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1.
BMC Womens Health ; 24(1): 249, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637783

RESUMEN

BACKGROUND: Image-guided adaptive brachytherapy (IGABT) demonstrates an excellent local control rate and low toxicity while treating cervical cancer. For intracavitary/interstitial (IC/IS) brachytherapy (BT), several applicators are commercially available. Venezia (Elekta, Sweden), an advanced gynecological applicator, is designed for IC/IS BT for treating locally advanced cervical cancer. There are two types of interstitial needles for the Venezia applicator: the round needle and sharp needle. Generally, a round needle is safer because it has less risk of damaging the organ at risk than a sharp needle. However, there is currently no evidence to suggest that a round needle is better than a sharp needle for the Venezia applicator in IC/IS BT. Herein, we documented our experience of using both round and sharp needles with the Venezia applicator in IC/IS BT for cervical cancer. CASE PRESENTATION: A 71-year-old woman was diagnosed with clinical stage T2bN0M0 and the International Federation of Gynecology and Obstetrics stage IIB cervical squamous cell carcinoma. Definitive therapy, including a high-dose-rate BT boost, was planned using a round needle with the Venezia applicator in IC/IS BT. After inserting four interstitial round needles during the first and second BT sessions, an unexpectedly large gap (1.5 cm) was detected between the cervix and ovoid. We therefore used a sharp needle with the Venezia applicator for IC/IS BT during the third and fourth BT sessions. Three sharp needles were firmly inserted during the third and fourth BT sessions. CONCLUSIONS: The study findings suggest that the interstitial round needle should not be used for cervical cancer patients undergoing IC/IS BT using the Venezia applicator.


Asunto(s)
Braquiterapia , Carcinoma de Células Escamosas , Neoplasias del Cuello Uterino , Femenino , Humanos , Anciano , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/patología , Cuello del Útero/patología , Carcinoma de Células Escamosas/radioterapia , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador
2.
J Contemp Brachytherapy ; 14(3): 260-267, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36199991

RESUMEN

Purpose: Novel hybrid Venezia applicator enables intracavitary and interstitial brachytherapy (BT) for locally advanced cervical cancer. However, the method to determine the optimal interstitial needle number, position, and depth using this applicator is unknown. Therefore, we aimed to establish a method for reliable needle optimization. Material and methods: We produced a template model of the Venezia applicator with whole needles, and acquired computed tomography (CT) images (template CT). Using this template CT as a map, clinicians could define interstitial needle's insertion route in advance. During treatment, we first placed tandem and ovoid, and acquired a CT (tandem + ovoid CT). This was fused to the template CT by matching the contour of applicators with high accuracy. Then, we determined the optimal interstitial needle number, position, and depth to fit high-risk clinical target volume (HR-CTV) and avoid organs at risk (OARs) on the fused CT (intra pre-plan). Next, we re-inserted the tandem and ovoids with interstitial needle into patient's uterus and vagina. We inserted the optimized interstitial needle using insertion tool of optimal depth immediately following the applicator insertion. Lastly, a real-time treatment planning CT was performed, followed by planning and treatment. Results: We achieved a good dose distribution of Venezia applicator BT using intra pre-plan method to optimize the number of interstitial needles, position, and depth. Conclusions: This novel intra pre-plan method of interstitial needle optimization using template CT fusion provides high reproducibility, efficiency, and safety for patients with cervical cancer treated with brachytherapy using Venezia applicator.

5.
J Phys Chem A ; 124(10): 2019-2028, 2020 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-32045526

RESUMEN

Plasma-assisted combustion can improve the thermal efficiency and stability of internal combustion engines; based on this, among various types of discharge method, surface dielectric barrier discharge (SDBD) induced partial oxidation of hydrocarbons was investigated in this study. To demonstrate the general mechanisms of SDBD-induced partial oxidation of gasoline, we used a five-component gasoline surrogate (S5R), which consisted of a mixture of alkanes (isooctane, n-heptane, and methylcyclohexane), alkenes (trimethyl pentene isomers), and toluene, as the model. The detailed process of SDBD-induced partial oxidation of hydrocarbon was investigated by Fourier transform infrared spectroscopy, ion attachment mass spectrometry, and density functional theory calculation. SDBD irradiation of the hydrocarbon/air mixture induced dissociation of oxygen molecule through direct electron impact and collision with excited nitrogen molecules, and the resultant oxygen atom then reacted with a hydrocarbon molecule. Alkane and toluene were converted to alkyl hydroperoxide by a reaction with the oxygen atom and subsequent attachment of O2. The resultant alkyl hydroperoxide then provided a ketone and/or aldehyde. In contrast, the alkenes underwent attachment of an oxygen atom and were either converted to fragments containing a carbonyl group or to etoposide. Regarding the analytical method, the partially oxidized products were selectively ionized from the hydrocarbon/air mixture when Na+ was used as the reagent ion for ion attachment mass spectrometry.

6.
Phys Chem Chem Phys ; 20(2): 1082-1090, 2018 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-29238767

RESUMEN

Plasma induced reforming processes of fuel-air mixtures were investigated to understand the mechanism of the plasma-assisted combustion technique, which can improve the thermal efficiency and stability of internal combustion engines. In this study, a mixture of air with isooctane or n-heptane fuels was reformed by non-thermal plasma in a flow reactor, generated by a dielectric barrier discharge, and then directly analyzed using ion attachment mass spectrometry. Plasma irradiation of an air/hydrocarbon mixture produced an oxygen atom which then reacted with a hydrocarbon, leading to hydroxyl and alkyl radicals. The alkyl radical was immediately converted to alkyl hydroperoxide, which is suggested to be a long-living intermediate for the fuel reforming process. Finally, ketone and aldehyde were formed through the alkyloxy radical intermediate. The details of each reaction process were investigated by ab initio calculations. The proposed plasma induced fuel reforming processes are strongly supported by the computational results.

7.
Int J Biomed Imaging ; 2017: 7089213, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28255295

RESUMEN

Optical colonoscopy is the most common approach to diagnosing bowel diseases through direct colon and rectum inspections. Periodic optical colonoscopy examinations are particularly important for detecting cancers at early stages while still treatable. However, diagnostic accuracy is highly dependent on both the experience and knowledge of the medical doctor. Moreover, it is extremely difficult, even for specialist doctors, to detect the early stages of cancer when obscured by inflammations of the colonic mucosa due to intractable inflammatory bowel diseases, such as ulcerative colitis. Thus, to assist the UC diagnosis, it is necessary to develop a new technology that can retrieve similar cases of diagnostic target image from cases in the past that stored the diagnosed images with various symptoms of colonic mucosa. In order to assist diagnoses with optical colonoscopy, this paper proposes a retrieval method for colonoscopy images that can cope with multiscale objects. The proposed method can retrieve similar colonoscopy images despite varying visible sizes of the target objects. Through three experiments conducted with real clinical colonoscopy images, we demonstrate that the method is able to retrieve objects of any visible size and any location at a high level of accuracy.

8.
Nature ; 539(7627): 81-84, 2016 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-27750277

RESUMEN

Seismic shear wave anisotropy is observed in Earth's uppermost lower mantle around several subducted slabs. The anisotropy caused by the deformation-induced crystallographic preferred orientation (CPO) of bridgmanite (perovskite-structured (Mg,Fe)SiO3) is the most plausible explanation for these seismic observations. However, the rheological properties of bridgmanite are largely unknown. Uniaxial deformation experiments have been carried out to determine the deformation texture of bridgmanite, but the dominant slip system (the slip direction and plane) has not been determined. Here we report the CPO pattern and dominant slip system of bridgmanite under conditions that correspond to the uppermost lower mantle (25 gigapascals and 1,873 kelvin) obtained through simple shear deformation experiments using the Kawai-type deformation-DIA apparatus. The fabrics obtained are characterized by [100] perpendicular to the shear plane and [001] parallel to the shear direction, implying that the dominant slip system of bridgmanite is [001](100). The observed seismic shear- wave anisotropies near several subducted slabs (Tonga-Kermadec, Kurile, Peru and Java) can be explained in terms of the CPO of bridgmanite as induced by mantle flow parallel to the direction of subduction.

9.
J Vet Med Sci ; 78(5): 785-90, 2016 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-26822002

RESUMEN

To elucidate current status of fasciolosis and eurytremosis in beef cattle of Japan, inspection data of Tokyo Metropolitan Shibaura Slaughterhouse where beef cattle were shipped from all over Japan were analyzed, and questionnaire to farmers was conducted to assess the relationship between recognition of the disease occurrence in one's own farm and attention to the diseases. The occurrence of fasciolosis and eurytremosis in beef cattle gradually decreased from 18.6% to 0.06% and from 0.58% to 0.02% during the period of 1964 to 2010, respectively. When the current data from 2009 to 2012 were analyzed, the occurrence of fasciolosis was recognized in cattle produced and fattened all over Japan, indicating the disease was prevalent nationwide. While, 97.5% of Eurytrema infection were detected in cattle produced in Okinawa, Shimane and Kagoshima, indicating the disease was endemic in these regions. Higher occurrence (>0.7%) of fasciolosis was observed in minor breeds, such as Japanese Shorthorn. Japanese Black showed 0.09% and 0.05% of occurrence for fasciolosis and eurytremosis, respectively, but F1 crossbred with Japanese Black showed lower occurrence (0.007% and 0.002%, respectively). No tendency of occurrence in the age of cattle at slaughter was recognized, indicating the infections may have occurred at the growing and early fattening stage of cattle. The questionnaire survey revealed that farmers experiencing fasciolosis had more knowledge about the disease, however, factors, such as testing parasite infections and use of anti-Fasciola dewormers, were not affected by the recognition of occurrence.


Asunto(s)
Enfermedades de los Bovinos/parasitología , Fascioliasis/veterinaria , Infecciones por Trematodos/veterinaria , Mataderos , Animales , Bovinos/parasitología , Enfermedades de los Bovinos/epidemiología , Fascioliasis/epidemiología , Femenino , Japón/epidemiología , Masculino , Encuestas y Cuestionarios , Infecciones por Trematodos/epidemiología
10.
Opt Express ; 22 Suppl 1: A90-8, 2014 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-24922003

RESUMEN

The breakdown plasma and successive flow leading to combustion are controlled by the combination of a nano-second Nd:YAG laser and a femto-second Ti:Sapphire (TiS) laser. The behaviors are captured by an intensified charged coupled device (ICCD) camera and a high-speed schlieren optical system. The TiS laser determines the initial position of the breakdown by supplying the initial electrons in the optical axis of focusing YAG laser pulses. We show that the initial position of the breakdown can be controlled by the incident position of the TiS laser. In addition, the ignition lean limit of the flammable mixture changes depending on the TiS laser incident position, which is influenced by hot gas distribution and the flow in the flame kernel.

11.
Phys Rev Lett ; 105(7): 075004, 2010 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-20868054

RESUMEN

A three-dimensional simulation of laser-guided discharges based on percolation is presented. The model includes both local growth of a streamer due to the enhanced electric field at the streamer's tip and propagation of a leader by remote ionization such as that caused by runaway electrons. The stochastic behavior of the discharge through a preformed plasma channel is reproduced by the calculation, which shows complex path with detouring and bifurcation. The probability of guiding is investigated with respect to the ionized, conductive fraction along the channel.

12.
J Mol Cell Cardiol ; 43(6): 710-6, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17961593

RESUMEN

Leukemia inhibitory factor (LIF), a cardiac hypertrophic cytokine, increases L-type Ca(2+) current (I(CaL)) via ERK-dependent and PKA-independent phosphorylation of serine 1829 in the Cav(1.2) subunit. The signaling cascade through gp130 is involved in this augmentation. However, there are two major cascades downstream of gp130, i.e. JAK/STAT3 and SHP2/ERK. In this study, we attempted to clarify which of these two cascades plays a more important role. Knock-in mouse line, in which the SHP2 signal was disrupted (gp130(F759/F759) group), and wild-type mice (WT group) were used. A whole-cell patch clamp experiment was performed, and intracellular Ca(2+) concentration ([Ca(2+)](i) transient) was monitored. The I(CaL) density and [Ca(2+)](i) transient were measured from the untreated cells and the cells treated with LIF or IL-6 and soluble IL-6 receptor (IL-6+sIL-6r). Action potential duration (APD) was also recorded from the ventricle of each mouse, with or without LIF. Both LIF and IL-6+sIL-6r increased I(CaL) density significantly in WT (+27.0%, n=16 p<0.05, and +32.2%, n=15, p<0.05, respectively), but not in gp130(F759/F759) (+9.4%, n=16, NS, and -6.1%, n=13, NS, respectively). Administration of LIF and IL-6+sIL-6r increased [Ca(2+)](i) transient significantly in WT (+18.8%, n=13, p<0.05, and +32.0%, n=21, p<0.05, respectively), but not in gp130(F759/F759) (-3.8%, n=7, NS, and -6.4%, n=10, NS, respectively). LIF prolonged APD(80) significantly in WT (10.5+/-4.3%, n=12, p<0.05), but not in gp130(F759/F759) (-2.1+/-11.2%, n=7, NS). SHP2-mediated signaling cascade is essential for the LIF and IL-6+sIL-6r-dependent increase in I(CaL), [Ca(2+)](i) transient and APD.


Asunto(s)
Potenciales de Acción/efectos de los fármacos , Canales de Calcio Tipo L/metabolismo , Señalización del Calcio/efectos de los fármacos , Receptor gp130 de Citocinas/metabolismo , Factor Inhibidor de Leucemia/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/enzimología , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Animales , Flavonoides/farmacología , Humanos , Interleucina-6/metabolismo , Ratones
13.
Opt Express ; 15(5): 2535-40, 2007 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-19532490

RESUMEN

Broad Raman-multi-frequency spectra were generated from the resonant two-color excitation of the deuterium molecule rotational Raman transition (J=0?2), using ultraviolet bi-harmonic lasers with a quartz hollow fiber. Fifty pure rotational Raman spectral lines (34 lines that have intensity within 10% of the strongest spectral line) from 230 to 290 nm were generated at a gas pressure of 30 kPa. Furthermore, vibrational-rotational Raman spectral lines of almost 300 lines from 220 to 600 nm were also generated by increasing the gas pressure to 60 kPa.

14.
Science ; 313(5792): 1426-8, 2006 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-16873612

RESUMEN

Volcanism on Earth is known to occur in three tectonic settings: divergent plate boundaries (such as mid-ocean ridges), convergent plate boundaries (such as island arcs), and hot spots. We report volcanism on the 135 million-year-old Pacific Plate not belonging to any of these categories. Small alkalic volcanoes form from small percent melts and originate in the asthenosphere, as implied by their trace element geochemistry and noble gas isotopic compositions. We propose that these small volcanoes erupt along lithospheric fractures in response to plate flexure during subduction. Minor extents of asthenospheric melting and the volcanoes' tectonic alignment and age progression in the direction opposite to that of plate motion provide evidence for the presence of a small percent melt in the asthenosphere.

15.
Nature ; 436(7052): 837-40, 2005 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-16100780

RESUMEN

The Hawaiian-Emperor volcanic island and seamount chain is usually attributed to a hot mantle plume, located beneath the Pacific lithosphere, that delivers material sourced from deep in the mantle to the surface. The shield volcanoes of the Hawaiian islands are distributed in two curvilinear, parallel trends (termed 'Kea' and 'Loa'), whose rocks are characterized by general geochemical differences. This has led to the proposition that Hawaiian volcanoes sample compositionally distinct, concentrically zoned, regions of the underlying mantle plume. Melt inclusions, or samples of local magma 'frozen' in olivine phenocrysts during crystallization, may record complexities of mantle sources, thereby providing better insight into the chemical structure of plumes. Here we report the discovery of both Kea- and Loa-like major and trace element compositions in olivine-hosted melt inclusions in individual, shield-stage Hawaiian volcanoes--even within single rock samples. We infer from these data that one mantle source component may dominate a single lava flow, but that the two mantle source components are consistently represented to some extent in all lavas, regardless of the specific geographic location of the volcano. We therefore suggest that the Hawaiian mantle plume is unlikely to be compositionally concentrically zoned. Instead, the observed chemical variation is probably controlled by the thermal structure of the plume.

16.
Circ Res ; 94(9): 1242-8, 2004 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-15044319

RESUMEN

We have previously reported that leukemia inhibitory factor (LIF) gradually increased cardiac L-type Ca2+ channel current (I(CaL)), which peaked at 15 minutes in both adult and neonatal rat cardiomyocytes, and this increase was blocked by the mitogen-activated protein kinase kinase inhibitor PD98059. This study investigated the molecular basis of LIF-induced augmentation of I(CaL) in rodent cardiomyocytes. LIF induced phosphorylation of a serine residue in the alpha(1c) subunit (Ca(v)1.2) of L-type Ca2+ channels in cultured rat cardiomyocytes, and this phosphorylation was inhibited by PD98059. When constructs encoding either a wild-type or a carboxyl-terminal-truncated rabbit Ca(v)1.2 subunit were transfected into HEK293 cells, LIF induced phosphorylation of the resultant wild-type protein but not the mutant protein. Cotransfection of constitutively active mitogen-activated protein kinase kinase also resulted in phosphorylation of the Ca(v)1.2 subunit in the absence of LIF stimulation. In in-gel kinase assays, extracellular signal-regulated kinase phosphorylated a glutathione S-transferase fusion protein of the carboxyl-terminal region of Ca(v)1.2 (residues 1700 through 1923), which contains the consensus sequence Pro-Leu-Ser-Pro. A point mutation within this consensus sequence, which results in a substitution of alanine for serine at residue 1829 (S1829A), was sufficient to abolish the LIF-induced phosphorylation. LIF increased I(CaL) in HEK cells transfected with wild-type Ca(v)1.2 but not with the mutated version. These results provide direct evidence that LIF phosphorylates the serine residue at position 1829 of the Ca(v)1.2 subunit via the actions of extracellular signal-regulated kinase and that this phosphorylation increases I(CaL) in cardiomyocytes.


Asunto(s)
Canales de Calcio Tipo L/efectos de los fármacos , Interleucina-6/fisiología , Miocitos Cardíacos/efectos de los fármacos , Sustitución de Aminoácidos , Angiotensina II/farmacología , Animales , Animales Recién Nacidos , Aorta , Calcio/metabolismo , Canales de Calcio Tipo L/química , Canales de Calcio Tipo L/genética , Canales de Calcio Tipo L/metabolismo , Línea Celular , Células Cultivadas/efectos de los fármacos , Células Cultivadas/metabolismo , Secuencia de Consenso , Flavonoides/farmacología , Humanos , Interleucina-6/farmacología , Riñón , Factor Inhibidor de Leucemia , MAP Quinasa Quinasa 1 , Quinasas de Proteína Quinasa Activadas por Mitógenos/fisiología , Músculo Liso Vascular/citología , Miocitos Cardíacos/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Técnicas de Placa-Clamp , Fosforilación/efectos de los fármacos , Fosfoserina/análisis , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Estructura Terciaria de Proteína , Conejos , Ratas , Ratas Wistar , Proteínas Recombinantes/farmacología , Eliminación de Secuencia , Especificidad de la Especie , Transfección
17.
Hypertension ; 41(6): 1372-9, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12719447

RESUMEN

Both integrin-based focal adhesion complexes and receptor tyrosine kinases have been proposed as scaffolds on which the G protein-coupled receptor (GPCR)-induced signaling complex might assemble. We have recently reported that Ca2+-sensitive tyrosine kinase, Pyk2, and epidermal growth factor receptor (EGFR) act as independently regulated scaffolds in cardiomyocytes. In this report, we investigated the activation and regulation of p130Cas, Crk, Pyk2, and c-Src by a well-known hypertrophic agonist, endothelin-1 (ET), and determined their contributions to the activation of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in cardiomyocytes. Like Pyk2, ET-induced tyrosine phosphorylation of p130Cas was significantly inhibited by either chelating intracellular Ca2+ ([Ca2+]i) or a protein kinase C inhibitor, calphostin C. This activation of p130Cas was also abrogated by the tetrapeptide RGDS, which disrupts integrin heterodimerization; cytochalasin D, which depolymerizes the actin cytoskeleton; or a selective Src family kinase inhibitor, PP2, but not by an EGFR inhibitor, AG1478. We also observed ET-induced temporal associations of Pyk2 with active c-Src, followed by p130Cas with Pyk2, c-Src, and Crk. Overexpression of a dominant-negative mutant of p130Cas (CasDeltaSD), Crk (CrkSH2m), Pyk2 (PKM), or C-terminal Src kinase (Csk), but not of a deletion mutant of EGFR (533delEGFR), attenuated ET-induced JNK activation. Similarly, an ET-induced increase in c-jun promoter luciferase activity was inhibited by overexpression of CasDeltaSD, CrkSH2m, PKM, or Csk. In contrast, ET-induced ERK activation and c-fos gene expression were predominantly regulated by EGFR. Collectively, the focal adhesion-dependent p130Cas/Crk/Pyk2/c-Src-mediated pathway is selectively involved in ET-induced JNK activation in cardiomyocytes.


Asunto(s)
Endotelina-1/farmacología , Sistema de Señalización de MAP Quinasas , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Miocitos Cardíacos/enzimología , Proteínas , Animales , Proteína Tirosina Quinasa CSK , Calcio/fisiología , Células Cultivadas , Proteína Sustrato Asociada a CrK , Activación Enzimática , Quinasa 2 de Adhesión Focal , Adhesiones Focales/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos , Mutación , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/fisiología , Fosforilación , Proteína Quinasa C/fisiología , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/fisiología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/fisiología , Proteínas Proto-Oncogénicas c-crk , Proteínas Proto-Oncogénicas pp60(c-src)/fisiología , Ratas , Ratas Wistar , Proteína p130 Similar a la del Retinoblastoma , Activación Transcripcional , Tirosina/metabolismo , Familia-src Quinasas
18.
Proc Natl Acad Sci U S A ; 99(11): 7548-53, 2002 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-12032320

RESUMEN

Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of Shh is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse mutant sasquatch (Ssq). The genetic lesions in both lie within the same respective intron of the LMBR1/Lmbr1 gene, which resides approximately 1 Mb away from Shh. Genetic analysis of Ssq reveals that the Lmbr1 gene is incidental to the phenotype and that the mutation directly interrupts a cis-acting regulator of Shh. This regulator is most likely the target for generating PPD mutations in human.


Asunto(s)
Intrones , Proteínas de la Membrana/genética , Polidactilia/genética , Transactivadores/genética , Animales , Clonación Molecular , Cruzamientos Genéticos , Proteínas Hedgehog , Heterocigoto , Humanos , Hibridación Fluorescente in Situ , Ratones , Mutación , Fenotipo , Recombinación Genética , Mapeo Restrictivo , Translocación Genética
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