gebhart/patrepeval huggingface dataset:
Suppressor cell activity in a randomized trial of patients receiving active specific immunotherapy with melanoma cell vaccine and low dosages of cyclophosphamide. (1990)

Previous studies have shown that melanoma patients develop an immune response to cell surface melanoma-associated antigens. The presence of this antibody response to cell surface antigens has been correlated with a better clinical outcome when melanoma patients are treated with an allogeneic melanoma cell vaccine (MCV) as an active immunotherapy protocol. It was hypothesized that the inability to consistently induce or enhance existing immune responses to melanoma-associated antigens was related to the downregulation by suppressor cells. Patients received treatments of MCV 3 times in a 4-week interval and then every fourth week. The biological response modifier cyclophosphamide (CYP) is an immunomodulator of suppressor T-cell function. In this study we set out to determine whether CYP given prior to MCV could reduce suppressor cell activity during vaccination. In a randomized trial stage II and III melanoma patients (n = 41) were given MCV alone or in conjunction with CYP at dosages of 300, 150, or 75 mg/m2. CYP was given 3 days prior to each MCV treatment. Suppressor cell activity in patients was monitored by a concanavalin A suppressor assay using peripheral blood lymphocytes from serial phlebotomies during a 12-week period of treatment. In each trial group there were patients who had major reduction in suppressor cell activity (greater than 50%). Overall, the greatest reduction in suppressor cell activity occurred in patients receiving 300 mg/m2 CYP compared to the other CYP dosages or MCV alone. For the first two treatments at all CYP dosages there was a greater number of patients showing reduced suppressor cell activity compared to later treatments. In a comparison of patients receiving MCV alone to MCV + CYP 300 mg/m2 phenotypic analysis of lymphocyte subsets showed significant (P = 0.03) reduction in the CD8+CD11B+ (suppressor) cells of the latter group. These studies suggest that CYP can be used at low dosages in conjunction with MCV to reduce suppressor cell activity.
Maximum blood flow rates for arterial cannulae used in neonatal ECMO. (1991)

The arterial cannulae used in neonatal ECMO cause hemolysis and red blood cell damage at elevated blood flows. Hemolysis in extracorporeal circuits has been found to occur with shear stress greater than 132 dynes/cm2, turbulence as measured by Reynold's number greater than 1,000, and velocity greater than 120 to 200 cm/sec. These parameters need to be considered when sizing the proper arterial cannula for a required flow rate. In-vitro measurements of the pressure drop across six arterial cannulae at varying flow rates were performed using human blood with a hematocrit of 43%. Shear stress, Reynold's number, velocity, and pressure drop were calculated for each catheter at flow rates from 50 to 1,000 cc/min. The maximum mean flow rate to maintain the shear stress, Reynold's number, velocity, and pressure drop within the accepted range, was determined for each cannula. Recommended maximum blood flow rates for each of the six cannulae are given. Internal diameter, length, and cannula geometry appear to be the factors most affecting the flow achievable without causing red blood cell damage and hemolysis. Ten French Biomedicus, 10 French Cook, and 10 French Elecath arterial cannulae appear best suited to deliver the range of blood flow rates used in neonatal ECMO.
Analysis of training neural compensation model for system dynamics modeling (2002)

Incorporating a nominal model as a priori knowledge with a neural network to model a physical system has shown better performance than using only a conventional network model. However, there has been no explicit mathematical reason to describe why this technique, called neural compensation modeling, results in such improvement. The purpose of this paper is to analyze this concept by deriving a mathematical explanation of the neural compensation model compared to a convention network model. The explanation is derived based on normalization procedures of training sets and the properties of norms. In addition, the analysis is illustrated by using a motor coil thermal system.
Building a Parallel Metabolism within the Cell (2008)

One of the key aims of synthetic biology is to engineer artificial processes inside living cells. This requires components that interact in a predictable manner, both with each other and with existing cellular systems. However, the activity of many components is constrained by their interactions with other cellular molecules and often their roles in maintaining cell health. To escape this limitation, researchers are pursuing an "orthogonal" approach, building a parallel metabolism within the cell. Components of this parallel metabolism can be sourced from evolutionarily distant species or reengineered from existing cellular molecules by using rational design and directed evolution. These approaches allow the study of basic principles in cell biology and the engineering of cells that can function as environmental sensors, simple computers, and drug factories.
Efficacy and Safety of a New Botulinum Toxin Type A Free of Complexing Proteins (2015)

MT10107 is botulinum neurotoxin type A derived drug which utilizes the 150 kDa portion without complexing proteins and human serum albumin contents. To evaluate the efficacy and the safety of MT10107, it was compared with onabotulinumtoxinA in this double-blind, randomized controlled trial. Twenty-five healthy males received a randomly selected dose of MT10107 into the extensor digitorum brevis (EDB) muscle of one foot, and an equivalent dose of onabotulinumtoxinA (BOTOX) was injected into the contralateral EDB muscle. While efficacy of the administered substance was determined by measuring paretic effects on the EDB, the local spread of toxin effects was evaluated by the paretic effects on the nearby abductor hallucis (AH) and abductor digiti quinti (ADQ) muscles. Paretic effects were defined as the percentage of reduction of the compound muscle action potential (CMAP) amplitudes, measured at 14, 30, 90 days after the injection, compared to the baseline value. Intergroup (MT10107 and onabotulinumtoxinA) differences were not significant in the percentage reduction of the amplitudes in the EDB muscles. In this study, there was no significant difference in efficacy and safety between the two test drugs. MT10107 may be effective and safe as much as onabotulinumtoxinA to produce the desired paretic effect.
Cyclic GMP-Dependent Protein Kinase II Plays a Critical Role in C-Type Natriuretic Peptide-Mediated Endochondral Ossification (2002)

Longitudinal bone growth is determined by endochondral ossification at the growth plate, which is located at both ends of long bones and vertebrae, and involves many systemic hormones and local regulators. C-type natriuretic peptide (CNP), a third member of the natriuretic peptide family, occurs at the growth plate and acts locally as a positive regulator of endochondral ossification through the intracellular accumulation of cyclic GMP (cGMP). The increase in cGMP concentrations is known to activate different signaling mediators, such as cyclic nucleotide phosphodiesterases, cGMP-regulated ion channels, and cGMP-dependent protein kinases (cGKs). The type II cGK (cGKII)-deficient mice (Prkg2(-/-) mice) develop dwarfism as a result of impaired endochondral ossification, suggesting that cGKII is important for the CNP-mediated endochondral ossification. However, given that Prkg2(-/-) mice differ from CNP-deficient mice (Nppc(-/-) mice) in the growth plate histology, which downstream mediator(s) of cGMP play key roles in the process is still an enigma. Here we show that targeted expression of CNP in the growth plate chondrocytes fails to rescue the skeletal defect of Prkg2(-/-) mice. Using cultured fetal mouse tibias, an in vitro model system of endochondral ossification, we also demonstrated that CNP cannot increase the longitudinal bone growth, and chondrocytic proliferation and hypertrophy, and cartilage matrix synthesis in Prkg2(-/-) mice. This study provides in vivo and in vitro genetic evidence that cGKII plays a critical role in CNP-mediated endochondral ossification.
The N Terminus of Connexin37 Contains an α-Helix That Is Required for Channel Function (2009)

The cytoplasmic N-terminal domain of connexins has been implicated in multiple aspects of gap junction function, including connexin trafficking/assembly and channel gating. A synthetic peptide corresponding to the first 23 amino acids of human connexin37 was prepared, and circular dichroism and nuclear magnetic resonance studies showed that this N-terminal peptide was predominantly alpha-helical between glycine 5 and glutamate 16. The importance of this structure for localization of the protein at appositional membranes and channel function was tested by expression of site-directed mutants of connexin37 in which amino acids leucine 10 and glutamine 15 were replaced with prolines or alanines. Wild type connexin37 and both substitution mutants localized to appositional membranes between transfected HeLa cells. The proline mutant did not allow intercellular transfer of microinjected neurobiotin; the alanine mutant allowed transfer, but less extensively than wild type connexin37. When expressed alone in Xenopus oocytes, wild type connexin37 produced hemichannel currents, but neither of the double substitution mutants produced detectable currents. The proline mutant (but not the alanine mutant) inhibited co-expressed wild type connexin37. Taken together, our data suggest that the alpha-helical structure of the connexin37 N terminus may be dispensable for protein localization, but it is required for channel and hemichannel function.
Maternal vaccination against subclinical necrotic enteritis in broilers (2003)

The inclusion of antibacterial feed additives has until now been the major strategy for controlling Clostridium perfringens-associated necrotic enteritis in broilers. In the present study, the effect of maternal immunization against the disease was examined. Broiler breeder hens were injected intramuscularly with candidate vaccines based on C. perfringens type A and type C toxoids adjuvanted with aluminium hydroxide. Vaccination resulted in a strong serum immunoglobulin G response to C. perfringens alpha-toxin in parent hens, and specific antibodies were transferred to their progeny. Subclinical necrotic enteritis in broilers was induced under field conditions or in a disease model, and the occurrence of specific enteric and hepatic lesions was evaluated in randomly selected birds. In three experiments, estimates of odds ratio for developing such lesions were 0.23, 0.33 and 0.56 in maternally toxoid C-immunized broilers compared with non-immunized controls. In toxoid A-immunized birds, odds ratios were estimated at 0.41, 0.61 and 0.63. From these results, immunoprophylaxis seems to be an interesting alternative for the control of necrotic enteritis in broilers.
Magnesium Gating of the Inwardly Rectifying K+ Channel (1991)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
Sickle cell disease (1987)

PreviewBecause early diagnosis is the key to managing sickle cell disease, Drs Thomas and Holbrook favor newborn screening for the abnormal hemoglobins. In this article they review the many distressing manifestations of this hereditary disease and emphasize the importance of long-term preventive care.
Identification of two novel microalgal enzymes involved in the conversion of the ω3-fatty acid, eicosapentaenoic acid, into docosahexaenoic acid (2004)

Marine microalgae such as Pavlova and Isochrysis produce abundant amounts of the omega3-PUFAs (polyunsaturated fatty acids), EPA (eicosapentaenoic acid, 20:5n-3) and DHA (docosahexaenoic acid, 22:6n-3). The pathway leading to the conversion of EPA into DHA in these lower eukaryotes is not well established although it is predicted to involve an elongation step, catalysed by an elongating enzyme complex, leading to the conversion of EPA into omega3-DPA (omega-3-docosapentaenoic acid, 22:5n-3); followed by a desaturation step, catalysed by a Delta4-desaturase, which results in the conversion of DPA into DHA. To date, the enzymes involved in the elongation of EPA have not been identified from any lower eukaryote. In the present study, we describe the identification of microalgal genes involved in the two-step conversion of EPA into DHA. By expressed sequence tag analysis, a gene (pavELO) encoding a novel elongase was identified from Pavlova, which catalysed the conversion of EPA into omega3-DPA in yeast. Unlike any previously identified elongase from higher or lower eukaryotes, this enzyme displayed unique substrate specificity for both n-6 and n-3 C20-PUFA substrates, with no activity towards any C18- or C22-PUFA substrates. In addition, a novel Delta4-desaturase gene (IgD4) was isolated from Isochrysis, which was capable of converting omega3-DPA into DHA, as well as adrenic acid (22:4n-6) into omega6-DPA. Yeast co-expression studies, with pavELO and IgD4, revealed that these genes were capable of functioning together to carry out the two-step conversion of EPA into DHA.
Perispinal etanercept: Potential as an Alzheimer therapeutic (2008)

Tumor necrosis factor-alpha (TNF) is one of a number of systemic and immunomodulating cytokines that generally act to promote acute-phase reactions but can drive degenerative changes when chronically elevated. Traditional focus on TNF has been directed at these inflammation-related functions. Of particular relevance to intersections between neuroinflammation and neurodegeneration is the ability of TNF to increase expression of interleukin-1 (IL-1), which in turn increases production of the precursors necessary for formation of amyloid plaques, neurofibrillary tangles, and Lewy bodies. More recent data have revealed that TNF, one of the few gliotransmitters, has strikingly acute effects on synaptic physiology. These complex influences on neural health suggest that manipulation of this cytokine might have important impacts on diseases characterized by glial activation, cytokine-mediated neuroinflammation, and synaptic dysfunction. Toward such manipulation in Alzheimer's disease, a six-month study was conducted with 15 probable-Alzheimer patients who were treated weekly with perispinal injection of Etanercept, an FDA-approved TNF inhibitor that is now widely used for treatment of rheumatoid arthritis and other systemic diseases associated with inflammation. The results demonstrated that perispinal administration of etanercept could provide sustained improvement in cognitive function for Alzheimer patients. Additionally, the authors were impressed by the striking rapidity with which these improvements occurred in the study patients. An example of this rapid improvement is presented in this issue as a case report by Tobinick and Gross. Such rapid gain of function inspires speculation about the role of gliotransmission or other equally rapid synaptic events in the relationship of TNF to Alzheimer-impacted neurophysiology. Because of the inability of large molecules such as etanercept to cross the blood brain barrier following conventional systemic administration, it is likely that the more direct drug delivery system pioneered by Tobinick also contributed to the effectiveness of the treatment. If so, this system could be useful in drug delivery to the brain in other neural disorders, as well as in animal research studies, many of which currently employ delivery strategies that inflict damage to neural cells and thus engender neuroinflammatory responses.
A naturally occurring NAR variable domain binds the Kgp protease from Porphyromonas gingivalis (2002)

The new antigen receptor (NAR) from sharks consists of a single immunoglobulin variable domain attached to five constant domains, and is hypothesised to function as an antibody. Two closely related NARs with affinity for the Kgp (lysine-specific) gingipain protease from Porphyromonas gingivalis were selected by panning an NAR variable domain library. When produced in Escherichia coli, these recombinant NARs were stable, correctly folded, and specifically bound Kgp (K(d)=1.31+/-0.26x10(-7) M). Binding localised to the Kgp adhesin domains, however without inhibiting adhesin activity. These naturally occurring proteins indicate an immune response to pathogenic bacteria and suggest that the NAR is a true antibody-like molecule.
Measurement strategy and instrumental performance of a computer screen photo-assisted technique for the evaluation of a multi-parameter colorimetric test strip (2005)

A measuring strategy for the evaluation of a seven parameters colorimetric test using a computer screen photo-assisted technique (CSPT) is demonstrated. CSPT is a versatile approach aimed at point of care or home tests that uses regular computer sets and web cameras as the whole instrument. Issues such as the stability and the equivalency on different platforms of the determinations have been addressed in the present work. The method uses an embedded local reference simultaneously measured with the tests and solves the evaluation as a classification problem. The achieved performance tested along 580 classifications covering all the ranges of the assay, using synthetic samples, yielded 97.2% correct determinations compared with 89.7% for the case of colorimetric determinations. The errors were concentrated in only two parameters that show a significant correlation with a set of quality indices used to assess the performance of the classification.
Cell and chloroplast division requires ARTEMIS (2002)

Chloroplasts are endosymbiotic organelles of cyanobacterial origin. It seems reasonable to assume that cell division and organelle division still share general principles, as shown for the FtsZ proteins. However, further components involved in this process are largely unknown. Here we describe ARTEMIS, a nuclear-encoded protein of chloroplast inner envelope membranes that is required for organelle division. ARTEMIS consists of three distinct modules: an N-terminal receptor-like region, a centrally positioned glycine-rich stretch containing a nucleoside triphosphate-binding site, and a C-terminal YidC/Oxa1p/Alb3 protein translocase-like domain. Analysis of Arabidopsis En-1 transposon mutants as well as ARTEMIS antisense plants revealed chloroplasts arrested in the late stages of division. Chloroplasts showed clearly separated and distinct multiple thylakoid systems, whereas the final organelle fission remained unaccomplished. Inactivation of a cyanobacterial gene with sequence similarity to the YidC/Oxa1p/Alb3-like domain of ARTEMIS resulted in aberrant cell division, which could be rescued by the Arabidopsis protein. ARTEMIS represents a so-far-unrecognized link between prokaryotic cell fission and chloroplast division.
Written, Unwritten, and Vastly Rewritten: Meyer Levin's In Search and Philip Roth's "Defender of the Faith," The Plot Against America , and Indignation (2011)

Meyer Levin's first autobiography, In Search (1950), explores the sometimes anguished quest for Jewish identity in ways that anticipate and may have helped to shape the psychological concerns and narrative strategies of Roth's "Defender of the Faith" (1959) and The Plot Against America (2004). When read in the context of In Search, "Defender of the Faith" foreshadows Roth's artistic approach to ostensibly autobiographical, retrospective narration in The Plot Against America, also casting light on references, in Indignation (2008) and The Humbling (2009), to amputation, insensate outlooks, and ethnic and creative insecurity. Whatever his agreement or dissent from Levin's outlook on Judaism, In Search appears to have remained for Roth a perpetual fount of creative inspiration for retrospective narrative technique and for psychoanalytical literary realism.
Surgical Treatment of Vascular Ring Including Right Cervical Aortic Arch (1999)

Cervical aortic arch is a developmental entity consisting of persistence of the right or left third branchial arch and regression of the fourth branchial arches. In most cases, the aorta is redundant and crosses behind the esophagus to the opposite side. In the presence of an aberrant subclavian artery contralateral to the side of the aortic arch and a ligamentum arteriosum, a vascular ring is formed around the trachea and esophagus. Two young patients with right-sided cervical aortic arch, aberrant left subclavian artery, and ligamentum arteriosum presented with dysphagia and exertional dyspnea. In one patient, through a left thoracotomy, the ligamentum arteriosum was divided, and the trachea and esophagus were dissected thoroughly above and below the level of the ring. In addition, the aberrant left subclavian artery was divided at its origin from a large diverticulum and implanted into the left common carotid artery; the aortic diverticulum was resected. In the other patient, who had associated 22q11 chromosomal deletion, in addition to left-sided compression of the trachea and esophagus, there was additional marked compression of the right anterolateral trachea by the redundant ascending aorta. Through a median sternotomy, the ligamentum arteriosum was divided, and the trachea and esophagus were widely mobilized; an additional aortopexy of the ascending aorta to the right of the sternum resulted in the absence of tracheal compression. The cases of the two reported patients illustrate the clinical variability of vascular ring, including a right cervical aortic arch and the consequently versatile surgical approach that is needed to successfully address this combination of vascular anomalies.
Precise CD4 T‐cell counting using red diode laser excitation: For richer, for poorer (2002)

Accurate CD4 counts can be generated at minimal cost on red diode laser-operated flow cytometers, retaining the potential for high throughput capacity without compromising precision. With further improvements in volumetric technology and clinical software, these cytometers may develop into a new generation of inexpensive battery-operated laboratory hardware that combines cellular phenotyping with bead-based multiplexing immunoassays for (HIV) serology.