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1.
J Stroke Cerebrovasc Dis ; 31(12): 106840, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36283236

RESUMEN

OBJECTIVES: Direct carotid-cavernous fistulas are high-flow abnormal connections between the carotid artery and cavernous sinus, which are associated with significant morbidity and mortality if left untreated. In addition to endovascular coil embolization, there is an evolving role for alternative stand-alone or adjunctive treatment approaches. We describe a case of flow diversion as an adjunctive treatment approach in a treatment-resistant direct carotid-cavernous fistula and review the literature on the use of flow diversion in this clinical context. MATERIALS AND METHODS: We describe the clinical course, imaging findings, and outcome of a patient who developed a traumatic carotid-cavernous fistula requiring multiple interventions. We also performed an updated literature review of all published cases of flow diversion use in the treatment of direct CCFs. RESULTS: Our patient achieved angiographic cure and significant improvement in symptoms at 6-month follow-up. A total of 53 cases of flow diversion use in direct carotid-cavernous fistulas were identified from a literature search. In one third of cases, flow diversion was used as a stand-alone treatment modality. Angiographic resolution was achieved in 90% of cases at a median follow-up duration of 6 months. One half of reported cases had complete resolution of symptoms and a further third noted clinical improvement in at least some of their symptoms. CONCLUSIONS: There is an emerging role for flow diversion as a safe and effective stand-alone or adjunctive treatment option for direct carotid-cavernous fistulas. Our case further supports a role for flow diversion in treatment-resistant fistulas with high-risk features. As treatment approaches continue to evolve, prospective, randomized data will be needed to establish the role of flow divertors in the hierarchy of available treatments for carotid-cavernous fistulas.


Asunto(s)
Fístula del Seno Cavernoso de la Carótida , Seno Cavernoso , Embolización Terapéutica , Humanos , Estudios Prospectivos , Embolización Terapéutica/efectos adversos , Fístula del Seno Cavernoso de la Carótida/diagnóstico por imagen , Fístula del Seno Cavernoso de la Carótida/etiología , Fístula del Seno Cavernoso de la Carótida/terapia , Seno Cavernoso/diagnóstico por imagen , Prótesis Vascular/efectos adversos
2.
Phys Rev Lett ; 126(3): 032503, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33543956

RESUMEN

A nuclear spectroscopy experiment was conducted to study α-decay chains stemming from isotopes of flerovium (element Z=114). An upgraded TASISpec decay station was placed behind the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. The fusion-evaporation reactions ^{48}Ca+^{242}Pu and ^{48}Ca+^{244}Pu provided a total of 32 flerovium-candidate decay chains, of which two and eleven were firmly assigned to ^{286}Fl and ^{288}Fl, respectively. A prompt coincidence between a 9.60(1)-MeV α particle event and a 0.36(1)-MeV conversion electron marked the first observation of an excited state in an even-even isotope of the heaviest man-made elements, namely ^{282}Cn. Spectroscopy of ^{288}Fl decay chains fixed Q_{α}=10.06(1) MeV. In one case, a Q_{α}=9.46(1)-MeV decay from ^{284}Cn into ^{280}Ds was observed, with ^{280}Ds fissioning after only 518 µs. The impact of these findings, aggregated with existing data on decay chains of ^{286,288}Fl, on the size of an anticipated shell gap at proton number Z=114 is discussed in light of predictions from two beyond-mean-field calculations, which take into account triaxial deformation.

3.
Phys Rev Lett ; 124(25): 252502, 2020 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-32639781

RESUMEN

In an experiment performed at Lawrence Berkeley National Laboratory's 88-inch cyclotron, the isotope ^{244}Md was produced in the ^{209}Bi(^{40}Ar,5n) reaction. Decay properties of ^{244}Md were measured at the focal plane of the Berkeley Gas-filled Separator, and the mass number assignment of A=244 was confirmed with the apparatus for the identification of nuclide A. The isotope ^{244}Md is reported to have one, possibly two, α-decaying states with α energies of 8.66(2) and 8.31(2) MeV and half-lives of 0.4_{-0.1}^{+0.4} and ∼6 s, respectively. Additionally, first evidence of the α decay of ^{236}Bk was observed and is reported.

4.
Phys Rev Lett ; 117(22): 222302, 2016 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-27925748

RESUMEN

The ^{54}Fe nucleus was populated from a ^{56}Fe beam impinging on a Be target with an energy of E/A=500 MeV. The internal decay via γ-ray emission of the 10^{+} metastable state was observed. As the structure of this isomeric state has to involve at least four unpaired nucleons, it cannot be populated in a simple two-neutron removal reaction from the ^{56}Fe ground state. The isomeric state was produced in the low-momentum (-energy) tail of the parallel momentum (energy) distribution of ^{54}Fe, suggesting that it was populated via the decay of the Δ^{0} resonance into a proton. This process allows the population of four-nucleon states, such as the observed isomer. Therefore, it is concluded that the observation of this 10^{+} metastable state in ^{54}Fe is a consequence of the quark structure of the nucleons.

5.
Nano Lett ; 15(10): 6869-74, 2015 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-26356189

RESUMEN

We investigate the ultrafast optoelectronic properties of single Al0.3Ga0.7As/GaAs core-shell nanowires. The nanowires contain GaAs-based quantum wells. For a resonant excitation of the quantum wells, we find a picosecond photocurrent which is consistent with an ultrafast lateral expansion of the photogenerated charge carriers. This Dember-effect does not occur for an excitation of the GaAs-based core of the nanowires. Instead, the core exhibits an ultrafast displacement current and a photothermoelectric current at the metal Schottky contacts. Our results uncover the optoelectronic dynamics in semiconductor core-shell nanowires comprising quantum wells, and they demonstrate the possibility to use the low-dimensional quantum well states therein for ultrafast photoswitches and photodetectors.

6.
Nano Lett ; 15(5): 3295-302, 2015 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-25923841

RESUMEN

Strong surface and impurity scattering in III-V semiconductor-based nanowires (NW) degrade the performance of electronic devices, requiring refined concepts for controlling charge carrier conductivity. Here, we demonstrate remote Si delta (δ)-doping of radial GaAs-AlGaAs core-shell NWs that unambiguously exhibit a strongly confined electron gas with enhanced low-temperature field-effect mobilities up to 5 × 10(3) cm(2) V(-1) s(-1). The spatial separation between the high-mobility free electron gas at the NW core-shell interface and the Si dopants in the shell is directly verified by atom probe tomographic (APT) analysis, band-profile calculations, and transport characterization in advanced field-effect transistor (FET) geometries, demonstrating powerful control over the free electron gas density and conductivity. Multigated NW-FETs allow us to spatially resolve channel width- and crystal phase-dependent variations in electron gas density and mobility along single NW-FETs. Notably, dc output and transfer characteristics of these n-type depletion mode NW-FETs reveal excellent drain current saturation and record low subthreshold slopes of 70 mV/dec at on/off ratios >10(4)-10(5) at room temperature.


Asunto(s)
Aluminio/química , Arsenicales/química , Galio/química , Nanotecnología , Nanocables/química , Electrones , Semiconductores , Silicio/química
7.
Phys Rev Lett ; 115(24): 242502, 2015 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-26705628

RESUMEN

Two short-lived isotopes ^{221}U and ^{222}U were produced as evaporation residues in the fusion reaction ^{50}Ti+^{176}Yb at the gas-filled recoil separator TASCA. An α decay with an energy of E_{α}=9.31(5) MeV and half-life T_{1/2}=4.7(7) µs was attributed to ^{222}U. The new isotope ^{221}U was identified in α-decay chains starting with E_{α}=9.71(5) MeV and T_{1/2}=0.66(14) µs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.

8.
J Biol Chem ; 288(9): 6629-39, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-23322779

RESUMEN

Conditionally active proteins regulated by a physiological parameter represent a potential new class of protein therapeutics. By systematically creating point mutations in the catalytic and linker domains of human MMP-1, we generated a protein library amenable to physiological parameter-based screening. Mutants screened for temperature-sensitive activity had mutations clustered at or near amino acids critical for metal binding. One mutant, GVSK (Gly(159) to Val, Ser(208) to Lys), contains mutations in regions of the catalytic domain involved in calcium and zinc binding. The in vitro activity of GVSK at 37 °C in high Ca(2+) (10 mm) was comparable with MMP-1 (wild type), but in low Ca(2+) (1 mm), there was an over 10-fold loss in activity despite having similar kinetic parameters. Activity decreased over 50% within 15 min and correlated with the degradation of the activated protein, suggesting that GVSK was unstable in low Ca(2+). Varying the concentration of Zn(2+) had no effect on GVSK activity in vitro. As compared with MMP-1, GVSK degraded soluble collagen I at the high but not the low Ca(2+) concentration. In vivo, MMP-1 and GVSK degraded collagen I when perfused in Zucker rat ventral skin and formed higher molecular weight complexes with α2-macroglobulin, an inhibitor of MMPs. In vitro and in vivo complex formation and subsequent enzyme inactivation occurred faster with GVSK, especially at the low Ca(2+) concentration. These data suggest that the activity of the human MMP-1 mutant GVSK can be regulated by Ca(2+) both in vitro and in vivo and may represent a novel approach to engineering matrix-remodeling enzymes for therapeutic applications.


Asunto(s)
Calcio/metabolismo , Metaloproteinasa 1 de la Matriz/metabolismo , Mutación Missense , Sustitución de Aminoácidos , Animales , Calcio/química , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Humanos , Metaloproteinasa 1 de la Matriz/química , Metaloproteinasa 1 de la Matriz/genética , Unión Proteica , Estructura Terciaria de Proteína , Proteolisis , Ratas , Ratas Zucker , Zinc/química , Zinc/metabolismo
9.
Phys Rev Lett ; 113(9): 092501, 2014 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-25215980

RESUMEN

Search for a new kind of superfluidity built on collective proton-neutron pairs with aligned spin is performed studying the Gamow-Teller decay of the T=1, J(π)=0+ ground state of (62)Ge into excited states of the odd-odd N=Z nucleus (62)Ga. The experiment is performed at GSI Helmholtzzentrum für Shwerionenforshung with the (62)Ge ions selected by the fragment separator and implanted in a stack of Si-strip detectors, surrounded by the RISING Ge array. A half-life of T1/2=82.9(14) ms is measured for the (62)Ge ground state. Six excited states of (62)Ga, populated below 2.5 MeV through Gamow-Teller transitions, are identified. Individual Gamow-Teller transition strengths agree well with theoretical predictions of the interacting shell model and the quasiparticle random phase approximation. The absence of any sizable low-lying Gamow-Teller strength in the reported beta-decay experiment supports the hypothesis of a negligible role of coherent T=0 proton-neutron correlations in (62)Ga.

10.
J Anim Ecol ; 83(1): 286-95, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23998642

RESUMEN

Snakes often occur in species-rich assemblages, and sympatry is thought to be facilitated primarily by low diet overlap, not interspecific interactions. We selected, a priori, three species pairs consisting of species that are morphologically and taxonomically similar and may therefore be likely to engage in interspecific, consumptive competition. We then examined a large-scale database of snake detection/nondetection data and used occupancy modelling to determine whether these species occur together more or less frequently than expected by chance while accounting for variation in detection probability among species and incorporating important habitat categories in the models. For some snakes, we obtained evidence that the probabilities that habitat patches are used are influenced by the presence of potentially competing congeneric species. Specifically, timber rattlesnakes (Crotalus horridus) were less likely than expected by chance to use areas that also contained eastern diamond-backed rattlesnakes (Crotalus adamanteus) when the proportion of evergreen forest was relatively high. Otherwise, they occurred together more often than expected by chance. Complex relationships were revealed between habitat use, detection probabilities and occupancy probabilities of North American racers (Coluber constrictor) and coachwhips (Coluber flagellum) that indicated the probability of competitive exclusion increased with increasing area of grassland habitat, although there was some model uncertainty. Cornsnakes (Pantherophis guttatus or Pantherophis slowinskii) and ratsnakes (Pantherophis alleghaniensis, Pantherophis spiloides, or Pantherophis obsoletus) exhibited differences in habitat selection, but we obtained no evidence that patterns of use for this species pair were influenced by current interspecific interactions. Overall, our results are consistent with the hypothesis that competitive interactions influence snake assemblage composition; the strength of these effects was affected by landscape-scale habitat features. Furthermore, we suggest that current interspecific interactions may influence snake occupancy, challenging the paradigm that contemporary patterns of snake co-occurrence are largely a function of diet partitioning that arose over evolutionary time.


Asunto(s)
Ecosistema , Serpientes/clasificación , Serpientes/fisiología , Animales , Conducta Alimentaria , Dinámica Poblacional , Sudeste de Estados Unidos , Especificidad de la Especie
11.
Phys Rev Lett ; 111(11): 112502, 2013 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-24074079

RESUMEN

A high-resolution α, x-ray, and γ-ray coincidence spectroscopy experiment was conducted at the GSI Helmholtzzentrum für Schwerionenforschung. Thirty correlated α-decay chains were detected following the fusion-evaporation reaction 48Ca + 243Am. The observations are consistent with previous assignments of similar decay chains to originate from element Z=115. For the first time, precise spectroscopy allows the derivation of excitation schemes of isotopes along the decay chains starting with elements Z>112. Comprehensive Monte Carlo simulations accompany the data analysis. Nuclear structure models provide a first level interpretation.

12.
Foodborne Pathog Dis ; 10(4): 362-7, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23510496

RESUMEN

Human Noroviruses (HuNoVs) are the most frequent cause of outbreaks of acute gastroenteritis following the ingestion of raw or improperly cooked oysters. Although highly sensitive methods to detect HuNoV in oysters using reverse transcriptase-polymerase chain reaction (RT-PCR) are available, rapid methods to process samples for RT-PCR are still needed. The conventional approach is to concentrate the virus first before RNA purification to maximize assay sensitivity, but the procedures used are cumbersome. We developed a new hybridization method that is much faster and more effective compared to existing technology. The procedure includes an initial extraction of total RNA from the digestive diverticula of oysters using TRI Reagent, followed by HuNoV RNA purification using a capture probe and then HuNoV detection by real-time RT-PCR. The detection limit is approximately 100 PCR detection units of HuNoV per sample. Compared to published methods that require an initial virus concentration step before RNA extraction, the new method is much faster to complete. Approximately 3 h are needed to purify HuNoV RNA using the new method compared to at least 8 h using conventional methods. Coupled with real-time RT-PCR, the new method can detect HuNoV in contaminated oysters within 8 h. The effectiveness of the method was demonstrated using live artificially contaminated oysters and wild oysters.


Asunto(s)
Crassostrea/virología , Norovirus/aislamiento & purificación , ARN Viral/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Animales , Contaminación de Alimentos/análisis , Microbiología de Alimentos , Hibridación de Ácido Nucleico/métodos
13.
J Contam Hydrol ; 256: 104196, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37182507

RESUMEN

Elevated groundwater nitrate concentrations have been linked to deleterious health and environmental effects. A significant source of the nitrate is nitrogen fertilizers applied to agricultural landscapes. Beneficial Management Practices (BMPs), including the optimization of fertilizer use and selective crop rotations, have proven to be effective in some cases. The city of Woodstock in southern Ontario relies on public wells for all of its municipal supply. Several of the wells have experienced chronic increases in nitrate concentrations exceeding the maximum allowable limit of 10 mg/L N-NO3-. While BMPs are established, an interim reduction plan based on enhanced in situ denitrification (Cross Injection System, CIS) in a 15 m thick zone of high nitrate mass flux within the aquifer zone was evaluated. Based in the results of preliminary acetate injection experiments, a C:N ratio of 2.35, (approximately 260 mg acetate/L), was selected to optimize the denitrification reaction. Injections were performed for six hours a day every day for a period of approximately two months. Dissolved oxygen (DO) and nitrate concentrations recorded over time indicated that reduction of both commenced within a few days of the beginning of the acetate injections and reduced levels were maintained for the remainder of the two-month injection period. Denitrification occurred throughout the profile although nitrate reduction was the highest in the lower groundwater velocity zones. An overall reduction of nitrate of 50% was achieved through the treated section of the aquifer. It is estimated that an upscaled treatment system utilizing a treatment width of only 70 m would be sufficient to reduce the nitrate concentrations to below the drinking water limit demonstrating the potential for the CIS method to functions as an interim groundwater nitrate reduction strategy.


Asunto(s)
Agua Potable , Agua Subterránea , Contaminantes Químicos del Agua , Nitratos/análisis , Desnitrificación , Contaminantes Químicos del Agua/análisis , Acetatos , Monitoreo del Ambiente/métodos
14.
Sci Total Environ ; 900: 166466, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37611712

RESUMEN

Long-term road salt application has increased chloride (Cl-) concentrations in public drinking water wells in many cold climate communities. A range of Best Management Practices (BMPs) have been adopted to mitigate the impact of road deicing compounds on groundwater quality. Chronic increases in chloride levels have been observed in several municipal well fields within the southern Ontario Regional Municipality of Waterloo (RMOW). In response, the RMOW and City of Kitchener implemented a plan to reduce salt application on roads by 25% within the local capture zones of one of the impacted well fields, the Greenbrook Well Field. Here the influence of salt reduction BMPs on subsurface water quality are examined by documenting changes in pore water Cl- concentrations and stored salt mass in vadose zone core samples collected at sites near the well field both before and after the implementation of the BMPs. The data indicate that ~6 years after salt reduction measures were initiated, average pore water Cl- concentration and average cumulative stored chloride mass in the vadose zone had decreased by approximately 60% and 40%, respectively. Groundwater samples collected from shallow monitoring wells installed at each field site showed similar post-BMP reductions in shallow groundwater Cl- concentration (~35%). Long-term (1973-2022) trends in raw water Cl- concentration data from the deeper public drinking water supply wells clearly demonstrate a slow, time-lagged response of the municipal supply wells to the salt reduction BMPs. The combined results suggest that controlled reductions in road salt applications within vulnerable, capture zone regions of public supply wells can reduce the impact of road salt deicing practices on municipal groundwater supplies over time.

15.
Ecol Appl ; 22(4): 1084-97, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22827120

RESUMEN

Habitat loss and degradation are thought to be the primary drivers of species extirpations, but for many species we have little information regarding specific habitats that influence occupancy. Snakes are of conservation concern throughout North America, but effective management and conservation are hindered by a lack of basic natural history information and the small number of large-scale studies designed to assess general population trends. To address this information gap, we compiled detection/nondetection data for 13 large terrestrial species from 449 traps located across the southeastern United States, and we characterized the land cover surrounding each trap at multiple spatial scales (250-, 500-, and 1000-m buffers). We used occupancy modeling, while accounting for heterogeneity in detection probability, to identify habitat variables that were influential in determining the presence of a particular species. We evaluated 12 competing models for each species, representing various hypotheses pertaining to important habitat features for terrestrial snakes. Overall, considerable interspecific variation existed in important habitat variables and relevant spatial scales. For example, kingsnakes (Lampropeltis getula) were negatively associated with evergreen forests, whereas Louisiana pinesnake (Pituophis ruthveni) occupancy increased with increasing coverage of this forest type. Some species were positively associated with grassland and scrub/shrub (e.g., Slowinski's cornsnake, Elaphe slowinskii) whereas others, (e.g., copperhead, Agkistrodon contortrix, and eastern diamond-backed rattlesnake, Crotalus adamanteus) were positively associated with forested habitats. Although the species that we studied may persist in varied landscapes other than those we identified as important, our data were collected in relatively undeveloped areas. Thus, our findings may be relevant when generating conservation plans or restoration goals. Maintaining or restoring landscapes that are most consistent with the ancestral habitat preferences of terrestrial snake assemblages will require a diverse habitat matrix over large spatial scales.


Asunto(s)
Ecosistema , Modelos Biológicos , Serpientes/fisiología , Animales , Demografía , Monitoreo del Ambiente , Serpientes/clasificación , Sudeste de Estados Unidos , Especificidad de la Especie
16.
Nanotechnology ; 23(23): 235602, 2012 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-22595881

RESUMEN

We identify the entire growth parameter space and rate-limiting mechanisms in non-catalytic InAs nanowires (NWs) grown by molecular beam epitaxy. Surprisingly huge growth temperature ranges are found with maximum temperatures close to ~600°C upon dramatic increase of V/III ratio, exceeding by far the typical growth temperature range for catalyst-assisted InAs NWs. Based on quantitative in situ line-of-sight quadrupole mass spectrometry, we determine the rate-limiting factors in high-temperature InAs NW growth by directly monitoring the critical desorption and thermal decomposition processes of InAs NWs. Both under dynamic (growth) and static (no growth, ultra-high vacuum) conditions the (111)-oriented InAs NWs evidence excellent thermal stability at elevated temperatures even under negligible supersaturation. The rate-limiting factor for InAs NW growth is hence dominated by In desorption from the substrate surface. Closer investigation of the group-III and group-V flux dependences on growth rate reveals two apparent growth regimes, an As-rich and an In-rich regime defined by the effective As/In flux ratio, and maximum achievable growth rates of > 6 µm h(-1). The unique features of high-T growth and excellent thermal stability provide the opportunity for operation of InAs-based NW materials under caustic environment and further allow access to temperature regimes suitable for alloying non-catalytic InAs NWs with GaAs.


Asunto(s)
Arsenicales/química , Cristalización/métodos , Indio/química , Nanoestructuras/química , Nanoestructuras/ultraestructura , Titanio/química , Catálisis , Calor , Sustancias Macromoleculares/química , Ensayo de Materiales , Conformación Molecular , Tamaño de la Partícula , Propiedades de Superficie
17.
eNeuro ; 9(2)2022.
Artículo en Inglés | MEDLINE | ID: mdl-35387844

RESUMEN

PEGPH20, a human recombinant hyaluronidase, has been proposed as a coadjutant to pancreatic cancer chemotherapy. In early trials, patients reported increased widespread muscle pain as the main adverse reaction to PEGPH20. To understand how PEGPH20 caused musculoskeletal pain, we systemically administered PEGPH20 to male mice and measured voluntary wheel activity and pain-related behaviors. These were paired with ex vivo electrophysiology of primary sensory neurons, whole DRG real-time PCR, and immunohistochemistry of hindpaw muscle. PEGPH20 induced significantly lower wheel running, compared with vehicle-treated animals, and decreased mechanical withdrawal thresholds 5 d after PEGPH20 injections. Chemo-sensory muscle afferents showed increased responses to noxious chemical stimulation of their receptive fields (RFs) in the PEGPH20-treated group. This was correlated with upregulation of the NGF receptor TrkA, the transient receptor potential vanilloid type 1 (TRPV1) channel and ATP-sensitive channel P2X3 in the DRG. Immunohistochemistry of hindpaw muscles revealed damage to the muscle architecture and extensive infiltration of the tissue by cells of the myelomonocytic lineage 3 d after PEGPH20 injection. Peripheral macrophage ablation in macrophage Fas-induced apoptosis (MaFIA) mice, however, did not prevent the decreased voluntary activity and instead caused even lower levels of running. These results suggest that disruption of hyaluronic acid (HA) within the muscle extracellular matrix (ECM) sensitizes chemo-nociceptive muscle afferents possibly leading to altered pain-like behaviors. Ablation experiments suggest macrophages are necessary for adequate recovery of voluntary activity after HA disruption. These data support a role for HA and macrophages in tissue integrity and muscle pain development in patients taking PEGPH20.


Asunto(s)
Ácido Hialurónico , Neoplasias Pancreáticas , Animales , Ganglios Espinales/fisiología , Humanos , Ácido Hialurónico/uso terapéutico , Masculino , Ratones , Actividad Motora , Músculo Esquelético , Mialgia , Neoplasias Pancreáticas/tratamiento farmacológico
18.
AAPS J ; 24(6): 110, 2022 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-36266598

RESUMEN

Multiple FDA-approved and clinical-development stage therapeutics include recombinant human hyaluronidase PH20 (rHuPH20) to facilitate subcutaneous administration. As rHuPH20-reactive antibodies potentially interact with endogenous PH20, we investigated rHuPH20 immunogenicity risk through hyaluronidase tissue expression, predicted B cell epitopes, CD4+ T cell stimulation indices and related these to observed clinical immunogenicity profiles from 18 clinical studies. Endogenous hyaluronidase PH20 expression in humans/mice was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative RT-PCR, and deep RNA-Seq. rHuPH20 potential T cell epitopes were evaluated in silico and confirmed in vitro. Potential B cell epitopes were predicted for rHuPH20 sequence in silico, and binding of polyclonal antibodies from various species tested on a rHuPH20 peptide microarray. Clinical immunogenicity data were collected from 2643 subjects. From 57 human adult and fetal tissues previously screened by RT-PCR, 22 tissue types were analyzed by deep RNA-Seq. Hyaluronidase PH20 messenger RNA expression was detected in adult human testes. In silico analyses of the rHuPH20 sequence revealed nine T cell epitope clusters with immunogenic potential, one cluster was homologous to human leukocyte antigen. rHuPH20 induced T cell activation in 6-10% of peripheral blood mononuclear cell donors. Fifteen epitopes in the rHuPH20 sequence had the potential to cross-react with B cells. The cumulative treatment-induced incidence of anti-rHuPH20 antibodies across clinical studies was 8.8%. Hyaluronidase PH20 expression occurs primarily in adult testes. Low CD4+ T cell activation and B cell cross-reactivity by rHuPH20 suggest weak rHuPH20 immunogenicity potential. Restricted expression patterns of endogenous PH20 indicate low immunogenicity risk of subcutaneous rHuPH20.


Asunto(s)
Epítopos de Linfocito T , Hialuronoglucosaminidasa , Humanos , Adulto , Masculino , Ratones , Animales , Hialuronoglucosaminidasa/genética , Hialuronoglucosaminidasa/metabolismo , Epítopos de Linfocito T/genética , Epítopos de Linfocito B , Leucocitos Mononucleares , Proteínas Recombinantes/metabolismo , Testículo/metabolismo , Anticuerpos , Factores de Riesgo , ARN Mensajero , ADN Polimerasa Dirigida por ARN
19.
Front Chem ; 10: 976635, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36092655

RESUMEN

Flerovium (Fl, element 114) is the heaviest element chemically studied so far. To date, its interaction with gold was investigated in two gas-solid chromatography experiments, which reported two different types of interaction, however, each based on the level of a few registered atoms only. Whereas noble-gas-like properties were suggested from the first experiment, the second one pointed at a volatile-metal-like character. Here, we present further experimental data on adsorption studies of Fl on silicon oxide and gold surfaces, accounting for the inhomogeneous nature of the surface, as it was used in the experiment and analyzed as part of the reported studies. We confirm that Fl is highly volatile and the least reactive member of group 14. Our experimental observations suggest that Fl exhibits lower reactivity towards Au than the volatile metal Hg, but higher reactivity than the noble gas Rn.

20.
Phys Rev Lett ; 107(17): 172502, 2011 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-22107511

RESUMEN

A ß-decaying high-spin isomer in (96)Cd, with a half-life T(1/2)=0.29(-0.10)(+0.11) s, has been established in a stopped beam rare isotope spectroscopic investigations at GSI (RISING) experiment. The nuclei were produced using the fragmentation of a primary beam of (124)Xe on a (9)Be target. From the half-life and the observed γ decays in the daughter nucleus, (96)Ag, we conclude that the ß-decaying state is the long predicted 16(+) "spin-gap" isomer. Shell-model calculations, using the Gross-Frenkel interaction and the πν(p(1/2),g(9/2)) model space, show that the isoscalar component of the neutron-proton interaction is essential to explain the origin of the isomer. Core excitations across the N=Z=50 gaps and the Gamow-Teller strength, B(GT) distributions have been studied via large-scale shell-model calculations using the πν(g,d,s) model space to compare with the experimental B(GT) value obtained from the half-life of the isomer.

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