gebhart/patrepeval huggingface dataset:
Phase I Comparability of Recombinant Human Albumin and Human Serum Albumin (2004)

Recombinant human albumin (rHA) is a highly purified animal-, virus-, and prion-free product developed as an alternative to human serum albumin (HSA), to which it is structurally equivalent. The present investigation compared the safety, tolerability, and pharmacokinetics/pharmacodynamics of rHA with HSA. Two double-blind, randomized trials were performed in healthy volunteers using intramuscular (IM) and intravenous (IV) administration. The IM trial included 500 volunteers, each receiving 5 repeat doses of 5 mg (100 subjects), 15 mg (100 subjects), or 65 mg (300 subjects) of rHA or HSA. Thirty volunteers participated in the IV trial, each receiving ascending doses (10 g, 20 g, and 50 g) of either rHA or HSA. In both trials, all adverse events were recorded and conventionally classified; potential allergic responses were also monitored. Blood samples were taken in both studies to test for IgG or IgE antibodies against test products and potential impurities. For the IV study, pharmacokinetic/pharmacodynamic assessments were performed, including measurement of serum albumin, colloid osmotic pressure, and hematocrit pre- and postinfusion. Nine subjects in the IM study (4 recipients of rHA and 5 of HSA) reported drug-related, potentially allergic events; all but 2 of these were skin related. No serious or potentially allergic events were reported with either product in the IV study. There was no immunological response to either product, and dose level did not influence the study outcomes. Serum albumin, colloid osmotic pressure changes, and hematocrit ratio were as expected, with no differences between rHA and HSA. rHA and HSA exhibited similar safety, tolerability, and pharmacokinetic/pharmacodynamic profiles, with no evidence of any immunological response.
Barcoded oligonucleotides ligated on RNA amplified for multiplexed and parallel in situ analyses (2021)

We present barcoded oligonucleotides ligated on RNA amplified for multiplexed and parallel insitu analyses (BOLORAMIS), a reverse transcription-free method for spatially-resolved, targeted, in situ RNA identification of single or multiple targets. BOLORAMIS was demonstrated on a range of cell types and human cerebral organoids. Singleplex experiments to detect coding and non-coding RNAs in human iPSCs showed a stem-cell signature pattern. Specificity of BOLORAMIS was found to be 92% as illustrated by a clear distinction between human and mouse housekeeping genes in a co-culture system, as well as by recapitulation of subcellular localization of lncRNA MALAT1. Sensitivity of BOLORAMIS was quantified by comparing with single molecule FISH experiments and found to be 11%, 12% and 35% for GAPDH, TFRC and POLR2A, respectively. To demonstrate BOLORAMIS for multiplexed gene analysis, we targeted 96 mRNAs within a co-culture of iNGN neurons and HMC3 human microglial cells. We used fluorescence in situ sequencing to detect error-robust 8-base barcodes associated with each of these genes. We then used this data to uncover the spatial relationship among cells and transcripts by performing single-cell clustering and gene-gene proximity analyses. We anticipate the BOLORAMIS technology for in situ RNA detection to find applications in basic and translational research.
Fatigue crack propagation in high‐density polyethylene (1991)

Abstract An investigation of the influence of crystalline microstructure on fatigue crack propagation (FCP) in high‐density polyethylene (HDPE) is reported. Various thermal histories were used to generate samples with the same crystallinity and supermolecular structure for three different molecular weight HDPEs. Estimation of tie chain densities were obtained from measurements of brittle fracture stress and predicted from the estimated chain dimensions of the polymers using the modified version of the approach originally taken by Huang and Brown. A significant decrease in FCP resistance and a clear transition to a more brittle fracture surface was observed with decreasing molecular weight. Detailed studies of damaged zones preceding the growing crack show a transition to a more highly branched crack structure for those samples associated with a higher FCP resistance. These results strongly suggest that the branched damaged zone structure improves the FCP resistance by enlarging and blunting the crack tip and, therefore, consuming more energy during the fatigue crack propagation. Additional efforts were made to prepare samples with the same crystallinity and tie chain density, but different supermolecular structure. However, in contrast to reports in the literature, no significant difference in FCP resistance was observed for specimens with different average spherulite sizes. This is probably because the propagating crack front is preceded by a significant zone of plastic deformation and is not expected to directly encounter the spherulites.
Novel Antiviral Strategies to Combat Human Arenavirus Infections (2005)

Arenaviruses merit significant attention both as tractable model systems to study acute and persistent viral infections, and as clinically important human pathogens. Evidence indicates that LCMV remains present in the USA and Europe and capable of causing significant morbidity in infected individuals, likely being a neglected human pathogen. Moreover, new arenaviruses are being discovered in the Americas on the average of one every three years, with some of them causing severe hemorrhagic fever. In addition, weaponized forms of these viruses pose a real threat as agents of bioterrorism. Therefore, it is important to develop effective vaccines and better antiviral drugs to combat the dual threats of naturally occurring and intentionally introduced Arenavirus infections. The development of arenavirus reverse genetic systems is allowing investigators to conduct a detailed molecular characterization of the viral cis-acting signals and trans-acting factors that control each of the steps of the Arenavirus life cycle, including RNA synthesis, packaging and budding. We will discuss how this new knowledge is facilitating the establishment of novel assays to identify and characterize compounds capable of interfering with specific steps of the virus life cycle. Likewise, the ability to generate predetermined specific mutations within the arenavirus genome, and analyze their phenotypic expression, would significantly contribute to the elucidation of arenavirus-host interactions, including the bases of their ability to persist, as well as to cause severe HF (hemorrhagic fever) disease in humans. These approaches could also lead to the development of novel potent and safe Arenavirus vaccines.
Molecular and Cellular Mechanisms of Myocardial Stunning (1999)

The past two decades have witnessed an explosive growth of knowledge regarding postischemic myocardial dysfunction or myocardial "stunning." The purpose of this review is to summarize current information regarding the pathophysiology and pathogenesis of this phenomenon. Myocardial stunning should not be regarded as a single entity but rather as a "syndrome" that has been observed in a wide variety of experimental settings, which include the following: 1) stunning after a single, completely reversible episode of regional ischemia in vivo; 2) stunning after multiple, completely reversible episodes of regional ischemia in vivo; 3) stunning after a partly reversible episode of regional ischemia in vivo (subendocardial infarction); 4) stunning after global ischemia in vitro; 5) stunning after global ischemia in vivo; and 6) stunning after exercise-induced ischemia (high-flow ischemia). Whether these settings share a common mechanism is unknown. Although the pathogenesis of myocardial stunning has not been definitively established, the two major hypotheses are that it is caused by the generation of oxygen-derived free radicals (oxyradical hypothesis) and by a transient calcium overload (calcium hypothesis) on reperfusion. The final lesion responsible for the contractile depression appears to be a decreased responsiveness of contractile filaments to calcium. Recent evidence suggests that calcium overload may activate calpains, resulting in selective proteolysis of myofibrils; the time required for resynthesis of damaged proteins would explain in part the delayed recovery of function in stunned myocardium. The oxyradical and calcium hypotheses are not mutually exclusive and are likely to represent different facets of the same pathophysiological cascade. For example, increased free radical formation could cause cellular calcium overload, which would damage the contractile apparatus of the myocytes. Free radical generation could also directly alter contractile filaments in a manner that renders them less responsive to calcium (e.g., oxidation of critical thiol groups). However, it remains unknown whether oxyradicals play a role in all forms of stunning and whether the calcium hypothesis is applicable to stunning in vivo. Nevertheless, it is clear that the lesion responsible for myocardial stunning occurs, at least in part, after reperfusion so that this contractile dysfunction can be viewed, in part, as a form of "reperfusion injury." An important implication of the phenomenon of myocardial stunning is that so-called chronic hibernation may in fact be the result of repetitive episodes of stunning, which have a cumulative effect and cause protracted postischemic dysfunction. A better understanding of myocardial stunning will expand our knowledge of the pathophysiology of myocardial ischemia and provide a rationale for developing new therapeutic strategies designed to prevent postischemic dysfunction in patients.
Rapid Desensitization of the Metabotropic Glutamate Receptor that Facilitates Glutamate Release in Rat Cerebrocortical Nerve Terminals (1994)

The metabotropic autoreceptor of glutamatergic nerve terminals from the cerebral cortex of adult rats has been characterized. Receptor activation involves a rapid and transient increase in diacylglycerol, which is sensitive to L-2-amino-3-phosphonopropionate (L-AP3) and L-2-amino-4-phosphonobutanoic acid (L-AP4) and is partially blocked by pertussis toxin. Protein kinase C (PKC) has a negative feedback control in this transduction pathway because the activation of the kinase, either by phorbol esters or by the endogenous diacylglycerol produced by the receptor, results in a reversible receptor desensitization, with loss of the ability to further facilitate glutamate release. It is concluded that the facilitatory metabotropic receptor located at the glutamatergic nerve endings belongs to the subclass coupled to phosphoinositide hydrolysis and that the rapid and use-dependent desensitization of the facilitatory pathway may underlie a mechanism to prevent its permanent activation and thereby to avoid neurotoxicity.
Silicon p-FETs from Ultrahigh Density Nanowire Arrays (2006)

Statistical numbers of field-effect transistors (FETs) were fabricated from a circuit of 17-nm-wide, 34-nm-pitch Si nanowires boron doped at a level of 10^(18) cm^(-3). Top-gated 4-μm-wide Si nanowire p-FETs yielded low off-currents (∼10^(-12) A), high on/off ratios (10^5−10^6), good on current values (30 μA/μm), high mobilities (∼100 cm^2/V−s), and low subthreshold swing values (∼80 mV/decade between 10^(-12) and 10^(-10) A increasing to 200 mV/decade between 10^(-10)−10^(-8) A).
Effect of Droplet Morphology on Growth Dynamics and Heat Transfer during Condensation on Superhydrophobic Nanostructured Surfaces (2012)

Condensation on superhydrophobic nanostructured surfaces offers new opportunities for enhanced energy conversion, efficient water harvesting, and high performance thermal management. These surfaces are designed to be Cassie stable and favor the formation of suspended droplets on top of the nanostructures as compared to partially wetting droplets which locally wet the base of the nanostructures. These suspended droplets promise minimal contact line pinning and promote passive droplet shedding at sizes smaller than the characteristic capillary length. However, the gas films underneath such droplets may significantly hinder the overall heat and mass transfer performance. We investigated droplet growth dynamics on superhydrophobic nanostructured surfaces to elucidate the importance of droplet morphology on heat and mass transfer. By taking advantage of well-controlled functionalized silicon nanopillars, we observed the growth and shedding behavior of suspended and partially wetting droplets on the same surface during condensation. Environmental scanning electron microscopy was used to demonstrate that initial droplet growth rates of partially wetting droplets were 6× larger than that of suspended droplets. We subsequently developed a droplet growth model to explain the experimental results and showed that partially wetting droplets had 4-6× higher heat transfer rates than that of suspended droplets. On the basis of these findings, the overall performance enhancement created by surface nanostructuring was examined in comparison to a flat hydrophobic surface. We showed these nanostructured surfaces had 56% heat flux enhancement for partially wetting droplet morphologies and 71% heat flux degradation for suspended morphologies in comparison to flat hydrophobic surfaces. This study provides insights into the previously unidentified role of droplet wetting morphology on growth rate, as well as the need to design Cassie stable nanostructured surfaces with tailored droplet morphologies to achieve enhanced heat and mass transfer during dropwise condensation.
Oligosaccharides from human milk induce growth arrest via G2/M by influencing growth-related cell cycle genes in intestinal epithelial cells (2008)

Oligosaccharides are present in human milk in large amounts and in a high variety. We have previously shown that these oligosaccharides are strong inhibitors of proliferation and inducers of differentiation in intestinal cell lines. To elucidate the molecular mechanism, we investigated the influence on cell cycle events via flow cytometry and expression levels by using quantitative real-time RT-PCR. Human intestinal cells, i.e. HT-29, HIEC and Caco-2 cells, were exposed to neutral or acidic human milk oligosaccharides. Both fractions induced a concentration-dependent G2/M arrest. Cell cycle analysis for HT-29 revealed 37 % of cells in G1 and 35 % in G2/M (neutral oligosaccharides) and incubation with acidic oligosaccharides led to 42 % cells in G1 and 40 % in G2/M. In control experiments without oligosaccharides we found 71 % of cells to be in G1 and 17 % in G2/M. This G2/M arrest was associated with changes in mRNA expression of cyclin A and B. A G2/M arrest with concomitant alterations of cell cycle gene expression could also be shown for HIEC and Caco-2 cells. Analysing the expression of cyclin-dependent kinase inhibitors p21(cip1) and p27(kip1) and the tumour suppressor p53 we observed that the expression of p21(cip1) was p53-independent and necessary for arresting cells in the G2/M phase, while p27(kip1) was associated with differentiation effects. Both neutral and acidic human milk oligosaccharides were able to induce epidermal growth factor receptor, extracellular signal-regulated kinase 1/2 and p38 phosphorylation. These results suggest that oligosaccharides from human milk inhibited intestinal cell proliferation and altered cell cycle dynamics by affecting corresponding regulator genes and mitogen-activated protein kinase signalling.
Distributed power control in cellular radio systems (1994)

The capacity of cellular mobile radio systems can be increased by controlling the transmitter powers so as to balance the carrier to interference ratios at the receivers. A distributed algorithm for implementing such power control was proposed earlier for satellite systems by Meyerhoff (1974). The authors tighten the mathematical arguments and apply this scheme to cellular systems. The mobile units adjust their transmitter powers at discrete time instants. Specifically at each time instant the mobile multiplies its current power by a factor equal to a constant over its current carrier to interference ratio (CIR). So power is increased or decreased based on the value of the current CIR. After a number of such power adjustments all the mobiles converge to a common CIR. They also present numerical results which show that the above scheme has the potential to converge faster than the scheme proposed by J. Zander (see IEEE Transactions on Vehicular Technology, vol.41, no.3, August 1992) for high CIR values.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Light‐Controlled Tools (2012)

Spatial and temporal control over chemical and biological processes plays a key role in life, where the whole is often much more than the sum of its parts. Quite trivially, the molecules of a cell do not form a living system if they are only arranged in a random fashion. If we want to understand these relationships and especially the problems arising from malfunction, tools are necessary that allow us to design sophisticated experiments that address these questions. Highly valuable in this respect are external triggers that enable us to precisely determine where, when, and to what extent a process is started or stopped. Light is an ideal external trigger: It is highly selective and if applied correctly also harmless. It can be generated and manipulated with well-established techniques, and many ways exist to apply light to living systems--from cells to higher organisms. This Review will focus on developments over the last six years and includes discussions on the underlying technologies as well as their applications.
Initial development and testing of a novel foam-based pressure sensor for wearable sensing (2005)

BACKGROUND: This paper provides an overview of initial research conducted in the development of pressure-sensitive foam and its application in wearable sensing. The foam sensor is composed of polypyrrole-coated polyurethane foam, which exhibits a piezo-resistive reaction when exposed to electrical current. The use of this polymer-coated foam is attractive for wearable sensing due to the sensor's retention of desirable mechanical properties similar to those exhibited by textile structures. METHODS: The development of the foam sensor is described, as well as the development of a prototype sensing garment with sensors in several areas on the torso to measure breathing, shoulder movement, neck movement, and scapula pressure. Sensor properties were characterized, and data from pilot tests was examined visually. RESULTS: The foam exhibits a positive linear conductance response to increased pressure. Torso tests show that it responds in a predictable and measurable manner to breathing, shoulder movement, neck movement, and scapula pressure. CONCLUSION: The polypyrrole foam shows considerable promise as a sensor for medical, wearable, and ubiquitous computing applications. Further investigation of the foam's consistency of response, durability over time, and specificity of response is necessary.
Development of a Dynamic Stem Cell Culture Platform for Mesenchymal Stem Cell Adhesion and Evaluation (2014)

The importance of providing a physiologically relevant environment for cell culture is well recognized. The combination of proper environmental cues which are provided in vivo by the bloodstream and extracellular matrix must be reproduced to properly examine cell response in vitro, and cannot be recapitulated using traditional culture on polystyrene. Here, we have developed a device, the dynamic stem cell culture platform (DSCCP), consisting of a biomimetic scaffold cultured within the dynamic environment of a perfusion bioreactor. By varying scaffold parameters including stiffness and protein inclusion at the material surface, we found that human mesenchymal stem cells (hMSCs) were able to adhere to modified substrates, while still maintaining multipotency. Culture in a perfusion bioreactor showed cell survival and proliferation, particularly on modified substrates. The DSCCP represents a complete platform for cell adhesion and subsequent evaluation, including the response of a cell population to drug treatment.
The contribution of Fc effector mechanisms in the efficacy of anti-CD154 immunotherapy depends on the nature of the immune challenge (2004)

Blockade of the CD154-CD40 co-stimulatory pathway with anti-CD154 mAbs has shown impressive efficacy in models of autoimmunity and allotransplantation. Clinical benefit was also demonstrated in systemic lupus erythematosus (SLE) and idiopathic thrombocytopenia patients with the humanized anti-CD154 mAb, 5C8 (hu5C8). However, thromboembolic complications that occurred during the course of the hu5C8 clinical trials have proven to be a major setback to the field and safe alternative therapeutics targeting the CD154-CD40 pathway are of great interest. Recently, effector mechanisms have been shown to play a part in anti-CD154 mAb-induced transplant acceptance in murine models, while this issue remains unresolved for humoral-mediated models. Herein, aglycosyl anti-CD154 mAbs with reduced binding to FcgammaR and complement were used as a novel means to test the role of effector mechanisms in non-human primate and murine models not amenable to gene knockout technology. While aglycosyl hu5C8 mAb was relatively ineffective in rhesus renal and islet allotransplantation, it inhibited primary and secondary humoral responses to a protein immunogen in cynomolgus monkeys. Moreover, an aglycosyl, chimeric MR1 mAb (muMR1) prolonged survival and inhibited pathogenic auto-antibody production in a murine model of SLE. Thus, the mechanisms required for efficacy of anti-CD154 mAbs depend on the nature of the immune challenge.
Development and characteristics of a biological tissue-equivalent phantom for microwaves (2000)

Various phantoms (simulated biological bodies) have been proposed as a biological model for studies of electromagnetic effects on the human body. This paper reports the characteristics of the phantom developed by the authors that realized electrical characteristics equivalent to the biological body. Examples of its communication and clinical applications are presented. The present phantom is made of agar, polyethylene powder, sodium chloride, TX-151, preservative, and deionized water and simulates the relative permittivity and conductivity of a high-water-content tissue. In the present phantom, electrical characteristics almost equal to those in the biological tissue are realized with a single composition ratio over the frequency range of 300 MHz to 2.5 GHz. It is also possible to simulate the electrical characteristics of an arbitrary high-water-content tissue by adjustment of the composition. No special equipment is needed for fabrication and the preservation is easy. Further, as examples of applications of this phantom to the human body, the SAR measurement examples are presented in the COST 244 human head model and coaxial-slot antenna for hyperthermia. The present phantom is useful as a human model to study the mutual effects of the human body and electromagnetic waves. © 2000 Scripta Technica, Electron Comm Jpn Pt 1, 84(4): 67–77, 2001
Hematologic Abnormalities and Acute Myeloid Leukemia in Children and Adolescents Administered Intensified Chemotherapy for the Ewing Sarcoma Family of Tumors (2000)

Patients treated for ESFT with intensive chemotherapy that includes large doses of alkylators, topoisomerase II inhibitors, and G-CSF characteristically have persistently elevated MCVs and decreased platelet counts after completion of therapy. These hematologic abnormalities may represent stem cell damage, predisposing patients to myelodysplasia and acute myeloid leukemia, but further study is needed to establish this relation.