gebhart/patrepeval huggingface dataset:
Molecular mechanisms of virulence in fungus-host interactions for Aspergillus fumigatus and Candida albicans. (1998)

Research on fungi that cause opportunistic infections has increased dramatically during the past few years, largely because these organisms cause significant morbidity and mortality. Most of this research has focused on defining the virulence factors produced by these pathogens, as well as developing methods for the diagnosis of fungal diseases. With regard to studies on the biology of Candida albicans, it is now possible to isolate genes, disrupt their expression, and observe the specific effects of gene disruption on virulence and growth of the organism. Moreover, growth and virulence of this pathogen is also being studied and the effect of environmental factors on gene expression investigated. This subject is especially important in view of the fact that C. albicans can colonize and invade a number of sites in the human body. Thus, its ability to grown in the oral and vaginal tracts, as well as in blood, requires the organism to adapt to a variety of environmental stresses. Here we present observations on the growth, morphogenesis and virulence of the opportunistic fungi C. albicans and Aspergillus fumigatus.
Intracellular insulin-receptor dissociation and segregation in a rat fibroblast cell line transfected with a human insulin receptor gene. (1988)

The cellular processing of insulin and insulin receptors was studied using a rat fibroblast cell line that had been transfected with a normal human insulin receptor gene, expressing approximately 500 times the normal number of native fibroblast insulin receptors. These cells bind and internalize insulin normally. Biochemical assays based on the selective precipitation by polyethylene glycol of intact insulin-receptor complexes but not of free intracellular insulin were developed to study the time course of intracellular insulin-receptor dissociation. Fibroblasts were incubated with radiolabeled insulin at 4 degrees C, and internalization of insulin-receptor complexes was initiated by warming the cells to 37 degrees C. Within 2 min, 90% of the internalized radioactivity was composed of intact insulin-receptor complexes. The total number of complexes reached a maximum by 5 min and decreased rapidly thereafter with a t 1/2 of approximately 10 min. There was a distinct delay in the appearance, rate of rise, and peak of intracellular free and degraded insulin. The dissociation of insulin from internalized insulin-receptor complexes was markedly inhibited by monensin and chloroquine. Furthermore, chloroquine markedly increased the number of cross-linkable intracellular insulin-receptor complexes, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiography. These findings suggest that acidification of intracellular vesicles is responsible for insulin-receptor dissociation. Physical segregation of dissociated intracellular insulin from its receptor was monitored, based on the ability of dissociated insulin to rebind to receptor upon neutralization of acidic intracellular vesicles with monensin. The results are consistent with the view that segregation of insulin and receptor occurs 5-10 min after initiation of dissociation. These studies demonstrate the intracellular itinerary of insulin-receptor complexes, including internalization, dissociation of insulin from the internalized receptor within an acidified compartment, segregation of insulin from the receptor, and subsequent ligand degradation.
Impact of an energy-conserving strategy on succinate production under weak acidic and anaerobic conditions in Enterobacter aerogenes (2015)

Focusing on increasing net ATP production during succinate synthesis leads to increased succinate yield and volumetric productivity in E. aerogenes. We propose that the metabolically engineered E. aerogenes ES08ΔptsG strain, which effectively produces succinate under weakly acidic and anaerobic conditions, has potential utility for economical succinate production.
Contribution to the Chemistry in Clouds: A Laboratory Study on the Kinetics and Mechanism of the Oxidation of Sulfur and Nitrogen Compounds by Hydroperoxides in Aqueous Phase (2001)

This chapter contains sections titled: Introduction Preparation and Properties of the Hydroperoxides Applied Kinetics and Mechanism of Sulfur(IV) Oxidation by Hydroperoxides Kinetics and Mechanism of the Oxidation of Dimethyl Sulfide and Dimethyl Sulfoxide by Hydroperoxides Kinetics and Mechanism of the Oxidation of Nitrous Acid by Hydroperoxides Kinetic Measurements on the Oxidation of Sulfur(IV) by Nitrous Acid General Reaction Pattern for the Oxidation of Sulfur(IV) and Nitrogen(III) Compounds by Hydroperoxides in Aqueous Solution Atmospheric Relevance of the Laboratory Studies
Mechanistic Modeling of the Pharmacodynamic and Pharmacokinetic Relationship of Tissue Factor Pathway Inhibitor-Neutralizing Antibody (BAY 1093884) in Cynomolgus Monkeys (2017)

BAY 1093884 is a fully human monoclonal antibody against the tissue factor pathway inhibitor (TFPI) in development as prophylaxis in patients with hemophilia with or without inhibitors. In vitro, BAY 1093884 binds to human, mouse, and monkey TFPI. The objective of this study was to find a pharmacodynamic (PD) biomarker after administration of BAY 1093884 to normal monkeys. In monkey plasma, BAY 1093884 exhibited an IC50 (concentration that inhibits 50%) of 4.65 and 6.19 nM for free TFPI and diluted prothrombin time (dPT), respectively. The BAY 1093884 pharmacokinetic (PK) profile and its PD effects on dPT and free TFPI levels were assessed after intravenous and subcutaneous administration of BAY 1093884 (5 and 20 mg/kg) to female cynomolgus monkeys. Free TFPI concentrations in plasma decreased rapidly and increased to baseline in a dose-dependent manner. dPT clotting time was shortened and correlated with free TFPI levels and drug concentration in plasma, demonstrating the relationship between PD activities (dPT clotting time and free TFPI levels) and drug concentration. BAY 1093884 exhibited nonlinear PK, and a target-mediated drug disposition model was used to characterize the BAY 1093884 versus TFPI concentration–response relationship. We concluded that a mechanism-based PK/PD binding model could be useful for predicting human response to BAY 1093884. For the first-in-human study, measurement of free TFPI will be included as part of the dose-escalation design.
Array interpolation and DOA MSE reduction (2005)

Interpolation or mapping of data from a given real array to data from a virtual array of more suitable geometry is well known in array signal processing. This operation allows arrays of any geometry to be used with fast direction-of-arrival (DOA) estimators designed for linear arrays. In an earlier companion paper , a first-order condition for zero DOA bias under such mapping was derived and was also used to construct a design algorithm for the mapping matrix that minimized the DOA estimate bias. This bias-minimizing theory is now extended to minimize not only bias, but also to consider finite sample effects due to noise and reduce the DOA mean-square error (MSE). An analytical first-order expression for mapped DOA MSE is derived, and a design algorithm for the transformation matrix that minimizes this MSE is proposed. Generally, DOA MSE is not reduced by minimizing the size of the mapping errors but instead by rotating these errors and the associated noise subspace into optimal directions relative to a certain gradient of the DOA estimator criterion function. The analytical MSE expression and the design algorithm are supported by simulations that show not only conspicuous MSE improvements in relevant scenarios, but also a more robust preprocessing for low signal-to-noise ratios (SNRs) as compared with the pure bias-minimizing design developed in the previous paper.
Myeloma kidney with isolated tubulointerstitial light chain deposition in a renal allograft (2009)

Abstract: Myeloma kidney and myeloma‐associated renal disorders including light chain deposition disease can occur as recurrent or de novo disease in renal allografts. These kidney disorders usually manifest with worsening allograft function and proteinuria. Identification of the precise cause of kidney disorder often requires kidney biopsy and demonstration of monoclonal light chains in the kidney. Here, we present an unusual case of light chain nephropathy in a living‐related kidney transplant recipient involving light chain crystallization in the proximal tubule occurring within less than three months after transplant. The etiology of renal failure prior to transplant in our patient is not clear. To the best of our knowledge, the ultrastructural changes seen in our patient have not been described in literature previously. Our patient was treated with steroids, which resulted in short‐term improvement in allograft dysfunction.
On the Future of Congestion Control for the Public Internet (2020)

The conventional wisdom requires that all congestion control algorithms deployed on the public Internet be TCP-friendly. If universally obeyed, this requirement would greatly constrain the future of such congestion control algorithms. If partially ignored, as is increasingly likely, then there could be significant inequities in the bandwidth received by different flows. To avoid this dilemma, we propose an alternative to the TCP-friendly paradigm that can accommodate innovation, is consistent with the Internet's current economic model, and is feasible to deploy given current usage trends.
Capacitor Energy Storage Requirements in Mixed-Submodule Hybrid Cascaded MMCs (2020)

This article investigates energy storage requirements in the submodules of a class of converters known as hybrid cascaded modular multilvel converters (HC-MMCs). The complexities arising from the usage of different submodule types and their non-conventional arrangement necessitate detailed analysis of submodule capacitor voltage ripples, which are needed for development of guidelines for sizing submodule capacitors. This paper characterizes electric charge variations in the submodule capacitors to derive expressions for capacitor voltage ripples, and to determine the energy storage requirements of the converter. The paper uses detailed electromagnetic transient (EMT) simulations and experimental results on a laboratory-scale MMC setup to verify and validate its findings.
Novel Payload Architectures for LISA (2006)

As part of the current LISA Mission Formulation Study, and based on prior internal investigations, Astrium Germany has defined and preliminary assessed novel payload architectures, potentially reducing overall complexity and improving budgets and costs. A promising concept is characterized by a single active inertial sensor attached to a single optical bench and serving both adjacent interferometer arms via two rigidly connected off‐axis telescopes. The in‐plane triangular constellation “breathing angle” compensation is accomplished by common telescope in‐field of view pointing actuation of the transmit/received beams line of sight. A dedicated actuation mechanism located on the optical bench is required in addition to the on bench actuators for differential pointing of the transmit and receive direction perpendicular to the constellation plane. Both actuators operate in a sinusoidal yearly period. A technical challenge is the actuation mechanism pointing jitter and the monitoring and calibration of the laser phase walk which occurs while changing the optical path inside the optical assembly during re‐pointing. Calibration or monitoring of instrument internal phase effects e.g. by a laser metrology truss derived from the existing interferometry is required. The architecture exploits in full the two‐step interferometry (strap down) concept, separating functionally inter spacecraft and intra‐spacecraft interferometry (reference mass laser metrology degrees of freedom sensing). The single test mass is maintained as cubic, but in free‐fall in the lateral degrees of freedom within the constellation plane. Also the option of a completely free spherical test mass with full laser interferometer readout has been conceptually investigated. The spherical test mass would rotate slowly, and would be allowed to tumble. Imperfections in roundness and density would be calibrated from differential wave front sensing in a tetrahedral arrangement, supported by added attitude information via a grid of tick marks etched onto the surface and monitored by the laser readout.
Substrate Dependence of Mechanical Response of Neurons and Astrocytes (2011)

The response of neural cells to mechanical cues is a critical component of the innate neuroprotective cascade aimed at minimizing the consequences of traumatic brain injury (TBI). Reactive gliosis and the formation of glial scars around the lesion site are among the processes triggered by TBI where mechanical stimuli play a central role. It is well established that the mechanical properties of the microenvironment influence phenotype and morphology in most cell types. It has been shown that astrocytes change morphology [1] and cytoskeletal content [2] when grown on substrates of varying stiffness, and that mechanically injured astrocyte cultures show alterations in cell stiffness [3]. Accurate estimates of the mechanical properties of central nervous system (CNS) cells in their in-vivo conditions are needed to develop multiscale models of TBI. Lu et al found astrocytes to be softer than neurons under small deformations [4]. In recent studies, we investigated the response of neurons to large strains and at different loading rates in order to develop single cell models capable of simulating cell deformations in regimes relevant for TBI conditions [5]. However, these studies have been conducted on cells cultured on hard substrates, and the measured cell properties might differ from their in-vivo counterparts due to the aforementioned effects. Here, in order to investigate the effects of substrate stiffness on the cell mechanical properties, we used atomic force microscopy (AFM) and confocal imaging techniques to characterize the response of primary neurons and astrocytes cultured on polyacrylamide (PAA) gels of varying composition. The use of artificial gels minimizes confounding effects associated with biopolymer gels (both protein-based and polysaccharide-based) where specific receptor bindings may trigger additional biochemical responses [1].
Abstract 511: Adipocyte-derived fibroblasts contribute to the desmoplastic reaction in breast cancer: A new link between breast cancer and obesity (2011)

Abstract Now, it is widely established that malignant tumors, not merely grow into a preexisting interstitial tissue, but they actively form a new stroma and modify their composition. Accordingly, one of the features of many carcinomas, particularly breast, is the presence of a dense collagenous stroma, the so-called desmoplastic response, comprising fibroblast-like cells which play a crucial role in tumor progression. Peritumoral fibroblasts are composed of several subpopulations that are morphologically undistinguishable and their origins remain debated. Our results suggest that a part of this fibroblast could arise from the “reorientation” of mature adipocytes, highly represented in breast tumour microenvironment. Using an original 2D coculture system, we show that mature adipocytes cocultivated with breast tumour cells for 3 to 8 days lose their lipid content as well as their adipocyte differentiation markers (HSL, Adipsin, Adiponectin, C/EBPα, PPARγ, Resistin). This process is associated with intense morphological and functional changes leading to an activated fibroblast phenotype (exhibition of actin stress fibers, increase of focal adhesion sites). In this way, we have identified for the first time a new fibroblastic population called Adipocyte Derived Fibroblast (ADF). Interestingly, the reorientation occur in vivo since the injection of far red fluorescent tumour cells into a mice fatpad containing GFP-expressing adipocytes induce the apparition of GFP-fibroblast-like cells that interdigitate with tumour cells. Moreover, our results show that the ADF phenotype depends on the reactivation of the Wnt/β-catenin pathway. Finally, ADFs exhibit an increase of migratory and invasive abilities, with enhanced profibrotic secretions (fibronectin and collagen 1) suggesting that these cells could be key players in desmoplastic reaction. Ongoing experiments are performed to assess the presence of ADFs in breast human tumors. Our results might provide an explanation for the poor prognosis observed in localized breast cancer in obese women, since the nature of the desmoplastic reaction and the secretion pattern of ADF might be profoundly altered in this physiopathogical condition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 511. doi:10.1158/1538-7445.AM2011-511
Poster Session 2: Thursday 8 December 2011, 14:00-18:00 * Location: Poster Area (2011)

Background: Left atrial (LA) volumes are well-known predictors of cardiovascular outcome in a variety of heart diseases. However, LA is a 3D asymmetric structure and its volume calculations using 2D echo methods may be hampered by geometrical assumptions about its shape, acquisition of foreshortened or off-axis LA views. To partially overcome these limitations 3D echo has been used, but no 3D software specifically tailored for the LA quantitation has been available until recently. We sought to assess the influence of the echo technique and the algorithm used on LA volume measurement. Methods and results: 58 healthy volunteers aged 18 to 65 (38+12 years, 31 women) with good acoustic window, underwent acquisition of 2D apical 4- and 2-chamber views for the assessment of the LA and a 3D full-volume data set from apical approach (31+6 vps) for LA quantitation. LA volumes were calculated on 2D images using both single- and bi-plane disc summation algorithms. 3D LA data sets were quantitated using a software developed for the left ventricle (4D AutoLVQ, GE Healthcare, Horten N) and adapted to LA volume measurements, as well as with a novel semi-automatic software tailored for LA quantitation developed by TomTec (Unterschleissheim,Germany). Comparison of LA maximal and minimal volumes obtained using the 4 algorithms are summarized in the Table. Conclusions: In comparison to LA volumes obtained using a 3D software dedicated for LA analysis, both 2D algorithms and the non-atrial specific 3D software underestimate significantly LA volumes. Whether the implementation of atrial-specific 3D softwares could improve the prognostic stratification of patients with LA enlargement in various conditions remains to be verified.
Effects of Age and Disease Severity on Systemic Corticosteroid Responses in Asthma (2017)

One in five patients with SA exhibit greater than or equal to 10% improvement in FEV<sub>1</sub> with parenteral corticosteroid. Those likely to respond had greater bronchodilator responsiveness and fractional exhaled nitric oxide levels. In adults, differences in airflow obstruction and symptoms between SA and NONSA persist after parenteral corticosteroids, suggesting a component of corticosteroid nonresponsive pathobiology in adults with SA that may differ in children. Clinical trial registered with www.clinicaltrials.gov (NCT 01606826).
A Timing-Based Framework for Designing Resilient Cyber-Physical Systems under Safety Constraint (2022)

Cyber-physical systems (CPS) are required to satisfy safety constraints in various application domains such as robotics, industrial manufacturing systems, and power systems. Faults and cyber attacks have been shown to cause safety violations, which can damage the system and endanger human lives. Resilient architectures have been proposed to ensure safety of CPS under such faults and attacks via methodologies including redundancy and restarting from safe operating conditions. The existing resilient architectures for CPS utilize different mechanisms to guarantee safety, and currently there is no approach to compare them. Moreover, the analysis and design undertaken for CPS employing one architecture is not readily extendable to another. In this paper, we propose a timing-based framework for CPS employing various resilient architectures and develop a common methodology for safety analysis and computation of control policies and design parameters. Using the insight that the cyber subsystem operates in one out of a finite number of statuses, we first develop a hybrid system model that captures CPS adopting any of these architectures. Based on the hybrid system, we formulate the problem of joint computation of control policies and associated timing parameters for CPS to satisfy a given safety constraint and derive sufficient conditions for the solution. Utilizing the derived conditions, we provide an algorithm to compute control policies and timing parameters relevant to the employed architecture. We also note that our solution can be applied to a wide class of CPS with polynomial dynamics and also allows incorporation of new architectures. We verify our proposed framework by performing a case study on adaptive cruise control of vehicles.
Lymphatic Tissue Engineering (2008)

In the last 5 years major advances have been made in the field of tissue engineering. However, while engineering of tissues from nearly every major system in the body have been studied and improved, little has been done with the engineering of viable lymphatic tissues. Recent advances in understanding of lymphatic biology have allowed the easy isolation of pure lymphatic cell cultures, increasing, in turn, the ability to study lymphatic biology in greater detail. This has allowed the elucidation of lymphatic properties on the structural, cellular, and molecular levels, making possible the successful development of the first lymphatic engineered tissues. Among such advances are the engineering of lymphatic capillaries, the development of a functioning bioreactor designed to culture lymph nodes in vitro, and in vivo growth of lymphatic organoids. However, there has been no research on the engineering of functional lymphangions. While the advances made in the study of lymphatic biology are encouraging, the complexities of the system make the engineering of certain functional lymphatic tissues somewhat more difficult.
Peptide mimetics of the thrombin-bound structure of fibrinopeptide A. (1992)

Recent work has suggested that the thrombin-bound conformation of fibrinopeptide A exhibits a strand-turn-strand motif, with a beta-turn centered at residues Glu-11 and Gly-12. Our molecular modeling analysis indicates that the published fibrinopeptide conformation cannot bind reasonably to thrombin but that reorientation of two residues by alignment with bovine pancreatic trypsin inhibitor provides a good fit within the deep thrombin cleft and satisfies all of the experimental nuclear Overhauser effect data. Based on this analysis, we have successfully designed and synthesized hybrid peptide mimetic substrates and inhibitors that mimic the proposed beta-turn structure. The results indicate that the turn conformation is an important aspect of thrombin specificity and that our turn mimetic design successfully mimics the thrombin-bound conformation of fibrinopeptide.