gebhart/patrepeval huggingface dataset:
Back-propagation neural networks for nonlinear self-tuning adaptive control (1990)

A back-propagation neural network is applied to a nonlinear self-tuning tracking problem. Traditional self-tuning adaptive control techniques can only deal with linear systems or some special nonlinear systems. The emerging back-propagation neural networks have the capability to learn arbitrary nonlinearity and show great potential for adaptive control applications. A scheme for combining back-propagation neural networks with self-tuning adaptive control techniques is proposed, and the control mechanism is analyzed. Simulation results show that the new self-tuning scheme can deal with a large unknown nonlinearity.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Programmable tools for targeted analysis of epigenetic DNA modifications (2021)

Modifications of the cytosine 5-position are dynamic epigenetic marks of mammalian DNA with important regulatory roles in development and disease. Unraveling biological functions of such modified nucleobases is tightly connected with the potential of available methods for their analysis. Whereas genome-wide nucleobase quantification and mapping are first-line analyses, targeted analyses move into focus the more genomic sites with high biological significance are identified. We here review recent developments in an emerging field that addresses such targeted analyses via probes that combine a programmable, sequence-specific DNA-binding domain with the ability to directly recognize or cross-link an epigenetically modified nucleobase of interest. We highlight how such probes offer simple, high-resolution nucleobase analyses in vitro and enable in situ correlations between a nucleobase and other chromatin regulatory elements at user-defined loci on the single-cell level by imaging.
Interaction of the antiarrhythmic agents SR 33589 and amiodarone with the β‐adrenoceptor and adenylate cyclase in rat heart (1995)

1. The effects of SR 33589 and amiodarone on the cardiac beta-adrenoceptor were studied in vitro and after chronic treatment by means of [125I]-(-)-iodocyanopindolol ([125I]-(-)-CYP) binding and measurement of adenylate cyclase activity. 2. Binding of [125I]-(-)-CYP was inhibited in a dose-dependent manner by SR 33589 (IC50=1.8 +/- 0.4 microM, nH=0.93 +/- 0.06) and amiodarone (IC50=8.7 +/- 2.0 microM, nH=9.2 +/- 0.03). Saturation binding experiments indicated a non-competitive interaction such that SR 33589 (1 and 3 microM) and amiodarone (5 and 10 microM) reduced the Bmax of [125I]-(-)-CYP binding without any effect on the KD. Kinetic studies showed that the rate of association of [125I]-(-)-CYP was unchanged while the rate of dissociation was increased both in the presence of SR 33589 (10 microM) and amiodarone (30 microM).3. Under the same conditions, the receptor stimulated adenylate cyclase activity was inhibited in a dose-dependent, but non-competitive manner, by SR 33589 (isoprenaline-, glucagon- and secretin-stimulated enzyme inhibited 50% at 6.8 +/- 0.6 microM, 31 +/- 10 microM and 12 +/- 3 microM, respectively) while the basal, GTP- and GPP(NH)p-stimulated enzyme was inhibited by 5-10% and the NaF and forskolin-stimulated enzyme by 50% at 500 microM. Amiodarone exhibited a similar pattern of inhibition. 4. After chronic oral treatment (50, 100, 150 mg kg(-1) per day, 14 days), both SR 33589 and amiodarone produced a dose-dependent decrease in Bmax without any effect on KD as determined from [125I]-(-)-CYP saturation experiments and a decrease of the isoprenaline- and glucagon-stimulated adenylate cyclase activity without any effect on basal enzyme activity or activity when stimulated by agents acting directly on regulatory catalytic units. 5. Unlike amiodarone, SR 33589 does not contain iodine substituents. Plasma levels of T3, T4, and rT3 were changed after SR 33589 treatment except a decrease in T4 level at the highest dose whilst the T4 T3 ratio and the level of rT3 were dose-dependently increased by amiodarone treatment. 6. In vitro, SR 33589 and amiodarone were characterized as non-competitive beta-adrenoceptor antagonists. Chronic treatment led to a down-regulation of the beta-adrenoceptor; the down-regulation cannot be attributed to an indirect effect mediated by the thyroid hormones. To reconcile these opposing observations, we propose that SR 33589 and amiodarone interact with the beta-adrenoceptor at a site close to the intracellular loops which are involved in the coupling with Gs and contain the phosphorylable sites.
Transport in lymphatic capillaries. II. Microscopic velocity measurement with fluorescence photobleaching (1996)

Despite its relevance to the physiology of lymph formation and propulsion, the instantaneous flow velocity in single lymphatic capillaries has not been measured to date. The method of fluorescence recovery after photobleaching (FRAP) was adapted for this purpose and used to characterize flow in the lymphatic capillaries in tail skin of anesthetized mice during a constant-pressure intradermal injection of fluorescein isothiocyanate-dextran (mol wt 2 x 10(6). The median lymph flow velocity was 4.7 microns/s, and the velocity magnitude ranged from 0 to 29 microns/s. The direction of flow was generally proximal, but stasis and backflow toward the site of injection was also detected. Evidence for oscillatory flow was detected in some FRAP experiments, and in separate experiments a periodicity of approximately 120 min-1, directly correlated to respiration frequency, was measured by tracking the motion of fluorescent latex microspheres (1 micron diam) introduced into the lymphatic capillary network. The velocity magnitude showed a correlation with duration of infusion but not with distance from injection site. It is speculated that the temporal decay of mean velocity magnitude could be related to the relaxation of local pressure gradients as partially collapsed vessels expand during the infusion.
Altered Expression of Insulin-like Growth Factor II Receptor in Human Pancreatic Cancer (1997)

The insulin-like growth factor-II (IGF-II) receptor (IGF-IIR) is a single-chain transmembrane protein identical to the mannose-6-phosphate receptor. In the present study we examined IGF-IIR expression in normal and cancerous human pancreatic tissues. In the normal pancreas, moderately strong IGF-IIR immunoreactivity was present in the cytoplasm of islet cells, and mild cytoplasmic immunoreactivity was evident occasionally in ductal and acinar cells. Some ductal cells also exhibited nuclear IGF-IIR immunoreactivity. In the pancreatic cancers, regions of strong IGF-IIR immunoreactivity were present in the duct-like cancer cells within the tumor mass, often exhibiting nuclear localization. Expression of IGF-IIR mRNA in the cancer cells was confirmed by in situ hybridization. By comparison with normal pancreatic tissues, 7 of 12 pancreatic cancers exhibited a 5.6-fold increase in IGF-IIR mRNA levels, whereas in 3 cancers the IGF-IIR transcript was below the level of detection. Furthermore, all six tested cultured human pancreatic cancer cell lines expressed the IGF-IIR mRNA transcript. Our data indicate that IGF-IIR is overexpressed in a significant number of human pancreatic cancers, where it has a tendency to localize in the nucleus, and raise the possibility that IGF-IIR may contribute to the pathobiology of pancreatic cancer.
IL-12p70-Dependent Th1 Induction by Human B Cells Requires Combined Activation with CD40 Ligand and CpG DNA (2004)

The detection of microbial molecules via Toll-like receptors (TLR) in B cells is not well characterized. In this study, we found that both naive and memory B cells lack TLR4 (receptor for LPS) but express TLR9 (receptor for CpG motifs) and produce IL-6, TNF-alpha, and IL-10 upon stimulation with CpG oligonucleotides (ODN), synthetic mimics of microbial DNA. Consistent with the lack of TLR4, purified B cells failed to respond to LPS. Similar to CpG ODN, CD40 ligand (CD40L) alone induced IL-6, TNF-alpha, and IL-10. Production of these cytokines as well as IgM synthesis was synergistically increased when both CpG ODN and CD40L were combined. Unlike IL-6, TNF-alpha, and IL-10, the Th1 cytokine IL-12p70 was detected only when both CpG ODN and CD40L were present, and its induction was independent of B cell receptor cross-linking. CpG ODN did not increase the capacity of CD40L-activated B cells to induce proliferation of naive T cells. However, B cells activated with CpG ODN and CD40L strongly enhanced IFN-gamma production in developing CD4 T cells via IL-12. Together, these results demonstrate that IL-12p70 production in human B cells is under the dual control of microbial stimulation and T cell help. Our findings provide a molecular basis for the potent adjuvant activity of CpG ODN to support humoral immune responses observed in vivo, and for the limited value of LPS.
Different types of V(D)J recombination and end-joining defects in DNA double-strand break repair mutant mammalian cells (2002)

The end-joining pathway of DNA double-strand break (DSB) repair is necessary for proper V(D)J recombination and repair of DSB caused by ionizing radiation. This DNA repair pathway can either use short stretches of (micro)homology near the DNA ends or use no homology at all (direct end-joining). We designed assays to determine the relative efficiencies of these (sub)pathways of DNA end-joining. In one version, a DNA substrate is linearized in such a way that joining on a particular microhomology creates a novel restriction enzyme recognition site. In the other one, the DSB is made by the RAG1 and RAG2 proteins. After PCR amplification of the junctions, the different end-joining modes can be discriminated by restriction enzyme digestion. We show that inactivation of the 'classic' end-joining factors (Ku80, DNA-PK(CS), ligase IV and XRCC4) results in a dramatic increase of microhomology-directed joining of the linear substrate, but very little decrease in overall joining efficiency. V(D)J recombination, on the other hand, is severely impaired, but also shows a dramatic shift towards microhomology use. Interestingly, two interstrand cross-linker-sensitive cell lines showed decreased microhomology-directed end-joining, but without an effect on V(D)J recombination. These results suggest that direct end-joining and microhomology-directed end-joining constitute genetically distinct DSB repair pathways.
Effect of Rifampicin on S-ketamine and S-norketamine Plasma Concentrations in Healthy Volunteers after Intravenous S-ketamine Administration (2011)

: A novel observation is the large effect of rifampicin on S-norketamine concentrations and indicates that rifampicin induces the elimination of S-ketamine's metabolite, S-norketamine, probably via induction of the CYP3A4 and/or CYP2B6 enzymes.
3D Insulator‐based dielectrophoresis using DC‐biased, AC electric fields for selective bacterial trapping (2014)

Insulator-based dielectrophoresis (iDEP) is a well-known technique that harnesses electric fields for separating, moving, and trapping biological particle samples. Recent work has shown that utilizing DC-biased AC electric fields can enhance the performance of iDEP devices. In this study, an iDEP device with 3D varying insulating structures analyzed in combination with DC biased AC fields is presented for the first time. Using our unique reactive ion etch lag, the mold for the 3D microfluidic chip is created with a photolithographic mask. The 3D iDEP devices, whose largest dimensions are 1 cm long, 0.18 cm wide, and 90 μm deep are then rapidly fabricated by curing a PDMS polymer in the glass mold. The 3D nature of the insulating microstructures allows for high trapping efficiency at potentials as low as 200 Vpp. In this work, separation of Escherichia coli from 1 μm beads and selective trapping of live Staphylococcus aureus cells from dead S. aureus cells is demonstrated. This is the first reported use of DC-biased AC fields to selectively trap bacteria in 3D iDEP microfluidic device and to efficiently separate particles where selectivity of DC iDEP is limited.
The Role of Recombinant Human Erythropoietin in the Treatment of Thalassemia (1998)

The rationale for treatment with recombinant human erythropoietin (rHuEPO) in thalassemia came from studies in baboons, thalassemic mice and in erythroid cultures. The results demonstrated an increase in gamma globin synthesis and consequently in fetal Hb (Hb F) resulting in improvement in erythropoietic parameters. In addition, endogenous serum Epo levels in various forms of thalassemia were inconsistent and not related to the severity of the anemia. Therefore, several preliminary studies with rHuEPO were performed, mainly on patients with beta thalassemia intermedia. The results indicate: a) a significant, dose-related (500 u/kg to 1000 u/kg x 3/week) increase in thalassemia erythropoiesis without changes in % of Hb F, MCV and MCH, mainly in splenectomized patients; b) the minimum effective dose is 500 u/kg x 3/week; c) there were no major side effects during the continuous treatment period of 9 months. In order to improve both quantitative and qualitative thalassemia erythropoiesis, several trials were undertaken combining rHuEPO with hydroxyurea (HU), which is known to increase % Hb F, MCV and MCH without a major effect on Hb levels. The designed trial included 3 to 6 months of HU alone (20 mg/kg x 4/week), or with rHuEPO alone (500 u/kg x 3/week or 375 u/kg x 2/week) or a combination of the two drugs. The results show an additive effect of the two drugs, in some of the patients. It is not known whether the addition of oral iron to rHuEPO is warranted for maximal erythropoietic response. The major limiting factor in designing large scale clinical trials is the relatively high cost of the drug. Nevertheless rHuEPO alone or in combination with other Hb F modulating drugs may have a positive effect in thalassemia with resulting improvement in the quality of life.
Protease-resistant form of insulin-like growth factor-binding protein 5 is an inhibitor of insulin-like growth factor-I actions on porcine smooth muscle cells in culture. (1997)

IGFs are pleiotrophic mitogens for porcine smooth muscle cells (pSMC) in culture. The effects of IGFs on cells are modulated by various insulin-like growth factor-binding proteins (IGFBP). IGFBP-5 is synthesized by pSMC and binds to the extracellular matrix. However, IGFBP-5 is also secreted into conditioned medium of cultured cells and is cleaved into fragments by a concomitantly produced protease. These fragments have reduced affinity for the IGFs and cleavage makes it difficult to assess the role of intact IGFBP-5. To study the consequence of accumulation of intact IGFBP-5 in medium, we determined the cleavage site in IGFBP-5 and prepared a protease resistant mutant. Amino acid sequencing of purified IGFBP-5 fragments suggested Arg138-Arg139 as the primary cleavage site. Arg138-Arg139-->Asn138-Asn139 mutations were introduced to create protease-resistant IGFBP-5, which has the same affinity for IGF-I as the native protein. This mutant IGFBP-5 remained intact even after 24 h of incubation and it inhibited several IGF-I actions when added to pSMC culture medium. The mutant IGFBP-5 (500 ng/ml) decreased IGF-I stimulated cellular DNA synthesis by 84%, protein synthesis by 77%, and it inhibited IGF-I stimulated migration of pSMC by 77%. It also inhibited IGF-I stimulation of IRS-1 phosphorylation. In contrast, the same amount of native IGFBP-5 did not inhibit IGF-I actions. The significance of inhibitory effects of the protease resistant IGFBP-5 was further demonstrated in pSMC transfected with mutant or native IGFBP-5 cDNAs. The mutant IGFBP-5 accumulated in culture medium of transfected cells, while native IGFBP-5 was degraded into fragments, PSMC overexpressing the mutant IGFBP-5 also responded poorly to IGF-I compared with mock transfected cells. IGF-I (5 ng/ml) increased [35S]methionine incorporation into control cells by 36% above the basal level, but it did not significantly change (4%) in pSMC cultures that were producing the mutant IGFBP-5. In conclusion, the accumulation of protease-resistant IGFBP-5 in the medium was inhibitory to IGF-I actions on pSMC. This suggests that proteolysis can prevent IGFBP-5 from acting as an inhibitor of IGF-I-stimulated effects and that it serves as an important mechanism for regulating cellular responsiveness to IGF-I.
Kinetic characterization of the unisite catalytic pathway of seven β-subunit mutant F1-ATPases from Escherichia coli (1989)

We have studied the kinetics of "unisite" ATP hydrolysis and synthesis in seven mutant Escherichia coli F1-ATPase enzymes. The seven mutations are distributed over a 105-residue segment of the catalytic nucleotide-binding domain in beta-subunit and are: G142S, K155Q, K155E, E181Q, E192Q, M209I, and R246C. We report forward and reverse rate constants and equilibrium constants in all seven mutant enzymes for the four steps of unisite kinetics, namely (i) ATP binding/release, (ii) ATP hydrolysis/synthesis, (iii) Pi release/binding, and (iv) ADP release/binding. The seven mutant enzymes displayed a wide range of deviations from normal in both rate and equilibrium constants, with no discernible common pattern. Notably, steep reductions in Kd ATP were seen in some cases, the value of Kd Pi was high, and K2 (ATP hydrolysis/synthesis) was relatively unaffected. Significantly, when the data from the seven mutations were combined with previous data from two other E. coli F1-beta-subunit mutations (D242N, D242V), normal E. coli F1, soluble and membranous mitochondrial F1, it was found that linear free energy relationships obtained for both ATP binding/release (log k+1 versus log K1) and ADP binding/release (log k-4 versus log K-4). Two conclusions follow. 1) The seven mutations studied here cause subtle changes in interactions between the catalytic nucleotide-binding domain and substrate ATP or product ADP. 2) The mitochondrial, normal E. coli, and nine total beta-subunit mutant enzymes represent a continuum in which subtle structural differences in the catalytic site resulted in changes in binding energy; therefore insights into the nature of energy coupling during ATP hydrolysis and synthesis by F1-ATPase may be ascertained by detailed studies of this group of enzymes.
Bacterial diversity in Adirondack mountain lakes as revealed by 16S rRNA gene sequences (1997)

Bacterial communities of seven lakes in the Adirondack Mountains of New York State were characterized by amplification and sequencing of 16S ribosomal DNA. Analysis of over 100 partial sequences revealed a diverse collection of lineages, largely of the class Proteobacteria (19% alpha subdivision, 31% beta subdivision, and 9% gamma subdivision), the phylum Cytophaga-Flavobacteria-Bacteroides (15%), and the order Actinomycetales (18%). Additionally, a number of the sequences were similar to those of the order Verrucomicrobiales. However, few of the sequence types are closely related to those of characterized species. The relative contributions of the groups of sequences differed among the lakes, suggesting that bacterial population structure varies and that it may be possible to relate aquatic bacterial community structure to water chemistry.
Analysis of ultrashort pulse-shape measurement using linear interferometers (1994)

A general interferometer composed of linear filters (both time stationary and frequency stationary) and a square-law detector is analyzed, and the possibilities for measuring the spectral phase of ultrashort optical pulses are enumerated. It is found that with purely time-stationary filters the phase spectrum cannot be determined with an integrating detector but that a detector with a finite bandwidth permits such a determination. It is also shown that the phase may be measured with a time-nonstationary filter and an integrating detector. The possibilities for realizing the system are evaluated.
Wireless distributed multimedia communications networks for the digital battlefield (2002)

The Focused Research Initiative (FRI) Group from Purdue University, the University of Illinois, the University of Michigan, Magnavox, and Hughes Network Systems (HNS) began work in July of 1995 on a five year program. The FRI Group is uniquely integrating several Department of Defense programs and the research and educational programs at three major universities, while achieving the benefits of collaboration with industry and the military. The concept of the digital battlefield requires digitization of all the information on the battlefield needed for the conduct of battle and mission accomplishment. Software is used to extract the information needed by a tactical commander, logistics commander, or individual soldier from the databases and to reformat, filter, and fuse the data to forms usable for each particular function reducing information overload. Functions include command and control, target detection and recognition, planning, analysis maps and overlays, intelligence, logistics, personnel, and position location. Wireless, distributed communications networks are required to acquire information from sources and to transmit it between databases and battlefield entities. Technology for distributed multimedia communications networks must be found to support the multimedia transmission of speech, video, high resolution maps and overlays, and other digital data in a highly mobile military environment requiring low probability of intercept and jamming resistance.
Design of 25-nm SALVO PMOS devices (2000)

The concept and preliminary designs of novel self-aligned local-channel V-gate by optical lithography (SALVO) devices are presented. SALVO uses optimized local-channel doping to sharpen the lateral junctions, in order to minimize short channel effects for gate lengths down to 25 nm. In addition, it utilizes the replacement-gate design with inner spacers to facilitate integration of alternative gate stack materials and to extend the application of optical lithography. SALVO PMOS designs with both metal gate and poly-metal gate electrodes were studied, the latter proving capable of delivering high performance 25 nm PMOS with currently manufacturable processes.
The Design of a Secure Internet Gateway. (1990)

The Internet supports a vast and growing community of computers users around the world. Unfortunately, this network can provide anonymous access to this community by the unscrupulous, careless, or dangerous. On any given Internet there is a certain percentage of poorly-maintained systems. AT&amp;amp;T has a large internal Internet that we wish to protect from outside attacks, while providing useful services between the two. This paper describes our Internet gateway. It is an application-level gateway that passes mail and many of the common Internet services between our internal machines and the Internet. This is accomplished without IP connectivity using a pair of machines: a trusted internal machine and an untrusted external gateway. These are connected by a private link. The internal machine provides a few carefully-guarded services to the external gateway. This configuration helps protect the internal internet even if the external machine is fully compromised. 1.
Molecular recognition analyzed by docking simulations: the aspartate receptor and isocitrate dehydrogenase from Escherichia coli. (1993)

Protein docking protocols are used for the prediction of both small molecule binding to DNA and protein macromolecules and of complexes between macromolecules. These protocols are becoming increasingly automated and powerful tools for computer-aided drug design. We review the basic methodologies and strategies used for analyzing molecular recognition by computer docking algorithms and discuss recent experiments in which (i) substrate and substrate analogues are docked to the active site of isocitrate dehydrogenase and (ii) maltose binding protein is docked to the extracellular domain of the receptor, which signals maltose chemotaxis.