gebhart/patrepeval huggingface dataset:
Field emission from isolated individual vertically aligned carbon nanocones (2002)

Field emission from isolated individual vertically aligned carbon nanocones (VACNCs) has been measured using a small-diameter moveable probe. The probe was scanned parallel to the sample plane to locate the VACNCs, and perpendicular to the sample plane to measure the emission turn-on electric field of each VACNC. Individual VACNCs can be good field emitters. The emission threshold field depends on the geometric aspect ratio (height/tip radius) of the VACNC and is lowest when a sharp tip is present. VACNCs exposed to a reactive ion etch process demonstrate a lowered emission threshold field while maintaining a similar aspect ratio. Individual VACNCs can have low emission thresholds, carry high current densities, and have long emission lifetime. This makes them very promising for various field emission applications for which deterministic placement of the emitter with submicron accuracy is needed.
TDX, a galectin‐1 and galectin‐3‐specific inhibitor, mitigates VEGF‐A‐induced angiogenesis (2013)

Both galectin‐1 (Gal‐1) and galectin‐3 (Gal‐3) are vital modulators for vascular endothelial growth factors receptor‐2 (VEGFR‐2) signaling pathway. To date, TDX is the only compound that specifically targets both galectins with high affinity. Our goal is to study TDX's efficacy against VEGF‐A‐mediated pathological angiogenesis. Here we showed that Gal‐1 and Gal‐3 interact with VEGFR‐2 in a carbohydrate‐dependent manner and that TDX: (i) reduces cautery‐induced corneal neovascularization in vivo, (ii) reduces VEGF‐A‐induced sprouting of human umbilical vein endothelial cells (HUVECs) as assessed by a three‐dimensional sprouting assay, (iii) efficiently abolishes VEGF‐A‐induced HUVEC chemotaxis, (iv) has little effect on HUVEC viability, and (v) does not affect total protein expression of VEGFR‐2 in HUVECs. Our data provide proof of principle that targeting Gal‐1 and Gal‐3 by the novel, small molecule inhibitor, TDX, ameliorates pathological angiogenesis. The findings provide a new therapeutic strategy for various disease conditions, including inflammation, diabetes, cancer metastasis, age‐related macular degeneration and corneal neovascularization. This work is supported by the NIH Grant R01EY007088 to N. Panjwani.
Involvement of the p53 tumor suppressor in repair of u.v.-type DNA damage. (1995)

The tumor suppressor p53 plays a central role in the cellular responses to genotoxic stress. Besides its well known role in activation of the G1 checkpoint after exposure to agents like ionizing radiation and its role in apoptosis, the possibility exists that p53 may have additional roles, such as in DNA repair. For example, p53, is known to bind to single strand DNA such as would occur during repair events, and the proteins encoded by two p53-regulated genes have previously been found to bind to at least one protein involved in DNA damage processing including nucleotide excision repair (NER). NER is an important and versatile DNA repair mechanism, which is the major pathway for repair of u.v.-type lesions and damage by a variety of important carcinogens and mutagens. If components of the p53 pathway are involved in NER, then disruption of p53 function by mutations or expression of certain viral proteins could have important implications in carcinogenesis and cancer treatment. In the present study we show that disruption of normal p53 function in human colon carcinoma RKO cells with either the human papillomavirus E6 oncoprotein or a dominant-negative mutant p53 transgene results in reduced repair of u.v.-induced DNA damage. The E6 and mutant p53-containing cell lines demonstrated reduced repair of u.v.-induced DNA lesions in host cell reactivation experiments with reporter plasmids, and reduced repair in in vitro DNA repair assays. With this in vitro assay, extracts from the E6- and mutant p53-containing lines also showed loss of induced repair following cellular u.v.-irradiation. The reduced DNA repair activity of the transfected cell lines also correlated with reduced clonogenic survival following u.v.-irradiation. These results indicate that p53 and/or p53-regulated gene products function in the NER pathway and that this process is inducible by DNA damage.
Reduced incidence of ischemic stroke in patients with severe factor XI deficiency (2008)

Inherited disorders of hemostasis are natural models for investigating mechanisms of thrombosis and development of antithrombotic therapy. Because mice with total factor XI deficiency are protected against ischemic stroke and do not manifest excessive bleeding, we investigated the incidence of ischemic stroke in patients with severe inherited factor XI deficiency. Incidence of ischemic stroke in 115 patients aged 45 years or more with severe factor XI deficiency (activity less than 15 U/dL) was compared with incidence in the Israeli population as estimated from a stroke survey of 1528 patients. Adjustment for major risk factors of stroke (hypertension, diabetes mellitus, hypercholesterolemia, current smoking) was based on comparison of their prevalence in the stroke survey to an Israeli health survey of 9509 subjects. Incidence of myocardial infarction in the factor XI cohort was also recorded. After adjustment for the 4 major risk factors of ischemic stroke, the expected incidence of ischemic stroke was 8.56 compared with one observed (P = .003). The reduced 1:115 incidence of ischemic stroke contrasted with a 19:115 incidence of myocardial infarction, similar to the expected incidence. Thus, severe factor XI deficiency probably is protective against ischemic stroke but not against acute myocardial infarction.
Prognostic and Predictive Gene Signature for Adjuvant Chemotherapy in Resected Non–Small-Cell Lung Cancer (2010)

This 15-gene expression signature is an independent prognostic marker in early-stage, completely resected NSCLC, and to our knowledge, is the first signature that has demonstrated the potential to select patients with stage IB to II NSCLC most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine.
Intermolecular Insertion of an N,N‐Heterocyclic Carbene into a Nonacidic CH Bond: Kinetics, Mechanism and Catalysis by (K‐HMDS)2 (HMDS=Hexamethyldisilazide) (2006)

The reaction of 2-[13C]-1-ethyl-3-isopropyl-3,4,5,6-tetrahydropyrimidin-1-ium hexafluorophosphate ([13C1]-1-PF6) with a slight excess (1.03 equiv) of dimeric potassium hexamethyldisilazide ("(K-HMDS)2") in toluene generates 2-[13C]-3-ethyl-1-isopropyl-3,4,5,6-tetrahydropyrimid-2-ylidene ([13C1]-2). The hindered meta-stable N,N-heterocyclic carbene [13C1]-2 thus generated undergoes a slow but quantitative reaction with toluene (the solvent) to generate the aminal 2-[13C]-2-benzyl-3-ethyl-1-isopropylhexahydropyrimidine ([13C1]-14) through formal C-H insertion of C2 (the "carbene carbon") at the toluene methyl group. Despite a significant pKa mismatch (Delta pKa 1+ and toluene estimated to be ca. 16 in DMSO) the reaction shows all the characteristics of a deprotonation mechanism, the reaction rate being strongly dependent on the toluene para substituent (rho = 4.8(+/-0.3)), and displaying substantial and rate-limiting primary (k(H)/k(D) = 4.2(+/-0.6)) and secondary (k(H)/k(D) = 1.18(+/-0.08)) kinetic isotope effects on the deuteration of the toluene methyl group. The reaction is catalysed by K-HMDS, but proceeds without cross over between toluene methyl protons and does not involve an HMDS anion acting as base to generate a benzyl anion. Detailed analysis of the reaction kinetics/kinetic isotope effects demonstrates that a pseudo-first-order decay in 2 arises from a first-order dependence on 2, a first-order dependence on toluene (in large excess) and, in the catalytic manifold, a complex noninteger dependence on the K-HMDS dimer. The rate is not satisfactorily predicted by equations based on the Brønsted salt-effect catalysis law. However, the rate can be satisfactorily predicted by a mole-fraction-weighted net rate constant: -d[2]/dt = ({x2 k(uncat)} + {(1-x2) k(cat)})[2]1[toluene]1, in which x2 is determined by a standard bimolecular complexation equilibrium term. The association constant (Ka) for rapid equilibrium-complexation of 2 with (K-HMDS)2 to form [2(K-HMDS)2] is extracted by nonlinear regression of the 13C NMR shift of C2 in [13C1]-2 versus [(K-HMDS)2] yielding: Ka = 62(+/-7) M(-1); delta(C(2)) in 2=237.0 ppm; delta(C(2)) in [2(K-HMDS)2] = 226.8 ppm. It is thus concluded that there is discrete, albeit inefficient, molecular catalysis through the 1:1 carbene/(K-HMDS)2 complex [2(K-HMDS)2], which is found to react with toluene more rapidly than free 2 by a factor of 3.4 (=k(cat)/k(uncat)). The greater reactivity of the complex [2(K-HMDS)2] over the free carbene (2) may arise from local Brønsted salt-effect catalysis by the (K-HMDS)2 liberated in the solvent cage upon reaction with toluene.
A framework for state-space estimation with uncertain models (2001)

Develops a framework for state-space estimation when the parameters of the underlying linear model are subject to uncertainties. Compared with existing robust filters, the proposed filters perform regularization rather than deregularization. It is shown that, under certain stabilizability and detectability conditions, the steady-state filters are stable and that, for quadratically-stable models, the filters guarantee a bounded error variance. Moreover, the resulting filter structures are similar to various (time- and measurement-update, prediction, and information) forms of the Kalman filter, albeit ones that operate on corrected parameters rather than on the given nominal parameters. Simulation results and comparisons with /spl Hscr//sub /spl infin// guaranteed-cost, and set-valued state estimation filters are provided.
Quelques picardismes du xvie siecle (2010)

The Latin-French dictionary of 1511, very used in education until 1541, is an adaptation of the Diccionario latino-catalan of 1507 by Gabriel Busa, which is in turn an adaptation or translation of the Dicionario Latino-espanol by Antonio de Nebrija (1492). The anonymous author of the Latin-French Dictionary is from Picardy (of Doullens) and in his work there are many words of this region. The study of the dictionary is useful to check the persistence of a language which became a dialect after several centuries of intense literary culture. Its lexis is between this time of splendour and the current period in which is considered a patois. In this work the Picard words recognized by the author as well other unconsciously used by him are underlined.
Tunable Focus Liquid Lens with Radial-Patterned Electrode (2015)

A dielectric liquid lens is prepared based on our previous work. By optimizing the device structure, the liquid lens presents a converging focus with good resolution and changes its focal length over a broad range with a low driving voltage. For a liquid lens with ~2.3 mm diameter in the relaxed state, it can resolve ~40 lp/mm. The resolution does not degrade during focus change. Its focal length can be varied from ~12 to ~5 mm when the applied voltage is changed from 0 to 28 Vrms. The response time of one cycle is ~2.5 s. Our liquid lens, with a low driving voltage for a large dynamic range, has potential applications in imaging, biometrics, optoelectronic, and lab-on-chip devices.
Neuregulin is a mitogen and survival factor for olfactory bulb ensheathing cells and an isoform is produced by astrocytes (1999)

The rat olfactory bulb is an exceptional CNS tissue. Unlike other areas of the brain, growing axons are able to enter the olfactory bulb and extend within this CNS environment throughout adult life. It appears that the glial cells of the olfactory system, known as olfactory bulb ensheathing cells (OBECs), may have an important role in this remarkable process of CNS neural regeneration. OBECs are unusual glial cells, possessing properties of both astrocytes and Schwann cells. In this study we show that astrocytes (in the form of astrocyte-conditioned medium; ACM) produce two critical regulatory functions for OBECs: mitogenic activity and a survival factor. Interestingly, the ACM-derived activity for OBECs appears to reside in a signalling protein(s) belonging to the neuregulin (NRG) family of growth factors, and specifically appears to coincide with one or more products of the nrg-1 gene. Our observations provide evidence for the following: recombinant human neu differentiation factors (NDFbeta1, -2 and -3) are mitogenic to OBECs; the activity in ACM can be neutralized by NDF antibodies; these same antibodies detect a 50-kDa, non-heparin binding protein in concentrated ACM; astrocytes express detectable nrg-1 transcripts; and OBECs express functional NRG receptors erbB2 and erbB4.
Variable-heating-rate wire-mesh pyrolysis apparatus (1989)

An electrically heated wire-mesh apparatus for pyrolysis studies has been developed which uses computer-driven feedback control for the heating system and thus can apply virtually any time-temperature history to the sample. Internal components are water cooled to prevent heat buildup during long runs. Using this system, coal pyrolysis has been studied at heating rates from 0.1 to about 5000 K/s and temperatures up to 1000 °C. Alternating current is used for heating; this allows the thermocouples to be attached directly to the sample holder and also makes power regulation relatively simple. For atmospheric-pressure experiments, a gas sweep can be forced through the sample holder to remove products from the heated zone and also to concentrate them in a trap which can be removed from the apparatus and weighed to establish tar yields directly. Although the design is optimized for atmospheric-pressure operation, relatively simple modifications allow operation under vacuum or at pressures of up to 160 bars in inert gas or hydrogen. The apparatus has been used to investigate a number of phenomena in coal pyrolysis and, most significantly, has demonstrated the existence of a heating-rate effect which is independent of reactor geometry.
Activation of Macrophages and B Lymphocytes by an Oligodeoxynucleotide Derived from an Acutely Pathogenic Simian Immunodeficiency Virus (1998)

Certain CpG-containing DNA sequences from bacteria, viruses, or invertebrates elicit responses in the vertebrate innate immune system. These responses also account for many nonspecific effects of oligodeoxynucleotides used for antisense approaches. Here we describe a sequence from an acutely pathogenic simian immunodeficiency virus (SIV) that induces release of cytokines from macrophages and B lymphocyte proliferation. Furthermore, several similar sequences in other immunodeficiency viruses were found that also activate macrophages. These results led to the question if CpG-containing DNA, which is thought to play an immunostimulatory role in bacterial infections, has a similar role in infections by immunodeficiency viruses.
μCB-seq: microfluidic cell barcoding and sequencing for high-resolution imaging and sequencing of single cells (2020)

Single-cell RNA sequencing (scRNA-seq) enables the investigation of complex biological processes in multicellular organisms with high resolution. However, many phenotypic features that are critical to understanding the functional role of cells in a heterogeneous tissue or organ are not directly encoded in the genome and therefore cannot be profiled with scRNA-seq. Quantitative optical microscopy has long been a powerful approach for characterizing diverse cellular phenotypes including cell morphology, protein localization, and chemical composition. Combining scRNA-seq with optical imaging has the potential to provide comprehensive single-cell analysis, allowing for functional integration of gene expression profiling and cell-state characterization. However, it is difficult to track single cells through both measurements; therefore, coupling current scRNA-seq protocols with optical measurements remains a challenge. Here, we report microfluidic cell barcoding and sequencing (μCB-seq), a microfluidic platform that combines high-resolution imaging and sequencing of single cells. μCB-seq is enabled by a novel fabrication method that preloads primers with known barcode sequences inside addressable reaction chambers of a microfluidic device. In addition to enabling multi-modal single-cell analysis, μCB-seq improves gene detection sensitivity, providing a scalable and accurate method for information-rich characterization of single cells.
Targeted polymeric therapeutic nanoparticles: design, development and clinical translation (2012)

Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development of targeted polymeric NPs and to highlight the challenges associated with the engineering of this novel class of therapeutics, including considerations of NP design optimization, development and biophysicochemical properties. Additionally, we highlight some recent examples from the literature, which demonstrate current trends and novel concepts in both the design and utility of targeted polymeric NPs (444 references).
Analysis of Mupirocin Resistance and Fitness in Staphylococcus aureus by Molecular Genetic and Structural Modeling Techniques (2004)

Chromosomal resistance to mupirocin in clinical isolates of Staphylococcus aureus arises from V(588)F or V(631)F mutations in isoleucyl-tRNA synthetase (IRS). Whether these are the only IRS mutations that confer mupirocin resistance or simply those that survive in the clinic is unknown. Mupirocin-resistant mutants of S. aureus 8325-4 were therefore generated to examine their ileS genotypes and the in vitro and in vivo fitness costs associated with them before and after compensatory evolution. Most spontaneous first-step mupirocin-resistant mutants carried V(588)F or V(631)F mutations in IRS, but a new mutation (G(593)V) was also identified. Second-step mutants carried combinations of previously identified IRS mutations (e.g., V(588)F/V(631)F and G(593)V/V(631)F), but additional combinations also occurred involving novel mutations (R(816)C, H(67)Q, and F(563)L). First-step mupirocin-resistant mutants were not associated with substantial fitness costs, a finding that is consistent with the occurrence of V(588)F or V(631)F mutations in the IRS of clinical strains. Second-step mutants were unfit, but fitness could be restored by subculture in the absence of mupirocin. In most cases, this was the result of compensatory mutations that also suppressed mupirocin resistance (e.g., A(196)V, E(190)K, and E(195)K), despite retention of the original mutations conferring resistance. Structural explanations for mupirocin resistance and loss of fitness were obtained by molecular modeling of mutated IRS enzymes, which provided data on mupirocin binding and interaction with the isoleucyl-AMP reactive intermediate.
Eradication of established tumors by vaccination with Venezuelan equine encephalitis virus replicon particles delivering human papillomavirus 16 E7 RNA. (2001)

The etiological role of human papillomaviruses (HPV) in cervical and other cancers suggests that therapeutic vaccines directed against requisite viral antigens may eradicate tumors or their precursors. A Venezuelan equine encephalitis (VEE) alphavirus vector delivering the HPV16 E7 RNA was evaluated for antitumor efficacy using a murine E7+ tumor model. Vaccination with VEE replicon particles expressing E7 (E7-VRP) induced class I-restricted CD8+ T-cell responses as determined by IFN-gamma enzyme-linked immunospot (ELISPOT), tetramer, and cytotoxicity assays. E7-VRP vaccination prevented tumor development in all of the mice and effectively eliminated 7-day established tumors in 67% of tumor-bearing mice. The induction of protective T-cell responses was dependent on CD8+, but not CD4+ T cells. Long-lasting T-cell memory responses developed in E7-VRP-vaccinated mice as determined by complete protection from tumor challenge 3 months after the final vaccination. These promising results highlight the potent CD8+ T-cell-mediated antitumor effects elicited by VEE replicon-based vectors and support their further development toward clinical testing against cervical intraepithelial neoplasia or carcinoma.
trans-4-Hydroxytamoxifen concentration and metabolism after local percutaneous administration to human breast. (1986)

trans-4-Hydroxytamoxifen (4-OHTAM), a very active metabolite of the antiestrogen tamoxifen, was percutaneously administered to the affected breast of nine patients before surgery for breast cancer in order to evaluate 4-OHTAM absorption through the skin and its subcellular localization and metabolism. After percutaneous administration of 80 muCi, [3H]-4-OHTAM was detected in breast tissue. It was especially concentrated in tumor tissue and nuclear and cytosolic fractions, in which it remained unmetabolized except for limited isomerization from the trans to the cis form. In contrast to breast tissue, concentrations of radioactivity remained low in plasma but with a high proportion of metabolites. In another experiment [3H]tamoxifen was percutaneously administered over the breast of 3 patients, resulting in tissue retention weaker and shorter than after [3H]-4-OHTAM. In addition [3H]-4-OHTAM was administered to either breast or abdominal skin; the appearance of radioactivity in plasma and urine was delayed after administration to the breast in comparison with administration to the abdomen. It therefore appears that 4-OHTAM passes through the skin and is concentrated in receptor structures of breast tissue, thus avoiding the hepatic metabolism subsequent to p.o. administration. We suggest that local percutaneous administration of this active antiestrogen could be useful in the treatment of hormone-dependent benign breast diseases.
Voltage-gated K+ channel activity in human prostate cancer cell lines of markedly different metastatic potential: Distinguishing characteristics of PC-3 and LNCaP cells (2001)

Prostate cancer cells of varying metastatic ability can be distinguished by their ion channel characteristics. The possible contribution(s) of K(+) channel activity to development of malignancy needs exploration.