gebhart/patrepeval huggingface dataset:
Generation of biologically active anti-Cryptococcus neoformans IgG, IgE and IgA isotype switch variant antibodies by acridine orange mutagenesis (1996)

Administration of MoAbs to Cryptococcus neoformans capsular glucuronoxylomannan (GXM) can alter the course of infection in mouse models. However, the effectiveness of these antibodies appears to depend on isotype and specificity. Comparison of isotype protection efficacy requires families of MoAbs with identical fine specificity and different constant region domain. The generation of such families by hybridoma technology is not always possible because the immune response produces MoAbs of limited classes or subclasses. In these instances isotype switch variants can be isolated in vitro. Unfortunately, standard methods of recovering spontaneous switch variants are often unsuccessful, mainly because of the low frequency of switching. In this study we demonstrate that acridine orange stimulation of an IgG3 anti-C. neoformans-producing hybridoma can be used to recover the entire set of isotype switch variants: IgGl, IgG2b, IgG2a, IgE and IgA. All isotype switch variants bind to GXM; fine specificity mapping, using an 11 amino acid peptide polysaccharide mimetope, revealed conservation of binding site specificity. Furthermore, all isotype switch variants reacted with an anti-idiotopic MoAb. The functional activity of this set of MoAbs was demonstrated by their ability to enhance phagocytosis and antifungal efficacy of human macrophage-like THP-1 cells, with IgG3 being the most effective and IgE being the least effective.
Long-Term Depression (1989)

LTD has now been established as a synaptic plasticity specific to the cerebellum. Cellular and molecular mechanisms of LTD have been elucidated to some extent, but still a number of questions are left open. The most crucial question may concern its time course, as to how long the LTD lasts beyond the limit of the present maximum observation time of 3 hr, and whether and how it is eventually transformed to a permanent memory. Molecular mechanisms underlying LTD should be investigated further in respect to Ca2+ binding and storage, protein kinase C, phosphorylation of glutamate receptors, GTP proteins, etc. The ineffectiveness of mass field potentials in representing LTD makes such studies relatively difficult, and a hope for future development may be placed in reproduction of LTD in tissue cultured Purkinje cells or even in isolated glutamate receptors in a simplified form. The cerebellar neuronal network incorporating LTD as a memory element has been conceived as a simple perceptron-like (Albus 1971) or adaptive filter-like (Fujita 1982a) parallel processing computer. Such a neuronal computer incorporated in a reflex or a more complex movement system would endow the system with subtle capabilities of adaptation and learning. The scheme of the floccular control of the VOR closely resembles that of a self-tuning regulator, a type of adaptive control system. For cerebellar control of voluntary movements, however, another version of the adaptive control system, the model reference control system, seems to be more applicable (Ito 1986). This system continuously readjusts its dynamics by referring to errors derived through comparison of its performance with that of an internal model. It is important to note that a model for an unknown system can be built based on the same principle, by feeding errors derived from their comparison to adjust the model. It may thus be conceived that an internal model is built within the cerebellum in the manner of model reference adaptive control, and that an internal model so formed is utilized for adaptive control of movement. A recent simulation study successfully reproduced learning in formation of an arm trajectory based on these principles of model reference control (Kawato et al 1987). On the experimental side, however, the complex neural organization for control of locomotion, posture, and voluntary movements still eludes full elucidation. Nevertheless, evidence is accumulating to support the cerebellar learning hypothesis.(ABSTRACT TRUNCATED AT 400 WORDS)
Analysis of transcriptional isoforms of collagen types IX, II, and I in the developing avian cornea by competitive polymerase chain reaction (1995)

The genes for the alpha 1(IX), alpha 1(II), and alpha 2(I) collagen chains can give rise to different isoforms of mRNA, generated by alternative promotor usage [for alpha 1(IX) and alpha 2(I)] or alternative splicing [for alpha 1(II)]. In this study, we employed competitive reverse transcriptase PCR to quantitate the amounts of transcriptional isoforms for these genes in the embryonic avian cornea from its inception (about 3 1/2 days of development) to 11 days. In order to compare values at different time points, the results were normalized to those obtained for the "housekeeping" enzyme, glycerol-3-phosphate dehydrogenase (G3PDH). These values were compared to those obtained from other tissues (anterior optic cup and cartilage) that synthesize different combinations of the collagen isoforms. We found that, in the cornea, transcripts from the upstream promotor of alpha 1(IX) collagen (termed "long IX") were predominant at stage 18-20 (about 3 1/2 days), but then fell rapidly, and remained at a low level. By 5 days (just before stromal swelling) the major mRNA isoform of alpha 1(IX) was from the downstream promoter (termed "short IX"). The relative amount of transcript for the short form of type IX collagen rose to a peak at about 6 days of development, and then declined. Throughout this period, the predominant transcriptional isoform of the collagen type II gene was IIA (i.e., containing the alternatively spliced exon 2). This indicates that the molecules of type II collagen that are assembled into heterotypic fibrils with type I collagen possess, at least transiently, an amino-terminal globular domain similar to that found in collagen types I, III, and V. For type I, the "bone/tendon" mRNA isoform of the alpha 2(I) collagen gene was predominant; transcripts from the downstream promotor were at basal levels. In other tissues expressing collagen types IX and II, long IX was expressed predominantly with the IIA form in the anterior optic cup at stage 22/23; in 14 1/2 day cartilage, long IX was expressed predominantly along with the IIB form of alpha 1(II). The downstream transcript of the alpha 2(I) gene (Icart) was found at high levels only in cartilage.
Genes misregulated inC. elegansdeficient in Dicer, RDE-4, or RDE-1 are enriched for innate immunity genes (2007)

We describe the first microarray analysis of a whole animal containing a mutation in the Dicer gene. We used adult Caenorhabditis elegans and, to distinguish among different roles of Dicer, we also performed microarray analyses of animals with mutations in rde-4 and rde-1, which are involved in silencing by siRNA, but not miRNA. Surprisingly, we find that the X chromosome is greatly enriched for genes regulated by Dicer. Comparison of all three microarray data sets indicates the majority of Dicer-regulated genes are not dependent on RDE-4 or RDE-1, including the X-linked genes. However, all three data sets are enriched in genes important for innate immunity and, specifically, show increased expression of innate immunity genes.
Peer Reviewed: Membrane Preconcentration CE. (1999)

A new approach to preconcentrating samples before separation.
Incomplete Inhibition of Sphingosine 1-Phosphate Lyase Modulates Immune System Function yet Prevents Early Lethality and Non-Lymphoid Lesions (2008)

These findings demonstrate that lymphocyte trafficking is particularly sensitive to variations in S1PL activity and suggest that there is a window in which partial inhibition of S1PL could produce therapeutic levels of immunosuppression without causing clinically significant S1P-related lesions in non-lymphoid target organs.
Differentiation of African trypanosomes is controlled by a density sensing mechanism which signals cell cycle arrest via the cAMP pathway (1997)

Differentiation of African trypanosomes from replicating slender bloodstream forms to nondividing stumpy forms limits the parasite population size, allowing survival of the mammalian host and establishment of a stable host-parasite relationship. Using a novel in vitro culture system we have shown that slender to stumpy differentiation is induced by parasite density alone and thus is independent of host cues. Here we investigate the density sensing mechanism and show that trypanosomes release a soluble activity of low relative molecular mass, termed stumpy induction factor (SIF), which accumulates in conditioned medium. SIF activity triggers cell cycle arrest in G1/G0 phase and induces differentiation with high efficiency and rapid kinetics. Membrane-permeable derivates of cAMP or the phosphodiesterase inhibitor etazolate perfectly mimic SIF activity. Furthermore, SIF activity elicits an immediate two- to threefold elevation of intracellular cAMP content upon addition to slender forms. We conclude that SIF and hence density sensing operate through the cAMP signalling pathway. Temporal correlation of markers indicates that cell cycle arrest invariably precedes differentiation. Thus, our results indicate that the cell cycle regulation of bloodstream forms is under dominant control of cAMP signalling. Irreversible commitment to the quiescent state is elicited by a cAMP agonist within a period shorter than one complete cell cycle.
Fusogenic liposome functions as an efficient immunoadjuvant in inducing humoral immune-responses to soluble antigen. (1998)

Previously we reported the preparation and characterization of fusogenic liposomes (FL) which have highly immunogenic envelope glycoprotcins derived from Sendai virus on their surface. In this report, we investigated the ability of antigen-encapsulated FL to stimulate antigen-specific humoral immunity in mice. Anti-OVA antibody production was markedly increased in serum from mice subcutaneously immunized with ovalbumin (OVA) in FL compared to OVA alone or OVA in simple liposomes. However, these enhancements were not observed in mice immunized with OVA simply mixed with empty-FL. Moreover, consistent with mitogenic effects of Sendai virus' envelope glycoprotein, empty-FL were mitogenic for cultured murine splenocytes and B cells were especially proliferated. And this stimulation depended on protein concentration derived from Sendai virus. These results indicate that fusogenic liposome functions as an efficient immunoadjuvants in inducing antigen-specific antibody production and that for efficient adjuvancy it is necessary to encapulate antigens into FL. Moreover it was speculated that B cell stimulation which was given by glycoprotein derived from Sendai virus participated in adjuvancy of FL.
Immunoproteomics: From biomarker discovery to diagnostic applications (2008)

Circulating antibodies reflect a molecular imprint of antigens that are related to autoimmune diseases, cancer or infection. Importantly, serum antibodies are useful clinical markers as they carry diagnostic information from all around the human body. Moreover, the amplification cascade governed by the humoral immune system causes a surplus of circulating antibodies after appearance of the corresponding (low abundance) antigen. In combination with the fact that antibodies are highly stable compared to many other serum proteins, they seem ideal to be implemented in clinical diagnostic assays for the detection of antigen-associated diseases. This review summarises advances in immunoproteomics with respect to technologies for biomarker discovery, with special emphasis on recently developed gel-free MS-based approaches, and looks forward to potential immunoproteomic applications in diagnostic medicine.
Presentation and Immunogenicity of Viral Epitopes on the Surface of Hybrid Hepatitis B Virus Core Particles Produced in Bacteria (1990)

We recently reported the enhanced immunogenicity of a peptide epitope when it was presented as a fusion protein with hepatitis B core antigen. In those experiments the fusion protein was expressed in vaccinia virus. We have now refined the system so that large amounts of highly immunogenic particles can be produced using a simple bacterial expression system. We describe the expression of three different viral epitopes as chimeric particles that induce good antibody responses to each epitope after one dose of low amounts of antigen. Finally we demonstrate that the immunogenicity is a reflection of both T helper cell sites within the core protein and also the particulate nature of the immunogens.
FGFR1 Emerges as a Potential Therapeutic Target for Lobular Breast Carcinomas (2006)

Our findings suggest that receptor FGFR1 inhibitors may be useful as therapeutics in a subset of CLCs.
Design of a Mobile Underwater Charging System (2016)

Autonomous Underwater Vehicles (AUVs) are extremely capable vehicles for numerous ocean related missions. AUVs are energy limited, resulting in short mission endurance on the scale of hours to days. Underwater Gliders (UGs) are able to operate on the order of months to years by using nontraditional propulsion methods. UGs, however, are unable to perform missions requiring high speed or direct forward motion due to the nature of their buoyancy driven motion. This work reviews the current state of the art in recharging AUVs and offers an underwater recharging network concept at a significantly reduced cost to traditional methods. The solution includes the design of a UG capable of serving as charge carrying agent that couples with and charges AUVs autonomously. The vehicle design is built on the work done previously at the Nonlinear and Autonomous Systems Lab on the development of ROUGHIE (Research Oriented Underwater Glider for Hands-on Investigative Engineering). The ROUGHIE2 design is a rethinking of the original ROUGHIE capabilities to serve as a mobile charger by increasing depth rating, endurance, and payload capacity. The recharging concept presented will be easy to adapt to many different AUVs and UGs making this technology universal to small AUVs.
Carbohydrate and fatty acid metabolism of cultured adult cardiac myocytes (1986)

The energy metabolism of exogenous and endogenous substrates was investigated in Ca-tolerant adult ventricular myocytes in short-term culture. CO2 production from exogenous glucose (5 mM), lactate (5 mM), and palmitate (100 microM) were 8, 20, and 29 mumol X h-1 X g wet wt-1. Endogenous lipolysis shared in energy production by 78, 61, and 31%, respectively. Fatty acids represented the main respiratory fuel even when 10(-7) M insulin, 5 mM lactate, or 5 mM dichloroacetate were supplied in addition to glucose. With palmitate, triglyceride contents were doubled within 3 h of cell incubation. With 5 mM glucose as sole exogenous substrate the energy turnover in these resting cells resembled that of arrested hearts, corresponding to 2 ml O2 X min-1 X 100 g wet wt-1. It is concluded that the basic features of substrate metabolism resemble those of the intact myocardium in that fatty acids represent the major fuel, but the contribution of endogenous lipolysis is greater than in the beating heart.
Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines (2004)

The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.
Large‐Scale Synthesis of Rings of Bundled Single‐Walled Carbon Nanotubes by Floating Chemical Vapor Deposition (2006)

Rings of bundled single-walled carbon nanotubes with perfectly toroidal geometries (see figure), are fabricated in high yields by a floating chemical vapor deposition process involving the thermal decomposition of acetylene. The nanotube rings can be grown with varying densities on a wide variety of substrates at relatively low temperatures, which is a significant advantage for nanoelectronics applications.
Understanding dengue pathogenesis: implications for vaccine design. (2005)

In the second half of the twentieth century dengue spread throughout the tropics, threatening the health of a third of the world's population. Dengue viruses cause 50-100 million cases of acute febrile disease every year, including more than 500,000 reported cases of the severe forms of the disease--dengue haemorrhagic fever and dengue shock syndrome. Attempts to create conventional vaccines have been hampered by the lack of suitable experimental models, the need to provide protection against all four serotypes simultaneously and the possible involvement of virus-specific immune responses in severe disease. The current understanding of dengue pathogenesis is outlined in this review, with special emphasis on the role of the immune response. The suspected involvement of the immune system in increased disease severity and vascular damage has raised concerns about every vaccine design strategy proposed so far. Clearly more research is needed on understanding the correlates of protection and mechanisms of pathogenesis. There is, however, an urgent need to provide a solution to the escalating global public health problems caused by dengue infections. Better disease management, vector control and improved public health measures will help reduce the current disease burden, but a safe and effective vaccine is probably the only long-term solution. Although concerns have been raised about the possible safety and efficacy of both conventional and novel vaccine technologies, the situation is now so acute that it is not possible to wait for the perfect vaccine. Consequently the careful and thorough evaluation of several of the current candidate vaccines may be the best approach to halting the spread of disease.
Requirement for Neo1p in Retrograde Transport from the Golgi Complex to the Endoplasmic Reticulum (2003)

Neo1p from Saccharomyces cerevisiae is an essential P-type ATPase and potential aminophospholipid translocase (flippase) in the Drs2p family. We have previously implicated Drs2p in protein transport steps in the late secretory pathway requiring ADP-ribosylation factor (ARF) and clathrin. Here, we present evidence that epitope-tagged Neo1p localizes to the endoplasmic reticulum (ER) and Golgi complex and is required for a retrograde transport pathway between these organelles. Using conditional alleles of NEO1, we find that loss of Neo1p function causes cargo-specific defects in anterograde protein transport early in the secretory pathway and perturbs glycosylation in the Golgi complex. Rer1-GFP, a protein that cycles between the ER and Golgi complex in COPI and COPII vesicles, is mislocalized to the vacuole in neo1-ts at the nonpermissive temperature. These phenotypes suggest that the anterograde protein transport defect is a secondary consequence of a defect in a COPI-dependent retrograde pathway. We propose that loss of lipid asymmetry in the cis Golgi perturbs retrograde protein transport to the ER.
[Vitamin D treatment and renal osteodystrophy: indications and modalities]. (1995)

1. 1 alpha (OH) vitamin D3 derivatives have an inconstant long term inhibitory effect on PTH secretion. As a matter of fact they act by three mechanisms, one of these being antagonistic: 1) a direct inhibitory action on the prepro-PTH gene; 2) an indirect inhibitory action by increasing plasma calcium; 3) an indirect stimulatory action by increasing plasma phosphate. These two latter phenomena are due to the stimulation of the intestinal absorption of these ions as well as to an intrinsic osteolytic action which may override the inhibition of the bone release of these ions in relation with the decrease of the PTH plasma levels. 2. The use of 1 alpha (OH)D3 derivatives in patients on chronic dialysis is justified in about 30% of the patients on dialysis when in spite of native vitamin D repletion and adequate predialysis control of plasma calcium (2.5 +/- 2 mmol/l) and of plasma phosphate (1.4 - 1.7 mmol/l), the PTH plasma levels are 3 or 5 fold the upper limit of normal whether the patient is on hemodialysis or on CAPD. When hyperphosphatemia is > 1.7 mmol/l it is first necessary to correct it by the use of higher doses of alkaline calcium salts given with the meals as phosphate binder together with a negative perdialytic calcium balance induced by a lower dialysate calcium in order to avoid hypercalcemia. Control of hyperphosphatemia is indeed a necessary prerequisite for the long term PTH suppressive efficacy of 1 alpha OH vitamin D derivatives. 3. The use of 1 alpha(OH)D3 derivatives in the treatment of the predialysis uremic patients is even more limited because there is no additional mean to decrease the risk of hypercalcemia when oral calcium is used as phosphate binder because of the danger of aluminum and magnesium phosphate binders. Fortunately in the adult, oral calcium used as phosphate binder in association with phosphate restriction and correction of possible vitamin D depletion and acidosis is usually efficace to control hyperparathyroïdism without 1 alpha OH vitamin D3. This is not the case in the child to whom protein and phosphate restriction should not be prescribed because of its incompatibility with the Recommended Diet Allowance. Fortunately the high remodeling rate of his growing bones, decreases the risk of hypercalcemia due to the combination of CaCO3 and 1 alpha OH vitamin D3.