gebhart/patrepeval huggingface dataset:
Antibody specificity controls in vivo effector mechanisms of anti-CD20 reagents (2003)

Despite the success of anti-CD20 monoclonal antibody (mAb) in the treatment of lymphoma, there remains considerable uncertainty about their mechanism(s) of action. Here, we show that certain of these reagents (rituximab and 1F5), which redistribute CD20 into membrane rafts, are bound efficiently by C1q, deposit C3b, and result in complement-dependent cytotoxicity (CDC). This activity is important in vivo, because complement depletion using cobra venom factor (CVF) markedly reduced the efficacy of rituximab and 1F5 in 2 lymphoma xenograft models. However, complement depletion had no effect on the potent therapeutic activity of B1, a mAb that does not redistribute CD20 into membrane rafts, bind C1q, or cause efficient CDC. Equivalent immunotherapy also occurred in the presence or absence of natural killer (NK) cells. Perhaps most surprising was the observation that F(ab')2 fragments of B1 but not 1F5 were able to provide substantial immunotherapy, indicating that non-Fc-dependent mechanisms are involved with B1. In accordance with this, B1 was shown to induce much higher levels of apoptosis than rituximab and 1F5. Thus, although complement is important for the action of rituximab and 1F5, this is not so for B1, which more likely functions through its ability to signal apoptosis.
Microneedles: an emerging transdermal drug delivery system (2011)

Abstract Objectives One of the thrust areas in drug delivery research is transdermal drug delivery systems (TDDS) due to their characteristic advantages over oral and parenteral drug delivery systems. Researchers have focused their attention on the use of microneedles to overcome the barrier of the stratum corneum. Microneedles deliver the drug into the epidermis without disruption of nerve endings. Recent advances in the development of microneedles are discussed in this review for the benefit of young scientists and to promote research in the area. Key findings Microneedles are fabricated using a microelectromechanical system employing silicon, metals, polymers or polysaccharides. Solid coated microneedles can be used to pierce the superficial skin layer followed by delivery of the drug. Advances in microneedle research led to development of dissolvable/degradable and hollow microneedles to deliver drugs at a higher dose and to engineer drug release. Iontophoresis, sonophoresis and electrophoresis can be used to modify drug delivery when used in concern with hollow microneedles. Microneedles can be used to deliver macromolecules such as insulin, growth hormones, immunobiologicals, proteins and peptides. Microneedles containing ‘cosmeceuticals’ are currently available to treat acne, pigmentation, scars and wrinkles, as well as for skin tone improvement. Summary Literature survey and patents filled revealed that microneedle-based drug delivery system can be explored as a potential tool for the delivery of a variety of macromolecules that are not effectively delivered by conventional transdermal techniques.
Enzyme Microarrays: On‐Chip Determination of Inhibition Constants Based on Affinity‐Label Detection of Enzymatic Activity (2004)

High-throughput screening of libraries of potential inhibitors is possible by using an enzyme microarray method that combines low sample consumption with accuracy and speed. Information about enzyme inhibition can be obtained “on-chip” by the addition of a fluorescently tagged affinity label to a microarray of functional enzymes (see picture).
Reduced mRNA levels for the multidrug‐resistance genes in cAMP‐dependent protein kinase mutant cell lines (1992)

We have previously shown that in Chinese hamster ovary (CHO) cells, a mutant cell line with a defective regulatory subunit (RI) for the cAMP-dependent protein kinase (Abraham et al: Mol. Cell. Biol., 7:3098-3106, 1987), and a transfectant cell line expressing the same mutant kinase, showed increased sensitivity to a number of drugs that are known to be substrates for the multidrug transporter (P-glycoprotein). In the current study we have investigated the mechanism by which cAMP-dependent protein kinase controls drug resistance. We report here that the sensitivity of the kinase defective CHO cell lines to multiple drugs results from decreased RNA levels for the multidrug-resistance gene. Similar results were obtained with mouse Y1 adrenal cells. Wild-type Y1 cells had high levels of P-glycoprotein due to expression of both the mdr1b and mdr2 genes, whereas the cAMP-dependent protein kinase mutant Kin 8 cells had decreased RNA levels for these genes. A Kin 8 transfectant with restored cAMP-dependent protein kinase activity recovered mdr expression, indicating a cause and effect relationship between the protein kinase mutations and mdr expression. No changes in nuclear run-off assays could be detected, suggesting a non-transcriptional mechanism of regulation. Wild-type Y1 cells are more drug sensitive despite having higher levels of P-glycoprotein than the mutant cells. This paradoxical result may be explained by the higher rate of synthesis of steroids by the wild-type Y1 cells, which appear to be inhibitors of P-glycoprotein transport activity.
Nitrogen-Containing Furanose and Pyranose Analogues from Hyacinthus orientalis (1998)

Aqueous methanol extracts from the bulbs of Hyacinthusorientalis were subjected to various ion-exchange column chromatographic steps to give 2(R),5(R)-bis(hydroxymethyl)-3(R),4(R)-dihydroxypyrrolidine (DMDP) (1), 2,5-dideoxy-2,5-imino-dl-glycero-d-manno-heptitol (homoDMDP) (2), 2,5-imino-2,5,6-trideoxy-d-manno-heptitol (6-deoxy-homoDMDP) (3), 2,5-imino-2,5,6-trideoxy-d-gulo-heptitol (4), 1-deoxynojirimycin (5), 1-deoxymannojirimycin (6), alpha-homonojirimycin (7), beta-homonojirimycin (8), alpha-homomannojirimycin (9), beta-homomannojirimycin (10), and 7-O-beta-d-glucopyranosyl-alpha-homonojirimycin (MDL 25,637) (11). The structures of the new natural products 3 and 4 were determined by spectroscopic analysis, including extensive 1D and 2D NMR studies. Compound 2 was found to be a potent inhibitor of bacterial beta-glucosidase, mammalian beta-galactosidases, and mammalian trehalases, while 3 was a potent inhibitor of rice alpha-glucosidase and rat intestinal maltase. Compound 4 was observed to be a good inhibitor of alpha-l-fucosidase.
Improbability of effective vaccination against human immunodeficiency virus because of its intracellular transmission and rectal portal of entry. (1992)

The worldwide effort to produce a vaccine against AIDS continues to disregard the fact that even human immunodeficiency virus (HIV)-specific neutralizing antibodies and cell-mediated immunity are ineffective against virus within cells without viral antigens on the cell membrane--and that much of HIV infection is transmitted in this manner. According to a recent report, a simian immunodeficiency virus vaccine that protected monkeys against an intravenous challenge with cell-free virus was, as predicted, ineffective against an intravenous challenge with the same amount of virus in infected cells. Moreover, antibody and HIV have been found to coexist in cell-free plasma from asymptomatic and symptomatic patients. Excluding direct introduction of HIV into the blood-stream, the most common and efficient form of transmission of HIV infection is by receptive anal intercourse, and semen contains large numbers of infected cells per milliliter. Recent reports showing that colorectal cells can be persistently infected by HIV and that HIV RNA and cDNA are present in the cells of the colon of dead AIDS patients indicate that either cell-free or intracellular HIV has the capacity to multiply at the portal of entry in the colorectal area without interference from neutralizing antibodies. The available data provide no basis for testing any HIV vaccine in human beings either before or after infection. The main challenge is to find a way to kill cells with chromosomally integrated HIV cDNA without harming normal cells, perhaps by identifying repressor proteins that might be produced by the cells with integrated HIV cDNA and thus could become specific targets for cell-killing drugs.
The role of genetic and genomic attributes in the success of polyploids (2000)

In 1950, G. Ledyard Stebbins devoted two chapters of his book Variation and Evolution in Plants (Columbia Univ. Press, New York) to polyploidy, one on occurrence and nature and one on distribution and significance. Fifty years later, many of the questions Stebbins posed have not been answered, and many new questions have arisen. In this paper, we review some of the genetic attributes of polyploids that have been suggested to account for the tremendous success of polyploid plants. Based on a limited number of studies, we conclude: (i) Polyploids, both individuals and populations, generally maintain higher levels of heterozygosity than do their diploid progenitors. (ii) Polyploids exhibit less inbreeding depression than do their diploid parents and can therefore tolerate higher levels of selfing; polyploid ferns indeed have higher levels of selfing than do their diploid parents, but polyploid angiosperms do not differ in outcrossing rates from their diploid parents. (iii) Most polyploid species are polyphyletic, having formed recurrently from genetically different diploid parents. This mode of formation incorporates genetic diversity from multiple progenitor populations into the polyploid "species"; thus, genetic diversity in polyploid species is much higher than expected by models of polyploid formation involving a single origin. (iv) Genome rearrangement may be a common attribute of polyploids, based on evidence from genome in situ hybridization (GISH), restriction fragment length polymorphism (RFLP) analysis, and chromosome mapping. (v) Several groups of plants may be ancient polyploids, with large regions of homologous DNA. These duplicated genes and genomes can undergo divergent evolution and evolve new functions. These genetic and genomic attributes of polyploids may have both biochemical and ecological benefits that contribute to the success of polyploids in nature.
A Survey of Face Recognition Techniques (2009)

Face recognition presents a challenging problem in the field of image analysis and computer vision, and as such has received a great deal of attention over the last few years because of its many applications in various domains. Face recognition techniques can be broadly divided into three categories based on the face data acquisition methodology: methods that operate on intensity images; those that deal with video sequences; and those that require other sensory data such as 3D information or infra-red imagery. In this paper, an overview of some of the well-known methods in each of these categories is provided and some of the benefits and drawbacks of the schemes mentioned therein are examined. Furthermore, a discussion outlining the incentive for using face recognition, the applications of this technology, and some of the difficulties plaguing current systems with regard to this task has also been provided. This paper also mentions some of the most recent algorithms developed for this purpose and attempts to give an idea of the state of the art of face recognition technology.
A control theoretic model of driver steering behavior (1990)

Following well-established feedback control design principles, a control theoretic model of driver steering behavior is presented. While accounting for the inherent manual control limitations of the human, the compensation dynamics of the driver are chosen to produce a stable, robust, closed-loop driver-vehicle system with a bandwidth commensurate with the demands of the driving task being analyzed. A technique for selecting driver model parameters is a natural by-product of the control theoretic modeling approach. Experimental verification shows the ability of the model to produce driver-vehicle responses similar to those obtained in a simulated lane-keeping driving task on a curving road.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis and Characterization of Glycomethacrylate Hybrid Stars from Silsesquioxane Nanoparticles (2005)

A silsesquioxane nanoparticle based macroinitiator of ca. 58 functions was synthesized and characterized using 1H NMR, MALDI-TOF MS, and elemental analysis. The macroinitiator was used to synthesize glycomethacrylate stars with approximately 25 arms of different lengths using 3-O-methacryloyl-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (MAIGlc) as the monomer via atom transfer radical polymerization (ATRP). Well-defined glycostars could be synthesized by restricting the polymerization to low conversion. The molecular weights of the star polymers were determined using gel permeation chromatography (GPC) with viscosity and multiangle light scattering (MALS) detectors. To determine the efficiency of the initiating sites, the arms were cleaved from the core by solvolysis with sodium methoxide and thoroughly characterized, indicating that ca. 25 arms per star had been synthesized. The morphology of the glycostars was visualized using scanning force microscopy (SFM) and field emission scanning electron microscopy (FE-SEM). Deprotection of the isopropylidene groups resulted in water-soluble stars that were characterized using SFM, SEM, asymmetric flow field-flow fractionation (AF-FFF), dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), and bright-field transmission electron microscopy (TEM).
How a Smart Environment Can Use Perception (2001)

Perception is a vital part of a smart environment, both as a way to sense the state of the space and a way to detect commands from its users. This paper catalogs different sorts of perception for smart environments using the EasyLiving project at Microsoft Research as the main example.
152. Nucleofection and Phage phiC31 Integrase Mediate Stable Introduction of a Dystrophin Fusion Gene into Muscle Derived Stem Cell and Human Myoblasts (2004)

Intramuscular injection of plasmid DNA followed by electrical stimulation (electroporation) is an efficient mean for non viral delivery of DNA in vivo in smaller animals like mice and rats. In animals with increased body mass however, transfection is less efficient, often caused by the difficulty of DNA distribution relative to the electric field. We have developed a new device for the combined DNA injection and electroporation in which the injection needles also serve as electrodes. DNA is injected through two needles during insertion into the muscle and is thus distributed along the entire needle path enabling a perfect match between the DNA and the electric field. Using this device we have aimed to optimize electroporation conditions such as injection volume, DNA concentration, and field strength for use in larger animals.
Visually searching the Web for content (1997)

New visual information in the form of images, graphics, animations and videos is published on the World Wide Web at an incredible rate. However, cataloging it exceeds the capabilities of current text-based Web search engines. WebSeek provides a complete system that collects visual information from the Web by automated agents, then catalogs and indexes it for fast searching and retrieval.
Neural encoding of single-formant stimuli in the cat. II. Responses of anteroventral cochlear nucleus units (1994)

1. We have studied responses of anteroventral cochlear nucleus (AVCN) units to single-formant stimuli (SFS), in an effort to make quantitative comparisons with responses observed in auditory-nerve fibers (ANFs) to the same stimuli (Wang and Sachs 1993) and to reveal some of the signal processing mechanisms at the AVCN. Single-unit recordings and subsequent analyses were performed on each type of commonly recorded units, namely primarylike (Pri), primarylike with notch (PN), sustained chopper (ChS), transient chopper (ChT), and onset chopper (OnC), as well as a few onset (On) units, from the AVCN in anesthetized cats. The responses were obtained at a wide range of sound levels and at a frequency range of 1-10 kHz. Modulation in the envelopes of discharge patterns was quantified by a measure called modulation depth. 2. At moderate to high sound levels, most AVCN units were found to have enhanced modulation depth compared with that of ANFs, although the degree of enhancement varies among different types. All AVCN units, except Pri type, showed an enhancement in modulation depth over that of the highest of ANFs at moderate to high sound levels in the order of (from the highest to the lowest) On, OnC, ChT/PN, and ChS. Specifically, 1) modulation depth in Pri units was comparable to that of high spontaneous rate (SR) ANFs at low sound levels and to that of low/medium SR ANFs at high sound levels (in dB SPL). When sound level was normalized by unit threshold, Pri units, on average, exhibited only limited enhancement in envelope modulation at high sound levels (> 80 dB re threshold); 2) PN units showed substantially enhanced modulation depth over that of all SR groups of ANFs at moderate to high sound levels in dB SPL or dB re threshold scales; 3) significant enhancement in modulation depth was seen in both ChS and ChT units, with a slightly higher modulation depth in ChT type across sound levels (in dB SPL or dB re threshold); 4) modulation depth of OnC units was higher than those of primary-like (Pri and PN) and chopper (ChS and ChT) units at a wide range of sound levels; 5) responses from a limited sample of On units showed the highest modulation depth among all types of AVCN units. 3. Detailed analysis revealed that the enhanced modulation depth in the responses of AVCN units is the result of increased envelope peak height and decreased envelope minimum, relative to those of ANFs.(ABSTRACT TRUNCATED AT 400 WORDS)
Crystal structure of human wildtype and S581L‐mutant glycyl‐tRNA synthetase, an enzyme underlying distal spinal muscular atrophy (2007)

Dominant mutations in the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS), including S581L, lead to motor nerve degeneration. We have determined crystal structures of wildtype and S581L-mutant human GlyRS. The S581L mutation is approximately 50A from the active site, and yet gives reduced aminoacylation activity. The overall structures of wildtype and S581L-GlyRS, including the active site, are very similar. However, residues 567-575 of the anticodon-binding domain shift position and in turn could indirectly affect glycine binding via the tRNA or alternatively inhibit conformational changes. Reduced enzyme activity may underlie neuronal degeneration, although a dominant-negative effect is more likely in this autosomal dominant disorder.
Role of Calcitonin Gene-Related Peptide in Light-Aversive Behavior: Implications for Migraine (2009)

Migraine is a chronic neurological disorder characterized by recurrent episodes of severe unilateral throbbing head pain and associated symptoms, such as photophobia. Our current understanding of the mechanisms underlying migraine has been hampered by limitations in ascertaining migraine symptoms in animal models. Clinical studies have established the neuropeptide calcitonin gene-related peptide (CGRP) as a key player in migraine. Here, we establish a genetic model of photophobia by engineering increased sensitivity to CGRP in mice. These transgenic mice (nestin/hRAMP1) display light-aversive behavior that is greatly enhanced by intracerebroventricular injection of CGRP and blocked by coadministration of the CGRP receptor antagonist olcegepant. This behavior appears to be an indicator of photophobia and cannot be fully explained by gross abnormality of ocular anatomy or differences in general anxiety or motor activity. Our findings demonstrate that a single gene, receptor activity-modifying protein 1 (RAMP1), can be a modifier of photophobia and, by extension, suggest that genetic or epigenetic modulation of RAMP1 levels may contribute to migraine susceptibility. Moreover, they validate CGRP hypersensitive mice as a tool for exploring the neurobiology and novel therapies for migraine and other disorders involving photophobia.
Multicarrier CDMA system with cochannel interference cancellation (2002)

In a conventional quasi-synchronous system, synchronized users, so-called in-sync users, experience less interference than do out of sync users. The authors propose a new technique to cancel the cochannel interference for an out-of-sync user in the forward link of a cellular CDMA system. They use multicarrier direct sequence waveforms, which can yield both robustness against multipath fading and narrowband interference suppression, in addition to cochannel interference suppression.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cellular recognition and trafficking of amorphous silica nanoparticles by macrophage scavenger receptor A (2010)

The cellular uptake of engineered nanoparticles (ENPs) is known to involve active transport mechanisms, yet the biological molecules involved are poorly understood. We demonstrate that the uptake of amorphous silica ENPs by macrophage cells, and the secretion of proinflammatory cytokines, is strongly inhibited by silencing expression of scavenger receptor A (SR-A). Conversely, ENP uptake is augmented by introducing SR-A expression into human cells that are normally non-phagocytic. Confocal microscopy analyses show that the majority of single or small clusters of silica ENPs co-localize with SR-A and are internalized through a pathway characteristic of clathrin-dependent endocytosis. In contrast, larger silica ENP agglomerates (>500 nm) are poorly co-localized with the receptor, suggesting that the physical agglomeration state of an ENP influences its cellular trafficking. As SR-A is expressed in macrophages throughout the reticulo-endothelial system, this pathway is likely an important determinant of the biological response to ENPs.
Clinical Performance of the Implantable Cardioverter‐Defibrillator (1984)

The automatic implantable cardioverter-defibrillator has been implanted in 276 patients with ventricular tachyarrhythmias refractory to therapy with a follow-up period up to 50 months (average 9.75 months). The functional performance of the device has so far been most encouraging. The risks and complications associated with its use are acceptable and quite similar to those observed in patients with implanted pacemakers. Acceleration of ventricular tachycardia to a faster rhythm or to ventricular fibrillation is dealt with successfully through recycling. Actuarial analysis indicates that the device has a significant impact on the survival rate of the implantees, reducing the one-year mortality rate attributed to arrhythmias to only 2%.
Generative and discriminative algorithms for spoken language understanding (2007)

Spoken Language Understanding (SLU) for conversational systems (SDS) aims at extracting concept and their relations from spontaneous speech. Previous approaches to SLU have modeled concept relations as stochastic semantic networks ranging from generative approach to discriminative. As spoken dialog systems complexity increases, SLU needs to perform understanding based on a richer set of features ranging from a-priori knowledge, long dependency, dialog history, system belief, etc. This paper studies generative and discriminative approaches to modeling the sentence segmentation and concept labeling. We evaluate algorithms based on Finite State Transducers (FST) as well as discriminative algorithms based on Support Vector Machine sequence classifier based and Conditional Random Fields (CRF). We compare them in terms of concept accuracy, generalization and robustness to annotation ambiguities. We also show how non-local non-lexical features (e.g. a-priori knowledge) can be modeled with CRF which is the best performing algorithm across tasks. The evaluation is carried out on two SLU tasks of different complexity, namely ATIS and MEDIA corpora.