gebhart/patrepeval huggingface dataset:
Now Presenting: γδ T Cells (2005)

T lymphocytes of the immune system require that foreign molecules called antigens be presented to them for their clonal expansion and stimulation of their effector functions. Presentation of peptide antigens to activate naA¯ve T cells was previously thought to reside solely in dendritic cells. A Perspective by [Modlin and Sieling][1] describes new evidence that challenges this premise. A population ofT cells efficiently presents peptide antigens toT cells, the predominant T cell population in mammals. This suggests thatT cells function as part of innate (rapid, short-lived) and adaptive (slower, long-lasting) immunity, the two arms of the immune response.

 [1]: http://www.sciencemag.org/cgi/content/full/309/5732/252
Natural killer cells in HIV-1 infection: role of NK cell-mediated non-cytolytic mechanisms in pathogenesis of HIV-1 infection. (2003)

Natural killer (NK) cells exhibit both cytolytic and non-cytolytic effector functions against HIV-infected targets. Their precise role in immunopathogenesis of HIV-1 infection is yet to be fully understood. This review addresses the non-cytolytic functions exhibited by NK cells, their potential role in pathogenesis of HIV-1 infection and the effect of HIV-1 viremia on NK cell functions. Activated NK cells are capable of secreting CC-chemokines and suppressing HIV-1 replication in a non-cytolytic fashion. However, HIV-1 viremia suppresses the ability of NK cells to secrete CC-chemokines. Suppression of HIV-1 viremia by highly active antiretroviral therapy (HAART) restores the ability of NK cells to secrete CC-chemokines and suppress endogenous HIV-1 replication by non-cytolytic mechanisms. Better understanding of the mechanisms involved in HIV-1-NK cell interactions would be helpful in delineating novel therapeutic strategics against HIV-1.
Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during alpha-adrenergic stimulation of neonatal rat ventricular cells. Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression. (1991)

To study the mechanisms which mediate the transcriptional activation of cardiac genes during alpha adrenergic stimulation, the present study examined the regulated expression of three cardiac genes, a ventricular embryonic gene (atrial natriuretic factor, ANF), a constitutively expressed contractile protein gene (cardiac MLC-2), and a cardiac sodium channel gene. alpha 1-Adrenergic stimulation activates the expression and release of ANF from neonatal ventricular cells. As assessed by RNase protection analyses, treatment with alpha-adrenergic agonists increases the steady-state levels of ANF mRNA by greater than 15-fold. However, a rat cardiac sodium channel gene mRNA is not induced, indicating that alpha-adrenergic stimulation does not lead to an increase in the expression of all cardiac genes. Studies employing a series of rat ANF luciferase and rat MLC-2 luciferase fusion genes identify 315- and 92-base pair cis regulatory sequences within an embryonic gene (ANF) and a constitutively expressed contractile protein gene (MLC-2), respectively, which mediate alpha-adrenergic-inducible gene expression. Transfection of various ANF luciferase reporters into neonatal rat ventricular cells demonstrated that upstream sequences which mediate tissue-specific expression (-3003 to -638) can be segregated from those responsible for inducibility. The lack of inducibility of a cardiac Na+ channel gene, and the segregation of ANF gene sequences which mediate cardiac specific from those which mediate inducible expression, provides further insight into the relationship between muscle-specific and inducible expression during cardiac myocyte hypertrophy. Based on these results, a testable model is proposed for the induction of embryonic cardiac genes and constitutively expressed contractile protein genes and the noninducibility of a subset of cardiac genes during alpha-adrenergic stimulation of neonatal rat ventricular cells.
Use of a catchlike property of human skeletal muscle to reduce fatigue (1991)

This study compared the force output produced by variable frequency, short-duration trains (VFTs) of electrical pulses with the forces produced by constant frequency, short-duration trains (CFTs). Human quadriceps femoris muscle was stimulated with a 300-msec train of pulses once every second for 180 seconds. Each subject (n = 12) participated in 4 randomly assigned experimental sessions. During 3 sessions, a CFT of 80, 40 or 20 pps was used. During a fourth session, a VFT, which consisted of all 3 of the above frequencies, was used. The force at 100 msec, average force of each contraction and peak force were calculated for every 30th contraction. By the 90th contraction, the force at 100 msec and the average force were significantly greater for the VFT than for each CFT. Thus, the VFT, by using a catchlike property, may provide significant advantages over any CFT when using electrical stimulation for functional electrical stimulation.
Iterative point matching for registration of free-form curves (1992)

Geometric matching in general is a difficult unsolved problem in computer vision. Fortunately, in many practical applications, some a priori knowledge exists which considerably simplifies the problem. In visual navigation, for example, the motion between successive positions is usually either small or approximately known, but a more precise registration is required for environment modeling. The algorithm described in this report meets this need. Objects are represented by free-form curves, i.e., arbitrary space curves of the type found in practice. A curve is available in the form of a set of chained points. The proposed algorithm is based on iteratively matching points on one curve to the closest points on the other. A least-squares technique is used to estimate 3-D motion from the point correspondences, which reduces the average distance between curves in the two sets. Both synthetic and real data have been used to test the algorithm, and the results show that it is efficient and robust, ...
Established immunoglobulin producing myeloma (IgE) and lymphoblastoid (IgG) cell lines from an IgE myeloma patient. (1970)

Two IgEL and one IgGK producing cell lines have been established in vitro from peripheral blood and bone marrow of an E myeloma patient. Morphologic and immunologic studies indicate that cells of the IgE producing lines are derived from the same clone of myeloma cells which grew in vivo. They have remained essentially unaltered with a stable near-diploid karyotype and continuous production of intact IgE molecules during 18 months in culture. The IgGK producing line has all the characteristics ascribed to permanent lymphoblastoid lines and is considered to be of non-malignant lymphoid origin. The process of establishment is described and it is suggested that lymphoblastoid cells have a selective advantage over myeloma cells. Permanent myeloma cell lines can therefore probably be obtained only if cells capable of forming established lymphoblastoid lines are very few or absent in the original biopsy. The establishment of a permanent cell line continuously producing intact molecules of IgE should permit further studies on the biological role of this class of immunoglobulins.
Lipids as Targeting Signals: Lipid Rafts and Intracellular Trafficking (2004)

Our view of biological membranes has evolved dramatically over the last few decades. In the bilayer model from Singer & Nicholson (Science 1972;175:720-731), both proteins and lipids freely diffuse within the plane of the membrane. Currently, however, membranes are viewed as a mosaic of different compartments or domains maintained by an active cytoskeleton network (Ritchie et al. Mol Membr Biol 2003; 20:13-18). Due to interactions between membrane components, several types of subdomains can form with different characteristics and functions. Lipids are likely to play an important role in the formation of so-called lipid-enriched microdomains or lipid rafts, adding another order of complexity to the membrane model. Rafts represent a type of domain wherein lipids of specific chemistry may dynamically associate with each other, to form platforms important for membrane protein sorting and construction of signaling complexes (Simons & Toomre. Nat Rev Mol Cell Biol 2000;1:31-39). Currently, there are several hypotheses concerning the nature of rafts (reviewed in (Edidin. Annu Rev Biophys Biomol Struct 2003;32: 257-283; Zurzolo et al. EMBO Rep 2003;4:1117-1121)). The most commonly cited one, proposed by Kai Simons (Simons & Ikonen. Nature 1997;387:569-572; Pralle et al. J Cell Biol 2000;148:997-1008), suggests that rafts are relatively small structures ( approximately 50 nm) enriched in cholesterol and sphingolipids within which associated proteins are likely to be concentrated. Another proposal (Anderson & Jacobson. Science 2002;296:1821-1825) suggests that rafts are constructed of lipid shells. These are small dynamic assemblies wherein 'raft' proteins are preferentially associated with certain types of lipids. These 'shells' are thermodynamically stable mobile entities in the plane of the membrane that are able to target the protein they encase to preexisting rafts/caveolae domains. In this review we summarize the data suggesting a specific role for lipid domains in intracellular trafficking and sorting and present a modification of the raft model that may help explain the observed phenomena.
Campylobacter Jejuni: Current Status and Future Trends (1992)

Clinical and Epidemiologic Aspects Reservoirs and Antimicrobial Resistance Clinical Microbiology Pathogenesis of Campylobacter Infections Immune Responses and Antigenic Analysis Molecular Pathogenesis
"Opening" Pandora's Box: The Status of the Diplomatic Bag in International Relations (1988)

This Note argues that article 27 [of the Vienna Convention on Diplomatic Relations] provides for the absolute inviolability of the diplomatic bag. Part I discusses the history of the Vienna Convention and its provisions concerning the diplomatic bag. Part II sets forth instances of abuse of the diplomatic bag, proposed remedies, and the arguments in favor of such remedies. Part III suggests that the proper construction of article 27 of the Vienna Convention is that the diplomatic bag is absolutely inviolable and, thus, immune from nonintrusive examinations. This Note concludes that the status of the bag should be reconsidered in order to enable governments to curb its abuses.
Thermal therapy techniques for skin and superficial tissue disease (2000)

There are numerous diseases and abnormal growths and conditions that afflict the skin and underlying superficial tissues. In addition to cancers such as primary, recurrent, and metastatic melanomas and carcinomas, there are many non-malignant conditions such as psoriasis plaques, port wine stains, warts, and superficial cut and bum wounds. Many of these clinical conditions have been shown responsive to treatment with thermal therapy - either low temperature freezing (cryotherapy),. moderate temperature warming to about 41-45°C (hyperthermia), or high temperature (>50°C) ablation or coagulation necrosis therapy. Because both very low and very high temperature therapies are for the most part non-selectively destructive in nature, they normally are used for applications where therapy can be localized precisely in the desired target and some necrosis of adjacent normal tissues is acceptable. With the exception of precision controlled cryotherapy or laser surgery (e.g. wart, mole, tattoo and port wine stain removal) or focal thermal surgery of small deep-seated nodules, it is generally preferred to use moderate thermal therapy (hyperthermia) in the treatment of skin and subcutaneous tissue disease in order to preserve the protective barrier characteristic of intact skin within the target region while inducing more subtle long term therapeutic improvement in the disease condition. This type of subtle thermal therapy is usually administered in combination with one or more other therapies such as radiation or chemotherapy - something with a differential effect on the target and surrounding normal tissues that can be magnified by the adjuvant use of heat.
A Convergent Route to 5-(Arylsulfanyl)-6-sulfonamido-3-benzofuranones (2000)

A procedure for the synthesis of 5-(arylsulfanyl)-2,3-dihydro-6-sulfonamido-3-benzofuranones (1) via 5-bromo-3-methoxy-6-nitrobenzofuran (4) as a common advanced synthetic intermediate has been developed. The key step consists of a regioselective nucleophilic aromatic substitution of the bromine atom of 4 by an aryl or heteroarylthiol.
Methoxytetrahydropyrans. A new series of selective and orally potent 5-lipoxygenase inhibitors (1992)

Investigation of the SAR of the lead (methoxyalkyl)thiazole 1-[3-(naphth-2-ylmethoxy)phenyl]-1-thiazol-2-ylprop yl methyl ether (1, ICI 211965) led to the methoxytetrahydropyrans, a new series of 5-lipoxygenase (5-LPO) inhibitors exemplified by the parent compound 4-[3-(naphth-2-ylmethoxy)phenyl]-4- methoxy-3,4,5,6-tetrahydro-2H-pyran (4f). In vitro 4f inhibited leukotriene C4 (LTC4) synthesis in zymosan-stimulated plasma-free mouse macrophages and LTB4 synthesis in A-23187-stimulated human whole blood (IC50s 0.5 nM and 0.07 microM, respectively). In the rat 4f inhibited LTB4 synthesis in blood ex vivo and in zymosan-inflamed air pouch exudate with an ED50 3 h after oral dosing of 10 mg/kg in each system. In seeking more potent orally active compounds, strategies were explored in congeners of 4f for reducing lipophilicity without sacrificing potency. For example, replacement of 2-naphthyl of 4f by various aza- and oxoheterocycles afforded compounds in which log P is reduced by 1.7-2.3 units while potency in human whole blood in vitro was maintained or enhanced relative to 4f. In addition, the oxoheterocyclic replacements provided compounds with improved oral potency and the preferred compound from this group is 6-[[3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4- yl)phenoxy]methyl]-1-methylquinol-2-one (4y). In the in vitro systems, 4y inhibited LT formation with IC50s in mouse macrophages and human whole blood of 3 nM and 0.02 microM, respectively. 4y did not inhibit the synthesis of cyclooxygenase (CO) products at concentrations up to 500 microM in human blood, a selectivity for 5-LPO over CO of greater than 20,000-fold. In the rat 4y inhibited the formation of LTB4 in blood ex vivo and in inflammatory exudate with ED50s 3 h after oral dosing of 0.9 and 0.3 mg/kg, respectively. 4y was more potent in vitro in human whole blood and in rat blood ex vivo at 3 h than either the 5-LPO inhibitor A-64077 or the FLAP antagonist MK-886. Based on these data 4y (ICI D2138) has been entered into development as an orally active, selective 5-LPO inhibitor for clinical evaluation in inflammatory conditions in which LTs are believed to play a role.
Antigen presentation by splenic B cells: resting B cells are ineffective, whereas activated B cells are effective accessory cells for T cell responses. (1985)

In this study, we have investigated the ability of splenic B cells to act as antigen-presenting cells. Previous data had established that lipopolysaccharide (LPS)-activated B cells were effective antigen-presenting cells; however, the relative capacity of resting B cells to carry out this function remains controversial. Splenic B cells from naive BALB/c mice were depleted of macrophages, dendritic cells, and T cells, and were fractionated on the basis of cell density by using Percoll gradient centrifugation. Fractions were collected from the 50/60, 60/65, and 65/72% interfaces and from greater than 72% (pellet). Cytofluorograph analysis of the fractionated B cells showed that the two lower density fractions (50/60 and 60/65) contained a number of cells which, by cell size determination, appeared to be activated B cells, whereas the two higher density fractions (65/72 and greater than 72) appeared to contain predominantly small resting B cells contaminated by many fewer activated B cells. Functionally, the capacity of fractionated B cells to act as accessory cells for a concanavalin A response or present the antigens chicken ovalbumin (OVA) or OVA-tryptic digest gave similar results, which indicated a striking hierarchy of accessory cell function in the different Percoll fractions. When normalized to the most active low-density fraction (50/60%), the activity of the other fractions were: 60/65 = 78%; 65/72 = 25%; and greater than 72 = 4%. The differences in the functional capacity between the various Percoll fractions did not appear to be due to differences in Ia expression. Although the expression of Ia varied approximately 12-fold within any one fraction, there was little difference in the mean amount of Ia on cells obtained from the various fractions. Kinetic studies showed that activation of B cells with LPS and dextran sulfate resulted in the expression of two stages of functional development. The first stage was an increased efficiency of accessory cell function that was abrogated by irradiation with 4000 rad followed by a second stage, which was characterized by the acquisition of resistance to treatment with 4000 rad. When nonfractionated B cells that had been stimulated with LPS and DexSO4 were sorted on the basis of cell size into a small B cell fraction and a large B cell fraction, only the large B cells were able to present antigen. Taken together, these data suggest that much of the accessory cell function associated with splenic B cells can be accounted for by the relatively small percentage of activated B cells present in the spleen.(ABSTRACT TRUNCATED AT 400 WORDS)
Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity (2015)

Changes of histone modification status at critical lineage-specifying gene loci in multipotent precursors can influence cell fate commitment. The contribution of these epigenetic mechanisms to natural killer (NK) cell lineage determination from common lymphoid precursors is not understood. Here we investigate the impact of histone methylation repressive marks (H3 Lys27 trimethylation; H3K27(me3)) on early NK cell differentiation. We demonstrate that selective loss of the histone-lysine N-methyltransferase Ezh2 (enhancer of zeste homolog 2) or inhibition of its enzymatic activity with small molecules unexpectedly increased generation of the IL-15 receptor (IL-15R) CD122(+) NK precursors and mature NK progeny from both mouse and human hematopoietic stem and progenitor cells. Mechanistic studies revealed that enhanced NK cell expansion and cytotoxicity against tumor cells were associated with up-regulation of CD122 and the C-type lectin receptor NKG2D. Moreover, NKG2D deficiency diminished the positive effects of Ezh2 inhibitors on NK cell commitment. Identification of the contribution of Ezh2 to NK lineage specification and function reveals an epigenetic-based mechanism that regulates NK cell development and provides insight into the clinical application of Ezh2 inhibitors in NK-based cancer immunotherapies.
Pneumonia due to Moraxella (Branhamella) catarrhalis. (1989)

Branhamella catarrhalis is a Neisseriae-like organism that is the newest member of the family of pneumonic pathogens. The organism is seasonal, encountered only during the respiratory disease season. The majority of patients with pneumonia (80% to 90%) have underlying chronic pulmonary disease, and their clinical illness may be difficult to distinguish from exacerbations of lung disease by other causes. B catarrhalis is the most common bacterial pathogen in this setting after Haemophilus influenzae and Streptococcus pneumoniae. The organism is easy to identify in the laboratory, with a quality gram stain of sputum being the key to recognition. Most patients show patchy non-cavitary infiltrates on chest roentgenograms. Because 75% of isolates produce beta lactamase, empiric therapy with penicillin or amoxicillin is likely to fail. Recommended drugs include erythromycin, trimethoprim/sulfamethoxazole, amoxicillin/clavulanic acid (Augmentin), or one of the newer broad spectrum cephalosporins.
Recognition of protein coding regions in DNA sequences (1982)

We give a test for protein coding regions which is based on simple and universal differences between protein-coding and noncoding DNA. The test is simple enough to use without a computer and is completely objective. The test has been thoroughly proven on 400,000 bases of sequence data: it misclassifies 5% of the regions tested and gives an answer of "No Opinion" one fifth of the time. We predict some new coding and noncoding regions in published sequences.
Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer. (1995)

The TGF beta type II receptor (RII) was found to be mutated within a polyadenine tract in 100 of 111 (90%) colorectal cancers with microsatellite instability. Other polyadenine tracts of similar length were mutated in these samples but not as frequently as RII. In most cases, the polyadenine tract mutations affected both alleles of RII, and in four tumors heterozygous for the polyadenine mutations, three had additional mutations that were expected to inactivate the other RII allele. These genetic data support the idea that RII behaves like a tumor suppressor during CR cancer development and is a critical target of inactivation in mismatch repair-deficient tumors.
Automated detection of retinal layer structures on optical coherence tomography images (2005)

Segmentation of retinal layers from OCT images is fundamental to diagnose the progress of retinal diseases. In this study we show that the retinal layers can be automatically and/or interactively located with good accuracy with the aid of local coherence information of the retinal structure. OCT images are processed using the ideas of texture analysis by means of the structure tensor combined with complex diffusion filtering. Experimental results indicate that our proposed novel approach has good performance in speckle noise removal, enhancement and segmentation of the various cellular layers of the retina using the STRATUSOCTTM system.
BLOOD-BRAIN BARRIER DRUG TARGETING: THE FUTURE OF BRAIN DRUG DEVELOPMENT (2003)

As human longevity increases, the likelihood of the onset of diseases of the brain (and other organs) also increases. Clinical therapeutics offer useful long-term treatments, if not cures, if drugs can be delivered appropriately and effectively. Unfortunately, research in drug transport to the brain has not advanced very far. Through better characterization of the transport systems utilized within the blood-brain barrier, a greater understanding of how to exploit these systems will lead to effective treatments for brain disorders. Pardridge reviews the functions of the various known transport systems in the brain and discusses how the development of BBB drug-targeting programs in pharmaceutical and academic settings may lead to more efficacious treatments.