In a patient with permanent neonatal syndromic diabetes clinically similar to cases with ONECUT1 biallelic mutations, we identified a disease-causing deletion located upstream of ONECUT1. Through genetic, genomic, and functional studies, we identified a crucial regulatory region acting as an enhancer of ONECUT1 specifically during pancreatic development. This enhancer region contains a low-frequency variant showing a strong association with type 2 diabetes and other glycemic traits, thus extending the contribution of this region to common forms of diabetes.
View Article and Find Full Text PDFWithin the pancreas, Keratin 19 (KRT19) labels the ductal lineage and is a determinant of pancreatic ductal adenocarcinoma (PDAC). To investigate KRT19 expression dynamics, we developed a human pluripotent stem cell (PSC)-based KRT19-mCherry reporter system in different genetic backgrounds to monitor KRT19 expression from its endogenous gene locus. A differentiation protocol to generate mature pancreatic duct-like organoids was applied.
View Article and Find Full Text PDFBackground: The reactivation of genetic programs from early development is a common mechanism for injury-induced organ regeneration. T-box 3 (TBX3) is a member of the T-box family of transcription factors previously shown to regulate pluripotency and subsequent lineage commitment in a number of tissues, including limb and lung. TBX3 is also involved in lung and heart organogenesis.
View Article and Find Full Text PDFPatient-derived induced pluripotent stem cells (iPSCs) provide a unique platform to study hereditary disorders and predisposition syndromes by resembling germline mutations of affected individuals and by their potential to differentiate into nearly every cell type of the human body. We employed plucked human hair from two siblings with a family history of cancer carrying a pathogenic variant, P16-p.G101W/P14-p.
View Article and Find Full Text PDFProton therapy is an expanding radiotherapy modality in the United States and worldwide. With the number of proton therapy centers treating patients increasing, so does the need for consistent, high-quality clinical commissioning practices. Clinical commissioning encompasses the entire proton therapy system's multiple components, including the treatment delivery system, the patient positioning system, and the image-guided radiotherapy components.
View Article and Find Full Text PDFS100 proteins are widely expressed small molecular EF-hand calcium-binding proteins of vertebrates, which are involved in numerous cellular processes, such as Ca homeostasis, proliferation, apoptosis, differentiation, and inflammation. Although the complex network of S100 signalling is by far not fully deciphered, several S100 family members could be linked to a variety of diseases, such as inflammatory disorders, neurological diseases, and also cancer. The research of the past decades revealed that S100 proteins play a crucial role in the development and progression of many cancer types, such as breast cancer, lung cancer, and melanoma.
View Article and Find Full Text PDFIn proton therapy delivered with range modulated beams, the energy spectrum of protons entering the delivery nozzle can affect the dose uniformity within the target region and the dose gradient around its periphery. For a cyclotron with a fixed extraction energy, a rangeshifter is used to change the energy but this produces increasing energy spreads for decreasing energies. This study investigated the magnitude of the effects of different energy spreads on dose uniformity and distal edge dose gradient and determined the limits for controlling the incident spectrum.
View Article and Find Full Text PDFCalculations of dose per monitor unit (D/MU) are required in addition to measurements to increase patient safety in the clinical practice of proton radiotherapy. As in conventional photon and electron therapy, the D/MU depends on several factors. This study focused on obtaining range and modulation dependence factors used in D/MU calculations for the double scattered proton beam line at the Midwest Proton Radiotherapy Institute.
View Article and Find Full Text PDFA proton beam delivery system on a gantry with continuous uniform scanning and dose layer stacking at the Midwest Proton Radiotherapy Institute has been commissioned and accepted for clinical use. This paper was motivated by a lack of guidance on the testing and characterization for clinical uniform scanning systems. As such, it describes how these tasks were performed with a uniform scanning beam delivery system.
View Article and Find Full Text PDFBackground: Protons beams deliver targeted radiation doses with greater precision than is possible with electrons or megavoltage X-ray photons, but to retain this advantage, patient positioning systems at proton clinics must meet tighter accuracy requirements. For this and other reasons, robots were incorporated into the treatment room systems at MPRI.
Methods: The Midwest Proton Radiotherapy Institute (MPRI) is the first radiotherapy facility in the United States to use commercial robots with six degrees of freedom for patient positioning, rather than a traditional bed with four degrees of freedom.
We describe a double-scattering experiment with a novel tagged neutron beam to measure differential cross sections for np backscattering to better than +/-2% absolute precision. The measurement focuses on angles and energies where the cross section magnitude and angle dependence constrain the charged pion-nucleon coupling constant, but existing data show serious discrepancies among themselves and with energy-dependent partial-wave analyses. The present results are in good accord with the partial-wave analyses, but deviate systematically from other recent measurements.
View Article and Find Full Text PDFWe report on the first determination of upper limits on the branching ratio (BR) of eta decay to pi0pi0gamma and to pi0pi0pi0gamma. Both decay modes are strictly forbidden by charge conjugation (C) invariance. Using the Crystal Ball multiphoton detector, we obtained BR(eta-->pi0pi0gamma)<5 x 10(-4) at the 90% confidence level, in support of C invariance of isoscalar electromagnetic interactions of the light quarks.
View Article and Find Full Text PDFData from the first physics run at the Relativistic Heavy-Ion Collider at Brookhaven National Laboratory, Au+Au collisions at sqrt[s(NN)]=130 GeV, have been analyzed by the STAR Collaboration using three-pion correlations with charged pions to study whether pions are emitted independently at freeze-out. We have made a high-statistics measurement of the three-pion correlation function and calculated the normalized three-particle correlator to obtain a quantitative measurement of the degree of chaoticity of the pion source. It is found that the degree of chaoticity seems to increase with increasing particle multiplicity.
View Article and Find Full Text PDFWe report the first observation of the charge symmetry breaking d+d-->4He+pi(0) reaction near threshold. Measurements using a magnetic channel (gated by two photons) of the 4He scattering angle and momentum (from time of flight) permitted reconstruction of the pi(0) "missing mass," the quantity used to separate 4He+pi(0) events from the continuum of double radiative capture 4He+gamma+gamma events. We measured total cross sections for neutral pion production of 12.
View Article and Find Full Text PDFData are presented for the reaction pi(-)p-->pi(0)pi(0)n in the range from threshold to p(pi(-))=750 MeV/c. The systematics of the data and multipole analyses are examined for sensitivity to a f(0)(600) ("sigma") meson. A one-pion-exchange mechanism is found to be very weak, or absent.
View Article and Find Full Text PDFThe balance function is a new observable based on the principle that charge is locally conserved when particles are pair produced. Balance functions have been measured for charged particle pairs and identified charged pion pairs in Au+Au collisions at the square root of SNN = 130 GeV at the Relativistic Heavy Ion Collider using STAR. Balance functions for peripheral collisions have widths consistent with model predictions based on a superposition of nucleon-nucleon scattering.
View Article and Find Full Text PDFAzimuthal correlations for large transverse momentum charged hadrons have been measured over a wide pseudorapidity range and full azimuth in Au+Au and p+p collisions at sqrt[s(NN)]=200 GeV. The small-angle correlations observed in p+p collisions and at all centralities of Au+Au collisions are characteristic of hard-scattering processes previously observed in high-energy collisions. A strong back-to-back correlation exists for p+p and peripheral Au+Au.
View Article and Find Full Text PDFPhys Rev Lett
January 2003
Azimuthal anisotropy (v(2)) and two-particle angular correlations of high p(T) charged hadrons have been measured in Au+Au collisions at sqrt[s(NN)]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high p(T) partons. The monotonic rise of v(2)(p(T)) for p(T)<2 GeV/c is consistent with collective hydrodynamical flow calculations.
View Article and Find Full Text PDFThe STAR Collaboration reports the first observation of exclusive rho(0) photoproduction, AuAu-->AuAurho(0), and rho(0) production accompanied by mutual nuclear Coulomb excitation, AuAu-->Au*Au*rho(0), in ultraperipheral heavy-ion collisions. The rho(0) have low transverse momenta, consistent with coherent coupling to both nuclei. The cross sections at sqrt[s(NN)]=130 GeV agree with theoretical predictions treating rho(0) production and Coulomb excitation as independent processes.
View Article and Find Full Text PDFInclusive transverse momentum distributions of charged hadrons within 0.2
We report STAR results on the azimuthal anisotropy parameter v(2) for strange particles K(0)(S), Lambda, and Lambda at midrapidity in Au+Au collisions at sqrt[s(NN)]=130 GeV at the Relativistic Heavy Ion Collider. The value of v(2) as a function of transverse momentum, p(t), of the produced particle and collision centrality is presented for both particles up to p(t) approximately 3.0 GeV/c.
View Article and Find Full Text PDFWe report the first measurement of strange (Lambda) and antistrange (Lambda macro) baryon production from square root of [s(NN)]=130 GeV Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Rapidity density and transverse mass distributions at midrapidity are presented as a function of centrality. The yield of Lambda and Lambda; hyperons is found to be approximately proportional to the number of negative hadrons.
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