gebhart/patrepeval huggingface dataset:
Label-free three-dimensional imaging and quantitative analysis of long-term on-chip vasculogenesis using optical diffraction tomography (2021)

Three-dimensional (3D), label-free, and long-term imaging in organ-on-a-chip research is necessary to assess the dynamic development of multicellular structures inside a microfluidic chip and relevant physiological functions. However, imaging on-chip multicellular landscapes generally relies on the use of exogenous labels, which limits the long-term imaging of live cells due to photobleaching and phototoxicity. Here, we demonstrate the 3D label-free observation of 5-day on-chip vasculogenesis of human umbilical vein endothelial cells using optical diffraction tomography. The proposed method enables us to quantify both morphological and biochemical alterations during the vasculogenesis.
Creating xBD: A Dataset for Assessing Building Damage from Satellite Imagery (2019)

We present a preliminary report for xBD, a new large-scale dataset for the advancement of change detection and building damage assessment for humanitarian assistance and disaster recovery research.<br>Logistics, resource planning, and damage estimation are difficult tasks after a disaster, and putting first responders into post-disaster situations is dangerous and costly.<br>Using passive methods, such as analysis on satellite imagery, to perform damage assessment saves manpower, lowers risk, and expedites an otherwise dangerous process.<br>xBD provides pre- and post-event multi-band satellite imagery from a variety of disaster events with building polygons, classification labels for damage types, ordinal labels of damage level, and corresponding satellite metadata.<br>Furthermore, the dataset contains bounding boxes and labels for environmental factors such as fire, water, and smoke.<br>xBD will be the largest building damage assessment dataset to date, containing $\sim$700,000 building annotations across over 5,000 km\textsuperscript{2} of imagery from 15 countries.
A Cluster-Based Neuromorphic ISFET Architecture with Integrated Calibration (2020)

We design an Ion-Sensitive Field-Effect (ISFET) array leveraging on the two successful fields of neuromorphic electronics and chemical sensing to encode the signal in spikes and perform sensor processing between neighbouring pixels. The array is structured as clusters integrating 4 × 4 pixels with sensor compensation, taking advantage of spatial correlation of sensor non-idealities. The offset compensation is capable of calibrating in a range of 662 mV. The system shows a robust, scalable and power efficient architecture with a sensitivity ranging from 2.56 MHz/pH to 3.38 MHz/pH. The pixel occupies an area of 30μm × 24μm, and the cluster area is 205 μm × 205 μm. The layout of each pixel is spread out with digital blocks embedded in-between, which improves signal coupling by enlarging the chemical sensing area of each pixel. The system readout implements address event representation (AER) for triggering the outputs.
Two-photon recording of stable luminescent centers in chromone-doped polymer films (2014)

The study defines threshold values of energy density required for two-photon writing of stable fluorescent bit patterns within polymer layers containing chromones class chemical compounds by visual laser pulses in range of pulse widths from nanoseconds to femtoseconds. Photo-regrouping of non-luminescent chromones to fluorescent products is shown as the result of true type two-photon absorption (TPA) and stepwise TPA as well. In the latter case writing beam fluence can be reduced due to increase of the effective TPA coefficient, but laser-induced thermal damage of matrix becomes more probable too.
Multiphoton ionization of vinylchloride, trifluoroethylene, and benzene at 193 nm (1987)

The multiphoton ionization–fragmentation pattern of vinylchloride, trifluoroethylene and benzene has been measured at 193 nm using time-of-flight mass spectrometry and gas chromatographic analysis. Relative cross sections for multiphoton ionization and the laser power dependence have been determined for the three species at 193 nm at low laser fluence (&amp;lt;10 mJ/cm2) and relative cross sections for multiphoton ionization of benzene have been obtained at 193 and 248 nm. The dominant fragmentation and ionization channels in the two substituted ethylenes are discussed.
Preliminary Experience with Nonthoracotomy Implantahle Cardioverter Defihrillators in Young Patients (1994)

Implantable cardioverter defibrillators represent an important treatment option for patients with life-threatening tachyarrhythmias. However, the requirement for surgical access to the thorax contributes to significant procedural morbidity with ICD implantation. This study was performed to assess an initial experience with a nonthoracotomy approach to ICD lead implantation in young patients. An international survey identified 17 patients, ranging in age from 12-20 years (mean = 16.7 +/- 2.4) and weighing from 33-89 kg (mean = 60.6 +/- 13.3), who had undergone placement of the Medtronic Transvene defibrillator lead system. Implant indications were aborted sudden cardiac death in 15 patients and recurrent ventricular tachycardia or familial sudden death in 2 patients. At a median follow-up of 7.9 months, 9 of 17 patients had received at least one ICD therapy. There have been no deaths. Complications included patch or generator erosion (3 patients), lead dislodgement (1 patient), and ICD system infection requiring explanation (1 patient). The initial experience with nonthoracotomy ICDs in young patients appears promising. This approach may be particularly advantageous for patients who have undergone prior thoracotomy. Prospective clinical trials will be required to establish the applicability of these lead systems to select patient populations.
Electrical Properties, Deep Levels and Luminescence Related to Fe in Bulk Semi-Insulating β-Ga<sub>2</sub>O<sub>3</sub> Doped with Fe (2019)

Electrical properties, deep trap spectra, microcathodoluminescence (MCL) and photoluminescence (PL) spectra of bulk semi-insulating Fe doped β-Ga2O3 crystals with ohmic and Schottky contacts were studied. The Fermi level in these crystals is pinned by the Fe acceptor level near Ec-0.8 eV. This level is also dominant in high-temperature admittance spectra and in photo-induced current transient spectroscopy (PICTS) and determines the space charge region width in Schottky diodes. The concentration of the Fe acceptors filled with electrons is (1.3–1.5) × 1017 cm−3 from high-temperature/low-frequency capacitance-voltage C-V profiling and is considerably lower than the Fe concentration introduced by doping, suggesting that a considerable portion of Fe acceptors are not filled with electrons. This is important when considering the possible role of Fe centers in charge trapping in transistors. MCL and PL spectra measurements also revealed the presence of sharp lines near 1.8 eV corresponding to the 4T1→6A1 intracenter transition in Fe3+. Additional deep centers observed in photocurrent spectra had optical ionization thresholds near 1.5 eV and 2.3 eV.
Leveraging cell-type-specific regulatory networks to interpret genetic variants in abdominal aortic aneurysm (2021)

Abdominal aortic aneurysm (AAA) is a common degenerative cardiovascular disease whose pathobiology is not clearly understood. The cellular heterogeneity and cell-type-specific gene regulation of vascular cells in human AAA have not been well-characterized. Here, we performed analysis of whole-genome sequencing data in AAA patients versus controls with the aim of detecting disease-associated variants that may affect gene regulation in human aortic smooth muscle cells (AoSMC) and human aortic endothelial cells (HAEC), two cell types of high relevance to AAA disease. To support this analysis, we generated H3K27ac HiChIP data for these cell types and inferred cell-type-specific gene regulatory networks. We observed that AAA-associated variants were most enriched in regulatory regions in AoSMC, compared with HAEC and CD4<sup>+</sup> cells. The cell-type-specific regulation defined by this HiChIP data supported the importance of <i>ERG</i> and the <i>KLF</i> family of transcription factors in AAA disease. The analysis of regulatory elements that contain noncoding variants and also are differentially open between AAA patients and controls revealed the significance of the interleukin-6-mediated signaling pathway. This finding was further validated by including information from the deleteriousness effect of nonsynonymous single-nucleotide variants in AAA patients and additional control data from the Medical Genome Reference Bank dataset. These results shed important insights into AAA pathogenesis and provide a model for cell-type-specific analysis of disease-associated variants.
SURROGATE DATA PATHOLOGIES AND THE FALSE-POSITIVE REJECTION OF THE NULL HYPOTHESIS (2001)

It is shown that inappropriately constructed random phase surrogates can give false-positive rejections of the surrogate null hypothesis. Specifically, the procedure erroneously indicated the presence of deterministic, nonlinear structure in a time series that was constructed by linearly filtering normally distributed random numbers. It is shown that the erroneous identification was due to numerical errors in the estimation of the signal's Fourier transform. In the example examined here, the introduction of data windowing into the algorithm eliminated the false-positive rejection of the null hypothesis. Additional guidelines for the use of surrogates are considered, and the results of a comparison test of random phase surrogates, Gaussian scaled surrogates and iterative surrogates are presented.
Positron Emission Tomography in Alzheimer‘s Disease: Early Prediction and Differentiation (2008)

The development of biomarkers for the preclinical detection of neurodegenerative diseases such as Alzheimer’s disease (AD) is a vital step in developing prevention therapies. One consistent feature of AD is a reduction in the cerebral metabolic rate of glucose (CMRglc), a measure of neuronal function. In vivo brain 2-[18F]fluoro-2-deoxy-D-glucose-PET imaging demonstrates consistent and progressive CMRglc reductions in AD patients, the extent and topography of which correlate with symptom severity. There is increasing evidence that CMRglc reductions occur at the preclinical stages of AD and predict decline years in advance of clinical symptoms. This review will give an overview of FDG-PET results in individuals at risk for developing dementia, including: presymptomatic individuals carrying mutations responsible for early-onset familial AD; patients with mild cognitive impairment, often a prodrome to late-onset sporadic AD; nondemented carriers of the ApoE ε4 allele, a strong genetic risk factor for late-onset AD; cognitively normal subjects with a family history of AD; subjects with subjective memory complaints; and normal elderly who were followed longitudinally until they expressed the clinical symptoms and later received postmortem confirmation of AD. We will then review the most recent studies using FDG-PET as an early differential diagnostic tool in AD.
Perioperative chemoimmunotherapy with durvalumab (Durva) in combination with cisplatin/gemcitabine (Cis/Gem) for operable muscle-invasive urothelial carcinoma (MIUC): Preplanned interim analysis of a single-arm phase II trial (SAKK 06/17). (2020)

499 Background: Cisplatin-based neoadjuvant chemotherapy followed by surgery is the standard of care for patients (pts) with MIUC but relapse rates remain high. Immune checkpoint inhibitors have demonstrated efficacy in advanced urothelial carcinoma (UC). We hypothesize that the integration of the PD-L1 inhibitor durvalumab into perioperative management of MIUC improves outcome. Methods: SAKK 06/17 is an open label single arm phase II study including 61 pts. Operable MIUC cT2-T4a cN0-1 pts without contraindication for Cis were eligible. Four cycles of preoperative Cis/Gem q3w are administered in combination with 4 cycles Durva 1500mg q3w starting at cycle 2. Durva is continued after surgery q4w for 10 cycles. Primary endpoint is event free survival at 2 years. We report a preplanned interim analysis of the secondary endpoints safety, pathological complete remission ypT0 N0 (pCR,) and pathological response rate (PaR, defined as ≤ypT1N0) on the first 30 resected pts. Results: Among 34 eligible pts (27M, 7F; median age 70, range 41-81 years) included from 07/18 – 02/19, 33 pts (97%) had primary bladder cancer and 1 pt had upper tract UC. Clinical T2, T3, T4 and TxN1 stage were present at diagnosis in 68%, 18%, 15% and 15%, respectively. Four cycles of chemo-immunotherapy were completed per protocol in 34 pts (100%). No tumor progression was noted at preoperative restaging. AE related to Durvalumab were G3 in 5 pts (15%) and G4 in 3 pts (9%). Surgery was performed as planned in 30 pts (88%), 3 pts refused surgery and 1 pt had a frozen pelvis. Operation technique was open in 20 pts (67%) and laparoscopic/robot-assisted in 10 pts (33%). Postoperative complications included Clavien-Dindo III in 6 pts (20%) and IV in 2 pts (7%) with infections being most common (5 pts, 17%). pCR was found in 9 pts (30%) and additional 6 pts (20%) had ypT1/ypTis for a PaR of 50%. Conclusions: The combination of Cis/Gem and Durva as neoadjuvant treatment for MIUC is feasible with manageable toxicities and pCR and PaR rates in the expected range. The rate of postoperative complications warrants further close follow up. Clinical trial information: 2017-003565-10.
Regulation of cardiac excitation–contraction coupling by action potential repolarization: role of the transient outward potassium current (<i>I</i><sub>to</sub>) (2003)

The cardiac action potential (AP) is critical for initiating and coordinating myocyte contraction. In particular, the early repolarization period of the AP (phase 1) strongly influences the time course and magnitude of the whole-cell intracellular Ca(2+) transient by modulating trans-sarcolemmal Ca(2+) influx through L-type Ca(2+) channels (I(Ca,L)) and Na-Ca exchangers (I(Ca,NCX)). The transient outward potassium current (I(to)) has kinetic properties that make it especially effective in modulating the trajectory of phase 1 repolarization and thereby cardiac excitation-contraction coupling (ECC). The magnitude of I(to) varies greatly during cardiac development, between different regions of the heart, and is invariably reduced as a result of heart disease, leading to corresponding variations in ECC. In this article, we review evidence supporting a modulatory role of I(to) in ECC through its influence on I(Ca,L), and possibly I(Ca,NCX). We also discuss differential effects of I(to) on ECC between different species, between different regions of the heart and in heart disease.
The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning (2017)

Neuronal ApoE receptors are linked to learning and memory, but the pathways governing their abundance, and the mechanisms by which they affect the function of neural circuits are incompletely understood. Here we demonstrate that the E3 ubiquitin ligase IDOL determines synaptic ApoER2 protein levels in response to neuronal activation and regulates dendritic spine morphogenesis and plasticity. IDOL-dependent changes in ApoER2 abundance modulate dendritic filopodia initiation and synapse maturation. Loss of IDOL in neurons results in constitutive overexpression of ApoER2 and is associated with impaired activity-dependent structural remodeling of spines and defective LTP in primary neuron cultures and hippocampal slices. IDOL-deficient mice show profound impairment in experience-dependent reorganization of synaptic circuits in the barrel cortex, as well as diminished spatial and associative learning. These results identify control of lipoprotein receptor abundance by IDOL as a post-transcriptional mechanism underlying the structural and functional plasticity of synapses and neural circuits.
Signal transduction via leukocyte antigen CD43 (sialophorin). Feedback regulation by protein kinase C. (1990)

CD43 is a constitutively phosphorylated 115-kDa sialoglycoprotein expressed on a variety of blood cells including lymphocytes and monocytes. L10, a mAb directed against CD43, triggers T cell activation and enhances hydrogen peroxide production in monocytes. Activation of mononuclear cells by L10 initiates phosphoinositides hydrolysis, C2+ mobilization, and protein kinase C (PKC) activation. In turn, activated PKC hyperphosphorylates CD43, suggesting a potential role for PKC in the regulation of signaling via CD43. To address this issue, we have analyzed the effect of PKC activation by the tumor promoter PMA on L10-triggered rise in intracellular free Ca2+ concentrations ([Ca2+]i). Treatment of mononuclear cells with PMA profoundly inhibited the increase in [Ca2+]i induced by L10. The inhibition of CD43-mediated signaling by PMA was due, in part, to uncoupling of CD43 from the signal-transducing G protein. This was evidenced by the comparatively modest inhibition by PMA of the increase in [Ca2+]i induced by the direct G protein activator AlF4-. PMA treatment did not affect the surface expression of CD43. However, it induced the hyperphosphorylation of CD43, the extent of which correlated with the inhibition of CD43-mediated increase in [Ca2+]i. Staurosporine, a potent inhibitor of PKC, abrogated the hyperphosphorylation of CD43 and normalized CD43-mediated signaling in PMA-treated cells. Significantly, in the absence of PMA, staurosporine enhanced the rise in [Ca2+]i triggered by L10, suggesting that engagement of CD43 by activating ligands results in feedback inhibition by PKC. It is concluded that activation of PKC inhibits signaling via CD43 by mechanisms involving phosphorylation and uncoupling of CD43 from the signal-transducing apparatus and by distal, post-receptor events.
Cyclohydroamination of Aminoalkenes Catalyzed by Disilazide Alkaline‐Earth Metal Complexes: Reactivity Patterns and Deactivation Pathways (2013)

The behavior of the first aminophenolate catalysts of the large alkaline earth metals (Ae) [(LO(i))AeN(SiMe(2)R)(2)(thf)(x)] (i=1-4; Ae=Ca, Sr, Ba; R=H, Me; x=0-2) for the cyclohydroamination of terminal aminoalkenes is discussed. The complexes [(BDI)AeN(SiMe(2)H)(2)(thf)(x)] (Ae=Ca, Sr, Ba, x=1-2; (BDI)H=H(2)C[C(Me)N-2,6-(iPr)(2)C(6)H(3)](2))) and [(BDI)CaN(SiMe(3))(2)(thf)] supported by the β-diketiminate (BDI)(-) ligand have also been employed for comparative and mechanistic considerations. The catalytic performances decrease in the order Ca>Sr≫Ba, which is the opposite trend to that previously observed during the intermolecular hydroamination of activated alkenes catalyzed by the same alkaline-earth metal complexes. Catalyst efficacy increases when the chelating and donating ability of the aminophenolate ligands decreases. For given metals and ancillary scaffolds, disilazide catalysts that incorporate the N(SiMe(3))(2)(-) amido group outclass their congeners containing the N(SiMe(2)H)(2)(-) amide owing to the lower basicity of the N(SiMe(2)H)(2)(-) with respect to the N(SiMe(3))(2)(-) group, and also because Ae-N(SiMe(2)H)(2) catalysts suffer from irreversible deactivation through the dehydrogenative coupling of amine and hydrosilane moieties. This deactivation process takes place at 25°C in the case of [(LO(i))AeN(SiMe(2)H)(2)(thf)(x)] phenolate complexes and occurs even with the related [(BDI)AeN(SiMe(2)H)(2)(thf)(x)] complex, albeit under conditions harsher than those required for effective cyclohydroamination catalysis. A mechanistic scenario for cyclohydroamination catalyzed by [(LX)AeN(SiMe(2)H)(2)(thf)(x)] complexes ((LX)(-)=(LO(i))(-) or (BDI)(-)) is proposed. Although beneficial for the synthesis of Ae heteroleptic complexes able to resist deleterious Schlenk-type equilibria, the use of the N(SiMe(2)H)(2)(-) is prejudicial to catalytic activity in the case of catalyzed transformations that involve reactive amine (and potentially other) substrates. Mechanistic and kinetic investigations further illustrate the interplay between the catalytic activity, operative mechanism, and identity of the metal, ancillary ligand, and amido group. These studies suggest that the widely accepted mechanism for cyclohydroamination reactions cannot be extended systematically to all alkaline-earth catalysts. The [(BDI)CaN(SiMe(2)H)(2){H(2)NCH(2)C(CH(3))(2)CH(2)CH=CH(2)}(2)] complex, the first Ca-aminoalkene adduct structurally characterized, was prepared quantitatively and essentially behaves like [(BDI)CaN(SiMe(2)H)(thf)], thus serving as a model compound for mechanistic studies, as illustrated during stoichiometric reactions monitored by (1)H NMR spectroscopy.
Association of surgical approach with complication rate, progression-free survival time, and disease-specific survival time in cats with mammary adenocarcinoma: 107 cases (1991–2014) (2018)

OBJECTIVE To evaluate potential associations between surgical approach and complication rate, progression-free survival time, and disease-specific survival time in cats with mammary adenocarcinoma. DESIGN Retrospective case series. ANIMALS 107 client-owned cats. PROCEDURES Medical records of cats that underwent surgical excision of mammary adenocarcinoma by means of a unilateral or bilateral (staged or single-session) mastectomy at 9 hospitals between 1991 and 2014 were reviewed. Relevant clinicopathologic data and details of surgical and adjuvant treatments were recorded. Outcome data were obtained, including postoperative complications, progression-free survival time, and disease-specific survival time. RESULTS Complications occurred in 12 of 61 (19.7%) cats treated with unilateral mastectomy, 5 of 14 (35.7%) cats treated with staged bilateral mastectomy, and 13 of 32 (40.6%) cats treated with single-session bilateral mastectomy. Complications were significantly more likely to occur in cats undergoing bilateral versus unilateral mastectomy. Median progression-free survival time was longer for cats treated with bilateral mastectomy (542 days) than for cats treated with unilateral mastectomy (289 days). Significant risk factors for disease progression included unilateral mastectomy, tumor ulceration, lymph node metastasis, and tumors arising in the fourth mammary gland. Significant risk factors for disease-specific death included lymph node metastasis and development of regional or distant metastasis. Among cats that did not develop metastasis, unilateral mastectomy was a significant risk factor for disease-specific death. Treatment with chemotherapy was associated with a significantly decreased risk of disease-specific death. CONCLUSIONS AND CLINICAL RELEVANCE Results supported bilateral mastectomy for the treatment of mammary adenocarcinoma in cats to improve progression-free and disease-specific survival time. Performing bilateral mastectomy in a staged fashion may help to decrease the complication rate.