gebhart/patrepeval huggingface dataset:
Expression of Macrophage Migration Inhibitory Factor in Human Breast Cancer: Association with Nodal Spread (2002)

Macrophage migration inhibitory factor (MIF) is known to exert pleiotropic functions including inhibition of macrophage migration, anchoring, and counteraction of the anti-inflammatory and immunosuppressive activity of glucocorticoids. Ninety-three primary breast cancer tissues and 64 sera of primary breast cancer patients were analyzed for the expression of MIF. The clinico-pathological significance of MIF expression was evaluated. It was found that MIF was frequently over-expressed in primary breast cancer tissues. RT-PCR and western blotting analysis confirmed that wild-type MIF is expressed, and immunohistochemical analysis showed that MIF expression was localized at tumor cells as well as stromal cells, including tumor-associated macrophages. Intratumoral MIF protein concentrations detected by enzyme-linked immunosorbent assay (ELISA) varied with a median value of 1821 ng/mg protein (range: 8 - 8126 ng/mg protein), and correlated inversely with nodal involvement (P = 0.039). No significant correlation was observed with other clinico-pathological factors including tumor size, menopausal status and hormone receptors. The circulating level of MIF protein ranged up to 105.7 ng/ml (median: 17.3 ng/ml), and it was also found to correlate inversely with the number of involved nodes (P = 0.02). A comparative study with other soluble inflammatory mediators showed that intratumoral levels of MIF were significantly associated with those of interleukin-1 beta, suggesting that interactions between tumor cells and tumor-associated macrophages play an important role in the up-regulation of MIF. The multifunctional inflammatory/immune mediator MIF was frequently expressed in primary breast cancer, and its expression level was inversely associated with nodal spread. Thus, MIF seems to play a role in tumor-stroma interactions of primary breast cancers, particularly those with a phenotype of node-negative or minimal nodal spread.
Inhibition of the Escherichia coli Pyruvate Dehydrogenase Complex E1 Subunit and Its Tyrosine 177 Variants by Thiamin 2-Thiazolone and Thiamin 2-Thiothiazolone Diphosphates (2001)

Variants of the pyruvate dehydrogenase subunit (E1; EC ) of the Escherichia coli pyruvate dehydrogenase multienzyme complex with Y177A and Y177F substitutions were created. Both variants displayed pyruvate dehydrogenase multienzyme complex activity at levels of 11% (Y177A E1) and 7% (Y177F E1) of the parental enzyme. The K(m) values for thiamin diphosphate (ThDP) were 1.58 microm (parental E1) and 6.65 microm (Y177A E1), whereas the Y177F E1 variant was not saturated at 200 microm. According to fluorescence studies, binding of ThDP was unaffected by the Tyr(177) substitutions. The ThDP analogs thiamin 2-thiazolone diphosphate (ThTDP) and thiamin 2-thiothiazolone diphosphate (ThTTDP) behaved as tight-binding inhibitors of parental E1 (K(i) = 0.003 microm for ThTDP and K(i) = 0.064 microm for ThTTDP) and the Y177A and Y177F variants. This analysis revealed that ThTDP and ThTTDP bound to parental E1 via a two-step mechanism, but that ThTDP bound to the Y177A variant via a one-step mechanism. Binding of ThTDP was affected and that of ThTTDP was unaffected by substitutions at Tyr(177). Addition of ThDP or ThTDP to parental E1 resulted in similar CD spectral changes in the near-UV region. In contrast, binding of ThTTDP to either parental E1 or the Y177A and Y177F variants was accompanied by the appearance of a positive band at 330 nm, indicating that ThTTDP was bound in a chiral environment. In combination with x-ray structural evidence on the location of Tyr(177), the kinetic and spectroscopic data suggest that Tyr(177) has a role in stabilization of some transition state(s) in the reaction pathway, starting with the free enzyme and culminating with the first irreversible step (decarboxylation), as well as in reductive acetylation of the dihydrolipoamide acetyltransferase component.
Synthesis and biological activities of fatty acid conjugates of a cyclic lactam .alpha.-melanotropin (1992)

Four fatty acid conjugates of a cyclic lactam-bridged alpha-MSH fragment analogue were synthesized and their potencies and biological activities compared in several melanotropin bioassays. Palmitoyl, myristoyl, decanoyl, and hexanoyl conjugates of H-Asp-His-D-Phe-Arg-Trp-Lys-NH2 were prepared. In the in vitro mouse melanoma cell assay, each of the conjugates was 10-100 times more potent than alpha-MSH or the substrate peptide in elevating tyrosinase activity. The shorter conjugates of hexanoic and decanoic acid were as potent as alpha-MSH in the lizard skin bioassay, whereas the longer myristoyl and palmitoyl analogues were about 100 times less potent. The potency of the myristoyl and palmitoyl conjugates increased with time in contact with the skins. These observations may be related to the more lipid-like nature of these peptide-fatty acid conjugates. Each of the conjugates exhibited prolonged melanotropic activity in the lizard skin bioassays and in the mouse S91 melanoma tyrosinase bioassay, since the biological response continued following removal of the conjugates from the incubation media. The prolonged residual melanotropic activity resulted from conjugation of the fatty acids to the MSH fragment analogue since the analogue itself did not exhibit prolonged activity.
The CMS, A Cold Magnet Synchrotron to Upgrade the Proton Energy Range of the BNL Facility (1971)

The results of a design study of a nominally 100 GeV (or 150 GeV) proton synchrotron, making use of very pure aluminum conductor magnets, operating at 12°K, or superconducting magnets, operating at 4.5°K, are presented.
Melanocortin Receptors as Targets in the Treatment of Obesity (2007)

Penile erection is a complex physiologic event resulting from the interactions of the nervous system on a highly specialized vascular organ. Activation of central nervous system melanocortinergic (MC) receptors with either endogenous or synthetic melanotropic ligands may initiate and/or facilitate spontaneous penile erection. While the CNS contains principally the MC3 and MC4 receptor subtypes, there is conflicting data as to which receptor mediates erection. Although the MC4R is emerging as the principle effector of MC induced erection, the role of the MC3R is poorly understood. Manipulation of each receptor subtype with newly synthesized receptor specific agonists and antagonists, as well as knockout mice, has elucidated their individual contributions. Novel data from our laboratories suggests that antagonism of forebrain MC3R may enhance melanocortin-induced erections. Furthermore, melanocortin agents may interact with better-studied systems such as oxytocinergic pathways at the hypothalamic, brainstem or spinal level. Current therapies for erectile dysfunction target end organ vascular tissue. Manipulation of MC receptors may provide an alternative, centrally mediated therapeutic approach for erectile and other sexual dysfunctions. The non-specific "superpotent" MC agonist, PT-141, which is the carboxylate derivative of MT-II, has reached phase II human trials. Through their centrally mediated activity, melanocortin agonists have potential to treat erectile dysfunction as well as possible applications to the unmet medical needs of decreased sexual motivation and loss of libido.
Coronary Artery Wall Shear Stress Is Associated With Progression and Transformation of Atherosclerotic Plaque and Arterial Remodeling in Patients With Coronary Artery Disease (2011)

Compared with intermediate-WSS coronary segments, low-WSS segments develop greater plaque and necrotic core progression and constrictive remodeling, and high-WSS segments develop greater necrotic core and calcium progression, regression of fibrous and fibrofatty tissue, and excessive expansive remodeling, suggestive of transformation to a more vulnerable phenotype. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00576576.
The Fate and Toxicity of Raman-Active Silica-Gold Nanoparticles in Mice (2011)

Raman spectroscopy is an optical imaging method that is based on the Raman effect, the inelastic scattering of a photon when energy is absorbed from light by a surface. Although Raman spectroscopy is widely used for chemical and molecular analysis, its clinical application has been hindered by the inherently weak nature of the Raman effect. Raman-silica-gold-nanoparticles (R-Si-Au-NPs) overcome this limitation by producing larger Raman signals through surface-enhanced Raman scattering. Because we are developing these particles for use as targeted molecular imaging agents, we examined the acute toxicity and biodistribution of core polyethylene glycol (PEG)-ylated R-Si-Au-NPs after different routes of administration in mice. After intravenous administration, PEG-R-Si-Au-NPs were removed from the circulation by macrophages in the liver and spleen (that is, the reticuloendothelial system). At 24 hours, PEG-R-Si-Au-NPs elicited a mild inflammatory response and an increase in oxidative stress in the liver, which subsided by 2 weeks after administration. No evidence of significant toxicity was observed by measuring clinical, histological, biochemical, or cardiovascular parameters for 2 weeks. Because we are designing targeted PEG-R-Si-Au-NPs (for example, PEG-R-Si-Au-NPs labeled with an affibody that binds specifically to the epidermal growth factor receptor) to detect colorectal cancer after administration into the bowel lumen, we tested the toxicity of the core nanoparticle after administration per rectum. We observed no significant bowel or systemic toxicity, and no PEG-R-Si-Au-NPs were detected systemically. Although additional studies are required to investigate the long-term effects of PEG-R-Si-Au-NPs and their toxicity when carrying the targeting moiety, the results presented here support the idea that PEG-R-Si-Au-NPs can be safely used in living subjects, especially when administered rectally.
Interleukin 6 is the principal cytolytic T lymphocyte differentiation factor for thymocytes in human leukocyte conditioned medium. (1989)

The formation of CD8+ killer cells from nonlytic thymocyte precursors is mediated by interleukin 2 and a cytokine termed CTL differentiation factor (CDF). While several reports have focused on the effects of recombinant molecules on the development of CTL, the natural protein responsible for CTL development that is produced by normal leukocytes has not been conclusively identified. A 24 kD native protein with CDF activity was enriched from leukocyte conditioned medium and neutralizing antibodies were produced. Utilizing immunoaffinity chromatography and reverse phase chromatography, we purified this CDF to homogeneity. All 21 amino acid residues at the NH2-terminus of CDF were found to be identical to that of IL-6. Natural CDF and IL-6 share many of the same biological properties, including costimulation of thymocyte proliferation with IL-1. Antibodies against CDF or IL-6 can block the activity of either cytokine, and anti-CDF blocks the activity of bulk leukocyte conditioned medium. These results indicate that IL-6 is the principal CTL differentiation factor produced by stimulated human leukocytes.
Hemophagocytosis causes a consumptive anemia of inflammation (2011)

Cytopenias of uncertain etiology are commonly observed in patients during severe inflammation. Hemophagocytosis, the histological appearance of blood-eating macrophages, is seen in the disorder hemophagocytic lymphohistiocytosis and other inflammatory contexts. Although it is hypothesized that these phenomena are linked, the mechanisms facilitating acute inflammation-associated cytopenias are unknown. We report that interferon γ (IFN-γ) is a critical driver of the acute anemia observed during diverse microbial infections in mice. Furthermore, systemic exposure to physiologically relevant levels of IFN-γ is sufficient to cause acute cytopenias and hemophagocytosis. Demonstrating the significance of hemophagocytosis, we found that IFN-γ acts directly on macrophages in vivo to alter endocytosis and provoke blood cell uptake, leading to severe anemia. These findings define a unique pathological process of broad clinical and immunological significance, which we term the consumptive anemia of inflammation.
Liveness Detection for Voice User Interface via Wireless Signals in IoT Environment (2020)

Voice interface has been a dominant User Interface (UI) channel in the popular smart home environment. Although Voice Control System (VCS) brings users conveniences, it is extremely vulnerable to spoofing attacks (e.g., hidden/inaudible command attack) due to its broadcast nature. In this study, to thwart spoofing attacks, we propose WSVA, a device-free voice liveness detection system based on the prevalent wireless signals generated by IoT devices without requiring user to carry any additional sensor or device. The basic insight of WSVA to distinguish the authentic voice command from a spoofed one is checking the consistency between the voice signal and its corresponding mouth motions, which can be captured by wireless signals. To achieve this goal, WSVA builds a theoretical model to describe the correlations among the wireless signal changes, the mouth motions, and the syllables in the voice command. Then, WSVA selects appropriate features from both voice and wireless signals, and calculates the consistency between these two types of signals to determine whether the VCS is suffering from the spoofing attack. To demonstrate the feasibility of WSVA, we conduct a case study on Samsung SmartThings platform and include WSVA as a new application, which is expected to significantly enhance the security of the existing VCS. We evaluate WSVA with various voice commands in different scenarios. Experimental results demonstrate that WSVA achieves the overall 99 percent true accept rate with 1 percent false accept rate with a good scalability and low latency.
The evolution of cyclopropenium ions into functional polyelectrolytes (2015)

Versatile polyelectrolytes with tunable physical properties have the potential to be transformative in applications such as energy storage, fuel cells and various electronic devices. Among the types of materials available for these applications, nanostructured cationic block copolyelectrolytes offer mechanical integrity and well-defined conducting paths for ionic transport. To date, most cationic polyelectrolytes bear charge formally localized on heteroatoms and lack broad modularity to tune their physical properties. To overcome these challenges, we describe herein the development of a new class of functional polyelectrolytes based on the aromatic cyclopropenium ion. We demonstrate the facile synthesis of a series of polymers and nanoparticles based on monomeric cyclopropenium building blocks incorporating various functional groups that affect physical properties. The materials exhibit high ionic conductivity and thermal stability due to the nature of the cationic moieties, thus rendering this class of new materials as an attractive alternative to develop ion-conducting membranes.
Synthesis and Biological Evaluation of Ionizable Lipid Materials for the In Vivo Delivery of Messenger RNA to B Lymphocytes (2017)

B lymphocytes regulate several aspects of immunity including antibody production, cytokine secretion, and T-cell activation; moreover, B cell misregulation is implicated in autoimmune disorders and cancers such as multiple sclerosis and non-Hodgkin's lymphomas. The delivery of messenger RNA (mRNA) into B cells can be used to modulate and study these biological functions by means of inducing functional protein expression in a dose-dependent and time-controlled manner. However, current in vivo mRNA delivery systems fail to transfect B lymphocytes and instead primarily target hepatocytes and dendritic cells. Here, the design, synthesis, and biological evaluation of a lipid nanoparticle (LNP) system that can encapsulate mRNA, navigate to the spleen, transfect B lymphocytes, and induce more than 60 pg of protein expression per million B cells within the spleen is described. Importantly, this LNP induces more than 85% of total protein production in the spleen, despite LNPs being observed transiently in the liver and other organs. These results demonstrate that LNP composition alone can be used to modulate the site of protein induction in vivo, highlighting the critical importance of designing and synthesizing new nanomaterials for nucleic acid delivery.
Expression of fluorescently tagged connexins: a novel approach to rescue function of oligomeric DsRed‐tagged proteins1 (2001)

A novel, brilliantly red fluorescent protein, DsRed has become available recently opening up a wide variety of experimental opportunities for double labeling and fluorescence resonance electron transfer experiments in combination with green fluorescent protein (GFP). Unlike in the case of GFP, proteins tagged with DsRed were often found to aggregate within the cell. Here we report a simple method that allows rescuing the function of an oligomeric protein tagged with DsRed. We demonstrate the feasibility of this approach on the subunit proteins of an oligomeric membrane channel, gap junction connexins. Additionally, DsRed fluorescence was easily detected 12-16 h post transfection, much earlier than previously reported, and could readily be differentiated from co-expressed GFP. Thus, this approach can eliminate the major drawbacks of this highly attractive autofluorescent protein.
Structural characterization of azurin from Pseudomonas aeruginosa and some of its methionine-121 mutants (1993)

Azurin from Pseudomonas aeruginosa and two mutants where the methionine ligand has been mutated have been studied in order to directly investigate the functional and structural significance of this ligand in the blue copper proteins. Reduction potentials, X-ray absorption fine structure (XAFS), electron paramagnetic resonance (EPR), and optical spectra are obtained in an attempt to provide a direct correlation between the spectrochemical properties and the immediate structure of this redox center.
COMPARISON OF METHODS FOR SEPARATING OLIGOSACCHARIDES: ULTRAFILTRATION, GEL PERMEATION AND ADSORPTION CHROMATOGRAPHY (1980)

ABSTRACT Methods for the separation of glucose oligomers with a degree of polymerization (DP) of 5‐10 and l0‐20 were studied. Gel filtration using Bio‐Gel P‐2 fractionated glucose oligomers from corn syrups with dextrose equivalents (DE) of 36, 43, and 62. Corn syrup DE 43 was fractionated with Diaflow ultrafiltration (UF) membranes PMl0, UMl0, and UM2. Adsorption chromatography of corn syrup DE 43 was conducted with a charcoal‐celite column using a step‐wise elution schedule of ethanol:water mixtures. Gel permeation chromatography provided elution profiles of the various corn syrups; however, the respective glucose oligomers were not clearly resolved. Corn syrup DE 43 had the most oligosaccharides with the least content of sugars of large or small molecular size. Ultrafiltration using the UM2 and UMl0 membranes retained from 55‐70s of the oligosaccharides. Less than 7% of the oligomers were retained by the PM10 membrane. Adsorption chromatography was most efficient and effective in the separation of the discrete fractions with DP of 5‐10 and 10‐20.
Control of growth and organ size in Drosophila (2002)

Transplantation experiments have shown that developing metazoan organs carry intrinsic information about their size and shape. Organ and body size are also sensitive to extrinsic cues provided by the environment, such as the availability of nutrients. The genetic and molecular pathways that contribute to animal size and shape are numerous, yet how they cooperate to control growth is mysterious. The recent identification and characterization of several mutations affecting growth in Drosophila melanogaster promises to provide insights. Many of these mutations affect the extrinsic control of animal size; others affect the organ-intrinsic control of pattern and size. In this review, we summarize the characteristics of some of these mutations and their roles in growth and size control. In addition, we speculate about possible connections between the extrinsic and intrinsic pathways controlling growth and pattern.
Sequence-to-Sequence Neural Net Models for Grapheme-to-Phoneme Conversion (2015)

Sequence-to-sequence translation methods based on generation with a side-conditioned language model have recently shown promising results in several tasks. In machine translation, models conditioned on source side words have been used to produce target-language text, and in image captioning, models conditioned images have been used to generate caption text. Past work with this approach has focused on large vocabulary tasks, and measured quality in terms of BLEU. In this paper, we explore the applicability of such models to the qualitatively different grapheme-to-phoneme task. Here, the input and output side vocabularies are small, plain n-gram models do well, and credit is only given when the output is exactly correct. We find that the simple side-conditioned generation approach is able to rival the state-of-the-art, and we are able to significantly advance the stat-of-the-art with bi-directional long short-term memory (LSTM) neural networks that use the same alignment information that is used in conventional approaches.
High brightness inductively coupled plasma source for high current focused ion beam applications (2006)

A high brightness plasma ion source has been developed to address focused ion beam (FIB) applications not satisfied by the liquid metal ion source (LMIS) based FIB. The plasma FIB described here is capable of satisfying applications requiring high mill rates (&amp;gt;100μm3∕s) with non-gallium ions and has demonstrated imaging capabilities with sub- 100-nm resolution. The virtual source size, angular intensity, mass spectra, and energy spread of the source have been determined with argon and xenon. This magnetically enhanced, inductively coupled plasma source has exhibited a reduced brightness (βr) of 5.4×103Am−2sr−1V−1, with a full width half maximum axial energy spread (ΔE) of 10eV when operated with argon. With xenon, βr=9.1×103Am−2sr−1V−1 and ΔE=7eV. With these source parameters, an optical column with sufficient demagnification is capable of forming a sub-25-nm spot size at 30keV and 1pA. The angular intensity of this source is nominally three orders of magnitude greater than a LMIS making the source more amenable to creating high current focused beams, in the regime where spherical aberration dominates the LMIS-FIB. The source has been operated on a two lens ion column and has demonstrated a current density that exceeds that of the LMIS-FIB for current greater than 50nA. Source lifetime and current stability are excellent with inert and reactive gases. Additionally, it should be possible to improve both the brightness and energy spread of this source, such that the (βr∕ΔE2) figure-of-merit could be within an order of magnitude of a LMIS.