gebhart/patrepeval huggingface dataset:
From Error to Error: Logic Debugging in the Many-Core Era (2007)

Design and manufacturing of present day Multi-Core microprocessors has to overcome major technology obstacles, particularly in the areas of Power and Validation. More specifically, the state of the Art in the area of validation is such that upwards of 30% of the human resources in a modern microprocessor Design Team are dedicated to it. The term Validation Productivity Gap has been introduced to describe exactly these ever increasing resource requirements. Formal Verification techniques offer one of the technological approaches for addressing many aspects of this validation gap. Therefore it is of paramount importance to develop technologies and methodologies for reducing the time it takes to debug and rectify Logic Errors that are detected by Formal Verification Techniques. Such developments would offer a much needed productivity improvement both in pre- and post-Silicon validation activities.
Neural stem cell engineering: directed differentiation of adult and embryonic stem cells into neurons (2007)

Both adult neural stem cells and embryonic stem cells have shown the capacity to differentiation into multiple cell types of the adult nervous system. They will therefore serve as valuable systems for basic investigations of cell fate choice mechanisms, as well as play important future roles in applications ranging from regenerative medicine to drug screening. However, there are significant challenges remaining, including the identification of signaling factors that specify cell fate in the stem cell niche, the analysis of intracellular targets and mechanisms of these extracellular signals, and the development of ex vivo culture systems that can exert efficient control over cell function. This review will discuss progress in the identification of signaling mechanisms and culture systems that regulate neural differentiation, neuronal differentiation, and neuronal subtype specification.
Author response: The repurposing of Tebipenem pivoxil as alternative therapy for severe gastrointestinal infections caused by extensively drug-resistant Shigella spp (2022)

The oral carbapenem 'Tebipenem' has high level antibacterial activity against highly drug-resistant Shigella, and its mode of action and pharmacokinetics make it suitable for the treatment of severe diarrhoea caused by highly drug-resistant bacteria.
Slide‐free imaging of hematoxylin‐eosin stained whole‐mount tissues using combined third‐harmonic generation and three‐photon fluorescence microscopy (2019)

Intraoperative margin assessment of surgical tissues during cancer surgery is clinically important, especially in the case of tissue conserving surgery like Mohs micrographic surgery in which minimization of the surgical area is considered crucial. Frozen pathology is the gold standard of assessing excised tissues for signs of remaining cancerous lesions. The current protocol, however, is time-consuming and labor-intensive. Instead of the complex frozen sectioning, staining, and traditional white light microscopy imaging protocol, optically sectioned histopathological imaging of hematoxylin-eosin stained whole-mount skin tissues with a subfemtoliter resolution is demonstrated by using nonlinear microscopy in this study. With our proposed method, the reagents of staining and the contrast of imaging are fully consistent with the current clinical standard of frozen pathology, thus facilitating rapid intraoperative assessment of surgical tissues for future applications. Image: Slide-free nonlinear microscopy imaging of H&E stained whole-mount skin tissue showing the morphology of sweat glands.
Cancer metabolism, stemness and tumor recurrence (2013)

Here, we interrogated head and neck cancer (HNSCC) specimens (n = 12) to examine if different metabolic compartments (oxidative vs. glycolytic) co-exist in human tumors. A large panel of well-established biomarkers was employed to determine the metabolic state of proliferative cancer cells. Interestingly, cell proliferation in cancer cells, as marked by Ki-67 immunostaining, was strictly correlated with oxidative mitochondrial metabolism (OXPHOS) and the uptake of mitochondrial fuels, as detected via MCT1 expression (p < 0.001). More specifically, three metabolic tumor compartments were delineated: (1) proliferative and mitochondrial-rich cancer cells (Ki-67+/TOMM20+/COX+/MCT1+); (2) non-proliferative and mitochondrial-poor cancer cells (Ki-67-/TOMM20-/COX-/MCT1-); and (3) non-proliferative and mitochondrial-poor stromal cells (Ki-67-/TOMM20-/COX-/MCT1-). In addition, high oxidative stress (MCT4+) was very specific for cancer tissues. Thus, we next evaluated the prognostic value of MCT4 in a second independent patient cohort (n = 40). Most importantly, oxidative stress (MCT4+) in non-proliferating epithelial cancer cells predicted poor clinical outcome (tumor recurrence; p < 0.0001; log-rank test), and was functionally associated with FDG-PET avidity (p < 0.04). Similarly, oxidative stress (MCT4+) in tumor stromal cells was specifically associated with higher tumor stage (p < 0.03), and was a highly specific marker for cancer-associated fibroblasts (p < 0.001). We propose that oxidative stress is a key hallmark of tumor tissues that drives high-energy metabolism in adjacent proliferating mitochondrial-rich cancer cells, via the paracrine transfer of mitochondrial fuels (such as L-lactate and ketone bodies). New antioxidants and MCT4 inhibitors should be developed to metabolically target "three-compartment tumor metabolism" in head and neck cancers. It is remarkable that two "non-proliferating" populations of cells (Ki-67-/MCT4+) within the tumor can actually determine clinical outcome, likely by providing high-energy mitochondrial "fuels" for proliferative cancer cells to burn. Finally, we also show that in normal mucosal tissue, the basal epithelial "stem cell" layer is hyper-proliferative (Ki-67+), mitochondrial-rich (TOMM20+/COX+) and is metabolically programmed to use mitochondrial fuels (MCT1+), such as ketone bodies and L-lactate. Thus, oxidative mitochondrial metabolism (OXPHOS) is a common feature of both (1) normal stem cells and (2) proliferating cancer cells. As such, we should consider metabolically treating cancer patients with mitochondrial inhibitors (such as Metformin), and/or with a combination of MCT1 and MCT4 inhibitors, to target "metabolic symbiosis."
Two alternative DNA extraction methods to improve the detection of Mycobacterium-tuberculosis-complex members in cattle and red deer tissue samples (2016)

Both new methods yielded increased detection rates for MTC DNA detection in large sample volumes and consequently improve the official diagnostic protocol.
Specific Antiproliferative Activity against Several Human Cancer Cells with Metabolites from Onygena corvina (2019)

We succeeded in large volume artificial cultivation of Onygena corvina. The appearance (shape, color, and size) of fruiting bodies of cultured bacteria was almost the same as that of wild one. We screened their metabolites for antiproliferative activities against nine human cancer cells in vitro. Culture filtrates (metabolite-containing media) of O. corvina were lyophilized and resuspended in phosphate buffer to investigate them in vitro. As a result, these metabolites effectively inhibited the growth of some cancer cells in a concentration-dependent manner. In particular, the effect on lung carcinoma Hara cells was remarkable, but there was almost no effect on hepatoma HepG2 cells. In addition, almost no effect was exerted on three normal cells [human hepatocyte (NHH), human mammary epithelial cells (NHME), and human epidermal melanocytes (NHEM)] at the same concentration. Therefore, it was revealed that the human cell proliferation inhibitory effect of the O. corvina metabolites greatly differs in susceptibility depending on the type of cancer cell under the concentration range not affecting normal cells. In vivo experiments demonstrated that the oral administration of the O. corvina metabolites (OC-FD) decreased the tumor growth compared with untreated mice. The OCT extract obtained by extracting ethanol had the same anti-tumor activity as the OC-FD, but this activity was weaker than with OC-FD. On the other hand, when the same experiment was performed on OCT with 2.O.C.11 and 1.O.C.5, respectively, for the EtOAc soluble fraction and water layer, this demonstrated stronger inhibitory activity than when only the OC-FD or OCT was administered. These results revealed these active components may be both low-molecular weight with low polarity (EtOAc soluble) and high-molecular weight, such as a polysaccharide or protein (water soluble). These findings suggest that the unknown compounds in the metabolite-containing media from cultures of O. corvina are potential lead compounds for developing anticancer drugs with extremely mild side effects.
Iron (II) Metallo-Supramolecular Polymers Based on Thieno[3,2-b]thiophene for Electrochromic Applications (2021)

Four new bis(<i>tpy</i>) unimers with different linkers between the thieno[3,2-<i>b</i>]thiophene-2,5-diyl central unit and terpyridine-4'-yl (<i>tpy</i>) end-groups: no linker (<b>Tt</b>), ethynediyl (<b>TtE</b>), 1,4-phenylene (<b>TtPh</b>) and 2,2'-bithophene-5,5'-diyl (<b>TtB</b>) are prepared, characterized, and assembled with Fe<sup>2+</sup> ions to metallo-supramolecular polymers (Fe-MSPs). The Fe-MSP films prepared by spin-casting on Indium Tin Oxide (ITO) glass are characterized by atomic force microscope (AFM) microscopy, cyclic voltammetry, and UV/vis spectroscopy and studied for their electrochromism and effect of the unimer structure on their electrochromic performance. Of the studied MSPs, <b>Fe-Tt</b> shows the highest optical contrast as well as coloration efficiency (CE = 641 cm<sup>2</sup> C<sup>-1</sup>) and the fastest optical response. This makes it an excellent candidate for possible use in electrochromic devices.
ICONE11-36616 EXPERIMENTAL STUDY ON THERMO-HYDRAULIC INSTABILITY ON REDUCED-MODERATION NATURAL CIRCULATION BWR CONCEPT (2003)

Reduced-moderation natural circulation BWR has been promoted to solve the recent challenges in BWR nuclear power technology problems as one of advanced small and medium-sized reactors equipped with the passive safety features in conformity with the natural law. However, the elimination of recirculation pumps and high-density core due to the increase of conversion ratio could cause various thermo-hydraulic instabilities especially during the start-up stage. The occurrences of the thermo-hydraulic instabilities especially during the start-up stage. The occurrences of the thermo-hydraulic instabilities are not desirable and it is one of the main challenges in establishing reduced-moderation natural circulation BWR as a commercial reactor. The purpose of this present study is to experimentally investigate the driving mechanism of the thermo-hydraulic instabilities and the effect of system pressure on the unstable flow patterns. Hence, as the fundamental research for this study, a natural circulation loop that carries boiling fluid with parallel boiling channel has been constructed. Channel gap that has been set at 2mm in order to simulate reduced-moderation reactor core. Pressure ranges of 0.1 up to 0.7MPa, input heat flux range of 0 up to 577kW/m^2,and inlet subcooling temperatures of 5,10,and 15K respectively, are imposed in the experiments. This experiment clarifies that changes in unstable flow patterns with increase in heat flux can be classified into two in response to system pressure range. In case of atmospheric pressure, unstable flow patters has been classified in beyond order, (1) in-phase geysering, , (2) transition oscillation combined with both features of in-phase geysering and natural circulation oscillation, (3) natural circulation oscillation induced by hydrostatic head fluctuation, (4) density wave oscillation, and finally (5) stable boiling two-phase flow. On the other hand, in the system pressure range from 0.2 to 0.7MPa, unstable patters have been dramatically changed in the following order (1) out-of-phase geysering, (2) density wave oscillation and lastly (3) stable boiling two-phase flow. Transport mechanism of the thermo-hydraulic instabilities and changes in the flow patterns with increment in heat flux are almost equal to the results obtained in the previous natural circulation loop equipped with 5mm channel gap, except for in-phase geysering. Considering in-phase geysering, it is one of new kind of the instabilities since it had never been observed in the loop with wider channel gap. This instability will be explained in this paper on the transport mechanism in detail.
The measurement and application of thrombin generation (2005)

It is the capacity to generate thrombin, and the enzymatic work that thrombin does, that determines blood coagulability. Therefore, measurement of the enzymatic work potential of thrombin provides a method for quantifying the composite effect of the multiple factors that determine coagulation capacity. The application of measurement of thrombin generation to clinical decision making has been hampered by numerous technical difficulties and pitfalls, many of which have now been overcome. Technical advances now permit rapid, reproducible measurement. A review of clinical studies performed to date indicates the need to appreciate the precise methodology used in each case and the need to consider standardisation in future studies. Applying thrombin generation measurement to clinical decision making will require up-to-date estimates of risks relating to the disorder and the intended therapeutic intervention. Ultimately management studies will be required if the clinical utility of measurement of thrombin generation is to be proven.
Nutrition and Growth Kinetics in Nitrogen- or Phosphorus-limited Cultures of the Noxious Red Tide Dinoflagellate &lt;i&gt;Gymnodinium mikimotoi&lt;/i&gt; (1999)

The dinoflagellate, Gymnodinium mikimotoi, causes severe red tides which have been associated with mass mortality of marine fish and invertebrates in western Japan. To establish the background biological information to elucidate the mechanism of red tide outbreaks, nutrition and growth kinetics in nitrogen (N)- or phosphorus (P)-limited semi-continuous cultures were examined using an axenic strain. G. mikimotoi is able to grow using organic and inorganic N compounds as sole N sources. Nitrate, nitrite, and ammonium were found to be good nitrogen sources. Urea and uric acid were not so well utilized and none of the amino acids, except for glutamine and tryptophan, were utilized. G.mikimotoi was capable of using a wide variety of inorganic and organic phosphorus compounds of different molecular structure successfully as a sole P source. Under N-limited steady state conditions, dilution rate (=growth rate), as a function of cell nitrogen quota, followed the Droop equation. Similarly, dilution rate, as a function of cell P quota, followed the Droop equation under P-limited steady state culture. Kinetic parameters Dm and Kq obtained for N- and P-limited cultures were 0.54 day-1 and 3.13 pmol-cell-1, and 0.67 day-1 and 0.25 pmol-cell-1, respectively. The nutrient availability and kinetic parameters of G. mikimotoi were compared to other red tide organisms and the ecological implications of these characteristics were discussed.
Training Autoencoder using Three Different Reversed Color Models for Anomaly Detection (2020)

Autoencoders (AEs) have been applied in several applications such as anomaly detectors and object recognition systems. However, although the recent neural networks have relatively high accuracy but sometimes false detection may occur. This paper introduces AE as an anomaly detector. The proposed AE is trained using both normal and anomalous data based on convolutional neural network with three different color models Hue Saturation Value (HSV), Red Green Blue (RGB), and our own model (TUV). As a result, the trained AE reconstruct the normal images without change, whereas the anomalous image would be reconstructed reversely. The training and testing of the AE in case of RGB, HSV, and TUV color models were demonstrated and Cifar-10 dataset had been used for the evaluation process. It can be noticed that HSV color model has been more effective and achievable as an anomaly detector rather than other color models based on Z- and F-test analyses.
ChemInform Abstract: SYNTHESIS AND STRUCTURAL DETERMINATION OF DEHYDROCYCLOBUTATUSIN, A DITERPENOID WITH A FOUR‐MEMBERED RING (1977)

Abstract Bei der Photolyse von Barbatusin (I) entsteht Dehydrocyclobutatusin (II).
Conservation and divergence in cortical cellular organization between human and mouse revealed by single-cell transcriptome imaging (2021)

Abstract The human cerebral cortex has tremendous cellular diversity and complex cellular organization that are essential for brain function. How different types of cells are organized and interact with each other in the human cortex, and how cellular organizations and interaction patterns vary across species are, however, unclear. Here, we performed spatially resolved single-cell expression profiling of 4,000 genes in human middle and superior temporal gyrus using multiplexed error-robust fluorescence in situ hybridization (MERFISH). We identified &gt;100 neuronal and non-neuronal cell populations with distinct transcriptional signatures, generated a molecularly defined and spatially resolved cell atlas of these brain regions, and analyzed cell-cell interactions in a cell-type-specific manner. Comparison with the mouse cortex showed conservation in the laminar organization of cells and substantial divergence in cell-cell interactions between human and mouse. Notably, our data revealed a drastic increase in interactions between neurons and non-neuronal cells in the human cortex, uncovered human-specific cell-cell interaction patterns, and identified potential ligand-receptor basis of microglia-neuron interactions.
Multifocal Electroretinogram Can Detect the Abnormal Retinal Change in Early Stage of type2 DM Patients without Apparent Diabetic Retinopathy (2021)

Patients with type 2 DM without clinically apparent retinopathy had a delayed implicit time of P1 wave in temporal regions of the postpole of the retina compared with HC subjects. It demonstrates that mf-ERG can detect the abnormal retinal change in the early stage of type2 DM patients without apparent diabetic retinopathy. Multiparameters of mf-ERG can improve the diagnostic efficacy of DR, and it may be a potential clinical biomarker for early diagnosis of DR.
Two new translocations involving the 11q23 region map outside the MLL locus in myeloid leukemias. (2002)

Our cases add two new translocations to the list of chromosomal anomalies involving the long arm of chromosome 11, and show that apparent translocation t(11q23) may involve loci and genes other than MLL. Characterizing the molecular heterogeneity of 11q23 translocations may identify some prognostic significance.
Eco-friendly Organic Nanotubes Encapsulating Alkaline Phosphatase and Ecotoxicology of Nanotubes to Natural Bacterial Assemblages in Coastal Estuarine Waters (2019)

Phosphatase-encapsulated nanotubes have potential in environmental remediation of organophosphate contaminants (e.g., pesticides, nerve agents). We investigated alkaline phosphatase (AP) activity when encapsulated in self-assembled lithocholic acid nanotubes (LCA-AP) in water samples along a transect from Cypress bog headwaters through estuarine waters and to Atlantic Ocean seawater. Apparent Vmax (appVmax) for both LCA-AP and unencapsulated AP (Free-AP) was most rapid at mid-estuary and most inhibited at the humic-rich bog. LCA-AP retained a higher-activity percentage, suggesting that encapsulation may afford some protection from denaturing effects of humics. Apparent Km (appKm) of Free-AP (1–2.3 μM) was largely unaffected by preincubation with transect water, whereas appKm of LCA-AP was higher with bog water (5.3 μM) relative to other stations. When comparing Free-AP and LCA-AP, increasing salinity generally decreased the catalytic efficiency of the LCA-AP, but had little effect on that of the Free-AP. In addition, both showed the same pattern of lowest efficiency in bog water, which increased with salinity to 21 practical salinity units before decreasing at full-strength salinity. With the exception of the similarly low values in the bog water (1.04 for LCA-AP, 1.34 for Free-AP), absolute values of catalytic efficiency for LCA-AP were about 17% (range: 14.5–19.3%) of that for Free-AP. Nanotube addition had little ecotoxicological effect on heterotrophic bacterial production in waters sampled along the transect. Microbially associated, intrinsic AP activity showed a similar pattern along the transect to LCA-AP, suggesting that AP environmental control and regulation in nature may inform study of nanomaterials.
The Wnt Antagonist Dickkopf-1 Mobilizes Vasculogenic Progenitor Cells via Activation of the Bone Marrow Endosteal Stem Cell Niche (2008)

Therapeutic mobilization of vasculogenic progenitor cells is a novel strategy to enhance neovascularization for tissue repair. Prototypical mobilizing agents such as granulocyte colony-stimulating factor mobilize vasculogenic progenitor cells from the bone marrow concomitantly with inflammatory cells. In the bone marrow, mobilization is regulated in the stem cell niche, in which endosteal cells such as osteoblasts and osteoclasts play a key role. Because Wnt signaling regulates endosteal cells, we examined whether the Wnt signaling antagonist Dickkopf (Dkk)-1 is involved in the mobilization of vasculogenic progenitor cells. Using TOP-GAL transgenic mice to determine activation of beta-catenin, we demonstrate that Dkk-1 regulates endosteal cells in the bone marrow stem cell niche and subsequently mobilizes vasculogenic and hematopoietic progenitors cells without concomitant mobilization of inflammatory neutrophils. The mobilization of vasculogenic progenitors required the presence of functionally active osteoclasts, as demonstrated in PTPepsilon-deficient mice with defective osteoclast function. Mechanistically, Dkk-1 induced the osteoclast differentiation factor RANKL, which subsequently stimulated the release of the major bone-resorbing protease cathepsin K. Eventually, the Dkk-1-induced mobilization of bone marrow-derived vasculogenic progenitors enhanced neovascularization in Matrigel plugs. Thus, these data show that Dkk-1 is a mobilizer of vasculogenic progenitors but not of inflammatory cells, which could be of great clinical importance to enhance regenerative cell therapy.
Solvent-Directed Epoxide Opening with Primary Amines for the Synthesis of β-Amino Alcohols (2016)

An efficient synthesis of β-amino alcohols from a variety of epoxides and primary unbranched amines in the absence of any catalyst in high yields and regioselectivities is reported. A variety of polar mixed solvent systems allow for the selective formation of secondary amino alcohols over tertiary amino alcohols. The reaction scope extends to a wide variety of aromatic and aliphatic substituted epoxides and primary amines bearing complex functionality.
Simulation of a laser tracker system for relative positioning of autonomous underwater vehicles (2013)

In this paper we describe the simulative evaluation of a Multi Laser Tracking System (MLTS) to be used for relative position estimation of Autonomous Underwater Vehicles (AUV). Based on the parameters of an existing MLTS for land applications, we build up a simulation with two AUVs that perform range and bearing measurements between each other. On the base of these measurements that are disturbed by noise we perform position estimation, using different methods, and evaluate the accuracy against realistic requirements. Finally, we will provide an overview on the continuative research activities in order to realize a MLTS for underwater applications in reality.