237 research outputs found
Evolution of an elliptical bubble in an accelerating extensional flow
Mathematical models that describe the dynamical behavior of a thin gas bubble embedded in a glass fiber during a fiber drawing process have been discussed and analyzed.
The starting point for the mathematical modeling was the equations presented in [1] for a glass fiber with a hole undergoing extensional flow. These equations were reconsidered here with the additional reduction that the hole, i.e. the gas bubble, was thin as compared to the radius of the fiber and of finite extent. The primary model considered was one in which the mass of the gas inside the bubble was fixed. This fixed-mass model involved equations for the axial velocity and fiber radius, and equations for the radius of the bubble and the gas pressure inside the bubble. The model equations assumed that the temperature of the furnace of the drawing tower was known.
The governing equations of the bubble are hyperbolic and predict that the bubble cannot extend beyond the limiting characteristics specified by the ends of the initial bubble shape. An analysis of pinch-off was performed, and it was found that pinch-off can occur, depending on the parameters of the model, due to surface tension when the bubble radius is small.
In order to determine the evolution of a bubble, a numerical method of solution was presented. The method was used to study the evolution of two different initial bubble shapes, one convex and the other non-convex. Both initial bubble shapes had fore-aft symmetry, and it was found that the bubbles stretched and elongated severely during the drawing process. For the convex shape, fore-aft symmetry was lost in the middle of the drawing process, but the symmetry was re-gained by the end of the drawing tower. A small amount of pinch-off was observed at each end for this case, so that the final bubble length was slightly shorter than its theoretical maximum length. For the non-convex initial shape, pinch-off occurred in the middle of the bubble resulting in two bubbles by the end of the fiber draw.
The two bubbles had different final pressures and did not have fore-aft symmetry.
An extension of the fixed-mass model was considered in which the gas in the bubble was allowed to diffuse into the surrounding glass. The governing equations for this leaky-mass model were developed and manipulated into a form suitable for a numerical treatment
Biodistribution et toxicité des nanocapsules chargées en 188Re aprÚs injection intratumorale par convection enhanced delivery chez la souris
Objectifs
DĂ©terminer la faisabilitĂ©, lâintĂ©rĂȘt et la toxicitĂ© hĂ©matologique de lâadministration intratumorale par convection enhanced delivery (CED) de nanocapsules chargĂ©es en 188Re (NCL-188Re).
Matériels et méthodes
LâĂ©tude de biodistribution des NCL-188Re vs perrhĂ©nate (188ReO4â) a Ă©tĂ© rĂ©alisĂ©e sur des souris nude (n = 30). Les animaux ont Ă©tĂ© sĂ©parĂ©s en 2 groupes : injection intratumorale de 188ReO4â pour le premier groupe (n = 15, 3 MBq) et de NCL-188Re pour le second groupe (n = 15, 3 MBq). Les animaux ont Ă©tĂ© sacrifiĂ©s Ă 1 h (n = 10), 24 h (n = 10) et 72 h (n = 10) aprĂšs lâinjection, les organes prĂ©levĂ©s et comptĂ©s. La toxicitĂ© hĂ©matologique des NCL-188Re a Ă©tĂ© Ă©valuĂ©e par prises de sang de 50 ΌL (sinus rĂ©tro-orbitaire) rĂ©alisĂ©es Ă j2, j7, j14 et j21 aprĂšs traitement par NaCl (n = 4), NCL-188Re (3 MBq, n = 4), NCL-188Re (6 MBq, n = 4) et NCL-188Re (12 MBq, n = 4).
RĂ©sultats
La vectorisation par NCL a permis de limiter lâĂ©limination urinaire du 188Re puisque dĂšs 24 h post-IV 0,1 ± 0,1 % de la dose injectĂ©e (%D.I.) vs 81,9 ± 7,5 % D.I. sont retrouvĂ©s dans les urines pour les formes NCL188Re-SSS et 188ReO4-, respectivement, (p = 0,016). Celle-ci permet Ă©galement de retrouver une activitĂ© significativement supĂ©rieure dans la tumeur Ă tous les temps de lâĂ©tude. Lâadministration unique de NCL-188Re a induit une toxicitĂ© modĂ©rĂ©e pour les activitĂ©s injectĂ©es les plus Ă©levĂ©es (12 MBq) se manifestant principalement par une thrombopĂ©nie transitoire de nadir j14âj18. Il nâa pas Ă©tĂ© observĂ© de toxicitĂ© au niveau des autres lignĂ©es cellulaires pour les activitĂ©s administrĂ©es de 3 et 6 MBq.
Conclusions
Les rĂ©sultats obtenus montrent la faisabilitĂ© de lâinjection intratumorale par CED et lâintĂ©rĂȘt de la vectorisation du 188Re par les NCL. Les premiers signes de toxicitĂ© hĂ©matologiques sont en faveur du fractionnement des doses administrĂ©es et dâun meilleur ciblage par fonctionnalisation des NCL aux oestrogĂšnes pour permettre une meilleure rĂ©tention tumorale
Revisiting the S-matrix approach to the open superstring low energy effective lagrangian
The conventional S-matrix approach to the (tree level) open string low energy
effective lagrangian assumes that, in order to obtain all its bosonic
order terms, it is necessary to know the open string (tree level)
-point amplitude of massless bosons, at least expanded at that order in
. In this work we clarify that the previous claim is indeed valid for
the bosonic open string, but for the supersymmetric one the situation is much
more better than that: there are constraints in the kinematical bosonic terms
of the amplitude (probably due to Spacetime Supersymmetry) such that a much
lower open superstring -point amplitude is needed to find all the
order terms. In this `revisited' S-matrix approach we have
checked that, at least up to order, using these kinematical
constraints and only the known open superstring 4-point amplitude, it is
possible to determine all the bosonic terms of the low energy effective
lagrangian. The sort of results that we obtain seem to agree completely with
the ones achieved by the method of BPS configurations, proposed about ten years
ago. By means of the KLT relations, our results can be mapped to the NS-NS
sector of the low energy effective lagrangian of the type II string theories
implying that there one can also find kinematical constraints in the -point
amplitudes and that important informations can be inferred, at least up to
order, by only using the (tree level) 4-point amplitude.Comment: 34 pages, 3 figure, Submitted on Aug 4, 2012, Published on Oct 15,
201
Is poverty in our genes? A critique of Ashraf and Galor, "The 'out of Africa' hypothesis, human genetic diversity, and comparative economic development," American Economic Review (Forthcoming)
PloS one
The HIV-1 nucleocapsid protein (NC) is a small basic protein containing two zinc fingers (ZF) separated by a short linker. It is involved in several steps of the replication cycle and acts as a nucleic acid chaperone protein in facilitating nucleic acid strand transfers occurring during reverse transcription. Recent analysis of three-dimensional structures of NC-nucleic acids complexes established a new property: the unpaired guanines targeted by NC are more often inserted in the C-terminal zinc finger (ZF2) than in the N-terminal zinc finger (ZF1). Although previous NMR dynamic studies were performed with NC, the dynamic behavior of the linker residues connecting the two ZF domains remains unclear. This prompted us to investigate the dynamic behavior of the linker residues. Here, we collected 15N NMR relaxation data and used for the first time data at several fields to probe the protein dynamics. The analysis at two fields allows us to detect a slow motion occurring between the two domains around a hinge located in the linker at the G35 position. However, the amplitude of motion appears limited in our conditions. In addition, we showed that the neighboring linker residues R29, A30, P31, R32, K33 displayed restricted motion and numerous contacts with residues of ZF1. Our results are fully consistent with a model in which the ZF1-linker contacts prevent the ZF1 domain to interact with unpaired guanines, whereas the ZF2 domain is more accessible and competent to interact with unpaired guanines. In contrast, ZF1 with its large hydrophobic plateau is able to destabilize the double-stranded regions adjacent to the guanines bound by ZF2. The linker residues and the internal dynamics of NC regulate therefore the different functions of the two zinc fingers that are required for an optimal chaperone activity
Fischer carbene mediated covalent grafting of a peptide nucleic acid on gold surfaces and IR optical detection of DNA hybridization with a transition metalcarbonyl label
Amine-reactive surfaces comprising N-hydroxysuccinimide ester groups as well as much more unusual Fischer alkoxymetallocarbene groups were generated on gold-coated surfaces via self-assembled monolayers of carboxy- and azido-terminated thiolates, respectively. These functions were further used to immobilize homothymine peptide nucleic acid (PNA) decamer in a covalent fashion involving the primary amine located at its N-terminus. These stepwise processes were monitored by polarization modulation reflection - absorption infrared spectroscopy (PM-RAIRS) that gave useful information on the molecular composition of the organic layers. PNA grafting and hybridization with complementary DNA strand were successfully transduced by quartz crystal microbalance (QCM) measurements. Unfortunately, attempts to transduce the hybridization optically by IR in a label-free fashion were inconclusive. Therefore we undertook to introduce an IR reporter group, namely a transition metalcarbonyl (TMC) entity at the 5\u2032 terminus of complementary DNA. Evidence for the formation of PNA-DNA heteroduplex was brought by the presence of \u3bd(C 61O) bands in the 2000 cm-1 region of the IR spectrum of the gold surface owing to the metalcarbonyl label
Nucleic Acids Res
The HIV-1 transactivator of transcription (Tat) protein is thought to stimulate reverse transcription (RTion). The Tat protein and, more specifically, its (44-61) domain were recently shown to promote the annealing of complementary DNA sequences representing the HIV-1 transactivation response element TAR, named dTAR and cTAR, that plays a key role in RTion. Moreover, the kinetic mechanism of the basic Tat(44-61) peptide in this annealing further revealed that this peptide constitutes a representative nucleic acid annealer. To further understand the structure-activity relationships of this highly conserved domain, we investigated by electrophoresis and fluorescence approaches the binding and annealing properties of various Tat(44-61) mutants. Our data showed that the Tyr47 and basic residues of the Tat(44-61) domain were instrumental for binding to cTAR through stacking and electrostatic interactions, respectively, and promoting its annealing with dTAR. Furthermore, the annealing efficiency of the mutants clearly correlates with their ability to rapidly associate and dissociate the complementary oligonucleotides and to promote RTion. Thus, transient and dynamic nucleic acid interactions likely constitute a key mechanistic component of annealers and the role of Tat in the late steps of RTion. Finally, our data suggest that Lys50 and Lys51 acetylation regulates Tat activity in RTion
European guideline (EuroGuiDerm) on atopic eczema - part II: non-systemic treatments and treatment recommendations for special AE patient populations.
The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology
Italian S3-Guideline on the treatment of Atopic Eczema - Part 2: non-systemic treatments and treatment recommendations for special AE patient populations, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).
SIDeMaST (SocietĂ Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inïŹammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for pediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The ïŹrst part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology
Italian S3-Guideline on the treatment of Atopic Eczema - Part 1: Systemic therapy, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA).
SIDeMaST (SocietĂ Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This ïŹrst part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for pediatric, adolescent, pregnant and breastfeeding patients
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