gebhart/patrepeval huggingface dataset:
Effect of Rate on Adhesion and Static Friction of a Film-Terminated Fibrillar Interface (2009)

A film-terminated fibrillar interface has been shown to result in significant enhancement of adhesion and static friction compared to a flat control. This enhancement increases with interfibril spacing. In this, the first of a two-part study, by studying the effect of rate on adhesion and static friction, we show that both adhesion and static friction enhancement are due to a crack-trapping mechanism. For adhesion, as measured by an indentation experiment, an analytical model is used to relate the applied indenter displacement rate and measured forces to contact line velocity and energy release rate, respectively. The two mechanisms for adhesion enhancement--varying rate and crack-trapping--are found to be coupled multiplicatively.
A 1.2V 250mW 14b 100MS/s digitally calibrated pipeline ADC in 90nm CMOS (2008)

A 14b pipeline ADC is realized in 90nm CMOS at a 1.2V supply. Enabling techniques are range-scaling in the first pipeline stage with charge-reset and digital background calibration of non-linearity. The ADC achieves 73dB SNR and 91dB SFDR at 100MS/s sampling rate and 250mW power consumption. The 73dB SNDR performance is maintained within 3dB up to a Nyquist input frequency and the FOM is 0.7pJ/conv.
Abstract 3527: Combined high-throughput DNA genotyping and protein quantification in single cancer cells (2019)

Abstract Clonal genetic diversity is a hallmark of tumor biology. In many cancers, clonal evolution has been implicated as a driver of tumor initiation, progression, and relapse, and can be a prognostic indicator of disease outcome. Cancer cells are also phenotypically heterogeneous, constituting features which can enable intravasation and metastasis, or which can impart immunoevasive capabilities. Clinically, a combination of single-cell genotype and phenotype data from cancer biopsies could provide valuable insights into oncological disease states, such as metastatic risk or drug response. Here we present a multiomic technology for the simultaneous, high-throughput capture of DNA genotype and protein information from single cells, demonstrated through the analysis of acute myeloid leukemia (AML) derived cell lines. The experimental workflow leverages the high-throughput single-cell microfluidic droplet technology on the Mission Bio Tapestri platform, a system optimized to conduct multiplex targeted genomic DNA amplification from &amp;gt;50 AML-associated loci. In our modified workflow, cells are stained with a pool of monoclonal antibodies conjugated with barcoded oligonucleotides, enabling a sequencing-based readout of single-cell protein signatures. The sequencing data is analyzed with a bioinformatic pipeline that separates antibody signal from targeted genotyping data on a cell-by-cell basis. We find that on a mixed population of myelogenous leukemia cells and B-cells, single-cell genotype information effectively distinguishes between cell lines, while the protein data independently recapitulates the biological signal from conventional flow cytometric methods. In conclusion, this technology opens up a new era for discovery using multiomic analysis of the complex relationships between genotype and phenotype in cancer, paving the way for future studies analyzing primary tissue samples. Citation Format: Benjamin Demaree, Cyrille Delley, David Ruff, Sebastian Treusch, Dennis Eastburn, Keith Jones, Adam Abate. Combined high-throughput DNA genotyping and protein quantification in single cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3527.
Automatic recovery of statecharts from procedural code (2012)

We have developed a static-analysis algorithm that extracts statecharts from procedural implementations of state machines. The extracted statecharts are semantically-equivalent to the original program, and can be used for further development instead of the procedural code. We have implemented this algorithm in a tool called StatRec. We report on the results of running StatRec on a number of examples, including an implementation of the TCP protocol.
Sialylated human milk oligosaccharides program cognitive development through a non-genomic transmission mode (2021)

Breastmilk contains bioactive molecules essential for brain and cognitive development. While sialylated human milk oligosaccharides (HMOs) have been implicated in phenotypic programming, their selective role and underlying mechanisms remained elusive. Here, we investigated the long-term consequences of a selective lactational deprivation of a specific sialylated HMO in mice. We capitalized on a knock-out (KO) mouse model (B6.129-St6gal1<sup>tm2Jxm</sup>/J) lacking the gene responsible for the synthesis of sialyl(alpha2,6)lactose (6'SL), one of the two sources of sialic acid (Neu5Ac) to the lactating offspring. Neu5Ac is involved in the formation of brain structures sustaining cognition. To deprive lactating offspring of 6'SL, we cross-fostered newborn wild-type (WT) pups to KO dams, which provide 6'SL-deficient milk. To test whether lactational 6'SL deprivation affects cognitive capabilities in adulthood, we assessed attention, perseveration, and memory. To detail the associated endophenotypes, we investigated hippocampal electrophysiology, plasma metabolomics, and gut microbiota composition. To investigate the underlying molecular mechanisms, we assessed gene expression (at eye-opening and in adulthood) in two brain regions mediating executive functions and memory (hippocampus and prefrontal cortex, PFC). Compared to control mice, WT offspring deprived of 6'SL during lactation exhibited consistent alterations in all cognitive functions addressed, hippocampal electrophysiology, and in pathways regulating the serotonergic system (identified through gut microbiota and plasma metabolomics). These were associated with a site- (PFC) and time-specific (eye-opening) reduced expression of genes involved in central nervous system development. Our data suggest that 6'SL in maternal milk adjusts cognitive development through a short-term upregulation of genes modulating neuronal patterning in the PFC.
Photoactivated Bioconjugation Between ortho-Azidophenols and Anilines: A Facile Approach to Biomolecular Photopatterning (2014)

Methods for the surface patterning of small molecules and biomolecules can yield useful platforms for drug screening, synthetic biology applications, diagnostics, and the immobilization of live cells. However, new techniques are needed to achieve the ease, feature sizes, reliability, and patterning speed necessary for widespread adoption. Herein, we report an easily accessible and operationally simple photoinitiated reaction that can achieve patterned bioconjugation in a highly chemoselective manner. The reaction involves the photolysis of 2-azidophenols to generate iminoquinone intermediates that couple rapidly to aniline groups. We demonstrate the broad functional group compatibility of this reaction for the modification of proteins, polymers, oligonucleotides, peptides, and small molecules. As a specific application, the reaction was adapted for the photolithographic patterning of azidophenol DNA on aniline glass substrates. The presence of the DNA was confirmed by the ability of the surface to capture living cells bearing the sequence complement on their cell walls or cytoplasmic membranes. Compared to other light-based DNA patterning methods, this reaction offers higher speed and does not require the use of a photoresist or other blocking material.
IL-4-STAT6 Signal Transduction-Dependent Induction of the Clinical Phase of Sjogren’s Syndrome-Like Disease of the Nonobese Diabetic Mouse (2007)

NOD.B10-H2(b) and NOD/LtJ mice manifest, respectively, many features of primary and secondary Sjögren's syndrome (SjS), an autoimmune disease affecting primarily the salivary and lacrimal glands leading to xerostomia (dry mouth) and xerophthalmia (dry eyes). B lymphocytes play a central role in the onset of SjS with clinical manifestations dependent on the appearance of autoantibodies reactive to multiple components of acinar cells. Previous studies with NOD.IL4(-/-) and NOD.B10-H2(b).IL4(-/-) mice suggest that the Th2 cytokine, IL-4, plays a vital role in the development and onset of SjS-like disease in the NOD mouse model. To investigate the molecular mechanisms by which IL-4 controls SjS development, a Stat6 gene knockout mouse, NOD.B10-H2(b).C-Stat6(-/-), was constructed and its disease profile was defined and compared with that of NOD.B10-H2(b).C-Stat6(+/+) mice. As the NOD.B10-H2(b).C-Stat6(-/-) mice aged from 4 to 24 wk, they exhibited leukocyte infiltration of the exocrine glands, produced anti-nuclear autoantibodies, and showed loss and gain of saliva-associated proteolytic enzymes, similar to NOD.B10-H2(b).C-Stat6(+/+) mice. In contrast, NOD.B10-H2(b).C-Stat6(-/-) mice failed to develop glandular dysfunction, maintaining normal saliva flow rates. NOD.B10-H2(b).C-Stat6(-/-) mice were found to lack IgG1 isotype-specific anti-muscarinic acetylcholine type-3 receptor autoantibodies. Furthermore, the IgG fractions from NOD.B10-H2(b).C-Stat6(-/-) sera were unable to induce glandular dysfunction when injected into naive recipient C57BL/6 mice. NOD.B10-H2(b).C-Stat6(-/-) mice, like NOD.B10-H2(b).IL4(-/-) mice, are unable to synthesize IgG1 Abs, an observation that correlates with an inability to develop end-stage clinical SjS-like disease. These data imply a requirement for the IL-4/STAT6-pathway for onset of the clinical phase of SjS-like disease in the NOD mouse model.
Efficient Space-Time Block Codes Derived from Quasi-Orthogonal Structures (2007)

We propose a new class of block codes that outperforms known space-time block codes at low rates. The new codes are designed by using appropriate rotations and set partitioning on two quasi-orthogonal codes, and combining subsets of their codewords. Using these techniques we are able to obtain higher coding gain at a given rate and improve performance. Simulations confirm the advantages of this code compared to other codes operating at the same rate and signal-to-noise ratio (SNR). We also provide an efficient maximum likelihood (ML) decoding algorithm for the new code
Pseudomonas aeruginosa Population Structure Revisited (2009)

At present there are strong indications that Pseudomonas aeruginosa exhibits an epidemic population structure; clinical isolates are indistinguishable from environmental isolates, and they do not exhibit a specific (disease) habitat selection. However, some important issues, such as the worldwide emergence of highly transmissible P. aeruginosa clones among cystic fibrosis (CF) patients and the spread and persistence of multidrug resistant (MDR) strains in hospital wards with high antibiotic pressure, remain contentious. To further investigate the population structure of P. aeruginosa, eight parameters were analyzed and combined for 328 unrelated isolates, collected over the last 125 years from 69 localities in 30 countries on five continents, from diverse clinical (human and animal) and environmental habitats. The analysed parameters were: i) O serotype, ii) Fluorescent Amplified-Fragment Length Polymorphism (FALFP) pattern, nucleotide sequences of outer membrane protein genes, iii) oprI, iv) oprL, v) oprD, vi) pyoverdine receptor gene profile (fpvA type and fpvB prevalence), and prevalence of vii) exoenzyme genes exoS and exoU and viii) group I pilin glycosyltransferase gene tfpO. These traits were combined and analysed using biological data analysis software and visualized in the form of a minimum spanning tree (MST). We revealed a network of relationships between all analyzed parameters and non-congruence between experiments. At the same time we observed several conserved clones, characterized by an almost identical data set. These observations confirm the nonclonal epidemic population structure of P. aeruginosa, a superficially clonal structure with frequent recombinations, in which occasionally highly successful epidemic clones arise. One of these clones is the renown and widespread MDR serotype O12 clone. On the other hand, we found no evidence for a widespread CF transmissible clone. All but one of the 43 analysed CF strains belonged to a ubiquitous P. aeruginosa "core lineage" and typically exhibited the exoS(+)/exoU(-) genotype and group B oprL and oprD alleles. This is to our knowledge the first report of an MST analysis conducted on a polyphasic data set.
Enhancer sharing promotes neighborhoods of transcriptional regulation across eukaryotes (2016)

Enhancers physically interact with transcriptional promoters, looping over distances that can span multiple regulatory elements. Given that enhancer-promoter (EP) interactions generally occur via common protein complexes, it is unclear whether EP pairing is predominantly deterministic or proximity guided. Here we present cross-organismic evidence suggesting that most EP pairs are compatible, largely determined by physical proximity rather than specific interactions. By re-analyzing transcriptome datasets, we find that the transcription of gene neighbors is correlated over distances that scale with genome size. We experimentally show that non-specific EP interactions can explain such correlation, and that EP distance acts as a scaling factor for the transcriptional influence of an enhancer. We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation.
The Relation Between Depressive Symptoms and Semantic Memory in Amnestic Mild Cognitive Impairment and in Late-Life Depression (2011)

Semantic deficits have been documented in the prodromal phase of Alzheimer's disease, but it is unclear whether these deficits are associated with non-cognitive manifestations. For instance, recent evidence indicates that cognitive deficits in elders with amnestic mild cognitive impairment (aMCI) are modulated by concomitant depressive symptoms. The purposes of this study were to (i) investigate if semantic memory impairment in aMCI is modulated according to the presence (aMCI-D group) or absence (aMCI group) of depressive symptoms, and (ii) compare semantic memory performance of aMCI and aMCI-D groups to that of patients with late-life depression (LLD). Seventeen aMCI, 16 aMCI-D, 15 LLD, and 26 healthy control participants were administered a semantic questionnaire assessing famous person knowledge. Results showed that performance of aMCI-D patients was impaired compared to the control and LLD groups. However, in the aMCI group performance was comparable to that of all other groups. Overall, these findings suggest that semantic deficits in aMCI are somewhat associated with the presence of concomitant depressive symptoms. However, depression alone cannot account solely for the semantic deficits since LLD patients showed no semantic memory impairment in this study. Future studies should aim at clarifying the association between depression and semantic deficits in older adults meeting aMCI criteria. (JINS, 2011, 17, 865-874).
T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly (2016)

GH-secreting pituitary adenomas can be hypo-, iso- or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 3 months were included in the study. Hormonal, clinical and general MRI assessments were performed and assessed centrally. We included 120 patients with acromegaly. At diagnosis, 84, 17 and 19 tumors were T2-hypo-, iso- and hyper-intense, respectively. SSA treatment duration, cumulative and mean monthly doses were similar in the three groups. Patients with T2-hypo-intense adenomas had median SSA-induced decreases in GH and IGF-1 of 88% and 59% respectively, which were significantly greater than the decreases observed in the T2-iso- and hyper-intense groups (P < 0.001). Tumor shrinkage on SSA was also significantly greater in the T2-hypo-intense group (38%) compared with the T2-iso- and hyper-intense groups (8% and 3%, respectively; P < 0.0001). The response to SSA correlated with the calculated T2 intensity: the lower the T2-weighted intensity, the greater the decrease in random GH (P < 0.0001, r = 0.22), IGF-1 (P < 0.0001, r = 0.14) and adenoma volume (P < 0.0001, r = 0.33). The T2-weighted signal intensity of GH-secreting adenomas at diagnosis correlates with hormone reduction and tumor shrinkage in response to primary SSA treatment in acromegaly. This study supports its use as a generally available predictive tool at diagnosis that could help to guide subsequent treatment choices in acromegaly.
MicroRNA-29 Overexpression Delivered By Adeno-Associated Virus Suppresses Fibrosis in mdx:utrn+/- Mice (S61.003) (2014)

OBJECTIVE: To demonstrate the degree of muscle fibrosis in mdx:utrn +/- mice and in dystrophin-deficient patient-derived muscle biopsies, correlate changes with microRNA-29 (miR-29), and develop anti-fibrotic therapy using miR-29 delivered by adeno-associated virus (AAV).
BACKGROUND: Duchenne muscular dystrophy (DMD) is caused by dystrophin deficiency resulting in muscle loss and progressive weakness, and fibrotic scarring. Muscle fibrosis impairs blood flow and excludes endomysial-derived constituents hampering muscle repair and regeneration. Fibrosis contributes to limb contractures and loss of ambulation. Irrespective of the success of gene restoration (molecular or pharmacologic), functional improvement mandates reduction of muscle fibrosis. mRNA-29 is a potential gene regulator and an ideal candidate for reducing muscle fibrosis.
DESIGN/METHODS: Connective tissue was quantified from muscle biopsies of dystrophin-deficient patients, the mdx or mdx:utrn +/- mouse models. Endomysial fibrosis was quantified using Sirius Red-stained sections analyzed by NIH ImageJ Software. 59-nuclease assays were used to measure miR-29 expression correlated with levels of fibrosis. AAV was used to deliver miR-29 into mouse muscle via intramuscular injection.
RESULTS: Endomysial connective tissue levels were uniformly increased in the muscles of mdx mice, and in muscle biopsies from DMD patients. Findings correlated with downregulation of miR-29a and miR-29c in the mouse disease model, and in patient biopsies. Initial findings from mdx:utrn +/- mouse muscles treated with AAV-miR29c suggest a favorable anti-fibrotic response that is varied among the treatment groups.
CONCLUSIONS: Demonstration of increased fibrosis and decreased miR-29 expression in mdx:utrn +/- mice and dystrophin-deficient patients validates the mouse model as being representative of the human disease. Initial results using AAV-delivered miR29 as an anti-fibrotic therapy suggest that significant beneficial effects can be achieved with further optimization. These data provide a rationale for overexpression of miR-29 to reduce fibrosis in translational, preclinical studies in mdx:utrn +/- mice in preparation for clinical trials.
Study Supported by: NIH Ruth L. Kirschstein National Research Service Award (F32) Disclosure: Dr. Meadows has nothing to disclose. Dr. Kota has nothing to disclose. Dr. Malik has nothing to disclose. Dr. Clark has nothing to disclose. Dr. Sahenk has received research support from Sarepta Therapeutics. Dr. Harper has nothing to disclose. Dr. Mendell has received research support from Sarepta Therapeutics Inc.
Implementation of a qPCR assay coupled with genomic surveillance for real-time monitoring of SARS-CoV-2 variants of concern (2021)

Abstract We developed a genomic surveillance program for real-time monitoring of SARS-CoV-2 variants of concern in Uruguay. Here, we present the first results, including the proposed qPCR-VOC method, the general workflow and the report of the introduction and community transmission of the VOC P.1 in Uruguay in multiple independent events.
The Epithelial Calcium Channel TRPV5 Is Regulated Differentially by Klotho and Sialidase (2013)

The transient receptor potential vanilloid type 5 (TRPV5) Ca(2+) channel facilitates transcellular Ca(2+) transport in the distal convoluted tubule (DCT) of the kidney. The channel is glycosylated with a complex type N-glycan and it has been postulated that hydrolysis of the terminal sialic acid(s) stimulate TRPV5 activity. The present study delineates the role of the N-glycan in TRPV5 activity using biochemical assays in Human Embryonic Kidney 293 cells expressing TRPV5, isoelectric focusing and total internal reflection fluorescent microscopy. The anti-aging hormone klotho and other glycosidases stimulate TRPV5-dependent Ca(2+) uptake. Klotho was found to increase the plasma membrane stability of TRPV5, via the TRPV5 N-glycan. Sialidase mimicked this stimulatory action. However, this effect was independent of the N-glycosylation state of TRPV5, since the N-glycosylation mutant (TRPV5(N358Q)) was activated to the same extent. We showed that the increased TRPV5 activity after sialidase treatment is caused by inhibition of lipid raft-mediated internalization. In addition, sialidase modified the N-glycan of transferrin, a model glycoprotein, differently from klotho. Previous studies showed that after klotho treatment, galectin-1 binds the TRPV5 N-glycan and thereby increases TRPV5 activity. However, galectin-3, but not galectin-1, was expressed in the DCT. Furthermore, an increase in TRPV5-mediated Ca(2+) uptake was detected after galectin-3 treatment. In conclusion, two distinct TRPV5 stimulatory mechanisms were demonstrated; a klotho-mediated effect that is dependent on the N-glycan of TRPV5 and a sialidase-mediated stimulation that is lipid raft-dependent and independent of the N-glycan of TRPV5.
Tomosynthesis‐based localization of radioactive seeds in prostate brachytherapy (2003)

Accurately assessing the quality of prostate brachytherapy intraoperatively would be valuable for improved clinical outcome by ensuring the delivery of a prescribed tumoricidal radiation dose to the entire prostate gland. One necessary step towards this goal is the robust and rapid localization of implanted seeds. Several methods have been developed to locate seeds from x-ray projection images, but they fail to detect completely-overlapping seeds, thus necessitating manual intervention. To overcome this limitation, we have developed a new method where (1) a three-dimensional volume is reconstructed from x-ray projection images using a brachytherapy-specific tomosynthesis reconstruction algorithm with built-in blur compensation and (2) the seeds are located in this reconstructed volume. In contrast to other projection-based methods, our method can detect completely overlapping seeds. Our simulation results indicate that we can locate all implanted seeds in the prostate using a tomosynthesis angle of 30 degrees and seven projection images. The mean localization error is 1.27 mm for a case with 100 seeds. We have also tested our method using a prostate phantom with 61 implanted seeds and succeeded in locating all seeds automatically. We believe this new method can be useful for the intraoperative quality assessment of prostate brachytherapy in the future.
MACULAR HOLE DIAMETER AFTER VITRECTOMY FOR MACULAR HOLE AND RETINAL DETACHMENT (2005)

Persistent MHs after vitrectomy were enlarged according to axial length elongation in highly myopic eyes. Even if MH closure was not successful, the maximum effort to shorten postoperative MH size led to a better postoperative outcome.