gebhart/patrepeval huggingface dataset:
The Study of Mechanical Properties of Cells as a Biomarker for Cancer Diagnostics (2012)

The measurement of cellular mechanical properties can be impactful in many areas of biosciences due to the interdependencies of mechanics and cell state or function. Mechanical cues communicated via mechanosensing and mechanotransduction can regulate cellular behavior leading to biochemical and structural modifications; conversely, native cellular processes such as differentiation, activation, and malignant transformation triggered by biochemical cues have also shown to elicit significant changes to the cellular architecture. Measurement of these mechanical biophysical changes can therefore be used to infer cell state or function. To date, there are numerous approaches used to measure the mechanical properties of cells for biophysics research, yet these are limited in their translational ability as general research or clinical tools. The biggest challenges facing successful translation of these mechanical phenotyping tools are due to the technological complexity, manual sample handling and preparation requirements, and limited sample throughput. This dissertation focuses on developing a high-throughput, label-free alternative for mechano phenotyping termed deformability cytometry. For the first time in the biophysics field, the deformability cytometry platform achieves throughputs of more than 1,000 cells/second; a rate that is three orders of magnitude greater than previous techniques. Additionally, initial work involving platform validation and proof-of-concept applications for stem cell differentiation, leukocyte activation, and cancer diagnostics are explored. The dissertation also undertakes a major engineering challenge of this system - large dataset image processing - which has led to the development of process efficient image analysis algorithms to increase the utility and robustness of this mechano phenotyping technique. Lastly, a clinical proof-of-concept study consisting of 119 patient pleural effusion samples were collected and assayed using the deformability cytometry platform to determine the diagnostic performance of mechanical biomarkers for malignant effusions. Briefly, the result of this clinical study achieved an area-under-the-curve of 0.91 with sensitivity and specificity of 100% and 69%, respectively. The high diagnostic accuracy combined with the ease-of-use, minimal sample preparations needs, and large sample sizes, satisfies many translational hurdles for a label-free mechano phenotyping platform for applications in the biosciences community.
Hybrid Dual Aromatase-Steroid Sulfatase Inhibitors with Exquisite Picomolar Inhibitory Activity (2010)

Single agents against multiple drug targets are highly topical. Hormone-dependent breast cancer (HDBC) may be more effectively treated by dual inhibition of aromatase and steroid sulfatase (STS), and several dual aromatase-sulfatase inhibitors (DASIs) have been recently reported. The best compounds from two leading classes of DASI, 3 and 9, are low nanomolar inhibitors. In search of a novel class of DASI, core motifs of two leading classes were combined to give a series of hybrid structures, with several compounds showing markedly improved dual inhibitory activities in the picomolar range in JEG-3 cells. Thus, DASIs 14 (IC50: aromatase, 15 pM; STS, 830 pM) and 15 (IC50: aromatase, 18 pM; STS, 130 pM) are the first examples of an exceptional new class of highly potent dual inhibitor that should encourage further development toward multitargeted therapeutic intervention in HDBC.
Tariquidar sensitizes multiple myeloma cells to proteasome inhibitors via reduction of hypoxia-induced P-gp-mediated drug resistance (2017)

Multiple myeloma (MM) presents a poor prognosis and high lethality of patients due to development of drug resistance. P-glycoprotein (P-gp), a drug-efflux transporter, is upregulated in MM patients post-chemotherapy and is involved in the development of drug resistance since many anti-myeloma drugs (including proteasome inhibitors) are P-gp substrates. Hypoxia develops in the bone marrow niche during MM progression and has long been linked to chemoresistance. Additionally, hypoxia-inducible transcription factor (HIF-1α) was demonstrated to directly regulate P-gp expression. We found that in MM patients P-gp expression positively correlated with the hypoxic marker, HIF-1α. Hypoxia increased P-gp protein expression and its efflux capabilities in MM cells in vitro using flow cytometry. We reported herein that hypoxia-mediated resistance to carfilzomib and bortezomib in MM cells is due to P-gp activity and was reversed by tariquidar, a P-gp inhibitor. These results suggest combining proteasome inhibitors with P-gp inhibition for future clinical studies.
Inhibition of signaling via erbB-receptors by antibodies that target the Lewis Y-antigen (2004)

Introduction IGN311 is a humanized monoclonal IgG1 antibody that binds to the Lewis Y (LeY) carbohydrate overexpressed on epithelial cancers. IGN311 potently mediates human effector functions (ADCC, CDC). The overexpression of fucosyltransferases in tumor cells also results in glycosylation of cell surface receptors by LeY. The anti-LeY antibodies IGN311 and its murine parent version ABL 364 therefore might influence the signaling in tumor cells via inhibition of growth factor receptor functions.
Localization and expression of cartilage oligomeric matrix protein by human rheumatoid and osteoarthritic synovium and cartilage (1999)

Synovium and cartilage from patients with osteoarthritis or rheumatoid arthritis were analyzed for expression of cartilage oligomeric matrix protein. Immunostaining of synovium with antiserum to cartilage oligomeric matrix protein demonstrated positive staining in both diseases. In osteoarthritis, there was positive staining within the synovial cells and immediately subjacent connective tissue, with less intense staining in the deeper connective tissue. In rheumatoid arthritis, there was less intense staining within the synovial cells and marked intense staining in the deeper connective tissue. In situ hybridization performed with an antisense digoxigenin-labeled riboprobe to human cartilage oligomeric matrix protein confirmed the presence of cartilage oligomeric matrix protein mRNA in the cells of the synovial lining in both types of synovium. Quantitative polymerase chain reaction with a cartilage oligomeric matrix protein MIMIC demonstrated increased cartilage oligomeric matrix protein mRNA in rheumatoid cartilage and synovium as compared with osteoarthritic cartilage and synovium, respectively; mRNA levels in rheumatoid synovium were similar to those from osteoarthritic chondrocytes. As a result of the high expression of cartilage oligomeric matrix protein from rheumatoid synovium, inflammatory synovium should be considered as a potential tissue source of cartilage oligomeric matrix protein in any investigation of biological markers of cartilage metabolism. The upregulated expression of cartilage oligomeric matrix protein in inflammatory tissues suggests its in vivo regulation by cytokines.
Proceedings of the 2012 workshop on Data-driven user behavioral modelling and mining from social media (2012)

It is our great pleasure to welcome you to the workshop on Data-driven user behavioral modeling and mining from social media (DUBMOD), co-located with 23rd ACM Conference on Information and Knowledge Management -- CIKM'14. This workshop builds upon the success of our previously held workshops User modeling from social media (UMSOCIAL), in conjunction with ACM IUI 2012, Data-driven user behavioral modeling and mining from social media (DUBMMSM), in conjunction with ACM CIKM 2012 and Data-driven user behavioral modeling and mining from social media (DUBMOD), in conjunction with ACM CIKM 2013. The call for papers attracted 8 submissions. We accepted 7 papers. The papers represent various topics such as reaction time for user behavior model for social network, user profile for answer quality, predicting requests for Wikipedia articles, linking Pinterest pins to online webshops, scalable mining of social data, predicting online buying behavior, flickr group recommendation. We hope that workshop proceedings will serve as a valuable reference for researchers and practitioners from diverse areas, such as user modeling, social media analysis, natural language processing, data mining and machine learning.
Oxidative protein damage is associated with poor grip strength among older women living in the community (2007)

Background: Grip strength, an indicator of muscle strength, has been shown to be a predictor of poor outcomes among older adults. Protein carbonylation, an indicator of oxidative damage to proteins, leads to cellular dysfunction and a decline in tissue function, and oxidative stress is thought to be involved in the pathogenesis of sarcopenia. Specific Aims: The objective was to determine whether serum protein carbonyl concentrations are associated with grip strength in older women living in the community. Methods: A cross‐sectional study was conducted in 672 women, aged 65 and older, from the Women's Health and Aging Study (WHAS) I, the one‐third most disabled women residing in the community in Baltimore, Maryland. Protein carbonyl and grip strength was measured in each patient. Results: In a multivariate analysis adjusting for age, race, body mass index, and Mini‐Mental Status Examination score, protein carbonyls levels are associated with grip strength (beta = −6.77, p &lt; 0.01). Additional adjustment for hypertension, congestive heart failure, and depression in the multivariate analysis produced similar results. Conclusion: These results suggest oxidative protein damage is independently associated with low grip strength among older women living in the community. Increased oxidative stress may be contributing to loss of muscle strength in older adults. This research was supported by NIH R01 AG027012.
Improving Image Search based on User Created Communities (2011)

Tag-based retrieval of multimedia content is a difficult problem, not only because of the shorter length of tags associated with images and videos, but also due to mismatch in the terminologies used by searcher and content creator. To alleviate this problem, we propose a simple concept-driven probabilistic model for improving text-based rich-media search. While our approach is similar to existing topic-based retrieval and cluster-based language modeling work, there are two important differences: (1) our proposed model considers not only the query-generation likelihood from cluster, but explicitly accounts for the overall "popularity" of the cluster or underlying concept, and (2) we explore the possibility of inferring the likely concept relevant to a rich-media content through the user-created communities that the content belongs to. We implement two methods of concept extraction: a traditional cluster based approach, and the proposed community based approach. We evaluate these two techniques for how effectively they capture the intended meaning of a term from the content creator and searcher, and their overall value in improving image search. Our results show that concept-driven search, though simple, clearly outperforms plain search. Among the two techniques for concept-driven search, community-based approach is more successful, as the concepts generated from user communities are found to be more intuitive and appealing.
Session details: Parallelism, performance, and traces (2009)

No abstract available.
Allosteric Peptide Activators of Pro-Hepatocyte Growth Factor Stimulate Met Signaling (2010)

Hepatocyte growth factor (HGF) binds to its target receptor tyrosine kinase, Met, as a single-chain form (pro-HGF) or as a cleaved two-chain disulfide-linked α/β-heterodimer. However, only two-chain HGF stimulates Met signaling. Proteolytic cleavage of the Arg(494)-Val(495) peptide bond in the zymogen-like pro-HGF results in allosteric activation of the serine protease-like β-chain (HGF β), which binds Met to initiate signaling. We use insights from the canonical trypsin-like serine protease activation mechanism to show that isolated peptides corresponding to the first 7-10 residues of the cleaved N terminus of the β-chain stimulate Met phosphorylation by pro-HGF to levels that are ∼25% of those stimulated by two-chain HGF. Biolayer interferometry data demonstrate that peptide VVNGIPTR (peptide V8) allosterically enhances pro-HGF β binding to Met, resulting in a K(D)(app) of 1.6 μm, only 8-fold weaker than the Met/HGF β-chain affinity. Most notably, in vitro cell stimulation with peptide V8 in the presence of pro-HGF leads to Akt phosphorylation, enhances cell survival, and facilitates cell migration between 75 and 100% of that found with two-chain HGF, thus revealing a novel approach for activation of Met signaling that bypasses proteolytic processing of pro-HGF. Peptide V8 is unable to enhance Met binding or signaling with HGF proteins having a mutated activation pocket (D672N). Furthermore, Gly substitution of the N-terminal Val residue in peptide V8 results in loss of all activity. Overall, these findings identify the activation pocket of the serine protease-like β-chain as a "hot spot" for allosteric regulation of pro-HGF and have broad implications for developing selective allosteric activators of serine proteases and pseudoproteases.
Abstract 16357: Prevalence of Left Ventricular Thrombus (LVT) One Month Post Myocardial Infarction in Patients Discharged With Negative Inpatient Echocardiography - Incremental Utility of Delayed Enhancement Cardiac Magnetic Resonance (DE-CMR) Tissue Characterization (2014)

Background: DE-CMR is well validated for LVT but echocardiography (echo) is the predominant test used for screening. LVT prevalence 1 month post MI in patients with initial negative echo during MI hospitalization is unknown. Methods: ST elevation MI patients with inpatient echo negative for LVT were prospectively enrolled. 1 month post MI, multimodality screening for LVT was performed via same day DE-CMR as well as both contrast (C) and non contrast (NC) echo - C was used in all patients without contraindication (96%). Each test (C, NC, DE-CMR) was independently read for LVT. LVT and MI size were quantified on DE-CMR. Results: 192 patients were studied; all had echo (70% NC, 30% C) negative for LVT during hospitalization (3±2 days post MI). On followup (28±6 days), 8% (n=15) had LVT on DE-CMR, including 14% with LAD culprit vessel. Patients with LVT had lower EF (42±8 vs 55±11%, p Conclusions: LVT occurs 1 month post MI in nearly 10% of patients discharged with negative inpatient echo, commonly in those with apical MI but no aneurysm. Over 1/4 of post MI patients with LVT on DE-CMR have negative C echo, for which LVT detection varies in relation to LVT size.
The Psychiatric Risk Gene NT5C2 Regulates Adenosine Monophosphate-Activated Protein Kinase Signaling and Protein Translation in Human Neural Progenitor Cells (2019)

We provide an extensive neurobiological characterization of the psychiatric risk gene NT5C2, describing its previously unknown role in the regulation of AMPK signaling and protein translation in neural stem cells and its association with Drosophila melanogaster motility behavior.
Radio and chemosensitization by a novel DNA-PK inhibitor (NU7441) in colon cancer (2005)

4999 Enzyme-mediated repair of DNA double-strand breaks (DSBs) is a major mechanism of resistance to both ionizing radiation (IR) and drugs that cause DSBs as intermediates in repair processes. The major DNA DSB repair pathway in eukaryotes is nonhomologous end joining. An important component in this repair pathway is the DNA-dependent protein kinase (DNA-PK), whose catalytic subunit is a member of the phosphatidylinositol 3-kinase (PI 3-K)-related protein kinase (PIKK) family of enzymes. DNA-PK deficient cells are hypersensitive to IR and some DNA-damaging anticancer drugs, and inhibition of DNA-PK therefore represents a potential strategy for radio- and chemo-sensitization. NU7441 is a competitive and highly selective inhibitor of DNA-PK (IC 50 = 14 nM). The cellular specificity of NU7441 for DNA-PK was studied in V3 and V3-YAC cells, deficient and proficient in DNA-PK respectively. V3 cells were inherently more sensitive to IR and etoposide than V3-YAC cells and NU7441 increased the cytotoxicity of IR and etoposide in V3-YAC cells but not in V3 cells, confirming that DNA-PKcs is the cellular target of NU7441. Exposure of human colon cancer cell lines; SW620 and LoVo, to 1 μM NU7441 alone for 16 hr did not affect cell survival but did significantly enhance the cytotoxicity of IR, doxorubicin and etoposide. Survival of SW620 cells exposed to etoposide (1 μM), in combination with 1 μM NU7441 gave a dose modification ratio of 5. Similarly, NU7441 caused a 2.3 fold enhancement of doxorubicin (100 nM) and 7.3 fold of IR (5 Gy) cytotoxicity in SW620 cells. In LoVo cells the dose modification ratio of etoposide(1 μM), doxorubicin(100 nM) and IR (5 Gy) was 2.1, 10 and 5.5 fold respectively. NU7441 alone had no effect on cell cycle distribution, but accumulation in G2/M induced by exposure to IR (2 Gy) or the topoisomerase II poisons, doxorubicin (10 nM) or etoposide (0.1 μM) was increased 1.2 to 2 fold by NU7441 in SW620 cells. In vivo anti tumor efficacy studies indicate that inhibition of DNA-PK can enhance the effect of etoposide against SW620 tumour xenografts. Tumor growth delay following treatment with etoposide alone (10 mg/kg i.p. daily x5) to a RTV4 was 8 days and for etoposide plus NU7441 (10 mg/kg i.p daily x 5) was 11 days, representing a 60% enhancement of etoposide efficacy. NU7441 alone did not cause any measurable toxicity (max body weight loss = 4%) and only caused a marginal enhancement of etoposide toxicity ( max body weight loss = 12%). These experiments demonstrate that the cellular effects of NU7441 are specific for DNA-PKcs. Furthermore, at non cytotoxic concentrations in vitro and non toxic doses in vivo this compound is a potent chemo- and radiosensitizer in models of human colon cancer.
Acutely Decompensated Heart Failure with Preserved and Reduced Ejection Fraction Present with Comparable Haemodynamic Congestion (2017)

In acute conditions, HFpEF and HFrEF presented in a comparable state of venous congestion, with similarly altered RV and kidney function, despite higher BNP in HFrEF.
Analysis of Hierarchical B Pictures and MCTF (2006)

In this paper, an investigation of H.264/MPEG4-AVC conforming coding with hierarchical B pictures is presented. We analyze the coding delay and memory requirements, describe details of an improved encoder control, and compare the coding efficiency for different coding delays. Additionally, the coding efficiency of hierarchical B picture coding is compared to that of MCTF-based coding by using identical coding structures and a similar degree of encoder optimization. Our simulation results turned out that in comparison to the widely used IBBP...structure coding gains of more than 1 dB can be achieved at the expense of an increased coding delay. Further experiments have shown that the coding efficiency gains obtained by using the additional update steps in MCTF coding are generally smaller than the losses resulting from the required open-loop encoder control
Filter selection criteria for the discrimination of strongly overlapping chemical spectra (2015)

Increasing the selectivity of sensors, while at the same time reducing their complexity, size and cost, are challenges to the sensing community. To this end, an area of exploration has been the development of filter-based chemical sensors. We have recently introduced an approach that utilizes multiple, broadband, infrared (IR) filters to enable discrimination of target chemicals, in the presence of potential interferents that have IR spectral signatures in a limited waveband. Our analysis technique, comparative discrimination spectral detection (CDSD), utilizes a set of broad IR transmission filters, to discriminate between a specific target chemical and multiple interferents with strongly overlapping IR spectra. We have demonstrated the ability of this technique to correctly distinguish between chemicals in the carbon – hydrogen stretch region of the IR absorption spectrum (2700 – 3300 cm<sup>-1</sup>; 3.0 – 3.7 &mu;m). We present a numerical study exploring the choices of desired optical filter sets, and the resulting overall discrimination by these filter sets. Filter parameter choices, such as the peak transmission position and bandwidth, are fundamental in filter-based chemical sensing discrimination systems. In this paper, we describe a systematic numerical approach used to explore how optical filter properties, and filter overlap affect corresponding discrimination results. We describe the interaction between the overlapping spectra and various filter sets on both target and interferent chemicals. We discuss which filter parameters provide optimum selectivity for specific target chemicals and how this information can be utilized to select filters for future direct-filter sensors based on this methodology.
Graphene-induced tunable Lamb shifts beyond atomic fine structure (2018)

We show that highly tunable atomic energy levels can be achieved by exploiting plasmonic Lamb shifts. The shifts can be larger than fine-structure shifts and potentially larger than the Coulomb interactions at certain Fermi energies.
Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons (2010)

Neurogenesis in the hippocampus is characterized by the birth of thousand of cells that generate neurons throughout life. The fate of these adult newborn neurons depends on life experiences. In particular, spatial learning promotes the survival and death of new neurons. Whether learning influences the development of the dendritic tree of the surviving neurons (a key parameter for synaptic integration and signal processing) is unknown. Here we show that learning accelerates the maturation of their dendritic trees and their integration into the hippocampal network. We demonstrate that these learning effects on dendritic arbors are homeostatically regulated, persist for several months, and are specific to neurons born during adulthood. Finally, we show that this dendritic shaping depends on the cognitive demand and relies on the activation of NMDA receptors. In the search for the structural changes underlying long-term memory, these findings lead to the conclusion that shaping neo-networks is important in forming spatial memories.
Transforming growth factor-β dynamically regulates vascular smooth muscle differentiation in vivo (1998)

ABSTRACT Variations in the levels of smooth muscle-specific isoforms of contractile proteins have been reported to occur in many different vascular diseases. However, although much work has been done in vitro to investigate the regulation of smooth muscle cell differentiation, the molecular mechanisms which regulate the differentiation of vascular smooth muscle tissue in vivo are unknown. Using quantitative immunofluorescence, we show that in rat arteries levels of smooth muscle differentiation markers correlate with the levels of the cytokine TGF-β. In young mice with one allele of the TGF-β1 gene deleted, the levels of both TGF-β1 and smooth muscle differentiation markers are reduced compared to wild-type controls. This regulation of smooth muscle differentiation by TGF-β?during post-natal development also occurs dynamically in the adult animal. Following various pharmacological or surgical interventions, including treatment of mice with tamoxifen and balloon injury of rat carotid arteries, there is a strong correlation between the changes in the levels of TGF-β and changes in the levels of smooth muscle differentiation markers (r=0.9, P&amp;lt;0.0001 for n=26 experiments). We conclude that TGF-β dynamically regulates smooth muscle differentiation in rodent arteries in vivo.