bluuebunny/crossref_metadata_2025 huggingface dataset:
Rational of Current Practice of Prescribing Statin to Treat Dyslipidaemia as Primary Prevention of Coronary Heart Disease in Elderly People
Authors: Manwar Asif , Henein Michael Y , Amin Md Nurul , Mohsin Khaled
Published: June 2011

Background: The efficacy of statin therapy in preventing both primary and secondary coronary heart diseases in young and middle aged people is well known and well supported by numbers of landmark clinical trials. Literatures addressing reduction of cholesterol level in elderly (septogenarians & octogenarians) as primary prevention strategy for coronary heart diseases are scarce. The elderly population rarely suffer from primary heart attack and as such routine prescribing of statin to treat dyslipidaemia as primary prevention of coronary heart disease is controversial, particularly when there are reports that statin therapy in elderly population causes cancer, haemorrhagic stroke, dementia and so on. The present study was aimed at answering these questions in order to help formulating a separate guideline for statin therapy in elderly. Methods: The present study reviewed literatures of recent and recent past origin. A systematic literature search of MEDLINE, EMBASE, CINAHL, Web of Science, CANCERLIT and the Cochrane Systematic Review Database have been used to identify randomized clinical trials of statin use with the main focus on primary or secondary end point of CHD, acute coronary syndrome (ACS), cardiac death, overall death, stroke and cancer diagnosis or cancer death. To be included in this review, (1) the entire study subjects or a sub-group were of age 55 years or more (2) had a mean (or median) duration of patient follow-up of at least 1 year, (3) enrolled a minimum of 100 patients, and (4) reported data on the incidence of either cancer diagnosis or cancer death in the elderly population. Conclusions: The study concludes that statin therapy in elderly people may not provide additional benefit in the prevention of primary cardiovascular diseases or death due to primary cardiovascular events. Though most of the studies ruled out excess risk of cancer or other noncardiovascular events, their probability cannot be entirely ignored. However, there is report that addition of statin to the existing drug schedule of elderly subjects does not cause drug interaction. Large-scale, randomized trial on truly representative population with long term follow up will provide authentic data to answer the question whether statin therapy in elderly people with dyslipidaemia can prevent primary heart diseases. Key words: Statin; primary prevention; coronary heart disease; dyslipidemia; elderly people. Ibrahim Card Med J 2011; 1(1):45-55
Enhancing Photodynamyc Therapy Efficacy by Combination Therapy: Dated, Current and Oncoming Strategies
Authors: Postiglione Ilaria , Chiaviello Angela , Palumbo Giuseppe
Published: June 2011

Combination therapy is a common practice in many medical disciplines. It is defined as the use of more than one drug to treat the same disease. Sometimes this expression describes the simultaneous use of therapeutic approaches that target different cellular/molecular pathways, increasing the chances of killing the diseased cell. This short review is concerned with therapeutic combinations in which PDT (Photodynamyc Therapy) is the core therapeutic partner. Besides the description of the principal methods used to assess the efficacy attained by combinations in respect to monotherapy, this review describes experimental results in which PDT was combined with conventional drugs in different experimental conditions. This inventory is far from exhaustive, as the number of photosensitizers used in combination with different drugs is very large. Reports cited in this work have been selected because considered representative. The combinations we have reviewed include the association of PDT with anti-oxidants, chemotherapeutics, drugs targeting topoisomerases I and II, antimetabolites and others. Some paragraphs are dedicated to PDT and immuno-modulation, others to associations of PDT with angiogenesis inhibitors, receptor inhibitors, radiotherapy and more. Finally, a look is dedicated to combinations involving the use of natural compounds and, as new entries, drugs that act as proteasome inhibitors.
Is the Demand for Alcoholic Beverages in Developing Countries Sensitive to Price? Evidence from China
Authors: Tian Guoqiang , Liu Feng
Published: June 2011

Economic literature in developed countries suggests that demand for alcoholic beverages is sensitive to price, with an estimated price elasticity ranging from −0.38 for beer and −0.7 for liquor. However, few studies have been conducted in developing countries. We employ a large individual-level dataset in China to estimate the effects of price on alcohol demand. Using the data from China Health and Nutrition Survey for the years 1993, 1997, 2000, 2004 and 2006, we estimate two-part models of alcohol demand. Results show the price elasticity is virtually zero for beer and only −0.12 for liquor, which is far smaller than those derived from developed countries. Separate regressions by gender reveals the results are mainly driven by men. The central implication of this study is, while alcohol tax increases can raise government revenue, it alone is not an effective policy to reduce alcohol related problems in China.
Molecular Characterization and Expression Pattern of Tripartite Motif Protein 39 in Gallus gallus with a Complete PRY/SPRY Domain
Authors: Pan Chunqing , Zhao Heng , Shen Lin , Sheng Jiping
Published: June 2011

Members of tripartite motif (TRIM) proteins in mammals play important roles in multiple cellular processes in the immune system. In the present study we have obtained the chicken TRIM39 with the insertion of a base A at position 1006 bp, compared to the sequence in the NCBI database (Accession No: NM 001006196), which made TRIM39 fulfill the TRIM rule of domain composition with both PRY, and SPRY domains. The open reading frame consisted of 1392 bp encoding 463 amino acid residues. The amino acid sequences of TRIM39 protein in mammals were highly similar (from 91.48% to 99.61%), while chicken TRIM39 had relatively low homology with mammals (from 29.2% to 39.59%). Real time RT-PCR indicated that the mRNA expression level of TRIM39 was the highest in spleen, with a lower expression in liver, brain, and lung, suggesting it might be an important protein participating in the immune system.
Interfacial Chemistry and the Design of Solid-Phase Nucleic Acid Hybridization Assays Using Immobilized Quantum Dots as Donors in Fluorescence Resonance Energy Transfer
Authors: Algar W. Russ , Krull Ulrich J.
Published: June 2011

The use of quantum dots (QDs) as donors in fluorescence resonance energy transfer (FRET) offer several advantages for the development of multiplexed solid-phase QD-FRET nucleic acid hybridization assays. Designs for multiplexing have been demonstrated, but important challenges remain in the optimization of these systems. In this work, we identify several strategies based on the design of interfacial chemistry for improving sensitivity, obtaining lower limits of detection (LOD) and enabling the regeneration and reuse of solid-phase QD-FRET hybridization assays. FRET-sensitized emission from acceptor dyes associated with hybridization events at immobilized QD donors provides the analytical signal in these assays. The minimization of active sensing area reduces background from QD donor PL and allows the resolution of smaller amounts of acceptor emission, thus lowering the LOD. The association of multiple acceptor dyes with each hybridization event can enhance FRET efficiency, thereby improving sensitivity. Many previous studies have used interfacial protein layers to generate selectivity; however, transient destabilization of these layers is shown to prevent efficient regeneration. To this end, we report a protein-free interfacial chemistry and demonstrate the specific detection of as little as 2 pmol of target, as well as an improved capacity for regeneration.
Defining the Elements for Successful Implementation of a Small-City Radiotherapy Department
Authors: Craighead Peter S. , Dunscombe P.
Published: June 2011

Aims: Distributed delivery models for cancer care have been introduced to bring care closer to home and to provide better access to cancer patients needing radiotherapy. Very little work has been done to demonstrate the elements critical for success in a non-centralized approach. The present study set out to identify the elements that are important for implementing radiotherapy away from large cities. Methods and Results: This qualitative research project consisted of two separate components. In the first component, structured interviews were conducted with 5 external experts. Input on the expert responses was then sought from internal leaders in medical physics, radiation therapy, and radiation oncology. Those interviews were used to develop a proposed template of the elements needed in a small-city department. We tested the validity of all elements by surveying staff members from the radiation treatment program in Calgary, leading to a definition of the resources needed for the proposed department in Lethbridge. Seventy-five staff members contributed to the survey. Conclusions: Qualitative research methods allowed us to define important elements for a small-city radiotherapy department and to validate those elements with a large cohort of staff working in a tertiary centre. This work has influenced the planning of a small-city department in Lethbridge, emphasizing the importance of the elements identified to the service planners. We await the completion of the construction project and the opening of the centre so that we can re-evaluate the importance of the identified elements in actual practice. We recommend such an approach to jurisdictions that are considering devolved radiotherapy.
Digital Necrosis Induced by Erlotinib Treatment in Metastatic Adenocarcinoma of the Lung
Authors: Ballardini Pierluigi , Margutti Guido , Manfredini Roberto
Published: June 2011

Re: Husein–ElAhmed H, Callejas–Rubio JL, Del Olmo RO, Ríos–Fernandez R, Ortego–Centeno N. Severe Raynaud syndrome induced by adjuvant interferon alfa in metastatic melanoma. Curr Oncol 2010;17:122–3. [...]
Novel acridone-modified MCM-41 type silica: Synthesis, characterization and fluorescence tuning
Authors: Hemgesberg Maximilian , Dörr Gunder , Schmitt Yvonne , Seifert Andreas , Zhou Zhou , Klupp Taylor Robin , Bay Sarah , Ernst Stefan , Gerhards Markus , Müller Thomas J J , Thiel Werner R
Published: June 2011

A Mobil Composition of Matter (MCM)-41 type mesoporous silica material containing N-propylacridone groups has been successfully prepared by co-condensation of an appropriate organic precursor with tetraethyl orthosilicate (TEOS) under alkaline sol–gel conditions. The resulting material was fully characterized by means of X-ray diffraction (XRD), N2-adsorption–desorption, transmission electron microscopy (TEM), IR and UV–vis spectroscopy, as well as 29Si and 13C CP-MAS NMR techniques. The material features a high inner surface area and a highly ordered two-dimensional hexagonal pore structure. The fluorescence properties of the organic chromophore can be tuned via complexation of its carbonyl group with scandium triflate, which makes the material a good candidate for solid state sensors and optics. The successful synthesis of highly ordered MCM materials through co-condensation was found to be dependent on the chemical interaction of the different precursors.
The OP War, Libertarian Communication and Graphic Reportage in Georgian London
Authors: Baker James
Published: June 2011

On 18 September 1809, Covent Garden Theatre reopened, lavishly decorated after the devastating fire of the previous year. Far from being an occasion of celebration, an increase in prices and the architectural redistribution raised the ire of London's theatregoers, sparking months of sustained protest. Known as the Old Price riots, these protests received widespread attention in the metropolitan press. They also prompted various responses from London's satirical print trade. This article will explore the output of these two publicly facing media with respect to the Old Price riots as means of examining the differing processes of reportage they functioned within. It will argue that despite operating on a 'virtual' plane of reportage, that during the Old Price riots graphic satire escaped the confines of its virtuality and became an active agent in Georgian anti-authoritarian protest.
MOBBING DIAGNOSIS INSTRUMENT: STAGES OF CONSTRUCTION, STRUCTURE AND CONNECTEDNESS OF CRITERIA / MOBINGO DIAGNOZAVIMO INSTRUMENTAS: KONSTRAVIMO ETAPAI, STRUKTŪRA IR KRITERIJŲ SUSIETUMAS
Authors: Žukauskas Pranas , Vveinhardt Jolita
Published: June 2011

The article deals with mobbing diagnosis criteria in instruments designed by foreign scientists; it presents the process of development of the instrument for diagnosis of mobbing as discrimination in employee relations, designed by the authors, which involves five main stages. The results of expert assessment and their impact on further development of the instrument are discussed in more detail. The detailed structure of the instrument is presented, distinguishing characteristics and criteria and revealing some fragments of indicators in the article. The analysis of intercorrelations has confirmed especially high reliability of interconnectedness of criteria, i.e. 0.001.

Santrauka

Mobingo kaip diskriminacijos darbuotojų santykiuose, gerinant organizacijų klimatą, procesą sudarė penki etapai. Taikant teorinę analizę buvo išskirtos pagrindinės instrumento charakteristikos, sudaryta anketa pirmajam ekspertiniam vertinimui, kurioje pateikti tyrimo objektą atitinkantys kriterijai (pirmasis ekspertų vertinimas), remiantis ekspertų išvadomis, siūlymais ir kriterijų svorio vidurkiais, sudaryta anketa antrajam vertinimui, pateikiant kriterijus atitinkančius rodiklius (antrasis ekspertų vertinimas). Nustačius kriterijų svoriu vidurkį ir itin sumažinus rodiklių skaičių, instrumentas parengtas diagnostiniam žvalgomajam tyrimui. Atlikus tyrimą, pakoreguoti žvalgomojo tyrimo metu atskleisti instrumento trūkumai, padėję parengti jį pagrindiniam tyrimui: išskirtos keturios charakteristikos (mobingo požymiai; mobingo veiksmai; papildomi mobingo požymiai; organizacijos klimatas), kurias sudaro 27 kriterijai, išsiskaidantys į 156 indikatorius.
L'anthropologie à l'épreuve des politiques du témoignage
Authors: Vanthuyne Karine
Published: June 2011

Résumé La publication de Rigoberta Menchú and the Story of All Poor Guatemalans [Stoll, 1998] a suscité de vifs débats au sein des départements d’anthropologie d’outre-Atlantique. À la lumière d’une « double ethnographie » des « politiques du témoignage » sur la guerre au Guatemala, cet article entend proposer un mode alternatif d’« engagement » avec la prise de parole de nos enquêtés – c’est-à-dire, autre que ceux auxquels les débats suscités par la publication de l’ouvrage de David Stoll renvoient.
Increased Frequencies of Myelin Oligodendrocyte Glycoprotein/MHC Class II-Binding CD4 Cells in Patients with Multiple Sclerosis
Authors: Raddassi Khadir , Kent Sally C. , Yang Junbao , Bourcier Kasia , Bradshaw Elizabeth M. , Seyfert-Margolis Vicki , Nepom Gerald T. , Kwok William W. , Hafler David A.
Published: June 2011

Multiple sclerosis (MS) is an autoimmune disease characterized by infiltration of pathogenic immune cells in the CNS resulting in destruction of the myelin sheath and surrounding axons. We and others have previously measured the frequency of human myelin-reactive T cells in peripheral blood. Using T cell cloning techniques, a modest increase in the frequency of myelin-reactive T cells in patients as compared with control subjects was observed. In this study, we investigated whether myelin oligodendrocyte glycoprotein (MOG)-specific T cells could be detected and their frequency was measured using DRB1*0401/MOG97–109(107E-S) tetramers in MS subjects and healthy controls expressing HLA class II DRB1*0401. We defined the optimal culture conditions for expansion of MOG-reactive T cells upon MOG peptide stimulation of PMBCs. MOG97–109-reactive CD4+ T cells, isolated with DRB1*0401/MOG97–109 tetramers, and after a short-term culture of PMBCs with MOG97–109 peptides, were detected more frequently from patients with MS as compared with healthy controls. T cell clones from single cell cloning of DRB1*0401/MOG97–109(107E-S) tetramer+ cells confirmed that these T cell clones were responsive to both the native and the substituted MOG peptide. These data indicate that autoantigen-specific T cells can be detected and enumerated from the blood of subjects using class II tetramers, and the frequency of MOG97–109-reactive T cells is greater in patients with MS as compared with healthy controls.
Genomic Copy Number Analysis in Alzheimer′s Disease and Mild Cognitive Impairment: An ADNI Study
Authors: Swaminathan Shanker , Kim Sungeun , Shen Li , Risacher Shannon L. , Foroud Tatiana , Pankratz Nathan , Potkin Steven G. , Huentelman Matthew J. , Craig David W. , Weiner Michael W. , Saykin Andrew J. , (ADNI) The Alzheimer′s Disease Neuroimaging Initiative
Published: June 2011

Copy number variants (CNVs) are DNA sequence alterations, resulting in gains (duplications) and losses (deletions) of genomic segments. They often overlap genes and may play important roles in disease. Only one published study has examined CNVs in late‐onset Alzheimer′s disease (AD), and none have examined mild cognitive impairment (MCI). CNV calls were generated in 288 AD, 183 MCI, and 184 healthy control (HC) non‐Hispanic Caucasian Alzheimer′s Disease Neuroimaging Initiative participants. After quality control, 222 AD, 136 MCI, and 143 HC participants were entered into case/control association analyses, including candidate gene and whole genome approaches. Although no excess CNV burden was observed in cases (AD and/or MCI) relative to controls (HC), gene‐based analyses revealed CNVs overlapping the candidate gene CHRFAM7A, as well as CSMD1, SLC35F2, HNRNPCL1, NRXN1, and ERBB4 regions, only in cases. Replication in larger samples is important, after which regions detected here may be promising targets for resequencing.
Two-Dimensional Lattice Boltzmann Model for Droplet Impingement and Breakup in Low Density Ratio Liquids
Authors: Gupta Amit , Kumar Ranganathan
Published: June 2011

A two-dimensional lattice Boltzmann model has been employed to simulate the impingement of a liquid drop on a dry surface. For a range of Weber number, Reynolds number and low density ratios, multiple phases leading to breakup have been obtained. An analytical solution for breakup as function of Reynolds and Weber number based on the conservation of energy is shown to match well with the simulations. At the moment breakup occurs, the spread diameter is maximum; it increases with Weber number and reaches an asymptotic value at a density ratio of 10. Droplet breakup is found to be more viable for the case when the wall is non-wetting or neutral as compared to a wetting surface. Upon breakup, the distance between the daughter droplets is much higher for the case with a non-wetting wall, which illustrates the role of the surface interactions in the outcome of the impact.
Understanding evolution of product composition and volatility distribution through in-situ GC × GC analysis: a case study of longifolene ozonolysis
Authors: Isaacman G. , Worton D. R. , Kreisberg N. M. , Hennigan C. J. , Teng A. P. , Hering S. V. , Robinson A. L. , Donahue N. M. , Goldstein A. H.
Published: June 2011

Abstract. A method for predicting volatility and polarity based on chromatographic information was developed and applied to the smog chamber ozonolysis of the sesquiterpene longifolene. The products were collected and analyzed using a GC × GC Thermal Desorption Aerosol Gas Chromatograph/Mass Spectrometer (2D-TAG) and a quadrupole Aerodyne Aerosol Mass Spectrometer (AMS). All the secondary organic aerosol (SOA) was produced within the first half hour of the experiment. However, the oxidation level of the organic aerosol, as inferred from the fraction of ion m/z 44, suggested continued evolution of the SOA over the subsequent hours. Measurements of speciated organic compounds using 2D-TAG confirm that the composition of the particles changed over the course of the experiment. Nearly 200 oxidation products (thought to be mostly ketones and acids) were observed with 2D-TAG, but most could not be identified definitively due to a lack of standards and the absence of likely sesquiterpene oxidation products in available mass spectral databases. To categorize the observed products, the vapor pressure and oxygen-to-carbon ratio (O/C) of observed compounds were estimated based on their two-dimensional chromatographic retention times relative to those of known standards, establishing a retention time correlation (RTC) method for using 2D-TAG to better constrain important modelling parameters. The product distribution continuously evolved in volatility and oxygenation during 5 h of oxidation. Using peak area as the best available proxy for mass, we conclude that the product mixture includes many non-negligible products; the most abundant 3 compounds accounted for only half of the total observed peak area and 80 % of peak area was spread across 15 compounds. The data provide evidence for three conclusions: (1) 2D-TAG provides valuable volatility and oxygenation information even in the absence of definitive species identification, (2) complex particle-phase chemistry causes continued evolution of particle composition after new particles formation, and (3) minor products contribute significantly to SOA from the ozonolysis of longifolene.
Processing of GRAS/METOP radio occultation data recorded in closed-loop and raw-sampling modes
Authors: Gorbunov M. E. , Lauritsen K. B. , Benzon H.-H. , Larsen G. B. , Syndergaard S. , Sørensen M. B.
Published: June 2011

Abstract. Instrument GRAS (Global Navigation Satellite System Receiver for Atmospheric Sounding) on-board of the Metop-A satellite was activated on 27 October 2006. Currently, Metop-A is a fully operational satellite with GRAS providing from 650–700 occultations per day. We describe our processing of GRAS data based on the modification of our OCC software, which was modified to become capable of reading and processing GRAS data. We perform a statistical comparison of bending angles and refractivities derived from GRAS data with those derived from ECMWF analyses. We conclude that GRAS data have error characteristics close to those of COSMIC data. In the height range 10–30 km, the systematic refractivity difference GRAS–ECMWF is of the order of 0.1–0.2 %, and the standard deviation is 0.3–0.6 %. In the lower troposphere GRAS refractivity and bending angle indicate a negative bias, which reaches its maximum value in the tropics. In particular the retrieved refractivity is biased by up to 2.5 %. The negative bias pattern is similar to that found in the statistical validation of COSMIC data. This makes it probable that the bias should not be attributed to the instrument design or hardware.
Sensitivity studies for a space-based methane lidar mission
Authors: Kiemle C. , Quatrevalet M. , Ehret G. , Amediek A. , Fix A. , Wirth M.
Published: June 2011

Abstract. Methane is the third most important greenhouse gas in the atmosphere after water vapour and carbon dioxide. A major handicap to quantify the emissions at the Earth's surface in order to better understand biosphere-atmosphere exchange processes and potential climate feedbacks is the lack of accurate and global observations of methane. Space-based integrated path differential absorption (IPDA) lidar has potential to fill this gap, and a Methane Remote Lidar Mission (MERLIN) on a small satellite in Polar orbit was proposed by DLR and CNES in the frame of a German-French climate monitoring initiative. System simulations are used to identify key performance parameters and to find an advantageous instrument configuration, given the environmental, technological, and budget constraints. The sensitivity studies use representative averages of the atmospheric and surface state to estimate the measurement precision, i.e. the random uncertainty due to instrument noise. Key performance parameters for MERLIN are average laser power, telescope size, orbit height, surface reflectance, and detector noise. A modest-size lidar instrument with 0.45 W average laser power and 0.55 m telescope diameter on a 506 km orbit could provide 50-km averaged methane column measurement along the sub-satellite track with a precision of about 1 % over vegetation. The use of a methane absorption trough at 1.65 μm improves the near-surface measurement sensitivity and vastly relaxes the wavelength stability requirement that was identified as one of the major technological risks in the pre-phase A studies for A-SCOPE, a space-based IPDA lidar for carbon dioxide at the European Space Agency. Minimal humidity and temperature sensitivity at this wavelength position will enable accurate measurements in tropical wetlands, key regions with largely uncertain methane emissions. In contrast to actual passive remote sensors, measurements in Polar Regions will be possible and biases due to aerosol layers and thin ice clouds will be minimised.
The Level 2 research product algorithms for the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES)
Authors: Baron P. , Urban J. , Sagawa H. , Möller J. , Murtagh D. P. , Mendrok J. , Dupuy E. , Sato T. O. , Ochiai S. , Suzuki K. , Manabe T. , Nishibori T. , Kikuchi K. , Sato R. , Takayanagi M. , Murayama Y. , Shiotani M. , Kasai Y.
Published: June 2011

Abstract. This paper describes the algorithms of the level-2 research (L2r) processing chain developed for the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES). The chain has been developed in parallel to the operational chain for conducting researches on calibration and retrieval algorithms. L2r chain products are available to the scientific community. The objective of version 2 is the retrieval of the vertical distribution of trace gases in the altitude range of 18–90 km. An theoretical error analysis is conducted to estimate the retrieval feasibility of key parameters of the processing: line-of-sight elevation tangent altitudes (or angles), temperature and O3 profiles. The line-of-sight tangent altitudes are retrieved between 20 and 50 km from the strong ozone (O3) line at 625.371 GHz, with low correlation with the O3 volume-mixing ratio and temperature retrieved profiles. Neglecting the non-linearity of the radiometric gain in the calibration procedure is the main systematic error. It is large for the retrieved temperature (between 5–10 K). Therefore, atmospheric pressure can not be derived from the retrieved temperature, and, then, in the altitude range where the line-of-sight tangent altitudes are retrieved, the retrieved trace gases profiles are found to be better represented on pressure levels than on altitude levels. The error analysis for the retrieved HOCl profile demonstrates that best results for inverting weak lines can be obtained by using narrow spectral windows. Future versions of the L2r algorithms will improve the temperature/pressure retrievals and also provide information in the upper tropospheric/lower stratospheric region (e.g., water vapor, ice content, O3) and on stratospheric and mesospheric line-of-sight winds.
Impact of changes in grain size and pore space on the hydraulic conductivity and spectral induced polarization response of sand
Authors: Koch K. , Kemna A. , Irving J. , Holliger K.
Published: June 2011

Abstract. Understanding the influence of pore space characteristics on the hydraulic conductivity and spectral induced polarization (SIP) response is critical for establishing relationships between the electrical and hydrological properties of surficial unconsolidated sedimentary deposits, which host the bulk of the world's readily accessible groundwater resources. Here, we present the results of laboratory SIP measurements on industrial-grade, saturated quartz samples with granulometric characteristics ranging from fine sand to fine gravel. We altered the pore space characteristics by changing (i) the grain size spectra, (ii) the degree of compaction, and (iii) the level of sorting. We then examined how these changes affect the SIP response, the hydraulic conductivity, and the specific surface area of the considered samples. In general, the results indicate a clear connection between the SIP response and the granulometric as well as pore space characteristics. In particular, we observe a systematic correlation between the hydraulic conductivity and the relaxation time of the Cole-Cole model describing the observed SIP effect for the entire range of considered grain sizes. The results do, however, also indicate that the detailed nature of these relations depends strongly on variations in the pore space characteristics, such as, for example, the degree of compaction. This underlines the complexity of the origin of the SIP signal as well as the difficulty to relate it to a single structural factor of a studied sample, and hence raises some fundamental questions with regard to the practical use of SIP measurements as site- and/or sample-independent predictors of the hydraulic conductivity.
A simple design rule for 1st order form-closure of underactuated hands
Authors: Krut S. , Bégoc V.
Published: June 2011

Abstract. The property of form-closure of a grasp, as generally defined in the literature, is based on the assumption that contact points between the hand and the object are fixed in space. However, this assumption is false when considering a grasp exerted by an underactuated hand, since in this case, it is not possible to control the position of each phalanx independently. In spite of researchers' interest in studying form-closure, none of the available published work on this subject takes into consideration the particular kinematics of underactuated hands. Actually, there are few available tools to qualify or quantify the stability of a grasp exerted by an underactuated hand, thus the design of underactuated hands mostly results from an intuitive approach. This paper aims to reduce this gap. A classification of underactuated hands is proposed, based on the expression of contact forces. This highlights the influence of non-backdrivable mechanisms introduced in the transmission of the closing motion of the hand on the stability of the grasp. The way to extend the original definition of form-closure to underactuated grasps is illustrated. A more general definition is formulated, which checks the stability of the set "object + hand". Using this new definition, a simple rule is proposed for designing a hand capable of achieving 1st order form-closed grasps. This paper was presented at the IFToMM/ASME International Workshop on Underactuated Grasping (UG2010), 19 August 2010, Montréal, Canada.
On mechanical properties of planar flexure hinges of compliant mechanisms
Authors: Dirksen F. , Lammering R.
Published: June 2011

Abstract. The synthesis of compliant mechanisms yield optimized topologies that combine several stiff parts with highly elastic flexure hinges. The hinges are often represented in finite element analysis by a single node (one-node hinge) leaving doubts on the physical meaning as well as an uncertainty in the manufacturing process. To overcome this one-node hinge problem of optimized compliant mechanisms' topologies, one-node hinges need to be replaced by real flexure hinges providing desired deflection range and the ability to bear internal loads without failure. Therefore, several common types of planar flexure hinges with different geometries are characterized and categorized in this work providing a comprehensive guide with explicit analytical expressions to replace one-node hinges effectively. Analytical expressions on displacements, stresses, maximum elastic deformations, bending stiffness, center of rotation and first natural frequencies are derived in this work. Numerical simulations and experimental studies are performed validating the analytical results. More importance is given to practice-oriented flexure hinge types in terms of cost-saving manufacturability, i.e. circular notch type hinges and rectangular leaf type hinges.
Hip Resurfacing and Pseudotumour
Authors: Murray David W. , Grammatopoulos George , Gundle Roger , Gibbons C. L. Max H. , Whitwell Duncan , Taylor Adrian , Glyn-Jones Sion , Pandit Hemant G. , Ostlere Simon , Gill Harinderjit S. , Athanasou Nick , Mclardy-Smith Peter
Published: June 2011

Metal on metal hip resurfacing has been used widely over the last ten years but there has been recent concern about destructive soft tissue reactions, which have been called pseudotumours by some authors. This has generated considerable controversy. This review explains why pseudotumours occur after resurfacing and how they can be prevented. It also supports the continued use of resurfacing in appropriate patients by appropriately trained surgeons.
A Destructive Midfacial Mass in a Middle-Aged Man
Authors: Deng Ruixin , Li Ruoyu , Wang Xiaowen
Published: May 2024

A 43-year-old man presented with a destructive mass on the nose, with multiple areas of erosion, ulcers, and exudate covering the mass. Histological examination showed polymorphous lymphocytic infiltration in the full-thickness dermis. What is your diagnosis?
Adolescent and Adult Transitions From Major Depressive Disorder to Bipolar Disorder
Authors: Desai Boström Adrian E. , Cars Thomas , Hellner Clara , Lundberg Johan
Published: May 2024

Importance

Bipolar disorder (BD) often first appears in adolescence after onset of major depressive disorder (MDD), but diagnosis and treatment are commonly delayed. This delay is a concern because untreated BD is associated with adverse long-term outcomes, a more recurrent disease course and difficult-to-treat illness, and suicide attempts and deaths.

Objective

To examine the association of age at MDD onset with early transition to BD and the subsequent use of psychiatric inpatient services as a severity indicator.

Design, Setting, and Participants

This retrospective cohort study analyzed comprehensive data sourced from the Stockholm MDD Cohort data from 1997 to 2018, which encompass both outpatient and inpatient care. Individuals with an initial MDD episode from January 1, 2010, to December 31, 2013, who transitioned to BD by December 31, 2018, were identified. Data were analyzed between September 5 and December 28, 2023.

Exposures

Post MDD assessments included a depression severity index, comorbidities, psychotherapy, psychotropic drugs, and electroconvulsive therapy.

Main Outcomes and Measures

The main outcome was the transition from MDD to BD, dichotomized as occurring early (within 3 years of MDD onset) or late (3 years after MDD onset). Secondary outcomes encompassed the use of psychiatric inpatient services post transition and patterns of medication usage. A robust propensity score matching framework was used to estimate outcomes.

Results

The final balanced cohort included 228 individuals, with an equal distribution between adults (n = 114; mean [SD] age, 24.5 [6.3] years; 96 female [84.2%]; 20 experiencing an early transition to BD [17.5%]) and youths (n = 114; mean [SD] age, 15.3 [1.6] years; 93 female [81.6%]; 8 experiencing an early transition to BD [7.0%]). Youths were substantially less likely to transition early (odds ratio, 0.42; 95% CI, 0.20-0.88; P = .02), despite having more outpatient visits (mean [SD] visits per month, 1.21 [1.07] vs 0.97 [0.98] for adults; P = .01). Both groups experienced substantially reduced inpatient care following a BD diagnosis, concurring with a marked decline in antidepressant use without increased lithium use.

Conclusions and Relevance

These findings suggest that adolescents may experience delayed BD progression and that diagnosis substantially reduced inpatient care in all age groups, which coincided with a reduction in the use of antidepressants. These findings may inform pharmacologic strategies in patients with first-episode MDD at risk for BD.
Loss of p14 diminishes immunogenicity in melanoma via non‐canonical Wnt signaling by reducing the peptide surface density
Authors: Wohlfarth Jonas , Kosnopfel Corinna , Faber Dominic , Berthold Marion , Siedel Claudia , Bernhardt Melissa , Schlosser Andreas , Aprati Tyler , Liu David , Schrama David , Houben Roland , Schadendorf Dirk , Goebeler Matthias , Meierjohann Svenja , Schilling Bastian
Published: May 2024

Immunotherapy has achieved tremendous success in melanoma. However, only around 50% of advanced melanoma patients benefit from immunotherapy. Cyclin‐dependent kinase inhibitor 2A (CDKN2A), encoding the two tumor‐suppressor proteins p14ARFand p16INK4a, belongs to the most frequently inactivated gene loci in melanoma and leads to decreased T cell infiltration. While the role of p16INK4ahas been extensively investigated, knowledge about p14ARFin melanoma is scarce. In this study, we elucidate the impact of reduced p14ARFexpression on melanoma immunogenicity. Knockdown of p14ARFin melanoma cell lines diminished their recognition and killing by melanoma differentiation antigen (MDA)‐specific T cells. Resistance was caused by a reduction of the peptide surface density of presented MDAs. Immunopeptidomic analyses revealed that antigen presentation via human leukocyte antigen class I (HLA‐I) molecules was enhanced upon p14ARFdownregulation in general, but absolute and relative expression of cognate peptides was decreased. However, this phenotype is associated with a favorable outcome for melanoma patients. Limiting Wnt5a signaling reverted this phenotype, suggesting an involvement of non‐canonical Wnt signaling. Taken together, our data indicate a new mechanism limiting MDA‐specific T cell responses by decreasing both absolute and relative MDA‐peptide presentation in melanoma.
Leveraging the Power of Enzymes in Engineered Dead and Living Materials
Authors: Shannon Mark R. , Zhou Bini , Perriman Adam W.
Published: May 2024

Significant advances are being made in the incorporation of enzymes into functional materials, which leverage their inherent substrate specificity, efficient catalytic activity, and sustainable origin. These engineered “dead” materials, however, lack the incredible systems‐level control of enzyme activity that living organisms have evolved over millennia. This gap is now being bridged by the rapidly emerging field of engineered living materials (ELMs), which couples the tools of advanced synthetic biology with modern materials science. In this review, the impressive array of methodologies used to fabricate the extensive library of functional enzyme‐based dead materials is discussed, and the design strategies that facilitate their creation unpacked. The spectacular suite of natural and synthetic genetic and post‐translational control systems for enzymes in living organisms is then described. Finally, key recent examples of ELMs that utilize enzyme activity are reviewed, highlighting the central role of the living component in providing responsivity and adaptability to this new class of materials.
Solution‐Processed Ultralow Voltage Organic Transistors With Sharp Switching for Adaptive Visual Perception
Authors: Duan Shuming , Zhang Xianghong , Xi Yue , Liu Di , Zhang Xiaotao , Li Chunlei , Jiang Lang , Li Liqiang , Chen Huipeng , Ren Xiaochen , Hu Wenping
Published: May 2024

Neuromorphic visual systems can emulate biological retinal systems to perceive visual information under different levels of illumination, making them have considerable potential for future intelligent vehicles and vision automation. However, the complex circuits and high operating voltages of conventional artificial vision systems present great challenges for device integration and power consumption. Here, bioinspired synaptic transistors based on organic single crystal phototransistors are reported, which exhibit excitation and inhibition synaptic plasticity with time‐varying. By manipulating the charge dynamics of the trapping centers of organic crystal–electret vertical stacks, organic transistors can operate below 1 V with record high on/off ratios close to 108 and sharp switching with a subthreshold swing of 59.8 mV dec−1. Moreover, the approach offers visual adaptation with highly localized modulation and over 98.2% recognition accuracy under different illumination levels. These bioinspired visual adaptation transistors offer great potential for simplifying the circuitry of artificial vision systems and will contribute to the development of machine vision applications.
The m7G Methyltransferase Mettl1 Drives Cardiac Hypertrophy by Regulating SRSF9‐Mediated Splicing of NFATc4
Authors: Yu Shuting , Sun ZhiYong , Ju Tiantian , Liu Yingqi , Mei Zhongting , Wang Changhao , Qu Zhezhe , Li Na , Wu Fan , Liu KuiWu , Lu Meixi , Huang Min , Pang Xiaochen , Jia Yingqiong , Li Ying , Zhang Yaozhi , Dou Shunkang , Jiang Jianhao , Dong Xianhui , Huang Chuanhao , Li Wanhong , zhang Yi , Yuan Ye , Yang Baofeng , Du Weijie
Published: May 2024

Cardiac hypertrophy is a key factor driving heart failure (HF), yet its pathogenesis remains incompletely elucidated. Mettl1‐catalyzed RNA N7‐methylguanosine (m7G) modification has been implicated in ischemic cardiac injury and fibrosis. This study aims to elucidate the role of Mettl1 and the mechanism underlying non‐ischemic cardiac hypertrophy and HF. It is found that Mettl1 is upregulated in human failing hearts and hypertrophic murine hearts following transverse aortic constriction (TAC) and Angiotensin II (Ang II) infusion. YY1 acts as a transcriptional factor for Mettl1 during cardiac hypertrophy. Mettl1 knockout alleviates cardiac hypertrophy and dysfunction upon pressure overload from TAC or Ang II stimulation. Conversely, cardiac‐specific overexpression of Mettl1 results in cardiac remodeling. Mechanically, Mettl1 increases SRSF9 expression by inducing m7G modification of SRSF9 mRNA, facilitating alternative splicing and stabilization of NFATc4, thereby promoting cardiac hypertrophy. Moreover, the knockdown of SRSF9 protects against TAC‐ or Mettl1‐induced cardiac hypertrophic phenotypes in vivo and in vitro. The study identifies Mettl1 as a crucial regulator of cardiac hypertrophy, providing a novel therapeutic target for HF.
Innovative Energy Storage Smart Windows Relying on Mild Aqueous Zn/MnO2 Battery Chemistry
Authors: Palamadathil Kannattil Hamid , Martinez Soria Gallo Lluis , Harris Kenneth D. , Limoges Benoît , Balland Véronique
Published: May 2024

Rechargeable mild aqueous Zn/MnO2 batteries are currently attracting great interest thanks to their appealing performance/cost ratio. Their operating principle relies on two complementary reversible electrodeposition reactions at the anode and cathode. Transposing this operating principle to transparent conductive windows remains an unexplored facet of this battery chemistry, which is proposed here to address with the development of an innovative bifunctional smart window, combining electrochromic and charge storage properties. The proof‐of‐concept of such bifunctional Zn/MnO2 smart window is provided using a mild buffered aqueous electrolyte and different architectures. To maximize the device's performance, transparent nanostructured ITO cathodes are used to reversibly electrodeposit a high load of MnO2 (up to 555 mA h m−2 with a CE of 99.5% over 200 cycles, allowing to retrieve an energy density as high as 860 mA h m−2 when coupled with a zinc metal frame), while flat transparent FTO anodes are used to reversibly electrodeposit an homogenous coating of zinc metal (up to ≈280 mA h m−2 with a CE > 95% over 50 cycles). The implementation of these two reversible electrodeposition processes in a single smart window has been successfully achieved, leading for the first time to a dual‐tinting energy storage smart window with an optimized face‐to‐face architecture.
Identifying Radical Pathways for Cu(I)/Cu(II) Relay Catalyzed Oxygenation via Online Coupled EPR/UV–Vis/Near‐IR Monitoring
Authors: Wang Yongtao , Zhou Yujia , Sun Wenjing , Wang Xinyu , Yao Jia , Li Haoran
Published: May 2024

Copper‐catalyzed C─H oxygenation has drawn considerable attention in mechanistic studies. However, a comprehensive investigation combining radical pathways with a metal‐catalytic cycle is challenged by the intricate organic radicals and metallic intermediates. Herein, an online coupled EPR/UV–vis/near‐IR detecting method is developed to simultaneously monitor both reactive radical species and copper complex intermediates during the reaction. Focusing on copper‐catalyzed phenol oxygenation with cumene hydroperoxide, the short‐lived alkylperoxyl radical (EPR signal at g = 2.0143) as well as the unexpected square planar Cu(II)‐alkoxyl radical complex (near‐IR signal at 833 nm) are unveiled during the reaction, in addition to the observable phenoxyl radical in EPR, quinone product in UV–vis, and Cu(II) center in EPR. With a comprehensive picture of diverse intermediates evolving over the same timeline, a novel Cu(I)/Cu(II) proposed relay‐catalyzed sequential radical pathway. In this sequence, Cu(II) activates hydroperoxide through Cu(II)‐OOR into the alkylperoxide radical, while the reaction between Cu(I) and hydroperoxide leads to Cu(II)(•OR)OH with high H‐atom abstracting activity. These results provide a thorough understanding of the Cu(I)/Cu(II) relay catalysis for phenol oxygenation, setting the stage for mechanistic investigations into intricate radical reactions promoted by metallic complexes.
A Novel Drug Candidate for Sepsis Targeting Heparanase by Inhibiting Cytokine Storm
Authors: Wang Danyang , Wang Kaixuan , Liu Qiutong , Liu Mingyang , Zhang Guoqiang , Feng Ke , Wang Kun , Ding Xianwei , Zhu Haomiao , Yang Song , Liu Yonghui , Li Tiehai , Gong Peng , Wang Manli , Wang Peng George , Jin Hongzhen , Zhao Wei , Yu Fan
Published: May 2024

Sepsis is an infection‐triggered, rapidly progressive systemic inflammatory syndrome with a high mortality rate. Currently, there are no promising therapeutic strategies for managing this disease in the clinic. Heparanase plays a crucial role in the pathology of sepsis, and its inhibition can significantly relieve related symptoms. Here, a novel heparanase inhibitor CV122 is rationally designed and synthesized, and its therapeutic potential for sepsis with Lipopolysaccharide (LPS) and Cecal Ligation and Puncture (CLP)‐induced sepsis mouse models are evaluated. It is found that CV122 potently inhibits heparanase activity in vitro, protects cell surface glycocalyx structure, and reduces the expression of adhesion molecules. In vivo, CV122 significantly reduces the systemic levels of proinflammatory cytokines, prevents organ damage, improves vitality, and efficiently protects mice from sepsis‐induced death. Mechanistically, CV122 inhibits the activity of heparanase, reduces its expression in the lungs, and protects glycocalyx structure of lung tissue. It is also found that CV122 provides effective protection from organ damage and death caused by Crimean‐Congo hemorrhagic fever virus (CCHFV) infection. These results suggest that CV122 is a potential drug candidate for sepsis therapy targeting heparanase by inhibiting cytokine storm.