gebhart/patrepeval huggingface dataset:
ColocAI: artificial intelligence approach to quantify co-localization between mass spectrometry images (2019)

Abstract Motivation Imaging mass spectrometry (imaging MS) is a prominent technique for capturing distributions of molecules in tissue sections. Various computational methods for imaging MS rely on quantifying spatial correlations between ion images, referred to as co-localization. However, no comprehensive evaluation of co-localization measures has ever been performed; this leads to arbitrary choices and hinders method development. Results We present ColocAI, an artificial intelligence approach addressing this gap. With the help of 42 imaging MS experts from 9 labs, we created a gold standard of 2210 pairs of ion images ranked by their co-localization. We evaluated existing co-localization measures and developed novel measures using tf-idf and deep neural networks. The semi-supervised deep learning Pi model and the cosine score applied after median thresholding performed the best (Spearman 0.797 and 0.794 with expert rankings respectively). We illustrate these measures by inferring co-localization properties of 10273 molecules from 3685 public METASPACE datasets. Availability and Implementation https://github.com/metaspace2020/coloc Contact theodore.alexandrov@embl.de
Understanding the complex-I-ty of metformin action: limiting mitochondrial respiration to improve cancer therapy (2014)

Metformin has been a first-line treatment for type II diabetes mellitus for decades and is the most widely prescribed antidiabetic drug. Retrospective studies have found that metformin treatment is associated with both reduced cancer diagnoses and cancer-related deaths. Despite the prevalence of metformin use in the clinic, its molecular mechanism of action remains controversial. In a recent issue of Cancer & Metabolism, Andrzejewski et al. present evidence that metformin acts directly on mitochondria to inhibit complex I and limits the ability of cancer cells to cope with energetic stress. Here, we discuss evidence that supports the role of metformin as a cancer therapeutic.
Supplementary Table 3 from MAPRE1 as a Plasma Biomarker for Early-Stage Colorectal Cancer and Adenomas (2023)

&lt;p&gt;Normalized intensity of high density antibody array and CEA levels in the University of Michigan sample set&lt;/p&gt;
Free Volume, Transport, and Physical Properties of <i>n</i>-Alkyl Derivatized Thiol−Ene Networks: Chain Length Effect (2010)

The free volume, transport, and physical properties of a series of n-alkyl derivatized thiol−ene networks are reported. Derivatized thiol monomers were prepared via a nucleophile-catalyzed thio-Michael addition reaction of multifunctional thiols to n-alkyl acrylates ranging from n = 1 to n = 16 in length. Using UV-initiated photopolymerization, cross-linked networks were fabricated from these systematically modified thiol monomers. Each network consisted of the same molar concentration of alkyl chains. Both the thio-Michael reactions and the network photopolymerizations reached high conversion regardless of n-alkyl length, which is typical of the thiol−ene click reaction. The incorporation of alkyl chains led to the formation of new networks with markedly loose packing as probed by density measurements. The density decreased by 11% as n increased from 1 to 16. It is believed that the alkyl chains acted as spacers or pillars which expanded the cross-linked network scaffold increasing the free volume. The free volume behavior of these expanded networks was probed by positron annihilation lifetime spectroscopy (PALS). The hole volume size as measured by PALS doubled with an increase in alkyl chain length from 1 to 16. Oxygen transport measurements indicated an exponential increase in oxygen permeability across 2 orders of magnitude which was related to the increase in free volume. Glass transition temperatures were interestingly comparable for all derivatized networks regardless of n-alkyl length. Water contact angle was additionally evaluated for these derivatized networks. As expected, contact angle increased with increasing n-alkyl length, demonstrating that the surfaces were altered (becoming more hydrophobic) due to an increased concentration of methylene groups in the bulk.
Multiple Models Fitting as a Set Coverage Problem (2016)

This paper deals with the extraction of multiple models from noisy or outlier-contaminated data. We cast the multi-model fitting problem in terms of set coverage, deriving a simple and effective method that generalizes Ransac to multiple models and deals with intersecting structures and outliers in a straightforward and principled manner, while avoiding the typical shortcomings of sequential approaches and those of clustering. The method compares favorably against the state-of-the-art on simulated and publicly available real data-sets.
Caco-2 Permeability Studies and In Vitro hERG Liability Assessment of Tryptanthrin and Indolinone (2016)

Tryptanthrin and (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolinone (indolinone) were recently isolated from Isatis tinctoria as potent anti-inflammatory and antiallergic alkaloids, and shown to inhibit COX-2, 5-LOX catalyzed leukotriene synthesis, and mast cell degranulation at low µM to nM concentrations. To assess their suitability for oral administration, we screened the compounds in an in vitro intestinal permeability assay using human colonic adenocarcinoma cells. For exact quantification of the compounds, validated UPLC-MS/MS methods were used. Tryptanthrin displayed high permeability (apparent permeability coefficient > 32.0 × 10(-6) cm/s) across the cell monolayer. The efflux ratio below 2 (< 1.12) and unchanged apparent permeability coefficient values in the presence of the P-glycoprotein inhibitor verapamil (50 µM) indicated that tryptanthrin was not involved in P-glycoprotein interactions. For indolinone, a low recovery was found in the human colon adenocarcinoma cell assay. High-resolution mass spectrometry pointed to extensive phase II metabolism of indolinone (sulfation and glucuronidation). Possible cardiotoxic liability of the compounds was assessed in vitro by measurement of an inhibitory effect on human ether-a-go-go-related gene tail currents in stably transfected HEK 293 cells using the patch clamp technique. Low human ether-a-go-go-related gene inhibition was found for tryptanthrin (IC50 > 10 µM) and indolinone (IC50 of 24.96 µM). The analysis of compounds using various in silico methods confirmed favorable pharmacokinetic properties, as well as a slight inhibition of the human ether-a-go-go-related gene potassium channel at micromolar concentrations.
TAp63 contributes to sexual dimorphism in POMC neuron functions and energy homeostasis (2018)

Sexual dimorphism exists in energy balance, but the underlying mechanisms remain unclear. Here we show that the female mice have more pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus than males, and female POMC neurons display higher neural activities, compared to male counterparts. Strikingly, deletion of the transcription factor, TAp63, in POMC neurons confers "male-like" diet-induced obesity (DIO) in female mice associated with decreased POMC neural activities; but the same deletion does not affect male mice. Our results indicate that TAp63 in female POMC neurons contributes to the enhanced POMC neuron functions and resistance to obesity in females. Thus, TAp63 in POMC neurons is one key molecular driver for the sexual dimorphism in energy homeostasis.
Post-Operative Stoma Management Based on 3D Image Reconstruction and Pattern Recognition (2018)

A stoma appliance is an external to the body bag for the collection of intestinal output via an aperture in the patient's abdominal wall. The bag is attached to the skin using a wafer, and many stomas have irregular shapes, making a manual wafer fitting very difficult. Better post-operative wafer fitting has been identified as a key area for stoma care improvement. The ostomate (or the ostomate's caregiver) must know the diameter of the stoma to fit the appliance accurately. A cutting error of as little as 2 mm can result in serious complications, including damaged blood vessels or profuse, recurrent bleeding. A novel approach is presented for the design of a visual measurement assistive system called the Individualized Wafer Fitting System (WFS). The system includes a 3D structured light scanner and associated software. The image processing algorithm and smartphone application interact with the sensor and the ostomate. Once the measurement is complete, the outline of the stoma is sent to a printer, which produces the template for cutting the individualized wafer. The system was tested on artificially made stomas as well as on a human subject for a proof of concept. The results show an error of 5% in cutting wafers customized for simple stomas.
Generation and reactivity of an elusive base-stabilised phosphinidene (2021)

Reduction of phosphorus dichloride 6, supported by the diaryloxyphenyl group (OCO) featuring two bulky phenoxy wingtips, by PMe<sub>3</sub>, generates a reactive intermediate that behaves as a base-stabilized phosphinidene (OCO)P (5). Warming up a solution of this species in toluene to room temperature results in trimerization to give the isolable cyclic triphosphine [(OCO)P]<sub>3</sub>, whereas <i>in situ</i> trapping with 2,3-dimethylbutadiene-1,3 afforded a 3,4-dimethylphospholene-3. Investigation of the reduction of 6 by the phosphine PMe<sub>3</sub> by NMR led to the observation of a persistent species between -10 °C and 10 °C. A DFT study of this process suggests that this compound cannot be the proposed phosphinidene 5, and is more likely the diphosphine (OCO)ClP-PCl(OCO) (12). Attempted reduction of 5 by the bulky carbene IPr resulted in unusual electrophilic substitution in the carbene olefin backbone by the chlorophosphinyl group.
Genetically Encoded Fluorescent Proteins Enable High-Throughput Assignment of Cell Cohorts Directly from MALDI-MS Images (2019)

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) provides a unique in situ chemical profile that can include drugs, nucleic acids, metabolites, lipids, and proteins. MSI of individual cells (of a known cell type) affords a unique insight into normal and disease-related processes and is a prerequisite for combining the results of MSI and other single-cell modalities (e.g. mass cytometry and next-generation sequencing). Technological barriers have prevented the high-throughput assignment of MSI spectra from solid tissue preparations to their cell type. These barriers include obtaining a suitable cell-identifying image (e.g. immunohistochemistry) and obtaining sufficiently accurate registration of the cell-identifying and MALDI-MS images. This study introduces a technique that overcame these barriers by assigning cell type directly from mass spectra. We hypothesized that, in MSI from mice with a defined fluorescent protein expression pattern, the fluorescent protein's molecular ion could be used to identify cell cohorts. A method was developed for the purification of enhanced yellow fluorescent protein (EYFP) from mice. To determine EYFP's molecular mass for MSI studies, we performed intact mass analysis and characterized the protein's primary structure and post-translational modifications through various techniques. MALDI-MSI methods were developed to enhance the detection of EYFP in situ, and by extraction of EYFP's molecular ion from MALDI-MS images, automated, whole-image assignment of cell cohorts was achieved. This method was validated using a well-characterized mouse line that expresses EYFP in motor and sensory neurons and should be applicable to hundreds of commercially available mice (and other animal) strains comprising a multitude of cell-specific fluorescent labels.
MULTISLOT TRANSMISSION LINES AND MICROWAVE PHASE SHIFTERS BASED ON (Ba,Sr)TiO<sub>3</sub> FILMS (2008)

ABSTRACT Microwave slot and coplanar transmission lines formed on a surface of ferroelectric films grown on dielectric substrates are used for various microwave devices with electrically tunable amplitude and phase frequency characteristics. The electric field intensity, which is required for the effective modulation of dielectric permittivity of the ferroelectric film is varied between 10 and 15 V/micron. Therefore rather narrow gaps with width no more than 10 microns can provide necessary electric field at bias voltage no more than 100 V. In this case the attenuation of the electromagnetic slot mode is considerably increased, so the implementation of such devices has no a sense. Keywords: Ferroelectric filmmultislot transmission linephase shifter 6. ACKNOWLEDGMENT This work was partly supported by the project # 2896 of the International science and technology center (ISTC) and Korea Institute of Science and technology (KIST) fund. The authors are also grateful to Russia-LG Electronics research center in Saint-Petersburg and its director Dr. V.G. Chernenko for a possibility to implement the microwave simulations with their original software package.
<i>MIF</i>allele-dependent regulation of the MIF coreceptor CD44 and role in rheumatoid arthritis (2016)

Fibroblast-like synoviocytes mediate joint destruction in rheumatoid arthritis and exhibit sustained proinflammatory and invasive properties. CD44 is a polymorphic transmembrane protein with defined roles in matrix interaction and tumor invasion that is also a signaling coreceptor for macrophage migration inhibitory factor (MIF), which engages cell surface CD74. High-expression MIF alleles (rs5844572) are associated with rheumatoid joint erosion, but whether MIF signaling through the CD74/CD44 receptor complex promotes upstream autoimmune responses or contributes directly to synovial joint destruction is unknown. We report here the functional regulation of CD44 by an autocrine pathway in synovial fibroblasts that is driven by high-expression MIF alleles to up-regulate an inflammatory and invasive phenotype. MIF increases CD44 expression, promotes its recruitment into a functional signal transduction complex, and stimulates alternative exon splicing, leading to expression of the CD44v3-v6 isoforms associated with oncogenic invasion. CD44 recruitment into the MIF receptor complex, downstream MAPK and RhoA signaling, and invasive phenotype require MIF and CD74 and are reduced by MIF pathway antagonists. These data support a functional role for high-MIF expression alleles and the two-component CD74/CD44 MIF receptor in rheumatoid arthritis and suggest that pharmacologic inhibition of this pathway may offer a specific means to interfere with progressive joint destruction.
Hip-spine syndrome: cross-sectional-study of spinal alignment in patients with coxalgia (2018)

In the present study, large leg length discrepancy and hip pain may contribute to spinal coronal misalignment. In addition, advanced stage of OA and decreasing ROM of the hip may lead to increased spinal sagittal misalignment. These findings suggest that when evaluating spinal alignment, the progression of OA, LLD, and pain and ROM of the hip joint should be assessed.
Aperture size selection for improved brain tumor detection and quantification in multi-pinhole 123I-CLINDE SPECT imaging (2020)

A next-generation multi-pinhole system dedicated to brain SPECT imaging is being constructed by our research team, which we call AdaptiSPECT-C. The system prototype used herein consists of 25 square detector modules and a total of 100 apertures grouped by 4 per module. The system is specifically designed for multi-purpose brain imaging and capable of adapting in real-time each aperture size and whether it is open or shuttered closed. The use of such system would provide optimum high-performance patient-personalized imaging for a wide range of brain imaging tasks. In this work we investigated the effect of pinhole diameter variation on spherical tumor quantification for the promising brain tumor imaging agent <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">123</sup> I-CLINDE. To assess the quality of the images reconstructed for the different aperture sizes, we used a customized multiple-sphere tumor phantom derived from the XCAT software with a tumor size of 1 cm in diameter. Our results suggest through quantification and visual inspection that an aperture diameter in the range of 2 to 5 mm in diameter for the adaptive AdaptiSPECT-C system is likely the most suited for high performance brain tumor 123I-CLINDE imaging. In addition, our study concludes that a 4 mm pinhole diameter given its excellent spatial-resolution-to-sensitivity trade-off is promising for scout acquisition in localizing target tumor regions within the brain. We have initiated a task-based performance on the tumor detection and localization accuracy for a range of simulated tumor sizes using the channelized non-pre-whitening (CNPW) matched-filter scanning-observer.
The Role of Subinhibitory Concentrations of Daptomycin and Tigecycline in Modulating Virulence in Staphylococcus aureus (2021)

<i>Staphylococcus aureus</i> (<i>S. aureus</i>) infections are notoriously complicated by the ability of the organism to grow in biofilms and are difficult to eradicate with antimicrobial therapy. The purpose of the current study was to clarify the influence of sub-inhibitory concentrations (sub-MICs) of daptomycin and tigecycline antibiotics on biofilm adhesion factors and exoproteins expressions by <i>S. aureus</i> clinical isolates. Six clinical isolates representing positive biofilm <i>S. aureus</i> clones (3 methicillin-sensitive <i>S. aureus</i> (MSSA) and 3 methicillin-resistant <i>S. aureus</i> (MRSA)) were grown with sub-MICs (0.5 MIC) of two antibiotics (daptomycin and tigecycline) for 12 h of incubation. RNA extracted from culture pellets was used via relative quantitative real-time-PCR (qRT-PCR) to determine expression of specific adhesion (<i>fnbA</i>, <i>fnbB</i>, <i>clfA</i>, <i>clfB</i>, <i>fib</i>, <i>ebps</i>, <i>cna</i>, <i>eno</i>) and biofilm (<i>icaADBC</i>) genes. To examine the effect of sub-MIC of these antibiotics on the expression of extracellular proteins, samples from the culture supernatants of six isolates were collected after 12 h of treatment with or without tigecycline in order to profile protein production via 2D gel sodium dodecyl sulfate-polyacrylamide gel electrophoresis (2D gel-SDS-PAGE). Sub-MIC treatment of all clinical MRSA and MSSA strains with daptomycin or tigecycline dramatically induced or suppressed <i>fnbA</i>, <i>fnbB</i>, <i>clfA</i>, <i>clfB</i>, <i>fib</i>, <i>ebps</i>, <i>cna</i>, <i>eno</i>, and <i>icaADBC</i> gene expression. Furthermore, sub-MIC use of tigecycline significantly reduced the total number of separated protein spots across all the isolates, as well as decreasing production of certain individual proteins. Collectively, this study showed very different responses in terms of both gene expression and protein secretion across the various isolates. In addition, our results suggest that sub-MIC usage of daptomycin and tigecycline could signal virulence induction by <i>S. aureus</i> via the regulation of biofilm adhesion factor genes and exoproteins. If translating findings to the clinical treatment of <i>S. aureus</i>, the therapeutic regimen should be adapted depending on antibiotic, the virulence factor and strain type.
MPG-Verbundprojekt: Nanochemie für eine zukünftige Automobiltechnik (2002)

Newspaper article about the MPG joint research project "Nanochemie für eine zukünftige Automobiltechnik - Möglichkeiten der Optimierung von kupferbasierten Katalysatoren für die on-board Gewinnung von Wasserstoff aus Methanol" supported by the ZEIT-Stiftung, Hamburg
Quantitative SAXS Analysis of the P123/Water/Ethanol Ternary Phase Diagram (2006)

The ternary phase diagram of the amphiphilic triblock copolymer PEO-PPO-PEO ((EO)(20)(PO)(70)(EO)(20) commercialized under the generic name P123), water, and ethanol has been investigated at constant temperature (T = 23 degrees C) by small-angle X-ray scattering (SAXS). The microstructure resulting from the self-assembly of the PEO-PPO-PEO block copolymer varies from micelles in solution to various types of liquid crystalline phases such as cubic, 3D hexagonal close packed spheres (HCPS), 2D hexagonal, and lamellar when the concentration of the polymer is increased. In the isotropic liquid phase, the micellar structural parameters are obtained as a function of the water-ethanol ratio and block copolymer concentration by fitting the scattering data to a model involving core-shell form factor and a hard sphere structure factor of interaction. The micellar core, the aggregation number, and the hard sphere interaction radius decrease when increasing the ethanol/water ratio in the mixed solvent. We show that the fraction of ethanol present in the core is responsible for the swelling of the PPO blocks. In the different liquid crystalline phases, structural parameters such as lattice spacing, interfacial area of PEO block, and aggregation number are also evaluated. In addition to classical phases such as lamellar, 2D hexagonal, and liquid isotropic phases, we have observed a two-phase region in which cubic Fm3m and P6(3)mmc (hexagonally close packing of spheres (HCPS)) phases coexist. This appears at 30% (w/w) of P123 in pure water and with 5% (w/w) of ethanol. At 10% (w/w) ethanol, only the HCPS phase remains present.
Bernoulli Rank-$1$ Bandits for Click Feedback (2017)

The probability that a user will click a search result depends both on its relevance and its position on the results page. The position based model explains this behavior by ascribing to every item an attraction probability, and to every position an examination probability. To be clicked, a result must be both attractive and examined. The probabilities of an item-position pair being clicked thus form the entries of a rank-$1$ matrix. We propose the learning problem of a Bernoulli rank-$1$ bandit where at each step, the learning agent chooses a pair of row and column arms, and receives the product of their Bernoulli-distributed values as a reward. This is a special case of the stochastic rank-$1$ bandit problem considered in recent work that proposed an elimination based algorithm Rank1Elim, and showed that Rank1Elim's regret scales linearly with the number of rows and columns on "benign" instances. These are the instances where the minimum of the average row and column rewards $μ$ is bounded away from zero. The issue with Rank1Elim is that it fails to be competitive with straightforward bandit strategies as $μ\rightarrow 0$. In this paper we propose Rank1ElimKL which simply replaces the (crude) confidence intervals of Rank1Elim with confidence intervals based on Kullback-Leibler (KL) divergences, and with the help of a novel result concerning the scaling of KL divergences we prove that with this change, our algorithm will be competitive no matter the value of $μ$. Experiments with synthetic data confirm that on benign instances the performance of Rank1ElimKL is significantly better than that of even Rank1Elim, while experiments with models derived from real data confirm that the improvements are significant across the board, regardless of whether the data is benign or not.