gebhart/patrepeval huggingface dataset:
Colocalization Features for Classification of Tumors\nUsing Desorption Electrospray Ionization Mass Spectrometry Imaging (2019)

Supervised\nmodeling of mass spectrometry imaging (MSI) data is\na crucial component for the detection of the distinct molecular characteristics\nof cancerous tissues. Currently, two types of supervised analyses\nare mainly used on MSI data: pixel-wise segmentation of sample images\nand whole-sample-based classification. A large number of mass spectra\nassociated with each MSI sample can represent a challenge for designing\nmodels that simultaneously preserve the overall molecular content\nwhile capturing valuable information contained in the MSI data. Furthermore,\nintensity-related batch effects can introduce biases in the statistical\nmodels. Here we introduce a method based on ion colocalization features\nthat allows the classification of whole tissue specimens using MSI\ndata, which naturally preserves the spatial information associated\nthe with the mass spectra and is less sensitive to possible batch\neffects. Finally, we propose data visualization strategies for the\ninspection of the derived networks, which can be used to assess whether\nthe correlation differences are related to coexpression/suppression\nor disjoint spatial localization patterns and can suggest hypotheses\nbased on the underlying mechanisms associated with the different classes\nof analyzed samples.
Electro Optical Performance Of An Improved Deformable Mirror Device (1988)

The design, fabrication and performance of an improved 128 X 128 deformable mirror device (DMD) is presented. The DMD is a fast, low power, analog response, spatial light modulator. The improved DMD consists of a monolithically formed array of cantilever beams which are electrostatically deflected by an underlying MOS transistor address matrix. The on-chip address circuitry supports a single video input to the chip with all demux operations performed on-chip. The original DMD (1,2) differs in two respects from the improved version. Instead of monolithically formed cantilever beams, the original DMD utilizes a hybrid architecture wherein a continuous metalized membrane is placed over an underlying address chip by a mechanical lay-down process. In addition, instead of the single video input of the improved DMD, the original version has 128 inputs corresponding to the 128 columns of the x-y transistor matrix. The deformable mirrors of the improved DMD are cantilever beams formed by two layers of high reflectivity aluminum alloy. A thin layer forms the hinge and a thicker layer forms the cantilever beam and the surrounding support metal. The beam, hinge and support metalare formed over an underlying planarizing spacer layer, which is selectively removed by plasma etching to form an air gap underlying each cantilever beam pixel. This paper describes the design, fabrication and performance of the improved 128 X 128 cantilever beam DMD, including preliminary data on the Fourier plane behavior of this device and a discussion of its application to optical correlation. Dynamic range of the DMD in the Fourier plane at the Nyquist frequency has been measured at greater than 45 db and is limited by the CCD image detector used to record the intensity distribution.
Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c- MYC transcription (2002)

The nuclease hypersensitivity element III(1) upstream of the P1 promoter of c-MYC controls 85-90% of the transcriptional activation of this gene. We have demonstrated that the purine-rich strand of the DNA in this region can form two different intramolecular G-quadruplex structures, only one of which seems to be biologically relevant. This biologically relevant structure is the kinetically favored chair-form G-quadruplex, which is destabilized when mutated with a single G --> A transition, resulting in a 3-fold increase in basal transcriptional activity of the c-MYC promoter. The cationic porphyrin TMPyP4, which has been shown to stabilize this G-quadruplex structure, is able to suppress further c-MYC transcriptional activation. These results provide compelling evidence that a specific G-quadruplex structure formed in the c-MYC promoter region functions as a transcriptional repressor element. Furthermore, we establish the principle that c-MYC transcription can be controlled by ligand-mediated G-quadruplex stabilization.
Copresentation of natural HIV-1 agonist and antagonist ligands fails to induce the T cell receptor signaling cascade (1998)

It is not known how human immunodeficiency virus type 1 (HIV-1)-derived antagonist peptides interfere with intracellular activation of cytotoxic T lymphocytes (CTL). We identified Gag epitope variants in HIV-1-infected patients that act as antagonists of CTL responses to unmutated epitopes. We then investigated the effect that presentation of each variant has on the early events of T cell receptor (TCR) signal transduction. We found that altered peptide ligands (APL) failed to induce phosphorylation of pp36, a crucial adaptor protein involved in TCR signal transduction. We further investigated the effect that simultaneous presentation of APL and native antigen at low, physiological, peptide concentrations (1 nM) has on TCR signal transduction, and we found that the presence of APL can completely inhibit induction of the protein tyrosine phosphorylation events of the TCR signal transduction cascade.
Effects of Monoclonal Antibodies against Nerve Growth Factor on Healthy Bone and Joint Tissues in Mice, Rats, and Monkeys: Histopathologic, Biomarker, and Microcomputed Tomographic Assessments (2018)

Tanezumab, an anti-nerve growth factor (NGF) antibody, is in development for management of chronic pain. During clinical trials of anti-NGF antibodies, some patients reported unexpected adverse events requiring total joint replacements, resulting in a partial clinical hold on all NGF inhibitors. Three nonclinical toxicology studies were conducted to evaluate the effects of tanezumab or the murine precursor muMab911 on selected bone and joint endpoints and biomarkers in cynomolgus monkeys, Sprague-Dawley rats, and C57BL/6 mice. Joint and bone endpoints included histology, immunohistochemistry, microcomputed tomography (mCT) imaging, and serum biomarkers of bone physiology. Responses of bone endpoints to tanezumab were evaluated in monkeys at 4 to 30 mg/kg/week for 26 weeks and in rats at 0.2 to 10 mg/kg twice weekly for 28 days. The effects of muMab911 at 10 mg/kg/week for 12 weeks on selected bone endpoints were determined in mice. Tanezumab and muMab911 had no adverse effects on any bone or joint parameter. There were no test article-related effects on bone or joint histology, immunohistochemistry, or structure. Reversible, higher osteocalcin concentrations occurred only in the rat study. No deleterious effects were observed in joints or bones in monkeys, rats, or mice administered high doses of tanezumab or muMab911.
Verbal Pseudocoordination in English: A syntactic analysis with reference to diachronic, dialectal and cross-linguistic variation (2013)

Pseudocoordination is a term that encompasses any natural language phenomenon in which apparent coordination (the presence of and) does not correspond to strictly coordinative syntax or semantics. For verbal pseudocoordination in English, two representative examples are try and do and go and get. The goals of this paper are to: 1) report the descriptive data that must be accounted for in any analysis of verbal pseudocoordination in English; and 2) analyze the syntactic properties of the try-and-type of verbal pseudocoordination, which will be shown to share some properties with coordination and others with to-subordination. An Appendix will also provide an overview of verbal pseudocoordination in other languages and a typology of verbal pseudocoordination in English that explains the diachronic development of these structures. 1.
Microbiome profile informs cleansing and storage practices for reusable feeding tube stylets in critical care (2022)

The abundance of several potentially opportunistic pathogens indicated plausible risk for gut contamination secondary to reinsertion of stylets into small-bore feeding tubes. Stylet cleansing with 70% isopropyl alcohol reduced bacterial burden on the stylets, although viability was unknown. Careful cleansing, handling, and storage protocols for reusable stylets are necessary to minimize contamination.
Cryptosporidium parvumInduces B7‐H1 Expression in Cholangiocytes by Down‐Regulating MicroRNA‐513 (2009)

Expression of B7 costimulatory molecules represents an important compartment of immune response of epithelial cells after microbial infection. We report here that the protozoan parasite Cryptosporidium parvum induced B7-H1 expression in cultured human cholangiocytes. Induced expression of B7-H1 was identified in cells after exposure to infective C. parvum parasite or parasite lysate. Interestingly, the level of microRNA-513 (miR-513) was reduced in cells after exposure to C. parvum, which resulted in a relief of 3' untranslated region-mediated translational suppression of B7-H1. Overexpression of miR-513 through transfection of miR-513 precursor inhibited C. parvum-induced B7-H1 protein expression. Moreover, enhanced apoptotic cell death was identified in activated human T cells after coculture with C. parvum-infected cholangiocytes. The apoptosis of activated T cells was partially blocked by a neutralizing antibody to B7-H1 or transfection of cholangiocytes with miR-513 precursor. These data suggest a role of miR-513 in regulating B7-H1 expression by cholangiocytes in response to C. parvum infection.
Observation of J/ψp resonances consistent with pentaquark states in Λ[0 over b] → J/ψK[superscript -]p decays (2015)

Observations of exotic structures in the J/ψp channel, which we refer to as charmonium-pentaquark states, in Λ[0 over b] → J/ψK[superscript -]p decays are presented. The data sample corresponds to an integrated luminosity of 3 fb[superscript -1] acquired with the LHCb detector from 7 and 8 TeV pp collisions. An amplitude analysis of the three-body final state reproduces the two-body mass and angular distributions. To obtain a satisfactory fit of the structures seen in the J/ψp mass spectrum, it is necessary to include two Breit-Wigner amplitudes that each describe a resonant state. The significance of each of these resonances is more than 9 standard deviations. One has a mass of 4380 ± 8 ± 29 MeV and a width of 205 ± 18 ± 86 MeV, while the second is narrower, with a mass of 4449.8 ± 1.7 ± 2.5 MeV and a width of 39 ± 5 ± 19 MeV. The preferred J[superscript P] assignments are of opposite parity, with one state having spin 3/2 and the other 5/2.
The Chk2 Tumor Suppressor Is Not Required for p53 Responses in Human Cancer Cells (2003)

Ionizing radiation damages chromosomal DNA and activates p53-dependent transcription in mammalian cells. The Chk2 protein kinase has been hypothesized to be the primary mediator of this response. We have rigorously tested this hypothesis in human cells by disrupting the CHK2 gene through homologous recombination. We found that the p53 response was unexpectedly robust in such cells. Phosphorylation of p53 at serine 20, accumulation of p53 protein, transcriptional activation of p53 target genes, and cell cycle arrest and apoptotic death phenotypes were completely intact regardless of CHK2 status. Our results indicate that Chk2 kinase is not required for p53 activation in human cells and explain why CHK2 and TP53 mutations can jointly occur in human tumors.
Association of p53 mutations with metastatic prostate cancer. (1995)

In prostate cancer, mutation of the p53 tumor suppressor gene has been associated with locally advanced disease and hormone-resistant disease that is predominantly localized to bone. However, little is known regarding the status of the p53 gene in metastatic prostate cancer that has not been treated with hormonal manipulation. We evaluated formalin-fixed, paraffin-embedded malignant tissues from 86 patients with various stages of prostate cancer, including pathologically confined, locally advanced, and metastatic disease, to detect abnormal p53 nuclear protein accumulation using immunohistochemistry. No abnormal p53 immunostaining was detected in 18 patients with prostate cancer confined to the gland. Two tumors from 21 patients with locally advanced disease (extracapsular extension and/or seminal vesicle invasion) had abnormal nuclear p53 accumulation, and a mutation in exon 7 of the p53 gene was detected in tumor DNA from one patient using single-strand conformation polymorphism-direct sequencing analysis. Of the remaining 47 patients studied in whom tissues from the prostate gland and a metastatic site (44 lymph node, 2 bone, and 1 lung) were available, only 3 had received hormonal therapy prior to obtaining metastatic tissue. In four patients both primary and metastatic tumors demonstrated accumulation of p53 protein, whereas seven additional patients exhibited p53 accumulation only at the metastatic site. In three patients the metastatic tumors harbored missense single-base substitutions in exon 5, as detected using single-strand conformation polymorphism-direct sequencing. These results indicate that p53 abnormalities are associated with lymph node metastases derived from prostate cancer patients that had not undergone hormonal therapy.
Domed and Released Thin-Film Construct—An Approach for Material Characterization and Compliant Interconnects (2011)

An approach for microfabricating precisely defined spherical 3-D domes through a simple low-temperature polymer reflow process was developed. Release of a thin metal film patterned over the domed structure was accomplished by the removal of the underlying polymer using two different methods: dry thermal decomposition and wet supercritical release. The domed shape impacted the effect of stiction during the release step and assisted in the release of large millimeter-size film geometries. The dome and release procedures were used to fabricate an experimental test specimen that functions as either a tensile or interfacial fracture test for thin films on rigid substrates. Other potential applications of the domed metal structures such as compliant electrical interconnects are discussed.
Characterization and Optimization of Cell Seeding in Scaffolds by Factorial Design: Quality by Design Approach for Skeletal Tissue Engineering (2011)

Cell seeding into scaffolds plays a crucial role in the development of efficient bone tissue engineering constructs. Hence, it becomes imperative to identify the key factors that quantitatively predict reproducible and efficient seeding protocols. In this study, the optimization of a cell seeding process was investigated using design of experiments (DOE) statistical methods. Five seeding factors (cell type, scaffold type, seeding volume, seeding density, and seeding time) were selected and investigated by means of two response parameters, critically related to the cell seeding process: cell seeding efficiency (CSE) and cell-specific viability (CSV). In addition, cell spatial distribution (CSD) was analyzed by Live/Dead staining assays. Analysis identified a number of statistically significant main factor effects and interactions. Among the five seeding factors, only seeding volume and seeding time significantly affected CSE and CSV. Also, cell and scaffold type were involved in the interactions with other seeding factors. Within the investigated ranges, optimal conditions in terms of CSV and CSD were obtained when seeding cells in a regular scaffold with an excess of medium. The results of this case study contribute to a better understanding and definition of optimal process parameters for cell seeding. A DOE strategy can identify and optimize critical process variables to reduce the variability and assists in determining which variables should be carefully controlled during good manufacturing practice production to enable a clinically relevant implant.
A new method to evaluate lower eyelid sag using three‐dimensional image analysis (2005)

Lower eyelid sags as well as wrinkles represent age-related morphological changes of the skin surface. However, a quantitative method to evaluate lower eyelid sagging has not been previously established. We designed a new quantitative evaluation method that uses non-invasive skin scanning, which is based on the difference between the superficial dimension of the sagging surface of the lower eyelid and the dimension of its projection area. In 97 females, 2-D and the 3-D images were taken. By 3-D image analysis, the difference between the superficial dimension of the sagging surface of the lower eyelid and the dimension of its virtual projection area was assessed, and was defined as the sag parameter. This parameter was significantly correlated with the sag score (a photographic scale to assess the degree of sagging) and with aging. The accuracy of the sag parameter was confirmed in a clinical test using a sag treatment lotion and a placebo lotion. The sag score decreased in skin treated with the sag treatment lotion, but the change was not significantly different from that of the placebo treated skin. On the contrary, the sag parameter was significantly reduced (P < 0.05) after topical application of the sag treatment lotion compared with the placebo-treated skin. These results indicate that the sag parameter as proposed herein is useful in clinical studies to evaluate slight changes in lower eyelid sagging.
Sensory neuropathy-causing mutations in ATL3 cause aberrant ER membrane tethering (2017)

SUMMARY The ER is a complex network of sheets and tubules that is continuously being remodeled. The relevance of this membrane dynamics is underscored by the fact that mutations in Atlastins (ATL), the ER fusion proteins in mammals, cause neurodegeneration. How defects in this process disrupt neuronal homeostasis is largely unknown. Here we show by EM volume reconstruction of transfected cells, neurons and patient fibroblasts that the HSAN-causing ATL3 mutants promote aberrant ER tethering hallmarked by bundles of laterally attached ER tubules. In vitro , these mutants cause excessive liposome tethering, recapitulating the results in cells. Moreover, ATL3 variants retain their dimerization-dependent GTPase activity, but are unable to promote membrane fusion, suggesting a defect on an intermediate step of the ATL3 functional cycle. Our data therefore show that the effects of ATL3 mutations on ER network organization stretch beyond a loss of fusion, shedding a new light on neuropathies caused by atlastin defects.
Paramagnetic centers in the nickel-containing, deazaflavin-reducing hydrogenase from Methanobacterium thermoautotrophicum (1983)

Two hydrogenases from the methanogenic bacterium Methanobacterium thermoautotrophicum strain DeltaH have been purified and contain tightly bound nickel as well as the anticipated iron/sulfur atoms with a fixed ratio of 15-20 iron atoms per nickel. One hydrogenase reduces the 8-hydroxy-5-deazaflavin coenzyme factor 420 (F(420)), whereas the other has been purified as a methyl viologen-reducing hydrogenase. Both enzymes possess an EPR signal attributed to paramagnetic nickel as demonstrated by hyperfine coupling in (61)Ni-containing hydrogenases. Comparison to model compounds suggests a nickel(III) oxidation state in the inactive forms of these aerobically purified enzymes. Loss of the nickel(III) signal accompanies reductive activation but is not kinetically correlated with regain of high specific activity. On replacement of H(2) by argon in the gas phase over reduced, active, F(420)-reducing enzyme, several EPR signals appear, including a signal at g = 2.004 that is probably enzyme-bound FADH semiquinone, two signals at g = 2.140 and 2.196 that reflect a new form of paramagnetic nickel(III), and also a signal at g = 2.036 that may be an iron signal. The F(420)-reducing hydrogenase in the second paramagnetic nickel form is either itself active or in facile equilibrium with active enzyme. The size of the signal at g = 2.036 may correlate with the degree of activation of the enzyme. In contrast to the hydrogenase of Clostridium pasteurianum [Erbes, D. L., Burris, R. H. & Orme-Johnson, W. H. (1975) Proc. Natl. Acad. Sci. USA 72, 4795-4799], which appears to use only iron/sulfur prosthetic groups and which reacts with one-electron-transfer agents, this methanogen hydrogenase seems to utilize iron, nickel, and flavin redox sites and to reduce obligate one-electron (viologen) and two-electron (deazaflavin) oxidants.
Global computational alignment of tumor and cell line transcriptional profiles (2020)

Abstract Cell lines are key tools for preclinical cancer research, but it remains unclear how well they represent patient tumor samples. Identifying cell line models that best represent the features of particular tumor samples, as well as tumor types that lack in vitro model representation, remain important challenges. Gene expression has been shown to provide rich information that can be used to identify tumor subtypes, as well as predict the genetic dependencies and chemical vulnerabilities of cell lines. However, direct comparisons of tumor and cell line transcriptional profiles are complicated by systematic differences, such as the presence of immune and stromal cells in tumor samples and differences in the cancer-type composition of cell line and tumor expression datasets. To address these challenges, we developed an unsupervised alignment method (Celligner) and applied it to integrate several large-scale cell line and tumor RNA-Seq datasets. While our method aligns the majority of cell lines with tumor samples of the same cancer type, it also reveals large differences in tumor/cell line similarity across disease types. Furthermore, Celligner identifies a distinct group of several hundred cell lines from diverse lineages that present a more mesenchymal and undifferentiated transcriptional state and which exhibit distinct chemical and genetic dependencies. This method could thus be used to guide the selection of cell lines that more closely resemble patient tumors and improve the clinical translation of insights gained from cell line models.
Image Quality Evaluation and Tolerance Analysis for Camera Lenses with Diffractive Element (2006)

A novel image quality evaluation method, which is based on combination of the rigorous grating diffraction theory and the ray-optic method, is proposed. It is applied for design optimization and, tolerance analysis of optical imaging systems implementing diffractive optical elements (DOE). The evaluation method can predict the quality and resolution of the image on the image sensor plane through the optical imaging system. Especially, we can simulate the effect of diffraction efficiencies of DOE in the camera lenses module, which is very effective for predicting different color sense and MTF performance. Using this method, we can effectively determine the fabrication tolerances of diffractive and refractive optical elements such as the variations' in profile thickness, and the shoulder of the DOE, as well as conventional parameters such as decenter and tilt in optical-surface alignments. A DOE-based 2M-resolution camera lens module designed by the optimization process based on the proposed image quality evaluation method shows <TEX>${\sim}15%$</TEX> MTF improvement compared with a design without such an optimization.