gebhart/patrepeval huggingface dataset:
Tree-Structured Methods for Longitudinal Data (1992)

Abstract The thrust of tree techniques is the extraction of meaningful subgroups characterized by common covariate values and homogeneous outcome. For longitudinal data, this homogeneity can pertain to the mean and/or to covariance structure. The regression tree methodology is extended to repeated measures and longitudinal data by modifying the split function so as to accommodate multiple responses. Several split functions are developed based either on deviations around subgroup mean vectors or on two sample statistics measuring subgroup separation. For the methods to be computationally feasible, it is necessary to devise updating algorithms for the split function. This has been done for some commonly used covariance specifications: independence, compound symmetry, and first-order autoregressive models. Data analytic issues, such as handling missing values and time-varying covariates and determining appropriate tree size are discussed. An illustrative example concerning immune function loss in a cohort of human immunodeficiency virus (HIV)-seropositive gay men also is presented.
Take a scientific look at the noise hazard. (1976)

President Roosevelt does not believes Gould's deficiencies in math are enough to prevent him from being an officer and would like to see him appointed as a second lieutenant.
Consumption and Portfolio Choice over the Life Cycle (2005)

This article solves a realistically calibrated life cycle model of consumption and portfolio choice with non-tradable labor income and borrowing constraints. Since labor income substitutes for riskless asset holdings, the optimal share invested in equities is roughly decreasing over life. We compute a measure of the importance of human capital for investment behavior. We find that ignoring labor income generates large utility costs, while the cost of ignoring only its risk is an order of magnitude smaller, except when we allow for a disastrous labor income shock. Moreover, we study the implications of introducing endogenous borrowing constraints in this incomplete-markets setting.
Medical aspects of automotive fatalities (1966)

I make no secret of being for business. I have a business. I was raised and educated on automotive money. I do not like government encroachment on my business and I don't like to see it invade the automotive business. So to see publicity implying that the automobile companies are the major blame for fatalities and injuries seems unfair, especially when the government steps in. We know there are many other factors far more important in the causes of fatalities; factors such as lack of driver education, inadequate drivers, inadequate roads, congestion, obsolete cars, and lack of safety margins along roads. We even forget that the number of fatalities per year has not changed much in many years while miles driven and cars on the road have increased beyond comprehension. As doctors, have we taken adequate stock of our role in fatalities. We are all confronted with patients whose ability to drive is certainly to be questioned. It is certainly our responsibility to make sure that these patients do not drive cars by all that is in our power of persuasion, and to notify where applicable, authorities about these people, so that their licenses can be revoked. This problem is simple in the grossly inadequate patient. It becomes a real problem in the more subtle portions of our psychological, physiological and mechanical ability evaluations of patients, and a considerable amount of work certainly needs to be done along this line.
Michael Addition of Secondary Nitroalkanes to β-Substituted α,β-Unsaturated Compounds (1984)

Addition du nitro-2 propane a des crotonate, cinnamate de methyle, chalcone, crotonitrile, (phenyl styryl) sulfone et (phenyl propenyl) sulfoxyde
Optical coherence techniques for plasma spectroscopy (invited) (2001)

A new electro-optically modulated optical solid-state (MOSS) spectrometer has been constructed for high temporal resolution measurement of the coherence of line radiation from plasmas. The instrument is an electro-optically modulated fixed delay polarization interferometer, or Fourier transform spectrometer. It has high light throughput compared with conventional grating based instruments of comparable resolving power while being compact and robust against alignment errors. By employing electro-optical path-length modulation techniques, the spectral information is transferred to the temporal frequency domain and can be obtained using a single photodetector. A wide field-of-view MOSS camera has been developed for imaging applications, while multiple-delay variants of the basic single fixed delay instrument have also been successfully tested. We discuss applications including passive Doppler spectroscopy, charge exchange recombination spectroscopy, and Zeeman and motional Stark effects. For Doppler tomographic applications, we show that such time-domain instruments have certain fundamental advantages, not least of which is a simple relationship between fringe visibility and the line integral of the intensity weighted velocity distribution function.
Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas (2006)

Chordomas are malignant tumours that occur along the spine and are thought to derive from notochordal remnants. There is significant morphological variability between and within chordomas, with some showing prominent areas of chondroid differentiation. Our microarray data from a broad range of connective tissue neoplasms indicate that, at the transcriptional level, chordomas resemble cartilaginous neoplasms. Here we show that chordomas express many genes known to be involved in cartilage development, but they also uniquely express genes distinguishing them from chondroid neoplasms. The brachyury transcription factor, known to be involved in notochordal development, is only expressed by chordomas. Using a polyclonal antibody, we show that brachyury is expressed in the embryonic notochord and in all 53 chordomas analysed, labelling both chondroid and chordoid areas of these tumours. In contrast, the protein was not detected in over 300 neoplasms, including 163 chondroid tumours. Brachyury was not detected in the nucleus pulposus, arguing against the hypothesis that this tissue derives directly from the notochord. These data provide compelling evidence that chordomas derive from notochord and demonstrate that brachyury is a specific marker for the notochord and notochord-derived tumours.
Phosphorylation of Puma modulates its apoptotic function by regulating protein stability (2010)

Puma is a potent BH3-only protein that antagonises anti-apoptotic Bcl-2 proteins, promotes Bax/Bak activation and has an essential role in multiple apoptotic models. Puma expression is normally kept very low, but can be induced by several transcription factors including p53, p73, E2F1 and FOXO3a, whereby it can induce an apoptotic response. As Puma can to bind and inactivate all anti-apoptotic members of the Bcl-2 family, its activity must be tightly controlled. We report here, for the first time, evidence that Puma is subject to post-translational control through phosphorylation. We show that Puma is phosphorylated at multiple sites, with the major site of phosphorylation being serine 10. Replacing serine 10 with alanine causes reduced Puma turnover and enhanced cell death. Interestingly, Puma turnover occurs through the proteasome, and substitution of serine 10 causes elevated Puma levels independently of macroautophagy, Bcl-2 family member binding, caspase activity and apoptotic death. We conclude, therefore, that phosphorylation of Puma at serine 10 promotes Puma turnover, represses Puma's cell death potential and promotes cell survival. Owing to the highly pro-apoptotic nature of Puma, these studies highlight an important additional regulatory step in the determination of cellular life or death.
Therapeutic Fc‐fusion proteins: Current analytical strategies (2020)

Fc-Fusion proteins represent a successful class of biopharmaceutical products, with already 13 drugs approved in the European Union and United States as well as three biosimilar versions of etanercept. Fc-Fusion products combine tailored pharmacological properties of biological ligands, together with multiple functions of the fragment crystallizable domain of immunoglobulins. There is a great diversity in terms of possible biological ligands, including the extracellular domains of natural receptors, functionally active peptides, recombinant enzymes, and genetically engineered binding constructs acting as cytokine traps. Due to their highly diverse structures, the analytical characterization of Fc-Fusion proteins is far more complex than that of monoclonal antibodies and requires the use and development of additional product-specific methods over conventional generic/platform methods. This can be explained, for example, by the presence of numerous sialic acids, leading to high diversity in terms of isoelectric points and complex glycosylation profiles including multiple N- and O-linked glycosylation sites. In this review, we highlight the wide range of analytical strategies used to fully characterize Fc-fusion proteins. We also present case studies on the structural assessment of all commercially available Fc-fusion proteins, based on the features and critical quality attributes of their ligand-binding domains.
Relay selection for alert messaging in vanets based on bi-directional stable communication approach (2014)

Wireless communication alert messaging protocols based on vehicular ad hoc networks (VANETs) have promising role to play in reducing road accidents. Reliable reception of the alert messages to all concerned vehicles within a certain time limit is a prime objective to achieve when employing alert messaging in VANETs. In this work, we propose a bi-directional link quality assessment based alert messaging protocol. Simulated performance evaluation is presented while stressing on reachability of the alert messages in varying network density scenarios. The proposed communication model is compared to conventional distance based alert messaging as being the most widely used technique for relay nodes selection. The proposed protocol outperforms in reachability the conventional one, while adhering well below to delay requirements of alert messages propagation for most endangered vehicles.
Guanine nucleotide depletion and toxicity in mouse T lymphoma (S-49) cells. (1981)

Incubation of mouse T lymphoma (S-49) cells with the inosinate dehydrogenase inhibitor mycophenolic acid produced a depletion of both GTP and dGTP, and resulted in growth inhibition, partial reduction in RNA synthesis, and drastic inhibition of DNA synthesis. Similar results suggested to others that the depletion of dGTP is primarily responsible for toxicity. However, guanosine was as effective as deoxyguanosine at preventing mycophenolic acid toxicity although deoxyguanosine was more effective at elevating dGTP levels. Moreover, in hypoxanthine-guanine phosphoribosyltransferase-deficient mutants of S-49 (6MPR-3-3) deoxyguanosine was unable to prevent mycophenolic acid toxicity or to re-establish normal DNA synthesis, although it returned cellular dGTP but not GTP levels to normal. No other nucleotide levels changed in a way which could account for the toxicity. Incubation of cells with a combination of deoxyadenosine, deoxycytidine, and erythro-9-(2-hydroxy-3-nonyl)adenine produced a selective depletion of dGTP to levels similar to that produced by mycophenolic acid, but did not affect cell growth. Studies with cells synchronized by centrifugal elutriation show that the toxicity of mycophenolic acid is specific to the S-phase of the cell cycle. Addition of actinomycin D at a concentration that inhibited RNA synthesis increased the availability of GTP and re-established normal DNA synthesis in mycophenolic acid-treated S-49 cells. These results suggest that the depletion of GTP rather than that of dGTP produces toxic effects in S-49 cells and that GTP is required for DNA synthesis.
Chiral organometallic half-sandwich complexes with defined metal configuration (2003)

Chiral organometallic half-sandwich complexes with stereogenic metal atoms are close relatives of chiral organic compounds with stereogenic carbon atoms. Similarities and differences between these two classes of compounds are outlined. Some representative metal complexes are discussed in an introductory section followed by a more detailed treatment of the available strategies to control the metal configuration by means of chiral auxiliaries. Special sections are devoted to the discussion of the configurational stability of chiral-at-metal complexes and their applications in stoichiometric and catalytic stereoselective reactions.
Plasma expanders stabilize human microvessels in microfluidic scaffolds (2012)

Plasma expanders such as dextran and hydroxyethyl starch (HES) are important components of solutions designed to maintain vascular volume in the clinical setting and to preserve organs ex vivo before transplantation. Here, we show that these polymers also exert stabilizing effects on engineered microvessels in microfluidic type I collagen and fibrin scaffolds. Standard growth media, which did not contain dextran or HES, led to severe leakage, vascular collapse, and catastrophic failure of perfusion. Remarkably, vessels that were provided with 3% dextran or 5% HES had few focal leaks, maintained adhesion to the scaffold, and were typically viable and patent for at least 2 weeks. We found that the junctional marker VE-cadherin localized to a wide band in the presence of plasma expanders, but only at concentrations that also stabilized vessels. In conjunction with a previous computational model (Wong et al., Biomaterials 2010;31:4706-4714), our results suggest that plasma expanders stabilize microvessels via physical mechanisms that enhance VE-cadherin localization at junctions and thereby limit vascular leakiness.
A 2.5 ns clock access 250 MHz 256 Mb SDRAM with a synchronous mirror delay (2002)

A 245.7 mm/sup 2/ 256 Mb SDRAM uses: (1) 60.2% cell-occupancy ratio array, (2) prefetched pipeline using first-in first-out buffer with parallel/serial converter, (3) synchronous mirror delay circuit.
Septocylindrins A and B:  Peptaibols Produced by the Terrestrial Fungus <i>S</i><i>eptocylindrium</i> sp. LL-Z1518 (2007)

Two new peptaibols, septocylindrin A (1) and septocylindrin B (2), related to the well-studied membrane-channel-forming peptaibol alamethicin, were obtained from a terrestrial isolate of the fungus Septocylindrium sp. Both 1 and 2 are linear 19-amino acid peptides with a modified phenylalanine C-terminus. Analysis of the HRMS data indicated that they differ only in the 18th residue, where 1 contains Glu and 2 contains Gln. The structures of these two peptaibols were determined by extensive NMR and HRMS analysis. The absolute configurations of amino acids present in 1 were determined using Marfey's methodology. Both compounds were isolated through bioassay-guided fractionation and exhibited significant antibacterial and antifungal activity.
Automated Targeting of Cells to Electrochemical Electrodes Using a Surface Chemistry Approach for the Measurement of Quantal Exocytosis (2010)

Here we describe a method to fabricate a multi-channel high-throughput microchip device for measurement of quantal transmitter release from individual cells. Instead of bringing carbon-fiber electrodes to cells, the device uses a surface chemistry approach to bring cells to an array of electrochemical microelectrodes. The microelectrodes are small and "cytophilic" in order to promote adhesion of a single cell whereas all other areas of the chip are covered with a thin "cytophobic" film to block cell attachement and facilitate movement of cells to electrodes. This cytophobic film also insulates unused areas of the conductive film, thus the alignment of cell docking sites to working electrodes is automatic. Amperometric spikes resulting from single-granule fusion events were recorded on the device and had amplitudes and kinetics similar to those measured using carbon-fiber microelectrodes. Use of this device will increase the pace of basic neuroscience research and may also find applications in drug discovery or validation.
Combining cancer vaccines with chemotherapy (2005)

Clinical experience is now demonstrating the efficacy of combining chemotherapy and targeted therapies. Although the combination of chemotherapy and immunotherapy would at first seem to be counterproductive, supportive preclinical and clinical data have revealed that cyclophosphamide, gemcitabine and doxorubicin enhance the efficacy of vaccines when used as a form of 'pretreatment'. Possible mechanisms of action include inhibition of regulatory T cells, enhancement of antigen presentation by tumours, or some yet unknown method. As such, more preclinical and clinical trials are needed to explore the synergistic effects of chemotherapy combined with immunotherapy, particularly the proper dose and timing of chemotherapy.
Third Report on the Excavations at Stonehenge (1923)

My last report presented a year ago concluded with an account of the third excavation of the ditch outside the circular earthwork. A fourth excavation in continuation of the third was begun immediately afterwards and carried 26 ft. to the west. It was made 2 ft. wider, as the ditch here appeared to have been wider and deeper, but except for this there was no appreciable difference from former sections. The upper soil had been much disturbed by rabbits or persons digging them out, the burrows being occasionally found to be 4 ft. deep. The upper layer of humus, and the rubble layer beneath it, contained chips of the building of Stonehenge to the number of 570, but none was found lower than the junction with the silt. With the chips were four small worn pieces of Bronze Age pottery, 10 of the Roman Period, a small quartzite maul, about 60 animal bone fragments, and the greater part of a human ulna bone.
A 3D Local Interaction Strategy for Swarm Robot (2011)

A decentralized control strategy for a robot swarm is presented, where each robot try to form a regular tetrahedron with its three neighbors. The proposed method is based on virtual spring and demands minimum local information. Four neighboring robots can form a regular tetrahedron formation regardless of their initial positions. A neighbor selection procedure is used to extend the strategy In addition, an obstacle avoidance mechanism, based on artificial physics, is also introduced. As a result, the basic swarm behaviors such as aggregation, flocking and obstacle avoidance are demonstrated through simulation.
In situ charging potential monitoring for a high current ribbon beam (2003)

We discuss measurements and modeling associated with the high current ion beam space charge neutralization. We show the importance of the electron temperature in maintaining low beam potential and induced voltage on implanted wafers.
Novel transimpedance filter topology for instrumentation (1997)

In this paper, a novel transimpedance filter topology is described. It resembles typical Q-Enhancement configurations. Low- and band-pass responses have been fully developed taking into consideration several parameters such as frequency response, input-output impedances and noise. Design conditions are obtained to optimize the performance. Transimpedance filters find direct application with some sensors and D/A converters which provide a current as output signal, avoiding a current to voltage conversion.
Room-Temperature Transverse-Rupture Strength of WC-10%Ni Cemented Carbide (1977)

It has been previously reported by the present authors that the transverse-rupture strength of WC-Co cemented carbide at room temperature is quantitatively understood from the viewpoint of microstructural defects acting as fracture sources. Thus, the strength of WC-Ni cemented carbide was examined in relation to the defect as above, in order to make clear the strength of this alloy in comparison with that of WC-Co alloy. The WC-10%Ni medium carbon alloys with various carbide grain sizes were vacuum-sintered and used as specimens.The results obtained were as follows: (1) It was confirmed that the strength of WC-10%Ni alloy was controlled by the microstructural defect in the same way as in WC-Co alloy. However, in this case, pores were only observed as the defect. (2) Considering the strength (σ0) of the sound matrix around defects, σ0 of WC-10%Ni alloy was lower than that of WC-10%Co alloy. The difference in σ0 between the two alloys, however, became smaller with decreasing carbide grain size, and σ0 of both alloys nearly accorded when the grain size approached the value of 1.0∼1.2 μ. (3) The hardness of WC-10%Ni alloy was lower than that of WC-10%Co alloy, and the similar tendency was also observed in respect of carbide grain size. (4) The more excellent mechanical properties of WC-Co alloy were assumed to be due to the strain-induced transformation of its binder phase which is peculiar to this alloy.
Dynamic and static stretch responses in muscle spindle receptors in fatigued muscle (1985)

Dynamic and static stretch responses in muscle spindles were investigated in fatigued muscle to determine if acute adaptations do occur in receptor discharge as has been shown after contractions of short duration. Fatigue to 60-50% maximum tetanic tension was induced in the isolated gastrocnemius muscle in 16 cats by sustained, 7 X threshold electrical stimulation (100 Hz) of the cut L7 ventral root and S1 ventral root. Group Ia and II afferent fiber responses to slow ramp stretches (5 mm X s-1) and vibration (100 Hz) applied to the Achilles tendon were monitored before and immediately after muscle tetany to fatigue. Changes in firing characteristics were similar when results from faster (25-30 mm X s-1) ramp stretches were contrasted. During muscle fatigue, decreases in response latency to displacement and increases in resting discharge, mean frequency during stretch, and frequency of firing to vibration were predominant in both afferent fiber types. Static responses were generally lower, indicating a decrease in position sensitivity. Resting muscle force and passive peak muscle stiffness were consistently higher following contraction. The sum effects of these proprioceptive afferent and mechanical muscle responses would be to increase muscle stiffness and thus resist yield in muscle length to perturbations at lower muscle forces. The magnitude of these adaptations in proprioceptive discharge appears dependent on intrafusal muscle fiber activation.
Phase averaging and interpolation using resistor strings or resistor rings for multi-phase clock generation (2006)

Circuit techniques using resistor strings (R-strings) and resistor rings (R-rings) for phase averaging and interpolation are described. Phase averaging can reduce phase errors, and phase interpolation can increase the number of available phases. In addition to the waveform shape, the averaging and the interpolation performances of the R-strings and R-rings are determined by the clock frequency normalized by a RC time constant of the circuits. To attain better phase accuracy, a smaller RC time constant is required, but at the expense of larger power dissipation. To demonstrate the resistor ring's capability of phase averaging and interpolation, a 125-MHz 8-bit digital-to-phase converter (DPC) was designed and fabricated using a standard 0.35-/spl mu/m SPQM CMOS technology. Measurement results show that the DPC attains 8-bit resolution using the proposed phase averaging and interpolation technique.