gebhart/patrepeval huggingface dataset:
Adenosine and other low molecular weight factors released by muscle cells inhibit tumor cell growth. (1998)

In this study, we investigated the basis of the resistance of muscles to tumor metastases. We found that a low molecular weight fraction (Mr <3000) of skeletal muscle cell-conditioned medium (MCM) markedly inhibits the proliferation of carcinoma, sarcoma, or melanoma cell lines in vitro. The MCM exerts a cytostatic effect on tumor cell growth and arrests the cells in G0/G1 of the cell cycle. However, normal cell proliferation of cells such as bone marrow cells or fibroblasts was found to be refractory to the influence of the MCM. A reduction in melanoma growth was observed in mice treated with the MCM. Adenosine was identified as one of the active components in the MCM by using high-performance liquid chromatography separations, mass spectra, and nuclear magnetic resonance analyses. At a concentration of 4 microM, equal to that found in the MCM, adenosine inhibits the proliferation of tumor cell lines (Nb2 lymphoma, K-562 leukemia, and LNCaP prostate carcinoma cells) while stimulating the proliferation of normal murine bone marrow cells. By similar methods, additional inhibitory components were detected in the MCM in a molecular mass range of 600-800 Da. The ability of adenosine and other low molecular weight components to specifically inhibit tumor cell growth in vitro and in vivo may account for the resistance of muscle to tumor metastases.
Dissociating the pro‐cognitive effects of donepezil and an M1 PAM (2022)

Abstract Background Donepezil, an FDA approved drug for dementia in Alzheimer’s disease, increases the extracellular concentration of acetylcholine non‐selectively stimulating cholinergic receptors indiscriminately leading to dose‐limiting side effects. Muscarinic M1 sub‐receptor specific positive allosteric modulators (PAMs) have shown promise in addressing symptoms in Alzheimer’s disease, Schizophrenia and more 1 . M1 PAMs have little to no agonistic properties, avoiding peripheral side effects, and are mostly centrally located allowing for the modulation of endogenous signaling of the brain 2 . Method We tested non‐human primates in two tasks measuring cognitive flexibility and attentional control 3 at varying doses of donepezil and an M1 PAM (VU0453595). Attentional control was measured with a visual search task requiring animals to search for a learned target object among distractors of variable number and similarity to the target object. Cognitive flexibility was measured with a feature‐reward learning task that required animals to learn the value of objects of varying feature complexity by trial and error. Flexibility was indexed as the speed of learning, the degree of latent inhibition and the amount of target perseveration after switching the rewarded feature. Result Donepezil enhanced attention control at a high dose (0.3 mg/kg) but enhance flexibility only moderately at a lower dose (0.06 mg/kg). In contrast, VU0453595 did not modulate attention, but at 0.1 mg/kg enhanced flexible learning, reduced target perseverations, and increased reaction time measures of decision confidence. At the dose with the most pronounced cognitive benefits donepezil resulted in gastrointestinal side effects, while VU0453595 did not cause side effects. Conclusion These results suggest that donepezil engages the brain networks underlying cognitive flexibility and interference control at different doses 4 , while the M1 receptor plays a major role in facilitating flexible behavioral adaptation but with no role in controlling interference. Such receptor specific results can be used to better curate to patient‐specific needs in order to address the most debilitating symptoms with the highest efficacy. 1. Melancon, B. J. et al. (2013) Drug Discovery Today https://doi.org/10.1016/j.drudis.2013.09.005. 2. Ghoshal, A. et al. (2016) Neuropsychopharmacology doi:10.1038npp.2015.189 3. Womelsdorf, T. et al. (2021) Frontiers in Behavioral Neuroscience https://doi.org/10.3389/fnbeh.2021.721069 4. Hassani, S.A. et al. (2021) Biological Psychiatry Global Open Science https://doi.org/10.1016/j.bpsgos.2021.11.012.
Single-cell analysis of the epigenomic and transcriptional landscape of innate immunity to seasonal and adjuvanted pandemic influenza vaccination in humans (2021)

Abstract Emerging evidence indicates a fundamental role for the epigenome in immunity. Here, we used a systems biology approach to map the epigenomic and transcriptional landscape of immunity to influenza vaccination in humans at the single-cell level. Vaccination against seasonal influenza resulted in persistently reduced H3K27ac in monocytes and myeloid dendritic cells, which was associated with impaired cytokine responses to TLR stimulation. Single cell ATAC-seq analysis of 120,305 single cells revealed an epigenomically distinct subcluster of monocytes with reduced chromatin accessibility at AP-1-targeted loci after vaccination. Similar effects were also observed in response to vaccination with the AS03-adjuvanted H5N1 pandemic influenza vaccine. However, this vaccine also stimulated persistently increased chromatin accessibility at loci targeted by interferon response factors (IRFs). This was associated with elevated expression of antiviral genes and type 1 IFN production and heightened resistance to infection with the heterologous viruses Zika and Dengue. These results demonstrate that influenza vaccines stimulate persistent epigenomic remodeling of the innate immune system. Notably, AS03-adjuvanted vaccination remodeled the epigenome of myeloid cells to confer heightened resistance against heterologous viruses, revealing its potentially unappreciated role as an epigenetic adjuvant.
The regulation of erythropoiesis by Hedgehog (Hh) signalling (2017)

Dhh (Desert Hedgehog) is one of three Hedgehog (Hh) proteins essential for testis development and Schwann cell function. Gli1, Gli2, and Gli3 are dedicated transcription factors that transduce the Hh pathway. A study published by our group showed significant changes in erythrocyte differentiation in Dhh-deficient mice, under steady state and stress-induced conditions, implicating Dhh as a negative regulator of murine erythropoiesis (Lau et al., 2012). To investigate these phenotypic differences, we created an mCherry reporter mouse line for Dhh using Bacterial Artificial Chromosome ‘recombineering’ and hypothesised that Dhh is produced by the splenic stroma, especially red pulp fibroblasts (RPFs), under steady state and anaemic stress. Erythroblast kinetics were also analysed in Hedgehog-related mouse lines during haematopoietic recovery. After validating the mCherry line as a faithful reporter of Dhh using testes, brain and thymic tissue, we found that Dhh (mCherry) is expressed by a fraction of all splenic ICAM-1+ stromal cells in particular RPFs and also fibroblast reticular cells (FRCs), disproving our steady state hypothesis. During anaemia, Dhh was not upregulated but showed most expression in the RPF subset in support of our hypothesis, while some follicular dendritic cells (FDCs) and marginal reticular cells (MRCs) significantly upregulated Dhh. Interestingly, Dhh was more highly detected in antigen-presenting cells (APCs) and some non-APCs under normal and anaemic conditions, potentially implicating Dhh in white pulp splenic functions. Irradiating Dhh-deficient mice corroborated Dhh as a negative erythropoietic regulator by analysing reticulocytes and splenic erythroid progenitors, in line with Dhh-deficient mice exhibiting less Gli-binding activity in their BM and spleen. In Gli3-heterozygote mice elevated Shh but reduced Dhh expression was found in the spleen, supporting our hypothesis that Gli3 represses Shh. Irradiating Gli3-heterozygote mice showed significant expansion of erythroblast differentiation in the BM but not the spleen, highlighting the intricacies of the Hh signalling pathway in erythropoiesis.
Excursion Prevention Strategyto Increase Chip Performance by Photomask Tuning (2020)

Advanced process control in lithography and overall patterning is of tremendous importance for advanced semiconductor Fabs to ensure chip performance and yield. The final patterning result and thus yield depend on many process parameters such as lithography processes, exposure tool performance, etch process, CMP etc. To control these effects various knobs, e.g. on the scanner for both wafer inter- and intra-field process control have been introduced recently, including sophisticated in-line metrology.In this holistic lithography concept the metrology is supported by simulation and by inline data. Additionally, offline data such as the mask CDU data can be added as mask wafer interaction is also an important contribution to wafer intra-field performance. The metrology algorithm now looks for such locations where the simulation finds the weakest process features due to strong deviations of focus, dose, stage dynamics or other input parameters. These concepts are optimized to find the sites where the process may break. Our concept of “excursion preventions” is a complimentary approach. It concentrates pro-actively on the task to minimize the distributions of critical input parameters as much as possible, independently upon a certain pre-defined specification for that parameter is met or not. In our presentation, we will describe this concept by improving wafer intra-field CDU using CD Correction (CDC) by MaskTuning (based on wafer Intra-Filed data). Mask Tuning by the For Tune system uses ultra-short pulse laser technology to locally change the mask transmission and hence improves CDU on wafer (CDC). To ensure a save patterning with a large enough process window without any negative yield or reliability impact, our concept looks for the tail of the final CD distribution instead of traditional 3sigma numbers. By using a calibrated 3-D resist model, we simulate the pattering result under all permutations of input parameter distributions like dose, focus and mask CDU and imaging stochastics. As a result of the simulation, we get thousands of CD-results. The tail of that CD distribution still needs to be larger the minimum CD needed for a safe etch transfer. The simulation will be additionally supported by experimental data. Secondly, we will show in detail how the pro-active optimization of wafer intra-field CDU by MaskTuning using the For Tune CDC process will give us more patterning margin and process stability over any other process excursion (e.g. focus deviations). Furthermore, we will present the simulated yield improvement based on the weak points (hot spots) improvement.
Design of a Drilling Rig for 10,000 ft Water Depth using a Pressured Riser (2002)

Abstract This paper presents the requirements for a drilling rig to drill in up to 10,000 ft of water using a pressured riser. An analysis of deepwater wells drilled was carried out to determine what characteristics (Water depth, drilled depth, number of casing strings etc..) these wells had. A "look forward" portfolio of wells was constructed as the target for the design of the rig. A full QRA was conducted to examine the impact of emerging technologies such as Expandables and Dual Gradient and to determine which choices for rig components were appropriate. The paper includes an outline rig design for deepwater for West Africa and one for GOM operations. An outline specification for the well systems (BOP, riser configuration) is also included. A comparison is made of the impact of drilling deepwater wells with this "new" approach versus using the "conventional subsea BOP" arrangement. The paper also includes details of how the "new" approach may be applied to existing rig types and how it may be applied to a new-build. The cost implications of this step change are examined. Fully risked well cost comparisons (‘new" vs "conventional") are provided along with some comment on the risks and consequences of the available choices. The paper concludes that the "new" rig specifications detailed will allow for deepwater drilling in up to 10,000 ft water depth and that in some cases there will be significant overall well cost savings.
Plasma Spectroscopy Diagnostics in Pulsed-Power X-Ray Radiography Diode Research (2005)

Spectroscopic investigations in the visible and near UV are underway to study plasmas present in X-ray radiography diodes during the time of the electron beam propagation. These studies are being performed on the RITS-3 accelerator (5.25 MV and 120 kA) at Sandia National Laboratories using several diode configurations. The proper characterization of the plasmas occurring during the time of the X-ray pulse can lead to a greater understanding of diode behavior and X-ray spot size evolution. By studying these plasmas along with the use of selective dopants, insights into such phenomena as impedance collapse, thermal and non-thermal species behavior, charge and current neutralization, anode and cathode plasma formation and propagation, and beam/foil interactions, can be obtained. Information from line and continuum emission and absorption can give key plasma parameters such as temperatures, densities, charge states, and expansion velocities. This information is important for proper modeling and future predictive capabilities for the design and improvement of flash X-ray radiography diodes. Diagnostics include a gated, intensified multichannel plate camera combined with a 1 meter Czerny-Turner monochromator with a multi-fiber spectral input, allowing for both temporal and spatial resolution. Recent results are presented.
Ultra-Thin All-Epitaxial Plasmonic Detectors (2021)

We present an infrared photodetector leveraging an all-epitaxial device architecture consisting of a 'designer' plasmonic metal integrated with a quantum-engineered detector structure, all in a mature III-V semiconductor material system. Incident light is coupled into surface plasmon-polariton modes at the detector/'designer' metal interface, and the strong confinement of these modes allows for a sub-diffractive ($\sim λ_0 / 33$) detector absorber layer thickness, effectively decoupling the detector's absorption efficiency and dark current. We demonstrate high-performance detectors operating at non-cryogenic temperatures (T = 195 K), without sacrificing external quantum efficiency, and superior to well established and commercially-available detectors. This work provides a practical and scalable plasmonic optoelectronic device architecture with real world mid-infrared applications.
In vivo Identification and Specificity assessment of mRNA markers of hypoxia in human and mouse tumors (2011)

The portrayed technique allows multiple pairwise measurements of mRNA transcript levels and extent of hypoxia in individual tumors at a smallest possible volumetric scale which (by limiting averaging effects inherent to whole-tumor analysis) strengthen the conclusiveness on true hypoxia-specificity of candidate genes while limiting the required number of tumors. Among tested genes, our study identified CA9, GLUT1 and possibly LOX as highly specific biomarkers of tumor hypoxia in vivo.
Therapeutic approaches for treating hemophilia A using embryonic stem cells (2016)

Hemophilia A is an X-linked rescessive bleeding disorder that results from F8 gene aberrations. Previously, we established embryonic stem (ES) cells (tet-226aa/N6-Ainv18) that secrete human factor VIII (hFVIII) by introducing the human F8 gene in mouse Ainv18 ES cells. Here, we explored the potential of cell transplantation therapy for hemophilia A using the ES cells. Transplant tet-226aa/N6-Ainv18 ES cells were injected into the spleens of severe combined immunodeficiency (SCID) mice, carbon tetrachloride (CCl4)-pretreated wild-type mice, and CCl4-pretreated hemophilia A mice. F8 expression was induced by doxycycline in drinking water, and hFVIII-antigen production was assessed in all cell transplantation experiments. Injecting the ES cells into SCID mice resulted in an enhanced expression of the hFVIII antigen; however, teratoma generation was confirmed in the spleen. Transplantation of ES cells into wild-type mice after CCl4-induced liver injury facilitated survival and engraftment of transplanted cells without teratoma formation, resulting in hFVIII production in the plasma. Although CCl4 was lethal to most hemophilia A mice, therapeutic levels of FVIII activity, as well as the hFVIII antigen, were detected in surviving hemophilia A mice after cell transplantation. Immunolocalization results for hFVIII suggested that transplanted ES cells might be engrafted at the periportal area in the liver. Although the development of a safer induction method for liver regeneration is required, our results suggested the potential for developing an effective ES-cell transplantation therapeutic model for treating hemophilia A in the future.
Problems with Co-Funding in Canada (2005)

The Canadian Federal Government has prudently invested substantial new resources in research operations and infrastructure, thereby bringing the level of research support in Canada on par with that of most other G8 countries and enabling a world-class research enterprise. Much of this renewed
Direct Synthesis of Hydrogen Peroxide over Au–Pd Supported Nanoparticles under Ambient Conditions (2019)

The direct synthesis of hydrogen peroxide (H2O2) from molecular H2 and O2 over Au–Pd/TiO2 catalysts prepared using a modified impregnation methodology is studied. Initially we investigated the role of the Au:Pd ratio on the catalytic activity toward H2O2 formation and its subsequent degradation under conditions that have previously been found to be optimal for the formation of H2O2 using high pressure reactants and low temperatures. Subsequently, we have conducted a detailed study of H2O2 synthesis under ambient conditions which are both more challenging for achieving high yields of H2O2 but more likely to be used for future industrial applications.
Effects of fish oil on arteriosclerosis in the Japanese quail (1989)

The effects of fish oil on the development of arteriosclerosis were assessed using a special susceptible strain (SEA) of Japanese quail (Coturnix coturnix japonica). Sixty four quail were randomly divided into two groups and placed on isocaloric and approximately isocholesterolic (2% by weight) diets. Group A (control) was supplemented with 10% beef tallow oil, while group B received 10% Menhaden fish oil. The birds were sacrificed at 10 weeks (early) and 15-16 weeks (late). Based on semiquantitative histological grading of the arteriosclerotic lesions in the proximal aorta and brachiocephalic arteries, a score from 1 (no lesion) to 5 (severe, diffuse lesions) was assigned. A total of 57 quail were evaluated (seven died prior to scheduled sacrifice). At the early period, the mean arteriosclerosis scores for group A (n = 8) and group B (n = 8) were 3.3 (SD 1.0) and 1.9(1.0) respectively (p less than 0.017); 63% of the quail in group A and 13% of those in group B had a score greater than or equal to 3 (p less than 0.25, NS). At the late period, the scores for group A (n = 20) and group B (n = 21) were 3.8(0.6) and 2.6(0.9), respectively (p less than 0.001); 95% of the birds in group A and 43% of those in group B had a score greater than or equal to 3 (p less than 0.005). Histopathological examination of the arteriosclerotic lesions revealed disruption of the innermost elastic lamina, increased proteoglycan deposition in the medial interlamellar spaces, and the distinct involvement of macrophage like cells. Compared to human disease, arteriosclerosis in the quail is marked by distinct similarities, as well as differences. The SEA strain of Japanese quail appears to be a practical model for the study of arteriosclerosis; fish oil reduces the severity of disease in these birds when fed a high cholesterol diet.
Biomimetic Micropatterning of Electrospun Scaffolds for Tissue Engineering (2015)

The nanostructure of the extracellular matrix (ECM) can direct cell attachment, alignment, and organization. Similarly, ECM microstructures such as tubes and branched networks organize cells into larger functional units. To mimic this complex cellular microenvironment in tissue engineered scaffolds, we need new fabrication methods capable of constructing structures on both the nano- and micro-scale. Furthermore, these methods should be compatible with a variety of biomaterials to allow tailoring of mechanical and degradation properties. Electrospinning is a useful technique for creating fibrous scaffolds, but there have been few reports introducing microstructures. This dissertation describes the development of a new versatile fabrication approach that combines electrospinning with a fused deposition modeling (FDM) 3D printer to create microstructures that mimic tissues. We hypothesized that these structures would improve cell migration and positioning within electrospun scaffolds. We tested this hypothesis by patterning scaffolds for peripheral nerves and microvascular networks. We first demonstrate the feasibility of templated electrospinning for generating linear channels in fibrous nerve guides that mimic the endoneurial/fascicular tubes of nerve and promote faster Schwann cell infiltration. This micropatterning technique was combined with FDM production of branched templates to create microvascular networks within fibrous scaffolds. Finally, material properties were improved by developing a technique to fabricates scaffolds with electrospun poly(glycerol sebacate)(PGS).
The Effect of Patient Position on Intrarenal Anatomy (1999)

The LIP angle broadens when the patient lies in a prone 20 degrees head down position. This maneuver could improve the surgeon's ability to access the lower pole calices when performing flexible ureteronephroscopy.
NETWORKS OF NEURONS AND POPULATION ACTIVITY (2014)

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Quasi-D Diesel Engine Combustion Modeling With Improved Diesel Spray Tip Penetration, Ignition Delay and Heat Release Sub-Models (2016)

Increasingly stringent fuel economy and CO2 emission regulations provide a strong impetus for development of high efficiency engine technologies. Diesel engines dominate the heavy duty market and significant segments of the global light duty market due to their intrinsically higher thermal efficiency compared to spark ignited (SI) engine counterparts. Predictive simulation tools can significantly reduce the time and cost associated with optimization of engine injection strategies, and enable investigation over a broad operating space unconstrained by availability of prototype hardware. In comparison with 0-D/1-D and 3-D simulations, Quasi-D models offer a balance between predictiveness and computational effort, thus making them very suitable for enhancing the fidelity of engine system simulation tools. A most widely used approach for diesel engine applications is a multi-zone spray and combustion model pioneered by Hiroyasu and his group. It divides diesel spray into packets and tracks fuel evaporation, air entrainment, gas properties and ignition delay (induction time) individually during the injection and combustion event. However, original sub-models are not well suited for modern diesel engines, and the main objective of this work is to develop a multi-zonal simulation capable of capturing the impact of high-injection pressures and Exhaust Gas Recirculation (EGR). In particular, a new spray tip penetration sub-model is developed based on measurements obtained in a high-pressure, high-temperature constant volume combustion vessel for pressures as high as 1450 bar. Next, ignition delay correlation is modified to capture the effect of reduced oxygen concentration in engines with EGR, and an algorithm considering the chemical reaction rate of hydrocarbon-oxygen mixture improves prediction of the heat release rates. Spray and combustion predictions were validated with experiments on a single-cylinder diesel engine with common rail fuel injection, charge boosting, and EGR.