gebhart/patrepeval huggingface dataset:
Differential expression of costimulatory molecules B7‐1 and B7‐2 on microglial cells induced by Th1 and Th2 cells in organotypic brain tissue (2001)

Autoreactive T-cells are involved in demyelination, neurodegeneration, and the recruitment of peripheral macrophages and nonspecific activated T-cells in autoimmune diseases such as multiple sclerosis (MS). The ligation of costimulatory B7 molecules on microglia with CD28/CTLA-4 on T-cells is thought to be crucial to the onset and course of MS and its rodent model experimental autoimmune encephalomyelitis (EAE). It is currently unclear as to how far the nature of infiltrating T-cells has an impact on the expression of the B7 molecules on microglia, the resident antigen-presenting cells (APCs) of the brain. We studied the expression of B7-1 and B7-2 on microglia after encounter with preactivated Th1 and Th2 cells from transgenic mice whose T-cells express a receptor (TCR) either specific to myelin basic protein (MBP) or ovalbumin (OVA) using murine organotypic entorhinal-hippocampal slice cultures (OEHSC). Our main finding was that Th1 cells downregulate the constitutive expression of B7-2 and induce B7-1 expression while Th2 cells do not induce this B7-1 upregulation. The main difference between MBP- and OVA-specific cells was seen in experiments were Th1 cells had direct contact to APCs but not to brain tissue. In contrast to MBP-specific Th1 cells, OVA-specific Th1 cells required the addition of antigen to upregulate B7-1 and downregulate B7-2. When the cells were allowed to have contact to brain tissue, no difference was seen in the pattern of B7 regulation between OVA- and MBP-specific T-cells. Our data suggest that T-cells are able to modulate B7 expression on microglial cells in the brain independent of antigen presentation through TCR/MHC-II ligation but presumably by soluble mediators.
Rectangular monolithic infinite-cascade thermojunctions (1978)

A simple design of thermocouple for use as a cooling device is discussed. This design would be expected to act as an infinite array of infinitesimal stages and allow greater efficiency both in terms of heat pumping and in terms of temperature difference obtainable than a discretely staged device of conventional design. However, the theoretical analysis and experimental results indicate that though the device should produce a greater temperature difference than a single-stage thermoelectric cooler, it is not as efficient as a heat pump.
Optimized nano-transfersomal films for enhanced sildenafil citrate transdermal delivery: ex vivo and in vivo evaluation (2016)

Sildenafil citrate (SLD) is a selective cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor used for the oral treatment of erectile dysfunction and, more recently, for other indications, including pulmonary hypertension. The challenges facing the oral administration of the drug include poor bioavailability and short duration of action that requires frequent administration. Thus, the objective of this work is to formulate optimized SLD nano-transfersomal transdermal films with enhanced and controlled permeation aiming at surmounting the previously mentioned challenges and hence improving the drug bioavailability. SLD nano-transfersomes were prepared using modified lipid hydration technique. Central composite design was applied for the optimization of SLD nano-transfersomes with minimized vesicular size. The independent variables studied were drug-to-phospholipid molar ratio, surfactant hydrophilic lipophilic balance, and hydration medium pH. The optimized SLD nano-transfersomes were developed and evaluated for vesicular size and morphology and then incorporated into hydroxypropyl methyl cellulose transdermal films. The optimized transfersomes were unilamellar and spherical in shape with vesicular size of 130 nm. The optimized SLD nano-transfersomal films exhibited enhanced ex vivo permeation parameters with controlled profile compared to SLD control films. Furthermore, enhanced bioavailability and extended absorption were demonstrated by SLD nano-transfersomal films as reflected by their significantly higher maximum plasma concentration (C max) and area under the curve and longer time to maxi mum plasma concentration (T max) compared to control films. These results highlighted the potentiality of optimized SLD nano-transfersomal films to enhance the transdermal permeation and the bioavailability of the drug with the possible consequence of reducing the dose and administration frequency.
Label‐Free Identification of White Blood Cells Using Machine Learning (2019)

White blood cell (WBC) differential counting is an established clinical routine to assess patient immune system status. Fluorescent markers and a flow cytometer are required for the current state-of-the-art method for determining WBC differential counts. However, this process requires several sample preparation steps and may adversely disturb the cells. We present a novel label-free approach using an imaging flow cytometer and machine learning algorithms, where live, unstained WBCs were classified. It achieved an average F1-score of 97% and two subtypes of WBCs, B and T lymphocytes, were distinguished from each other with an average F1-score of 78%, a task previously considered impossible for unlabeled samples. We provide an open-source workflow to carry out the procedure. We validated the WBC analysis with unstained samples from 85 donors. The presented method enables robust and highly accurate identification of WBCs, minimizing the disturbance to the cells and leaving marker channels free to answer other biological questions. It also opens the door to employing machine learning for liquid biopsy, here, using the rich information in cell morphology for a wide range of diagnostics of primary blood. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
Structural stabilization of GTP-binding domains in circularly permuted GTPases: Implications for RNA binding (2006)

GTP hydrolysis by GTPases requires crucial residues embedded in a conserved G-domain as sequence motifs G1-G5. However, in some of the recently identified GTPases, the motif order is circularly permuted. All possible circular permutations were identified after artificially permuting the classical GTPases and subjecting them to profile Hidden Markov Model searches. This revealed G4-G5-G1-G2-G3 as the only possible circular permutation that can exist in nature. It was also possible to recognize a structural rationale for the absence of other permutations, which either destabilize the invariant GTPase fold or disrupt regions that provide critical residues for GTP binding and hydrolysis, such as Switch-I and Switch-II. The circular permutation relocates Switch-II to the C-terminus and leaves it unfastened, thus affecting GTP binding and hydrolysis. Stabilizing this region would require the presence of an additional domain following Switch-II. Circularly permuted GTPases (cpGTPases) conform to such a requirement and always possess an 'anchoring' C-terminal domain. There are four sub-families of cpGTPases, of which three possess an additional domain N-terminal to the G-domain. The biochemical function of these domains, based on available experimental reports and domain recognition analysis carried out here, are suggestive of RNA binding. The features that dictate RNA binding are unique to each subfamily. It is possible that RNA-binding modulates GTP binding or vice versa. In addition, phylogenetic analysis indicates a closer evolutionary relationship between cpGTPases and a set of universally conserved bacterial GTPases that bind the ribosome. It appears that cpGTPases are RNA-binding proteins possessing a means to relate GTP binding to RNA binding.
Effects of ring substituents and linker chains on the bifunctional intercalation of diacridines into deoxyribonucleic acid (1980)

Sedimentation experiments with closed circular duplex PM2 deoxyribonucleic acid (DNA) and viscosity measurements with sonicated rodlike DNA fragments have been performed to investigate unwinding and extension of the DNA helix associated with binding of homologous series of diacridines. When the acridine nuclei are linked via 9-amino substituents with chains permitting interchromophore separation in the critical region between 8.8 and 11.3 A, it is found that substituents at positions 2, 3, and 6 restrict bifunctional intercalation to compounds capable of sandwiching at least two base pairs in the intercalated complex. Unsubstituted diacridines, and derivatives bearing an ethyl group at position 4, can bis-intercalate with a significantly shorter linking chain. The presence of amino groups in the linker does not affect the ability to bis-intercalate but increases the helix unwinding angle by 30--40% and decreases the helix extension per bound ligand molecule by 11--18%. Bifunctional reaction is observed with a diacridine linked via the 4--4' positions showing that 9-aminoacridine can intercalate in at least two major orientations with the 9 or 10 position directed toward the helix axis. Both orientations can be accommodated simultaneously within a single diacridine linked via the 9--4' positions with a bridge sufficiently long to encompass two base pairs. An acridone substituted at positions 4 and 5 with positively charged side chains intercalates with a helix unwinding angle indistinguishable from that of ethidium whereas an uncharged bisacridone failed to yield a detectable complex with DNA. Tilorone dihydrochloride, a structurally similar antiviral drug, was found to intercalate with an unwinding angle approximately half that of ethidium. The potentially bifunctional bisquinoline drug dequalinium causes relaxation of the supercoiling of PM2 DNA but probably not by simultaneous intercalation of both its chromophores.
Identification of a second trans-acting gene controlling maltose fermentation in Saccharomyces carlsbergensis. (1986)

Maltose fermentation in Saccharomyces spp. requires the presence of a dominant MAL locus. The MAL6 locus has been cloned and shown to encode the structural genes for maltose permease (MAL61), maltase (MAL62), and a positively acting regulatory gene (MAL63). Induction of the MAL61 and MAL62 gene products requires the presence of maltose and the MAL63 gene. Mutations within the MAL63 gene produce nonfermenting strains unable to induce the two structural gene products. Reversion of these mal63 nonfermenters to maltose fermenters nearly always leads to the constitutive expression of maltase and maltose permease, and constitutivity is always linked to MAL6. We demonstrated that for one such revertant, strain C2, constitutivity did not require the MAL63 gene, since deletion disruption of this gene did not affect the constitutive expression of the structural genes. In addition, constitutivity was trans acting. Deletion disruption of the MAL6-linked structural genes for maltase and maltose permease in this strain did not affect the constitutive expression of a second, unlinked maltase structural gene. We isolated new maltose-fermenting revertants of a nonfermenting strain which carried a deletion disruption of the MAL63 gene. All 16 revertants isolated expressed maltase constitutively. In one revertant studied in detail, strain R10, constitutive expression was demonstrated to be linked to MAL6, semidominant, trans acting, and residing outside the MAL63-MAL61-MAL62 genes. From these studies we propose the existence of a second trans-acting regulatory gene at the MAL6 locus. We call this new gene MAL64. We mapped the MAL64 gene 2.3 centimorgans to the left of MAL63. The role of the MAL64 gene product in maltose fermentation is discussed.
Difference in sero-diagnostic values among KL-6-associated mucins classified as cluster 9 (1994)

KL-6 classified as Cluster 9 (MUC-I) is a circulating high-molecular-weight mucin-like molecule. Serum level of KL-6 was measured by a sandwich assay using KL-6 antibody as not only a catcher but also as a tracer. We established 2 additional monoclonal antibodies (MAbs), LISA 101 and EH-123, reacting with KL-6 epitopes different from the epitope recognized by KL-6 antibody. The KL-6-associated mucins detected by the sandwich assay using LISA 101 or EH-123 antibody as a catcher and KL-6 antibody as a tracer were designated as LISA 1-6 and CAM 123-6 respectively. The diagnostic values as the serum markers of KL-6, LISA 1-6 and CAM 123-6 were evaluated measuring their levels in the same serum from healthy individuals and from patients with pulmonary, pancreatic and breast adenocarcinomas. KL-6 was increased abnormally at high rates of more than 50% in pancreatic cancer and in benign lung diseases, LISA 1-6 only in pancreatic cancer, and CAM 123-6 only in pulmonary adenocarcinoma. In benign lung diseases, however, LISA 1-6 and CAM 123-6 were increased abnormally at the rates of only 5.3% and 0% respectively. These observations clearly indicate that LISA 1-6 and CAM 123-6 constitute a part of KL-6, but that they are superior to KL-6 as tumor markers for pancreatic cancer and for pulmonary adenocarcinoma respectively, because of their much lower false-positive rates.
Magnetostatic wave technology: a review (1988)

Magnetostatic wave (MSW) technology has been under investigation for more than a decade. Using ferrimagnetic films such as liquid-phase epitaxial (LPE) yttrium iron garnet (YIG) films, MSW devices and subsystems offer instantaneous bandwidths of up to 1 GHz at operating frequencies in the microwave bands (0.5-26.5 GHz). Because MSWs travel with velocities two-to-four orders of magnitude slower than electromagnetic waves, compact devices can be built using hybrid and monolithic microwave integrated circuit (MMIC) techniques. These devices include delay lines, dispersive delay lines, filters, resonators, and directional couplers. Subsystems using these devices, such as electronically tunable delay lines channelized filter banks, delay-line discriminators, oscillators, and frequency multipliers can be used for applications in signal identification, control and processing directly at microwave frequencies. An overview of the MSW technology is presented and an assessment of the various devices and subsystems that can be built using thin and thick LPE-YIG films is provided.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
[Ultrasound guidance for placement of central venous catheters]. (1999)

Central venous cannulation is associated with a number of serious complications like arterial punction and pneumothorax and with discomfort for the awake patient when repeated attempts are made. Ultrasound guidance during cannulation has been shown to reduce complications, increase the success rate and thus reduce the need for multiple catheter placement attempts. We describe two methods using ultrasound for central venous cannulation and we recommend the use of ultrasound guidance, particularly in high-risk patients.
Heparin Derivatives as Inhibitors of BACE-1, the Alzheimer's β-Secretase, with Reduced Activity against Factor Xa and Other Proteases (2006)

Heparan sulfate (HS) regulates processing of the amyloid precursor protein by the Alzheimer's beta-secretase (BACE-1). An HS analogue, porcine intestinal mucosal heparin, was systematically modified at the principal positions of O-sulfation and N-sulfation/acetylation and tested for BACE-1 inhibitory and anti factor Xa activities. The derivative with the highest anti-BACE-1 to anti-Xa activity ratio contained N-acetyl and 2-O- and 6-O-sulfates and also exhibited attenuated activities against cathepsin-D and renin, two other structurally related aspartyl proteases.
Ku-Dependent and Ku-Independent End-Joining Pathways Lead to Chromosomal Rearrangements During Double-Strand Break Repair in <i>Saccharomyces cerevisiae</i> (2003)

Chromosomal double-strand breaks (DSBs) can be repaired by either homology-dependent or homology-independent pathways. Nonhomologous repair mechanisms have been relatively less well studied, despite their potential importance in generating chromosomal rearrangements. We have developed a Saccharomyces cerevisiae-based assay to identify and characterize homology-independent chromosomal rearrangements associated with repair of a unique DSB generated within an engineered URA3 gene. Approximately 1% of successfully repaired cells have accompanying chromosomal rearrangements consisting of large insertions, deletions, aberrant gene conversions, or other more complex changes. We have analyzed rearrangements in isogenic wild-type, rad52, yku80, and rad52 yku80 strains, to determine the types of events that occur in the presence or absence of these key repair proteins. Deletions were found in all strain backgrounds, but insertions were dependent upon the presence of Yku80p. A rare RAD52- and YKU80-independent form of deletion was present in all strains. These events were characterized by long one-sided deletions (up to 13 kb) and extensive imperfect overlapping sequences (7-22 bp) at the junctions. Our results demonstrate that the frequency and types of repair events depend on the specific genetic context. This approach can be applied to a number of problems associated with chromosome stability.
Within and Without: Chinese Writers Overseas (2005)

Thousands of Chinese outside China have been writing in Chinese and other languages since the past century. Some wrote merely to record their personal experiences. Others wrote to express their thoughts and feelings. We are beginning to have some idea of the aspirations and limitations of these writers and their struggles to define their place in their respective communities and countries, and in the larger world of literature. Each writer is a Self with regard to his or her immediate migrant community. As a member of the community, the writer is likely to have a different Self in relation to other ethnic groups in the adopted country, especially toward the dominant majority that has the political power to define national identity for all minorities. An additional Other would be the images of China. Also, some submit themselves to the test of globalization. Their condition can be better understood through the old Chinese dichotomy of nei and wai, with many dimensions of what is within and what is without. This dichotomy of within-without allows us to recognize the dilemmas of overseas Chinese writers as subjective and dynamic phenomena.
Plasma Renin Activity vs. Concentration (1976)

I begin writing in response to a question I am asked: whether the “self” of the artist can be emancipatory. My first instinct is to assert that we need to dispel any idea of “the self of the artist” entirely. As it is well known, every new generation of artists is faced with the task of creating work that is uncommodifiable, knowing that it will not remain so for long. It is the song, the dance, the lie of the avant-garde. To believe that the ‘self of the artist’ exists through opposition or exception is a fallacy. To believe that the ...
Fluorescent and radiolabeled triphenylphosphonium probes for imaging mitochondria (2013)

Triphenylphosphonium-fluorochromes (TPP-fluorochromes) are a new class of spectrally variable, mitochondrially targeted probes, with an [(18)F] labeling option which, when enabled, allows imaging of a cardiac perfusion deficit using PET/CT.
Identification and androgen regulation of two proteins released by T47D human breast cancer cells. (1987)

Three [35S]methionine-labeled polypeptides released by T47D human breast cancer cells have been identified as corresponding to two proteins previously described in breast gross cystic disease fluid. A Mr 43,000 protein was immunoprecipitated by polyclonal antibodies to the Zn-alpha 2-glycoprotein. A Mr 18,000 and a Mr 13,000 polypeptide were both immunoprecipitated by four monoclonal antibodies directed against four separate epitopes of Mr 15,000 gross cystic disease fluid protein, a major protein that is characteristic of apocrine gland secretions. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, purified Mr 15,000 gross cystic disease fluid protein migrated at the level of the Mr 18,000 protein of T47D cells. The proteins were regulated by androgens and progestins. In addition to a general stimulation of protein secretion, 5 alpha-dihydrotestosterone (DHT) specifically increased, by 2- to 20-fold, the release of the Mr 43,000 and Mr 18,000 proteins into the medium. DHT also increased the cellular level of the Mr 18,000 protein, as shown by immunoprecipitation with a Mr 15,000 gross cystic disease fluid protein antibody, which suggests a stimulation of protein synthesis. The progestin 17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione also increased the release in the medium of the Mr 43,000 and Mr 18,000 proteins, but higher molar concentrations were required than in the case of DHT. The induction of these proteins by DHT and 17,21-dimethyl-19nor,4,9-pregnadiene-3,20-dione was specifically inhibited by the antiandrogen flutamide which has no effect on other progestin-regulated proteins. This suggests an effect mediated by the androgen receptor. This is the first report on the identification of two proteins induced by androgens in a human breast cancer cell line. These proteins should be useful in studying the role of androgens in human mammary tumors and their mechanism of action in cell culture.
Thermal effects in shielded MR heads for tape applications (1991)

The authors discuss some factors that limit the permissible input power in multi-track magnetoresistive (MR) tape heads. The possible consequences of increasing the power dissipation in MR heads as a means of increasing readback signal amplitude are discussed. A simple model to describe the temperature rise of a shielded MR element is given. Evidence for exceeding the Curie point of ferrite used in shielded MR heads is seen with element temperatures in excess of 340 degrees C recorded prior to element burnout.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
<title>Image projection optical system for measuring pattern electroretinograms</title> (1994)

The use of the pattern-electroretinogram (PERG) as a noninvasive diagnostic tool for the early detection of glaucoma has been supported by a number of recent studies. We have developed a unique device which uses a laser interferometer to generate a sinusoidal fringe pattern that is presented to the eye in Maxwellian view for the purpose of producing a PERG response. The projection system stimulates a large visual field and is designed to bypass the optics of the eye in order to measure the true retinal response to a temporally alternating fringe pattern. The contrast, spatial frequency, total power output, orientation, alternating temporal frequency, and field location of the fringe pattern presented to the eye can all be varied by the device. It is critical for these parameters to be variable so that optimal settings may be determined for the normal state and any deviation from it, i.e. early or preclinical glaucoma. Several interferometer designs and optical projection systems were studied in order to design a compact system which provided the desired variable pattern stimulus to the eye. This paper will present a description of the clinical research instrument and its performance with the primary emphasis on the optical system design as it relates to the fringe pattern generation and other optical parameters. Examples of its use in the study of glaucoma diagnosis will also be presented.