We develop and validate a new algorithm called
primary track recovery
(ptr) that effectively deconvolves known physics and detector effects from nuclear recoil tracks in gas time projection chambers ...(TPCs) with high-resolution readout. This gives access to the primary track charge, length, and vector direction (helping to resolve the “head-tail” ambiguity). Additionally, ptr provides a measurement of the transverse and longitudinal diffusion widths, which can be used to determine the absolute position of tracks in the drift direction for detector fiducialization. Using simulated helium recoils in an atmospheric pressure TPC with a 70:30 mixture of
He:CO
2
we compare the performance of ptr to traditional methods for all key track variables. We find that the algorithm reduces reconstruction errors, including those caused by charge integration, for tracks with mean length-to-width ratios 1.4 and above, corresponding to recoil energies of 20 keV and above in the studied TPCs. We show that ptr improves on existing methods for head-tail disambiguation, particularly for highly inclined tracks, and improves the determination of the absolute position of recoils on the drift axis via transverse diffusion. We find that ptr can partially recover charge structure integrated out by the detector in the
z
direction, but that its determination of energy and length have worse resolution compared to existing methods. We use experimental data to qualitatively verify these findings and discuss implications for future directional detectors at the low-energy frontier.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report on the design, production, and performance of compact 40-cm3 Time Projection Chambers (TPCs) that detect fast neutrons by measuring the three-dimensional (3D) ionization distribution of ...nuclear recoils in 4He:CO2 gas at atmospheric pressure. We use these detectors to characterize the fast-neutron flux inside the Belle II detector at the SuperKEKB electron–positron collider in Tsukuba, Japan, where the primary design constraint is a small form factor. We find that the TPCs meet or exceed all design specifications, and are capable of measuring the 3D surface shape and charge density profile of ionization clouds from nuclear recoils and charged tracks in exquisite detail. Scaled-up detectors based on the detection principle demonstrated here may be suitable for directional dark matter searches, measurements of coherent neutrino–nucleus scattering, and other experiments requiring precise detection of neutrons or nuclear recoils.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present the first measurements of absolute branching fractions of Ξ_{c}^{0} decays into Ξ^{-}π^{+}, ΛK^{-}π^{+}, and pK^{-}K^{-}π^{+} final states. The measurements are made using a dataset ...comprising (772±11)×10^{6} BBover ¯ pairs collected at the ϒ(4S) resonance with the Belle detector at the KEKB e^{+}e^{-} collider. We first measure the absolute branching fraction for B^{-}→Λover ¯_{c}^{-}Ξ_{c}^{0} using a missing-mass technique; the result is B(B^{-}→Λover ¯_{c}^{-}Ξ_{c}^{0})=(9.51±2.10±0.88)×10^{-4}. We subsequently measure the product branching fractions B(B^{-}→Λover ¯_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→Ξ^{-}π^{+}), B(B^{-}→Λover ¯_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→ΛK^{-}π^{+}), and B(B^{-}→Λover ¯_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+}) with improved precision. Dividing these product branching fractions by the result for B^{-}→Λover ¯_{c}^{-}Ξ_{c}^{0} yields the following branching fractions: B(Ξ_{c}^{0}→Ξ^{-}π^{+})=(1.80±0.50±0.14)%, B(Ξ_{c}^{0}→ΛK^{-}π^{+})=(1.17±0.37±0.09)%, and B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+})=(0.58±0.23±0.05)%. For the above branching fractions, the first uncertainties are statistical and the second are systematic. Our result for B(Ξ_{c}^{0}→Ξ^{-}π^{+}) can be combined with Ξ_{c}^{0} branching fractions measured relative to Ξ_{c}^{0}→Ξ^{-}π^{+} to yield other absolute Ξ_{c}^{0} branching fractions.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
We report the first observation of the radiative decay of the ϒ(1S) into a charmonium state. The significance of the observed signal of ϒ(1S)→γχ_{c1} is 6.3 standard deviations including systematics. ...The branching fraction is calculated to be Bϒ(1S)→γχ_{c1}=4.7_{-1.8}^{+2.4}(stat)_{-0.5}^{+0.4}(sys)×10^{-5}. We also searched for ϒ(1S) radiative decays into χ_{c0,2} and η_{c}(1S,2S), and set upper limits on their branching fractions. These results are obtained from a 24.9 fb^{-1} data sample collected with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider at a center-of-mass energy equal to the ϒ(2S) mass using ϒ(1S) tagging by the ϒ(2S)→ϒ(1S)π^{+}π^{-} transitions.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
An abstract of the study conducted by Zeitoni et al presenting the current status of a database with more than 400 PDX covering major cancer types and have been extensively characterized for ...histological features, molecular data, and for tumor growth with sensitivity to relevant standard-of-care compounds and targeted therapies. Among other things, Zeitoni et al added that the availability of well-characterized preclinical tumor models with histological and molecular data improves the selection of appropriate models for in vivo/in vitro drug testing and is essential to increase the success rate of preclinical studies and facilitate predictive biomarker discovery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A
bstract
Using a data sample of 980 fb
−
1
collected with the Belle detector at the KEKB asymmetric-energy
e
+
e
−
collider, we study for the first time the singly Cabibbo-suppressed decays
Ω
c
0
→
...Ξ
−
π
+
and Ω
−
K
+
and the doubly Cabibbo-suppressed decay
Ω
c
0
→
Ξ
−
K
+
. Evidence for an
Ω
c
0
signal in the
Ω
c
0
→
Ξ
−
π
+
mode is reported with a significance of 4
.
5
σ
including systematic uncertainties. The ratio of branching fractions to the normalization mode
Ω
c
0
→
Ω
−
π
+
is measured to be
B
Ω
c
0
→
Ξ
−
π
+
/
B
Ω
c
0
→
Ω
−
π
+
=
0.253
±
0.052
stat
.
±
0.030
syst
.
.
No significant signals of
Ω
c
0
→
Ξ
−
K
+
and Ω
−
K
+
modes are found. The upper limits at 90% confidence level on ratios of branching fractions are determined to be
B
Ω
c
0
→
Ξ
−
K
+
/
B
Ω
c
0
→
Ω
−
π
+
<
0.070
and
B
Ω
c
0
→
Ω
−
K
+
/
B
Ω
c
0
→
Ω
−
π
+
<
0.29
.
IntroductionPatient-derived xenograft (PDX) models emulate tumour complexity and heterogeneity, and reflect the variation in pathologic and genetic diversity within the population. As such, these ...models are a valuable source in preclinical drug development. We employ hydrogel embedding as a 3D culture technique to generate short term cultures of dissociated PDX material. This miniaturised setup allows economical screening of drug libraries, testing of drug combinations and pre-selection of relevant models for in vivo follow up.Material and methodsIn a high throughput approach, small amounts of tumour material are seeded in 384 well plates. Following exposure to multiple concentrations of standard-of-care chemotherapeutics, small molecules, targeted therapies, antibodies and antibody-drug-conjugate, the cultures are fixed and stained with cellular markers at the experimental endpoint. A 3D stack acquisition of each well is obtained, followed by high content image analysis using an in-house developed analysis platform, OminerTM. This enables measurement of relevant features such as tumour volume, tumour invasion, nucleus size and fraction of apoptotic cells; hence detailed tumour culture responses can be quantified, generating dose-dependent profiles for selected features.Results and discussionsWe successfully developed >50 cultures derived from breast, stomach, pancreatic, colon, bladder and lung cancer. Each model has unique growth characteristics and morphologic differences are prominent both between the different tissues of origin and similar pathologies. Histologic characterisation of the 3D tumour cultures show hallmarks of the original tumour, such as retention of relevant biomarkers. We present drug response data for various cancer indications, including multiple lung and breast cancer pathologies.ConclusionWe demonstrate phenotypic variation amongst different PDX models and differential responses to anti-tumour therapies. This method facilitates the comparison and in depth interrogation of responses to both established, biosimilar and novel cancer drugs - and allows follow up in the same model in vivo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
IntroductionIn vitro cell based drug testing tools have been widely used in drug discovery and early development to evaluate novel drug entities for further evaluation in preclinical in vivo models. ...However, the question on how closely these systems resemble and recapitulate the original tumours has prompted researchers and clinical oncologists to seek complementary in vitro strategies. Patient-derived xenograft (PDX) mouse models are a widely accepted tool for propagation of primary human tumour specimens, faithfully preserving the biological features and the genetic expression profiles.In order to increase accessibility of these physiological relevant tumour surrogates in drug development, we investigated whether ex-vivo culturing of PDX-derived tumours as 3D Microtissues retain the in-vivotumour characteristics. The resulting 3D PDX Tumour Microtissues will increase throughput and compatibility with existing platforms while reducing costs and animal testing.Material and methodsTo this end, PDX cell suspensions of Lung, Breast and Melanoma origin were used to aggregated in Akura 96 plates and characterised over 10 days in culture. The 3D tumour microtissues were monitored for growth characteristics, phenotype, cancer biomarkers and drug efficacy. In addition to screening for standard diagnostic marker for proliferating (Ki67), apoptotic cells (cleaved Caspase 3), stromal (FAP) and epithelial-tumour cells (pan-CK, E-Cadherin), we also assessed the expression of cancer type specific biomarkers. Immunohistochemistry assessment of 3D tumour microtissues demonstrated the resemblance with the respective in-vivo PDX tumour model. The viability and growth rate of PDX-derived tumour microtissues was assessed by size analysis and ATP assay. 3D tumour growth rate reflected the diversity of tumour growth progression in vivo. Subsequently, these tumour microtissues were assessed using either non-specific cytotoxic drugs or molecular-targeted drug therapy in a single agent treatment regimen. The efficacy of specific targeted therapies was based on the distinct molecular signatures of PDX tumour models.Results and discussionsIn conclusion, in vitro 3D InSight Tumour Microtissues from patient-derived xenograft (PDX) lines demonstrated retention of morphological and molecular features of the parental tumours.ConclusionWe suggest that 3D PDX Tumour Microtissues are physiological relevant and higher throughput compatible in vitro models for efficacy assessment and drug candidate screenings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A
bstract
We report the first measurement of the exclusive cross sections
e
+
e
−
→
B
B
¯
,
e
+
e
−
→
B
B
¯
∗
, and
e
+
e
−
→
B
∗
B
¯
∗
in the energy range from 10
.
63 GeV to 11
.
02 GeV. The
B
...mesons are fully reconstructed in a large number of hadronic final states and the three channels are identified using a beam-constrained-mass variable. The shapes of the exclusive cross sections show oscillatory behavior with several maxima and minima. The results are obtained using data collected by the Belle experiment at the KEKB asymmetric-energy
e
+
e
−
collider.
Into the Winter Whiteness Schueler, Matthew J.
Clinical infectious diseases,
02/2012, Volume:
54, Issue:
suppl_1
Journal Article
Peer reviewed
Open access
A father recounts a transformative journey of love, loss, and learning as his son developed and eventually died of a fungal infection that occurred during a period of immunocompromise after a bone ...marrow transplantation to treat hypodiploid leukemia. He then thanks the many physicians, researchers, family members, and friends who came together to memorialize his son and create knowledge, hope, and wisdom, so that others will not have to suffer a similar journey.
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