gebhart/patrepeval huggingface dataset:
Genes for the major protein antigens of Mycobacterium tuberculosis: the etiologic agents of tuberculosis and leprosy share an immunodominant antigen. (1987)

Mycobacterium tuberculosis genes encoding immunologically relevant proteins were isolated by systematically screening a lambda gt11 recombinant DNA expression library with a collection of murine monoclonal antibodies directed against protein antigens of this pathogen. These antibodies, previously characterized by a World Health Organization workshop on monoclonal antibodies against mycobacteria, were used to isolate DNA sequences encoding five major protein antigens of this pathogen. To evaluate the extent of crossreactivity between these M. tuberculosis antigens and antigens of Mycobacterium leprae, recombinant antigens were probed with monoclonal antibodies directed against the protein antigens of these bacilli. One of the antigens, a 65-kDa protein, has determinants common to M. tuberculosis and M. leprae. We find not only that this antigen is recognized by mouse monoclonal antibodies but that it is the major protein recognized by anti-M. tuberculosis rabbit sera. The 65-kDa proteins of M. tuberculosis and M. leprae appear to play a role in the humoral and cell-mediated immune response to these pathogens.
Progress towards the field deployment of coherent optical fiber systems (1990)

A description is given of the first demonstration of a coherent optical transmission system deployed in an operational network. The miniaturized external cavity laser and the automated endless polarization control scheme which made it possible to mount this demonstration are described in detail, together with specific system results. A discussion is presented of the possible field deployment of other coherent system options, based on FSK modulation of DFB and DBR lasers, and polarisation diversity reception. The considerable potential afforded by coherent techniques for meeting future network requirements is highlighted. The demonstrated advantages of greater power budget and wavelength selectivity, combined with the use of optical amplifier multiwavelength repeaters, make coherent techniques particularly relevant to the growing demand for greater transmission capacity, transparency, and network flexibility. An increasingly urgent need for robust coherent optical technology can thus be anticipated, for wideband transmission and passive routing, for both telecommunications and computer networks of the near future.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Improved telomere detection using a telomere repeat probe (TTAGGG)ngenerated by PCR (1991)

Journal Article Improved telomere detection using a telomere repeat probe (TTAGGG)n generated by PCR Get access J.W. IJdo, J.W. IJdo 1Howard Hughes Medical InstituteNew Haven, CT 06510, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar R.A. Wells, R.A. Wells 1Howard Hughes Medical InstituteNew Haven, CT 06510, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Baldini, A. Baldini 2Department of Human Genetics, Yale University School of MedicineNew Haven, CT 06510, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar S.T. Reeders S.T. Reeders 1Howard Hughes Medical InstituteNew Haven, CT 06510, USA2Department of Human Genetics, Yale University School of MedicineNew Haven, CT 06510, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 19, Issue 17, 11 September 1991, Page 4780, https://doi.org/10.1093/nar/19.17.4780 Published: 11 September 1991 Article history Accepted: 30 April 1991 Published: 11 September 1991
Dehydroepiandrosterone and 16α-bromo-epiandrosterone: inhibitors of Epstein-Barr virus-induced transformation of human lymphocytes (1981)

Dehydroepiandrosterone (DHEA), a major adrenal secretory product in men and women, is a potent inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). Long-term treatment with this steroid has previously been found to suppress spontaneous breast cancer development in C3H mice. DHEA is now shown to inhibit Epstein-Barr virus (EBV)-induced morphologic transformation and stimulation of DNA synthesis in human lymphocytes. 16 alpha-Br-epiandrosterone, a DHEA analog that is about 60 times as potent as DHEA as an inhibitor of G6PDH, is much more effective as an inhibitor of EBV-induced transformation.
Role of cell-associated enveloped vaccinia virus in cell-to-cell spread (1992)

The roles of intracellular naked (INV), cell-associated enveloped (CEV), and extracellular enveloped (EEV) forms of vaccinia virus in cell-to-cell and longer-range spread were investigated by using two closely related strains of vaccinia virus, WR and IHD-J. We confirmed previous results that WR and IHD-J produced similar amounts of INV and formed similar-size primary plaques but that IHD-J produced 10 to 40 times more EEV and spread to distant cells much more efficiently than did WR. Nevertheless, cells infected with WR and IHD-J had similar amounts of CEV, indicating that wrapping and transport of WR virions were unimpaired. A WR mutant with a deletion in VP37, the major outer envelope protein, formed normal amounts of INV; however, the generation of CEV was blocked and plaque formation was inhibited. These results suggested that CEV is the form of virus that mediates cell-to-cell spread. Marker rescue experiments indicated that the differences in EEV production by WR and IHD-J were not due to sequence differences in VP37. The low amount of WR EEV could be attributed to retention of CEV on the cell membrane. In support of this hypothesis, mild treatment with trypsin released as much or more infectious virus from cells infected with WR as it did with cells infected with IHD-J. Most of the virus released by trypsin sedimented with the buoyant density of EEV. Also, addition of trypsin to cells following inoculation with WR led to a comet-shaped distribution of secondary plaques characteristic of IHD-J. These results demonstrated that the release of CEV from the cell surface was limiting for extracellular virus formation and affirmed the role of EEV in long-range spread.
Synthesis of a purine acyclonucleoside series having pronounced antiviral activity. The glyceropurines (1984)

The synthesis of a series of purine analogues of the acyclonucleoside compound A* (A-Star, 1) is described. Compounds in this series have been shown to have pronounced activity against herpesviruses. These compounds have been designated "the glycerosides". The glyceropurines are described in this report. Nucleotides have been constructed containing glyceroadenine (A*, compound 1). These nucleotides are resistant to degradation by phosphodiesterases. The compound A* is both a poor substrate and a poor inhibitor of adenosine deaminase.
Genetic regulation of protective immune response in congenic strains of mice vaccinated with a subunit malaria vaccine (1996)

The C-terminal 19-kDa, epidermal growth factor-like region of the merozoite surface protein 1 (MSP1) has been used as a vaccine to induce protective immunity to Plasmodium yoelii in mice and to Plasmodium falciparum in monkeys. To analyze the mechanisms and genetic regulation of this MSP1 vaccine-induced protection, we studied the immunologic correlates of protection in H-2 recombinant and congenic mouse strains on the B10 background. Multiple H-2-linked loci were found to contribute, each with a different mechanism. One locus mapped to the I-A region based on the strong protection in C57BL/10 mice compared with intermediate protection in B10.A(4R) mice and the lack of a difference between B10.AKM and B10.MBR mice. Differences in efficacy of passively transferred antisera from vaccinated C57BL/10 vs B10.A(4R) mice indicated that the protection regulated by the I-A locus was at least in part Ab dependent. Two loci mapped to the right of I-A (FE, H-2S, or H-2D) based on a correlation with the number of H-2k loci to the right of I-A in mice that were I-Ak. One effect was Ab independent and may correspond to a possible negative effect of the I-Ek locus. T cells from protected and nonprotected strains differed in their production of IFN-gamma and TNF-alpha following immunization with MSP1(19), but it was unclear how the differential patterns of cytokine expression related to the level of protection. Thus, MSP1(19) vaccine-induced protection is regulated by H-2-linked loci corresponding to two different immune mechanisms. These findings may indicate the need for more than one Ag in a vaccine to protect an HLA-diverse population.
Solid-Phase Synthesis of Oligonucleotide Conjugates Useful for Delivery and Targeting of Potential Nucleic Acid Therapeutics (2009)

Olignucleotide-based drugs show promise as a novel form of chemotherapy. Among the hurdles that have to be overcome on the way of applicable nucleic acid therapeutics, inefficient cellular uptake and subsequent release from endosomes to cytoplasm appear to be the most severe ones. Covalent conjugation of oligonucleotides to molecules that expectedly facilitate the internalization, targets the conjugate to a specific cell-type or improves the parmacokinetics offers a possible way to combat against these shortcomings. Since workable chemistry is a prerequisite for biological studies, development of efficient and reproducible methods for preparation of various types of oligonucleotide conjugates has become a subject of considerable importance. The present review summarizes the advances made in the solid-supported synthesis of oligonucleotide conjugates aimed at facilitating the delivery and targeting of nucleic acid drugs.
In vitro and in vivo kinetic handling of nitrite in blood: effects of varying hemoglobin oxygen saturation (2007)

Growing evidence suggests that nitrite, acting via reduction to nitric oxide by deoxyhemoglobin, may play an important role in local control of blood flow during hypoxia. To investigate the effect of hypoxia (65 Torr arterial Po(2)) on the kinetic properties of nitrite, a bolus injection of sodium nitrite (10 mg/kg iv) was given to normoxic or hypoxic newborn lambs, and the time course of plasma nitrite and methemoglobin (MetHb) concentrations was measured. The in vivo kinetics of nitrite disappearance from plasma were biphasic and were not affected by hypoxia. Changes in MetHb, a product of the nitrite-hemoglobin reaction, also did not differ with the level of oxygenation. Hypoxia potentiated the hypotensive effects of nitrite on pulmonary and systemic arterial pressures. The disappearance of nitrite from plasma was equivalent to the increase in MetHb on a molar basis. In contrast, nitrite metabolism in sheep blood in vitro resulted in more than one MetHb per nitrite equivalent under mid- and high-oxygenation conditions: oxyhemoglobin (HbO(2)) saturation = 50.3 +/- 1.7% and 97.0 +/- 1.3%, respectively. Under the low-oxygenation condition (HbO(2) saturation = 5.2 +/- 0.9%), significantly less than 1 mol of MetHb was produced per nitrite equivalent, indicating that a significant portion of nitrite is metabolized through pathways that do not produce MetHb. These data support the idea that the vasodilating effects of nitrite are potentiated under hypoxic conditions due to the reduction of nitrite to nitric oxide by deoxyhemoglobin.
In‐vivo validation of on‐line and off‐line geometric coronary measurements using insertion of stenosis phantoms in porcine coronary arteries (1992)

Geometric coronary artery measurements with the Phillips Digital Cardiac Imaging System (DCI) and the Cardiovascular Angiography Analysis System (CAAS) were validated using percutaneous insertion of radiolucent stenosis phantoms in swine coronary arteries. Angiographic visualization of the stenosis lumens (phi 0.5, 0.7, 1.0, 1.4, 1.9 mm) was simultaneously recorded on DCI and cinefilm. The acquisition systems were calibrated by either the diameter of the guiding catheter (catheter CAL) or the isocenter method (isocenter CAL). Minimal luminal diameters (MLD) obtained with CAAS and DCI on 20 corresponding cineframes were compared with the true phantom diameters (PD). The accuracy of MLD measurements with the CAAS using isocenter CAL was -0.07mm, the precision 0.21 mm (r = 0.91; y = 0.30 + 0.79x; SEE = 0.19), with catheter CAL the accuracy was 0.09 mm, the precision 0.23 mm (r = 0.89; y = 0.19 + 0.74x; SEE = 0.19). The accuracy of MLD measurements using the DCI with isocenter CAL was 0.08 mm, the precision 0.15 min (r = 0.96; y = 0.08 + 0.86x; SEE = 0.14), with catheter CAL the accuracy was 0.18 mm, the precision 0.21 mm (r = 0.92; y = 0.09 + 0.76x; SEE = 0.17). DCI underestimated PD with isocenter CAL (p less than 0.05) and with catheter CAL (p less than 0.001). MLD can be measured with high accuracy, both applying on-line digital as well as off-line cineangiographic analysis. The results of digital measurements demonstrate high reliability of the new digital software package.
CGRP function‐blocking antibodies inhibit neurogenic vasodilatation without affecting heart rate or arterial blood pressure in the rat (2008)

We showed for the first time that anti-CGRP antibodies exert a long lasting inhibition of neurogenic vasodilatation in two different rat models of arterial blood flow. We have provided strong preclinical evidence that anti-CGRP antibody may be a suitable drug candidate for the preventive treatment of migraine.
Methyl Salicylate Is a Critical Mobile Signal for Plant Systemic Acquired Resistance (2007)

In plants, the mobile signal for systemic acquired resistance (SAR), an organism-wide state of enhanced defense to subsequent infections, has been elusive. By stimulating immune responses in mosaic tobacco plants created by grafting different genetic backgrounds, we showed that the methyl salicylate (MeSA) esterase activity of salicylic acid-binding protein 2 (SABP2), which converts MeSA into salicylic acid (SA), is required for SAR signal perception in systemic tissue, the tissue that does not receive the primary (initial) infection. Moreover, in plants expressing mutant SABP2 with unregulated MeSA esterase activity in SAR signal-generating, primary infected leaves, SAR was compromised and the associated increase in MeSA levels was suppressed in primary infected leaves, their phloem exudates, and systemic leaves. SAR was also blocked when SA methyl transferase (which converts SA to MeSA) was silenced in primary infected leaves, and MeSA treatment of lower leaves induced SAR in upper untreated leaves. Therefore, we conclude that MeSA is a SAR signal in tobacco.
Role of the dorsal anterior cingulate cortex in obsessive-compulsive disorder: converging evidence from cognitive neuroscience and psychiatric neurosurgery (2016)

OBJECTIVE Advances in understanding the neurobiological basis of psychiatric disorders will improve the ability to refine neuromodulatory procedures for treatment-refractory patients. One of the core dysfunctions in obsessive-compulsive disorder (OCD) is a deficit in cognitive control, especially involving the dorsal anterior cingulate cortex (dACC). The authors' aim was to derive a neurobiological understanding of the successful treatment of refractory OCD with psychiatric neurosurgical procedures targeting the dACC. METHODS First, the authors systematically conducted a review of the literature on the role of the dACC in OCD by using the search terms "obsessive compulsive disorder" and "anterior cingulate." The neuroscience literature on cognitive control mechanisms in the dACC was then combined with the literature on psychiatric neurosurgical procedures targeting the dACC for the treatment of refractory OCD. RESULTS The authors reviewed 89 studies covering topics that included structural and functional neuroimaging and electrophysiology. The majority of resting-state functional neuroimaging studies demonstrated dACC hyperactivity in patients with OCD relative to that in controls, while task-based studies were more variable. Electrophysiological studies showed altered dACC-related biomarkers of cognitive control, such as error-related negativity in OCD patients. These studies were combined with the cognitive control neurophysiology literature, including the recently elaborated expected value of control theory of dACC function. The authors suggest that a central feature of OCD pathophysiology involves the generation of mis-specified cognitive control signals by the dACC, and they elaborate on this theory and provide suggestions for further study. CONCLUSIONS Although abnormalities in brain structure and function in OCD are distributed across a wide network, the dACC plays a central role. The authors propose a theory of cognitive control dysfunction in OCD that attempts to explain the therapeutic efficacy of dACC neuromodulation. This theoretical framework should help to guide further research into targeted treatments of OCD and other disorders of cognitive control.
Total Synthesis of Myxovirescins, 1 Strategy and Construction of the “Southeastern” Part [O(1)–C(14)] (1994)

Abstract In this and the following two papers the synthesis of myxovirescins A 1 , A 2 and M 2 , 28‐membered macrocyclic lactam‐lactones with antibiotic acitivity, is described. A retrosynthetic analysis of the myxovirescin family of ca. 30 target molecules leads to a strategy which could be applied to approximately half of them by slight variations of the building blocks used (Schemes 1–3 and following paper). The southeastern part of the molecule, containing the atoms O(1)–C(14) of myxovirescins A and M is described in this first paper (Scheme 3). The assembly is achieved by using the following appropriately protected units: ( S )‐2‐hydroxy‐pentanoic acid, ([1,3]dithian‐2‐ylmethyl)‐amine (Scheme 4), the triflate of ( S,R )‐2,2‐dimethyl‐5‐vinyl‐[1,3]dioxolan‐4‐ylmethanol, ( E )‐3‐bromo‐2‐buten‐1‐ol, and ( E )‐2‐bromo‐2‐buten‐1,4‐diol (Scheme 5), the starting materials for these being malic acid, aminoacetaldehyde, ribose, crotyl alcohol and butyne‐1,4‐diol. The building blocks are put together by using the following key steps: Kolbe electrolysis, amide formation, lithiodithiane alkylation, and Suzuki coupling (Schemes 6 and 8). The only newly created chirality center [C(6) of the target molecules] is generated stereoselectively by a Li‐selectride reduction/Mitsunobu inversion (Table 1, Scheme 7). The termini of the O(1)–C(14) fragment ( 2 in Scheme 8) carry a (protected) hydroxy acid and an aldehyde group for the Julia coupling and lactonization, respectively, in the final steps of the synthesis. All intermediates are fully characterized. The X‐ray crystal structures of two compounds prepared for incorporation as N(4)–C(11) and as C(12)–C(14) of the target molecules are also described (Figures 1 and 2). magnified image
Cell Culture Kinetics and Modeling (2005)

Kinetics of cell growth and metabolism is desired for a better understanding of cell physiology and for the optimization and control of animal cell cultures. Consequently, it has been the objective of a large number of investigations in the past (1-22). A large number of factors were reported to affect the kinetics of growth, death, and product formation of animal cells in bioreactors. Despite these efforts, uncertainties and even controversies often exist in the literature regarding the relative importance of these factors in different cell lines (23-26). This may be mainly due to the lack of quantitative knowledge of the signiﬁcance of these factors and particularly of the range of concentrations or values in which these factors are important. A mathematical description of the interactions of different factors in kinetic models can be very useful to solve this problem because they make it possible to separate and identify the effects of different factors. It can help better in interpreting and understanding experimental results obtained under different conditions. Models can also be used to check different hypotheses regarding regulation mechanisms. In addition, they can be useful as a guide tool for developing model-based process control and monitoring strategies.
The Vascularity of Dental Pulp in Cats (1992)

The fraction of the volume of the coronal pulp of cat canines that is occupied by blood vessels was estimated by measurement of the cross-sectional areas of all the vessels in a complete transverse section of the pulp from each of four teeth. The sections were taken 0.5 mm from the pulp cornu. Overall, 14.4% of the area of the pulp was occupied by vessels. In the core of the pulp, the average value was 42.9%, and superficially, near the odontoblast layer, it was between 5 and 10%. The average capillary density was 1402/mm2, which is higher than in most other tissues. Laser Doppler flow meters can be used for recording blood flow from the coronal pulp of intact teeth, but these instruments are linear only if the moving blood cells occupy no more than 1% of the tissue volume. The present results suggest that this figure is exceeded in pulp.
Antitumor Activity of Immunotoxins with T-Cell Receptor–like Specificity against Human Melanoma Xenografts (2008)

In this study, we have explored the use of Fab-toxin proteins (immunotoxin) to target antigen-specific MHC-peptide complexes of in vitro and in vivo cancer cells. A human phage display library was used to screen for T-cell receptor (TCR)-like antibodies that are highly specific for the peptide melanoma-associated antigen MART-1(26-35) presented by HLA-A201. We also used previously selected TCR-like antibodies specific for the peptide melanoma-associated antigen gp100(280-288) presented by HLA-A201. The recombinant immunotoxin constructs were generated by fusing the targeting Fab fragment to a truncated form of Pseudomonas exotoxin, PE38KDEL. These immunotoxins bound with high affinity to the EBV-transformed JY cell line pulsed with the aforementioned peptides and internalized within 30 min. A significant inhibition of protein synthesis, which resulted in cell death, was detected at 24 h. MART-1-specific and gp100-specific immunotoxins bound and killed HLA-A201 melanoma MART-1(+) and gp100(+) cell lines that were presented at natural levels but do not bind to HLA-A201(-) or to HLA-A201(+) MART-1(-) and gp100(-) cell lines. In severe combined immunodeficient mice, MART-1 and gp100 immunotoxins significantly and discriminately inhibited human melanoma growth. These results show that MHC class I/peptide complexes can serve as a specific target for passive immunotherapy of cancer.
A Newly Recognized Fastidious Gram-Negative Pathogen as a Cause of Fever and Bacteremia (1990)

This pathogen may have been unidentified until now because of its slow growth, broad susceptibility to antimicrobial agents, and possible requirement of blood-cell lysis for recovery in culture. It should be sought as a cause of unexplained fever, especially in persons with defective cell-mediated immunity.
A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals. (1996)

Amphiphysin, a major autoantigen in paraneoplastic Stiff-Man syndrome, is an SH3 domain-containing neuronal protein, concentrated in nerve terminals. Here, we demonstrate a specific, SH3 domain-mediated, interaction between amphiphysin and dynamin by gel overlay and affinity chromatography. In addition, we show that the two proteins are colocalized in nerve terminals and are coprecipitated from brain extracts consistent with their interactions in situ. We also report that a region of amphiphysin distinct from its SH3 domain mediates its binding to the alpha c subunit of AP2 adaptin, which is also concentrated in nerve terminals. These findings support a role of amphiphysin in synaptic vesicle endocytosis.