gebhart/patrepeval huggingface dataset:
Mouse models of human phenylketonuria. (1993)

Phenylketonuria (PKU) results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine (PHE) to tyrosine. Although this inborn error of metabolism was among the first in humans to be understood biochemically and genetically, little is known of the mechanism(s) involved in the pathology of PKU. We have combined mouse germline mutagenesis with screens for hyperphenylalaninemia to isolate three mutants deficient in phenylalanine hydroxylase (PAH) activity and cross-reactive protein. Two of these have reduced PAH mRNA and display characteristics of untreated human PKU patients. A low PHE diet partially reverses these abnormalities. Our success in using high frequency random germline point mutagenesis to obtain appropriate disease models illustrates how such mutagenesis can complement the emergent power of targeted mutagenesis in the mouse. The mutants now can be used as models in studying both maternal PKU and somatic gene therapy.
Rational Development of LEA29Y (belatacept), a High-Affinity Variant of CTLA4-Ig with Potent Immunosuppressive Properties (2005)

Current success in organ transplantation is dependent upon the use of calcineurin-inhibitor-based immunosuppressive regimens. Unfortunately, current immunotherapy targets molecules with ubiquitous expression resulting in devastating non-immune side effects. T-cell costimulation has been identified as a new potential immunosuppressive target. The best characterized pathway includes CD28, its homologue CTLA4 and their ligands CD80 and CD86. While an immunoglobulin fusion protein construct of CTLA4 suppressed rejection in rodents, it lacked efficacy in primate transplant models. In an attempt to increase the biologic potency of the parent molecule a novel, modified version of CTLA4-Ig, LEA29Y (belatacept), was constructed. Two amino acid substitutions (L104E and A29Y) gave rise to slower dissociation rates for both CD86 and CD80. The increased avidity resulted in a 10-fold increase in potency in vitro and significant prolongation of renal allograft survival in a pre-clinical primate model. The use of immunoselective biologics may provide effective maintenance immunosuppression while avoiding the collateral toxicities associated with conventional immunsuppressants.
The Src Family of Tyrosine Kinases Is Important for Embryonic Stem Cell Self-renewal (2004)

cYes, a member of the Src family of non-receptor tyrosine kinases, is highly expressed in mouse and human embryonic stem (ES) cells. We demonstrate that cYes kinase activity is regulated by leukemia inhibitory factor (LIF) and serum and is down-regulated when cells differentiate. Moreover, selective chemical inhibition of Src family kinases decreases growth and expression of stem cell genes that mark the undifferentiated state, including Oct3/4, alkaline phosphatase, fibroblast growth factor 4, and Nanog. A synergistic effect on differentiation is observed when ES cells are cultured with an Src family inhibitor and low levels of retinoic acid. Src family kinase inhibition does not interfere with LIF-induced JAK/STAT3 (Janus-associated tyrosine kinases/signal transducer and activator of transcription 3) or p42/p44 MAPK (mitogen-activated protein kinase) phosphorylation. Together the results suggest that the activation of the Src family is important for maintaining mouse and human ES in an undifferentiated state and may represent a third, independent pathway, downstream of LIF in mouse ES cells.
Guidelines for the safe administration of inhaled nitric oxide. (1994)

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator, potentially useful in the treatment of pulmonary hypertension and ventilation-perfusion mismatch. High doses of inhaled NO and its oxidative product nitrogen dioxide (NO2) may cause acute lung injury. Using a standard infant ventilator, ventilator circuit and test lung, an administration and monitoring strategy has been defined for inhaled NO and these observations validated in eight ventilated infants. In 90% oxygen, doses of inhaled NO > or = 80 parts per million may result in toxic NO2 concentrations.
A support vector machine for predicting spontaneous termination of paroxysmal atrial fibrillation episodes (2006)

The aim of this work is to predict the spontaneous termination of atrial fibrillation (AF) episodes. The database includes three record groups: non-terminating AF (N), AF that terminates one minute after recording end (S), and AF that terminates immediately after recording end (T). A first goal consisted on separating N from T group records (event 1), and a second, for separating S from T records (event 2). A Support Vector Machine was used for the classification problem. For event 1, four indexes were extracted: the atrial fibrillatory frequency (AFF) and the mean, standard deviation, and approximate entropy of RR intervals. For event 2, the AFF, the energy of the 3-7 Hz and 7-11 Hz bands, from the ten and five final seconds of the records, were used. The groups were divided in two sets: learning and test. For event 1, a 100 % in learning, and 86.66 % in test set were correctly classified. For the event 2, we classified 100 % in the learning, and 80 % in the test set. 1.
Mechanism by Which Mcl-1 Regulates Cancer-Specific Apoptosis Triggered by mda-7/IL-24, an IL-10–Related Cytokine (2010)

Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), a cytokine belonging to the IL-10 family, selectively induces apoptosis in cancer cells without harming normal cells by promoting an endoplasmic reticulum (ER) stress response. The precise molecular mechanism by which the ER stress response culminates in cell death requires further clarification. The present study shows that in prostate carcinoma cells, the mda-7/IL-24-induced ER stress response causes apoptosis by translational inhibition of the antiapoptotic protein myeloid cell leukemia-1 (Mcl-1). Forced expression of Mcl-1 blocked mda-7/IL-24 lethality, whereas RNA interference or gene knockout of Mcl-1 markedly sensitized transformed cells to mda-7/IL-24. Mcl-1 downregulation by mda-7/IL-24 relieved its association with the proapoptotic protein Bak, causing oligomerization of Bak and leading to cell death. These observations show the profound role of the Bcl-2 protein family member Mcl-1 in regulating cancer-specific apoptosis induced by this cytokine. Thus, our studies provide further insights into the molecular mechanism of ER stress-induced cancer-selective apoptosis by mda-7/IL-24. As Mcl-1 is overexpressed in the majority of prostate cancers, mda-7/IL-24 might provide an effective therapeutic for this disease.
Novelty detection in jet engines (1999)

Neural network classifiers can be trained to estimate the posterior probability of a fault occurring given the values of a set of input parameters. With jet engines, however, faults are extremely rare and hence their prior probability is very low. The principle of novelty detection offers an alternative approach to the problem of fault detection. Novelty detection only requires the normal class to be defined. A statistical description of normality is learnt by including normal examples only in the training data; abnormalities are then identified by testing for novelty against this description. A real advantage of novelty detection is that anomalies which have not previously been seen will also be highlighted. (5 pages)
Fate of lyophilized xenogeneic corneal lenticules in intrastromal implantation and epikeratophakia. (1987)

The antigenicity of intrastromal and epikeratophakia xenografts of lyophilized corneal tissue was evaluated in nonimmune and immune recipients. Lyophilized feline lenticules were implanted into intrastromal pockets in unsensitized rabbits and rabbits sensitized to the donor cat. In both cases, the grafts remained clear. Sensitized rabbits with clear intrastromal grafts received fresh tissue penetrating keratoplasty grafts from the same donor cat, placed adjacent to the intrastromal grafts. The fresh tissue penetrating keratoplasty grafts were rapidly rejected, while the lyophilized intrastromal grafts remained clear. Cats sensitized to rabbits received lyophilized and rehydrated epikeratophakia grafts shaped from rabbit cornea; these lyophilized grafts also remained clear for the 3-month period of the study. The results indicate that lyophilized and rehydrated corneal stroma, which is devoid of living cells, is not antigenic and is not subjected to immunologic attack, even in cases where the donor and host are of different species and the host has been previously immunized to the donor.
Through-glass copper via using the glass reflow and seedless electroplating processes for wafer-level RF MEMS packaging (2013)

We present a novel method for the fabrication of void-free copper-filled through-glass-vias (TGVs), and their application to the wafer-level radio frequency microelectromechanical systems (RF MEMS) packaging scheme. By using the glass reflow process with a patterned silicon mold, a vertical TGV with smooth sidewall and fine pitch could be achieved. Bottom-up void-free filling of the TGV is successfully demonstrated through the seedless copper electroplating process. In addition, the proposed process allows wafer-level packaging with glass cap encapsulation using the anodic bonding process, since the reflowed glass interposer is only formed in the device area surrounded with silicon substrate. A simple coplanar waveguide (CPW) line was employed as the packaged device to evaluate the electrical characteristics and thermo-mechanical reliability of the proposed packaging structure. The fabricated packaging structure showed a low insertion loss of 0.116 dB and a high return loss of 35.537 dB at 20 GHz, which were measured through the whole electrical path, including the CPW line, TGVs and contact pads. An insertion loss lower than 0.1 dB and a return loss higher than 30 dB could be achieved at frequencies of up to 15 GHz, and the resistance of the single copper via was measured to be 36 mΩ. Furthermore, the thermo-mechanical reliability of the proposed packaging structure was also verified through thermal shock and pressure cooker test.
Pulmonary intravascular macrophages: their contribution to the mononuclear phagocyte system in 13 species (1999)

The organ uptake of intravenously injected particles was examined in 13 species. All animals were injected intravenously with 198Au colloid and magnetic iron oxide particles. Vascular clearance kinetics of 198Au colloid was similar in all species. Pulmonary uptake of 198Au colloid ranged from 17 to 60% in sheep, calves, pigs, and cats but was <1.1% in monkeys, hyraxes, rabbits, guinea pigs, rats, mice, and chickens. For iron oxide particles, pulmonary uptake ranged from 80 to 99% in sheep, calves, pigs, goats, and cats and 15 to 18% in hamsters, hyraxes, and monkeys and was <10% in rabbits, chicken, mice, rats, and guinea pigs. In all species, the bulk of the remainder of particle uptake was in the liver. Pulmonary intravascular macrophages are the cellular site of lung uptake in calves, cats, pigs, goats, and sheep, whereas monocytes and neutrophils predominate in other species. Kupffer cells were the site of uptake in the liver. Our data show marked species differences in the fate of circulating particles; ruminants, pigs, and cats have extensive pulmonary localization due to phagocytosis by pulmonary intravascular macrophages.
A triaxial accelerometer and portable data processing unit for the assessment of daily physical activity (1997)

The present study describes the development of a triaxial accelerometer (TA) and a portable data processing unit for the assessment of daily physical activity. The TA is composed of three orthogonally mounted uniaxial piezoresistive accelerometers and can be used to register accelerations covering the amplitude and frequency ranges of human body acceleration. Interinstrument and test-retest experiments showed that the offset and the sensitivity of the TA were equal for each measurement direction and remained constant on two measurement days. Transverse sensitivity was significantly different for each measurement direction, but did not influence accelerometer output (< 3% of the sensitivity along the main axis). The data unit enables the on-line processing of accelerometer output to a reliable estimator of physical activity over eight-day periods. Preliminary evaluation of the system in 13 male subjects during standardized activities in the laboratory demonstrated a significant relationship between accelerometer output and energy expenditure due to physical activity, the standard reference for physical activity (r = 0.89). Shortcomings of the system are its low sensitivity to sedentary activities and the inability to register static exercise. The validity of the system for the assessment of normal daily physical activity and specific activities outside the laboratory should be studied in free-living subjects.
INTERNATIONAL ABSTRACTS OF PLASTIC AND RECONSTRUCTIVE SURGERY (1996)

AMERICAN SOCIETY OF PLASTIC SURGEONS PLASTIC & RECONSTRUCTIVE SURGERY PRS GLOBAL OPEN ASPS EDUCATION NETWORK AMERICAN SOCIETY OF PLASTIC SURGEONS PLASTIC & RECONSTRUCTIVE SURGERY PRS GLOBAL OPEN ASPS EDUCATION NETWORK
Use of the AlGaAs native oxide in AlGaAs-GaAs quantum well heterostructure laser devices (1995)

At atmospheric conditions high Al Composition Al{sub x}Ga{sub 1-x}As (x {ge}0.7) in Al{sub x}Ga{sub 1-x}As-GaAs heterostructures is subject to failure via hydrolyzation. In contrast, {open_quotes}wet{close_quotes} oxidation at higher temperatures ({ge}400{degrees}C) produces stable AlGaAs native oxides that prove to be useful in quantum well heterostructure devices. The {open_quotes}wet{close_quotes} oxidation process results in the conversion of high Al composition heterostructure material into a stable low refractive index, current-blocking native oxide, which can be used to define cavities and current paths. The oxidation can be used to passivate exposed Al-bearing surfaces. Its selective, anisotropic nature is also useful for the fabrication of both planar and non-planar devices, including buried-oxide heterostructures. The III-V native oxide has been used in the fabrication of single-stripe and stripe array lasers, ring lasers, coupled-cavity lasers, buried-oxide verticle cavity lasers, deep-oxide waveguides, deep-oxide lasers, and high reliability LED`s. Also, the native oxide of A1As has been demonstrated in field effect transistor operation. The use of the III-V native oxide in various device applications is described.
A Selection Hierarchy for Possible Strategic Alliances of Taiwanese Telecom Operators (2007)

With the trend towards globalization, the competitive challenges that enterprises have to encounter in the market are much larger than before. In this climate strategic alliances were considered as a pragmatic and effective way by which enterprises could grow and maintain a competitive position in the new millennium. However up to 70% of alliances typically fail (Gonzalez, 2001). Research indicates that managers attribute preparations for the alliance as a key attribute to failure (Cyrus, 2000). In this paper we identified and evaluated the criteria used by those in the Taiwanese telecoms industry for selecting strategic alliances partners. Fuzzy Delphi was initially used to sieve the selection criteria drawn from related literature. Managers from a large telecom company were then asked to evaluate the importance of those criteria. Finally Fuzzy AHP was used to calculate the weight of the criteria. The results of this research show that the most important criterion for selection is the prior experience of cooperation.
Invited review: the synergy between virtual reality and robotics (1999)

To a large extent the robotics and the newer virtual reality (VR) research communities have been working in isolation. This article reviews three areas where integration of the two technologies can be beneficial. First, we consider VR-enhanced CAD design, robot programming, and plant layout simulation. Subsequently, we discuss how VR is being used in supervisory teleoperation, for single operator-single robot systems, single operator multiplexed to several slave robots, and collaborative control of a single robot by multiple operators. Here VR can help overcome problems related to poor visual feedback as well as system instabilities due to time delays. Finally, we show how robotics can be beneficial to VR in general, since robots can serve as force feedback interfaces to the simulation. Newer back-drivable manipulators offer increased safety for the user that closely interacts with the robot. The synergy between the fields of robotics and virtual reality is expected to grow in years to come.
Regulation of the sol Locus Genes for Butanol and Acetone Formation in Clostridium acetobutylicum ATCC 824 by a Putative Transcriptional Repressor (1999)

A gene (orf1, now designated solR) previously identified upstream of the aldehyde/alcohol dehydrogenase gene aad (R. V. Nair, G. N. Bennett, and E. T. Papoutsakis, J. Bacteriol. 176:871-885, 1994) was found to encode a repressor of the sol locus (aad, ctfA, ctfB and adc) genes for butanol and acetone formation in Clostridium acetobutylicum ATCC 824. Primer extension analysis identified a transcriptional start site 35 bp upstream of the solR start codon. Amino acid comparisons of SolR identified a potential helix-turn-helix DNA-binding motif in the C-terminal half towards the center of the protein, suggesting a regulatory role. Overexpression of SolR in strain ATCC 824(pCO1) resulted in a solvent-negative phenotype owing to its deleterious effect on the transcription of the sol locus genes. Inactivation of solR in C. acetobutylicum via homologous recombination yielded mutants B and H (ATCC 824 solR::pO1X) which exhibited deregulated solvent production characterized by increased flux towards butanol and acetone formation, earlier induction of aad, lower overall acid production, markedly improved yields of solvents on glucose, a prolonged solvent production phase, and increased biomass accumulation compared to those of the wild-type strain.
<title>Feature competition and domain of attraction in artificial-perceptron pattern recognizer</title> (1993)

As we reported previously, learning of a multi-layered hard-limited perceptron can be formulated into a set of simultaneous linear inequalities. Solving these inequalities under a given training set would then allow us to achieve the goal of learning in this system. If the dimension N of the input vector is much larger than the number M of different patterns to be learned, then there is considerable freedom for the system to select a proper solution of the connection matrix. In most cases, even a single layer perceptron will do the learning satisfactorily. This paper reports the results of some theoretical and experimental studies of this one-layered, hard-limited perceptron trained under the novel, one-step, noniterative learning scheme. Particularly, the analysis of some important properties of this novel learning system, such as automatic feature competition, domain of convergence, and robustness of recognition, are discussed in detail.
Tolerance and Cancer: Mechanisms of Tumor Evasion and Strategies for Breaking Tolerance (2004)

The development of malignant disease might be seen as a failure of immune surveillance. However, not all tumors are naturally immunogenic, and even among those that are immunogenic, the uncontrolled rapid growth of a tumor may sometimes out-run a robust immune response. Nevertheless, recent evidence suggests that mechanisms of tolerance that normally exist to prevent autoimmune disease may also preclude the development of an adequate antitumor response and that tumors themselves have the ability to thwart the development of effective immune responses against their antigens. A major challenge has been to develop approaches to breaking this tolerance in tumor-bearing hosts, and recent advances in our understanding of antigen presentation and tolerance have led to some promising strategies. An alternative approach is to use T cells from nontumor-bearing, allogeneic hosts in the form of lymphocyte infusions, with or without hematopoietic cell transplantation. Immunotherapy may occur in this setting via the response of nontolerant, tumor antigen-specific T cells from nontumor-bearing hosts or via the powerful destructive effect of an alloresponse directed against antigens shared by malignant cells in the recipient. Approaches to exploiting this beneficial effect without the deleterious consequence of graft-versus-host disease in allogeneic hematopoietic cell recipients are discussed.
(GaAl)As lasers with a heterostructure for optical confinement and additional heterojunctions for extreme carrier confinement (1973)

This paper shows the design advantages of using four- and five-layer heterostructure lasers in order to separately optimize the optical distribution and carrier confinement for a particular application. Given an arbitrary gain/carrier density relationship the parameters can be optimized for minimum threshold current. Theoretical results for both wide optical cavity and close confined lasers are given. These show the optical distributions for four- and five-layer lasers and how the threshold current varies with the active region width. Experimental results report a reduction from 55° half-power polar diagram width to 32° by the addition of a fourth layer to increase the optical cavity width of a double-heterostructure laser. The threshold current against reciprocal length characteristics for three- and four-layer devices are considered in terms of the theory given and hence a plot of gain against injected carrier density is obtained that extends over an order of magnitude of gain.
Fv1-like restriction of N-tropic replication-competent murine leukaemia viruses in mCAT-1-expressing human cells (2002)

To study the replication of murine leukaemia viruses in human cells we have used full-length as well as EGFP-tagged ecotropic viruses in combination with mCAT-1-expressing human cells. We present results showing that N-tropic murine leukaemia viruses are restricted in both infection and replication in such cells while B-tropic viruses, modified at capsid position 110, escape restriction. These results support a recently reported Fv1 -like restriction in mammalian cells. We extend the analysis of Fv1 -like restriction by demonstrating that NB-tropic viruses also escape restriction and human mCAT-1-expressing cells are thus similar to murine Fv1 b cells with respect to infection though the ecotropic receptor pathway.