gebhart/patrepeval huggingface dataset:
Spatial analysis of human lung cancer reveals organized immune hubs enriched for stem-like CD8 T cells and associated with immunotherapy response (2023)

The organization of immune cells in human tumors is not well understood. Immunogenic tumors harbor spatially-localized multicellular 'immunity hubs' defined by expression of the T cell-attracting chemokines <i>CXCL10/CXCL11</i> and abundant T cells. Here, we examined immunity hubs in human pre-immunotherapy lung cancer specimens, and found that they were associated with beneficial responses to PD-1-blockade. Immunity hubs were enriched for many interferon-stimulated genes, T cells in multiple differentiation states, and <i>CXCL9/10/11</i> + macrophages that preferentially interact with CD8 T cells. Critically, we discovered the stem-immunity hub, a subtype of immunity hub strongly associated with favorable PD-1-blockade outcomes, distinct from mature tertiary lymphoid structures, and enriched for stem-like TCF7+PD-1+ CD8 T cells and activated <i>CCR7</i> + <i>LAMP3</i> + dendritic cells, as well as chemokines that organize these cells. These results elucidate the spatial organization of the human intratumoral immune response and its relevance to patient immunotherapy outcomes.
Approaches to achieve surface sensitivity in the in situ XAS of electrocatalysts (2021)

In situ and operando techniques providing information regarding adsorbate bonding and atomic arrangements on the electrode surface along with pure electrochemical measurements are needed to more fully understand the detailed mechanism of electrocatalytic reactions on high surface areas/nanoparticle electrocatalysts. X-ray adsorption spectroscopy (XAS) is a powerful tool to interrogate the electronic structure and local coordination environment of such electrocatalysts under working conditions, but it should be acknowledged that standard XAS methods are not intrinsically surface sensitive. This review will present recent in situ XAS studies on single-atom, metal, and metal oxide electrocatalysts, highlighting the approaches taken to achieve surface sensitivity by careful designing of the sample under investigation.
The Results in Patients Implanted with the Nucleus Double Array Cochlear Implant: Pitch Discrimination and Auditory Performance (2002)

The additional apical array leads to significant improvement in auditory performance in patients with obliterated cochleae by increasing the number of intracochlear electrodes. Despite reduced pitch discrimination, the apical array provides important information for speech recognition. For this reason the Double Array provides a profound advantage for patients with obliterated or surgically inaccessible cochleae.
GWAS meta-analysis (N=279,930) identifies new genes and functional links to intelligence (2017)

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to intelligence 3–7 , but much about its genetic underpinnings remains to be discovered. Here, we present the largest genetic association study of intelligence to date (N=279,930), identifying 206 genomic loci (191 novel) and implicating 1,041 genes (963 novel) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and identify 89 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain and specifically in striatal medium spiny neurons and cortical and hippocampal pyramidal neurons. Gene-set analyses implicate pathways related to neurogenesis, neuron differentiation and synaptic structure. We confirm previous strong genetic correlations with several neuropsychiatric disorders, and Mendelian Randomization results suggest protective effects of intelligence for Alzheimer’s dementia and ADHD, and bidirectional causation with strong pleiotropy for schizophrenia. These results are a major step forward in understanding the neurobiology of intelligence as well as genetically associated neuropsychiatric traits.
Proenkephalin as a new biomarker for pediatric acute kidney injury – reference values and performance in children under one year of age (2020)

Objectives Acute kidney injury (AKI) is common in critically ill children, but current biomarkers are suboptimal. Proenkephalin A 119-159 (PENK) is a promising new biomarker for AKI in adults, but pediatric data is lacking. We determined PENK reference intervals for healthy children, crucial for clinical implementation, and explored concentrations in critically ill infants aged under 1 year. Methods Observational cohort study in healthy infants and critically ill children aged 0-1 years. Reference values were determined using generalized additive models. Plasma PENK concentrations between healthy children and critically ill children with and without AKI, were compared using linear mixed modelling. The performance of PENK as AKI biomarker was compared to cystatin C (CysC) and β-trace protein (BTP) using receiver-operating-characteristic (ROC) analysis. Results PENK concentrations in 100 healthy infants were stable during the first year of life (median 517.3 pmol/L). Median PENK concentrations in 91 critically ill children, were significantly higher in those with AKI (n=40) (KDIGO Stage 1 507.9 pmol/L, Stage 2 704.0 pmol/L, Stage 3 930.5 pmol/L) than non-AKI patients (n=51, 432.2 pmol/L) (p < 0.001). PENK appeared to relate better to AKI diagnosis than CysC and BTP (AUROC PENK 0.858, CysC 0.770 and BTP 0.711) in the first 24 h after recruitment. Conclusions PENK reference values are much higher in young infants than adults, but clearly discriminate between children with and without AKI, with comparable or better performance than CysC and BTP. Our results illustrate the importance of establishing age-normalized reference values and indicate PENK as a promising pediatric AKI biomarker.
pH-Sensitive Swelling and Drug-Release Properties of Chitosan—Poly(ethylene oxide) Semi-interpenetrating Polymer Network (1996)

Chitosan-poly(ethylene oxide) (PEO) semi-interpenetrating polymer network (semi-IPN) was developed for pH-sensitive drug delivery into the stomach. In simulated gastric fluid (SGF, pH 1.2), chitosan-PEO semi-IPN had a swelling ratio of 18.4 after 6 h. In contrast, the swelling ratio in simulated intestinal fluid (SIF, pH 7.2) was only 1.80. The presence of pepsin and pancreatin in SGF and SIF, respectively, did not effect the swelling behavior. The release of riboflavin from chitosan-PEO hydrogel was also found to be dependent on the pH of the medium. More than 50% of the drug was released from chitosan-PEO semi-IPN after 6 h in SGF. In SIF, on the other hand, only 29% was released after 6 h. The presence of enzymes did decrease the release of drug from the hydrogels by complexing with the cationic chitosan matrix. The results clearly show that chitosan-PEO semi-IPN, containing high molecular weight PEO, meets the requirements of pH responsive drug delivery system, and could be useful for site-specific delivery into the stomach.
A Truly-Redundant Aerial Manipulator System With Application to Push-and-Slide Inspection in Industrial Plants (2019)

We present the design, motion planning, and control of an aerial manipulator for non-trivial physical interaction tasks, such as pushing while sliding on curved surfaces-a task which is motivated by the increasing interest in autonomous non-destructive tests for industrial plants. The proposed aerial manipulator consists of a multidirectional-thrust aerial vehicle-to enhance physical interaction capabilities-endowed with a 2-DoFs lightweight arm-to enlarge its workspace. This combination makes it a trulyredundant manipulator going beyond standard aerial manipulators based on collinear multirotor platforms. The controller is based on a PID method with a “displaced” positional part that ensures asymptotic stability despite the arm elasticity. A kinodynamic task-constrained and control-aware global motion planner is used. Experiments show that the proposed aerial manipulator system, equipped with an Eddy current probe, is able to scan a metallic pipe sliding the sensor over its surface and preserving the contact. From the measures, a weld on the pipe is successfully detected and mapped.
An epigenetic marker panel for recurrence risk prediction of low grade papillary urothelial cell carcinoma (LGPUCC) and its potential use for surveillance after transurethral resection using urine (2014)

By a candidate gene approach, we analyzed the promoter methylation (PM) of 8 genes genes (ARF, TIMP3, RAR-β2, NID2, CCNA1, AIM1, CALCA and CCND2) by quantitative methylation specific PCR (QMSP) in DNA of 17 non-recurrent and 19 recurrent noninvasive low grade papillary urothelial cell carcinoma (LGPUCC) archival tissues. Among the genes tested, by establishing an empiric cutoff value, CCND2, CCNA1, NID2, and CALCA showed higher frequency of methylation in recurrent than in non-recurrent LGPUCC: CCND2 10/19 (53%) vs. 2/17 (12%) (p=0.014); CCNA1 11/19 (58%) vs. 4/17 (23.5%) (p=0.048); NID2 13/19 (68%) vs. 3/17 (18%) (p=0.003) and CALCA 10/19 (53%) vs. 4/17 (23.5%) (p=0.097), respectively. We further analyzed PM of CCND2, CCNA1, and CALCA in urine DNA from UCC patients including LGPUCC and controls. The frequency of CCND2, CCNA1 and CALCA was significantly higher (p<0.0001) in urine of UCC cases [ 38/148 (26%), 50/73 (68%) and 94/148 (63.5%) respectively] than controls [0/56 (0%), 10/60 (17%) and 16/56 (28.5%), respectively)]. Most importantly we found any one of the 3 markers methylation positive in 25 out of 30 (83%) cytology negative LGPUCC cases. We also explored the biological function of CCNA1 in UCC. Prospective confirmatory studies are needed to develop a reliable tool for prediction of recurrence using primary LGPUCC tissues and/or urine.
Sugar Additives Improve Signal Fidelity for Implementing Two-Phase Resorufin-Based Enzyme Immunoassays (2014)

Enzymatic signal amplification based on fluorogenic substrates is commonly used for immunoassays; however, when transitioning these assays to a digital format in water-in-mineral oil emulsions, such amplification methods have been limited by the leakage of small reporting fluorescent probes. In the present study, we used a microfluidic system to study leakage from aqueous droplets in a controlled manner and confirmed that the leakage of fluorescent resorufin derivatives is mostly due to the presence of the lipophilic surfactant Span80, which is commonly used to preserve emulsion stability. This leakage can be overcome by the addition of specific sugars that most strongly interfered with the surfactants ability to form micelles in water. The application of the microfluidic system to the quantitative analysis of droplets and the implementation of the described sugar additives would allow for alternatives to fluorinated surfactant-based platforms and improve the signal fidelity in enzyme immunoassays implemented through multiphase microfluidics.
Evaluation of a Newly Developed Percutaneous Thrombectomy Basket Device in Sheep With Central Pulmonary Embolisms (2006)

Extraction of pulmonary embolism with the self-expanding suction basket is feasible. However, successful recanalization is limited by catheter maneuverability in the pulmonary arterial system.
Nickel-Catalyzed Cross-Electrophile Reductive Couplings of Neopentyl Bromides with Aryl Bromides (2020)

5-Cyanoimidazole was identified as an inexpensive ligand for nickel-catalyzed cross-electrophile couplings by screening a diverse set of pharmaceutical compound library. A strategic screening approach led to the discovery of this novel ligand, which was successfully applied in the preparation of various alkylated arene products with good to high yields. Furthermore, the properties of this ligand allowed expanding the scope of reductive couplings to challenging substrates, such as sterically hindered neopentyl halides, which are known to generate motifs that are prevalent in biologically active molecules.
Supramolecular Control of Oligothienylenevinylene−Fullerene Interactions:  Evidence for a Ground-State EDA Complex (2005)

Complementary hydrogen-bonding interactions between a barbituric acid-substituted fullerene derivative (1) and corresponding receptor (2) bearing thienylenevinylene units are used to assemble a 1:1 supramolecular complex (K = 5500 M(-1)). Due to the close proximity of the redox-active moieties within the assembly, strong ground-state electron-donor-acceptor interactions are observed. Photoinduced electron transfer from electron-rich thienylenevinylene subunits to the fullerene is very fast (k(et) = 5.5 x 10(12) s(-1)), as determined by fs-time-resolved transient absorption spectroscopy. [reaction: see text]
Effects of Bottom Electrodes (Pt and IrO2) on Physical and Electrical Properties of Bi4-xLaxTi3O12 (BLT) Thin Film (2001)

Bi 3.35 La 0.85 Ti 3 O 12 (BLT) thin (90 nm) films were prepared on Pt (200 nm) and IrO 2 (200 nm) electrodes by metalorganic decomposition (MOD) method, and crystallized by rapid thermal annealing (RTA) and the subsequent furnace annealing. BLT films were c -axis oriented on both electrodes irrespective of RTA temperature (600 and 700°C). However, the degree of c -axis orientation was much higher on IrO 2 than on Pt, and significantly reduced only on Pt with decreasing RTA temperature. This result was related to the different stress of BLT film which is negligible on Pt, but 500 MPa (tensile) on IrO 2 in the RTA temperature range of 600–700°C. The crystalline orientation of BLT film directly affected switching polarization ( P * - P ∧ ) which had much smaller value of 5 µC/cm 2 on IrO 2 than 12 µC/cm 2 on Pt, and was increased to 16 µC/cm 2 only on Pt with the decrease of RTA temperature. On the other hand, leakage characteristics were not changed with bottom electrode materials.
Predicting T cell recognition of MHC class I restricted neoepitopes (2018)

Epitopes that arise from a somatic mutation, also called neoepitopes, are now known to play a key role in cancer immunology and immunotherapy. Recent advances in high-throughput sequencing have made it possible to identify all mutations and thereby all potential neoepitope candidates in an individual cancer. However, most of these neoepitope candidates are not recognized by T cells of cancer patients when tested in vivo or in vitro, meaning they are not immunogenic. Especially in patients with a high mutational load, usually hundreds of potential neoepitopes are detected, highlighting the need to further narrow down this candidate list. In our study, we assembled a dataset of known, naturally processed, immunogenic neoepitopes to dissect the properties that make these neoepitopes immunogenic. The tools to use and thresholds to apply for prioritizing neoepitopes have so far been largely based on experience with epitope identification in other settings such as infectious disease and allergy. Here, we performed a detailed analysis on our dataset of curated immunogenic neoepitopes to establish the appropriate tools and thresholds in the cancer setting. To this end, we evaluated different predictors for parameters that play a role in a neoepitope's immunogenicity and suggest that using binding predictions and length-rescaling yields the best performance in discriminating immunogenic neoepitopes from a background set of mutated peptides. We furthermore show that almost all neoepitopes had strong predicted binding affinities (as expected), but more surprisingly, the corresponding non-mutated peptides had nearly as high affinities. Our results provide a rational basis for parameters in neoepitope filtering approaches that are being commonly used. <b>Abbreviations:</b> SNV: single nucleotide variant; nsSNV: nonsynonymous single nucleotide variant; ROC: receiver operating characteristic; AUC: area under ROC curve; HLA: human leukocyte antigen; MHC: major histocompatibility complex; PD-1: Programmed cell death protein 1; PD-L1 or CTLA-4: cytotoxic T-lymphocyte associated protein 4.
Bone marrow-derived progenitor cells attenuate inflammation in lipopolysaccharide-induced acute respiratory distress syndrome (2014)

Acute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill patients. Novel treatment strategies are required to address this common clinical problem. The application of exogenous adult stem cells was associated with a beneficial outcome in various pre-clinical models of ARDS. In the present study we evaluated the functional capacity and homing ability of bone marrow-derived progenitor cells (BMDPC) in vitro and investigated their potential as a treatment strategy in lipopolysaccharide (LPS)-induced ARDS. Evaluation of the BMDPC showed functional capacity to form endothelial outgrowth cell colonies, which stained positive for CD133 and CD31. Furthermore, DiI-stained BMDPC were demonstrated to home to injured lung tissue. Rats treated with BMDPC showed significantly reduced histopathological changes, a reduced expression of ICAM-1 and VCAM-1 by the lung tissue, an inhibition of proinflammatory cytokine synthesis, a reduced weight loss and a reduced mortality (p < 0.03) compared to rats treated with LPS alone. These findings suggest that the application of exogenous BMDPC can attenuate inflammation in LPS-induced ARDS and thereby reduce the severity of septic organ damage. Cell therapy strategies using adult stem cells might therefore become a novel and alternative option in ARDS therapy.
From Pictorial Structures to deformable structures (2012)

Pictorial Structures (PS) define a probabilistic model of 2D articulated objects in images. Typical PS models assume an object can be represented by a set of rigid parts connected with pairwise constraints that define the prior probability of part configurations. These models are widely used to represent non-rigid articulated objects such as humans and animals despite the fact that such objects have parts that deform non-rigidly. Here we define a new Deformable Structures (DS) model that is a natural extension of previous PS models and that captures the non-rigid shape deformation of the parts. Each part in a DS model is represented by a low-dimensional shape deformation space and pairwise potentials between parts capture how the shape varies with pose and the shape of neighboring parts. A key advantage of such a model is that it more accurately models object boundaries. This enables image likelihood models that are more discriminative than previous PS likelihoods. This likelihood is learned using training imagery annotated using a DS “puppet.” We focus on a human DS model learned from 2D projections of a realistic 3D human body model and use it to infer human poses in images using a form of non-parametric belief propagation.
Tailored Synthesis of Octopus‐type Janus Nanoparticles for Synergistic Actively‐Targeted and Chemo‐Photothermal Therapy (2016)

A facile, reproducible, and scalable method was explored to construct uniform Au@poly(acrylic acid) (PAA) Janus nanoparticles (JNPs). The as-prepared JNPs were used as templates to preferentially grow a mesoporous silica (mSiO2 ) shell and Au branches separately modified with methoxy-poly(ethylene glycol)-thiol (PEG) to improve their stability, and lactobionic acid (LA) for tumor-specific targeting. The obtained octopus-type PEG-Au-PAA/mSiO2 -LA Janus NPs (PEG-OJNP-LA) possess pH and NIR dual-responsive release properties. Moreover, DOX-loaded PEG-OJNP-LA, upon 808 nm NIR light irradiation, exhibit obviously higher toxicity at the cellular and animal levels compared with chemotherapy or photothermal therapy alone, indicating the PEG-OJNP-LA could be utilized as a multifunctional nanoplatform for in vitro and in vivo actively-targeted and chemo-photothermal cancer therapy.
Biomechanical Efficacy of Tape Cerclage as an Augment or Stand-alone for Coracoclavicular Ligament Reconstruction (2022)

Tape cerclage augmentation may provide a useful augment for CC ligament reconstruction.
Nonlinear Optical Microscopy for Melanoma: Challenges, Tools and Opportunities (2018)

The natural pigments known as melanins are thought to play a role in the etiology and progression of melanoma, but many of their roles are currently not well understood. While quantification of melanins have, up until now, have been performed in bulk tissue ex vivo, new imaging technologies have unlocked the means to visualize and quantify melanins at the sub-cellular scale. The nonlinear imaging methods known as pump-probe, coherent Raman, and sum-frequency absorption microscopies provide subcellular resolution imaging of melanins, enabling label-free, longitudinal quantification of both eumelanin and pheomelanin in situ and in vivo. These nonlinear imaging toolkits have been well proven in both animal models and human samples, moving them tantalizingly close to clinical application. Future efforts integrating these tools into practical, mobile imaging systems will provide immense benefit both to clinical research and practice.
Two-Photon Poly(phenylenevinylene) DFB Laser (2010)

Two-photon pumped lasing of a poly(phenylenevinylene)-titania-silica (PPV-TiO2-SiO2) nanocomposite comprised of PPV synthesized within the void spaces of a multilayer nanoparticle TiO2 and SiO2 1D photonic crystal is reported for the first time. With this distributed feedback (DFB) device, we have discovered the surprising result that two photon lasing requires only a factor of 2 higher intensity than one photon lasing thereby allowing laser excitation densities far below those that cause material degradation. The lower excitation density makes possible laser operation in the high-repetition rate regime and the use of compact and cheap NIR pump sources. All this makes our device rather interesting for optical telecommunication applications.
Architecture of datapath-oriented coarse-grain logic and routing for FPGAs (2004)

In this paper, we propose a new datapath-oriented FPGA architecture that utilizes coarse-grain logic and routing resources to increase the area efficiency of datapath circuits. Using a set of custom-built datapath-oriented CAD tools and a set of datapath benchmarks, we investigated several variants of our proposed architecture. We found that the architecture achieves the highest area efficiency when 40% to 50% of the total routing tracks are coarse-grain. Furthermore, compared to conventional FPGA architectures, our datapath-oriented architecture uses about 10% less area to implement the same circuits.