gebhart/patrepeval huggingface dataset:
PKR is required for NLRP3 inflammasome activation and HMGB1 release (114.7) (2012)

Abstract The NLR family pyrin domain-containing 3 (NLRP3) inflammasome, an intracellular oligomeric protein complex, regulates release of caspase-1 activation-dependent cytokines, including IL-1β, IL-18, and high-mobility group box 1 (HMGB1). During the course of studying HMGB1 release mechanisms from macrophages, we unexpectedly observed that double-stranded RNA dependent protein kinase (PKR) is required for NLRP3 inflammasome activation. PKR inactivation by genetic deletion or pharmacological inhibition blocked NLRP3 inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminum, and live E coli. Overexpression of PKR significantly enhanced the reconstituted NLRP3 inflammasome-induced caspase-1 activation and IL-1β maturation; whereas blocking PKR significantly inhibited the reconstituted NLRP3 inflammasome activation. PKR physically interacts with NLRP3, and PKR autophosphorylation is required for efficient PKR and NLRP3 interaction. Importantly, PKR autophosphorylation in a cell free system with recombinant NLRP3, ASC and pro-casapse-1 reconstitutes inflammasome activity. Together, these results indicate that PKR is required for inflammasome activation, and that it should be possible to target this molecule to inhibit inflammasome activity during inflammation.
The <i>lytE</i> Gene of <i>Bacillus subtilis</i> 168 Encodes a Cell Wall Hydrolase (1998)

Bacillus subtilis cell wall-bound protein CWBP33 is encoded by lytE, a gene expressed during the exponential growth phase. Sequence analysis of LytE, a 33-kDa protein, reveals two domains. The N-terminal domain contains a threefold-repeated motif common to several peptidoglycan binding proteins, while the C-terminal domain, probably carrying the catalytic activity, has homology with certain exoproteins. Zymographs unambiguously reveal that the absence of CWBP33, due to inactivation of lytE, is accompanied by the loss of a lytic activity. In lytE mutants, the cell autolysis rate is significantly decreased, although autolysis of corresponding, purified cell walls does not seem to be affected.
Necessary conditions for the photogeneration of nitrosyl linkage isomers (2009)

We investigate the fundamental necessary conditions for optical generation of nitrosyl linkage isomers in ML(5)NO compounds (M = transition metal, L arbitrary ligand) on the examples of K(3)[Mn(CN)(5)NO].2H(2)O and Na(2)[Fe(CN)(5)NO].2H(2)O. We show that the NO linkage isomers of the side-on bonded type (SII, 90 degrees rotation of NO) and of the isonitrosyl type M-ON, where NO is O-bound to the metal M (SI, 180 degrees rotation of NO), can be generated if two conditions are fullfilled. First the optical excitation must lead to a change in the bond between the NO group and the central metal atom M, either by a metal-to-ligand charge transfer of type d -->pi*(NO) or by a d-->d(z(2)) transition, which changes the sigma bonding of the NO group to the metal, such that the vibrational deformation mode delta(M-N-O) can drive the system into the SII configuration. Second the excited state potential must posses a minimum close to the saddle point of the ground state surface between GS and SII, SI, or cross that surface, such that the relaxation from the excited state into the metastable minima can occur. The same is true for transfers between the two metastable states SII and SI. As a further constraint with respect to the amount of population, i.e. the number of complexes which can be transferred into SII or SI, the cross sections sigma(GS,SII,SI) of the states GS, SII, and SI must be considered. If sigma(GS) > sigma(SII) and sigma(SI) > sigma(SII) SII can be occupied while SI can be significantly occupied if sigma(GS) > sigma(SI) and sigma(SII) > sigma(SI). More simply speaking the depletion rate of the metastable state should be smaller than its population rate for a given wavelength.
Combined midfoot osteotomy for severe forefoot adductus. (2003)

A one-stage procedure combining a closing wedge osteotomy of the cuboid with an opening wedge of the medial cuneiform was used for the treatment of severe forefoot adductus. Results were reviewed in 33 patients (50 feet) followed-up for at least 2 years postoperatively. Clinical and radiographic improvement in forefoot position was achieved in 90% of cases. The mean calcaneo-second metatarsal angle improved from 37 degrees preoperatively to 18 degrees at final follow-up. The mean talo-first metatarsal angle improved from 15 degrees preoperatively to 3 degrees at final follow-up. The medial to lateral column ratio demonstrated 33% improvement after surgical treatment. Two feet were unimproved because of graft migration. Patients younger than age 5 years without a well-defined medial cuneiform ossific nucleus had a high rate of medial graft extrusion with loss of correction. This procedure should be reserved for patients aged 5 years or older. Ten patients followed-up for more than 6 years had no deterioration in results. This procedure provides effective, safe, predictable, and lasting correction of forefoot adductus.
Inactivation of Bacteriophage T4, of Poly-D-Alanyl Bacteriophage and of Penicilloyl Bacteriophage by Immunospecifically Isolated IgM and IgG Antibodies (1969)

Abstract Anti-bacteriophage T4, anti-poly-d-alanyl and anti-penicilloyl antibodies were isolated from the sera of goats and rabbits at different times after immunization by means of water-insoluble immunoadsorbents prepared with bromoacetyl cellulose. The isolated antibody preparations were separated into IgM and IgG fractions. The relative efficiency of the isolated IgM and IgG antibodies in inactivating bacteriophage T4, poly-d-alanyl bacteriophage and penicilloyl bacteriophage differed with respect to the time after injection at which sera were collected, the method of plating and the specificity of the respective antibody used for the inactivation, leading to the conclusion that it is not possible to determine the respective concentration of antibodies of the two classes exclusively from phage inactivation measurements.
Hierarchical networks with Byzantine Robustness (2011)

In traditional networks, a single malicious (“Byzantine”) packet switch can cause global disruption; for instance, by giving incorrect routing information, flooding the network with traffic, or forwarding data incorrectly. Previous work (which we'll call NPBR for “Network Protocols with Byzantine Robustness”) presented a network design resilient to Byzantine failures, that guaranteed that nodes A and B can communicate, with some fair share of bandwidth, provided that at least one honest path connects them. NPBR, for reasons described in this paper, only works in a fairly small, flat network. This paper presents a network design that not only provides the same guarantees as NPBR, in a large hierarchical network, but provides additional guarantees, which we will describe in the paper. Furthermore, our design does not require any router to keep state larger than necessary for its portion of the network hierarchy. In this paper we summarize NPBR, explain why it does not extend to a hierarchy, and then present a design suitable for a hierarchy.
Oblivious Stash Shuffle (2017)

This is a companion report to Bittau et al. We restate and prove security of the Stash Shuffle.
Orientational Behavior of Single Molecules in Molecular Sieves:  A Study of Oxazine Dyes in AlPO<sub>4</sub>-5 Crystals (2003)

Three differently sized oxazine dye molecules, oxazine-1, oxazine-170, and oxazine-750, with molecular widths of 0.85, 1.0, and 1.1 nm, respectively, have been built into the one-dimensional pores of AlPO4-5 with a pore diameter of 0.73 nm during a template assisted synthesis. There is evidence that a deformed oxazine-1 molecule can tightly fit into these pores, whereas the larger molecules produce defect sites. The orientations of the used dyes were measured with polarization dependent fluorescence confocal microscopy. Ensemble measurements on the samples containing the oxazine dyes in high concentration reveal a preferential orientation of the molecules along the main axis of the crystal. However, the ensemble measurements cannot reveal the orientational distribution function of tilt angles. Therefore, this distribution function was obtained by measuring the orientations of many individual molecules using single molecule spectroscopy. The thinnest molecule, oxazine-1, shows a Gaussian type distribution of tilt angles with a half width at half-maximum of ξ = 18°. The medium sized oxazine-170 shows a broader Gaussian tilt function with ξ = 48°, whereas the broadest molecule oxazine-750 does not show a preferential orientation. These results clearly show that there is a structure directing influence of the host on the guest molecules in dependence of their size, even if the molecule is larger than the pore size. Additionally, distinct orientational jumps of individual oxazine-1 molecules were observed. Dynamic events such as these cannot be revealed by conventional ensemble spectroscopy.
Phenanthropiperidines and related compounds (1970)

Syntheses of variously substituted diphenylpiperidine derivatives were accomplished and their reactions, as intermediates in a new synthetic route to the physiologically active phenanthroindolizidine alkaloids and their analogues, were investigated. The s5nithesis involves Michael addition of phenylacetonitrile donors to ethyl cinnamate acceptors, yielding a series of ethyl-3,4-diphenyl-4-cyanobutanoates bearing aromatic methoxy, methylenedioxy and iodo substituents. Reductive cyclisation of these cyanoesters with Raney-nickel or copper chromite catalysts gave, imder exactly controlled conditions, either secondary or tertiary diphenylpiperidine derivatives or the corresponding dC - lactams. The ratio of the cis- and trans- racemates formed in each reaction was found to vary with changes in reduction temperature and with the substituent pattern of the starting material.
Production of Two Overlapping Bose-Einstein Condensates by Sympathetic Cooling (1997)

A new apparatus featuring a double magneto-optic trap and an Ioffe-type magnetic trap was used to create condensates of $2\ifmmode\times\else\texttimes\fi{}{10}^{6}$ atoms in either of the $|F\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}2,m\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}2〉$ or $|F\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}1,m\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}\ensuremath{-}1〉$ spin states of ${}^{87}$Rb. Overlapping condensates of the two states were also created using nearly lossless sympathetic cooling of one state via thermal contact with the other evaporatively cooled state. We observed that (i) the scattering length of the $|1,\ensuremath{-}1〉$ state is positive, (ii) the rate constant for binary inelastic collisions between the two states is $2.2(9)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}14}{\mathrm{cm}}^{3}/\mathrm{s}$, and (iii) there is a repulsive interaction between the two condensates. Similarities and differences between the behaviors of the two spin states are observed.
Minimum-Energy Cooperative Routing in Wireless Networks with Channel Variations (2011)

This paper considers the problem of finding minimum-energy cooperative routes in a wireless network with variable wireless channels. We assume that each node in the network is equipped with a single omnidirectional antenna and, motivated by the large body of physical layer research indicating its potential utility, that multiple nodes are able to coordinate their transmissions at the physical layer in order to take advantage of spatial diversity. Such coordination, however, is intrinsically intertwined with routing decisions, thus motivating the work. We first formulate the energy cost of forming a cooperative link between two nodes based on a two-stage transmission strategy assuming that only statistical knowledge about channels is available. Utilizing the link cost formulation, we show that optimal static routes in a network can be computed by running Dijkstra's algorithm over an extended network graph created by cooperative links. However, due to the variability of wireless channels, we argue that a many-to-one cooperation model in static routing is suboptimal. Hence, we develop an opportunistic routing algorithm based on many-to-many cooperation, and show that optimal routes in a network can be computed by a stochastic version of the Bellman-Ford algorithm. We use static and opportunistic optimal algorithms as baselines to develop heuristic link selection algorithms that are energy efficient while being computationally simpler than the optimal algorithms. We simulate our algorithms and show that while optimal cooperation and link selection can reduce energy consumption by almost an order of magnitude compared to non-cooperative approaches, our simple heuristics achieve similar energy savings while being computationally efficient as well.
Leukocyte-Platelet Aggregates in Rat Peripheral Blood After Ischemic Stroke and Reperfusion (2005)

Ischemic stroke and reperfusion (ISR) is associated with an inflammatory response characterized, in part, by the formation of leukocyte-platelet aggregates (LPA). Aggregate formation may amplify the immunologic and hemostatic functions of both cell types and thus exacerbate reperfusion injury after ischemic stroke. LPA formation in peripheral blood may also serve as a biomarker of the severity of injury. However, it is not fully known whether ISR causes LPA formation that can be detected in the peripheral blood. Therefore, the purpose of this study was to measure LPA in the peripheral blood after ISR using a rat model. The filament method was used to perform ISR. Blood was collected from the jugular vein before ischemia, after 4 hours of ischemia, and after 1 hour of reperfusion. Flow cytometry was used to quantify LPA in peripheral blood. Separate ISR groups were treated with tirofiban, a platelet GPIIb/IIIa inhibitor, and fucoidan, a selectin adhesion molecule inhibitor, and analyzed for LPA. Leukocyte CD11b expression and reactive oxygen species production were also analyzed to note the role of polymorphonuclear neutrophilic (PMN) activation on LPA formation. After ISR, LPA levels in peripheral blood were twice as large as preischemic levels. Both GPIIb/IIIa and selectin adhesion molecule inhibition (p < .05) decreased LPA to preischemic values. PMN CD11b expression was increased above baseline but did not differ between groups. Reactive oxygen species production did not differ between groups during reperfusion. These data suggest that ischemic stroke and reperfusion results in an increase in LPA that can be consistently measured in peripheral blood. LPA formation may be a useful biomarker and potential therapeutic target after ischemic stroke and reperfusion.
Quinazoline Antifolate Thymidylate Synthase Inhibitors: Replacement of Glutamic Acid in the C2-Methyl Series (1995)

The synthesis of a series of analogues of the potent thymidylate synthase (TS) inhibitor N-[4-[N-[(3,4-dihydro-2-methyl-4-oxo-6- quinazolinyl)methyl]-N-prop-2-ynylamino]benzoyl]-L-glutamic acid (ICI 198583, 1) is described in which the glutamic acid residue has been replaced by other alpha-amino acids. Most of these analogues were prepared by coupling of tert-butyl-4-(prop-2-ynylamino)benzoate (37) with 6-(bromomethyl)-3,4-dihydro-2-methyl-4-oxoquinazoline (34) followed by deprotection of the tert-butyl ester to the acid and azide-mediated coupling to the appropriate amino acid or amino acid ester. In cases where the amino acid ester was unreactive with the acid azide, a modification was used in which the quinazolinone moiety was protected as its 3-(pivaloyloxy)methyl derivative. This permitted the generation of the more reactive acid chloride of the p-aminobenzoate unit. In general these modifications result in compounds that have equivalent potency to 1 as inhibitors of isolated TS except where the amino acid lacks a lipophilic alpha-substituent. These compounds appear to require the reduced folate carrier (RFC) for transport into cells, but since they are not converted intracellularly into polyglutamated forms, they have a lower level of cytotoxicity compared to 1. The removal of the alpha-carboxylic acid has given a second set of analogues of 1 which contain simple alkyl amide, benzyl, substituted benzyl, and heterocyclic benzyl amide derivatives. These are considerably less potent than 1 as TS inhibitors but display 1-10 microM cytotoxicities due to the fact that they do not require RFC transport and can presumably readily enter cells by passive diffusion through the cell membrane. Molecular modeling and NMR studies indicated that the incorporation of, respectively, 7-methyl and 2'-fluoro substituents would favor the optimum conformation of these molecules for interaction with the TS enzyme. Accordingly, these substituents were incorporated into selected examples to give the series of analogues 47-55. These all show enhanced (approximately 10-fold) inhibition of TS compared to their unsubstituted counterparts. In the substituted benzylamides (51, 52) and heterocyclic benzyl amides (53-55) the ability to enter cells by passive diffusion results in highly potent (< 1 microM) cytotoxic agents.
Immunohistochemical studies on cholecystokinin (CCK)-immunoreactive neurons in the rat using sequence specific antisera and with special reference to the caudate nucleus and primary sensory neurons. (1989)

In the present immunohistochemical study the occurrence and distribution of CCK-immunoreactive neurons were analyzed in the brain, spinal cord and sensory ganglia using sequence specific antisera. Thus, antibodies directed towards the C-terminal portion of CCK-33, to the N-terminal portion of CCK-8 and to the mid portion of CCK-33 as well as monoclonal antibodies were used. For comparison antisera raised against calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH) and 5-hydroxytryptamine (5-HT) were used. Untreated, colchicine treated, 6-hydroxydopamine (6-OH-DA) treated and ibotenic acid treated rats were analyzed. The results indicate that most CCK systems in the rat central nervous system contain genuine CCK. These include, for example, the hippocampal formation, the hypothalamus, several subcortical forebrain areas, the ventral mesencephalon, nucleus tractus solitarii, some neurons in the ventral medulla oblongata as well as local and possibly descending neurons in the spinal cord. An exception was primary sensory neurons in which CCK-like immunoreactivity (LI) could only be demonstrated with C-terminally directed antisera and probably represents cross-reactivity with CGRP or a similar peptide. The central branches of such primary afferents were found both in the dorsal vagal complex, in the spinal trigeminal nucleus and in the dorsal horn of the spinal cord. Special attention was focused on CCK-LI in mesencephalic dopamine neurons and in their projection areas including nucleus accumbens, tuberculum olfactorium and particularly the caudate nucleus. In the latter structure CCK-LI exhibited a heterogenous pattern probably representing fibres of different types and origin. Thus, CCK-LI coexists with dopamine in two anatomically and morphologically distinguishable systems, one located in the periventricular area, increasing in size in the caudal direction to occupy most of the cauda, and a second system consisting of very fine dots in the medial half of the caudate nucleus. These two fibre types disappeared after 6-OH-DA treatment. A third system consisted of strongly fluorescent patches distributed at all levels of the caudate nucleus, mainly in its medial half. A diffuse, weakly fluorescent network of CCK-positive fibres was also found over the entire caudate nucleus. The latter two systems did not disappear after 6-OH-DA. Finally, local CCK-positive cell bodies were seen in small numbers, mainly in the ventral aspects of the caudate nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)
STAR-Liège Clinical Trial Interim Results: Safe and Effective Glycemic Control for All (2019)

While the benefits of glycemic control for critically ill patients are increasingly demonstrated, the ability to deliver safe, effective control to intermediate target ranges is widely debated due to the increased risk of hypoglycemia. This study analyzes interim clinical trial results of the fully computerized model-based Stochastic TARgeted (STAR) glycemic control framework at the University Hospital of Liège, Belgium. Patients with dysglycemia were randomly assigned to the full version of STAR, modulating both insulin and nutrition inputs, or STAR-IO, an insulin only version of STAR. Both arms target the normoglycemic 80-145 mg/dL (4.4-8.0 mmol/L) band. Results are further compared to retrospective data from 20 patients under the standard unit protocol targeting a higher 100-150 mg/dL (5.6-8.3 mmol/L) band. Much higher time in target band is provided under the full version of STAR, with similar safety and significantly lower incidence of mild hyperglycemia (blood glucose > 145 mg/dL or 8.0 mmol/L) and severe hyperglycemia (blood glucose > 180 mg/dL or 10.0 mmol/L). As a result, lower median blood glucose levels are safely and consistently achieved with lower glycemic variability, suggesting STAR's potential to improve clinical outcomes. These interim results show the possibility to achieve safe, effective control for all patients using STAR, and suggest glycemic control to lower targets could be beneficial.
<i>Trans</i> -acting antisense RNAs mediate transcriptional gene cosuppression in <i>S. cerevisiae</i> (2009)

Homology-dependent gene silencing, a phenomenon described as cosuppression in plants, depends on siRNAs. We provide evidence that in Saccharomyces cerevisiae, which is missing the RNAi machinery, protein coding gene cosuppression exists. Indeed, introduction of an additional copy of PHO84 on a plasmid or within the genome results in the cosilencing of both the transgene and the endogenous gene. This repression is transcriptional and position-independent and requires trans-acting antisense RNAs. Antisense RNAs induce transcriptional gene silencing both in cis and in trans, and the two pathways differ by the implication of the Hda1/2/3 complex. We also show that trans-silencing is influenced by the Set1 histone methyltransferase, which promotes antisense RNA production. Finally we show that although antisense-mediated cis-silencing occurs in other genes, trans-silencing so far depends on features specific to PHO84. All together our data highlight the importance of noncoding RNAs in mediating RNAi-independent transcriptional gene silencing.
Applications of enzymes in synthetic carbohydrate chemistry (1995)

By photosynthesis 200 billion tons of glucose are formed per annum most of which remains in the sugar state. Thus, the well-known properties of saccharides as the basis for structural materials and energy stores is well established. Increasingly, focus is being addressed to their functions as recognition molecule. Therefore, carbohydrate chemistry became en vogue again as documented by classical syntheses of complex hetero-oligosaccharides employing protecting and activating group chemistry. In recent years enzymatic methods for acylation and deacylation in saccharide chemistry came into use. Novel saccharides could be approached following aldolase-catalyzed de novo syntheses. The very complex task of stereospecific glycosylation was addressed by use of enzymes. With glycohydrolases via transglycosylation as well as with glycosyltransferases including cofactor regenerating circles advances were made. Modified acceptor and also donor substrates allowed access to oligosaccharides in preparative quantities. This paper will discuss these modern developments and will focus on some selected examples from others' and our own laboratory.