gebhart/patrepeval huggingface dataset:
Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration (2018)

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.
Orthotopic liver transplantation for urea cycle enzyme deficiency (1992)

Hyperammonemia, abnormalities in plasma amino acids and abnormalities of standard liver functions were corrected by orthotopic liver transplantation in a 14-day-old boy with carbamyl phosphate synthetase-I deficiency and in a 35-yr-old man with argininosuccinic acid synthetase deficiency. The first patient had high plasma glutamine levels and no measurable citrulline, whereas citrulline values were markedly increased in Patient 2. Enzyme analysis of the original livers showed undetectable activity of carbamyl phosphate synthetase-I in Patient 1 and argininosuccinic acid synthetase in Patient 2. Both patients were comatose before surgery. Intellectual recovery of patient 1 has been slightly retarded because of a brain abscess caused by Aspergillus infection after surgery. Both patients are well at 34 and 40 mo, respectively, after surgery. Our experience has shown that orthotopic liver transplantation corrects the life-threatening metabolic abnormalities caused by deficiencies in the urea cycle enzymes carbamyl phosphate synthetase-I and argininosuccinic acid synthetase. Seven other patients--six with ornithine transcarbamylase deficiency and another with carbamyl phosphate synthetase-I deficiency--are known to have been treated elsewhere with liver transplantation 1 1/2 yr or longer ago. Four of these seven recipients also are well, with follow-ups of 1 1/2 to 5 yr. Thus liver transplantation corrects the metabolic abnormalities of three of the six urea cycle enzyme deficiencies, and presumably would correct all.
SERUM LEVELS OF A TISSUE INHIBITOR OF METALLOPROTEINASES‐1 (TIMP‐1) IN BLADDER CANCER PATIENTS (1994)

Tissue inhibitors of metalloproteinases (TIMP‐1 and ‐2) are common inhibitors of matrix metallo‐proteinases (MMPs), thereby blocking degradation of extracellular matrix components. TIMP‐1 and ‐2 have been reported to exhibit inhibitory activities against tumor invasion and metastasis. We measured the serum TIMP‐1 levels in 16 healthy volunteers and in 69 patients with bladder cancer using a sandwich enzyme immunoassay, and evaluated the correlation between serum TIMP‐1 levels and clinicopathological features. Patients with bladder cancer showed significantly higher serum TIMP‐1 levels (251.1 96.0 ng/ml; p&lt;0.01) than those of healthy volunteers (168.5 33.2ng/ml), and a positive correlation between the TIMP‐1 level and invasion and metastasis was observed. This is considered to be the result of the reactive production of TIMP‐1 in cancerous tissues. Thus, serum TIMP‐1 levels may become a reliable clinical marker of the progression of bladder cancer.
The Wellcome Foundation Lecture, 1986 - The molecular control of normal and leukaemic granulocytes and macrophages (1987)

The development of semisolid culture methods supporting the clonal proliferation and maturation of granulocytes and macrophages led to the discovery of a group of specific glycoproteins, the colony-stimulating factors (CSFs), whose function it is to control the proliferation and functional activity of granulocytes, macrophages and associated blood cells. The four known CSFs in the mouse and man have been purified and complementary DNAs (cDNAs) for each have been cloned. The injection of bacterially synthesized recombinant CSF into mice has demonstrated that these CSFs can function in vivo to regulate granulocyte and macrophage formation. A major physiological role played by these CSFs is to control resistance to invading microorganisms through mechanisms capable of extremely rapid activation. Because the CSFs are the only known proliferative factors for these cells, the CSFs are involved in the initiation and the emergence of myeloid leukaemia but, conversely, at least one of the CSFs, G-CSF, is able to suppress myeloid leukaemic populations because of the ability of the CSFs to initiate differentiation commitment in responding granulocytic and macrophage populations. The CSFs are promising agents for clinical use in the treatment of infections in patients with depressed granulocyte-macrophage formation and possibly in the management of some types of myeloid leukaemia.
Contact Guidance On Microfabricated Substrata: The Response Of Teleost Fin Mesenchyme Cells To Repeating Topographical Patterns (1988)

The mesenchymal tissue component of the teleost pectoral fin bud has been explanted onto microfabricated quartz discs containing patterns of regular grooves of dimensions similar to those encountered by contact-guided cells in the intact fin system. Computer-aided analysis of cell migration on five separate patterns, from 1.8 to 7.4 microns repeat spacing, revealed that migration was predominantly aligned parallel to the long axis of the grooves, with individual cells becoming highly polarized, and the highest index of alignment (3.7) produced on the widest repeat spacings. When these cells are cultured on planar quartz, which is both chemically and physically isotropic, they flatten and adopt a morphology similar to that shown by cultured fibroblastic cell types on flat surfaces, suggesting that fin mesenchymal cells are not intrinsically predisposed to adopt an arborized morphology, like that observed in the intact fin bud. These results clearly demonstrate a directional migration in response to substratum topography, from a cell type known to be contact guided in vivo, and in the complete absence of adhesive heterogeneities.
Verifiable AKA for beyond 3G wireless packet services (2006)

Security in third generation wireless systems has been enhanced from second generation systems to support network authentication of devices and enhanced key size. However, the basic model of security for 3G systems is still circuit-switched based. We propose a security model in this paper based on forward security that is more efficient to support packet switched services for beyond 3G networks with negligible overhead on the user equipment or AAA (authentication, authorization, and accounting) server. Forward security is applicable with secret keys changing with time periods and could be easily verifiable by the verifier using the single fixed key. The intruder/eavesdropper who is able to compromise a packet would not be able to derive the meaning of the whole data content since the cipher key/integrity key compromised is only applicable to the packet sent at the current time period. The intruder cannot compromise the packets sent for the packet-switched (PS) session over other time periods and thereby serves to be several times more secure to the existing 3GPP AKA (authentication and key agreement) security model
Functional Control of Cold- and Menthol-Sensitive TRPM8 Ion Channels by Phosphatidylinositol 4,5-Bisphosphate (2005)

Cold is detected by a small subpopulation of peripheral thermoreceptors. TRPM8, a cloned menthol- and cold-sensitive ion channel, has been suggested to mediate cold transduction in the innocuous range. The channel shows a robust response in whole-cell recordings but exhibits markedly reduced activity in excised membrane patches. Here we report that phosphatidylinositol 4,5-bisphosphate (PIP2) is an essential regulator of the channel function. The rundown of the channel is prevented by lipid phosphatase inhibitors. Application of exogenous PIP2 both activates the channel directly and restores rundown activity. Whole-cell experiments involving intracellular dialysis with polyvalent cations, inhibition of PIP2 synthesis kinases, and receptor-mediated hydrolysis of PIP2 show that PIP2 also modulates the channel activity in the intact cells. The crucial role of PIP2 on the function of TRPM8 suggests that the membrane PIP2 level may be an important regulator of cold transduction in vivo. The opposite effects of PIP2 on the vanilloid receptor TRPV1 and TRPM8 also implies that the membrane lipid may have dual actions as a bimodal switch to selectively control the heat- and cold-induced responses in nociceptors expressing both channels.
Quantitative high-resolution microradiographic imaging of amyloid deposits in a novel murine model of AA amyloidosis (2005)

The mouse model of experimentally induced systemic AA amyloidosis is long established, well validated, and closely analogous to the human form of this disease. However, the induction of amyloid by experimental inflammation is unpredictable, inconsistent, and difficult to modulate. We have previously shown that murine AA amyloid deposits can be imaged using iodine-123 labeled SAP scintigraphy and report here substantial refinements in both the imaging technology and the mouse model itself. In this regard, we have generated a novel prototype of AA amyloid in which mice expressing the human interleukin 6 gene, when given amyloid enhancing factor, develop extensive and progressive systemic AA deposition without an inflammatory stimulus, i.e., a transgenic rapidly inducible amyloid disease (TRIAD) mouse. Additionally, we have constructed high-resolution micro single photon emission computed tomography (SPECT)/computed tomography (CT) instrumentation that provides images revealing the precise anatomic location of amyloid deposits labeled by radioiodinated serum amyloid P component (SAP). Based on reconstructed microSPECT/CT images, as well as autoradiographic, isotope biodistribution, and quantitative histochemical analyses, the (125)I-labeled SAP tracer bound specifically to hepatic and splenic amyloid in the TRIAD animals. The ability to discern radiographically the extent of amyloid burden in the TRIAD model provides a unique opportunity to evaluate the therapeutic efficacy of pharmacologic compounds designed to inhibit fibril formation or effect amyloid resolution.
[Alcohol, lipid metabolism and coronary heart disease]. (1996)

Numerous epidemiological studies have unequivocally proven a protection from the development of coronary heart disease by moderate long-lasting alcohol consumption. During the past 20 years studies in different ethnic groups starting from an American cohort and spanning to the recently performed analysis in the MONICA-project gave evidence for a decreased morbidity and mortality from coronary heart disease at 1 to 3 drinks a day when compared to total abstainers. A part of the protection is thought to be mediated through alcohol effects on plasma lipoprotein metabolism. Substantial increases in high-density lipoprotein cholesterol and its subfractions occur and are believed to be responsible for as much as half of the alcohol-mediated benefits. In addition, moderate decreases in low-density lipoprotein cholesterol and probably also in lipoprotein(a), established cardiovascular risk factors, may contribute accordingly. Furthermore, antioxidants like flavonoids and polyphenols found in red wines by protecting low density lipoproteins from oxidative modification may explain the "French paradox", the decreased incidence of coronary heart disease in France despite a high consumption of saturated fats. Also, alcoholic vasodilation, decreases in platelet aggregability, changes in prostacyclin/thromboxane ratios and increased fibrinolytic activities are to be considered as additional benefits caused by moderate alcohol consumption.
Tracheal matrices, obtained by a detergent-enzymatic method, support in vitro the adhesion of chondrocytes and tracheal epithelial cells (2005)

Several attempts have been performed to achieve a suitable tracheal replacement for the treatment of different conditions characterized by a lack of sufficient tissue for surgical reconstruction. Actually, tracheal homografts can induce long-term stenosis and their growth potential is not known. Thus, in this work porcine tracheal matrices have been obtained by a detergent-enzymatic method. The treatment decreased the antigenicity of matrices which were able to support the in vitro adhesion of both chondrocytes and tracheal epithelial cells. On the contrary, only few cells were observed in tracheal matrices prepared with formalin, Thimerosal, and acetone, suggesting that the long-term stenosis occurring in vivo is probably because of an insufficient cell ingrowth. In summary, our results indicate that the detergent-enzymatic method allows us to obtain tracheal matrices which can function as a promising support to achieve an in vitro tissue-engineered cell-matrix construct.
A comparison of native ATM-multicast to IP-multicast with emphasis on mapping between the two (2002)

Given the growing use of ATM, there is great interest in migrating the protocols which run on today's common networking technologies to ATM. There is particular interest in running the IP protocol on top of ATM. This provides an easy bridge between current networking protocols and applications and future ATM-only protocols and applications One of the move recent IP protocols, IP-multicast, has been used for video-conferencing over the Internet. This application is a good example of a current technology that could benefit from the higher bandwidths offered by ATM. IP-multicast provides a method for sending copies of packets to every member of a group simply by sending the packet to the group's address. In order to perform this IP-multicasting on top of ATM efficiently, it is expected that a mapping of IP multicast subnet functionality to ATM must be developed. The paper examines current developments in ATM and their relation to IP-multicast in an attempt to identify schemes for achieving IP-multicast subnet functionality in ATM.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Ipilimumab: An Anti-CTLA-4 Antibody for Metastatic Melanoma (2011)

Ipilimumab (MDX-010, Yervoy; Bristol-Myers Squibb), a fully human monoclonal antibody against CTL antigen 4 (CTLA-4), was recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma. In both early- and late-phase trials, ipilimumab has shown consistent activity against melanoma. For example, in a randomized phase III trial that enrolled patients with previously treated metastatic disease, ipilimumab, with or without a peptide vaccine, improved overall survival: Median overall survival was 10.1 and 10.0 months in the ipilimumab and ipilimumab plus vaccine arms, respectively, versus 6.4 months in the vaccine-alone group (hazard ratio, 0.68; P ≤ 0.003). Serious (grade 3-5) immune-related adverse events occurred in 10% to 15% of patients. Thus, although it provides a clear survival benefit, ipilimumab administration requires careful patient monitoring and sometimes necessitates treatment with immune-suppressive therapy. Here, we review the mechanism of action, preclinical data, and multiple clinical trials that led to FDA approval of ipilimumab for metastatic melanoma.
Simply Assembled and Recyclable Polymer-Supported Olefin Metathesis Catalysts (2000)

Polymer-supported ruthenium catalysts (PCy(3))(2)Ru(=C(H)Ph)Cl(2), (PCy(3))Ru(IMes)(=C(H)Ph)Cl(2), and (PCy(3))Ru(SIMes)(=C(H)Ph)Cl(2), where IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene and SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene, have been prepared and found to be effective "boomerang" catalysts for ring-closing metathesis. They are recyclable, show comparable or better reactivity than their homogeneous counterparts, tolerate functional groups, and perform very well with dienes and moderately well with highly hindered substrates.
204 Years of near Infrared Technology: 1800–2003 (2003)

Near infrared spectroscopy has come of age. Today, it takes its place along side other major analytical technologies. Though it has inherent problems, its advantages make it an appealing tool for solving all sorts of analytical problems, for all sorts of samples, found in numerous fields, including food, agriculture, chemical, pharmaceuticals, textiles, polymers, cosmetics and medical—just to mention a few. Healthy, strong and still growing, NIR spectroscopy is a source of thrills and chills for many, whether from new measurement technology, chemometrics or from understanding and being able to express “old” ideas in fresher, clearer ways. a Modern NIR instruments integrate numerous technologies for determining absorbances at specific wavelengths: Monochromator, Fourier Transform, Filters [including, narrow-band interference filters, tilting filters, Acousto Optical Tunable Filters (AOTF) and Liquid Crystal Tunable Filters (LCTF)], Hadamard, Diode Emitters and Diode Arrays. Software for developing calibrations, utilising some types of classical and/or modern multivariate methods, is available with every commercial instrument. In addition, software vendors, independent of manufacturers, have designed and are marketing advanced chemometric packages for carrying out a variety of multivariate tasks, including mathematical spectral pretreatment, calibration and prediction, plus the implementation of process control statistics. The plethora of instruments and software has provided a sound basis for developing all sorts of applications throughout numerous fields. As a result, there are today more than 25,000 citations in the NIR literature and, since 1960, Medline alone has logged 2341 citations with NIR implications for the medical community, all tributes to the strength and viability of this fascinating spectroscopy. This review is a look at the big picture of NIR spectroscopy. It covers the field of NIR from the beginning to present day—204 years (1800–2003)—in six sections: Introduction, Reviews, Books, Instrumentation, Applications and Conclusions: Past, Present and Future.
Antiviral effects of selected IMPDH and DHODH inhibitors against foot and mouth disease virus (2019)

Foot-and-mouth disease virus (FMDV) is an important pathogen that affects livestock breeding and causes huge economic losses worldwide. Currently, the development of antiviral agents to combat FMDV infection at the early stages is being explored. As viral replication critically depends on the host for nucleoside supply, host enzymes involved in nucleotides biosynthesis may represent potential targets for the development of antiviral agents. In the present study, the effects of IMP dehydrogenase (AVN-944 and mycophenolate mofetil) and dihydroorotate dehydrogenase (teriflunomide) inhibitors were evaluated both in vitro and in vivo. The results revealed that these compounds were effective in suppressing FMDV (O/MY98/BY/2010 and A/GD/MM/2013) infection. With regard to the antiviral mechanism, time-of-addition experiments revealed that these compounds were effective when added at the early stages of viral lifecycle (0-8 h post infection). However, exogenous guanosine/uridine eliminated the antiviral activity of these compounds. Importantly, treatment AVN-944 and teriflunomide significantly improved the survival of mice that were subcutaneously treated with FMDV. Together, the results of the present study indicate the broad-spectrum activities of anti-FMDV agents targeting IMP dehydrogenase or dihydroorotate dehydrogenase, which could be useful in developing strategies to prevent FMD.
Porous surface layered prosthetic devices. (1975)

The method of fabrication and properties of a dual structured implant system consisting of a metallic porous surface layer is described. The ingrowth of bone tissue into the outer porous surface layer results in part fixation, while the solid inner core region provides the necessary mechanical strength for a device used for the replacement of heavy load bearing joint regions such as the hip and knee. Additionally, novel implant systems are suggested using the porous coating concept.
Endothelial production of C-type natriuretic peptide and its marked augmentation by transforming growth factor-beta. Possible existence of "vascular natriuretic peptide system". (1992)

C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is thus far known to be distributed mainly in the central nervous system and is considered to act as a neuropeptide, in contrast to atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which act as cardiac hormones. Recently, we and others have demonstrated that the ANP-B receptor, which is selectively activated by CNP, is localized not only in the central nervous system but in peripheral tissues, including blood vessels. This finding has made us speculate regarding the peripheral production of CNP. In the present study, cultured endothelial cells were examined for CNP production by RIA and Northern blot analysis. CNP-like immunoreactivity was detected in the conditioned media of endothelial cells. Northern blot analysis detected CNPmRNA with a size of 1.2 kb. In addition, transforming growth factor (TGF)-beta, one of the key growth factors for vascular remodeling, markedly stimulated the expression of CNPmRNA and induced a tremendous increase in CNP secretion. We could also detect CNP transcript in the bovine thoracic aorta using the reverse transcription-polymerase chain reaction method. The present study demonstrates the endothelial production of CNP and suggests that a member of the natriuretic peptide family may act as a local regulator in vascular walls. Since evidence for the pathophysiological importance of the vascular renin-angiotensin system has been accumulating and the natriuretic peptide system is known to be antagonistic to the renin-angiotensin system, the possible existence of "vascular natriuretic peptide system" may prove to be of physiological and clinical relevance.