gebhart/patrepeval huggingface dataset:
Reactivity of an anionic Pd(ii) metallacycle with CH2X2(X = Cl, Br, I): formal insertion of methylene into a Pd–Carylbond (2004)

Whereas the reaction of the anionic palladium metallacycle [K[Pd(CH2CMe2-o-C6H4)(kappa2-Tp)]] with CH2Cl2 leads to the isolation of the stable Pd(IV) chloromethyl complex [Pd(CH2CMe2-o-C6H4)(kappa3-Tp)(CH2Cl)], the analogous reactions with CH2Br2 and CH2I2 give rise to the six membered metallacycles [Pd(CH2CMe2-o-C6H4(CH2))(kappa3-Tp)X](X = Br or I), as a result of the formal insertion of CH2 into the Pd-C(aryl) bond.
Nuclear Targeting of 6-Phosphofructo-2-kinase (PFKFB3) Increases Proliferation via Cyclin-dependent Kinases (2009)

The regulation of metabolism and growth must be tightly coupled to guarantee the efficient use of energy and anabolic substrates throughout the cell cycle. Fructose 2,6-bisphosphate (Fru-2,6-BP) is an allosteric activator of 6-phosphofructo-1-kinase (PFK-1), a rate-limiting enzyme and essential control point in glycolysis. The concentration of Fru-2,6-BP in mammalian cells is set by four 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4), which interconvert fructose 6-phosphate and Fru-2,6-BP. The relative functions of the PFKFB3 and PFKFB4 enzymes are of particular interest because they are activated in human cancers and increased by mitogens and low oxygen. We examined the cellular localization of PFKFB3 and PFKFB4 and unexpectedly found that whereas PFKFB4 localized to the cytoplasm (i.e. the site of glycolysis), PFKFB3 localized to the nucleus. We then overexpressed PFKFB3 and observed no change in glucose metabolism but rather a marked increase in cell proliferation. These effects on proliferation were completely abrogated by mutating either the active site or nuclear localization residues of PFKFB3, demonstrating a requirement for nuclear delivery of Fru-2,6-BP. Using protein array analyses, we then found that ectopic expression of PFKFB3 increased the expression of several key cell cycle proteins, including cyclin-dependent kinase (Cdk)-1, Cdc25C, and cyclin D3 and decreased the expression of the cell cycle inhibitor p27, a universal inhibitor of Cdk-1 and the cell cycle. We also observed that the addition of Fru-2,6-BP to HeLa cell lysates increased the phosphorylation of the Cdk-specific Thr-187 site of p27. Taken together, these observations demonstrate an unexpected role for PFKFB3 in nuclear signaling and indicate that Fru-2,6-BP may couple the activation of glucose metabolism with cell proliferation.
Activity, stability and 3-D structure of the Cu(ii) form of a chitin-active lytic polysaccharide monooxygenase from Bacillus amyloliquefaciens (2016)

The enzymatic deconstruction of recalcitrant polysaccharide biomass is central to the conversion of these substrates for societal benefit, such as in biofuels. Traditional models for enzyme-catalysed polysaccharide degradation involved the synergistic action of endo-, exo- and processive glycoside hydrolases working in concert to hydrolyse the substrate. More recently this model has been succeeded by one featuring a newly discovered class of mononuclear copper enzymes: lytic polysaccharide monooxygenases (LPMOs; classified as Auxiliary Activity (AA) enzymes in the CAZy classification). In 2013, the structure of an LPMO from Bacillus amyloliquefaciens, BaAA10, was solved with the Cu centre photoreduced to Cu(i) in the X-ray beam. Here we present the catalytic activity of BaAA10. We show that it is a chitin-active LPMO, active on both α and β chitin, with the Cu(ii) binding with low nM K<sub>D</sub>, and the substrate greatly increasing the thermal stability of the enzyme. A spiral data collection strategy has been used to facilitate access to the previously unobservable Cu(ii) state of the active centre, revealing a coordination geometry around the copper which is distorted from axial symmetry, consistent with the previous findings from EPR spectroscopy.
Plasticity of plasticity? Changes in the pattern of perceptual correlates of reorganization after amputation (1998)

We report a follow-up study on seven arm amputees in whom magnetic source imaging had originally revealed a strong correlation between the amount of cortical invasion of the deafferented cortex and the amount of pain evoked sensation mislocalized to the phantom limb. This re-examination was performed in order to corroborate the phenomenon of mislocalization. On follow-up examination for mislocalization 4 weeks later, a close correlation had remained between the original amount of cortical representational reorganization of the amputation zone (at the first examination) and the number of sites from where painful stimuli evoked sensations referred to the phantom limb, i.e. the amount of perceptual mislocalization, at the second examination. However, contrary to our expectation, the topography of referred sensation had completely changed in every patient. These results suggest that while the overall extent of reorganization is a rather stable phenomenon, the concomitant changes in the pattern of sensory processing are not. This may be due to the fact that alterations of sensory processing are not hardwired, but are rather mediated by an extensive and interconnected neural network with fluctuating synaptic strengths. This mechanism may be of importance for neurological rehabilitation.
Transparent optical packet switching: network architecture and demonstrators in the KEOPS project (1998)

This paper reviews the work carried out in the ACTS KEOPS (Keys to Optical Packet Switching) project, describing the results obtained to date. The main objective of the project is the definition, development, and assessment of optical packet switching and routing networks, capable of providing transparency to the payload bit rate, using optical packets of fixed duration and low bit rate headers in order to enable easier processing at the network/node interfaces. The feasibility of the KEOPS concept is assessed by modeling, laboratory experiments, and testbed implementation of optical packet switching nodes and network/node interfacing blocks, including a fully equipped demonstrator. The demonstration relies on advanced optoelectronic components, developed within the project, which are described.
Statistical Analysis of 168 Bilateral Subthalamic Nucleus Implantations by Means of the Probabilistic Functional Atlas (2005)

PFA-based planning may be superior to the current practice of using anatomic atlases that provide delineation of the target structure only, because it is more precise and provides a unique target point in the stereotactic space. This best stereotactic target is the point in the individualized atlas with the highest probability, meaning the highest probability of having the best target on the basis of the patients previously operated on. This best target is located in the hot STN, the size of which determines the precision of targeting. Because the size of the hot STN in comparison to the whole STN remains very small (1-2%) independent of whether or not lateral compensation is applied, target planning and execution have to be performed with high precision. The methodology presented, based on the PFA and on the functional volume, is general and can be applied to other structures and data sets. As numerous centers keep gathering large amounts of electrophysiological human and animal data, this work may facilitate opening new avenues in exploiting these data.
Genetic Analysis of the Twin Arginine Translocator Secretion Pathway in Bacteria (2002)

The twin arginine translocation (Tat) pathway of bacteria and plant chloroplasts mediates translocation of essentially folded proteins across the cytoplasmic membrane. The detailed understanding of the mechanism of protein targeting to the Tat pathway has been hampered by the lack of screening or selection systems suitable for genetic analysis. We report here the development of a highly quantitative protein reporter for genetic analysis of Tat-specific export. Specifically, export via the Tat pathway rescues green fluorescent protein (GFP) fused to an SsrA peptide from degradation by the cytoplasmic proteolytic ClpXP machinery. As a result, cellular fluorescence is determined by the amount of GFP in the periplasmic space. We used the GFP-SsrA reporter to isolate gain-of-function mutants of a Tat-specific leader peptide and for the genetic analysis of the "invariant" signature RR dipeptide motif. Flow cytometric screening of trimethylamine N-oxide reductase (TorA) leader peptide libraries resulted in isolation of six gain-of function mutants that conferred significantly higher steady-state levels of export relative to the wildtype TorA leader. All the gain-of-function mutations occurred within or near the (S/T)RRXFLK consensus motif, highlighting the significance of this region in interactions with the Tat export machinery. Randomization of the consensus RR dipeptide in the TorA leader revealed that a basic side chain (R/K) is required at the first position whereas the second position can also accept Gln and Asn in addition to basic amino acids. This result indicates that twin arginine translocation does not require the presence of an arginine dipeptide within the conserved sequence motif.
Aquaporins: The Molecular Basis of Facilitated Water Movement Through Living Plant Cells? (1994)

Osmotic effects observed with living cells indicate that their plasma membranes are freely permeable to water while essentially creating a barrier to other molecules. The hydraulic conductivity of biological membranes is sometimes still ascribed to the simple diffusion of water molecules through the lipid bilayer. However, more than 30 years ago the idea was advanced that hydraulic water movement through living cells occurs by bulk flow of water through pores in the membrane (Sidel and Solomon, 1957). Certain membranes of animal cells are unusually permeable to water and there is now a substantial body of evidence for the existence of water transport channels in such membranes (reviewed by Finkelstein, 1987; Verkman, 1992). For example, membranes from red blood cells and renal proximal tubules are exceptionally permeable to water; the membranes of the convoluted dista1 tubules of the kidney are also highly water permeable, and water permeability can be modulated by hormones. The hydraulic conductivity of plant cells has been thoroughly investigated and numerous reviews on this subject have been published (for a recent review, see Steudle, 1992).
An intelligent physical layer for cognitive radio networks (2008)

In this paper, we present an intelligent physical layer for cognitive mesh networks. It is well recognized that wireless mesh networks suffer from the inherent property of per hop delay attributed to store and forward routing and channel contention. We show that an intelligent physical layer coupled with efficient traffic engineering and channel allocation mechanism will reduce latency. In this paper, we discuss the evolution of an OFDM receiver, with sufficient software control to aid reconfigurability, capable of receiving and decoding information on different set of subcarriers, and also capable of switching the incoming signals to a different part of the available spectrum on the fly. Equipped with this enhanced receiver we propose a mechanism for wireless worm-hole routing, which employs frequency domain switching between subchannels where each subchannel is defined by a set of subcarriers. The OFDM receiver handles three primitives: transmit, receive and relay rather than just transmit or receive. Instead of a contention based, store and forward routing, a relay oriented physical layer has been proposed to reduce latency. The processing pipeline at an intermediate node no longer involves higher layer processing, and the hardware relays the incoming signal on-the-fly to a different part of the spectrum allowing for a full duplex transmission as the transmitter can relay signals while it is receiving on a different subchannel.
Direct Measurement of Nucleoside Monophosphate Delivery from a Phosphoramidate Pronucleotide by Stable Isotope Labeling and LC−ESI--MS/MS (2004)

Amino acid phosphoramidates of nucleosides have been shown to be potent antiviral and anticancer agents with the potential to act as nucleoside monophosphate prodrugs. To access their ability to deliver 3'-azido-3'-deoxythymidine (AZT) 5'-monophosphate to cells, the decomposition pathway of an 18O-labeled AZT amino acid phosphoramidate was investigated by capillary reverse-phase high-performance liquid chromatography interfaced with negative ion electrospray ionization mass spectrometry (LC-ESI(-)-MS/MS). 18O-labeled L-AZT tryptophan phosphoramidate methyl ester ([18O]2) was synthesized with an 18O/16O relative ratio of 1.22 +/- 0.18. For CEM cells, a human T-lymphoblast leukemia cell line, incubated with [18O]2, values of 1.55 +/- 0.37, 0.34, and 0.13 were found for the 18O/16O relative ratio of intracellular AZT-MP for time intervals of 0.5, 4, and 20 h, respectively. The decrease in the level of labeled AZT-MP in CEM cells corresponded to a rapid increase in the amount of intracellular AZT presumably by dephosphorylation of AZT-MP. In contrast, for peripheral blood mononuclear cells (PBMCs), the 18O/16O relative ratio values of intracellular AZT-MP were 1.43, 1.06, and 0.61 for time intervals of 0.5, 4, and 20 h, respectively. Intracellular AZT in PBMCs was nearly undetectable for each time interval. Taken together, these results are consistent with the detection of direct P-N bond cleavage by CEM cells and PBMCs. However, AZT phosphoramidates are able to more effectively deliver AZT-MP to PBMCs than to CEM cells. Differential expression of 5'-nucleotidase in CEM cells relative to PBMCs is likely the reason for this discrepancy. Although applied to a phosphoramidate pronucleotide, the judicious use of 18O labeling and LC-MS is a general approach that could be applied to the investigation of the intracellular fate of other pronucleotides.
Regulation of glucokinase in liver. (1976)

Our findings provide scientific evidence to support the clinical situation in which the interinjection interval of 3-6 mos of botulinum toxin A at a similar dosage is used.
Wound Infection After Elective Colorectal Resection (2004)

The incidence of incisional SSI in patients undergoing elective colorectal resection in our cohort was substantially higher than generally reported in the literature, the NNIS or predicted by an institutional surgical infection complication registry. Although some of these differences may be attributable to patient population differences, we believe these discrepancies highlight the potential limitations of systematic outcomes measurement tools which are independent of the primary clinical care team. Accurate surgical complication documentation by the primary clinical team is critical to identify the true frequency and etiology of surgical complications such as incisional SSI, to rationally approach their reduction and decrease their associated costs to patients and the health care system.
Polysilicon Surface Modification Technique To Reduce Sticking Of Microstructures (2005)

A new and simple surface modification technique is proposed to reduce sticking of microstructures fabricated by surface micromachining. This technique realizes very rugged surface at substrate polysilicon, resulting in reduced sticking through decrease of real contact area. The surface, which consists of honeycomb shaped grain holes at the substrate polysilicon layer, is defined by two-step dry etch without additional masking step for photolithography nor deposition of thin films. By varying the time for etching grain holes of substrate polysilicon, controlled surface roughness can be obtained. Test structures, including various length of polysilicon cantilever beams and micro bridges, fabricated by surface micromachining with proposed surface modification shows twice increase of detachment length without sticking to substrate.
Afferent connections of the habenular nuclei in the rat. A horseradish peroxidase study, with a note on the fiber‐of‐passage problem (1977)

The afferent connections of the habenular complex in the rat were examined by injecting horseradish peroxidase (HRP) into discrete portions of the habenular nuclei by microelectrophoresis. 1. HRP deposits confined to the lateral half of the lateral habenular nucleus labeled a multitude of cells in the entopeduncular nucleus. Numerous labeled cells also appeared in such cases in the lateral hypothalamus, indicating that the lateral habenular nucleus is a major convergence point of projections from these otherwise apparently quite separate cell regions. Moderate-to-small numbers of labeled cells were also found in the nuclei of the diagonal band, substantia innominata, lateral preoptic area and more caudally, in the ventral tegmental area, the region of the mesencephalic raphe, and the central gray substance. 2. HRP injected into the medial part of the lateral habenular nucleus labeled cells in the same regions, but more in the diagonal band and fewer in the entopeduncular nucleus than were labeled by more lateral injections. The contrast suggests that the projections from the basal forebrain and entopeduncular nucleus to the lateral habenular nucleus are somewhat topographically organized. 3. Injections of the medial habenular nucleus labeled an abundance of cells in the posterior parts of the supracommissural septum, but also a small number of cells in the diagonal band and mesencephalic raphe. 4. HRP injected into the stria medullaris labeled cells in all of the afore-mentioned areas and, in addition, cells in several olfactory structures, confirming that HRP may be taken up by fibers of passage and label their cells of origin, and suggesting that olfactory structures contribute fibers to the stria medullaris that do not terminate in the habenula.
Building Useful Models from Imbalanced Data with Sampling and Boosting (2008)

Building useful classification models can be a challeng-ing endeavor, especially when training data is imbal-anced. Class imbalance presents a problem when tra-ditional classification algorithms are applied. These al-gorithms often attempt to build models with the goal of maximizing overall classification accuracy. While such a model may be very accurate, it is often not very useful. Consider the domain of software quality pre-diction where the goal is to identify program modules that are most likely to contain faults. Since these mod-ules make up only a small fraction of the entire project, a highly accurate model may be generated by classi-fying all examples as not fault prone. Such a model would be useless. To alleviate the problems associated with class imbalance, several techniques have been pro-posed. We examine two such techniques: data sampling and boosting. Five data sampling techniques and one commonly used boosting algorithm are applied to five datasets from the software quality prediction domain. Our results suggest that while data sampling can be very effective at improving classification performance when training data is imbalance, boosting (which has received considerably less attention in research related to mining imbalanced data) usually results in even better perfor-mance.
Human antibody response to a strain-specific HIV-1 gp120 epitope associated with cell fusion inhibition. (1988)

PEPSCAN analysis, performed using 536 overlapping nonapeptides derived from the HTLV-III B nucleotide sequence of the region encoding the external envelope protein of 120 kDa (gp120), identified in the V3 region of gp120 a major binding site for antibodies of HIV-1-infected humans. The minimal amino acid sequence of this antibody binding site was demonstrated by multiple length scanning to be five to eight amino acids in length: (G)PGRAF(VT), i.e. amino acids 312-319. A peptide (Neu 21) containing this binding site for human antibodies (KSIRIQRGPGRAFVTIG) was synthesized and shown to induce HTLV-III B cell fusion-inhibiting antibodies in rabbits and mice. Antibodies binding to this HTLV-III B/LAV-1-specific peptide were shown to be primarily of the IgG 1 subclass, appeared within 6 months after HIV-1 antibody seroconversion in six out of 14 men studied, and persisted throughout the follow-up period of 10-24 months. The other eight seroconverting men did not develop antibodies to Neu 21 during the observation period. The appearance of antibodies to Neu 21 paralleled the capacity of the serum to inhibit HTLV-III B in cell fusion. HIV-1-infected men with Kaposi's sarcoma exhibited a similar frequency of antibodies to the synthetic peptide Neu 21 (14 out of 39, 36%) as asymptomatic HIV-1-infected men (112 out of 319, 35%). Adults with Pneumocystis carinii pneumonia had a significantly lower frequency (11 out of 78, 14%) of antibodies to Neu 21. Similarly, a low prevalence of antibodies to Neu 21 (8 out of 43, 19%) was observed among symptomatic HIV-1-infected children.
Heterophile Antibody Interference in a Multiplexed Fluorescent Microsphere Immunoassay for Quantitation of Cytokines in Human Serum (2004)

While modern immunoassays provide sensitive and specific means for the quantitation of cytokines in biological fluids, heterophile antibodies are still a well-recognized cause of interference in the measurement of cytokines in these assays. We have developed a multiplexed fluorescent microsphere immunoassay for the simultaneous quantification of 10 cytokines in only 75 microl of serum. During the development of this multiplexed assay, the amount of assay interference due to heterophile antibodies was also determined, and methods for detecting heterophile interference and minimizing its effect were incorporated into the assay. Heterophile antibodies resulted in significantly elevated cytokine values compared to those of normal blood bank samples. These falsely elevated values, and thus the components of the assay the heterophile antibodies were binding to, were identified through the use of internal controls. This information was then used to design assay-specific blockers and absorbents that were shown to significantly reduce falsely elevated cytokine values while not affecting the standard and control values. The fluorescent multiplexed microsphere-based immunoassay can be used to quantitate multiple cytokines from a single sample and should be a useful tool in furthering our understanding of the role of cytokines in disease processes.
Structural characterization of α1,3-galactosyltransferase knockout pig heart and kidney glycolipids and their reactivity with human and baboon antibodies (2010)

GalT-KO pig heart and kidney completely lacked Gal glycolipid antigens whilst glycolipids synthesized by competing pathways were increased. Baboon and human serum antibodies showed a different reactivity pattern to pig glycolipid antigens indicating that non-human primates have limitations as a human pre-clinical model for immune rejection studies.