gebhart/patrepeval huggingface dataset:
Tumor pretargeting with avidin improves the therapeutic index of biotinylated tumor necrosis factor alpha in mouse models. (1999)

The clinical use of tumor necrosis factor alpha (TNF) as an anticancer drug is limited to local or locoregional administration because of dose-limiting systemic toxicity. We investigated in animal models whether the therapeutic index of systemically administered human or murine TNF can be increased by tumor pretargeting strategies based on the biotin-avidin system. Pretargeting of s.c. mouse WEHI-164 fibrosarcoma and RMA lymphoma genetically engineered to express the Thy 1.1 antigen on the cell membrane was achieved by i.p. injection of a biotinylated anti-Thy 1.1 antibody and avidin. This pretreatment increased the antitumor activity of systemically administered biotin-TNF conjugates by at least 5-fold. In contrast, pretargeting did not increase the toxicity of biotin-TNF, as judged by animal survival and weight loss after treatment. Ex vivo analysis of tumor cells 24 h after treatment showed that biotin-TNF persisted for several hours on the surface of pretargeted tumors, but not when avidin was omitted. The potentiation of the antitumor effects was related primarily to indirect mechanisms, involving a host-mediated response. The results indicate that tumor pretargeting improves the antitumor activity of TNF. Tumor pretargeting with avidin, which is currently used to increase the uptake of radioactive-labeled biotin in patients, could represent a new strategy for improving the therapeutic index of TNF.
Optical single sideband transmission at 10 Gb/s using only electrical dispersion compensation (1999)

A system is presented which uses optical single sideband transmission at 10 Gb/s together with electrical dispersion compensation at the receiver. Transmission with a bit error rate better than 10/sup -10/ on nondispersion shifted fiber is experimentally demonstrated over 320 km and the dispersion from 1000 km of fiber was effectively equalized in simulation. In the transmitter, driving one or two modulators with a combination of a baseband digital signal and the Hilbert transform of that signal creates an optical single sideband signal. In terms of reducing the effects of chromatic dispersion, transmitting the signal in a single sideband format has two advantages over a double sideband format. First, the optical bandwidth of the transmitted single sideband signal is approximately one half of a conventional double sideband signal. Second, an optical single sideband signal with transmitted carrier can be "self-homodyne" detected and the majority of the phase information preserved since no spectrum back folding occurs upon detection. This allows the received signal to be partially equalized in the electrical domain.
Functional Characterization of Src-interacting Na/K-ATPase Using RNA Interference Assay (2006)

We have shown that the Na/K-ATPase and Src form a signaling receptor complex. Here we determined how alterations in the amount and properties of the Na/K-ATPase affect basal Src activity and ouabain-induced signal transduction. Several alpha1 subunit knockdown cell lines were generated by transfecting LLC-PK1 cells with a vector expressing alpha1-specific small interference RNA. Although the alpha1 knockdown resulted in significant decreases in Na/K-ATPase activity, it increased the basal Src activity and tyrosine phosphorylation of focal adhesion kinase, a Src effector. Concomitantly it also abolished ouabain-induced activation of Src and ERK1/2. When the knockdown cells were rescued by a rat alpha1, both Na/K-ATPase activity and the basal Src activity were restored. In addition, ouabain was able to stimulate Src and ERK1/2 in the rescued cells at a much higher concentration, consistent with the established differences in ouabain sensitivity between pig and rat alpha1. Finally both fluorescence resonance energy transfer analysis and co-immunoprecipitation assay indicated that the pumping-null rat alpha1 (D371E) mutant could also bind Src. Expression of this mutant restored the basal Src activity and focal adhesion kinase tyrosine phosphorylation. Taken together, the new findings suggest that LLC-PK1 cells contain a pool of Src-interacting Na/K-ATPase that not only regulates Src activity but also serves as a receptor for ouabain to activate protein kinases.
A Fluorogenic Probe for the Copper(I)-Catalyzed Azide−Alkyne Ligation Reaction:  Modulation of the Fluorescence Emission via 3(n,π*)−(π,π*) Inversion (2004)

Chemoselective ligation reactions represent a powerful approach for labeling of proteins or small molecules in a biological environment. We report here a fluorogenic probe that is activated by click chemistry, a highly versatile bio-orthogonal and chemoselective ligation reaction which is based on the azide moiety as the functional group. The electron-donating properties of the triazole ring that is formed in the course of the coupling reaction was effectively utilized to modulate the fluorescence output of an electronically coupled coumarin fluorophore. Under physiological conditions the probe is essentially nonfluorescent and undergoes a bright emission enhancement upon ligation with an azide. Time-resolved emission spectroscopy and semiempirical quantum-mechanical calculations suggest that the fluorescence switching is due to an inversion of the energy ordering of the emissive 1(pi,pi*) and nonemissive 3(n,pi*) excited states. The rapid kinetics of the ligation reaction render the probe attractive for a wide range of applications in biology, analytical chemistry, or material science.
Diplexing feed assemblies for application to dual-reflector antennas (2003)

We investigate possible configurations for dual-band waveguide diplexing assemblies appropriate for use as feed systems for dual-reflector antennas. Specific applications are where the bands are well separated and, individually, have relatively wide bandwidths. Two crucial problems are addressed: the demanding bandwidth requirements of the feed horn and the subsequent means of diplexing the signals. We present results arising from the analysis of candidate systems and discuss a preferred option in detail.
Diffuse reflectance spectroscopy of human colon tissue (1998)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, 1998.
Autonomous interface agents (1997)

Article Free Access Share on Autonomous interface agents Author: Henry Lieberman Media Laboratory, Massachusetts Institute of Technology, Cambridge, Mass Media Laboratory, Massachusetts Institute of Technology, Cambridge, MassView Profile Authors Info & Claims CHI '97: Proceedings of the ACM SIGCHI Conference on Human factors in computing systemsMarch 1997 Pages 67–74https://doi.org/10.1145/258549.258592Online:27 March 1997Publication History 161citation2,036DownloadsMetricsTotal Citations161Total Downloads2,036Last 12 Months76Last 6 weeks17 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Prostate mechanical imaging: 3-D image composition and feature calculations (2006)

We have developed a method and a device entitled prostate mechanical imager (PMI) for the real-time imaging of prostate using a transrectal probe equipped with a pressure sensor array and position tracking sensor. PMI operation is based on measurement of the stress pattern on the rectal wall when the probe is pressed against the prostate. Temporal and spatial changes in the stress pattern provide information on the elastic structure of the gland and allow two-dimensional (2-D) and three-dimensional (3-D) reconstruction of prostate anatomy and assessment of prostate mechanical properties. The data acquired allow the calculation of prostate features such as size, shape, nodularity, consistency/hardness, and mobility. The PMI prototype has been validated in laboratory experiments on prostate phantoms and in a clinical study. The results obtained on model systems and in vivo images from patients prove that PMI has potential to become a diagnostic tool that could largely supplant DRE through its higher sensitivity, quantitative record storage, ease-of-use and inherent low cost.
Evaluation of the Efficacy of Four Feed Additives Against the Adverse Effects of T-2 Toxin in Growing Broiler Chickens (2005)

The possible protective effect of 4 feed additives against the toxic effects of T-2 toxin in growing broiler chickens was investigated in a 28-d fully randomized trial consisting of 6 dietary treatments (control with no T-2 toxin or feed additive added, 2 ppm T-2 toxin alone, 2 ppm T-2 toxin plus 2.0 g/kg Mycofix, 2 ppm T-2 toxin plus 2.0 g/kg Mycosorb, 2 ppm T-2 toxin plus 2.5 g/kg MycoAd, and 2 ppm T-2 toxin plus 3.0 g/kg Zeolex). When no feed additive was included, 2 ppm dietary T-2 toxin significantly decreased BW and increased feed:gain ratio. When 2.0 g/kg Mycofix were added to the diet, the feed additive protected against the adverse effects of T-2 toxin on BW, BW gain, and feed:gain ratio; however, no protection against the adverse effects of T-2 toxin on final BW and BW gain were obtained by supplementation of any of the other 3 feed additives. A significant increase in relative gizzard weight was observed in chicks fed 3 of the additives (Mycosorb, MycoAd, and Zeolex) but not in those fed T-2 toxin alone or combined with Mycofix. Chicks supplemented with Zeolex plus T-2 toxin had a significantly decreased aspartate aminotransferase serum activity compared with controls. The results of the present trial indicate that the only feed additive capable of counteracting the adverse effects on performance caused by the dietary administration of 2 ppm T-2 toxin was the additive based on the enzymatic inactivation of the 12,13-epoxide ring of the trichothecenes (Mycofix). This study also confirms previous reports showing that aluminosilicates are not effective against trichothecene mycotoxins.
Mechanisms of Suicidal Erythrocyte Death (2005)

Erythrocyte injury such as osmotic shock, oxidative stress or energy depletion stimulates the formation of prostaglandin E2 through activation of cyclooxygenase which in turn activates a Ca2+ permeable cation channel. Increasing cytosolic Ca2+ concentrations activate Ca2+ sensitive K+ channels leading to hyperpolarization, subsequent loss of KCl and (further) cell shrinkage. Ca2+ further stimulates a scramblase shifting phosphatidylserine from the inner to the outer cell membrane. The scramblase is sensitized for the effects of Ca2+ by ceramide which is formed by a sphingomyelinase following several stressors including osmotic shock. The sphingomyelinase is activated by platelet activating factor PAF which is released by activation of phospholipase A2. Phosphatidylserine at the erythrocyte surface is recognised by macrophages which engulf and degrade the affected cells. Moreover, phosphatidylserine exposing erythrocytes may adhere to the vascular wall and thus interfere with microcirculation. Erythrocyte shrinkage and phosphatidylserine exposure ('eryptosis') mimic features of apoptosis in nucleated cells which however, involves several mechanisms lacking in erythrocytes. In kidney medulla, exposure time is usually too short to induce eryptosis despite high osmolarity. Beyond that high Cl- concentrations inhibit the cation channel and high urea concentrations the sphingomyelinase. Eryptosis is inhibited by erythropoietin which thus extends the life span of circulating erythrocytes. Several conditions trigger premature eryptosis thus favouring the development of anemia. On the other hand, eryptosis may be a mechanism of defective erythrocytes to escape hemolysis. Beyond their significance for erythrocyte survival and death the mechanisms involved in 'eryptosis' may similarly contribute to apoptosis of nucleated cells.
Neuropeptides and appetite control (2002)

Obesity is important in the aetiology of type 2 diabetes, and presents a major barrier to its successful prevention and management. Obesity develops when energy intake exceeds energy expenditure over time. A complex system has evolved to maintain energy homeostasis, but this is biased towards weight gain. Meal size is controlled by a series of short-term hormonal and neural signals that derive from the gastrointestinal tract, such as cholecystokinin whereas others may initiate meals, such as the recently discovered hormone, ghrelin. Other hormones such as insulin and leptin, together with circulating nutrients, indicate long-term energy stores. All these signals act at several central nervous system (CNS) sites but the pathways converge on the hypothalamus, which contains a large number of peptide and other neurotransmitters that influence food intake. As energy deficit is most likely to compromise survival, it is not surprising that the most powerful of these pathways are those that increase food intake and decrease energy expenditure when stores are depleted. When energy stores are low, production of leptin from adipose tissue, and thus circulating leptin concentrations fall, leading to increased production of hypothalamic neurotransmitters that strongly increase food intake, such as neuropeptide Y (NPY), galanin and agouti-related protein (AGRP) and decreased levels of alpha-melanocyte-stimulating hormone (alpha-MSH), cocaine and amphetamine-regulated transcript (CART) and neurotensin that reduce food intake and increase energy expenditure. The finding that mutations in leptin and POMC lead to severe early onset obesity in humans has highlighted the importance of these peptides in humans. This new understanding may eventually lead to new treatments for obesity that will be of particular benefit in the prevention and treatment of type 2 diabetes.
Leukocyte traffic to sites of inflammation (1992)

The adhesion of circulating leukocytes to the vascular endothelium is essential for effective host inflammatory and immune responses. Adhesion proteins expressed by both the leukocyte and endothelial cell have been well characterized, and studies of these molecules have shown that both cell types are actively involved in regulating these binding events. Most leukocyte (leukocyte integrins) and endothelial cell (vascular selectins, ICAM-1, and VCAM) adhesion proteins increase in expression and function in response to mediators released by inflamed tissues. In contrast, the expression and function of one type of leukocyte molecule, L-selectin (previously called LECAM-1, LAM-1, gp90MEL-14), is "down-regulated" by inflammatory signals. The purpose of this review is to summarize in vitro and in vivo regulatory and functional studies of some of the molecular mechanisms which regulate leukocyte-endothelial cell adhesion, with particular emphasis on L-selectin, and to present a hypothetical model of how these molecules may be orchestrated in vivo resulting in the control of host inflammatory responses.
Adaptive plenoptic sampling (2011)

The plenoptic function enables Image-based rendering (IBR) to be viewed in terms of sampling and reconstruction. Thus the spatial sampling rate can be determined through spectral analysis of the plenoptic function. In this paper we present a method of non-uniformly sampling a scene, with a smoothly varying surface, given a finite number of samples. This method approximates such a scene with a set of slanted planes subject to the constraint of finite number of samples. We use the recent spectral analysis of a single slanted plane to determine a piecewise constant spatial sampling rate for the scene. Finally, we show that this sampling rate results in a non-uniform sampling scheme that reconstructs the plenoptic function beyond that of uniform sampling.
Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging Infection (2007)

Before the emergence of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) in 2003, only 12 other animal or human coronaviruses were known. The discovery of this virus was soon followed by the discovery of the civet and bat SARS-CoV and the human coronaviruses NL63 and HKU1. Surveillance of coronaviruses in many animal species has increased the number on the list of coronaviruses to at least 36. The explosive nature of the first SARS epidemic, the high mortality, its transient reemergence a year later, and economic disruptions led to a rush on research of the epidemiological, clinical, pathological, immunological, virological, and other basic scientific aspects of the virus and the disease. This research resulted in over 4,000 publications, only some of the most representative works of which could be reviewed in this article. The marked increase in the understanding of the virus and the disease within such a short time has allowed the development of diagnostic tests, animal models, antivirals, vaccines, and epidemiological and infection control measures, which could prove to be useful in randomized control trials if SARS should return. The findings that horseshoe bats are the natural reservoir for SARS-CoV-like virus and that civets are the amplification host highlight the importance of wildlife and biosecurity in farms and wet markets, which can serve as the source and amplification centers for emerging infections.
Expression and Stereochemical and Isotope Effect Studies of Active 4-Oxalocrotonate Decarboxylase (2000)

4-Oxalocrotonate decarboxylase (4-OD) and vinylpyruvate hydratase (VPH) from &lt;i&gt;Pseudomonas\nputida mt-2 &lt;/i&gt;form a complex that converts 2-oxo-3-hexenedioate to 2-oxo-4-hydroxypentanoate in the\ncatechol meta fission pathway. To facilitate mechanistic and structural studies of the complex, the two\nenzymes have been coexpressed and the complex has been purified to homogeneity. In addition, Glu-106, a potential catalytic residue in VPH, has been changed to glutamine, and the resulting E106QVPH\nmutant has been coexpressed with 4-OD and purified to homogeneity. The 4-OD/E106QVPH complex\nretains full decarboxylase activity, with comparable kinetic parameters to those observed for 4-OD in the\nwild-type complex, but is devoid of any detectable hydratase activity. Decarboxylation of (5&lt;i&gt;S&lt;/i&gt;)-2-oxo-3-[5-D]hexenedioate by either the 4-OD/VPH complex or the mutant complex generates 2-hydroxy-2,4&lt;i&gt;E&lt;/i&gt;-[5-D]pentadienoate in D&lt;sub&gt;2&lt;/sub&gt;O. Ketonization of 2-hydroxy-2,4-pentadienoate by the wild-type complex is\nhighly stereoselective and results in the formation of 2-oxo-(3&lt;i&gt;S&lt;/i&gt;)-[3-D]-4-pentenoate, while the mutant\ncomplex generates a racemic mixture. These results indicate that 2-hydroxy-2,4-pentadienoate is the product\nof 4-OD and that 2-oxo-4-pentenoate results from a VPH-catalyzed process. On this basis, the previously\nproposed hypothesis for the conversion of 2-oxo-3-hexenedioate to 2-oxo-4-hydroxypentanoate has been\nrevised [Lian, H., and Whitman, C. P. (1994) &lt;i&gt;J. Am. Chem. Soc. 116&lt;/i&gt;, 10403−10411]. Finally, the observed\n&lt;sup&gt;13&lt;/sup&gt;C kinetic isotope effect on the decarboxylation of 2-oxo-3-hexenedioate by the 4-OD/VPH complex\nsuggests that the decarboxylation step is nearly rate-limiting. Because the value is not sensitive to either\nmagnesium or manganese, it is likely that the transition state for carbon−carbon bond cleavage is late\nand that the metal positions the substrate and polarizes the carbonyl group, analogous to its role in\noxalacetate decarboxylase.
THE β-KETOADIPATE PATHWAY AND THE BIOLOGY OF SELF-IDENTITY (1996)

The beta-ketoadipate pathway is a chromosomally encoded convergent pathway for aromatic compound degradation that is widely distributed in soil bacteria and fungi. One branch converts protocatechuate, derived from phenolic compounds including p-cresol, 4-hydroxybenzoate and numerous lignin monomers, to beta-ketoadipate. The other branch converts catechol, generated from various aromatic hydrocarbons, amino aromatics, and lignin monomers, also to beta-ketoadipate. Two additional steps accomplish the conversion of beta-ketoadipate to tricarboxylic acid cycle intermediates. Enzyme studies and amino acid sequence data indicate that the pathway is highly conserved in diverse bacteria, including Pseudomonas putida, Acinetobacter calcoaceticus, Agrobacterium tumefaciens, Rhodococcus erythropolis, and many others. The catechol branch of the beta-ketoadipate pathway appears to be the evolutionary precursor for portions of the plasmid-borne ortho-pathways for chlorocatechol degradation. However, accumulating evidence points to an independent and convergent evolutionary origin for the eukaryotic beta-ketoadipate pathway. In the face of enzyme conservation, the beta-ketoadipate pathway exhibits many permutations in different bacterial groups with respect to enzyme distribution (isozymes, points of branch convergence), regulation (inducing metabolites, regulatory proteins), and gene organization. Diversity is also evident in the behavioral responses of different bacteria to beta-ketoadipate pathway-associated aromatic compounds. The presence and versatility of transport systems encoded by beta-ketoadipate pathway regulons is just beginning to be explored in various microbial groups. It appears that in the course of evolution, natural selection has caused the beta-ketoadipate pathway to assume a characteristic set of features or identity in different bacteria. Presumably such identities have been shaped to optimally serve the diverse lifestyles of bacteria.
HER2 Drives Luminal Breast Cancer Stem Cells in the Absence of HER2 Amplification: Implications for Efficacy of Adjuvant Trastuzumab (2013)

Although current breast cancer treatment guidelines limit the use of HER2-blocking agents to tumors with HER2 gene amplification, recent retrospective analyses suggest that a wider group of patients may benefit from this therapy. Using breast cancer cell lines, mouse xenograft models and matched human primary and metastatic tissues, we show that HER2 is selectively expressed in and regulates self-renewal of the cancer stem cell (CSC) population in estrogen receptor-positive (ER(+)), HER2(-) luminal breast cancers. Although trastuzumab had no effects on the growth of established luminal breast cancer mouse xenografts, administration after tumor inoculation blocked subsequent tumor growth. HER2 expression is increased in luminal tumors grown in mouse bone xenografts, as well as in bone metastases from patients with breast cancer as compared with matched primary tumors. Furthermore, this increase in HER2 protein expression was not due to gene amplification but rather was mediated by receptor activator of NF-κB (RANK)-ligand in the bone microenvironment. These studies suggest that the clinical efficacy of adjuvant trastuzumab may relate to the ability of this agent to target the CSC population in a process that does not require HER2 gene amplification. Furthermore, these studies support a CSC model in which maximal clinical benefit is achieved when CSC targeting agents are administered in the adjuvant setting. Cancer Res; 73(5); 1635-46. ©2012 AACR.