gebhart/patrepeval huggingface dataset:
Photoacoustic thermal diffusion flowmetry (2012)

Thermal Diffusion Flowmetry (TDF) (also called Heat Clearance Method or Thermal Clearance Method) is a longstanding technique for measuring blood flow or blood perfusion in living tissues. Typically, temperature transients and/or gradients are induced in a volume of interest and the temporal and/or spatial temperature variations which follow are measured and used for calculation of the flow. In this work a new method for implementing TDF is studied theoretically and experimentally. The heat deposition which is required for TDF is implemented photothermally (PT) and the measurement of the induced temperature variations is done by photoacoustic (PA) thermometry. Both excitation light beams (the PT and the PA) are produced by directly modulated 830 nm laser diodes and are conveniently delivered to the volume under test by the same optical fiber. The method was tested experimentally using a blood-filled phantom vessel and the results were compared with a theoretical prediction based on the heat and the photoacoustic equations. The fitting of a simplified lumped thermal model to the experimental data yielded estimated values of the blood velocity at different flow rates. By combining additional optical sources at different wavelengths it will be possible to utilize the method for non-invasive simultaneous measurement of blood flow and oxygen saturation using a single fiber probe.
Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro (1999)

Nitrogen-containing bisphosphonates were shown to cause macrophage apoptosis by inhibiting enzymes in the biosynthetic pathway leading from mevalonate to cholesterol. This study suggests that, in osteoclasts, geranylgeranyl diphosphate, the substrate for prenylation of most GTP binding proteins, is likely to be the crucial intermediate affected by these bisphosphonates. We report that murine osteoclast formation in culture is inhibited by both lovastatin, an inhibitor of hydroxymethylglutaryl CoA reductase, and alendronate. Lovastatin effects are blocked fully by mevalonate and less effectively by geranylgeraniol whereas alendronate effects are blocked partially by mevalonate and more effectively by geranylgeraniol. Alendronate inhibition of bone resorption in mouse calvaria also is blocked by mevalonate whereas clodronate inhibition is not. Furthermore, rabbit osteoclast formation and activity also are inhibited by lovastatin and alendronate. The lovastatin effects are prevented by mevalonate or geranylgeraniol, and alendronate effects are prevented by geranylgeraniol. Farnesol and squalene are without effect. Signaling studies show that lovastatin and alendronate activate in purified osteoclasts a 34-kDa kinase. Lovastatin-mediated activation is blocked by mevalonate and geranylgeraniol whereas alendronate activation is blocked by geranylgeraniol. Together, these findings support the hypothesis that alendronate, acting directly on osteoclasts, inhibits a rate-limiting step in the cholesterol biosynthesis pathway, essential for osteoclast function. This inhibition is prevented by exogenous geranylgeraniol, probably required for prenylation of GTP binding proteins that control cytoskeletal reorganization, vesicular fusion, and apoptosis, processes involved in osteoclast activation and survival.
Glucose and diabetic vascular disease 1 (1992)

The central therapeutic problem in diabetes mellitus is prevention and treatment of the chronic vascular disease associated with this disorder. Prolonged exposure to hyperglycemia is the primary factor associated with the development of diabetes-specific microvascular disease, and the relationship between deranged glucose metabolism and arterial disease is complicated by many other factors that influence atherogenesis in nondiabetics. Until relatively recently, knowledge about diabetic vascular disease was limited mainly to clinical description. New information about abnormal vascular physiology, ultrastructure, biochemistry, cell biology, and molecular biology now makes it possible to understand in an integrated fashion the major specific mechanisms by which hyperglycemia damages diabetic vessels. Continued progress in this area will further optimize the development of safe and effective drugs for the treatment of diabetic vascular disease.
Skeletal framework of mammalian heart muscle. Arrangement of inter- and pericellular connective tissue structures. (1983)

We have studied the connective tissue of mammalian heart muscle in order to obtain an integrated description of extracellular structures and their dispositions relative to cardiac myocytes. Light microscopy and several types of electron microscopy have been employed in these investigations. The epimysium, the sheath of connective tissue that surrounds the muscle, contains relatively large fibers of collagen and elastin. In papillary muscles of rat, the large collagen fibers of the epimysium form a weave pattern at slack length (sarcomere lengths 1.8 to 2.0 micron) but are well aligned in states of stretch along the long axis of the muscle (sarcomere length 2.3 to 2.5 micron). We propose that the epimysial collagen network protects the sarcomeres from being stretched beyond lengths favorable to maximal force production. The endomysium is defined as the connective tissue that surrounds and interconnects myocytes; it consists of intercellular struts (bundles of collagen fibrils, often attached near Z-band level), a weave of bundles of collagen fibrils that envelopes myocytes, and a collagen fibril-microthread-granule lattice that bridges cells and fills the extracellular matrix. In contracted muscles festoons of sarcolemma are attached to Z-bands, thus forming regions for transmission of force across the sarcolemma. Perimysial bundles of collagen connect epimysium to endomysium and surround groups of myocytes. Collagen fibers often have a twisted configuration, probably for enhanced tensile strength. Superimposed on the large extracellular structures is the polyanion-rich lattice comprised of unit collagen fibrils, microthreads, and granules. Amorphous ground substance forms a matrix in which the fibrils of collagen fibers are embedded; it appears continuous with the cell coat in regions of fiber attachment. Elastic fibers interconnect cells and helically wind around myocytes. Circumferential forces from elastin stretched about shortened, thickened myocytes in systole should promote elongation in tandem with intramyocyte forces of elongation.
Systematic Change Management in Dimensional Data Warehousing (1998)

Design and maintenance of data warehouses has become an important research topic. In parallel to this, the topic of temporal databases is also an active area of research. This article covers the application of temporal ideas to data warehouse design. First, we present the notion of a data warehouse in general and describe the most approved method of structuring data in data warehouses, namely star schemas. Then we point to two star schema problems related to management of changing information---handling of slowly changing dimensions and state-oriented data. We present a rather new approach to data modelling in data warehouses, so-called temporal star schemas, that is a solution to the mentioned problems. In the literature, it is claimed that temporal star schemas can store more data in less space and make queries on the data faster, in comparison to regular star schemas. The comparison of instances of both schemas according to the size and query performance is the main topic ...
Characterization and Functionality of Proliferative Human Sertoli Cells (2010)

It has long been thought that mammalian Sertoli cells are terminally differentiated and nondividing postpuberty. For most previous in vitro studies immature rodent testes have been the source of Sertoli cells and these have shown little proliferative ability when cultured. We have isolated and characterized Sertoli cells from human cadaveric testes from seven donors ranging from 12 to 36 years of age. The cells proliferated readily in vitro under the optimized conditions used with a doubling time of approximately 4 days. Nuclear 5-ethynyl-2'-deoxyuridine (EdU) incorporation confirmed that dividing cells represented the majority of the population. Classical Sertoli cell ultrastructural features, lipid droplet accumulation, and immunoexpression of GATA-4, Sox9, and the FSH receptor (FSHr) were observed by electron and fluorescence microscopy, respectively. Flow cytometry revealed the expression of GATA-4 and Sox9 by more than 99% of the cells, and abundant expression of a number of markers indicative of multipotent mesenchymal cells. Low detection of endogenous alkaline phosphatase activity after passaging showed that few peritubular myoid cells were present. GATA-4 and SOX9 expression were confirmed by reverse transcription polymerase chain reaction (RT-PCR), along with expression of stem cell factor (SCF), glial cell line-derived neurotrophic factor (GDNF), and bone morphogenic protein 4 (BMP4). Tight junctions were formed by Sertoli cells plated on transwell inserts coated with fibronectin as revealed by increased transepithelial electrical resistance (TER) and polarized secretion of the immunoregulatory protein, galectin-1. These primary Sertoli cell populations could be expanded dramatically in vitro and could be cryopreserved. The results show that functional human Sertoli cells can be propagated in vitro from testicular cells isolated from adult testis. The proliferative human Sertoli cells should have important applications in studying infertility, reproductive toxicology, testicular cancer, and spermatogenesis, and due to their unique biological properties potentially could be useful in cell therapy.
Nanoparticles in Targeted Cancer Therapy: Mesoporous Silica Nanoparticles Entering Preclinical Development Stage (2011)

Nanotechnology may help overcome persisting limitations of current cancer treatment and thus contribute to the creation of more effective, safer and more affordable therapies. While some nanotechnology-based drug delivery systems are already being marketed and others are in clinical trial, most still remain in the preclinical development stage. Mesoporous silica nanoparticles have been highlighted as an interesting drug delivery platform, due to their flexibility and high drug load potential. Although numerous reports demonstrate sophisticated drug delivery mechanisms in vitro, the therapeutic benefit of these systems for in vivo applications have been under continuous debate. This has been due to nontranslatable conditions used in the in vitro studies, as well as contradictory conclusions drawn from preclinical (in vivo) studies. However, recent studies have indicated that the encouraging cellular studies could in fact be repeated also in vivo. Here, we report on these recent advances regarding therapeutic efficacy, targeting and safety issues related to the application of mesoporous silica nanoparticles in cancer therapy.
The Canadian Uro‐Oncology Group multicentre phase II study of docetaxel administered every 3 weeks with prednisone in men with metastatic hormone‐refractory prostate cancer progressing after mitoxantrone/prednisone (2008)

Docetaxel was associated with high rates of PSA and pain response in this study. Non-haematological toxicity was similar to that during first-line treatment, but rates of febrile neutropenia and toxic death appeared to be slightly higher. In selected patients with progressive metastatic HRPC previously treated with mitoxantrone, docetaxel appears to be a beneficial therapeutic option.
Fibroblast-dependent tumorigenicity of cells in nude mice: implication for implantation of metastases. (1986)

The inadequate nature of the microenvironment is one of several factors considered in the failure of tumor engraftment in athymic mice; in the present work, we have tried to more adequately reconstitute it by injecting tumor cells together with fibroblasts. We have demonstrated that the s.c. co-inoculation of fibroblasts with different kinds of tumor cells of animal origin [rat rhabdomyosarcoma (RMS) 9-4/0, rat hepato-carcinoma FAO] or human origin (colonic adenocarcinoma HT29, Ewing's sarcoma pleural metastasis EW-S1) is necessary for tumor take and growth when the number of tumor cells alone is below the tumorigenic dose. We have shown that the s.c. coinoculation of 10(6) fibroblasts and 10(2) RMS 9-4/0 tumor cells induced a tumor take in all the recipient mice, while 10(2) tumor cells alone never gave any tumor. With a tumorigenic number of RMS 9-4/0 tumor cells (10(4), addition of 10(6) fibroblasts decreased the delay between cell injection and tumor appearance, thereby increasing tumor take and growth rate. These results were observed not only in nude animals (mice and rats) used as recipient animals but also in normal WAG rats receiving the syngeneic RMS 9-4/0 tumor cells, and they were independent of the nature or origin of the different fibroblasts cells. This helper effect has also been observed in the normal WAG rats. I.v. injection of tumor cells from a poorly metastatic 9-4/8 subline, derived from the RMS 9-4/0 line and mixed with 10(6) fibroblasts, gave a high number of lung colonies. Addition of 10(6) irradiated 9-4/8 tumor cells instead of fibroblasts did not increase the lung colonizing potential. Fibroblast-conditioned medium mixed with tumor cells instead of fibroblasts also enhanced tumor take and size but to a lesser extent than did the fibroblasts themselves. Only endothelial cells cultured from porcine aorta had a similar helper effect among the cells tested. It is argued in the discussion that the proliferating state of cultivated fibroblasts is a determinant factor conferring upon them the ability to promote tumor cell growth, while fibroblasts very numerous at the implantation site but quiescent might not be efficient in cooperation. Changes in fibroblast morphology and physiology may be necessary in order for tumor cells to express their tumorigenicity.
Footprinting of mammalian promoters: use of a CpG DNA methyltransferase revealing nucleosome positions at a single molecule level (2005)

Promoters are molecular 'modules', which are controlled as individual entities yet are often analyzed by nuclease digestion methodologies which, a priori, destroy this modularity. About 40% of mammalian genes contain CpG islands in their promoters and exonic regions, which are normally unmethylated. We developed a footprinting strategy to map the chromatin structure at unmethylated CpG islands by treatment of isolated nuclei with the CpG-specific DNA methyltransferase SssI (M.SssI), followed by genomic bisulfite sequencing of individual progeny DNA molecules. This gave single molecule resolution over the promoter region and allowed for the physical linkage between binding sites on individual promoter molecules to be maintained. Comparison of the p16 promoters in two human cell lines, J82 and LD419, expressing the p16 gene at 25-fold different levels showed that the two cell lines contain remarkably different, heterogeneously positioned nucleosomes over the promoter region, which were not distinguishable by standard methods using nucleases. Our high resolution approach gives a 'digitized' visualization of each promoter providing information regarding nucleosome occupancy and may be utilized to define transcription factor binding and chromatin remodeling.
Further studies of blood infectivity in an experimental model of transmissible spongiform encephalopathy, with an explanation of why blood components do not transmit Creutzfeldt‐Jakob disease in humans (1999)

Epidemiologic evidence of the absence in humans of disease transmission from plasma components can probably be explained by 1) the absence of significant plasma infectivity until the onset of symptomatic disease, and comparatively low levels of infectivity during the symptomatic stage of disease; 2) the reduction of infectivity during plasma processing; and 3) the need for at least five to seven times more infectious agent to transmit disease by the intravenous than intracerebral route. These and other factors probably also account for the absence of transmission after the administration of whole blood or blood components.
Increase of P-glycoprotein-mediated drug resistance by hsp 90b (1996)

The expression of heat shock proteins hsp27, hsp60, hsp70, hsp90 alpha and hsp90 beta in extracts of three cell lines (LoVo DxR, KBChR8-5 and S180 DxR) expressing the MDR (multidrug resistance) positive phenotype as well as in the sensitive parental lines has been investigated. We present evidence that heat shock protein hsp90 beta is associated with the P-glycoprotein (Pgp or P170) one of the most prominent components of the drug resistance machinery. In the doxorubicin-resistant cell line LoVo DxR, but not in the sensitive parental line, hsp90 beta is expressed constitutively as shown by Northern blotting. The expression of hsp90 beta in the sensitive LoVo cell line, however, can be induced by exposure of the doxorubicin-sensitive parental cell line to different stress factors (dexamethasone, doxorubicin, heat treatment or cadmium chloride). We were able to demonstrate that hsp90 beta can be co-precipitated along with Pgp and vice versa. In native agarose gels both proteins migrated together as one single band as shown by Western blot analysis. This intracellular protein-protein interaction may present a mechanism for the modulation of Pgp function possibly by a stabilization of the protein which seems to be attributed to hsp90 beta (in the human colon carcinoma cell line and in the murine cell line S180). Antisense experiments with oligonucleotides directed against hsp90 beta and Pgp, respectively, showed a synergistic effect of the selected hsp90 beta antisense oligonucleotide in combination with the previously described Pgp antisense oligonucleotide in reducing the doxorubicin resistance. The hsp90 beta antisense oligonucleotide when applied in addition to the Pgp antisense oligonucleotide increased the doxorubicin sensitivity of the resistant human colon carcinoma cell line 2-fold. On the contrary, the hsp90 beta antisense oligonucleotide alone in contrast to the Pgp antisense oligonucleotide alone did not cause a reduction of the chemoresistance. Moreover, Pgp half-life was reduced in the presence of both antisense oligonucleotides as compared with an incubation with an anti-Pgp antisense oligonucleotide alone.
A Logic Simulation Machine (1982)

Special-purpose CAD hardware is increasingly being considered as a means to meet the challenge posed to conventional (software-based) CAD tools by the growing complexity of VLSI circuits. In this paper we describe the architecture of a logic simulation machine employing distributed and parallel processing. Our architecture can accommodate different levels of modeling ranging from simple gates to complex functions, and support timing analysis. We estimate that simulation implemented by the proposed special-purpose hardware will be between 10 and 60 times faster than currently used software algorithms running on general-purpose computers. With the available technology, a throughput of 1,000,000 gate evaluations/second can be achieved.
On Loss Functions for Deep Neural Networks in Classification (2017)

Deep neural networks are currently among the most commonly used classifiers. Despite easily achieving very good performance, one of the best selling points of these models is their modular design -one can conveniently adapt their architecture to specific needs, change connectivity patterns, attach specialised layers, experiment with a large amount of activation functions, normalisation schemes and many others. While one can find impressively wide spread of various configurations of almost every aspect of the deep nets, one element is, in authors' opinion, underrepresented -while solving classification problems, vast majority of papers and applications simply use log loss. In this paper we try to investigate how particular choices of loss functions affect deep models and their learning dynamics, as well as resulting classifiers robustness to various effects. We perform experiments on classical datasets, as well as provide some additional, theoretical insights into the problem. In particular we show that L1 and L2 losses are, quite surprisingly, justified classification objectives for deep nets, by providing probabilistic interpretation in terms of expected misclassification. We also introduce two losses which are not typically used as deep nets objectives and show that they are viable alternatives to the existing ones.
Low Density Parity Check (LDPC) Staircase and Triangle Forward Error Correction (FEC) Schemes (2008)

This document specifies an Internet standards track protocol for the Internet community, and requests discussion and suggestions for improvements. Please refer to the current edition of the "Internet Official Protocol Standards" (STD 1) for the standardization state and status of this protocol. Distribution of this memo is unlimited.
Phospholipids Inhibit Lipopolysaccharide (LPS)-Induced Cell Activation: A Role for LPS-Binding Protein (2005)

The inhibition of LPS-induced cell activation by specific antagonists is a long-known phenomenon; however, the underlying mechanisms are still poorly understood. It is commonly accepted that the membrane-bound receptors mCD14 and TLR4 are involved in the activation of mononuclear cells by LPS and that activation may be enhanced by soluble LPS-binding protein (LBP). Hexaacylated Escherichia coli lipid A has the highest cytokine-inducing capacity, whereas lipid A with four fatty acids (precursor IVa, synthetic compound 406) is endotoxically inactive, but expresses antagonistic activity against active LPS. Seeking to unravel basic molecular principles underlying antagonism, we investigated phospholipids with structural similarity to compound 406 with respect to their antagonistic activity. The tetraacylated diphosphatidylglycerol (cardiolipin, CL) exhibits high structural similarity to 406, and our experiments showed that CL strongly inhibited LPS-induced TNF-alpha release when added to the cells before stimulation or as a CL/LPS mixture. Also negatively charged and to a lesser degree zwitterionic diacyl phospholipids inhibited LPS-induced cytokine production. Using Abs against LBP, we could show that the activation of cells by LPS was dependent on the presence of cell-associated LBP, thus making LBP a possible target for the antagonistic action of phospholipids. In experiments investigating the LBP-mediated intercalation of LPS and phospholipids into phospholipid liposomes mimicking the macrophage membrane, we could show that preincubation of soluble LBP with phospholipids leads to a significant reduction of LPS intercalation. In summary, we show that LBP is a target for the inhibitory function of phospholipids.
Optimized velvet-noise decorrelator (2018)

Decorrelation of audio signals is a critical step for spatial sound reproduction on multichannel configurations. Correlated signals yield a focused phantom source between the reproduction loudspeakers and may produce undesirable comb-filtering artifacts when the signal reaches the listener with small phase differences. Decorrelation techniques reduce such artifacts and extend the spatial auditory image by randomizing the phase of a signal while minimizing the spectral coloration. This paper proposes a method to optimize the decorrelation properties of a sparse noise sequence, called velvet noise, to generate short sparse FIR decorrelation filters. The sparsity allows a highly efficient time-domain convolution. The listening test results demonstrate that the proposed optimization method can yield effective and colorless decorrelation filters. In comparison to a white noise sequence, the filters obtained using the proposed method preserve better the spectrum of a signal and produce good quality broadband decorrelation while using 76% fewer operations for the convolution. Satisfactory results can be achieved with an even lower impulse density which decreases the computational cost by 88%.