gebhart/patrepeval huggingface dataset:
Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo (2010)

AZD6244 and MK2206 are targeted small-molecule drugs that inhibit MEK and AKT respectively. The efficacy of this combination in lung cancer is unknown. Our previous work showed the importance of activated AKT in mediating resistance of non-small cell lung cancer (NSCLC) to AZD6244. Thus we hypothesized that dual inhibition of both downstream MEK and AKT pathways would induce synergistic antitumor activity. In this study, we evaluated the efficacy of AZD6244 and MK2206 individually on a large panel of lung cancer cell lines. Then, we treated 28 human lung cancer cell lines with a combination of AZD6244 and MK2206 at clinically applicable drug molar ratios. The AZD6244-MK2206 combination therapy resulted in a synergistic effect on inhibition of lung cancer cell growth compared to the results of single drug treatment alone. MK2206 enhanced AZD6244-induced Bim overexpression and apoptosis in A549 and H157 cells. When we tested the combination of AZD6244 and MK2206 at ratios of 8∶1, 4∶1, 2∶1, and 1∶8, we found that the synergistic effect of the combination therapy was ratio-dependent. At ratios of 8∶1, 4∶1, and 2∶1, the drug combination consistently demonstrated synergy, whereas decreasing the ratio to 1∶8 resulted in a loss of synergy and produced an additive or antagonistic effect in most cell lines. Furthermore, the AZD6244-MK2206 combination therapy showed synergy in the suppression of A549 and H157 xenograft tumor growth and increased mean animal survival time. The AZD6244-MK2206 combination therapy resulted in effective inhibition of both p-ERK and p-AKT expression in tumor tissue. In addition, a significant increase of apoptosis was detected in tumor tissue from mice treated with AZD6244-MK2206 compared with that from the single agent treated mice. Our study suggests that the combination of AZD6244 and MK2206 has a significant synergistic effect on tumor growth in vitro and in vivo and leads to increased survival rates in mice bearing highly aggressive human lung tumors.
Behavior and Regional Cortical BOLD Signal Fluctuations Are Altered in Adult Rabbits After Neonatal Volatile Anesthetic Exposure (2020)

Neonatal and infant exposure to volatile anesthetics has been associated with long-term learning, memory, and behavioral deficits. Although early anesthesia exposure has been linked to a number of underlying structural abnormalities, functional changes associated with these impairments remain poorly understood. To investigate the relationship between functional alteration in neuronal circuits and learning deficiency, resting state functional MRI (rsfMRI) connectivity was examined in adolescent rabbits exposed to general anesthesia as neonates (1 MAC isoflurane for 2 h on postnatal days P8, P11, and P14) and unanesthetized controls before and after training with a trace eyeblink classical conditioning (ECC) paradigm. Long-range connectivity was measured between several key regions of interest (ROIs), including primary and secondary somatosensory cortices, thalamus, hippocampus, and cingulate. In addition, metrics of regional BOLD fluctuation amplitudes and coherence, amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) were calculated. Our results showed that the trace ECC learning rate was significantly lower in the anesthesia-exposed group. No anesthesia-related changes in long-range connectivity, fALFF, or ReHo were found between any ROIs. However, ALFF was significantly higher in anesthesia-exposed rabbits in the primary and secondary somatosensory cortices, and ALFF in those areas was a significant predictor of the learning performance for trace ECC. The absence of anesthesia-related changes in long-range thalamocortical connectivity indicates that functional thalamocortical input is not affected. Higher ALFF in the somatosensory cortex may indicate the developmental disruption of cortical neuronal circuits after neonatal anesthesia exposure, including excessive neuronal synchronization that may underlie the observed cognitive deficits.
Invited Discussion: Surgical Treatment of Treacher Collins Syndrome (2006)

From the Division of Plastic Surgery, Stanford University Medical Center, Stanford, CA. Received December 27, 2005 and accepted for publication January 3, 2006. Reprints: Stephen A. Schendel, MD, 770 Welch Road, Suite 400, Stanford, CA 94303. E-mail: [email protected].
Multi-feature entropy distance approach with vibration and acoustic emission signals for process feature recognition of rolling element bearing faults (2017)

To accurately reveal rolling bearing operating status, multi-feature entropy distance method was proposed for the process character analysis and diagnosis of rolling bearing faults by the integration of four information entropies in time domain, frequency domain and time–frequency domain and two kinds of signals including vibration signals and acoustic emission signals. The multi-feature entropy distance method was investigated and the basic thought of rolling bearing fault diagnosis with multi-feature entropy distance method was given. Through rotor simulation test rig, the vibration and acoustic emission signals of six rolling bearing faults (ball fault, inner race fault, outer race fault, inner ball faults, inner–outer faults and normal) are gained under different rotational speeds. In the view of the multi-feature entropy distance method, the process diagnosis of rolling bearing faults was implemented. The analytical results show that multi-feature entropy distance fully reflects the process feature of rolling bearing faults with the change of rotating speed; the multi-feature entropy distance with vibration and acoustic emission signals better reports signal features than single type of signal (vibration or acoustic emission signal) in rolling bearing fault diagnosis; the proposed multi-feature entropy distance method holds high diagnostic precision and strong robustness (anti-noise capacity). This study provides a novel and useful methodology for the process feature extraction and fault diagnosis of rolling element bearings and other rotating machinery.
Endothelial Specificity Of Icam2, Flt-1, And Tie2 Promoters In Vitro And In Vivo (2007)

To identify an endothelial cell-specific promoter suitable for vascular-specific targeting, we tested five promoters in vitro--Tie2SE, Tie2LE, ICAM2, Flt-1 and vWF--for promoter activity and specificity in endothelial cells, smooth muscle cells and non-vascular resident cells as well as tissues. These promoters, except for vWF, exhibited good endothelial activity and specificity in vitro. In a syngenic heart transplantation model, the ICAM2 promoter was variably functional in coronary endothelial cells of donor hearts. Thus, the ICAM2, Flt-1, Tie2SE and Tie2LE promoters hold promise for endothelial-specific targeting, but in vitro expression may not predict in vivo expression.
Further insight into BRUTUS domain composition and functionality (2016)

BRUTUS (BTS) is a hemerythrin (HHE) domain containing E3 ligase that facilitates the degradation of POPEYE-like (PYEL) proteins in a proteasomal-dependent manner. Deletion of BTS HHE domains enhances BTS stability in the presence of iron and also complements loss of BTS function, suggesting that the HHE domains are critical for protein stability but not for enzymatic function. The RING E3 domain plays an essential role in BTS' capacity to both interact with PYEL proteins and to act as an E3 ligase. Here we show that removal of the RING domain does not complement loss of BTS function. We conclude that enzymatic activity of BTS via the RING domain is essential for response to iron deficiency in plants. Further, we analyze possible BTS domain structure evolution and predict that the combination of domains found in BTS is specific to photosynthetic organisms, potentially indicative of a role for BTS and its orthologs in mitigating the iron-related challenges presented by photosynthesis.
Challenges of Modeling and Simulation of Clustered Bronzeville Community Microgrid (BCM) and IIT Campus Microgrid (ICM) Using RTDS (2020)

This paper presents the modeling and simulation of a microgrid cluster. This cluster is created by interconnecting the Illinois Institute of Technology (IIT) campus microgrid (ICM) and Bronzeville community microgrid (BCM), both located adjacent to each other in the city of Chicago. RTDS is used for modeling and simulating this microgrid cluster. With the help of real-time simulation, the microgrid cluster capabilities can be tested under a variety of conditions before the physical connection is provided in the grid. The challenges in the model development are discussed and addressed which can be used as guidelines for researchers in this field. Preliminary test results on the clustered ICM-BCM are provided in this paper.
Imine-based chiroptical sensing for analysis of chiral amines: from method design to synthetic application (2014)

A robust chiroptical method for fast enantiopurity determination of chiral amines utilizing HPLC-CD, applied to monitoring crude transamination reactions.
Experimental Study of Transient Processes in a Coil Capacitor when Connecting to a Source of Sinusoidal Voltage (2021)

Results are presented from theoretical modeling and experimental studies of transient processes in a coil capacitor (coilcap) when connecting to a source of sinusoidal voltage. It is shown that transient processes behave as in an RLC circuit with lumped parameters; i.e., resonance, beating, overvoltage, and overcurrent modes are all possible.
New insights into photorespiration obtained from metabolomics (2013)

Photorespiration, one of the cornerstone pathways of primary metabolism, allows plant growth in a high oxygen-containing environment. While the oxygenase reaction of Rubisco directly influences photosynthesis per se, several other processes are also affected by photorespiration, including nitrogen assimilation, respiration, amino acid metabolism, 1-C metabolism and redox metabolism, cumulating to impose a severe impact across multiple signalling pathways. Accordingly, although the plant photorespiratory cycle is complex and highly compartmentalised, little is currently known about the participating transport proteins, and relatively few of them have been properly identified. Despite its centrality, uniqueness, and mystery, the biochemistry of photorespiration has historically been quite poorly understood, in part because at least some of its enzymes and intermediates tend to be labile and of low abundance. Fortunately, the integration of molecular and genetic approaches with biochemical ones, such as metabolite profiling, is now driving rapid advances in knowledge of the key metabolic roles and connections of the enzymes and genes of the photorespiratory pathway. While these experiments have revealed a surprising complexity in the response and established connections between photorespiration and other metabolic pathways, the mechanisms behind the observed responses have still to be fully elucidated. Here we review recent progress into photorespiration and its interaction with other metabolic processes, paying particular attention to data emanating from metabolic profiling studies.
Perspective: Stepping Stones to Unraveling the Pathophysiology of Mal de Debarquement Syndrome with Neuroimaging (2018)

Mal de debarquement syndrome (MdDS) is a neurological condition typically characterized by a sensation of motion, which in most cases manifests after disembarking from a vehicle (e.g., boat, plane, and car). However, the same symptoms can also occur spontaneously. Two main theories of the pathophysiology of MdDS are briefly summarized here. In this perspective, we aimed to report the most recent findings on neuroimaging studies related to MdDS, as well as to suggest further potential research questions that could be addressed with the use of neuroimaging techniques. A detailed analysis of previous work on MdDS has led to five main research questions that could be addressed in new neuroimaging studies. Furthermore, in this perspective, we propose new stepping-stones to addressing critical research questions related to MdDS and its pathophysiology. We propose considerations for new studies, as well as a detailed analysis of the current limitations and challenges present when studying MdDS patients. We hope that our examination of the nuances of MdDS as a neurological disorder will contribute to more directed research on this topic.
B7-H3 expression in colorectal cancer: associations with clinicopathological parameters and patient outcome (2014)

Overexpression of B7-H3 in colorectal cancer was confirmed, but in contrast to previous results, nuclear B7-H3 was not a strong prognostic biomarker in this cohort. The discrepancy might be related to the use of single-core tissue microarrays for detection of the heterogeneously expressed B7-H3, and the role of B7-H3 in colorectal cancer still needs further examination.
Eutrophication of the Finnish coastal waters : origin, fate and effects of riverine nutrient fluxes (1994)

Suomen rannikkovesien rehevöityminen: jokivesien tuomien ravinteiden alkuperä, käyttäytyminen ja vaikutukset.
Landesverfassungsgerichtsbarkeit, Verfassungsgerichtsverbund und Verfassungsdemokratie in der Bundesrepublik Deutschland (2022)

The 4th edition of the first volume of this work provides an update of the commentary on the preamble and articles 1 to 19 in case law and literature. The structure of the book has been retained and its content supplemented by more recent developments, such as the implications of Europeanisation and digitalisation as well as the Corona pandemic. As of the 4th edition, Frauke Brosius-Gersdorf has taken over the editorship of the commentary.
Nonlinear model of single hippocampal neurons with dynamical thresholds (2009)

Neurons transform a series of presynaptic spikes into a series of postsynaptic spikes through a number of nonlinear mechanisms. A nonlinear model with a dynamical threshold was built using a Volterra Laguerre kernel method to characterize the spike train to spike train transformations of hippocampal CA1 pyramidal neurons. Inputs of the model were broadband Poisson random impulse trains with a 2 Hz mean frequency, and outputs of the model were the corresponding evoked post-synaptic potential (PSP) and spike train data recorded from CA1 cell bodies using a whole-cell recording technique. The model consists of four major components, i.e., feedforward kernels representing the transformation of presynaptic spikes to PSPs; a dynamical threshold kernel determining threshold value based on output inter-spike-intervals (ISIs); a spike detector; and a feedback kernel representing the spike-triggered after-potentials.
Interleukin-1 deficiency prolongs ovarian lifespan in mice (2014)

Oocyte endowment dwindles away during prepubertal and adult life until menopause occurs, and apoptosis has been identified as a central mechanism responsible for oocyte elimination. A few recent reports suggest that uncontrolled inflammation may adversely affect ovarian reserve. We tested the possible role of the proinflammatory cytokine IL-1 in the age-related exhaustion of ovarian reserve using IL-1α and IL-1β-KO mice. IL-1α-KO mice showed a substantially higher pregnancy rate and litter size compared with WT mice at advanced age. The number of secondary and antral follicles was significantly higher in 2.5-mo-old IL-1α-KO ovaries compared with WT ovaries. Serum anti-Müllerian hormone, a putative marker of ovarian reserve, was markedly higher in IL-1α-KO mice from 2.5 mo onward, along with a greater ovarian response to gonadotropins. IL-1β-KO mice displayed a comparable but more subtle prolongation of ovarian lifespan compared with IL-1α-KO mice. The protein and mRNA of both IL-1α and IL-1β mice were localized within the developing follicles (oocytes and granulosa cells), and their ovarian mRNA levels increased with age. Molecular analysis revealed decreased apoptotic signaling [higher B-cell lymphoma 2 (BCL-2) and lower BCL-2-associated X protein levels], along with a marked attenuation in the expression of genes coding for the proinflammatory cytokines IL-1β, IL-6, and TNF-α in ovaries of IL-1α-KO mice compared with WT mice. Taken together, IL-1 emerges as an important participant in the age-related exhaustion of ovarian reserve in mice, possibly by enhancing the expression of inflammatory genes and promoting apoptotic pathways.
Three-Dimensional Stereo Measurements in Bubbly Pipe Flows With Particle Tracking Velocimetry (2000)

Abstract In a two-phase bubbly flow, the continuous phase velocity field can be captured using standard PIV techniques, and the gas phase configuration can be determined using, for example, a shadow technique. If the PIV system includes a three-dimensional shadow PIV measurement set up, the bubble locations in the standard PIV measurements can be determined. Then, the bubble images are removed, and a typical anlysis of the liquid phase can be performed. An experimental set up that combines the traditional PIV technique with a shadow technique will be described and sample PIV images will be analyzed to demonstrate an advanced velocity vector analysis method in a two-phase bubbly flow system.
Adenosine Prevents the Death of Mesencephalic Dopaminergic Neurons by a Mechanism that Involves Astrocytes (1999)

The purinergic nucleoside adenosine effectively prevented the death of dopaminergic neurons that occurs spontaneously and progressively in cultures of rat mesencephalon. Adenosine also significantly increased dopamine uptake, attesting to the state of differentiation and functional integrity of the neurons that were rescued. The effects of adenosine were (a) specific to the dopaminergic neurons in these cultures, (b) long-lived, (c) still observed when the treatment was delayed after plating, (d) potentiated by inhibition of adenosine deaminase, and (e) abolished when this enzyme was added in excess to the culture medium. The action of adenosine was mimicked by 5'-(N-ethylcarboxamido)adenosine and dibutyryl-cyclic AMP, but not by CGS-21680, suggesting the possible involvement of A2B subtype purinergic receptors. ATP was also neuroprotective, but its action resulted principally from conversion to adenosine by ectonucleotidases. Several anticancer drugs, including cytosine arabinoside, have been shown previously to prevent apoptosis in cultured dopaminergic neurons by a mechanism that requires the inhibition of proliferating astrocytes. In the presence of adenosine, astrocytes were more differentiated, and their proliferation rate was significantly reduced, suggesting that the neurotrophic effect of the adenine nucleoside resulted also from the repression of the astroglial cells. We did not find evidence of a trophic intermediary in adenosine-treated cultures, however, leading to the hypothesis that limitation of astrocyte replication in itself and/or ensuing changes in the glial phenotype were crucial. Our results suggest that molecules that modulate adenine nucleotide/nucleoside release may be useful for the treatment of chronic neurodegenerative conditions affecting dopaminergic neurons, such as Parkinson's disease.
A Study on Sound Feedback in a Virtual Environment for Gait Rehabilitation (2007)

For the rehabilitation of stroke and spinal cord injured patients, actuated gait orthoses are used to automate treadmill training. To increase motivation and provide task-specific feedback for these patients, virtual environments are developed and evaluated by many research groups. This paper describes the design, implementation and preliminary evaluation of sound feedback strategies for the actuated gait orthosis LOKOMAT. In the context of an obstacle scenario, the scenario parameters distance and foot height are displayed by sound. An evaluation study with 17 healthy subjects compared no sound feedback (control condition), distance feedback, height feedback, and combined feedback. Visual feedback was present in all conditions. Results indicate that subjects walk faster and hit fewer obstacles when acoustic feedback is present. The findings suggest that acoustic feedback is helpful as a complementary modality and can be applied to a variety of virtual, task-oriented rehabilitation environments.
Tuberculosis and HIV Coinfection: Genesis of the Supplement and Sponsors’ Contribution (2007)

This supplement to the Journal of Infectious Diseases on tuberculosis (TB)/HIV coinfection came together as a result of a collaboration between the National Institutes of Health (NIH)-funded Centers for AIDS Research (CFARs) at Harvard University and at the University of Pennsylvania and the Forum for Collaborative HIV Research. It is based on 2 programs addressing TB/HIV coinfection research challenges. A steering committee consisting of Bruce Walker Edward Nardell Megan Murray and Eric Rubin (Harvard University); Gerald Friedland (Yale University); and James Hoxie (University of Pennsylvania); with the support of the national network of CFARs organized a symposium entitled Confronting TB/HIV Co-infection that was held on 30 June 2005 at Harvard University. The Forum for Collaborative HIV Research together with the International AIDS Society and the Agence National de Recherches sur le Sida et les Hepatites Virales with special support from Tibotec sponsored a special session entitled HIV/TB: New Visions New Directions during the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro on 25 July 2005 followed by a roundtable discussion with representatives from the World Health Organization HIV/ AIDS and Stop TB departments; the Global Fund to Fight AIDS Tuberculosis and Malaria; the NIH; the Centers for Disease Control and Prevention (CDC); and leaders from the pharmaceutical industry research networks and advocacy organizations. (excerpt)