gebhart/patrepeval huggingface dataset:
Haemodynamic approach to reducing thrombosis and haemolysis in an impeller pump (1990)

In the experimental and clinical support of the failing heart, the impeller-type centrifugal pumps continue to be of interest because of their inherent advantages; however, the blood compatibility of these pumps still remains to be improved. From the viewpoint of haemodynamics, thrombosis and haemolysis could be reduced by eliminating the stagnation and turbulence of blood flow within the pump, which frequently takes place near the blood contracting surfaces of the pump, when the impeller contours do not coincide with the stream surfaces of the blood. It is suggested that it could be advantageous to design impeller contours according to the stream surfaces, by solving the partial differential equations of continuity, motion and energy. An impeller shroud and vane based on this approach would be fully rinsed by non-turbulent flow and there would then be neither stagnation nor turbulence within the pump, with the result that thrombosis and haemolysis could be reduced. A new impeller pump, developed according to this method, was evaluated as a left ventricular device in four dogs. The bypass flow was controlled at 40-50% of the total flow, each test lasting 6 h. All of the haematological parameters, measured every 2 h, remained within normal range. There was no thrombosis, and coagulation in the pump was avoided by a small dose of heparin to maintain the activated coagulation time (ACT) under 200" in the experiments.
Regional and progressive thinning of the cortical ribbon in Huntington’s disease (2002)

The authors propose that the cortex degenerates early in disease and that regionally selective cortical degeneration may explain the heterogeneity of clinical expression in HD. These measures might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications.
Protein Synthesis at Atomic Resolution: Mechanistics of Translation in the Light of Highly Resolved Structures for the Ribosome (2002)

Our understanding of the process of translation has progressed rapidly since the availability of highly resolved structures for the ribosome. A wealth of information has emerged in terms of both RNA and protein structure and the interplay between them. This has prompted us to revisit the astonishing "treasure trove" of functional data regarding the ribosome that has accumulated over the past decades. Here we try a systematic synopsis of these ribosomal functions in light of the cryo-electron microscopic structures (resolution >7 A) and the atomic x-ray structures (>2.4 A) of the ribosome.
A vertical piezoelectric inertial slider (1990)

We have developed a linear translation device using piezoelectric-induced slip-stick motion. Reproducible single steps of about 30 Å, as well as continuous stepping with an overall translation speed of 0.25 mm/s, are routinely realized. The notable feature of this device is that this performance is achieved in the vertical orientation with the translator moving against gravity. This remarkable result is made possible using cycloidal functions instead of sawtooth signals to activate the motion. We have realized a very simple translator which can be used in any orientation with a displacement onset voltage of 15 V. The instrument was successfully tested in the temperature range from 1.6 to 300 K. Since no mechanical connections are required, this design is well suited for many applications, including scanning tunneling microscopy.
Synthesis and Partial Characterization of Hydrogels Obtained via Glutaraldehyde Crosslinking of Acetylated Chitosan and of Hyaluronan Derivatives (2003)

Hydrophilic networks based on functionalized hyaluronic acid and on partially acetylated chitosan, respectively, have been obtained. In the case of hyaluronic acid (HA), primary amino functionalities have been introduced along the polysaccharide chains. The ensuing derivatives, i.e., HA-lysine (HA-K), HAdiamino pentane (HA-DAP), and HA-glycine-lysine (HA-GK), have been characterized by high field NMR spectroscopy. NMR 2D-DOSY experiments have allowed us to optimize the purification procedure. Chitosan was made soluble in water by partial acetylation. Cross-linking reactions have been performed using glutaraldehyde. The obtained networks have been qualitatively characterized by means of 13C CP-MAS NMR technique. The hydrogels have been characterized also in terms of water uptake.
Transport Properties of Polymeric Liquids (1992)

Transport Properties of Polymeric Liquids, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/physchem/43/1/annurev.pc.43.100192.002103-1.gif
Experimental study of Internet stability and backbone failures (2003)

In this paper, we describe an experimental study of Internet topological stability and the origins of failure in Internet protocol backbones. The stability of end-to-end Internet paths is dependent both on the underlying telecommunication switching system, as well as the higher level software and hardware components specific to the Internet's packet-switched forwarding and routing architecture. Although a number of earlier studies have examined failures in the public telecommunication system, little attention has been given to the characterization of Internet stability. We provide analysis of the stability of major paths between Internet Service Providers based on the experimental instrumentation of key portions of the Internet infrastructure. We describe unexpectedly high levels of path fluctuation and an aggregate low mean time between failures for individual Internet paths. We also provide a case study of the network failures observed in a large regional Internet backbone. We characterize the type, origin, frequency and duration of these failures.
A Broadband Packet Switch for Integrated Transport (1987)

This paper gives a broadband (total throughput approaching 1 terabit/s) self-routing packet switch design for providing flexible multiple bit-rate broadband services for an end-to-end fiber network. The switch fabric for the slotted broadband packet switch delivers exactly one packet to each output port from one of the input ports which request packet delivery to that output port. The denied requests would try again during the next slot. We discover an effective scheme, implemented by CMOS VLSI with manageable complexity, for performing this function. First, each input port sends a request for a port destination through a Batcher Sorting network, which sorts the request destinations in ascending order so that we may easily purge all but one request for the same destination. The winning request acknowledges its originating port from the output of the Batcher network, with the acknowledgment routed through a Batcher-banyan selfrouting switch. The acknowledged input port then sends the full packet through the same Batcher-banyan switch without any conflict. Unacknowledged ports buffer the blocked packet for reentry in the next cycle. We also give several variations for significantly improved performance. We then study switch performance based on some rudimentary protocols for traffic control. For the basic scheme, we analyze the throughput-delay characteristics for random traffic, modeled by random output port requests and a binomial distribution of packet arrival. We demonstrate with a buffer size of around 20 packets, we can achieve a 50 percent loading with almost no buffer overflow. Maximum throughput of switch is 58 percent. Next, we investigate the performance of the switch in the presence of periodic broadband traffic. We then apply circuit switching techniques and packet priority for high bit-rate services in our packet switch environment. We improve the throughput per port to close to 100 percent by means of parallel switch fabric, while maintaining the periodic nature of the traffic.
Association of Exogenous Estrogen and Endometrial Carcinoma (1975)

To determine the association between the incidence of endometrial cancer and the use of estrogen in menopausal and post-menopausal women, we retrospectively compared 317 patients with adenocarcinoma of the endometrium with an equal number of matched controls having other gynecologic neoplasms; 152 patients used estrogen, as compared to 54 of 317 controls. Thus, the risk of endometrial cancer was 4.5 times greater among women exposed to estrogen therapy. When estrogen use was adjusted for concomitant variables such as obesity, hypertension, diabetes, parity, referral pattern, age at diagnosis, year of diagnosis and other gynecologic neoplasms, the magnitude of the increased relative risk was associated with several of these variables, and was highest in patients without obesity and hypertension. Exogenous estrogen therapy is associated with an increased risk of endometrial carcinoma, but this increased relative risk is less apparent in patients with physiologic characteristics previously associated with an increased risk.
Role of Nitric Oxide in the Modulation of Angiogenesis (2003)

Angiogenesis, the development of new capillaries form pre-existing vessels, requires the coordinate activation of endothelial cells, which migrate and proliferate in response to growth factors to form functional vessels. Therapeutic angiogenesis is proposed to restore tissue integrity and function following damage and ischemia, while strategies aimed to block or suppress the neovascular growth are designed as adjuvant therapies for cancer treatment. Different experimental and clinical observations support the existence of a molecular/biochemical link between vasodilation, nitric oxide (NO) production and angiogenesis. NO significantly contributes to the prosurvival/proangiogenic program of capillary endothelium by triggering cell growth and differentiation via endothelial-constitutive NO synthase (ecNOS) activation, and cyclic GMP (cGMP) dependent gene transcription. Re-establishment of a balanced NO production in the cardiovascular system results in a reduction of cell damage during inflammatory and vascular diseases. Elevation of NOS activity in correlation with angiogenesis and tumor growth and aggressiveness has been extensively reported in experimental and human tumors. On these bases, the nitric oxide pathway appears to be a promising target for the development of pro- and anti-angiogenic therapeutic strategies. In particular, the use of NOS inhibitors or NO scavengers seems appropriate to reduce edema, block angiogenesis and facilitate antitumor drug delivery.
Polyunsaturated and Monounsaturated Fatty Acids in the Diet to Prevent Coronary Heart Disease via Cholesterol Reduction (1994)

For over 30 years the American Heart Association recommended to limit the fat intake to 30 energy % (E%) of total calories with 10 E% derived from polyunsaturated fatty acids (PUFA), 10 E% from monounsaturated fatty acids (MUFA) and 10 E% from saturated fatty acids (SFA). In 1988 and subsequent years, the National Cholesterol Education Program has changed this advise in favor of an increase of 15 E% MUFA and a reduction to 5 E% PUFA. This dramatic change was based largely on short-term dietary experiments, with formula diets with small numbers of subjects, and anecdotal epidemiological evidence from the population of Crete. The assertion that oleic acid may lower cholesterol and LDL remains unproven. However, isocaloric substitution of linoleic acid for oleic acid lowers cholesterol and LDL. Oleic acid has little or no effect on lipids and lipoproteins except as it replaces SFA. Large dietary feeding experiments in the 1950s and 1960s with persons with hypercholesterolemia and with patients after myocardial infarction were conducted with PUFA-enriched diets and proved effective in primary and secondary prevention of coronary heart disease. No such studies exist with MUFA-enriched diets. Therefore, the original recommendations remain the standard of dietary advise to healthy persons and patients after myocardial infarction.
A Novel Approach in Combined Liver and Kidney Transplantation With Long-term Outcomes (2016)

Delayed KT in CLKT (especially if delayed >48 h) is associated with improved kidney function with no DGF post-KT, and improved patient and graft survival.
Structure and Function of Recombinant Cobra Venom Factor (2004)

Cobra venom factor (CVF) is the complement-activating protein from cobra venom. It is a structural and functional analog of complement component C3. CVF functionally resembles C3b, the activated form of C3. Like C3b, CVF binds factor B, which is subsequently cleaved by factor D to form the bimolecular complex CVF,Bb. CVF,Bb is a C3/C5 convertase that cleaves both complement components C3 and C5. CVF is a three-chain protein that structurally resembles the C3b degradation product C3c, which is unable to form a C3/C5 convertase. Both C3 and CVF are synthesized as single-chain prepro-proteins. This study reports the recombinant expression of pro-CVF in two insect cell expression systems (baculovirus-infected Sf9 Spodoptera frugiperda cells and stably transfected S2 Drosophila melanogaster cells). In both expression systems pro-CVF is synthesized initially as a single-chain pro-CVF molecule that is subsequently proteolytically processed into a two-chain form of pro-CVF that structurally resembles C3. The C3-like form of pro-CVF can be further proteolytically processed into another two-chain form of pro-CVF that structurally resembles C3b. Unexpectedly, all three forms of pro-CVF exhibit functional activity of mature, natural CVF. Recombinant pro-CVF supports the activation of factor B in the presence of factor D and Mg2+ and depletes serum complement activity like natural CVF. The bimolecular convertase pro-CVF,Bb exhibits both C3 cleaving and C5 cleaving activity. The activity of pro-CVF and the resulting C3/C5 convertase is indistinguishable from CVF and the CVF,Bb convertase. The ability to produce active forms of pro-CVF recombinantly ensures the continued availability of an important research reagent for complement depletion because cobra venom as the source for natural CVF will be increasingly difficult to obtain as the Indian cobra is on the list of endangered species. Experimental systems to express pro-CVF recombinantly will also be invaluable for studies to delineate the structure and function relationship of CVF and its differences from C3 as well as to generate human C3 derivatives with CVF-like function for therapeutic complement depletion ("humanized CVF").
COPD: current therapeutic interventions and future approaches (2005)

Although long-acting bronchodilators have been an important advance for the management of chronic obstructive pulmonary disease (COPD), these drugs do not deal with the underlying inflammatory process. No currently available treatments reduce the progression of COPD or suppress the inflammation in small airways and lung parenchyma. Several new treatments that target the inflammatory process are now in clinical development. Some therapies, such as chemokine antagonists, are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD, whereas others target inflammatory cytokines such as tumour necrosis factor-alpha. Broad spectrum anti-inflammatory drugs are now in phase III development for COPD, and include phosphodiesterase-4 inhibitors. Other drugs that inhibit cell signalling include inhibitors of p38 mitogen-activated protein kinase, nuclear factor-kappaB and phosphoinositide-3 kinase-gamma. More specific approaches are to give antioxidants, inhibitors of inducible nitric oxide synthase and leukotriene B(4) antagonists. Other treatments have the potential to combat mucus hypersecretion, and there is also a search for serine proteinase and matrix metalloproteinase inhibitors to prevent lung destruction and the development of emphysema. More research is needed to understand the cellular and molecular mechanisms of chronic obstructive pulmonary disease and to develop biomarkers and monitoring techniques to aid the development of new therapies.
Multiple genes encode nuclear factor 1-like proteins that bind to the promoter for 3-hydroxy-3-methylglutaryl-coenzyme A reductase. (1988)

DNA-binding proteins of the nuclear factor 1 (NF1) family recognize sequences containing TGG. Two of these proteins, termed reductase promoter factor (RPF) proteins A and B, bind to the promoter for hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a negatively regulated enzyme in cholesterol biosynthesis. In the current study, we determined the sequences of peptides derived from hamster RPF proteins A and B and used this information to isolate a cDNA, designated pNF1/Red1, that encodes RPF protein B. The peptide sequence of RPF protein A, the other reductase-related protein, suggests that it is the hamster equivalent of NF1/L, which was previously cloned from rat liver. We also isolated a hamster cDNA for an additional member of the NF1 family, designated NF1/X. Thus, the hamster genome contains at least three genes for NF1-like proteins. It is likely to contain a fourth gene, corresponding to NF1/CTF, which was previously cloned from the human. The NH2-terminal sequences of all four NF1-like proteins (NF1/Red1, NF1/L, NF1/X, and NF1/CTF), which are virtually identical, contain the DNA-binding domain that recognizes TGG. Functional diversity may arise from differences in the COOH-terminal sequences. We hypothesize that the COOH-terminal domain interacts with adjacent DNA-binding proteins, thereby stabilizing the binding of a particular NF1-like protein to a particular promoter. This protein-protein interaction confers specificity to a class of proteins whose DNA-recognition sequence is widespread in the genome. Sterols may repress transcription of the reductase gene by disrupting this protein-protein interaction.
A simple 1-transistor capacitor-less memory cell for high performance embedded DRAMs (2003)

A new compact memory architecture is proposed for embedded dynamic random access memory (eDRAM) cells. By exploiting the floating body effect of partially depleted silicon on insulator (SOI) devices, a one-transistor memory cell can be integrated in a pure logic SOI technology without adding any process step. The data retention, device operation principles and reliability make it ideal for high performance eDRAM applications while reducing the cell area by a factor of two.
Regulation of Angiogenesis by the Kallikrein-Kinin System (2006)

High molecular weight kininogen (HK) is a plasma protein that is cleaved by plasma kallikrein in the clinical settings of sepsis and chronic inflammatory diseases such as rheumatoid arthritis and Crohn's disease. This proteolytic event results in a nonapeptide, bradykinin (BK), and a kinin-free derivative of HK, namely HKa. BK promotes angiogenesis by upregulation of bFGF through the B1 receptor or by stimulation of VEGF formation via the B2 receptor. Kininogen-deficient rats show diminished angiogenesis when neovascularization is stimulated. The formation of HKa results in exposure of domain 5 (D5). HKa or D5 inhibit endothelial cell migration and proliferation, both of which are needed for angiogenesis. In the chicken chorioallantoic membrane assay when neovascularization is stimulated by bFGF or VEGF, HKa or D5 inhibit angiogenesis. Monoclonal antibody C11C1, which prevents binding of HK to endothelial cells, also limits its conversion to BK thus downregulating angiogenesis. In vivo, mAb C11C1 inhibits tumor angiogenesis in mice as well as in experimental inflammatory arthritis and inflammatory bowel disease in Lewis rats. In vitro HKa or D5 inhibits endothelial cell adhesion to vitronectin and fibrinogen, resulting in anokis and apoptosis. The HKa receptor, uPAR, forms a signaling complex containing the integrin alphavbeta3 or alpha5beta1, caveolin, Src kinase Yes, focal adhesion kinase and paxcillin. HKa physically disrupts the complex by interfering with the binding of vitronectin to uPAR. Both mAb C11C1 and D5 have potential applications for controlling unwanted angiogenesis in inflammation and cancer.
Effects of Drug–Antibody Ratio on Pharmacokinetics, Biodistribution, Efficacy, and Tolerability of Antibody–Maytansinoid Conjugates (2017)

Antibody-drug conjugates (ADCs) are being actively pursued as a treatment option for cancer following the regulatory approval of brentuximab vedotin (Adcetris) and ado-trastuzumab emtansine (Kadcyla). ADCs consist of a cytotoxic agent conjugated to a targeting antibody through a linker. The two approved ADCs (and most ADCs now in the clinic that use a microtubule disrupting agent as the payload) are heterogeneous conjugates with an average drug-to-antibody ratio (DAR) of 3-4 (potentially ranging from 0 to 8 for individual species). Ado-trastuzumab emtansine employs DM1, a semisynthetic cytotoxic payload of the maytansinoid class, which is conjugated via lysine residues of the antibody to an average DAR of 3.5. To understand the effect of DAR on the preclinical properties of ADCs using maytansinoid cytotoxic agents, we prepared a series of conjugates with a cleavable linker (M9346A-sulfo-SPDB-DM4 targeting folate receptor α (FRα)) or an uncleavable linker (J2898A-SMCC-DM1 targeting the epidermal growth factor receptor (EGFR)) with varying DAR and evaluated their biochemical characteristics, in vivo stability, efficacy, and tolerability. For both formats, a series of ADCs with DARs ranging from low (average of ∼2 and range of 0-4) to very high (average of 10 and range of 7-14) were prepared in good yield with high monomer content and low levels of free cytotoxic agent. The in vitro potency consistently increased with increasing DAR at a constant antibody concentration. We then characterized the in vivo disposition of these ADCs. Pharmacokinetic analysis showed that conjugates with an average DAR below ∼6 had comparable clearance rates, but for those with an average DAR of ∼9-10, rapid clearance was observed. Biodistribution studies in mice showed that these 9-10 DAR ADCs rapidly accumulate in the liver, with maximum localization for this organ at 24-28% percentage injected dose per gram (%ID/g) compared with 7-10% for lower-DAR conjugates (all at 2-6 h post-injection). Our preclinical findings on tolerability and efficacy suggest that maytansinoid conjugates with DAR ranging from 2 to 6 have a better therapeutic index than conjugates with very high DAR (∼9-10). These very high DAR ADCs suffer from decreased efficacy, likely due to faster clearance. These results support the use of DAR 3-4 for maytansinoid ADCs but suggest that the exploration of lower or higher DAR may be warranted depending on the biology of the target antigen.