gebhart/patrepeval huggingface dataset:
Febrile nonhemolytic transfusion reactions to platelets (1995)

Although febrile nonhemolytic transfusion reactions to erythrocytes and platelets are not life threatening, the clinical symptoms associated with them cause discomfort for the patient, result in the use of premedicative drugs, and utilize nursing and laboratory resources. For many years it was assumed that febrile nonhemolytic transfusion reactions were caused by an interaction between leukocyte antibody in the patient's plasma and leukocytes present in the transfused product. Thus prevention has focused on the removal of leukocytes from the blood product by centrifugation or filtration just prior to transfusion. Recent data suggest that most febrile nonhemolytic transfusion reactions to platelets do not involve an immune-mediated event but are caused by the accumulation of biologic response modifiers in the platelet product during storage. Potential biologic response modifiers that have been investigated include histamine, lipids, complement fragments, and cytokines. The concentrations of these substances have been shown to increase in erythrocytes or platelet products or both during storage, and there is some clinical evidence that supports an association between elevated cytokine levels and the risk of reaction. If biologic response modifiers play a major role in febrile nonhemolytic transfusion reactions to platelets, then interventions to prevent these reactions should focus on ways to stop production of these substances or on mechanisms to remove these substances from the platelet product before transfusion. Possible interventions include prestorage leukoreduction, plasma removal from the platelet product before transfusion, and reduction of the platelet storage period to 3 days. Clinical studies to identify the most effective approach for preventing febrile nonhemolytic transfusion reactions have not yet been reported.
Dynamic social network analysis using latent space models (2005)

This paper explores two aspects of social network modeling. First, we generalize a successful static model of relationships into a dynamic model that accounts for friendships drifting over time. Second, we show how to make it tractable to learn such models from data, even as the number of entities n gets large. The generalized model associates each entity with a point in p -dimensional Euclidean latent space. The points can move as time progresses but large moves in latent space are improbable. Observed links between entities are more likely if the entities are close in latent space. We show how to make such a model tractable (sub-quadratic in the number of entities) by the use of appropriate kernel functions for similarity in latent space; the use of low dimensional KD-trees; a new efficient dynamic adaptation of multidimensional scaling for a first pass of approximate projection of entities into latent space; and an efficient conjugate gradient update rule for non-linear local optimization in which amortized time per entity during an update is O (log n ). We use both synthetic and real-world data on up to 11,000 entities which indicate near-linear scaling in computation time and improved performance over four alternative approaches. We also illustrate the system operating on twelve years of NIPS co-authorship data.
Immunogenic properties of octasaccharide-protein conjugates derived from Klebsiella serotype 11 capsular polysaccharide (1985)

The tetrasaccharide repeating unit of the capsular polysaccharide of Klebsiella serotype 11, K11PS, comprises the following sequence: [----3)-beta-D-GlcpA-(1----3)-alpha-D-Galp-(1----3)-beta-D-Glcp-(1 ----] with a 4,6-O-(1-carboxyethylidene)-alpha-D-galactopyranosyl residue linked to O-4 of the glucuronic acid residue. Octasaccharide (OS) derived from K11PS by bacteriophage phi 11-associated glycanase, was coupled to bovine serum albumin and to keyhole limpet hemocyanin. The immunogenicity of various antigens after intraperitoneal immunization was studied by measuring the levels of circulating antibodies. Injection of BALB/c mice with K11PS resulted in induction of 2-mercaptoethanol-sensitive immunoglobulin M antibodies. The responses observed in BALB/c nu/nu mice and in male (CBA/N X C3H/HeN)F1 mice indicate that K11PS is a thymus-independent type 2 antigen. Immunization of BALB/c mice with either OS-bovine serum albumin or OS-keyhole limpet hemocyanin resulted in the induction of circulating 2-mercaptoethanol-resistant immunoglobulin G antibodies. Results in BALB/c nu/nu mice indicate that the OS-protein conjugates are thymus-dependent antigens. Since the OS-keyhole limpet hemocyanin conjugate induced antibodies in both (CBA/N X C3H/HeN)F1 females and males, we propose to refer to this kind of antigen as a thymus-dependent type 1 antigen, whereas OS-bovine serum albumin, which evoked immunoglobulins in (CBA/N X C3H/HeN)F1 females only, can be referred to as a thymus-dependent type 2 antigen.
Highly efficient retroviral gene transfer into human primary T lymphocytes derived from peripheral blood. (1994)

T lymphocytes are a promising cell vehicle for gene therapy purposes. By cocultivating retroviral vector producing cells and target cells, highly efficient gene transfer was achieved with activated human T lymphocytes derived from peripheral blood with vectors carrying different forms of the bacterial beta-galactosidase gene including the regular LacZ gene, the Sh-ble::LacZ gene and the nlsLacZ gene. Infection kinetics of T cells activated by a combination of monoclonal antibodies directed against CD2 and CD28 indicated that the highest efficiencies of transduction were obtained when the cocultivation began 4 days after stimulation. In fact, with the FLac vector, a new retroviral vector which expresses the Sh-ble::LacZ gene, we observed up to 78% transduction efficiency assessed by X-gal staining performed 2 days after the end of the cocultivation. Expression of the transduced genes was observed throughout the period of culture. Neither the cocultivation step nor the expression of the transduced Sh-ble::LacZ gene altered cell culture proliferation or the expression of selected cell surface antigens. In addition, we showed that CD4+ and CD8+ T cells were equally transduced.
From Objects to Services: A Journey in Search of Component Reuse Nirvana. (2004)

Remember when we started our journey in searching for the "holy grail" of software "integrated circuits"? The Object Oriented (OO) approach provided the promise for developing and using such reusable components to build flexible systems that could be readily adapted to changing requirements.
Bursting Neurons Signal Input Slope (2002)

Brief bursts of high-frequency action potentials represent a common firing mode of pyramidal neurons, and there are indications that they represent a special neural code. It is therefore of interest to determine whether there are particular spatial and temporal features of neuronal inputs that trigger bursts. Recent work on pyramidal cells indicates that bursts can be initiated by a specific spatial arrangement of inputs in which there is coincident proximal and distal dendritic excitation (Larkum et al., 1999). Here we have used a computational model of an important class of bursting neurons to investigate whether there are special temporal features of inputs that trigger bursts. We find that when a model pyramidal neuron receives sinusoidally or randomly varying inputs, bursts occur preferentially on the positive slope of the input signal. We further find that the number of spikes per burst can signal the magnitude of the slope in a graded manner. We show how these computations can be understood in terms of the biophysical mechanism of burst generation. There are several examples in the literature suggesting that bursts indeed occur preferentially on positive slopes (Guido et al., 1992; Gabbiani et al., 1996). Our results suggest that this selectivity could be a simple consequence of the biophysics of burst generation. Our observations also raise the possibility that neurons use a burst duration code useful for rapid information transmission. This possibility could be further examined experimentally by looking for correlations between burst duration and stimulus variables.
Central Hypotensive Effects of the α 2a -Adrenergic Receptor Subtype (1996)

alpha2-Adrenergic receptors (alpha2ARs) present in the brainstem decrease blood pressure and are targets for clinically effective antihypertensive drugs. The existence of three alpha2AR subtypes, the lack of subtype-specific ligands, and the cross-reactivity of alpha2AR agonists with imidazoline receptors has precluded an understanding of the role of individual alpha2AR subtypes in the hypotensive response. Gene targeting was used to introduce a point mutation into the alpha2aAR subtype in the mouse genome. The hypotensive response to alpha2AR agonists was lost in the mutant mice, demonstrating that the alpha2aAR subtype plays a principal role in this response.
Use of multivariate statistics in understanding wine flavor (2002)

Abstract With the increase in sensitivity and selectivity of instruments, volatiles can now be analyzed under conditions very close to those by which humans perceive aroma. However, without sensory evaluation, even precise information about the volatile composition in the nasal passages cannot predict the flavor of the system as perceived by humans. To illustrate one facet of the complexity of flavor research, multivariate statistical methods that have been used in wine flavor studies to relate sensory descriptive analysis and volatile composition are reviewed. Principal component analysis of instrumental variables is a technique to find the fewest number of volatiles that match the configuration of the sensory profile data. Generalized procrustes analysis (GPA) and Partial least squares regression (PLS) are used to model data from different data sets, such as volatiles identified by GC-MS and intensity ratings for the sensory attributes. The GPA is used to determine if the two data sets "fit each other", whereas PLS determines underlying dimensions in each set of data that best explain the variation in the other set of data. Neither GPA nor PLS determine if any of the compounds associated with specific sensory attributes are actually responsible for specific aromas but they identify compounds on which the sensory studies should focus. These three methods are compared by the analysis of data from a study of Chardonnay wines that were profiled by descriptive analysis and the headspace volatiles identified by GC- MS, responsible for those aroma notes. However, they do identify compounds on which sensory studies should focus in subsequent research. Dedicated to the memory of Dr. Roy Teranishi Acknowledgments The field of flavor chemistry has been revolutionized over the last 50 years. Techniques for recovery and instrumental analysis of volatiles have advanced to the point where we can now directly analyze the composition of volatile compounds in the nasal passages. Another important advance is the increased emphasis on interpretation of the sensory significance of the chemical flavor data. Roy Teranishi was an enthusiastic pioneer in flavor chemistry in both of these areas. He participated in the development of analytical methods and was always keen to get the most meaning out of the flavor data. He was one of the first flavor chemists to link chemistry to sensory analysis, whether by humans or coyotes. He served as a mentor to many of us, as did his colleagues Emily Wick and Irwin Hornstein among others. This article is written in honor of Roy Teranishi, an unassuming leader and colleague, who has impacted our lives and careers as well as the fields of analytical and flavor chemistry. Notes Dedicated to the memory of Dr. Roy Teranishi
Doppler standard deviation imaging for clinical monitoring of in vivo human skin blood flow (2000)

We used a novel phase-resolved optical Doppler tomographic (ODT) technique with very high flow-velocity sensitivity (10microm/s) and high spatial resolution (10microm) to image blood flow in port-wine stain (PWS) birthmarks in human skin. In addition to the regular ODT velocity and structural images, we use the variance of blood flow velocity to map the PWS vessels. Our device combines ODT and therapeutic systems such that PWS blood flow can be monitored in situ before and after laser treatment. To the authors' knowledge this is the first clinical application of ODT to provide a fast semiquantitative evaluation of the efficacy of PWS laser therapy in situ and in real time.
Results of G004, a phase IIb actively controlled clinical trial with the TGF-b2 targeted compound AP 12009 for recurrent anaplastic astrocytoma (2006)

1566 Background: In 3 phase I/II dose-escalation studies the TGF-β2 specific compound AP 12009 proved to be well tolerated and revealed an excellent safety profile. Furthermore, antitumor activity including complete tumor remissions was observed. Methods: G004 is an international open-label, actively controlled, dose finding phase IIb trial in adult patients with histopathologically confirmed recurrent high-grade glioma. 145 patients with recurrent anaplastic astrocytoma (AA, WHO grade III) or glioblastoma (GBM, WHO grade IV) were enrolled into the study. Objective of the current phase IIb study is to compare the efficacy and safety of two doses of AP 12009 and standard treatment. Patients were randomized to receive either one of two doses of AP 12009 (10 μM or 80 μM) or standard chemotherapy (TMZ or PCV). AP 12009 was administered intratumorally by CED. 134 patients received treatment and all of them have completed active treatment. Primary endpoint is tumor response by local and central MRI reading and survival. Results: Here we report on patients with recurrent AA (for GBM see separate Abstract). 38 patients with AA (68% male, 32% female; median age 39, range 22–60; median Karnofsky performance status: 90, range 70–100) were treated. 26 patients received AP 12009 (10 μM or 80 μM), 12 patients were treated with TMZ or PCV. Up to now, in 89 patients treated with AP 12009 (both AA and GBM patients) 6 SAEs possibly related to the study drug and 37 procedure related SAEs (92% mild or moderate) were documented. Partial and complete tumor responses were observed. Exact response rates will be determined after central MRI reading is completed. Responses in the AP 12009 groups are long lasting. The results confirm the good safety profile of AP 12009 as well as the efficacy data seen in phase I studies. The median overall survival is not yet reached. Conclusions: The long-term tumor free survival of several patients may actually hint towards a potential to cure some patients with this devastating disease. Phase III clinical trials in both AA and GBM patients are currently in preparation. [Table: see text]
GCUA: general codon usage analysis. (1998)

J.McInerney@nhm.ac.uk
A Novel Silver(I)-Mediated DNA Base Pair (2002)

We have generated a novel silver(I)-mediated unnatural DNA base pair consisting of two 2,6-bis(ethylthiomethyl)pyridine nucleobases SPy. This metallo-base pair has a remarkably high pairing stability and selectivity which rivals that of the natural base pairs dA:dT and dC:dG. UV-melting experiments revealed that the dSPy:dSPy self-pair can replace natural base pairs at multiple sites and still form stable DNA duplexes.
Miniaturization of analytical systems (1998)

Miniaturization has been a long-term trend in clinical diagnostics instrumentation. Now a range of new technologies, including micromachining and molecular self-assembly, are providing the means for further size reduction of analyzers to devices with micro- to nanometer dimensions and submicroliter volumes. Many analytical techniques (e.g., mass spectrometry and electrophoresis) have been successfully implemented on microchips made from silicon, glass, or plastic. The new impetus for miniaturization stems from the perceived benefits of faster, easier, less costly, and more convenient analyses and by the needs of the pharmaceutical industry for microscale, massively parallel drug discovery assays. Perfecting a user-friendly interface between a human and a microchip and determining the realistic lower limit for sample volume are key issues in the future implementation of these devices. Resolution of these issues will be important for the long-term success of microminiature analyzers; in the meantime, the scope, diversity, and rate of progress in the development of these devices promises products in the near future.
Distributed algorithmic mechanism design (2002)

Distributed Algorithmic Mechanism Design (DAMD) combines theoretical computer science's traditional focus on computational tractability with its more recent interest in incentive compatibility and distributed computing. The Internet's decentralized nature, in which distributed computation and autonomous agents prevail, makes DAMD a very natural approach for many Internet problems. This paper first outlines the basics of DAMD and then reviews previous DAMD results on multicast cost sharing and interdomain routing. The remainder of the paper describes several promising research directions and poses some specific open problems..
Immunology of Pyelonephritis in the Primate Model (1982)

Ascending acute pyelonephritis was produced in monkeys by infusion of bacteria through a ureteral catheter to the point of intrarenal reflux. This led to a significant inflammatory response with death of renal tubular cells in the area of the tubular granulocytes and bacteria. We gave superoxide dismutase, and found that the inflammatory response was decreased and fewer tubular cells were killed. Ultrastructural change was also decreased in tubular cells adjoining phagocytosing neutrophils. This suggests that renal damage following a bacterial infection may be due to the production and release of superoxide into the tubular lumen during phagocytosis. We believe that it is the initial event which may lead to the eventual loss of renal tissue and function called chronic pyelonephritis.
[Inhibition of several strains of influenza virus type A and B by phenolic polymers]. (1986)

Ten synthetic polymers of diphenolic compounds (KOP, HYKOP, CHOP, 3,4-DHTOP Na-ADROP, NH4-ADROP, Na-NORADROP, NH4-NORADROP, GENOP, and 2,5-DHTOP) as well as two phenolic polymers of natural origin (Na-humate, NH4-humate) were tested for their effectiveness on several strains of influenza virus type A and B. The allantois-on-shell system was used for primary screening. Virus multiplication was assessed by means of the infectious titer. All substances tested were found to exert inhibitory effects on influenza virus type A, while 3,4-DHTOP, Na-ADROP, NH4-ADROP as well as GENOP were effective against either type. The highest titer reductions (greater than 4.0 log 10 ID50) were obtained with KOP and HYKOP against influenzavirus A/Brasil/11/78 and with 3,4-DHTOP, KOP and HYKOP against influenzavirus A/Hongkong/1/68. Only GENOP showed antiviral activity against all virus strains tested so far.
A method to produce microseed stock for use in the crystallization of biological macromolecules (1999)

A method is presented for producing a seed-stock mixture for macromolecular crystallization. A PTFE bead and micro-centrifuge tube act as mortar and pestle for pulverizing seed crystals of macromolecules. Energy for the bead's motion is supplied by a vortex mixer or an ultrasonic bath. The crushed crystal is serially diluted to prepare a seed-stock mixture of the desired concentration for crystallization. Crystals produced using both hanging-drop vapor diffusion and a capillary microbatch method show expected dilution behavior. This technique of producing seed stock is compared with traditional means and advantages over the standard protocol are demonstrated.
Electroluminescence of doped organic thin films (1989)

Electroluminescent (EL) devices are constructed using multilayer organic thin films. The basic structure consists of a hole-transport layer and a luminescent layer. The hole-transport layer is an amorphous diamine film in which the only mobile carrier is the hole. The luminescent layer consists of a host material, 8-hydroxyquinoline aluminum (Alq), which predominantly transports electrons. High radiance has been achieved at an operating voltage of less than 10 V. By doping the Alq layer with highly fluorescent molecules, the EL efficiency has been improved by about a factor of 2 in comparison with the undoped cell. Representative dopants are coumarins and DCMs. The EL quantum efficiency of the doped system is about 2.5%, photon/electron. The EL colors can be readily tuned from the blue-green to orange-red by a suitable choice of dopants as well as by changing the concentration of the dopant. In the doped system the electron-hole recombination and emission zones can be confined to about 50 Å near the hole-transport interface. In the undoped Alq, the EL emission zone is considerably larger due to exciton diffusion. The multilayer doped EL structure offers a simple means for the direct determination of exciton diffusion length.
Piezoelectric Mass-Sensing Devices as Biosensors—An Alternative to Optical Biosensors? (2000)

In the early days of electronic communication-as a result of the limited number of quartz resonators available-frequency adjustment was accomplished by a pencil mark depositing a foreign mass layer on the crystal. In 1959, Sauerbrey showed that the shift in resonance frequency of thickness-shear-mode resonators is proportional to the deposited mass. This was the starting point for the development of a new generation of piezoelectric mass-sensitive devices. However, it was the development of new powerful oscillator circuits that were capable of operating thickness shear mode resonators in fluids that enabled this technique to be introduced into bioanalytic applications. In the last decade adsorption of biomolecules on functionalized surfaces turned in to one of the paramount applications of piezoelectric transducers. These applications include the study of the interaction of DNA and RNA with complementary strands, specific recognition of protein ligands by immobilized receptors, the detection of virus capsids, bacteria, mammalian cells, and last but not least the development of complete immunosensors. Piezoelectric transducers allow a label-free detection of molecules; they are more than mere mass sensors since the sensor response is also influenced by interfacial phenomena, viscoelastic properties of the adhered biomaterial, surface charges of adsorbed molecules, and surface roughness. These new insights have recently been used to investigate the adhesion of cells, liposomes, and proteins onto surfaces, thus allowing the determination of the morphological changes of cells as a response to pharmacological substances and changes in the water content of biopolymers without employing labor-intense techniques. However, the future will show whether the quartz-crystal microbalance will assert itself against established label-free sensor devices such as surface plasmon resonance spectroscopy and interferometry.