gebhart/patrepeval huggingface dataset:
Supplementary Table 2 from Identification of Copy Number Abnormalities and Inactivating Mutations in Two Negative Regulators of Nuclear Factor-κB Signaling Pathways in Waldenstrom's Macroglobulinemia (2023)

Supplementary Table 2 from Identification of Copy Number Abnormalities and Inactivating Mutations in Two Negative Regulators of Nuclear Factor-κB Signaling Pathways in Waldenström's Macroglobulinemia
Data from VEGF/Neuropilin-2 Regulation of Bmi-1 and Consequent Repression of IGF-IR Define a Novel Mechanism of Aggressive Prostate Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;We show that the VEGF receptor neuropilin-2 (NRP2) is associated with high-grade, PTEN-null prostate cancer and that its expression in tumor cells is induced by PTEN loss as a consequence of c-Jun activation. VEGF/NRP2 signaling represses insulin-like growth factor-1 receptor (IGF-IR) expression and signaling, and the mechanism involves Bmi-1–mediated transcriptional repression of the &lt;i&gt;IGF-IR&lt;/i&gt;. This mechanism has significant functional and therapeutic implications that were evaluated. IGF-IR expression positively correlates with PTEN and inversely correlates with NRP2 in prostate tumors. NRP2 is a robust biomarker for predicting response to IGF-IR therapy because prostate carcinomas that express NRP2 exhibit low levels of IGF-IR. Conversely, targeting NRP2 is only modestly effective because NRP2 inhibition induces compensatory IGF-IR signaling. Inhibition of both NRP2 and IGF-IR, however, completely blocks tumor growth &lt;i&gt;in vivo&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Significance:&lt;/b&gt; These results identify a causal role for NRP2 and VEGF/NRP2 signaling in the behavior of aggressive prostate cancers by a mechanism that involves regulation of Bmi-1, a transcriptional repressor implicated in the etiology of prostate cancer induced by loss of PTEN function, and the repression of the IGF-IR. The therapeutic implications are significant because combined inhibition of NRP2 and IGF-IR overcomes the resistance induced by targeting each receptor individually. &lt;i&gt;Cancer Discov; 2(10); 906–21. ©2012 AACR&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;This article is highlighted in the In This Issue feature, p. 857.&lt;/p&gt;&lt;/div&gt;
Alzheimer’s Biomarkers From Multiple Modalities Selectively Discriminate Clinical Status: Relative Importance of Salivary Metabolomics Panels, Genetic, Lifestyle, Cognitive, Functional Health and Demographic Risk Markers (2018)

<b>Background</b>: Among the neurodegenerative diseases of aging, sporadic Alzheimer's disease (AD) is the most prevalent and perhaps the most feared. With virtually no success at finding pharmaceutical therapeutics for altering progressive AD after diagnosis, research attention is increasingly directed at discovering biological and other markers that detect AD risk in the long asymptomatic phase. Both early detection and precision preclinical intervention require systematic investigation of multiple modalities and combinations of AD-related biomarkers and risk factors. We extend recent unbiased metabolomics research that produced a set of metabolite biomarker panels tailored to the discrimination of cognitively normal (CN), cognitively impaired and AD patients. Specifically, we compare the prediction importance of these panels with five other sets of modifiable and non-modifiable AD risk factors (genetic, lifestyle, cognitive, functional health and bio-demographic) in three clinical groups. <b>Method</b>: The three groups were: CN (<i>n</i> = 35), mild cognitive impairment (MCI; <i>n</i> = 25), and AD (<i>n</i> = 22). In a series of three pairwise comparisons, we used machine learning technology random forest analysis (RFA) to test relative predictive importance of up to 19 risk biomarkers from the six AD risk domains. <b>Results</b>: The three RFA multimodal prediction analyses produced significant discriminating risk factors. First, discriminating AD from CN was the AD metabolite panel and two cognitive markers. Second, discriminating AD from MCI was the AD/MCI metabolite panel and two cognitive markers. Third, discriminating MCI from CN was the MCI metabolite panel and seven markers from four other risk modalities: genetic, lifestyle, cognition and functional health. <b>Conclusions</b>: Salivary metabolomics biomarker panels, supplemented by other risk markers, were robust predictors of: (1) clinical differences in impairment and dementia and even; (2) subtle differences between CN and MCI. For the latter, the metabolite panel was supplemented by biomarkers that were both modifiable (e.g., functional) and non-modifiable (e.g., genetic). Comparing, integrating and identifying important multi-modal predictors may lead to novel combinations of complex risk profiles potentially indicative of neuropathological changes in asymptomatic or preclinical AD.
Stimulating Progress in Regenerative Medicine: Improving the Cloning and Recovery of Cryopreserved Human Pluripotent Stem Cells with ROCK Inhibitors (2010)

Until recently, culturing human pluripotent stem cells was hampered by three prominent technical problems: a high degree of unwanted cellular stress when the cells are passaged, unacceptably low cloning efficiency and poor recovery of cryopreserved stocks. This review discusses recent developments that address these problems. A major focus of the review is the use of p160 Rho-associated coiled-coil kinase inhibitors for improving both the cloning efficiency and the recovery of cryopreserved human embryonic stem cells and human induced pluripotent stem cells. An underlying theme of this review is that the three problems have a common cause: separation of human pluripotent stem cells from one another increases cellular stress, which greatly decreases their viability unless special steps are taken.
Increased oxidative stress and impaired natriuresis in aldosterone (Aldo)‐infused, high‐sodium‐diet (HSD) fed P2Y2‐receptor knockout (KO) mice (2011)

P2Y2-R opposes Aldo, and interacts with PGE2 and NO in the kidney. We found elevated urinary levels of 8-isoprostane, a marker of oxidative stress (OS) in P2Y2-R KO mice fed HSD. We hypothesized that P2Y2-R facilitates Na excretion by counteracting OS due to HSD and that differences in aldosterone sensitivity might play a role. Hence we studied the combined effect of Aldo and HSD on NO, PGE2, and OS in P2Y2-R KO mice. Groups (n = 5) of WT and KO mice were chronically infused with Aldo (20 μg/day), and were fed low-Na (0.03%) diet for 3 days, followed by HSD (3.51% Na) for 4 days and euthanized. At that point KO mice had significantly impaired natriuresis, significant elevation in urinary PGE2 and 8-isoprostane, and decreased total urinary NO3/NO2 vs. WT mice. The mRNA expression of iNOS and eNOS were significantly lower and that of COX-2 higher in the kidneys of KO vs. WT mice. Kidneys of KO mice also showed elevated protein abundances of cortical NHE3 and medullary NKCC2, which may be due to decrease in NO. In addition, the enhanced OS in KO relative to WT mice might potentially modulate the outcome of interactions of NO with Na transporters. Finally, it appears that in the absence of P2Y2-R signaling, COX-2 is induced as a redundant mechanism in an attempt to alleviate Na retention. These observations underscore the Na-homeostatic value of P2Y2-R, especially in Na-retentive states, such as HSD and/or Aldo excess. Funding: VA, NKF, & AHA.
The Extractable and Bound Condensed Tannin Content of Leaves from Tropical Tree, Shrub and Forage Legumes (1996)

The extractable, protein-bound and fibre-bound condensed tannin (CT) concentrations in the leaves of tropical legumes grown in both Colombia and Northern Australia were determined by the butanol–HCl method, whilst extractable CT was also determined by the vanillin–HCl method. With the exception of Senna siameaall species contained CT. The very high CT concentration found in many plants growing in Colombia may have been partly due to soil fertility being much lower at the Colombian than the Northern Australian site.Acacia boliviana,Arachis pintoi,Centrosema latidens,Senna velutinaandGliricidia sepiumcontained <55 g total CT kg−1 DM, which suggests that they could comprise a reasonable proportion of ruminant diets. All other species grown in South America contained 100–240 g CT kg−1 DM, which suggests that they should only be fed in small amounts as supplements to dilute the CT concentration.Leucaenaspecies andCalliandra calothyrsusgrown in Northern Australia contained intermediate concentrations of total CT (60–90 g kg−1 DM). Most species contained 70–95% of total CT as extractable CT, with the exception ofFlemingia macrophylla, where 60% was extractable and 40% bound, andGliricidia sepium, where almost all the CT was bound to protein. Values forFlemingia macrophylladiffered between accessions. Extractable CT determined with vanillin–HCl was generally higher than extractable CT determined with butanol–HCl. Three accessions showed negligible (<1 g kg−1 DM) extractable CT with butanol–HCl but 10–12 g extractable CT kg−1 DM with vanillin–HCl. Two accessions showed undetectable levels of extractable CT but substantial levels of protein-bound CT, illustrating the importance of using a bound CT method for identifying forages containing CT. Relative to freeze drying, oven drying ofLeucaenaspecies reduced the concentration of extractable CT and increased concentrations of bound CT. The significance of the results for the nutrition of ruminant livestock are discussed, including the possible roles of protein-bound and fibre-bound CT.
O trabalho na rua e a exposição à violência no trabalho: um estudo com agentes de trânsito (2007)

Este estudo foi realizado com agentes de trânsito que, por diversas razões relacionadas à organização do trabalho e ao fato de terem a rua como espaço de trabalho, estão expostos a intensas situações de agressões verbais e, por vezes, físicas. Com base no estudo de uma situação particular, espera-se contribuir para a compreensão do impacto da violência na saúde mental dos trabalhadores que atuam na rua e seus reflexos na saúde, no desenvolvimento do trabalho e de suas relações. O trabalho baseou-se nos princípios teóricos/metodológicos da psicodinâmica do trabalho. Trata-se de um método circunscrito no âmbito da pesquisa-ação, que pressupõe uma ação transformadora na situação estudada. Resultados indicam que o convívio com a violência no exercício do trabalho produz nos trabalhadores, de um lado, um forte impacto na saúde mental e, de outro, o desenvolvimento de estratégias e uma inteligência relacionada ao trabalho para poderem continuar a trabalhar.
Studies in organic mass spectrometry. Part 24† Electron ionization mass spectra of some aryl(2-nitrobenzo[b]thiophen-3-yl)amines (1999)

The main fragmentation routes of eighteen title compounds and of three 5-chloro derivatives have been investigated with the aid of linked scan (B/E = constant) spectrometry, accurate mass measurements and deuterium labelling. Copyright 1999 John Wiley & Sons, Ltd.
The translational role of SOS1 in colorectal cancer (2022)

Abstract Background It has been challenging to develop agents directly targeting KRAS driver mutations in colorectal cancer (CRC). Recent efforts have focused on developing inhibitors targeting SOS1 as an attractive approach for KRAS -mutant cancers. Here, we aimed to study the translational role of SOS1 in CRC using patient-derived organoids (PDOs). Method In this study, we used CRC PDOs as preclinical models to evaluate their sensitivity to SOS1 inhibitor BI3406 and its cellular effects. We utilized large CRC datasets including GENIE cohort, TCGA PanCancer Atlas, and CPTAC-2 cohort to study the significance of molecular alterations of SOS1 in CRC. To identify potential predictive markers, we performed immunohistochemistry (IHC) on CRC tissue for SOS1/2 protein expression and RNA sequencing to identify discriminative gene sets for sensitivity to SOS1 inhibition. The findings were validated by DepMap data for SOS1 dependency. Result CRC PDOs instead of cell lines had differential sensitivities to BI3406. There was a significant correlation between SOS1 and SOS2 mRNA expressions (Spearman’s ρ 0.56, p&lt;0.001). SOS1/2 protein expression by IHC were universal with heterogeneous patterns in cancer cells but only minimal to none in surrounding non-malignant cells. SOS1 protein expression was associated with worse overall survival in patients with RAS/RAF mutant CRC ( p =0.04). We also found that SOS1/SOS2 protein expression ratio &gt; 1 by IHC ( p =0.03) instead of KRAS mutation ( p =1) was a better predictive marker to BI3406 sensitivity of CRC PDOs. This was concordant with the significant correlation between SOS1/SOS2 protein expression ratio by mass spectrometry and SOS1 dependency score. RNA-seq and gene set enrichment analysis revealed differentially expressed genes and 7 enriched gene sets involving cholesterol homeostasis, epithelial mesenchymal transition, and TNFα/NFκB signaling in BI3406-resistant CRC PDOs. We further discovered that GTP-bound RAS level underwent rebound at 48 hours upon treatment with BI3406 even in BI3406-sensitive PDOs with no change of KRAS effector genes downstream. Cellular adaptation mechanisms to SOS1 inhibition may involve upregulation of SOS1/2 mRNA and SOS1 protein expressions, which may be overcome by SOS1 knockdown/degradation or synergistic effect of BI3406 with trametinib. Conclusion In summary, CRC PDOs could serve as better models for translational study of SOS1 in CRC. High SOS1 protein expression was a worse prognostic factor in CRC. High SOS1/SOS2 protein expression ratio predicted sensitivity to SOS1 inhibition and dependency. Our preclinical findings supported further clinical development of SOS1-targeting agents in CRC.
Modeling of the Norwood circulation: effects of shunt size, vascular resistances, and heart rate (2001)

Hypoplastic left heart syndrome is the most common lethal cardiac malformation of the newborn. Its treatment, apart from heart transplantation, is the Norwood operation. The initial procedure for this staged repair consists of reconstructing a circulation where a single outlet from the heart provides systemic perfusion and an interpositioning shunt contributes blood flow to the lungs. To better understand this unique physiology, a computational model of the Norwood circulation was constructed on the basis of compartmental analysis. Influences of shunt diameter, systemic and pulmonary vascular resistance, and heart rate on the cardiovascular dynamics and oxygenation were studied. Simulations showed that 1) larger shunts diverted an increased proportion of cardiac output to the lungs, away from systemic perfusion, resulting in poorer O2 delivery, 2) systemic vascular resistance exerted more effect on hemodynamics than pulmonary vascular resistance, 3) systemic arterial oxygenation was minimally influenced by heart rate changes, 4) there was a better correlation between venous O2 saturation and O2 delivery than between arterial O2 saturation and O2 delivery, and 5) a pulmonary-to-systemic blood flow ratio of 1 resulted in optimal O2 delivery in all physiological states and shunt sizes.
Pulsed multiwavelength laser ranging system for measuring atmospheric delay: erratum (1981)

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 James B. Abshire, "Pulsed multiwavelength laser ranging system for measuring atmospheric delay: erratum," Appl. Opt. 20, 3821-3821 (1981) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Demonstration of using surface plasma enhanced magneto-optic Kerr effect to implement a compact micro-optofluidic sensor (2016)

A high-sensitivity biosensor is demonstrated by exploiting surface plasma (SP) enhanced transverse magneto-optical Kerr effect (TMOKE) on a packaged micro-optofluidic chip to implement a compact system for detecting chemical or biological objects. The SP grating made on a composite Au/Fe/Au layer exhibits a very dispersive Kerr parameter variation near the SP resonance wavelength. A preliminary experimental result on studying avidin-biotin interaction shows the sensitivity of avidin detection in PBS solution is about 31 nM.
Unique, Gender-Dependent Serum microRNA Profile in PLS3 Gene-Related Osteoporosis (2020)

Plastin 3 (PLS3), encoded by PLS3, is a newly recognized regulator of bone metabolism, and mutations in the encoding gene result in severe childhood-onset osteoporosis. Because it is an X chromosomal gene, PLS3 mutation-positive males are typically more severely affected whereas females portray normal to increased skeletal fragility. Despite the severe skeletal pathology, conventional metabolic bone markers tend to be normal and are thus insufficient for diagnosing or monitoring patients. Our study aimed to explore serum microRNA (miRNA) concentrations in subjects with defective PLS3 function to identify novel markers that could differentiate subjects according to mutation status and give insight into the molecular mechanisms by which PLS3 regulates skeletal health. We analyzed fasting serum samples for a custom-designed panel comprising 192 miRNAs in 15 mutation-positive (five males, age range 8-76 years, median 41 years) and 14 mutation-negative (six males, age range 8-69 years, median 40 years) subjects from four Finnish families with different PLS3 mutations. We identified a unique miRNA expression profile in the mutation-positive subjects with seven significantly upregulated or downregulated miRNAs (miR-93-3p, miR-532-3p, miR-133a-3p, miR-301b-3p, miR-181c-5p, miR-203a-3p, and miR-590-3p; p values, range .004-.044). Surprisingly, gender subgroup analysis revealed the difference to be even more distinct in female mutation-positive subjects (congruent p values, range .007-.086) than in males (p values, range .127-.843) in comparison to corresponding mutation-negative subjects. Although the seven identified miRNAs have all been linked to bone metabolism and two of them (miR-181c-5p and miR-203a-3p) have bioinformatically predicted targets in the PLS3 3' untranslated region (3'-UTR), none have previously been reported to associate with PLS3. Our results indicate that PLS3 mutations are reflected in altered serum miRNA levels and suggest there is crosstalk between PLS3 and these miRNAs in bone metabolism. These provide new understanding of the pathomechanisms by which mutations in PLS3 lead to skeletal disease and may provide novel avenues for exploring miRNAs as biomarkers in PLS3 osteoporosis or as target molecules in future therapeutic applications. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
On Oreology, the fracture and flow of “milk's favorite cookie®” (2022)

The mechanical experience of consumption (i.e., feel, softness, and texture) of many foods is intrinsic to their enjoyable consumption, one example being the habit of twisting a sandwich cookie to reveal the cream. Scientifically, sandwich cookies present a paradigmatic model of parallel plate rheometry in which a fluid sample, the cream, is held between two parallel plates, the wafers. When the wafers are counter-rotated, the cream deforms, flows, and ultimately fractures, leading to separation of the cookie into two pieces. We introduce Oreology (/ɔriːˈɒlədʒi/), from the Nabisco Oreo for “cookie” and the Greek rheo logia for “flow study,” as the study of the flow and fracture of sandwich cookies. Using a laboratory rheometer, we measure failure mechanics of the eponymous Oreo's “creme” and probe the influence of rotation rate, amount of creme, and flavor on the stress–strain curve and postmortem creme distribution. The results typically show adhesive failure, in which nearly all (95%) creme remains on one wafer after failure, and we ascribe this to the production process, as we confirm that the creme-heavy side is uniformly oriented within most of the boxes of Oreos. However, cookies in boxes stored under potentially adverse conditions (higher temperature and humidity) show cohesive failure resulting in the creme dividing between wafer halves after failure. Failure mechanics further classify the creme texture as “mushy.” Finally, we introduce and validate the design of an open-source, three-dimensionally printed Oreometer powered by rubber bands and coins for encouraging higher precision home studies to contribute new discoveries to this incipient field of study.
A shape-based approach to the segmentation of medical imagery using level sets (2003)

We propose a shape-based approach to curve evolution for the segmentation of medical images containing known object types. In particular, motivated by the work of Leventon, Grimson, and Faugeras, we derive a parametric model for an implicit representation of the segmenting curve by applying principal component analysis to a collection of signed distance representations of the training data. The parameters of this representation are then manipulated to minimize an objective function for segmentation. The resulting algorithm is able to handle multidimensional data, can deal with topological changes of the curve, is robust to noise and initial contour placements, and is computationally efficient. At the same time, it avoids the need for point correspondences during the training phase of the algorithm. We demonstrate this technique by applying it to two medical applications; two-dimensional segmentation of cardiac magnetic resonance imaging (MRI) and three-dimensional segmentation of prostate MRI.
Mechanical Properties Polypropylene-Wood (1998)

: The mechanical properties and morphology of polypropylene/wood flour (PP/WF) composites with different impact modifiers and maleated polypropylene (MAPP) as a compatibilizer have been studied. Two different ethylene/propylene/diene terpolymers (EPDM) and one maleated styrene-ethylene/butylene-styrene triblock copolymer (SEBS-MA) have been used as impact modifiers in the PP/WF systems. All three elastomers increased the impact strength of the PP/WF composites but the addition of maleated EPDM and SEBS gave the greatest improvements in impact strength. Addition of MAPP did not affect the impact properties of the composites but had a positive effect on the composite unnotched impact strength when used together with elastomers. Tensile tests showed that MAPP had a negative effect on the elongation at break and a positive effect on tensile strength. The impact modifiers were found to decrease the stiffness of the composites. Scanning electron microscopy showed that maleated EPDM an...
Supplementary Figure Legend from <i>In Situ</i> Vaccination with <i>CD204</i> Gene-Silenced Dendritic Cell, not Unmodified Dendritic Cell, Enhances Radiation Therapy of Prostate Cancer (2023)

&lt;p&gt;PDF file, 103K.&lt;/p&gt;
Normal mode analysis as a prerequisite for drug design: Application to matrix metalloproteinases inhibitors (2006)

We demonstrate the utility of normal mode analysis in correctly predicting the binding modes of inhibitors in the active sites of matrix metalloproteinases (MMPs). We show the accuracy in predicting the positions of MMP-3 inhibitors is strongly dependent on which structure is used as the target, especially when it has been energy minimized. This dependency can be overcome by using intermediate structures generated along one of the normal modes previously calculated for a given target. These results may be of prime importance for further in silico drug discovery.