gebhart/patrepeval huggingface dataset:
Function and regulation of transferrin and ferritin. (1998)

Iron represents a paradox for living systems by being essential for a wide variety of metabolic processes (oxygen transport, electron transport, DNA synthesis, etc) but also having the potential to cause deleterious effects. Because of Iron's virtual insolubility and potential toxicity under physiological conditions, specialized molecules for the acquisition, transport, and storage of iron in a soluble, nontoxic form have evolved to meet cellular and organismal iron requirements. Physiologically, the majority of cells in the organism acquire iron from a well-characterized plasma glycoprotein, transferrin. Iron uptake from transferrin is reasonably well understood, and involves the binding of transferrin to the transferrin receptor, internalization of transferrin within an endocytic vesicle by receptor-mediated endocytosis, and the release of iron from the protein by a decrease in endosomal pH. Most of the transferrin-bound iron is used for the synthesis of hemoglobin by developing erythroid cells. Senescent erythrocytes are internalized by the macrophages that liberate hemoglobin iron and release it back to plasma transferrin at a rate that normally matches the rate of iron transport for erythropoiesis. Unfortunately, the mechanisms and controls involved in the release of iron from macrophages have not been defined. After iron release from transferrin within endosomes, iron passes through the endosomal membrane by ill-understood mechanisms and then enters the poorly characterized intracellular labile pool. Iron in the labile pool that exceeds requirement for the synthesis of functional heme and nonheme iron-containing proteins is stored within the iron-storage protein, ferritin. Evidence in vitro indicates that relatively soluble ferrous iron can enter or be released from ferritin. However, we know virtually nothing about the exchange of iron with ferritin in intact cells, and some evidence indicates that the degradation of the ferritin protein may be an important mechanism for the release of iron within the cell. Cellular iron uptake and storage are coordinately regulated through a feedback control mechanism mediated at the post-transcriptional level by cytoplasmic factors know as iron-regulatory proteins 1 and 2. These proteins "sense" levels of iron in the transit pool and, when iron in this pool is scarce, they bind to stem-loop structures known as iron-responsive elements on the 5' untranslated region of the ferritin mRNA and 3' untranslated region of the transferrin mRNA. Such a binding inhibits translation of ferritin mRNA and stabilizes the mRNA for transferrin receptors. The opposite scenario develops when iron in the transit pool is plentiful. This remarkable regulatory mechanism prevents the expansion of a catalytically active intracellular iron pool, while maintaining sufficient concentrations of the metal for metabolic needs.
In vitro assembly of infectious virions of double-stranded DNA phage phi 29 from cloned gene products and synthetic nucleic acids (1995)

Up to 6 x 10(7) PFU of infectious virions of the double-stranded DNA bacteriophage phi 29 per ml were assembled in vitro, with 11 proteins derived from cloned genes and nucleic acids synthesized separately. The genomic DNA-gp3 protein conjugate was efficiently packaged into a purified recombinant procapsid with the aid of a small viral RNA (pRNA) transcript, a DNA-packaging ATPase (gp16), and ATP. The DNA-filled capsids were subsequently converted into infectious virions after the addition of four more recombinant proteins for neck and tail assembly. Electron microscopy and genome restriction mapping confirmed the identity of the infectious phi 29 virions synthesized in this system. A nonstructural protein, gp13, was indispensable for the assembly of infectious virions. The overproduced tail protein gp9 was present in solution in mostly dimeric form and was purified to homogeneity. The purified gp9 was biologically active for in vitro phi 29 assembly. Higher-order concentration dependence of in vitro phi 29 assembly on gp9 suggests that a complete tail did not form before attaching to the DNA-filled capsid, a result contrary to earlier findings for phages T4 and lambda. The work described here constitutes an extremely sensitive assay system for the analysis of components in phi 29 assembly and dissection of functional domains of structural components, enzymes, and pRNA (C.-S. Lee and P. Guo, Virology 202:1039-1042, 1995). Efficient packaging of foreign DNA in vitro and synthesis of viral particles from recombinant proteins facilitate the development of phi 29 as an in vivo gene delivery system. The finding that purified tail protein was able to incorporate into infectious virions might allow the construction of chimeric phi 29 carrying a tail fused to ligands for specific receptor of human cells.
Mechanical behavior of tantalum and tantalum-tungsten alloys: texture gradients and macro/micro-response (1996)

We have examined the mechanical response of unalloyed Ta and Ta-W alloy annealed plates over a wide range of loadings. It was observed in general that Ta exhibits nonuniform mechanical behavior, for example, hourglassing of compression samples and multiple instabilities during tensile deformation. In contrast, the Ta-W alloys do not exhibit any unusual nonuniform behavior. This work presents data revealing the spatial distribution of texture in Ta and Ta-W alloys. Significant variations in texture both through the thickness and from one area of the plate to another were found to be characteristic of Ta. The dominant feature of the texture variations was found to be enhanced <111> crystal direction fractions at the center of the plate, with a decreasing fraction near the surface. We find that the variation in texture in the Ta-W alloys is substantially less than that seen in Ta with primarily a <100> cube texture throughout. This study suggest that the texture gradients are responsible for the nonuniform mechanical response of Ta and that the uniform behavior of the Ta-W alloys is a consequence of the absence of texture gradients.
DNA‐replication Fidelity, Mismatch Repair and Genome Instability in Cancer Cells (1996)

It has been suggested that an early event in the multistep progression of a normal cell to a tumor cell could be a defect that leads to an elevated mutation rate, thus providing a pool of mutants upon which selection could act to yield a tumor. Such a mutator phenotype could result from a defect in any of several DNA transactions, including those that determine the DNA replication error rate or the ability to correct replication errors. Recent evidence for the latter is the mutator phenotype observed in tumor cells of patients having a hereditary form of colon cancer. These patients have a germline mutation in genes required for post-replication DNA mismatch repair. A second mutation arises somatically, yielding a greatly elevated mutation rate due to an inability to correct DNA replication errors. This connection between cancer, DNA replication errors and defective mismatch repair is the subject of this review, wherein we consider the key steps and principles for high fidelity replication and how their perturbation results in genome instability.
Ezrin Promotes Morphogenesis of Apical Microvilli and Basal Infoldings in Retinal Pigment Epithelium (1999)

Ezrin, a member of the ezrin/radixin/moesin (ERM) family, localizes to microvilli of epithelia in vivo, where it bridges actin filaments and plasma membrane proteins. Here, we demonstrate two specific morphogenetic roles of ezrin in the retinal pigment epithelium (RPE), i.e., the formation of very long apical microvilli and of elaborate basal infoldings typical of these cells, and characterize the role of ezrin in these processes using antisense and transfection approaches. In the adult rat RPE, only ezrin (no moesin or radixin) was detected at high levels by immunofluorescence and immunoelectron microscopy at microvilli and basal infoldings. At the time when these morphological differentiations develop, in the first two weeks after birth, ezrin levels increased fourfold to adult levels. Addition of ezrin antisense oligonucleotides to primary cultures of rat RPE drastically decreased both apical microvilli and basal infoldings. Transfection of ezrin cDNA into the RPE-J cell line, which has only trace amounts of ezrin and moesin, sparse and stubby apical microvilli, and no basal infoldings, induced maturation of microvilli and the formation of basal infoldings without changing moesin expression levels. Taken together, the results indicate that ezrin is a major determinant in the maturation of surface differentiations of RPE independently of other ERM family members.
Multiview Imaging and 3DTV (2007)

The eight articles in this special section are devoted to multi-view imaging and three dimensional television displays.
Space-time codes for wireless communication: code construction (2002)

We consider the design of channel codes for improving the data rate and/or the reliability of communications over fading channels using multiple transmit antennas. Here, data is encoded by a channel code and the encoded data is split into n streams that are simultaneously transmitted using n transmit antennas. The received signal at each receive antenna is a linear superposition of the n transmitted signals. We review the performance criteria for designing such codes under the assumption that the fading is slow and frequency non-selective established in Tarokh et al. Performance is determined by diversity gain quantified by ranks and coding gain quantified by determinants of certain matrices that are constructed from the code sequences. The performance criterion is then used to design trellis codes for high data rate wireless communication. These codes are easy to encode and decode. They provide the best trade-off between data rate, diversity gain, constellation size and trellis complexity. Simulation results are provided for 4 and 8 PSK signal sets with data rates of 2 and 3 bits/symbol, demonstrating excellent performance that is within 2-3 dB of the outage capacity for these channels.
Christopher Foote's Discovery of the Role of Singlet Oxygen [1O2 (1Δg)] in Photosensitized Oxidation Reactions (2006)

The chemistry of singlet molecular oxygen [1O2 (1Delta g)], its importance in atmospheric, biological, and therapeutic processes, and its use as a reagent in organic synthesis have been of considerable interest. Many aspects of singlet oxygen chemistry have emanated from the work of Christopher S. Foote and co-workers. Singlet oxygen is a historically interesting molecule with an unusual story connected with its discovery. Foote and Wexler conducted experiments in the 1960s where evidence was obtained supporting 1O2 generation via two independent routes: (1) a photochemical reaction (dye-sensitized photooxidation) and (2) a chemical reaction (NaOCl with H2O2). An important factor in the discovery of 1O2 as the critical reaction intermediate in dye-sensitized photooxygenations was Foote's reassessment of the chemical literature of the 1930s, when 1O2 was suggested to be a viable intermediate in dye-sensitized photooxidation reactions. Experiments that used silica gel beads provided evidence for a volatile diffusible oxidant such as 1O2. However, a contemporaneous quarrel surrounded this early work, and the possible existence of solution-phase 1O2 was ignored for over 2 decades. Not long after Foote's initial studies were published in 1964, the idea of singlet oxygen as an intermediate in photooxidation chemistry gained increasing recognition and verification in organic, gas phase, and biological processes. There are many documented impacts that 1O2 has had and continues to have on biology and medicine, for example, photodynamic therapy and plant defenses.
Analytical and Clinical Evaluation of Two Homogeneous Assays for LDL-Cholesterol in Hyperlipidemic Patients (2000)

Abstract Background: LDL-cholesterol (LDL-C) concentrations are the primary basis for treatment guidelines established for hyperlipidemic patients. LDL-C concentrations are commonly monitored by means of the Friedewald formula, which provides a relative estimation of LDL-C concentration when the triglyceride concentration is &amp;lt;2000 mg/L and there are no abnormal lipids. The Friedewald formula has several limitations and may not meet the current total error requirement of &amp;lt;12% in LDL-C measurements. Methods: We evaluated the analytical and clinical performance of two direct methods (Roche and Wako) by analyzing 313 fresh serum samples obtained from dyslipidemic patients in a lipid clinic and comparing them with modified β-quantification. Results: Both homogeneous assays displayed excellent precision (CV &amp;lt;2%). The Roche method showed a mean total error of 7.72%, and the Wako method showed a mean total error of 4.46% over a wide range of LDL-C concentrations. The Roche method correlated highly with the modified β-quantification assay (r = 0.929; y = 1.052x − 168 mg/L; n = 166) and showed a bias of −4.5% as a result of the assigned standard value. The Wako method also correlated highly with β-quantification (r = 0.966; y = 0.9125x + 104.8 mg/L; n = 145) without significant bias. The Roche method correctly classified 97% of patients with triglycerides &amp;lt;2000 mg/L, 75% of patients with type IIb hyperlipemia (HPL), and 84% of patients with type IV HPL based on the cutpoints of 1300 and 1600 mg/L, compared with 98%, 78.4%, and 89%, respectively, for the Wako method. In dysbetalipoproteinemic patients, both methods have a 30% mean positive bias compared with β-quantification. Conclusions: Both direct methods can be a useful alternative when ultracentrifugation is not available for the diagnosis and control of lipid-lowering medication for patients with mixed HPL, but not for patients with type III hyperlipidemia.
Liraglutide, a Long-Acting Human Glucagon-Like Peptide-1 Analog, Given as Monotherapy Significantly Improves Glycemic Control and Lowers Body Weight Without Risk of Hypoglycemia in Patients With Type 2 Diabetes (2007)

iraglutide is a long-acting human glucagon-like peptide-1 (GLP-1) analog (1-4), and the current study was undertaken to evaluate efficacy and safety after 14 weeks' treatment with liraglutide in patients with type 2 diabetes.
Corrigendum to: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. (2021)

ESC Guidelines for the diagnosis and
The effect of femoral stem geometry on interface motion in uncemented porous-coated total hip prostheses. Comparison of straight-stem and curved-stem designs. (1992)

We compared the magnitudes of motion between the prosthesis and bone during axial and torsional loading in seven matched pairs of fresh-frozen femora of cadavera in which an uncemented, collarless, isthmus-filling, straight-stem (Harris-Galante) prosthesis had been placed in one femur and an uncemented, collarless, proximal-filling, curved-stem (anatomic) prosthesis had been placed in the other femur. The comparison was performed in order to determine the effect of the geometry of the stem on the magnitude of motion. Single-limb-stance loads and combined axial and torsional loads were applied to the implanted femoral prostheses with the use of a jig that simulated acetabular and trochanteric loading. Extensometers were used to measure motion at the prosthesis-bone interface. The prostheses were then removed and were reinserted, with cement applied to the proximal porous coating to simulate ingrowth of bone. The single-limb-stance and combined axial and torsional loads were reapplied and the magnitude of motion was recorded again. No significant differences in the magnitudes of the motion were found between the femora in which the straight stem had been implanted and the femora in which the curved stem had been implanted, during either simulated single-limb-stance or low-intensity torsional loading. When large torsional moments (twenty-two newton-meters) were applied, significantly less motion occurred at the bone-prosthesis interface, both proximally (p = 0.019) and distally (p = 0.0013), in the femora with the curved-stem implant than in the femora with the straight-stem implant. When cement had been applied proximally, proximal and distal motion between the prosthesis and the femur was decreased during simulated single-limb-stance and during torsional loading in the femora with the straight stem and the femora with the curved stem.
Reduced BACE1 Activity Enhances Clearance of Myelin Debris and Regeneration of Axons in the Injured Peripheral Nervous System (2011)

β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is an aspartyl protease best known for its role in generating the amyloid-β peptides that are present in plaques of Alzheimer's disease. BACE1 has been an attractive target for drug development. In cultured embryonic neurons, BACE1-cleaved N-terminal APP is further processed to generate a fragment that can trigger axonal degeneration, suggesting a vital role for BACE1 in axonal health. In addition, BACE1 cleaves neuregulin 1 type III, a protein critical for myelination of peripheral axons by Schwann cells during development. Here, we asked whether axonal degeneration or axonal regeneration in adult nerves might be affected by inhibition or elimination of BACE1. We report that BACE1 knock-out and wild-type nerves degenerated at a similar rate after axotomy and to a similar extent in the experimental neuropathies produced by administration of paclitaxel and acrylamide. These data indicate N-APP is not the sole culprit in axonal degeneration in adult nerves. Unexpectedly, however, we observed that BACE1 knock-out mice had markedly enhanced clearance of axonal and myelin debris from degenerated fibers, accelerated axonal regeneration, and earlier reinnervation of neuromuscular junctions, compared with littermate controls. These observations were reproduced in part by pharmacological inhibition of BACE1. These data suggest BACE1 inhibition as a therapeutic approach to accelerate regeneration and recovery after peripheral nerve damage.
A High-Quality-Factor Film Bulk Acoustic Resonator in Liquid for Biosensing Applications (2010)

We report a high-quality-factor ( <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</i> ) film bulk acoustic resonator (FBAR) operating in liquid environments. By integrating a microfluidic channel to a longitudinal-mode FBAR, a <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</i> of up to 150 is achieved with direct liquid contacting. A transmission line model is used to theoretically predict the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</i> behavior of the FBAR. The model suggests an oscillatory pattern of <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</i> as a function of the channel thickness and the acoustic wavelength in the liquid, which is experimentally verified by precisely controlling the channel thickness. This FBAR biosensor is characterized in liquids for the real-time in situ monitoring of the competitive adsorption/exchange of proteins, the Vroman effect. The FBAR offers a minimum detectable mass of 1.35 ng/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and is successfully implemented in a Pierce oscillator as a portable sensing module.
Bone morphogenetic protein‐2 promotes osteosarcoma growth by promoting epithelial‐mesenchymal transition (EMT) through the Wnt/β‐catenin signaling pathway (2019)

The correlation between BMP-2 and osteosarcoma growth has gained increased interest in the recent years, however, there is still no consensus. In this study, we tested the effects of BMP-2 on osteosarcoma cells through both in vitro and in vivo experiments. The effect of BMP-2 on the proliferation, migration and invasion of osteosarcoma cells was tested in vitro. Subcutaneous and intratibial tumor models were used for the in vivo experiments in nude mice. The effects of BMP-2 on EMT of osteosarcoma cells and the Wnt/β-catenin signaling pathway were also tested using a variety of biochemical methods. In vitro tests did not show a significant effect of BMP-2 on tumor cell proliferation. However, BMP-2 increased the mobility of tumor cells and the invasion assay demonstrated that BMP-2 promoted invasion of osteosarcoma cells in vitro. In vivo animal study showed that BMP-2 dramatically enhanced tumor growth. We also found that BMP-2 induced EMT of osteosarcoma cells. The expression levels of Axin2 and Dkk-1 were both down regulated by BMP-2 treatment, while β-catenin, c-myc and Cyclin-D1 were all upregulated. The expression of Wnt3α and p-GSK-3β were also significantly upregulated indicating that the Wnt/β-catenin signaling pathway was activated during the EMT of osteosarcoma driven by BMP-2. From this study, we can conclude that BMP-2 significantly promotes growth of osteosarcoma cells (143B, MG63), and enhances mobility and invasiveness of tumor cells as demonstrated in vitro. The underlying mechanism might be that BMP-2 promotes EMT of osteosarcoma through the Wnt/β-catenin signaling pathway. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1638-1648, 2019.
Enteric Coated Mycophenolate Sodium is Therapeutically Equivalent to Mycophenolate Mofetil in de novoRenal Transplant Patients (2004)

The introduction of mycophenolate mofetil (MMF) represented a major advance in transplant medicine, although optimal use may be limited by gastrointestinal (GI) side-effects. An enteric-coated formulation of mycophenolate sodium (EC-MPS; myfortic) has been developed with the aim of improving the upper GI tolerability of mycophenolic acid. Therapeutic equivalence of EC-MPS (720 mg b.i.d.) and MMF (1000 mg MMF b.i.d.), with concomitant cyclosporine microemulsion (Neoral) and corticosteroids, was assessed in 423 de novo kidney transplant patients recruited to a 12-month, double-blind study. Efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, death or loss to follow up) at 6 months (EC-MPS 25.8% vs. MMF 26.2%; 95% CI: [-8.7, +8.0]) demonstrated therapeutic equivalence. At 12 months, the incidence of BPAR, graft loss or death was 26.3% and 28.1%, and of BPAR alone was 22.5% and 24.3% for EC-MPS and MMF, respectively. Among those with BPAR, the incidence of severe acute rejection was 2.1% with EC-MPS and 9.8% with MMF (p=ns). The safety profile and incidence of GI adverse events were similar for both groups. Within 12 months, 15.0% of EC-MPS patients and 19.5% of MMF patients required dose changes for GI adverse events (p=ns). Enteric-coated-MPS 720 mg b.i.d. is therapeutically equivalent to MMF 1000 mg b.i.d. with a comparable safety profile.
Gene Therapy for Adenosine Deaminase Deficiency (2000)

The clinical gene therapy trials for adenosine deaminase (ADA) deficiency have defined both the potential benefits and the present limitations of gene therapy with hematopoietic stem cells (HSC). Current clinical results indicate that (a) both umbilical cord blood and neonatal bone marrow HSC can be transduced with murine retroviral-based vectors, (b) the transduced HSC can engraft in nonmyeloablated patients, (c) the frequency of HSC transduction/engraftment is low (1/10,000), (d) an in vivo selective advantage can exist for transduced T lymphoid progeny, and (e) the transduced ADA gene is not expressed in nondividing T lymphocytes. Improving the clinical results of gene therapy for ADA deficiency and other genetic diseases involving HSC will require (a) developing new vectors that express the transduced gene in nondividing cells and (b) increasing the frequency of stable HSC transduction.