gebhart/patrepeval huggingface dataset:
Static load-displacement behavior of PDMS microfeatures for soft lithography (2012)

This paper develops a general model for the load-displacement behavior of polymer microfeatures, such as those encountered in polydimethylsiloxane (PDMS) stamps for soft lithography. Soft lithography is an attractive low-cost method of patterning surfaces via selective mechanical contact, often by printing a molecular monolayer or depositing thin films. The fidelity of the transferred pattern is dependent on successful mechanical contact, however, the soft elastomers used for stamps can often collapse or buckle under moderate pressures. This work seeks to complement the existing understanding of collapse pressure with an understanding of the complete load-displacement behavior of the stamp features. A model is developed for feature stiffness by examining an analytical solution in the limits of very large or very small feature aspect ratios and computing intermediate behavior through a large set of finite element simulations. This model is subsequently validated with experimental load-displacement data. Analytical models are used to predict particular modes of collapse, showing excellent agreement with experimental observations.
A Methodology for Determining Patients’ Eligibility for Clinical Trials (1993)

The task of determining patients' eligibility for clinical trials is knowledge and data intensive. In this paper, we present a model for the task of eligibility determination, and describe how a computer system can assist clinical researchers in performing that task. Qualitative and probabilistic approaches to computing and summarizing the eligibility status of potentially eligible patients are described. The two approaches are compared, and a synthesis that draws on the strengths of each approach is proposed. The result of applying these techniques to a database of HIV-positive patient cases suggests that computer programs such as the one described can increase the accrual rate of eligible patients into clinical trials. These methods may also be applied to the task of determining from electronic patient records whether practice guidelines apply in particular clinical situations.
Measuring the Aromatic Potential of Vitis vinifera L. Cv. Sauvignon Blanc Grapes by Assaying S-Cysteine Conjugates, Precursors of the Volatile Thiols Responsible for Their Varietal Aroma (2000)

The method presented for measuring the aromatic potential of Sauvignon blanc must is based on an assay of the S-cysteine conjugate precursors of three volatile thiols involved in the characteristic aroma of wines made from this grape variety: 4-mercapto-4-methylpentan-2-one, 4-mercapto-4-methylpentan-2-ol, and 3-mercaptohexan-1-ol. These compounds were released enzymatically from their precursors by percolating the must through an immobilized tryptophanase column (EC 4.1.99.1), catalyzing an alpha, beta-elimination reaction on the S-cysteine conjugate. The volatile thiols were analyzed by GC-MS, as were the deuterated analogues that had been released from synthesized deuterated precursors and were added as internal standards. The quantities of volatile thiols released under these conditions were proportional to the S-cysteine conjugate content of the must.
Translation-dependent unwinding of stem–loops by UPF1 licenses Regnase-1 to degrade inflammatory mRNAs (2019)

Regnase-1-mediated mRNA decay (RMD), in which inflammatory mRNAs harboring specific stem-loop structures are degraded, is a critical part of proper immune homeostasis. Prior to initial translation, Regnase-1 associates with target stem-loops but does not carry out endoribonucleolytic cleavage. Single molecule imaging revealed that UPF1 is required to first unwind the stem-loops, thus licensing Regnase-1 to proceed with RNA degradation. Following translation, Regnase-1 physically associates with UPF1 using two distinct points of interaction: The Regnase-1 RNase domain binds to SMG1-phosphorylated residue T28 in UPF1; in addition, an intrinsically disordered segment in Regnase-1 binds to the UPF1 RecA domain, enhancing the helicase activity of UPF1. The SMG1-UPF1-Regnase-1 axis targets pioneer rounds of translation and is critical for rapid resolution of inflammation through restriction of the number of proteins translated by a given mRNA. Furthermore, small-molecule inhibition of SMG1 prevents RNA unwinding in dendritic cells, allowing post-transcriptional control of innate immune responses.
Anti-neuroblastoma antibody chCE7 binds to an isoform of L1-CAM present in renal carcinoma cells (1999)

Immunoprecipitation after cell surface labeling of human neuroblastoma cells showed that the anti-neuroblastoma monoclonal antibody (mAb) chCE7 binds to a 200,000 M(r) cell surface protein. The protein was partially purified by immuno-affinity chromatography from a human renal carcinoma and a human neuroblastoma cell line, which both showed high levels of binding of MAb chCE7. NH(2)-terminal sequences of 18 and 15 amino acid residues were determined. Both sequences isolated from the renal carcinoma and the neuroblastoma cells showed strong homology to human cell adhesion molecule L1 (L1-CAM), and both were characterized by the NH(2)-terminal deletion of 5 amino acids, comprising exon 2 of L1-CAM. Reverse trancription-polymerase chain reaction (RT-PCR) analysis of the regions spanning exon 2 and exon 27 of L1-CAM indicated that in neuroblastoma cells both transcripts for the full-length and exon-deleted forms are present, whereas in the renal carcinoma cell lines only the exon-deleted L1-CAM isoform were detected. Western blot analysis showed that 6 of 7 tested renal carcinoma cell lines and 5 of 15 renal carcinoma tissues expressed L1-CAM. In normal adult kidney tissue, very low levels of protein expression were found. Northern blot analysis confirmed that in renal carcinoma and neuroblastoma cell lines L1-CAM mRNA levels are correlated with protein expression.
Theoretical investigation of the effects of substrate parameters on the performance of diode loaded microstrip patches (2002)

A rigorous full-wave analysis is used to determine the impedance behaviour and other related characteristics of several varactor diode loaded microstrip circular patches. The results presented illustrate the change in performance when different substrates are incorporated. From these results, valuable insight into the general performance trends of a microstrip patch loaded with a varactor diode can be established.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Characterization of the chicken β-globin insulator (1997)

Insulators, first identified in Drosophila, are DNA sequence elements that shield a promoter from nearby regulatory elements. We have previously reported that a DNA sequence at the 5' end of the chicken beta-globin locus can function as an insulator. It is capable of shielding a reporter gene from the activating effects of a nearby mouse beta-globin locus control region element in the human erythroleukemic cell line K562. In this report, we show that most of the insulating activity lies in a 250-bp CpG island (core element), which contains the constitutive DNase I-hypersensitive site (5'HS4). DNA binding assays with the core sequence reveal a complex protein binding pattern. The insulating activity of the core element is multiplied when tandem copies are used. Although CpG islands are often associated with promoters of housekeeping genes, we find little evidence that the core element is a promoter. Furthermore, the insulator differs from a promoter in its ability to block the locus control region effect directionally.
Therapy of Murine Tumors with Recombinant Bordetella pertussis Adenylate Cyclase Carrying a Cytotoxic T Cell Epitope (1999)

Bordetella pertussis secretes an invasive adenylate cyclase toxin, CyaA, that is able to deliver its N-terminal catalytic domain into the cytosol of eukaryotic target cells directly through the cytoplasmic membrane. We have shown previously that recombinant CyaA can be used to deliver viral CD8+ T cell epitopes to the MHC-class I presentation pathway to trigger specific CTL responses in vivo. In the present study, we show that mice immunized with a detoxified but still invasive CyaA carrying a CD8+ T cell epitope of OVA developed strong epitope-specific CTL responses, which kill tumor cells expressing this Ag. Treating mice with this recombinant molecule after the graft of melanoma cells expressing OVA induced a strong survival advantage compared with control animals. To our knowledge, this study represents the first demonstration that a nonreplicative and nontoxic vector carrying a single CTL epitope can stimulate efficient protective and therapeutic antitumor immunity.
Mechanistic Studies of the Triggered Release of Liposomal Contents by Matrix Metalloproteinase-9 (2008)

Matrix metalloproteinases (MMPs) constitute a class of extracellular-matrix-degrading enzymes overexpressed in many cancers and contribute to the metastatic ability of the cancer cells. We have recently demonstrated that liposomal contents can be released when triggered by the enzyme MMP-9. Herein, we report the results of our mechanistic studies of the MMP-9-triggered release of liposomal contents. We synthesized peptides containing the cleavage site for MMP-9 and conjugated them with fatty acids to prepare the corresponding lipopeptides. By employing circular dichroism (CD) spectroscopy, we demonstrated that the lipopeptides, when incorporated into liposomes, are demixed in the lipid bilayers and generate triple-helical structures. MMP-9 cleaves the triple-helical peptides, leading to the release of the liposomal contents. Other MMPs, which cannot hydrolyze triple-helical peptides, fail to release the contents from the liposomes. We also observed that the rate and extent of release of the liposomal contents depend on the mismatch between the acyl chains of the synthesized lipopeptide and phospholipid components of the liposomes. CD spectroscopic studies imply that the observed differences in the release reflect the ability of the liposomal membrane to anneal the defects following the enzymatic cleavage of the liposome-incorporated lipopeptides.
Methods in hair research: how to objectively distinguish between anagen and catagen in human hair follicle organ culture (2009)

The organ culture of human scalp hair follicles (HFs) is the best currently available assay for hair research in the human system. In order to determine the hair growth-modulatory effects of agents in this assay, one critical read-out parameter is the assessment of whether the test agent has prolonged anagen duration or induced catagen in vitro. However, objective criteria to distinguish between anagen VI HFs and early catagen in human HF organ culture, two hair cycle stages with a deceptively similar morphology, remain to be established. Here, we develop, document and test an objective classification system that allows to distinguish between anagen VI and early catagen in organ-cultured human HFs, using both qualitative and quantitative parameters that can be generated by light microscopy or immunofluorescence. Seven qualitative classification criteria are defined that are based on assessing the morphology of the hair matrix, the dermal papilla and the distribution of pigmentary markers (melanin, gp100). These are complemented by ten quantitative parameters. We have tested this classification system by employing the clinically used topical hair growth inhibitor, eflornithine, and show that eflornithine indeed produces the expected premature catagen induction, as identified by the novel classification criteria reported here. Therefore, this classification system offers a standardized, objective and reproducible new experimental method to reliably distinguish between human anagen VI and early catagen HFs in organ culture.
Proteinopathy-induced neuronal senescence: a hypothesis for brain failure in Alzheimer's and other neurodegenerative diseases (2009)

This integrative hypothesis, which we will refer to as the proteinopathy-induced senescent cell hypothesis of AD and other neurodegenerative diseases, links CNS proteinopathies to inflammation, physiological senescence, cellular dysfunction, and ultimately neurodegeneration. Future studies characterizing the senescent phenotype of CNS cells in AD and other neurodegenerative diseases will test the validity of this hypothesis. The implications of CNS senescence as a contributing factor to the neurodegenerative cascade and its implications for therapy are discussed.
P450-Catalyzed Intramolecular sp 3 C–H Amination with Arylsulfonyl Azide Substrates (2014)

The direct amination of aliphatic C-H bonds represents a most valuable transformation in organic chemistry. While a number of transition metal-based catalysts have been developed and investigated for this purpose, the possibility to execute this transformation with biological catalysts has remained largely unexplored. Here, we report that cytochrome P450 enzymes can serve as efficient catalysts for mediating intramolecular benzylic C-H amination reactions in a variety of arylsulfonyl azide compouds. Under optimized conditions, the P450 catalysts were found to support up to 390 total turnovers leading to the formation of the desired sultam products with excellent regioselectivity. In addition, the chiral environment provided by the enzyme active site allowed for the reaction to proceed in a stereo- and enantioselective manner. The C-H amination activity, substrate profile, and enantio/stereoselectivity of these catalysts could be modulated by utilizing enzyme variants with engineered active sites.
Modified joint transform correlator binarized by error diffusion II Spatially variant range limit (1994)

Nonlinear scaling of the joint power spectrum in one approach and noise-subtraction followed by nonlinear scaling in a second approach are analyzed in conjunction with error-diffusion binarization for joint transform correlator configurations in the presence of input-additive white Gaussian noise. Nonlinear scaling is performed with a spatially variant range limit. For the second approach the subtracted noise value is an estimate of the noise power spectral density. Computer simulations and optical experiments demonstrate the advantages of the proposed error-diffusion-based joint transform correlator approaches. In particular the approach based on noise subtraction before nonlinear scaling is advantageous even for very high noise levels.
Sarcopenia in older adults (2012)

Purpose of review Sarcopenia, or the decline of skeletal muscle tissue with age, is one of the most important causes of functional decline and loss of independence in older adults. The purpose of this article is to review the current definitions of sarcopenia, its potential causes and clinical consequences, and the potential for intervention. Recent findings Although no consensus diagnosis has been reached, sarcopenia is increasingly defined by both loss of muscle mass and loss of muscle function or strength. Its cause is widely regarded as multifactorial, with neurological decline, hormonal changes, inflammatory pathway activation, declines in activity, chronic illness, fatty infiltration, and poor nutrition, all shown to be contributing factors. Recent molecular findings related to apoptosis, mitochondrial decline, and the angiotensin system in skeletal muscle have highlighted biological mechanisms that may be contributory. Interventions in general continue to target nutrition and exercise. Summary Efforts to develop a consensus definition are ongoing and will greatly facilitate the development and testing of novel interventions for sarcopenia. Although pharmaceutical agents targeting multiple biological pathways are being developed, adequate nutrition and targeted exercise remain the gold standard for therapy.
Diurnal variation in the femoral articular cartilage of the knee in young adult humans (2000)

Our objective was to test the hypothesis that diurnal changes occur in thickness or volume of the femoral articular cartilage of the knee in asymptomatic young adults. Fat-suppressed three-dimensional (3D) spoiled gradient-echo magnetic resonance imaging (MRI) was employed. Six volunteers each were scanned early in the morning and at the end of a working day spent mainly standing. This protocol was repeated on 3 successive weeks. Femoral cartilage volumes were obtained via semiautomatic segmentation that employed a seeding algorithm. These segmentations then were regridded onto a 500-pixel template, and differences in the resulting thickness maps were assessed. Analysis of variance showed no significant diurnal variation in overall volume or thickness. The reproducibility for volume (test-retest coefficient of variation) was 1.6%. There were, however, statistically-significant diurnal changes in the thickness maps. Cartilage thickness decreased by up to 0.6 mm during the day in each of the following three specific locations: the patellofemoral compartment, the lateral tibiofemoral compartment, and the medial tibiofemoral compartment. Elsewhere, cartilage thickness was unchanged or increased by up to 0.5 mm. We conclude that, in asymptomatic young adults, cartilage volume does not change during the day; however, the cartilage does become thinner in locations that encounter the greatest biomechanical force.
Skin moisturizing effect and skin penetration of ascorbyl palmitate entrapped in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) incorporated into hydrogel. (2005)

This study was performed as a complimentary to our previous study regarding the chemical stability of ascorbyl palmitate (AP) in solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, in nanoemulsion (NE) incorporated into a hydrogel produced by high pressure homogenization. AP is known as an effective antioxidant that protects tissue integrity similar to vitamin C. Recently, its moisturizing activity in conventional topical formulations was found to be high. The aim of the present study was to investigate the moisturizing potential of AP in SLN and NLC incorporated into hydrogel as colloidal carrier systems. It has been known that SLN and NLC have occlusive effects, but AP incorporation moisturized skin significantly better than placebo in short-term (p < 0.001) and long-term trials (p < 0.01) for both SLN and NLC. In the second part of the study, SLN and NLC were found to sustain the penetration of AP through excised human skin about 1/2 and 2/3 times compared to NE (p < 0.001 and p < 0.01), respectively, due to the solid state of Witepsol E85 in the lipid phase.
Amplification and expression of recombinant genes in serum‐independent Chinese hamster ovary cells (1995)

CHO SSF3 cells grow as a suspension culture in unmodified commercial medium with only low-molecular weight ingredients. Continuous serum-free culture unexpectedly induced expression of a low dihydrofolate reductase activity in the originally dhfr- CHO cells. Nevertheless, it was possible with methotrexate to induce amplification of a gene coding for the hybrid plasminogen activator K2tu-PA cotransfected with a dhfr gene. Expression of K2tu-PA expression was proportionally increased to that of dhfr, which was measured with fluorescent methotrexate. Because no serum proteases were present, secreted K2tu-PA was not converted to the enzymatically active form, but was exclusively recovered in proenzyme form.
S819 Incidence, Outcomes, and Impact of COVID-19 on Inflammatory Bowel Disease: Propensity Matched Analysis of a Large Research Network (2021)

Introduction: Several studies have examined outcomes of COVID-19 in patients with IBD however these reports have inherent limitations including a lack of matched controls precluding accurate assessment of risk, and lack of follow up data to assess for IBD flares and risk of de novo IBD in COVID-19 affected populations. Methods: We performed a retrospective cohort study using a multi-institutional research network TriNETX. Patients with IBD >16 yrs of age with COVID-19 (up to Feb 7, 2021) were matched 1:1 with non-IBD COVID-19 patients based on demographic variables and known risk factors for severe COVID-19 infection. Outcomes of COVID-19 disease in IBD were compared to the matched control cohort, and outcomes in IBD subpopulations were explored. The incidence of COVID-19 disease in patients with IBD was compared to the general population, and the relationship of incident cases of IBD with prior COVID-19 disease was investigated. Results: A total of 628,947 patients with COVID-19 met inclusion criteria (3486 in IBD and 625,461 in the non- IBD cohort). Prevalence of COVID-19 in patients with IBD cohort was 5.95%. Patients with IBD had a lower incidence of COVID-19 compared to the general population; IRR: 0.79 (95% CI: 0.72-0.86). The IBD cohort had a higher rate of inpatient treatment with no difference in mortality, mechanical ventilation or AKI noted in the propensity-matched analysis. Patients with IBD corticosteroids at baseline were found to be at increased risk for mortality (RR: 2.08, 95% CI:1.06-4.10, hospitalization and 30-day composite outcome (hospitalization or mortality). No difference in composite outcome was noted in the 5-ASA, biologic agent, and anti-TNF group compared to non-IBD cohort. 210 patients (6.0%) and 243 patients (7.0%) developed an IBD flare in 1 month and 3 months after COVID-19 diagnosis respectively. A total of 774 patients (0.10%) with no prior history of IBD were diagnosed with de novo IBD after COVID-19 infection. The IBD diagnosis rate after COVID-19 was lower compared to a control group of patients who were never diagnosed with COVID-19, on propensity score-matched analysis (RR 0.59; 95% CI:0.54-0.65). Conclusion: In a large cohort of patients with IBD infected with COVID-19, we found a higher rate of in-patient treatment without differences in other clinical outcomes compared to a matched cohort of patients without IBD. The rate of de novo IBD after COVID-19 and disease exacerbations in cases of prior IBD was low, and no IBD therapy was linked to worse outcomes.
Anti-HIV-1 activity of anionic polymers: a comparative study of candidate microbicides (2002)

Micronized CAP is the only candidate topical microbicide with the capacity to remove rapidly by adsorption from physiological fluids HIV-1 of both the X4 and R5 biotypes and is likely to prevent virus contact with target cells. The interaction between micronized CAP and HIV-1 leads to rapid virus inactivation. Among other anionic polymers, cellulose sulfate, BufferGel and aryl sulfonates appear most effective in this respect.
Insulin-Like Growth Factor 1 and Prostate Cancer Risk: A Population-Based, Case-Control Study (1998)

Elevated serum IGF-1 levels may be an important predictor of risk for prostate cancer. However, our results do not support an important role for serum IGFBP-3 as a predictor of risk for this disease.