities of graphical displays, students need a sound understanding of graphicacy and support from the textbooks available to them to develop that understanding. The Teaching Note reports on a survey that examined the textbooks available to students attending two Scottish universities. The support of critical graphicacy skills was examined in conjunction with textbook characteristics. The survey, which was not restricted to textbooks designated as required reading, examined the textbooks for content on data measurement and graphical displays. The findings highlight a lack of support for graphicacy in the textbooks selected. The study concludes that accounting educators need to scrutinize more closely the selection of textbooks and calls for more extensive research into textbooks as a pedagogic tool

Transverse Demagnetization Dynamics of a Unitary Fermi Gas

Understanding the quantum dynamics of strongly interacting fermions is a problem relevant to diverse forms of matter, including high-temperature superconductors, neutron stars, and quark-gluon plasma. An appealing benchmark is offered by cold atomic gases in the unitary limit of strong interactions. Here we study the dynamics of a transversely magnetized unitary Fermi gas in an inhomogeneous magnetic field. We observe the demagnetization of the gas, caused by diffusive spin transport. At low temperatures, the diffusion constant saturates to the conjectured quantum-mechanical lower bound $\simeq \hbar/m$, where $m$ is the particle mass. The development of pair correlations, indicating the transformation of the initially non-interacting gas towards a unitary spin mixture, is observed by measuring Tan's contact parameter.Comment: 8 pages, 6 figures. Accepted versio

The reflexive potential of silence:Emotions, the ‘everyday’ and ethical international relations

This article argues on behalf of an autoethnographic methodology as one, but not the only, method suited to the excavation of the emotions of everyday international relations. I suggest, drawing on my own lived experiences of writing the Life in the United Kingdom Test specifically, and being ordered deported from the United Kingdom more broadly, that a reflexive practice informed by silence allows scholars to attend to the otherwise discounted and excluded forms of emotional knowledge. As my story unfolds, and the transformative potential of trauma is rehearsed, the possibility of excavating otherwise silenced emotions, guided by an affective empathy, comes to the fore. I suggest, building on my own lived experience, that as the researcher cum agent embraces this position, discounted and discarded stories are revisited. In so doing I present a piece of evocative autoethnography in and of itself while demonstrating the role that emotions can play in the construction of everyday practices of International Relations

Effects of Mineral Oils on Host Selection Behavior of Diaphorina Citri

Response of Diaphorina citri Kuwayama (Hemiptera: Psyllidae) on citrus leaves treated with horticultural and agricultural mineral oil (HMO & AMO) was evaluated under laboratory condition in choice and non-choice trials. Combination of HMO and AMO at concentration of 0 up to 2% was applied to citrus leaves. Mineral oil applications significantly reduced the proportion of D. citri stayed on citrus leaves for feeding with the proposed mechanisms: 1) oils covered leaves thus hampered it for releasing volatile compounds, 2) oil film preventing the direct contact of tarsus or palpus to leaf surfaces, and 3) the volatile compounds produced by mineral oils also blended with plant volatiles in the atmosphere and reduced the probability of olfactory receptors capturing the olfactory cues for locating the feeding site. Mineral oils also increased the mortality of D. citri due to the refusion for feeding on the treated citrus leaves. The effect of AMO was more prominent than HMO. Tanggapan Diaphorina citri Kuwayama (Hemiptera: Psyllidae) pada daun jeruk yang diperlakukan dengan minyak mineral (HMO dan AMO) dievaluasi dengan metode pilihan maupun tanpa pilihan di laboratorium. Kombinasi antara HMO dan AMO pada konsentrasi 0% sampai dengan 2% diaplikasikan pada daun jeruk. Minyak mineral secara nyata menurunkan proporsi D. citri hinggap untuk makan pada daun jeruk, yang mungkin disebabkan oleh mekanisme: 1) minyak melapisi daun sehingga tidak mampu melepaskan senyawa volatil, 2) lapisan minyak menghalangi kontak langsung antara tarsus atau palpus pada permukaan daun, dan 3) senyawa volatil dari minyak bercampur dengan volatil tanaman di udara sehingga menurunkan probabilitas reseptor olfaktori menangkap sinyal penanda lokasi inang. Minyak mineral juga meningkatkan mortalitas, akibat dari penolakan makan pada daun jeruk yang diperlakukan. Pengaruh AMO lebih besar dari pada HMO

The Hopf modules category and the Hopf equation

We study the Hopf equation which is equivalent to the pentagonal equation, from operator algebras. A FRT type theorem is given and new types of quantum groups are constructed. The key role is played now by the classical Hopf modules category. As an application, a five dimensional noncommutative noncocommutative bialgebra is given.Comment: 30 pages, Letax2e, Comm. Algebra in pres

Pengaruh Jenis Mangsa dan Suhu pada Perkembangan Menochilus Sexmaculatus Fabricius (Coleoptera: Coccinellidae) dan Peranannya dalam Pengendalian Diaphorina Citri Kuwayama (Hemiptera: Psyllidae)

Diaphorina citri Kuwayama (Hemiptera: Psyllidae) is the vector of citrus greening (Huanglongbing) bacterium and the most serious impediment to citrus culture. Classical biological control of this psyllid vector should contribute to suppress their population. This research was conducted to determine the performance of Menochilus sexmaculatus Fabricius (Coleoptera: Coccinellidae) when they were fed with D. citri. The larval performance index of M. sexmaculatus on D. citri compared with Aphis craccivora Koch (Hemiptera: Aphididae) diet was 1.3.M. sexmaculatus fed with D. citri had lower fitness than those fed with A. craccivora as shown by longer larval stadium, lower adult dry weight, less number of egg produced and lower percentage of egg hatched. M. sexmaculatus grew best at the temperature of 27oC. Employing the exclusion procedure under field condition,M. sexmaculatus could reduce the population of D. citri up to 90%. These findings showed that theM. sexmaculatus could be a potential predator in reducing D. citri, particularly when the more preferred prey A. craccivora was not present. Diaphorina citri Kuwayama (Hemiptera: Psyllidae) merupakan kelompok Psyllid yang menularkan penyebab penyakit Huanglongbing yang sangat berbahaya pada tanaman jeruk. Pengendalian hayati klasik telah banyak memberikan kontribusi dalam pengendalian di lapangan. Penelitian ini dilakukan untuk melihat penampilan Menochilus sexmaculatus Fabricius (Coleoptera: Coccinellidae) dengan pakan D. citri. Indeks penampilan larva M. sexmaculatus dengan pakan D. citri dibandingkan dengan Aphis craccivora Koch (Hemiptera: Aphididae) adalah 1,3. M. sexmaculatus yang diberi pakan D. citri menunjukkan penurunan kebugaran dibandingkan jika diberi pakan A. craccivora seperti yang ditunjukkan dengan stadium larva lebih lama, penurunan berat kering serangga dewasa, telur yang dihasilkan lebih sedikit, dan penurunan jumlah telur yang menetas. Menggunakan metode eksklusi pada kondisi lapangan, M. sexmaculatus mampu menurunkan populasi D. citri sampai 90%. M. sexmaculatus berkembang baik pada suhu 27oC. Hasil penelitian ini menunjukkan bahwa M. sexmaculatus berpotensi untuk menurunkan populasi D. citri, terutama jika inang utamanya A. craccivora tidak ditemukan