gebhart/patrepeval huggingface dataset:
Loss of SDF-1 receptor expression during positive selection in the thymus (1998)

SDF-1 is a member of the CXC chemokines. In contrast to other chemokines that are induced by inflammation, SDF-1 is constitutively produced by stromal cells. In order to investigate the physiological roles of SDF-1, we constructed a fusion protein, SDF-1-Cgamma1, composed from murine SDF-1alpha and the constant region of human IgG. SDF-1-Cgamma1 stained EL-4 T lymphoma cells and the staining was blocked by rhSDF-1beta. The expression levels of SDF-1R altered along with the T cell maturation. Most c-kit+ hematopoietic precursors in fetal liver in gestational day (GD) 14.5 embryo were SDF-1R-, while c-kit+ double-negative (DN) thymocytes in the embryo were positive for SDF-1R. The receptor expression increased along with T cell maturation up to double-positive (DP) cell stage. Interestingly, SDF-1R expression was down-modulated after positive selection; CD69+CD3hi DP and CD3hi single-positive thymocytes were SDF-1R-/lo. Northern blot analysis demonstrated that SDF-1 and CXCR4 mRNAs were abundantly expressed in the thymuses of embryo and adult mice. These results demonstrate that SDF-1R expression is involved in T cell development in the thymus, particularly in positive selection.
Evaluation of Serologic and Antigenic Relationships Between Middle Eastern Respiratory Syndrome Coronavirus and Other Coronaviruses to Develop Vaccine Platforms for the Rapid Response to Emerging Coronaviruses (2020)

Background. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs.
Reduced coronary dilatory capacity and ultrastructural changes of the myocardium in patients with angina pectoris but normal coronary arteriograms. (1981)

Hemodynamic and metabolic studies were performed in 15 patients without heart disease (controls, group A), in 21 patients with typical stress-induced anginal pain but normal coronary and left ventricular angiograms (angina pectoris with normal arteriogram, group B), and in 10 patients with angiographically proved coronary artery disease (CAD, group C). Coronary dilatory capacity, determined by measuring total myocardial blood flow at rest and during maximal coronary vasodilatation (dipyridamole, 0.5 mg/kg i.v.), was markedly reduced in group B and C patients. In group B patients, left ventricular catheter biopsy specimens revealed no evidence of small-vessel disease, but did show histologic alterations of mitochondria. During atrial pacing, the control subjects showed no changes in myocardial lactate uptake, whereas in group B patients, myocardial lactate production occurred. In contrast to controls, patients in group B showed a significant decline in ejection fraction and circumferential fiber shortening during isometric exercise. These findings suggest that myocardial ischemia is the cause of angina pectoris in patients who have angina but normal coronary arteriograms.
Isolation of human anti-MICA antibody from cancer patients responding to immunotherapies. (2012)

2502 Background: Immunotherapy is a promising modality for the treatment of cancer, and elucidating the mechanism of action is crucial to guiding patient selection and developing future immunotherapeutic strategies. Engagement of the immune molecule NKG2D by the cancer antigen MICA is important for immune surveillance of many cancers. Tumors can evade immune surveillance by shedding cell surface MICA, which leads to dampening of anti-tumor immunity. Investigations by our laboratory revealed that patients responding to immunotherapy can mount antibody responses targeting MICA, which permits re-engagement of immunity. Methods: Patients with advanced cancer treated at our institution with immunotherapies (tumor cell vaccination, ipilimumab) were identified, including several with long-term clinical remissions. Plasma was analyzed for MICA reactivity to three distinct MICA alleles, and rare memory B cells reactive to MICA were isolated using tetramerized MICA protein. Immunoglobulin heavy and light chain variable domains were sequenced with single cell RT-PCR to generate recombinant monoclonal antibody. Results: Plasma from patients treated with immunotherapy revealed considerable inter-patient variation in reactivity to MICA. Patients with marked plasma reactivity (including several with sustained clinical remissions) were selected for isolation of rare memory B cells reactive to MICA. From these cells, we have generated a recombinant fully-human MICA-reactive monoclonal antibody that exhibits binding to a variety of MICA alleles. Conclusions: We have developed novel methods to analyze anti-MICA antibody responses and isolate rare memory B cells from cancer patients who gained significant clinical benefit from immunotherapy. This has facilitated the generation of fully human recombinant anti-MICA monoclonal antibody. To our knowledge, this is the first example of a specific antibody reactive to a cancer antigen isolated from a cancer patient responding to immunotherapy. As these antibody responses likely played a role in tumor destruction, these results inform the development of new antibody-based immunotherapies targeting the NKG2D-MICA pathway.
Securinine, a Myeloid Differentiation Agent with Therapeutic Potential for AML (2011)

As the defining feature of Acute Myeloid Leukemia (AML) is a maturation arrest, a highly desirable therapeutic strategy is to induce leukemic cell maturation. This therapeutic strategy has the potential of avoiding the significant side effects that occur with the traditional AML therapeutics. We identified a natural compound securinine, as a leukemia differentiation-inducing agent. Securinine is a plant-derived alkaloid that has previously been used clinically as a therapeutic for primarily neurological related diseases. Securinine induces monocytic differentiation of a wide range of myeloid leukemia cell lines as well as primary leukemic patient samples. Securinine's clinical potential for AML can be seen from its ability to induce significant growth arrest in cell lines and patient samples as well as its activity in significantly impairing the growth of AML tumors in nude mice. In addition, securinine can synergize with currently employed agents such as ATRA and decitabine to induce differentiation. This study has revealed securinine induces differentiation through the activation of DNA damage signaling. Securinine is a promising new monocytic differentiation inducing agent for AML that has seen previous clinical use for non-related disorders.
<title>Shearing Interferometer With Scanned Photodiode Array And Microcomputer For Automatic Transparency Distortion Measurements</title> (1978)

A prototype optical system is described incorporating a scanning lateral shearing interferometer, self-scanned photodiode array, electronic bandpass filter, a counter and a microprocessor for the rapid automatic testing of large area transparencies such as air-craft windscreens. Optical anomalies as small as 0.005 diopters and ranging to ± 0.2 diopters can be readily measured. The system also automatically compensates for beam deviation and displacement during the scanning process with an adaptive gimbaled mirror which provides a measure of prismatic deviation to an accuracy of about ± 0.02 degrees.
Effect of Low-Intensity Laser Irradiation on the Process of Bone Repair (2005)

The effect of low-intensity laser (GaAsAl) irradiation on bone repair in the femurs of mice was investigated. An experimental model of hole injury with surgery drills was used in 20 mouse femurs followed by a study of the effect of low-energy laser irradiation on bone repair. The experimental model was divided into two groups. The first (10 left femurs) received laser irradiation immediately after injury and was followed for different time intervals (24, 48, and 72 h). The right femurs (control group) underwent hole injury but no laser irradiation. The rats were sacrificed after 14 days and the results were analyzed using a quantitative histometrical method. The Mann-Whitney test was used to perform the statistical analysis. Histometrical analysis revealed a more rapid accumulation of reparative new bone in the hole injury of the laser-irradiated legs. We conclude that GaAsAl laser irradiation after injury was effective on bone repair when compared to results in the control group.
c-erbB-2 overexpression in the dysplasia/carcinoma sequence of Barrett's oesophagus. (1995)

AIMS--To investigate overexpression of the oncoprotein c-erbB-2 in the dysplasia/carcinoma sequence of Barrett's columnar-lined oesophagus (CLO). METHODS--Immunohistochemical staining was performed using the monoclonal antibody NCL-CB-11 on formalin fixed tissue from 31 cases of Barrett's carcinoma, 20 cases of cancer associated dysplastic CLO, seven cases of dysplastic CLO without cancer, and 20 cases of non-dysplastic CLO. Membranous staining was regarded as positive for c-erbB-2 overexpression; cytoplasmic staining was recorded separately as its significance is uncertain. RESULTS--Membranous c-erbB-2 overexpression was observed in eight of 31 (26%) carcinomas and in none of the cases of dysplastic CLO. Variable cytoplasmic staining was seen in four of 31 (13%) tumours and seven of 27 (26%) cases of dysplastic CLO. No staining was observed in non-dysplastic CLO. CONCLUSIONS--C-erbB-2 overexpression is a relatively late event in the development of some Barrett's carcinomas and is unlikely to be involved in the early stages of neoplastic transformation of CLO.
[Contribution to the study of the haemolytic streptococci isolated from dogs (author's transl)]. (1975)

The authors studied bacteriologically 740 specimens from dogs maintained at the central kennel of the Faculdade de Ciências Médicas e Biológicas de Botucatu, being the main subject the isolation of streptococci strains from the tonsilar, vaginal conjuctival and preputial secretions. Strains with the same serological properties showed a different biochemical properties, which allowed us to appoint different biochemical types inside a same serological group. On the other hand, it was also possible to detect through the precipitation capillary tube technique, the serological groups G, C, A, D and B, being the G group (73%) the most frequent one. Biochemical properties of the human G group streptococci compared with the canine G group streptococci showed a statistically significant difference in the reactions of fibrinolysis of human plasma, glicerol, sorbitol, esculin, mannitol, inulin, raffinose, salicin, trehalos, hydrolysis of the sodium hypurate, growth on 20% bile broth, and growth at 45 degrees C. The authors stress the utility of the fibrinolysis of human plasma test for the characterization of canine origin streptococci.
High efficiency of endogenous antigen presentation by MHC class II molecules (1992)

MHC class II molecules are involved in the presentation of both exogenous and endogenous antigens to CD4 T cells. Using the trans-membrane hemagglutinin (HA) from measles virus and the secreted hen egg lysozyme (HEL) as antigen models, we have compared the efficiency of MHC class II presentation by naive antigen presenting cells (APCs) pulsed with exogenous antigen with that of their transfected counterparts synthesizing endogenous antigen. B cells expressing even a very low amount of trans-membrane HA were found to present endogenous HA to I-Ed restricted T cell hybridomas with a high efficiency whereas their naive counterparts required to be pulsed with a comparatively high amount of exogenous HA. Similarly, MHC class II presentation of endogenous secreted HEL was found to be much more efficient when compared with that of exogenous HEL. Biochemical studies did not reveal any enhanced intracellular degradation of endogenous HEL. As expected, HEL was released in the surrounding medium within < 1 h. MHC class II presentation of endogenous HEL could not be explained by re-uptake by bystander APCs of HEL secreted in the surrounding medium. No sensitization of naive APCs could be observed either when co-cultured with HEL secreting cells or when cultured for 10 days with a sub-threshold amount of exogenous HEL. At the cell surface, I-Ed molecules immunoprecipitated from HEL secreting cells were found to be slightly enriched in SDS-resistant forms. These data raised the question of how peptides derived from endogenous transmembrane and secreted antigens can so efficiently reach an MHC class II loading compartment.
Purification and characterization of N-acetylneuraminic acid-9-phosphate synthase from rat liver (2002)

Sialic acids are a group of carboxylated amino sugars important for a variety of cellular functions. N-Acetylneuraminic acid (Neu5Ac) is the predominant sialic acid in nature. Neu5Ac-9-phosphate synthase catalyzes the formation of Neu5Ac-9-phosphate from N-acetylmannosamine-6-phosphate and phosphoenolpyruvate. Neu5Ac-9-phosphate synthase was purified 11,700-fold from rat liver cytosol to apparent homogeneity by ammonium sulfate precipitation, chromatography on hydroxylapatite, phenyl-Sepharose, MonoQ, and finally gel filtration. SDS-PAGE and gel filtration chromatography indicated that the enzyme is a dimer composed of 37-kDa subunits. Analysis of trypic peptides by MALDI-TOF MS verified a high sequence similarity to the corresponding murine enzyme. The K(m) values of Neu5Ac-9-phosphate synthase were 35 microM for N-acetylmannosamine-6-phosphate and 100 microM for phosphoenolpyruvate. The enzyme displayed an absolute requirement for divalent cations, Mn(2+), Fe(2+), and Mg(2+) being the most effective. In contrast to human Neu5Ac-9-phosphate synthase, the rat enzyme did not utilize mannose-6-phosphate in the synthesis of 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid 9-phosphate. Neu5Ac-9-phosphate synthase was inactivated by the sulfhydryl modifying reagents, 5,5'-dithio-bis (2-nitrobenzoic acid) and N-ethylmaleimide, and protected from inactivation by the presence of the substrate phosphoenolpyruvate, but not by the presence of N-acetylmannosamine-6-phosphate, showing that at least one cysteine residue is located in the active site of the enzyme.
Human gene therapy: a brief overview of the genetic revolution. (2013)

Advances in biotechnology have brought gene therapy to the forefront of medical research. The prelude to successful gene therapy i.e. the efficient transfer and expression of a variety of human gene into target cells has already been accomplished in several systems. Safe methods have been devised to do this, using several viral and no-viral vectors. Two main approaches emerged: in vivo modification and ex vivo modification. Retrovirus, adenovirus, adeno-associated virus are suitable for gene therapeutic approaches which are based on permanent expression of the therapeutic gene. Non-viral vectors are far less efficient than viral vectors, but they have advantages due to their low immunogenicity and their large capacity for therapeutic DNA. To improve the function of non-viral vectors, the addition of viral functions such as receptor mediated uptake and nuclear translocation of DNA may finally lead to the development of an artificial virus. Gene transfer protocols have been approved for human use in inherited diseases, cancers and acquired disorders. In 1990, the first successful clinical trial of gene therapy was initiated for adenosine deaminase deficiency. Since then, the number of clinical protocols initiated worldwide has increased exponentially. Although preliminary results of these trials are somewhat disappointing, but human gene therapy dreams of treating diseases by replacing or supplementing the product of defective or introducing novel therapeutic genes. So definitely human gene therapy is an effective addition to the arsenal of approaches to many human therapies in the 21st century.
An interstrand-wedged duplex composed of alternating DNAbase pairs and covalently attached intercalators (2009)

An interstrand-wedged duplex involving alternating base pairs and covalently attached intercalators viaD-threoninols was constructed. In this novel duplex structure, natural DNA base pairs and artificially introduced planar molecules such as azobenzene derivatives are lined up one by one. Although each base pair is sandwiched by two intercalators and vice versa, the duplex is extremely stable compared with the corresponding native DNA duplex. Analysis by 1H-NMR showed that all of the expected internal base pairs are strongly formed even when the base pairs are sandwiched between azobenzene moieties. More interestingly, the stability of this new duplex structure decreased greatly when a mismatched base pair was introduced, indicating that this interstrand-wedged duplex has a high sequence specificity. Furthermore, the structure became very unstable when azobenzene moieties were photoisomerized to the cis form. It is expected that this new duplex motif will be very useful for the construction of a variety of functional nanostructures and nanodevices. The concept proposed here is a novel combination of the specificity of DNA hybridization and the versatility of synthesized organic molecules.
Fluorine-containing Amino Acids and Their Derivatives. 5. Synthesis of Novel Fluorinated Analogues of the Antitumor Agent, Methotrexate (1985)

A b s t r a c t -Novel methotrexate analogues w i t h y -f l u a r o -o r cr-difluoromethylsubstitued-glutamic a c i d were synthesized f o r antitumor screening. Methotrexate (MTX), a p o t e n t i n h i b i t o r o f d ih y d r o f o l a t e reductase, i s an a n t i t u m o r agent i n wide c l i n i c a l use against various types o f cancers.' Progress i n pharmacological and physicochemical research on t h i s drug and d i h y d r o f a l a t e reductase i t s e l f has l e d t o an understanding o f t h e fundamentals of t h e mode o f a c t i o n and t h e mechanism o f t r a n s p o r t and metabolism, enabling more accurate drug design based on t h
Mechanical and Electrical Properties of Silicon Nitride–Silicon Carbide Nanocomposite Material (1991)

Mechanical and electrical properties of nanocomposite materials composed of a Si 3 N 4 matrix and nanometer‐sized SiC particles are described. Composites containing less than 10 vol% SiC particles have the same order of resistivity and dielectricity as the non‐SiC material as well as highly improved mechanical properties. The composites are promising materials for use under harsh conditions.
A Threshold Level of Intratumor CD8+ T-cell PD1 Expression Dictates Therapeutic Response to Anti-PD1 (2015)

Despite successes, thus far, a significant proportion of the patients treated with anti-PD1 antibodies have failed to respond. We use mouse tumor models of anti-PD1 sensitivity and resistance and flow cytometry to assess tumor-infiltrating immune cells immediately after therapy. We demonstrate that the expression levels of T-cell PD1 (PD1(lo)), myeloid, and T-cell PDL1 (PDL1(hi)) in the tumor microenvironment inversely correlate and dictate the efficacy of anti-PD1 mAb and function of intratumor CD8(+) T cells. In sensitive tumors, we reveal a threshold for PD1 downregulation on tumor-infiltrating CD8(+) T cells below which the release of adaptive immune resistance is achieved. In contrast, PD1(hi) T cells in resistant tumors fail to be rescued by anti-PD1 therapy and remain dysfunctional unless intratumor PDL1(lo) immune cells are targeted. Intratumor Tregs are partly responsible for the development of anti-PD1-resistant tumors and PD1(hi) CD8(+) T cells. Our analyses provide a framework to interrogate intratumor CD8(+) T-cell PD1 and immune PDL1 levels and response in human cancer.
Expression and Characterization of Bone Morphogenetic Protein-2 in Chinese Hamster Ovary Cells (1992)

Bone is a dynamic tissue that responds to many factors including vitamin D, parathyroid hormone, estrogen, calcitonin, and bone morphogenetic proteins (BMPs). The ability to stimulate new bone growth would permit novel therapies for situations where bone mass has been lost due to accident or disease. Purified BMP-2, in conjunction with a suitable matrix, is sufficient to stimulate the synthesis of new bone (Wang et al., 1990). We have expressed recombinant human BMP-2 at high levels in Chinese hamster ovary cells using methotrexate-mediated gene amplification. Several forms of BMP-2 are secreted from CHO cells: (1) an amino-terminal propeptide of 40-45 kDa, (23) a mature active 30 kDa homodimer consisting of 18-22 kDa subunits, and (3) a small amount of uncleaved 60 kDa precursor protein. The mature, active protein is predominantly a 30 kDa homodimer consisting of subspecies of 18 and 22 kDa which differ by proteolytic processing at their amino termini. Mature BMP-2 and propeptide contain high mannose and complex N-linked oligosaccharides, respectively. The molar amount of secreted, processed propeptide is approximately 5-fold higher than mature BMP-2 in conditioned medium. BMP-2 associates with both the extracellular matrix and the surface of CHO cells, which may in part account for the unequal levels of extracellular propeptide and mature forms of the molecule in the conditioned medium. Recombinant BMP-2 can be expressed in sufficient quantities to assess its therapeutic potential for bone regeneration.
Hormones and Menopausal Status as Predictors of Depression in Womenin Transition to Menopause (2004)

Depressive symptoms as assessed herein increased during transition to menopause and decreased in postmenopausal women. Hormone associations provided corroborating evidence that the changing hormonal milieu contributes to dysphoric mood during transition to menopause.
Label-free biomarker detection from whole blood (2010)

Label-free nanosensors can detect disease markers to provide point-of-care diagnosis that is low-cost, rapid, specific and sensitive. However, detecting these biomarkers in physiological fluid samples is difficult because of ionic screening. Here, we overcome this limitation by using distinct components within the sensor to perform purification and detection. <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> A microfluidic purification chip captures multiple biomarkers simultaneously from blood samples and releases them, after washing, into purified buffer for sensing by a silicon nanoribbon detector. This two-stage approach isolates the detector from the complex environment of whole blood, and reduces its minimum required sensitivity by effectively pre-concentrating the biomarkers. We show specific and quantitative detection of two model cancer antigens from a 10 uL sample of whole blood in less than 20 minutes.
Properties and uses of embryonic stem cells: prospects for application to human biology and gene therapy (1998)

Embryonic stem cells are pluripotent cells derived from the early mouse embryo that can be propagated stably in the undifferentiated state in vitro. They retain the ability to differentiate into all cell types found in an embryonic and adult mouse in vivo, and can be induced to differentiate into many cell types in vitro. Exploitation of ES cell technology for the creation of mice bearing predetermined genetic alterations has received widespread attention because of the sophistication that it brings to the study of gene function in mammals. Analysis of cell differentiation in vitro has also been of value, leading to the identification of novel bioactive factors and the elucidation of cell specification mechanisms. In this paper, we summarise the features of pluripotent cell lines and their applications, foreshadowing the impact that these systems may have on human biology. While the isolation of definitive human pluripotent cell lines has not yet been achieved, potential applications for these cells in the study of human biology, particularly cell specification, can be envisaged. Of particular interest is the possibility that human embryonic stem cells with properties similar to mouse embryonic stem cells might provide a generic system for gene therapy.