gebhart/patrepeval huggingface dataset:
Angiotensin-converting enzyme inhibitor versus angiotensin II, AT1 receptor antagonist. Effects on smooth muscle cell migration and proliferation after balloon catheter injury. (1991)

The angiotensin-converting enzyme (ACE) inhibitor, benazeprilat and the angiotensin II (Ang II), AT1-specific receptor antagonist, DuP753, were compared for their effects on intimal lesion formation as well as smooth muscle cell (SMC) proliferation and migration in Sprague Dawley rats after carotid balloon injury. Both the ACE inhibitor (benazeprilat, 3 mg/kg/day) and the AT1 antagonist (DuP 753, 10 mg/kg/day) significantly reduced intimal lesion formation after balloon injury (by 35% and 49%, respectively). Medial SMC proliferation after injury was reduced 53% by the AT1 antagonist; however, the ACE inhibitor had no effect on SMC proliferation. SMC migration was reduced 94% by the AT1 antagonist and 68% by the ACE inhibitor. These data demonstrate the importance of Ang II in SMC proliferation and migration after balloon injury. They also demonstrate that in the balloon injury model, the ACE inhibitor reduced intimal lesion size by inhibiting SMC migration alone without affecting SMC proliferation. A more pronounced reduction in lesion size was obtained after AT1 antagonism, however, when both SMC migration and proliferation were inhibited.
Construction of hpaA gene from a clinical isolate ofHelicobacter pyloriand identification of fusion protein (2003)

A prokaryotic expression system with high efficiency of H.pylori hpaA gene was successfully established. The HpaA expressing fusion protein showed satisfactory immunoreactivity and antigenicity. High frequencies of HpaA expression in different H.pylori clinical strains and specific antibody production in H.pylori infected patients indicate that HpaA is an excellent and ideal antigen for developing H.pylori vaccine.
Rapid, nondenaturing RNA purification using weak anion-exchange fast performance liquid chromatography (2010)

We present a simple and fast method for large-scale purification of RNA oligonucleotides suitable for biochemical and structural studies. RNAs are transcribed in vitro with T7 RNA polymerase using linearized plasmid DNA templates. After addition of EDTA, the crude transcription reaction is subjected directly to weak anion-exchange chromatography using DEAE-sepharose to separate the T7 RNA polymerase, unincorporated rNTPs, small abortive transcripts, and the plasmid DNA template from the desired RNA product. The novel method does neither require tedious phenol/chloroform extraction of the T7 RNA polymerase nor denaturation of the RNA, which is desirable especially for larger RNAs. In addition, isotopically labeled rNTPs can be easily recycled from the column flow-through and oligomeric RNA aggregates can be separated from the natively folded monomeric RNA product.
Solid Freeform Fabrication: An Enabling Technology for Future Space Missions (2002)

The emerging class of direct manufacturing processes known as Solid Freeform Fabrication (SFF) employs a focused energy beam and metal feedstock to build structural parts directly from computer aided design (CAD) data. Some variations on existing SFF techniques have potential for application in space for a variety of different missions. This paper will focus on three different applications ranging from near to far term to demonstrate the widespread potential of this technology for space-based applications. One application is the on-orbit construction of large space structures, on the order of tens of meters to a kilometer in size. Such structures are too large to launch intact even in a deployable design; their extreme size necessitates assembly or erection of such structures in space. A low-earth orbiting satellite with a SFF system employing a high-energy beam for high deposition rates could be employed to construct large space structures using feedstock launched from Earth. A second potential application is a small, multifunctional system that could be used by astronauts on long-duration human exploration missions to manufacture spare parts. Supportability of human exploration missions is essential, and a SFF system would provide flexibility in the ability to repair or fabricate any part that may be damaged or broken during the mission. The system envisioned would also have machining and welding capabilities to increase its utility on a mission where mass and volume are extremely limited. A third example of an SFF application in space is a miniaturized automated system for structural health monitoring and repair. If damage is detected using a low power beam scan, the beam power can be increased to perform repairs within the spacecraft or satellite structure without the requirement of human interaction or commands. Due to low gravity environment for all of these applications, wire feedstock is preferred to powder from a containment, handling, and safety standpoint. The energy beams may be either electron beam or laser, and the developments required for either energy source to achieve success in these applications will be discussed.
Structural elements of kallistatin required for inhibition of angiogenesis (2003)

Kallistatin is a serpin first identified as a specific inhibitor of tissue kallikrein. Our recent studies showed that kallikrein promoted angiogenesis, whereas kallistatin inhibited angiogenesis and tumor growth. This study is aimed to identify the structural elements of kallistatin essential for its antiangiogenic function. Kallistatin mutants at the hinge region (A377T) and a major heparin-binding domain (K312A/K313A) were created by site-directed mutagenesis. Recombinant kallistatin mutant A377T did not bind or inhibit tissue kallikrein activity. Wild-type kallistatin and kallistatin mutant A377T, but not kallistatin mutant K312A/K313A lacking heparin-binding activity, inhibited VEGF-induced proliferation, growth, and migration of human microvascular endothelial cells. Similarly, wild-type kallistatin and kallistatin mutant A337T, but not kallistatin mutant K312A/K313A, significantly inhibited VEGF-induced capillary tube formation of cultured endothelial cells in Matrigel and capillary formation in Matrigel implants in mice. To elucidate the role of the heparin-binding domain in modulating angiogenesis, we showed that wild-type kallistatin interrupted the binding of (125)I-labeled VEGF to endothelial cells, whereas kallistatin mutant K312A/K313A did not interfere with VEGF binding. Consequently, wild-type kallistatin, but not kallistatin mutant K312A/K313A, suppressed VEGF-induced phosphorylation of Akt. Taken together, these results indicate that the heparin-binding domain, but not the reactive site loop of kallistatin, is essential for inhibiting VEGF-induced angiogenesis.
Activation of Detergent-Solubilized Diacylglycerol Acyltransferase by Anionic Phospholipids (1996)

Diacylglycerol acyltransferase (DGAT), which catalyzes the final step in triacylglycerol (TG) biosynthesis, is crucial for lipid accumulation and formation of lipid bodies in an oleaginous fungus, Mortierella ramanniana var. angulispora. Since solubilization of DGAT in the lipid body fraction from this fungus with 0.5% Triton X-100 gave very low recovery of the activity, some activation factors for solubilized DGAT activity were investigated. Addition of phospholipids, especially anionic phospholipids such as phosphatidic acid and phosphatidylserine, to the assay mixture greatly increased DGAT activity. The activation by these phospholipids was most prominent when 0.2% Triton X-100 was added to the assay mixture. The effect of phosphatidic acid was reproduced using DGAT fraction obtained by 0.5 M KCl elution on Mono S column chromatography. The results provide new insight on activation of DGAT during TG accumulation as well as optimal DGAT assay conditions for solubilized fractions.
The tumour–stromal interaction between intratumoral c-Met and stromal hepatocyte growth factor associated with tumour growth and prognosis in non-small-cell lung cancer patients (2004)

Immunohistochemical analyses of the effects of hepatocyte growth factor (HGF) and c-Met expression on tumour growth and angiogenesis were performed on 88 patients with non-small-cell lung cancers (NSCLCs). In all, 22 carcinomas (25.0%) were intratumoral HGF-positive, 14 carcinomas (15.9%) were stromal HGF-positive, and 36 carcinomas (40.9%) were intratumoral c-Met-positive. None of the carcinomas were stromal c-Met-positive. Examination of tumour growth revealed that the frequency of tumours with a high Ki-67 index was significantly greater for stromal HGF-positive tumours than for stromal HGF-negative tumours (P=0.0197). The frequency of tumours with a high Ki-67 index was also significantly greater for intratumoral c-Met-positive tumours than for intratumoral c-Met-negative tumours (P=0.0301). However, there was no significant difference in tumour vascularity with relation to intratumoral HGF status, stromal HGF status, and intratumoral c-Met status. The survival rate of patients with intratumoral c-Met-positive tumours was significantly lower than for patients with c-Met-negative tumours (P=0.0095). Furthermore, the survival rate of patients with both intratumoral c-Met-positive and stromal HGF-positive tumours was significantly lower than for patients with either positive tumours, and that of patients with both negative tumours (P=0.0183 and P=0.0011, respectively). A univariate analysis revealed that intratumoral c-Met expression was a significant prognostic factor of NSCLC patients (relative risk=2.642, P=0.0029). The present study demonstrates that tumour-stromal interaction between tumour cell-derived c-Met and stromal cell-derived HGF affects tumour growth and the prognosis of NSCLC patients.
A Bispecific Antifibrin-antiplatelet Urokinase Conjugate (BAAUC) Induces Enhanced Clot Lysis and Inhibits Platelet Aggregation (1999)

Thrombolysis is well established in the treatment of acute myocardial infarction. However, clinical application of thrombolytic agents has limitations with respect to efficacy and specificity. To achieve highly effective and at the same time clot-selective plasminogen activation urokinase was coupled to a bispecific antibody consisting of the monovalent Fab' from the antifibrin monoclonal antibody 59D8 and the monovalent Fab' from the anti-glycoprotein GPIIb/IIIa monoclonal antibody 7E3. The bispecific antifibrin-antiplatelet urokinase conjugate (BAAUC) was synthesized and characterized. Assays with either immobilized platelets, GPIIb/IIIa or fibrin showed an increase in plasminogen activation compared to uncoupled urokinase by 10-fold, 58-fold and 13-fold, respectivley (p < 0.0001 each). In vitro clot lysis was performed on platelet-rich and fibrin-rich clots and revealed an up to 5-fold higher potency of BAAUC compared to uncoupled urokinase (p < 0.0001). In vitro platelet aggregation was effectively inhibited by the hybrid molecule, whereas urokinase had no effect. BAAUC and two monospecific urokinase-conjugates, UK-59D8-IgG and UK-7E3-(Fab')2 were compared with each other with regard to similar tests. In vitro clot assays with platelet-rich and platelet-poor clots were performed. BAAUC achieved a significantly higher plasminogen activation compared to each of the monospecific conjugates (p < 0.05, respectively). We conclude that BAAUC, a bispecific plasminogen activator with antifibrin and antiplatelet properties has the potency to lyse both fibrin-rich and platelet-rich thrombi with high efficacy and to effectively inhibit platelet aggregation.
Turning Theory into Practice: The Development of Modern Transdermal Drug Delivery Systems and Future Trends (2013)

Despite its remarkable barrier function, the skin remains an attractive site for systemic drug delivery given its easy accessibility, large surface area and the possibility to bypass the gastrointestinal tract and the liver and so modify drug absorption kinetics. The pioneering work of Scheuplein, Higuchi and others in the 1960s helped to explain the processes involved in passive percutaneous absorption and led to the development of mathematical models to describe transdermal drug delivery. The intervening years have seen these theories turned to practice and a significant number of transdermal systems are now available including some that employ active drug delivery. This review briefly discusses the evolution of transdermal therapeutic systems over the years and the potential of newer transdermal technologies to deliver hydrophilic drugs and macromolecules through the skin.
Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis (2001)

The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with dinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS."
XXIII.—Some crystalline substances obtained from the fruits of various species of Citrus. Part I (1890)

W. A. Tilden and C. R. Beck, J. Chem. Soc., Trans., 1890, 57, 323 DOI: 10.1039/CT8905700323
Glow and Townsend dielectric barrier discharge in various atmosphere (2005)

International audience
Endocytosed HSP60s Use Toll-like Receptor 2 (TLR2) and TLR4 to Activate the Toll/Interleukin-1 Receptor Signaling Pathway in Innate Immune Cells (2001)

Heat shock proteins (HSPs) require no adjuvant to confer immunogenicity to bound peptides, as if they possessed an intrinsic "danger" signature. To understand the proinflammatory nature of HSP, we analyzed signaling induced by human and chlamydial HSP60. We show that both HSP60s activate the stress-activated protein kinases p38 and JNK1/2, the mitogen-activated protein kinases ERK1/2, and the I-kappaB kinase (IKK). Activation of JNK and IKK proceeds via the Toll/IL-1 receptor signaling pathway involving MyD88 and TRAF6. Human fibroblasts transfected with TLR2 or TLR4 plus MD-2 gain responsiveness to HSP60, while TLR2- or TLR4-defective cells display impaired responses. Initiation of signaling requires endocytosis of HSP60 that is effectively inhibited by serum component(s). The results revealed that adjuvanticity of HSP60 operates similar to that of classical pathogen-derived ligands.
No evidence for brain renin–angiotensin system activation during DOCA-salt hypertension (2021)

Brain renin-angiotensin system (RAS) activation is thought to mediate deoxycorticosterone acetate (DOCA)-salt hypertension, an animal model for human primary hyperaldosteronism. Here, we determined whether brainstem angiotensin II is generated from locally synthesized angiotensinogen and mediates DOCA-salt hypertension. To this end, chronic DOCA-salt-hypertensive rats were treated with liver-directed siRNA targeted to angiotensinogen, the angiotensin II type 1 receptor antagonist valsartan, or the mineralocorticoid receptor antagonist spironolactone (n = 6-8/group). We quantified circulating angiotensinogen and renin by enzyme-kinetic assay, tissue angiotensinogen by Western blotting, and angiotensin metabolites by LC-MS/MS. In rats without DOCA-salt, circulating angiotensin II was detected in all rats, whereas brainstem angiotensin II was detected in 5 out of 7 rats. DOCA-salt increased mean arterial pressure by 19 ± 1 mmHg and suppressed circulating renin and angiotensin II by >90%, while brainstem angiotensin II became undetectable in 5 out of 7 rats (<6 fmol/g). Gene silencing of liver angiotensinogen using siRNA lowered circulating angiotensinogen by 97 ± 0.3%, and made brainstem angiotensin II undetectable in all rats (P<0.05 vs. non-DOCA-salt), although brainstem angiotensinogen remained intact. As expected for this model, neither siRNA nor valsartan attenuated the hypertensive response to DOCA-salt, whereas spironolactone normalized blood pressure and restored brain angiotensin II together with circulating renin and angiotensin II. In conclusion, despite local synthesis of angiotensinogen in the brain, brain angiotensin II depended on circulating angiotensinogen. That DOCA-salt suppressed circulating and brain angiotensin II in parallel, while spironolactone simultaneously increased brain angiotensin II and lowered blood pressure, indicates that DOCA-salt hypertension is not mediated by brain RAS activation.
Glial β-amyloid precursor protein: expression in the dentate gyrus after entorhinal cortex lesion (1994)

Stereotactic lesioning of the rat entorhinal cortex leads to an induction of beta-amyloid precursor protein (APP) immunoreactivity in non-neuronal cells of the deafferented dentate gyrus. Double immunofluorescence against APP and the microglia-binding isolectin B4 from Griffonia simplicifolia revealed that APP immunoreactivity was confined to activated microglia. The microglial APP expression became detectable 3 days after lesioning, reached its peak after 7 days and disappeared after 10 days. The early accumulation of APP in microglia supports the view that microglia play an important role in the initial stages of amyloid plaque formation. Such a glial APP accumulation occurs rapidly in distant but anatomically connected areas. This is in line with the preferential localization of amyloid plaques in the dentate gyrus, which is the projection field of the degenerating neurones of the entorhinal cortex in patients with developing dementia.
Three‐Dimensional Gastrointestinal Organoid Culture in Combination with Nerves or Fibroblasts: A Method to Characterize the Gastrointestinal Stem Cell Niche (2015)

The gastrointestinal epithelium is characterized by a high turnover of cells and intestinal stem cells predominantly reside at the bottom of crypts and their progeny serve to maintain normal intestinal homeostasis. Accumulating evidence demonstrates the pivotal role of a niche surrounding intestinal stem cells in crypts, which consists of cellular and soluble components and creates an environment constantly influencing the fate of stem cells. Here we describe different 3D culture systems to culture gastrointestinal epithelium that should enable us to study the stem cell niche in vitro in the future: organoid culture and multilayered systems such as organotypic cell culture and culture of intestinal tissue fragments ex vivo. These methods mimic the in vivo situation in vitro by creating 3D culture conditions that reflect the physiological situation of intestinal crypts. Modifications of the composition of the culture media as well as coculturing epithelial organoids with previously described cellular components such as myofibroblasts, collagen, and neurons show the impact of the methods applied to investigate niche interactions in vitro. We further present a novel method to isolate labeled nerves from the enteric nervous system using Dclk1-CreGFP mice.
Efficient transaction processing in SAP HANA database (2012)

The SAP HANA database is the core of SAP's new data management platform. The overall goal of the SAP HANA database is to provide a generic but powerful system for different query scenarios, both transactional and analytical, on the same data representation within a highly scalable execution environment. Within this paper, we highlight the main features that differentiate the SAP HANA database from classical relational database engines. Therefore, we outline the general architecture and design criteria of the SAP HANA in a first step. In a second step, we challenge the common belief that column store data structures are only superior in analytical workloads and not well suited for transactional workloads. We outline the concept of record life cycle management to use different storage formats for the different stages of a record. We not only discuss the general concept but also dive into some of the details of how to efficiently propagate records through their life cycle and moving database entries from write-optimized to read-optimized storage formats. In summary, the paper aims at illustrating how the SAP HANA database is able to efficiently work in analytical as well as transactional workload environments.
Prenatal Blockage of Lymphotoxin β Receptor and TNF Receptor p55 Signaling Cascade Resulted in the Acceleration of Tissue Genesis for Isolated Lymphoid Follicles in the Large Intestine (2005)

Signaling by lymphotoxin (LT) and TNF is essential for the organogenesis of secondary lymphoid tissues in systemic and mucosal compartments. In this study, we demonstrated that the progeny of mice treated with fusion protein of LTbetaR and IgGFc (LTbetaR-Ig) or LTbetaR-Ig plus TNFR55-Ig (double Ig) showed significantly increased numbers of isolated lymphoid follicles (ILF) in the large intestine. Interestingly, double Ig treatment accelerated the maturation of large intestinal ILF. Three-week-old progeny of double Ig-treated mice showed increased numbers of ILF in the large intestine, but not in the small intestine. Furthermore, alteration of intestinal microflora by feeding of antibiotic water did not affect the increased numbers of ILF in the large intestine of double Ig-treated mice. Most interestingly, mice that developed numerous ILF also had increased levels of activation-induced cytidine deaminase expression and numbers of IgA-expressing cells in the lamina propria of the large intestine. Taken together, these results suggest that ILF formation in the large intestine is accelerated by blockage of LTbetaR and TNFR55 signals in utero, and ILF, like colonic patches, might play a role in the induction of IgA response in the large intestine.
Endocrinology and Metabolism (1981)

Part I: General Endocrinology.Introduction to the Endocrine System.The Clinical Manifestations of Endocrine Disease.Gene Expression and Recombinant DNA in Endocrinology and Metabolism.Biosynthesis, Secretion, and Metabolism of Hormones.Molecular Mechanisms of Hormone Action: Control of Target Cell Function by Peptide, Steroid, and Thyroid Hormones.Hormone Assays.Part II: Neuroendocrinology and the Pituitary.Neuroendocrine Physiology and Disease.Diseases of the Anterior Pituitary.Posterior Pituitary.Part III: Thyroid Disease.The Thyroid: Physiology, Hyperthyroidism, Hypothyroidism, and the Painful Thyroid.The Thyroid: Nodules and Neoplasia.Part IV: Adrenal Disease.The Adrenal Cortex.Diseases of the Sympathochromaffin System.The Endocrinology of Hypertension.Glucocorticoid Therapy.Part V: Gonadal Disease.The Testis.The Ovary: Basic Principles and Concepts.A: Physiology.B: Clinical.Sexual Differentiation.Part VI: Fuel Metabolism.The Endocrine Pancreas: Diabetes Mellitus.Hypoglycemia.The Obesities.Disorders of Lipid Metabolism.Part VII: Calcium and Bone Metabolism.Mineral Metabolism.Metabolic Bone Disease.Nephrolithiasis.Part VIII: Miscellaneous Disorders.Disorders of Growth and Development.Gastrointestinal Hormones and Carcinoid Tumors and Syndrome.Multiglandular Endocrine Disorders.Ectopic Hormone Production.Hormone-Responsive Tumors.Prostaglandins, Kallikreins and Kinins, and Bartter's Syndrome.Endocrinology of Aging.Endocrinology of Behaviour and Psychiatric Disorders.Hormones and Athletic Performance.