gebhart/patrepeval huggingface dataset:
LGR5 promotes the proliferation and tumor formation of cervical cancer cells through the Wnt/β-catenin signaling pathway (2014)

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a seven transmembrane receptor known as a potential stem cell marker for intestinal crypts and hair follicles, has recently been found to be overexpressed in some types of human cancers. However, the role of LGR5 in cervical cancer remains unclear. In this study, the expression of LGR5 gradually increases from normal cervix to cervical cancer in situ and to cervical cancers as revealed by immunohistochemistry and western blot analyses. Through knocking down or overexpressing LGR5 in SiHa and HeLa cells, the expression level of LGR5 was found to be positively related to cell proliferation in vitro and to tumor formation in vivo. Further investigation indicated that LGR5 protein could significantly promote the acceleration of cell cycle. Moreover, the TOP-Flash reporter assay and western blot for β-catenin, cyclinD1, and c-myc proteins, target genes of the Wnt/β-catenin pathway, indicated that LGR5 significantly activated Wnt/β-catenin signaling. Additionally, the blockage of Wnt/β-catenin pathway resulted in a significant inhibition of cell proliferation induced by LGR5. Taken together, these results demonstrate that LGR5 can promote proliferation and tumor formation in cervical cancer cells by activating the Wnt/β-catenin pathway.
Self-assembly and characterization of Pluronic P105 micelles for liver-targeted delivery of silybin (2009)

Polymeric micelles, based on lactobionic acid (LA)-conjugated Pluronic P105 (P105), were prepared to achieve liver-targeted delivery of silybin. In the triblock copolymer structure of PEO-PPO-PEO, LA was successfully conjugated with the terminal end of PEO to produce LA-P105. The success of synthesis was confirmed using FTIR and 1H NMR. The triblock copolymers with functional moiety were physically mixed with silybin to form micelles. Silybin-loaded LA-P105 micelles characterized by dynamic light scattering and transmission electron microscopy (TEM) were uniform spherical particles. There was a remarkable increase in the dissolubility for silybin in LA-P105 micelle solution (627 microg/mL) when compared with that for water (4.6 microg/mL). The pharmacokinetic experiments showed that the area under the curve of silybin plasma concentration-time profile in rats for LA-P105 micelles was lower than that for P105 micelles. Biodistribution studies indicated that a significantly increased amount of silybin was accumulated in liver, suggesting that LA locating on the surface of the micelles played an important role in transporting an increased amount of silybin into liver. This polymeric vehicle is, therefore, expected to be widely used as target-specific delivery vehicles for diverse water-insoluble therapeutic and diagnostic agents.
The Interaction Between Vision and Eye Movements (2016)

The existence of a central fovea, the small retinal region with high analytical performance, is arguably the most prominent design feature of the primate visual system. This centralization comes along with the corresponding capability to move the eyes to reposition the fovea continuously. Past research on visual perception was mainly concerned with foveal vision while the observers kept their eyes stationary. Research on the role of eye movements in visual perception emphasized their negative aspects, for example, the active suppression of vision before and during the execution of saccades. But is the only benefit of our precise eye movement system to provide high acuity of the small foveal region, at the cost of retinal blur during their execution? In this review, I will compare human visual perception with and without saccadic and smooth pursuit eye movements to emphasize different aspects and functions of eye movements. I will show that the interaction between eye movements and visual perception is optimized for the active sampling of information across the visual field and for the calibration of different parts of the visual field. The movements of our eyes and visual information uptake are intricately intertwined. The two processes interact to enable an optimal perception of the world, one that we cannot fully grasp by doing experiments where observers are fixating a small spot on a display.
Mission critical: the need for proteomics in the era of next-generation sequencing and precision medicine (2016)

Next generation sequencing (NGS) has ignited an unprecedented pace of discovery in the biomedical sciences that is fundamentally transforming the way that we understand, diagnose and treat disease, and has motivated the belief that true precision medicine - medicine that is tailored to an individual's genetic, biochemical and exposure profile - will be a reality in the near term. With minimal sample requirement, NGS can enable the concurrent genome-wide study of genetic variations, transcriptomes, and certain epigenetic modifications. However, interrogating proteins as efficiently as DNA and RNA can be interrogated with NGS is lacking and this hampers more comprehensive views of molecular physiology and limits advances in biomedical science and precision medicine. The fact is that innovations in proteomic technologies pale in comparison to the advances in NGS, with current methodologies suffering from issues related to reproducibility, sensitivity, sample requirements, and limited multiplexing capacity. The development of proteomic technologies to overcome these limitations would fill the void in systems biology research, catalyze clinical innovations, and expedite the realization of precision medicine.
Qualitative and Quantitative Analysis of Cardiac Progenitor Cells in Cases of Myocarditis and Cardiomyopathy (2018)

We aimed to identify and quantify CD117<sup>+</sup> and CD90<sup>+</sup> endogenous cardiac progenitor cells (CPC) in human healthy and diseased hearts. We hypothesize that these cells perform a locally acting, contributing function in overcoming medical conditions of the heart by endogenous means. Human myocardium biopsies were obtained from 23 patients with the following diagnoses: Dilatative cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), myocarditis, and controls from healthy cardiac patients. High-resolution scanning microscopy of the whole slide enabled a computer-based immunohistochemical quantification of CD117 and CD90. Those signals were evaluated by Definiens Tissue Phenomics® Technology. Co-localization of CD117 and CD90 was determined by analyzing comparable serial sections. CD117<sup>+</sup>/CD90<sup>+</sup> cardiac cells were detected in all biopsies. The highest expression of CD90 was revealed in the myocarditis group. CD117 was significantly higher in all patient groups, compared to healthy specimens (<sup>*</sup><i>p</i> < 0.05). The highest co-expression was found in the myocarditis group (6.75 ± 3.25 CD90<sup>+</sup>CD117<sup>+</sup> cells/mm<sup>2</sup>) followed by ICM (4 ± 1.89 cells/mm<sup>2</sup>), DCM (1.67 ± 0.58 cells/mm<sup>2</sup>), and healthy specimens (1 ± 0.43 cells/mm<sup>2</sup>). We conclude that the human heart comprises a fraction of local CD117<sup>+</sup> and CD90<sup>+</sup> cells. We hypothesize that these cells are part of local endogenous progenitor cells due to the co-expression of CD90 and CD117. With novel digital image analysis technologies, a quantification of the CD117 and CD90 signals is available. Our experiments reveal an increase of CD117 and CD90 in patients with myocarditis.
An electron microscope autoradiographic study of the carbohydrate recognition systems in rat liver. II. Intracellular fates of the 125I-ligands. (1979)

Electron microscope autoradiographic and biochemical methods were used to study the intracellular fates of several 125I-glycoproteins, known to be specifically bound and internalized by the different cell types in the liver. At the earliest times examined (1--2 min), 125I-glycoproteins (ASGP) were localized predominantly along the sinusoidal front of hepatocytes. Analysis of the distribution of autoradiographic grains indicated that: (a) approximately 40--60% of the 125I-ligand could be ascribed to the plasmalemma; (b) a significant fraction had already been internalized; yet (c) very little 125I-ligand was present in the lysosome-Golgi region. Between 4 and 15 min after administration of 125I-ASGPs, there was a dramatic redistribution of autoradiographic grains from regions of the plasmalemma and peripheral cytoplasm (30% decrease) to the lysosome-Golgi region (30% increase). At longer times (30 min), there was continued drainage of 125I-ASGP into this region. The grain density over secondary lysosomes was 60--90 times higher than that over recognizable Golgi elements, clearly indicating that lysosomes were the ultimate destination of the 125I-ASGP. However, no more than 60% of the total 125I-ligand could be localized to lysosome-rich regions of the hepatocyte, with the remaining 40% primarily in the intermediate cytoplasm. Biochemical evidence for proteolysis of the internalized 125I-ASGP (presumably within lysosomes) was obtained when [125I]-mono-iodotyrosine was found in the liver (i.e., hepatocytes) at times later than 15 min. The temporal redistribution observed for mannose and N-acetylglucosamine-terminated glycoproteins (ahexosamino-orosomucoid and agalacto-orosomucoid, respectively) in endothelial cells indicated that the 125I-ligands resided in macropinocytic vesicles (1--15 min) before their ultimate residence in dense bodies (15 min). The same 125I-ligands were also localized to structures resembling secondary lysosomes in Kupffer cells. The lysosomal nature of "these organelles" was implied from the appearance of [125I]mono-iodotyrosine in the liver at later times. 125I-beta-glucuronidase followed the same intracellular pathway in both cell types but was not degraded.
Combining Magnetic Hyperthermia and Photodynamic Therapy for Tumor Ablation with Photoresponsive Magnetic Liposomes (2015)

The ongoing nanotech revolution has the potential to transform diagnostic and therapeutic methods. Stimuli-triggered nanotherapies based on remotely activated agents have become attractive alternatives to conventional chemotherapy. Herein, we designed an optimized smart nanoplatform based on dually loaded hybrid liposomes to achieve enhanced tumor therapy. The aqueous core was highly loaded with iron oxide nanoparticles, while the lipid bilayer was supplied with a photosensitizer payload. The double cargo translated into double functionality: generation of singlet oxygen under laser excitation and heat production under alternating magnetic field stimulation, coupling photodynamic therapy (PDT) to magnetic hyperthermia (MHT). These liposomes address both therapeutic agents within tumor cells, and the combined PDT/MHT therapy resulted in complete cancer cell death in vitro while total solid-tumor ablation was achieved in an in vivo rodent model.
Blockade of superoxide generation prevents high‐affinity immunoglobulin E receptor‐mediated release of allergic mediators by rat mast cell line and human basophils (2002)

These results indicate that both RBL-2H3 cells and human basophils generate superoxide anion upon FcepsilonRI cross-linking either by antibody or by allergen challenge and that blockade of the generation prevents the release of allergic mediators. The findings strongly support the role of superoxide generation in the activation of mast cells and basophils under both physiological and pathological conditions. The findings suggest that drugs regulating the superoxide generation have potential therapeutic use for allergic disorders.
Renal Dopamine Receptors (1988)

DA, like most neurotransmitters, exerts its biological effects by occupation of specific receptors (Kebabian et al., 1986). Different DA receptor subtypes have been described in renal vascular and tubular structures of several species (Goldberg and Kohli, 1978; Brodde, 1982; Felder and Carey, 1987). This chapter will present the physiological, pharmacological and biochemical evidence supporting the concept of multiple DA receptor subtypes in the kidney.
Serum interleukin-6, tumor necrosis factor alpha and C-reactive protein in early prediction of severity of acute pancreatitis. (2004)

The serum concentration of IL-6 on the first day and/or the serum concentration of CRP on the 2nd day of admission are useful for early prediction of the severity of acute pancreatitis.
Optimum flight trajectory guidance based on total energy control of aircraft (1994)

The guidance technique for optimal vertical flight trajectory with a total energy control system (TECS) is discussed. The flight profile is optimized based on the point-mass energy state approximation model of aircraft with direct operating cost as its index function. The guidance law is developed with the total energy control concept used in TECS. To improve the guidance precision, several methods are adopted in the optimization and tracking process, and two preprocessing algorithms, the lead-compensation algorithm and the smooth filtering algorithm, are developed for the ideal optimal trajectory. Satisfactory digital simulation results for a Boeing-707 transport model are finally obtained.
New Applications (1975)

A range of new developments and studies in magnetic bubble technology was discussed by IBM scientists at the 20th Annual Conference on Magnetism and Magnetic Materials, held Dec. 3-6 in San Francisco, California. The conference was sponsored by the American Institute of Physics and the Magnetics Society of IEEE.
Hardwood Lignin Recovery Using Generator Waste Acid. Statistical Analysis and Simulation (2000)

A method to recover hardwood kraft lignin by acidification of black liquor using waste acid from a Mathieson chlorine dioxide generator is proposed. Optimum reaction conditions to maximize the lignin yield and minimize acidification costs were determined. To analyze the effects of the major variables, a 23 factorial model describing the effects of acidification temperature, degree of agitation, and rate of waste acid addition was developed. Increasing the acidification temperature improved the lignin precipitation and filterability. However, the maximum practical temperature was 70 °C because the lignin precipitate starts to form a tarlike substance at approximately 80 °C. Also, the rate of acid addition should be minimized. In practice, this will be determined by the mill reaction vessel size, which depends on the black liquor flow rate to be acidified. Last, the stirring rate should be kept as low as possible, although some agitation is still required to uniformly mix the acid and black liquor. A steady-state computer simulation of incorporating a proposed 21 ton/day hardwood lignin recovery plant to the kraft liquor cycle showed no adverse effects in the chemical balance of the mill.
Health-Care Communication and Selected Psychosocial Correlates of Adherence in Diabetes Management (1990)

Meeting the needs of older adults with diabetes mellitus requires understanding the multiple factors that interact to influence patient adherence to the prescribed regimen and adjustment to the disease. Herein, we propose a conceptual framework to explain patient adherence and to discuss practical strategies for enhancing adherence. The conceptual framework is based on the cycle of care and is expanded to incorporate major theories in health-behavior change. Based on this review, numerous factors were identified that can affect patient adherence. First, features of the regimen, such as complexity, duration, and extent of behavioral change, can negatively influence patient adherence. Second, psychosocial and environmental barriers to patient adherence are described. A major area of importance is patient-provider relationships. Specifically, patients' and professionals' attitudes, beliefs, communication processes, and subsequent reactions to the consultation can affect adherence. Suggestions are made regarding strategies to enhance adherence, including the need to assess and monitor the patient's beliefs and practices, enhance the communicative skills of health-care professionals and patients, and develop programs specifically targeted at promoting professional and patient problem-solving skills. The problem of generalizing from current research is that few empirical studies have focused on diabetes management among older adults.
A phase II trial of perifosine in patients with advanced renal cell carcinoma (RCC) who have failed tyrosine kinase inhibitors (TKI) (2009)

5101 Background: The recently demonstrated activity of inhibitors of TORC1 in RCC has raised the possibility that even greater effects may be achieved by targeting upstream of this pathway. Perifosine is a synthetic alkylphospholipid which inhibits Akt activity and also has cell-dependent effects upon the MAP-kinase pathway. Prior single-agent trials showed disease stabilization/regression in patients (pts) with advanced RCC; however, few pts were previously treated with a TKI. Therefore, we conducted a multi-center phase II trial to determine the safety and efficacy of perifosine in pts with advanced RCC refractory to VEGFR TKI. Methods: Primary objectives were to measure the % of pts progression-free at 12 weeks (wks) and overall progression-free survival (PFS) of perifosine (100 mg qhs). Secondary objectives included overall response rate (> PR), and safety, Eligibility: ECOG PS 0–1, pts with metastatic RCC who have RECIST defined progression on either sunitinib or sorafenib. Prior Rx with immunotherapy and bevacizumab was permitted. Normal organ and marrow function required. Results: From 4/07–10/08, 24 pts were treated at four sites. Median age 67 (range 47–78) and 16 were male; 90% of pts had predominantly clear cell histology. Prior sunitinib = 12; prior sorafenib = 12 (1.5 avg prior Rx). As of 12/08, all 24 pts were evaluable for PFS, response and toxicity as follows in the table . 6/24 pts remain on treatment (range 7 - 84 wks). Therapy was well tolerated with primarily Grade (G) 1 & 2 adverse events. G 3 & 4 events were: dyspnea (8%), hyponatremia (8%), pulmonary embolism (4%) and arthalgia (4%). Conclusions: Perifosine has promising activity in pts with RCC who have failed prior TKI therapy. The favorable toxicity profile suggests potential for combinational therapies with VEGF-targeted agents. Additional studies are under consideration to evaluate perifosine for clinical benefit in pts with previously treated RCC. [Table: see text] [Table: see text]
Simple, robust, and wide-range frequency offset monitor for automatic frequency control in digital coherent receivers (2007)

We demonstrate a simple, robust and +/-10 GHz range frequency offset monitor used for automatic local laser frequency control in optical digital coherent receiver. It can tolerate low OSNR, large distortion and unsynchronized clock. (2 pages)
Heterogeneity of insulin‐like growth factor binding proteins and relationships between structure and affinity (1987)

Circulating insulin-like growth factors (IGFs) are bound to specific, high-affinity binding proteins (BPs), and form complexes with relative molecular masses of about 150,000 ('large' complex) and 40,000 ('small' complex). The large complex appears to be under growth-hormone control and its proportions vary with those of the IGFs. Molecular heterogeneity among the binding proteins was revealed by polyacrylamide gel electrophoresis (SDS-PAGE) of serum in which they were cross-linked to 125I-labelled IGF I or II. Out of the six specific bands observed, of 150,000, 120,000, 49,000, 40,000 and 37,000 Mr, the last three appeared in both complexes, whereas the first three were visible only in the large complex. Some or all of the 49,000-37,000-Mr species may constitute the subunits of 150,000-Mr and/or 120,000-Mr IGF-BP complexes. With electrophoresis followed by transfer onto nitrocellulose and incubation with either 125I-labelled IGF I or II (western blot), the different binding proteins were identified per se. There were five molecular forms with Mr of 41,500, 38,500, 34,000, 30,000 and 24,000. In normal serum the 41,500 and 38,500-Mr forms were the major binding proteins. They appeared in both complexes, but were predominant in the large complex where they constitute the elementary binding units. These two proteins therefore bind to IGFs to form both 'monomeric' IGF-BP and 'oligomeric' (IGF-BP)n complexes. The 34,000, 30,000 and 24,000-Mr forms, by contrast, were visible only in the small complex. Different mechanisms appear to regulate the different binding proteins: in acromegalic serum the 41,500 and 38,500-Mr forms were augmented and the 34,000-Mr form diminished, whereas in hypopituitary serum the reverse was true and, in addition, the 30,000-Mr form was augmented. With chromatofocusing, the 34,000, 30,000 and 24,000-Mr forms eluted in three peaks between pH 6.0 and 4.0, whereas the 41,500 and 38,500-Mr forms eluted throughout the gradient, principally at pH 7.5 and 7.0. Competitive binding studies, done on binding proteins separated either by chromatofocusing or by SDS-PAGE and transfer onto nitrocellulose, revealed different affinities for the IGFs among the different molecular forms. The 41,500 and 24,000-Mr binding proteins preferentially bound IGF I and the 38,500, 34,000 and 30,000-Mr proteins preferentially bound IGF II. Our findings demonstrate the molecular heterogeneity of the binding proteins and the existence of a relationship between their structure and their affinities for the IGFs.(ABSTRACT TRUNCATED AT 400 WORDS)
A 3D Human Airway Model Enables Prediction of Respiratory Toxicity of Inhaled Drugs In Vitro (2017)

Respiratory tract toxicity represents a significant cause of attrition of inhaled drug candidates targeting respiratory diseases. One of the key issues to allow early detection of respiratory toxicities is the lack of reliable and predictive in vitro systems. Here, the relevance and value of a physiologically relevant 3D human airway in vitro model (MucilAir) were explored by repeated administration of a set of compounds with (n = 8) or without (n = 7) respiratory toxicity following inhalation in vivo. Predictability for respiratory toxicity was evaluated by readout of cytotoxicity, barrier integrity, viability, morphology, ciliary beating frequency, mucociliary clearance and cytokine release. Interestingly, the data show that in vivo toxicity can be predicted in vitro by studying cell barrier integrity by transepithelial electrical resistance (TEER), and cell viability determined by the Resazurin method. Both read-outs had 88% sensitivity and 100% specificity, respectively, while the former was more accurate with receiver operating characteristic (ROC) AUC of 0.98 (p = .0018) compared with ROC AUC of 0.90 (p = .0092). The loss of cell barrier integrity could mainly, but not fully, be attributed to a loss of cell coverage in 6 out of 7 compounds with reduced TEER. Notably, these effects occurred only at 400 µM, at concentration levels significantly above primary target cell potency, suggesting that greater attention to high local lung concentrations should be taken into account in safety assessment of inhaled drugs. Thus, prediction of respiratory toxicity in 3D human airway in vitro models may result in improved animal welfare and reduced attrition in inhaled drug discovery projects.
Q-switch rise time effect in flash-pumped solid state lasers (2010)

The effect of the rise time of the Pockels cell on the output laser pulse is investigated. The pump system in a flash pumped Nd:YAG laser with unstable resonator is numerically analyzed and simulated. The time dependent flash discharge current is calculated and the optical time-dependent variation of the flash pulse is deduced. The numerical simulation of the whole laser gives the solution of the system of four level Nd:YAG differential rate equations. The pump power is considered variable and dependent on the flash pump pulse shape and power. The Q-switch rise time is included in the rate equations as a variable time dependant loss parameter. The laser pulse shape and output characteristics are calculated. Numerical and some experimental results are presented and discussed.