gebhart/patrepeval huggingface dataset:
Dual therapeutic strategy targeting tumor cells and tumor microenvironment in triple-negative breast cancer (2020)

Objective: Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen receptors (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu). Only 30% of TNBC patients show a pathologic complete response, and the other 70% of patients exhibit a less pronounced response followed by relapse and metastasis to distant organs after neoadjuvant chemotherapy. Achievements of immunotherapy targeting programmed cell death 1 ligand 1 (PD-L1) in clinical trials for treating melanoma, nonsmall-cell lung cancer, renal cell carcinoma, and TNBC suggest that targeting the interaction of tumor cells with tumor microenvironment is highly beneficial for cancer treatment. Finding a novel dual-targeting therapy against tumor cells and the tumor microenvironment (TME) may provide options for improved responses in TNBC patients. Data Sources: We searched the potential targeted therapy candidates that regulate tumor cells as well as the TME of cancer diseases, including TNBC, based on our previous and recent other publications. Study Selection: We selected the potential targeted therapies supported by relevance clinical data, in vitro and in vivo studies. Results: In this review, we found the KDM5B, Cadherin 11, β-catenin, CDK2, signal peptide CUB-EGF domain-containing protein 2, and PDL1 regulate the tumor cells and TME of TNBC cells. In addition, we also highlighted the Antrocin, Ovatodiolide, and Pterostilbene as natural small compound possess anti-cancer through the disruption of tumor cell–TME interactions. Conclusion: The new therapy approach targeting tumor cells-TME interaction may improve the response and survival rate of TNBC patients. Later, natural small compounds could provide alternative therapy options for TNBC patients.
Networks link antigenic and receptor-binding sites of influenza hemagglutinin: Mechanistic insight into fitter strain propagation (2011)

Influenza viral passaging through pre-vaccinated mice shows that emergent antigenic site mutations on the viral hemagglutinin (HA) impact host receptor-binding affinity and, therefore, the evolution of fitter influenza strains. To understand this phenomenon, we computed the Significant Interactions Network (SIN) for each residue and mapped the networks of antigenic site residues on a representative H1N1 HA. Specific antigenic site residues are 'linked' to receptor-binding site (RBS) residues via their SIN and mutations within "RBS-linked" antigenic residues can significantly influence receptor-binding affinity by impacting the SIN of key RBS residues. In contrast, other antigenic site residues do not have such "RBS-links" and do not impact receptor-binding affinity upon mutation. Thus, a potential mechanism emerges for how immunologic pressure on RBS-linked antigenic residues can contribute to evolution of fitter influenza strains by modulating the host receptor-binding affinity.
<title>Femtosecond time-resolved backscattering from strongly scattering media</title> (1995)

Time-resolved backscattering from randomly scattering media is studied experimentally with the aim of human skin diagnosis. The experimental setup consists of a self-modelocked Ti:Sapphire laser and a light gating technique based on sum-frequency generation. Aqueous solutions of latex microspheres were used as scattering medium. The experimentally determined temporal profiles of the recorded backscattered photons significantly depend on the specific conditions of the whole optical system. A systematic variation of the optical parameters was performed and an optimum arrangement was determined. In a first set of experiments, relatively weak concentrations of the scatterers were investigated and scattering lengths were determined. In a second series of experiments two-layered samples of latex suspensions with scattering properties similar to human skin were studied. Under these scattering conditions penetration depths of more than 1 mm could be obtained.
Advanced control laws of DC–DC converters based on piecewise affine modelling. Application to a step‐down converter (2014)

This study proposes two control techniques for a buck converter operating in continuous conduction mode at a fixed switching frequency. The non‐linear behaviour of this switched system is represented by a discrete piecewise affine (PWA) model. The PWA representation offers a precise approximation of the converter's dynamics in the whole operating domain and also allows the investigation of system's stability and the design of different control laws. The first control approach corresponds to a piecewise linear (PWL) state‐feedback controller, designed by using a piecewise quadratic Lyapunov function and by solving a set of linear matrix inequalities. This control method guarantees the stability of the closed‐loop system for a wide range of operating points. The second control strategy is a model predictive control. The constrained optimal control problem is formulated and solved using the PWA approximation as a prediction model. The explicit form of the control law is derived off‐line as an affine state‐feedback controller and stored in a look‐up table for implementation. Both PWL and PWA controllers are validated experimentally, showing better performances in comparison with a proportional–integral or constant state‐feedback controller.
A polygenic two-hit hypothesis for prostate cancer (2023)

Prostate cancer is one of the most heritable cancers. Hundreds of germline polymorphisms have been linked to prostate cancer diagnosis and prognosis. Polygenic risk scores can predict genetic risk of a prostate cancer diagnosis. Although these scores inform the probability of developing a tumor, it remains unknown how germline risk influences the tumor molecular evolution. We cultivated a cohort of 1250 localized European-descent patients with germline and somatic DNA profiling. Men of European descent with higher genetic risk were diagnosed earlier and had less genomic instability and fewer driver genes mutated. Higher genetic risk was associated with better outcome. These data imply a polygenic "two-hit" model where germline risk reduces the number of somatic alterations required for tumorigenesis. These findings support further clinical studies of polygenic risk scores as inexpensive and minimally invasive adjuncts to standard risk stratification. Further studies are required to interrogate generalizability to more ancestrally and clinically diverse populations.
Reliability Analysis of Mechanical Component with Multiple Failure Modes (2013)

Most products are indeed governed by multiple failure modes. However, there are few cases in which reliability analysis applies to only one failure mode at a time. Furthermore, reliability data do not include information about failure modes, or the reliability analysis is performed using a representative failure mode. The Weibull shape parameter for failure modes is more important than one for products in the reliability qualification test. This paper presents reliability analysis methods for a mechanical component with multiple failure modes. These methods include the competing failure modes (CFM) method and the mixed Weibull method. Pneumatic cylinder test data with three failure modes are presented to estimate the shape parameter for each separate failure mode. In addition, reliability measures (B10 life, characteristic life) of the pneumatic cylinder considering three failure modes were compared with those assuming a single failure mode.
Genetic and pharmacological inhibition of ER stress-induced ATF4/CHOP pro-death pathway prevents myocilin misfolding and rescues mouse models of glaucoma (2016)

Purpose: We recently demonstrated that ER stress-induced pro-death markers including ATF4 and CHOP are significantly increased in human post-mortem glaucomatous trabecular meshwork (TM) tissues. The purpose of this study was to further explore the role of ATF4/CHOP in myocilin misfolding in TM and IOP elevation.\nMethods: ATF4 and CHOP levels were analyzed in the TM of Tg-MYOCY437H and dexamethasone (Dex)-treated mice by Western blotting (n=3). Conscious IOP was monitored by rebound tonometer in C57BL/6 mice injected intravitreally with Ad5 Null or ATF4 virus. IOP was measured in Chop-/-Tg-MYOCY437H mice and compared to Chop+/+Tg-MYOCY437H and WT mice. The effects of CRISPR-Cas9 mediated knockdown of ATF4/CHOP on myocilin accumulation was studied in TM-5 cells expressing mutant myocilin. Myocilin accumulation and ER stress was examined in TM cells treated with pharmacological inhibition of the ATF4/CHOP pathway with 100 and 200nM of ISRIB (an inhibitor of the integrated stress response) for 48 hours. Furthermore, ocular hypertensive Tg-MYOCY437H mice were treated with an intravitreal injection of ISRIB (2ul, 2mM) and IOP was measured 4 days post-injections.\nResults: Western blot analysis demonstrated increased ATF4 and CHOP levels in the iridocorneal angle tissues of Tg-MYOCY437H and Dex-treated mice. Forced expression of Ad5.ATF4 led to significant IOP elevation in WT mice (16mmHg in null vs 23mmHg in Ad5.ATF4-injected mice; p+/+Tg-MYOCY437H mice (22mmHg, n=16) had significantly elevated IOP compared to WT Chop+/+ littermates (16.5mmHg, n=4), while Chop-/-Tg-MYOCY437H mice (19mmHg, n=8) did not elevate IOP compared to Chop-/- littermates (18mmHg, n=6) indicating that deletion of Chop rescues ocular hypertension in Tg-MYOCY437H mice. In addition, Cas9 targeting of ATF4 or CHOP dramatically reduced ATF-4 and CHOP levels and also reduced myocilin accumulation and ER stress in TM-5 cells. Treatment of TM cells with ISRIB (100nM) dramatically reduced myocilin accumulation and also prevented ER stress. Pharmacological inhibition of the ATF4/CHOP pathway with ISRIB (2mM) significantly reduced elevated IOP in Tg-MYOCY437H mice (14.5mmHg in vehicle vs 10mmHg in ISRIB treated Tg-MYOCY437Hmice, p\nConclusion: These studies indicate that genetic or pharmacological inhibition of the ATF4/CHOP pathway may provide a novel approach to glaucoma treatment.
Dynamically adjustable annular laser trapping based on axicons (2006)

To study the chemotactic response of sperm to an egg and to characterize sperm motility, an annular laser trap based on axicons is designed, simulated with the ray-tracing tool, and implemented. The diameter of the trapping ring can be adjusted dynamically for a range of over 400 microm by simply translating one axicon along the optical axis. Trapping experiments with microspheres and dog sperm demonstrate the feasibility of the system, and the power requirement agrees with theoretical expectation. This new type of laser trapping could provide a prototype of a parallel, objective, and quantitative tool for animal fertility and biotropism study.
Influence of Spectral Peaks on EMG Parameter Estimation for Vibration-Exercise Analysis (2020)

Many studies have proposed vibration exercise (VE) as a novel training modality for neuromuscular conditioning and rehabilitation. Surface electromyography (sEMG) is widely used for effective measurement of muscle activity. Unfortunately, sharp spectral peaks (SSP) are usually present in the EMG signals recorded during VE. The explanation of these sharp peaks, as muscle activity or motion artifacts, is controversial, complicating EMG parameter extraction for the analysis of VE. The present study aims to quantify the impact of these SSP on the estimation of EMG parameters irrespective of their nature. High-density sEMG was therefore recorded from the biceps brachii muscle during VE with different vibration amplitudes (VA) and frequencies (VF). The power around (±0.5 Hz) VF and its first harmonic was calculated and normalized with the entire EMG power in order to obtain a relative power ( P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R</sub> ) of these peaks. In addition, before and after excluding the SSP, three EMG parameters, i.e., mean frequency (MF), root mean square (RMS), and conduction velocity (CV), were estimated and compared. Our results reveal an average P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R</sub> of 21.18± 15.68 %. The relative difference in EMG RMS and MF are 12.2± 3.8 % and 2.10± 1.04 %, respectively. In addition, the impact of these peaks on the MF and RMS seems also to be affected by vibration conditions, such as VA and VF. However, the CV estimation seems not to be significantly influenced by these peaks, indicating these peaks to be primarily reflecting muscle activity and therefore should be included in VE EMG analysis.
Identification of a novel, membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase. (2003)

Here we characterize a novel neuronal kinase, cyclin-dependent kinase 5 (cdk5)/p35-regulated kinase (cprk). Cprk is a member of a previously undescribed family of kinases that are predicted to contain two N-terminal membrane-spanning domains and a long C terminus, which harbors a dual-specificity serine/threonine/tyrosine kinase domain. Cprk was isolated in a yeast two-hybrid screen using the neuronal cdk5 activator p35 as "bait." Cprk interacts with p35 in the yeast-two hybrid system, binds to p35 in glutathione S-transferase fusion pull-down assays, and colocalizes with p35 in cultured neurons and transfected cells. In these cells, cprk is present with p35 in the Golgi apparatus. Cprk is expressed in a number of tissues but is enriched in brain and muscle and within the brain is found in a wide range of neuronal populations. Cprk displays catalytic activity in in vitro kinase assays and is itself phosphorylated by cdk5/p35. Cdk5/p35 inhibits cprk activity. Cdk5/p35 may therefore regulate cprk function in the brain.
Data-Adaptive Statistical Inference: foreword to the DGIJB special issue (2016)

International audience
Modeling liquid-crystal gradient-index lenses (2007)

The optical properties of one-dimensional gradient-refractive-index lens arrays based on liquid crystals are studied. We find that it is quite possible, using theoretical methods, to predict angular distributions of the light emanating from such arrays when they are illuminated with collimated monochromatic light. We compare four theoretical methods in relation to experiments. The experimental data and the model, based on a combination of eikonal methods and diffraction, are in close correspondence. Features such as maximal beam width and number of extrema in the angular light distribution are discussed and explained theoretically. We also studied dispersion effects, both experimentally and theoretically, with good agreement between the two.
Silicon (100)/SiO2 by XPS (2013)

Silicon (100) substrates are ubiquitous in microfabrication and, accordingly, their surface characteristics are important. Herein, we report the analysis of Si (100) via X-ray photoelectron spectroscopy (XPS) using monochromatic Al Kα radiation. Survey scans show that the material is primarily silicon and oxygen with small amounts of carbon, nitrogen, and fluorine contamination. The Si 2p region shows two peaks that correspond to elemental silicon and silicon dioxide. Using these peaks the thickness of the native oxide (SiO2) is estimated using the equation of Strohmeier. The oxygen peak is symmetric. These silicon wafers are used as the substrate for subsequent growth of templated carbon nanotubes in the preparation of microfabricated thin layer chromatography plates.
Multimodal single-cell analysis of non-random heteroplasmy distribution in human retinal mitochondrial disease (2022)

Variants within the high copy number mitochondrial genome (mtDNA) can disrupt organelle function and lead to severe multi-system disease. The wide range of manifestations observed in mitochondrial disease patients results from varying fractions of abnormal mtDNA molecules in different cells and tissues, a phenomenon termed heteroplasmy. However, the landscape of heteroplasmy across cell types within tissues and its influence on phenotype expression in affected patients remains largely unexplored. Here, we identify non- random distribution of a pathogenic mtDNA variant across a complex tissue using single-cell RNA sequencing, mitochondrial single-cell ATAC sequencing, and multimodal single-cell sequencing. We profile the transcriptome, chromatin accessibility state, and heteroplasmy in cells from the eyes of a patient with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and healthy control donors. Utilizing the retina as a model for complex multi-lineage tissues, we found that the proportion of the pathogenic m.3243A&gt;G allele was neither evenly nor randomly distributed across diverse cell types. All neuroectoderm- derived neural cells exhibited a high percentage of the mutant variant. However, a subset of mesoderm- derived lineage, namely the vasculature of the choroid, was near homoplasmic for the wildtype allele. Gene expression and chromatin accessibility profiles of cell types with high and low proportions of m.3243A&gt;G implicate mTOR signaling in the cellular response to heteroplasmy. We further found by multimodal single-cell sequencing of retinal pigment epithelial cells that a high proportion of the pathogenic mtDNA variant was associated with transcriptionally and morphologically abnormal cells. Together, these findings show the non- random nature of mitochondrial variant partitioning in human mitochondrial disease and underscore its implications for mitochondrial disease pathogenesis and treatment.
Robust learning of low-dimensional dynamics from large neural ensembles (2013)

Recordings from large populations of neurons make it possible to search for hy-pothesized low-dimensional dynamics. Finding these dynamics requires models that take into account biophysical constraints and can be fit efficiently and ro-bustly. Here, we present an approach to dimensionality reduction for neural data that is convex, does not make strong assumptions about dynamics, does not require averaging over many trials and is extensible to more complex statistical models that combine local and global influences. The results can be combined with spec-tral methods to learn dynamical systems models. The basic method extends PCA to the exponential family using nuclear norm minimization. We evaluate the effec-tiveness of this method using an exact decomposition of the Bregman divergence that is analogous to variance explained for PCA. We show on model data that the parameters of latent linear dynamical systems can be recovered, and that even if the dynamics are not stationary we can still recover the true latent subspace. We also demonstrate an extension of nuclear norm minimization that can separate sparse local connections from global latent dynamics. Finally, we demonstrate improved prediction on real neural data from monkey motor cortex compared to fitting linear dynamical models without nuclear norm smoothing. 1
Von Frey testing revisited: Provision of an online algorithm for improved accuracy of 50% thresholds (2019)

The von Frey testing procedure is standard for assessing peripheral and central sensitization but is associated with inaccuracies and lack of transparency in the associated math. Here, we describe these problems and present a novel statistical algorithm that calculates the exact thresholds using math beyond the traditional methods. The online platform is transparent, free of charge and easy to use also for the everyday user of von Frey filaments. Application of this resource will ultimately reduce errors due to methodological misinterpretations and increase reproducibility across laboratories.
Unique sequences in region VI of the flagellin gene of Salmonella typhi (1989)

Summary The HI (now renamed fliC ; lino et al. , 1988) alleles specifying antigenically different Salmonella flagellins are identical at their ends but differ greatly towards the middle, where there are two hypervariable segments (regions IV and VI). The flagellar antigen, d , of Salmonella typhi , is found also as phase‐1 antigen in many other Saimonella species. We cloned the H 1‐ d gene of a strain of S. typhi and determined the nucleotide sequence of its two hypervariable regions. Comparison with gene H 1‐ d of Salmonella muenchen showed substantial differences in region VI: four scattered amino acid differences and ten adjacent amino acids in the inferred S. typhi sequence, all of which differ from the corresponding nine amino acids in the S. muenchen sequence. The results of polymerase chain reaction amplification indicated the presence of the S. typhi version in all of 18 additional S. typhi strains and the presence of the S. muenchen version in all four non‐ S. typhi species with flagellar antigen d . The difference in amino acid sequence in segment VI may be responsible for the minor serological differences between antigens d of S. typhi and antigen d of S. muenchen.
Surface plasmon polariton mode validation using commercially available finite element method ANSYS HFSS (2018)

Numerical computation using HFSS finite element analysis was conducted in order to determine the dispersion relation (complex index) of the surface plasmon polariton (SPP) mode. SPP result from the interaction or coupling between electromagnetic fields in the form of light and delocalised electrons on a metal interface. SPPs has the effect of confining electromagnetic radiation on the order that is smaller than the wavelength. In this work, the correspondence by H.P Hsu (IEEE Trans. Microw. Theory Techn., 11(4), (1963).) was used in the study of SPP modes comparing both analytical calculations and numerical calculation from ANSYS HFSS to ascertain the veracity of the correspondence for SPP surface waves, and calculating the attenuation coefficient using quality factor, Q, obtained from HFSS eigenmode calculations. Silicon dioxide and silver with the use of measured complex permittivity for silver is used to conduct this study. Numerically-obtained results for propagation length and SPP effective index are compared to analytical calculations from the well-known SPP dispersion relationship.
COLORIMETRY PART I: THE BASICS & MATERIALS APPLICATIONS (1995)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text ROY S. BERNS, "COLORIMETRY PART I: THE BASICS & MATERIALS APPLICATIONS," Optics & Photonics News 6(9), 23- (1995) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Clear zone in osteoclast function: role of podosomes in regulation of bone-resorbing activity (1991)

The adhesion of osteoclasts to the bone matrix is mandatory for bone resorption. Contact of the osteoclast with bone surface induces, in fact, cell polarization and organization of the resorbing apparatus, the so-called "ruffled border." Cell-matrix interaction in osteoclasts is a complex phenomenon resulting from formation of the "clear zone," a cytoplasmic area presenting the adhering plasma membrane, or "sealing membrane." The sealing membrane surrounds the ruffled border and seals the resorbing compartment, namely the extracellular space in which bone resorption takes place. Adhesion at this level occurs via specialized discrete structures, the "podosomes." Podosomes present most of the protein commonly found in focal adhesions, but with a peculiar organization. They are dynamic elements suitable for regulation, according with the functional demand of the cell. Their assembly increases during bone resorption and is regulated by the cytosolic free calcium concentration and the activity of protein kinase C.