gebhart/patrepeval huggingface dataset:
Mitogenicity and transforming activity of the insulin-like growth factor-I receptor with mutations in the tyrosine kinase domain. (1994)

We have investigated the effect of mutations in tyrosines 1131, 1135, and 1136 of the human insulin-like growth factor-I receptor (IGF-IR) on the growth and transformation of mammalian cells. We have used for this purpose R- cells, which are 3T3-like fibroblasts derived from mouse embryos with a targeted disruption of the IGF-IR genes. These cells have no IGF-IR, do not grow in serum-free medium supplemented with the growth factors that sustain the growth of 3T3 cells, and cannot be transformed by simian virus 40 large tumor antigen or other oncogenes. The R- cells were transfected with plasmids expressing: 1) a wild type human IGF-IR cDNA; 2) a receptor with a triple mutation in the above mentioned tyrosines; and 3) receptors with single tyrosine mutations. Cells expressing the wild type or the single tyrosine mutants Y1 (Y1131F) and Y2 (Y1135F) grew in serum-free medium supplemented solely with IGF-I. Cells expressing the triple tyrosine mutant YF or the single mutant Y3 (Y1136F) failed to grow in response to IGF-I only. All mutants, though, failed to form colonies in soft agar, indicating that a fully functional IGF-IR is more critical for anchorage-independent growth than for monolayer growth. The triple mutant expression plasmid also functioned as a dominant negative, inhibiting the growth of wild type cells transformed by the simian virus tumor antigen.
Recent progress on electroelastomer artificial muscles and their application for biomimetic robots (2004)

Electroelastomers (electroactive elastomers, a.k.a. dielectric elastomers) such as those based on acrylic elastomer films with compliant electrodes, when highly prestrained, exhibited up to 380% electromechanical strain in area expansion at 5 to 6 kV. By rolling highly prestrained acrylic films around a compression spring, multifunctional electroelastomer rolls (MERs, or spring rolls) were obtained that combined load bearing, actuation, and sensing functions. The design was extended to two-degree-of-freedom (2-DOF) and 3-DOF spring rolls by patterning the electrodes along the circumferential spans of the rolls. Multiple-DOF spring rolls retained the linear actuation of 1-DOF spring rolls with additional bending actuation. New electroelastomers were developed that preserved the high strain and energy capability of the acrylic films but could respond one order of magnitude faster. One-DOF spring rolls using this new material exhibited response speeds up to 100 Hz, and power densities as high as 400 W/kg of actuator mass and 2000 W/kg of electroelastomer mass based on maximum force, stroke, and frequency. Further, new electroelastomers were prepared that exhibited 200% strain without the need for prestrain. These materials may enable new actuators containing no prestrain-supporting structures that are even lighter, more compact, and compliant. The new actuators would have a higher percentage of active mass and higher energy and power densities than those based on the prestrained acrylic films matching the characteristics of animals. A roll actuator containing no supporting structure was fabricated to output 33% strain. Preliminary lifetime measurements confirmed the potentially long lifetime of the electroelastomers. Improvements in MER design and materials have enabled a new generation of small walking robots, MERbot, with a multi-DOF spring roll as each of its six legs, as well as a new type of robot that can be quickly fabricated from a single flat multifunctional actuator structure. Such small flat robots can hop or jump two to three times their height and have been able to quickly clear obstacles equal to the robots' height.
Twenty years of cell‐penetrating peptides: from molecular mechanisms to therapeutics (2009)

The recent discovery of new potent therapeutic molecules that do not reach the clinic due to poor delivery and low bioavailability have made of delivery a key stone in therapeutic development. Several technologies have been designed to improve cellular uptake of therapeutic molecules, including cell-penetrating peptides (CPPs). CPPs were first discovered based on the potency of several proteins to enter cells. Numerous CPPs have been described so far, which can be grouped into two major classes, the first requiring chemical linkage with the drug for cellular internalization and the second involving formation of stable, non-covalent complexes with drugs. Nowadays, CPPs constitute very promising tools for non-invasive cellular import of cargo and have been successfully applied for in vitro and in vivo delivery of therapeutic molecules varying from small chemical molecule, nucleic acids, proteins, peptides, liposomes and particles. This review will focus on the structure/function and cellular uptake mechanism of CPPs in the general context of drug delivery. We will also highlight the application of peptide carriers for the delivery of therapeutic molecules and provide an update of their clinical evaluation.
OFDM/WDM PON With Laserless, Colorless 1  Gb/s ONUs Based on Si-PIC and Slow IC (2014)

We introduce a next-generation long-reach access optical network (35&#xA0;dB loss budget +2&#x2009;&#x2009;dB margin) delivering up to 40G/40G per passive 1&#x2236;256 optical distribution network, supporting symmetrical 1&#x2009;&#x2009;Gb/s rates per home user or up to 40&#x2009;&#x2009;Gb/s for business users (e.g., enterprises, antenna sites). The proposed system is based on a novel spectrally efficient orthogonal frequency division multiplexing/wavelength division multiplexing OFDM/WDM architecture symmetrically using 16-QAM OFDM polarization diversity in both the downstream and upstream in order to serve low-cost energy-efficient symmetric 1&#x2009;&#x2009;Gb/s optical network units (ONUs), which are self-coherent, laserless, colorless, and tunable-filter-free. Each ONU comprises a standard semiconductor optical amplifier (SOA), a silicon-based photonic integrated circuit (PIC), and mixed-signal electronic integrated circuits (ICs) performing the signal processing at a relatively slow rate as compared with the overall passive optical network (PON) throughput: digital to analog converters (DACs) and analog to digital converters (ADCs) at 417&#x2009;&#x2009;MS/s for the home user ONUs.
Expansion of genetically modified primary human hemopoietic cells using chemical inducers of dimerization (2000)

The inability to deliver a therapeutic gene to a sufficient percentage of hematopoietic stem cells is the major obstacle to using gene therapy to treat blood disorders. Providing genetically corrected stem cells with a reversible growth advantage could solve this problem. To this end we have employed small synthetic molecules that can reversibly dimerize and activate fusion proteins which contain a growth factor receptor signaling domain. We have shown that the thrombopoietin receptor (mpl) signaling domain can be used in this system to expand transduced multipotential progenitor cells from mouse bone marrow. In the present study we tested a similar retroviral vector in human CD34-selected cord blood cells. Following transduction, cells cultured in the presence of the dimerizing molecule AP1903 expanded 13.8- to 186-fold relative to cells cultured in the absence of AP1903. The cell type that emerged in suspension culture was erythroid. Contrary to our results in the murine system, cell expansion was transient. Activation of mpl caused the disappearance of BFU-E followed by a transient increase in CFU-E. In contrast, mpl activation had no discernable effect on transduced myeloid progenitor cells. AP1903-mediated expansion was restricted to transduced cells, as demonstrated by immunohistochemical staining. These findings indicate that synthetic dimerizing molecules can be used to expand primary human hematopoietic cells. (Blood. 2000;95:430-436)
Anti-VEGF Therapies in the Clinic (2012)

The development and use of antiangiogenesis agents, particularly those targeting vascular endothelial growth factor (VEGF), has become an integral component of anticancer regimens for many tumor types. This review is intended to highlight some of the most important clinical successes and failures of anti-VEGF therapies, and where possible, to suggest important lessons that have been learned. This review emphasizes data from agents that have been FDA approved and/or have completed phase III studies.
Nanoscale Anionic Macromolecules Can Inhibit Cellular Uptake of Differentially Oxidized LDL (2006)

Nanoscale particles could be synthetically designed to potentially intervene in lipoprotein matrix retention and lipoprotein uptake in cells, processes central to atherosclerosis. We recently reported on lipoprotein interactions of nanoscale micelles self-assembled from amphiphilic scorpion-like macromolecules based on a lauryl chloride-mucic acid hydrophobic backbone and poly(ethylene glycol) shell. These micelles can be engineered to present varying levels of anionic chemistry, a key mechanism to induce differential retentivity of low-density lipoproteins (LDL) (Chnari, E.; Lari, H. B.; Tian, L.; Uhrich, K. E.; Moghe, P. V. Biomaterials 2005, 26, 3749). In this study, we examined the cellular interactions and the ability of carboxylate-terminated nanoparticles to modulate cellular uptake of differentially oxidized LDL. The nanoparticles were found to be highly biocompatible with cultured IC21 macrophages at all concentrations examined. When the nanoparticles as well as LDL were incubated with the cells over 24 h, a marked reduction in cellular uptake of LDL was observed in a nanoparticle concentration-dependent manner. Intermediate concentrations of nanoparticles (10(-6) M) elicited the most charge-specific reduction in uptake, as indicated by the difference in uptake due to anionic and uncharged nanoparticles. At these concentrations, anionic nanoparticles reduced LDL uptake for all degrees of oxidation (no oxidation, mild, high) of LDL, albeit with qualitative differences in the effects. The anionic nanoparticles were particularly effective at reducing the very high levels of uptake of the most oxidized level of LDL. Since complexation of LDL with anionic nanoparticles is reduced at higher degrees of LDL oxidation, our results suggest that anionic nanoparticles interfere in highly oxidized (hox) LDL uptake, likely by targeting cellular/receptor uptake mechanism, but control unoxidized LDL uptake by mechanisms related to direct LDL-nanoparticle complexation. Thus, anionically functionalized nanoparticles can modulate the otherwise unregulated internalization of differentially oxidized LDL.
Tumor Immunotherapy Directed at PD-1 (2012)

The treatment of cancer by harnessing immune responses has long been pursued. Efforts to turn on the immune system against cancers with inactivated tumor vaccines or intratumor injections of bacterial products to induce local inflammation and recruit an antitumor immune response have led to anecdotal successes. Increasing knowledge about how the immune system is activated, coupled with advances in recombinant DNA technology, has allowed the clinical testing of immune-stimulating cytokines such as interferons and interleukins. These trials have led to a low frequency of durable tumor responses in selected cancers such as melanoma and renal-cell carcinoma at the expense of . . .
Expression of protein encoded by varicella-zoster virus open reading frame 63 in latently infected human ganglionic neurons. (1996)

The ganglionic cell type in which varicella-zoster virus (VZV) is latent in humans was analyzed by using antibodies raised against in vitro-expressed VZV open reading frame 63 protein. VZV open reading frame 63 protein was detected exclusively in the cytoplasm of neurons of latently infected human trigeminal and thoracic ganglia. This is, to our knowledge, the first identification of a herpesvirus protein expressed during latency in the human nervous system.
Equity Industry Returns and Monetary Policy (2001)

This article carries forward an extensive body of research, which has shown that prominent monetary-policy-related return patterns exist across several general security classes. The focus of this study is on the prevalence of the return patterns across various subcategories of equity securities. In particular, the authors attempt to reconcile previously contradictory findings that the monetary-policy-related return patterns should or should not differ across industries. They present evidence suggesting that industries differ substantially in their degree of sensitivity to monetary conditions and that the industries with the most prominent patterns appear to be those that rely most heavily on discretionary consumer spending. These results suggest that throughout the time period examined, portfolio managers could have used monetary conditions to improve portfolio performance. The extent to which this information can be exploited depends, of course, on the degree to which the relationship continues to exist in the future.
한국 청소년의 자살생각에 대한 위험요인과 보호요인 :성과 발달시기의 조절효과 (2005)

본 연구는 남녀 중고생 1,022명을 대상으로 자살생각에 영향을 미칠 것으로 예상되는 다양한 위험요인(생활스트레스, 우울, 무망감)과 보호요인(낙관주의, 자기 효능감, 사회적 지원)의 효과를 검증 해보고, 성과 발달시기가 이런 위험 및 보호요인이 자살생각에 미치는 효과를 어떻게 조절하는지를 탐색적으로 알아보고자 하였다. 연구결과, 선행연구나 이론으로부터 대표적 위험요인으로 알려져 있는 ‘생활스트레스’, ‘우울’ 과 ‘무망감’은 단순상관이나 회귀분석 모두에서 자살생각과 유의한 정적 상관을 보였다. 한편, 청소년의 자살생각에 대한 보호요인으로 가정한 ‘낙관주의’와 ‘자기효능감’은 단순상관에서는 유의한 부적 관계를 보였으나 회귀분석에서는 유의하지 못하거나 정적인 관계를 보였다. 이에 반해, ‘사회적 지원’은 단순상관이나 회귀분석 모두에서 자살생각과 유의한 부적 관계를 보이고 있어서 보호요인임을 확인할 수 있었다. 한국 청소년들의 자살생각에서 남녀 차이나 발달시기(중, 고등학교)의 차이는 유의하지 않았다. 성은 청소년의 자살생각에서 본 연구에서 중요하게 가정한, 위험 및 보호요인들을 유의하게 조절하지 못했다. 반면, 발달시기는 스트레스 및 사회적 지원이 자살생각에 미치는 영향을 유의하게 조절하는 것으로 나타났다. 중학생의 경우는 고등학생에 비해 생활 스트레스가 자살생각에 더 중요하게 작용하고, 고등학생의 경우는 중학생에 비해 사회적 지원이 자살생각에 더 큰 영향을 미치는, 상호작용효과가 유의했다. 마지막으로 본 연구의 결과가 후속 연구와 청소년의 자살 대책에 대해 시사하는 점을 논의했다.
A Novel Approach Using Time–Frequency Analysis of Pulse-Oximeter Data to Detect Progressive Hypovolemia in Spontaneously Breathing Healthy Subjects (2011)

Accurate and early detection of blood volume loss would greatly improve intraoperative and trauma care. This study has attempted to determine early diagnostic and quantitative markers for blood volume loss by analyzing photoplethysmogram (PPG) data from ear, finger and forehead sites with our high-resolution time-frequency spectral (TFS) technique in spontaneously breathing healthy subjects (n = 11) subjected to lower body negative pressure (LBNP). The instantaneous amplitude modulations present in heart rate (AM HR) and breathing rate (AMBR) band frequencies of PPG signals were calculated from the high-resolution TFS. Results suggested that the changes (P < 0.05) in AMBR and especially in AMHR values can be used to detect the blood volume loss at an early stage of 20% LBNP tolerance when compared to the baseline values. The mean percent decrease in AMHR values at 100% LBNP tolerance was 78.3%, 72.5%, and 33.9% for ear, finger, and forehead PPG signals, respectively. The mean percent increase in AMBR values at 100% LBNP tolerance was 99.4% and 19.6% for ear and finger sites, respectively; AMBR values were not attainable for forehead PPG signal. Even without baseline AMHR values, our results suggest that hypovolemia detection is possible with specificity and sensitivity greater than 90% for the ear and forehead locations when LBNP tolerance is 100%. Therefore, the TFS analysis of noninvasive PPG waveforms is promising for early diagnosis and quantification of hypovolemia at levels not identified by vital signs in spontaneously breathing subjects.
Microbial control of the production of hydrogen sulfide by sulfate‐reducing bacteria (1990)

A sulfide-resistant ctrain of Thiobacillus denitrificans, strain F, prevented the accumulation of sulfide by Desulfovibrio desulfuricans when both organisms were grown in liquid medium or in Berea sandstone cores. The wild-type strain of T. denitrificans did not prevent the accumulation of sulfide produced by D. desulfuricans. Strain F also prevented the accumulation of sulfide by a mixed population of sulfate-reducing bacteria enriched from an oil field brine. Fermentation balances showed that strain F stoichiometrically oxidized the sulfide produced by D. desulfuricans and the oil field brine enrichment to sulfate. These data suggest that strain F would be effective in controlling sulfide production in oil reservoirs and other environments.
Bispecific Antibodies for Multiple Myeloma: A Review of Targets, Drugs, Clinical Trials, and Future Directions (2020)

Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematological neoplasm in adults, comprising 1.8% of all cancers. With an annual incidence of ~30,770 cases in the United States, MM has a high mortality rate, leading to 12,770 deaths per year. MM is a genetically complex, highly heterogeneous malignancy, with significant inter- and intra-patient clonal variability. Recent years have witnessed dramatic improvements in the diagnostics, classification, and treatment of MM. However, patients with high-risk disease have not yet benefited from therapeutic advances. High-risk patients are often primary refractory to treatment or relapse early, ultimately resulting in progression toward aggressive end-stage MM, with associated extramedullary disease or plasma cell leukemia. Therefore, novel treatment modalities are needed to improve the outcomes of these patients. Bispecific antibodies (BsAbs) are immunotherapeutics that simultaneously target and thereby redirect effector immune cells to tumor cells. BsAbs have shown high efficacy in B cell malignancies, including refractory/relapsed acute lymphoblastic leukemia. Various BsAbs targeting MM-specific antigens such as B cell maturation antigen (BCMA), CD38, and CD138 are currently in pre-clinical and clinical development, with promising results. In this review, we outline these advances, focusing on BsAb drugs, their targets, and their potential to improve survival, especially for high-risk MM patients. In combination with current treatment strategies, BsAbs may pave the way toward a cure for MM.
Recognition, isolation, and characterization of rat liver D-methylmalonyl coenzyme A hydrolase. (1983)

Certain amino acids and other compounds are metabolized via: Propionyl-CoA carboxylase in equilibrium D-methylmalonyl-CoA racemase in equilibrium L-methylmalonyl-CoA (adenosylcobalamin) mutase in equilibrium succinyl-CoA in equilibrium tricarboxylic acid cycle. In cobalamin deficiency and in genetic disorders involving adenosylcobalamin or the mutase, large amounts of methylmalonic acid are excreted in the urine. Its origin is unknown, however, since nonesterified methylmalonic acid is not present in the above or other known pathways. To investigate the origin of methylmalonic acid, we fractionated rat liver by gel filtration and found a single peak (Mr = 35,000) of activity for the hydrolysis of DL-methylmalonyl-CoA to methylmalonic acid and CoA. The enzyme has been purified 3,100-fold with a yield of 2.1% from 1.6 kg of rat liver using a purification scheme consisting of ammonium sulfate fractionation, ion exchange chromatography on CM (carboxymethyl)-cellulose and DEAE-cellulose, affinity chromatography on CoA-agarose, and gel filtration on Sephadex G-100. The final preparation gave a single band on polyacrylamide gel electrophoresis. The molecular weight of the purified enzyme is 35,000 based on gel filtration, and sodium dodecyl sulfate-polyacrylamide electrophoresis in the presence and absence of 1% 2-mercaptoethanol. The enzyme was shown to be active on the D-isomer, but not on the L-isomer, of methylmalonyl-CoA by CD spectropolarimetry. The Km for D-methylmalonyl-CoA is 0.7 mM and the molar activity is 1,400 molecules of substrate/min/molecule of enzyme. At substrate concentrations of 0.5 mM, the relative rate of hydrolysis of CoA esters was as follows: D-methylmalonyl-CoA (100%), malonyl-CoA (16%), propionyl-CoA (3%), acetyl-CoA (1%), succinyl-CoA (less than 1%), and palmitoyl-CoA (less than 1%). This enzyme appears to account for the markedly increased amounts of methylmalonic acid that are excreted in the urine in cobalamin deficiency and in genetic disorders involving adenosylcobalamin or L-methylmalonyl-CoA mutase.
In vivo effects of cytokines on psoriatic skin grafted on nude mice: involvement of the tumour necrosis factor (TNF) receptor (1996)

Following engraftment of human involved psoriatic skin to nude mice there is a partial normalization of pathology associated with a loss of inflammatory leucocytes. However, the epidermis remains hyperproliferative, which may reflect a primary defect. The roles of TNF-alpha, IL-1 and IL-6 in epidermal hyperproliferation of grafted psoriatic lesions were investigated. Before and after treatment, grafts were analysed to determine epidermal thickness and labelling index (LI). HLA-DR, intercellular adhesion molecule-1 (ICAM-1), and TNF receptor (TNF-R; p75 and p55) expression were determined by immunoperoxidase staining. Psoriatic epidermis was found consistently to be negative for p55 TNF-R and p75 TNF-R before grafting. Following engraftment, TNF-R-positive cells (i.e. p55 by keratinocytes; p75 by epidermal dendritic cells) were identified throughout the epidermis. Higher numbers of p75 TNF-R epidermal dendritic cells were found in grafts following a course of TNF-alpha, IL-6 or IL-1 treatment. The p55 form of the TNF-R expressed by keratinocytes was significantly elevated after treatment with TNF-alpha or IL-6. HLA-DR and ICAM-1 were also expressed in these grafts. TNF-alpha, anti-IL-1, and anti-IL-6 treatment induced a marked decrease in the epidermal thickness and LI of psoriatic graft tissue, correcting the hyperproliferation associated with psoriatic epidermis. Supraphysiological levels of TNF-alpha may saturate and consequently down-regulate their own receptors, leading to a paradoxical inhibitory effect.
Multisegmented One‐Dimensional Nanorods Prepared by Hard‐Template Synthetic Methods (2006)

In the science and engineering communities, the nanoscience revolution is intensifying. As many types of nanomaterials are becoming more reliably synthesized, they are being used for novel applications in all branches of nanoscience and nanotechnology. Since it is sometimes desirable for single nanomaterials to perform multiple functions simultaneously, multicomponent nanomaterials, such as core-shell, alloyed, and striped nanoparticles, are being more extensively researched. Nanoscientists hope to design multicomponent nanostructures and exploit their inherent multiple functionalities for use in many novel applications. This review highlights recent advances in the synthesis of multisegmented one-dimensional nanorods and nanowires with metal, semiconductor, polymer, molecular, and even gapped components. It also discusses the applications of these multicomponent nanomaterials in magnetism, self-assembly, electronics, biology, catalysis, and optics. Particular emphasis is placed on the new materials and devices achievable using these multicomponent, rather than single-component, nanowire structures.
Role of the carbohydrate moiety in determining the survival of interferon in the circulation (1977)

The role of the carbohydrate moiety in influencing the survival time of human lymphoblastoid interferon in the rat circulation was monitored at varying time intervals after intravenous injection. The serum survival time of native interferon was drastically reduced by prior enzymatic cleavage of the terminal sialic acid residues to yield the galactose-terminal product, asialo-interferon. This phenomenon was completely reversed by further extensive digestion with a mixture of glycosidases which effectively removed over 85% of the total carbohydrate residues. These results suggest that the intact carbohydrate structure is neither essential for normal circulation time in vivo nor for biologic activity in vitro.