gebhart/patrepeval huggingface dataset:
Efficient Coding and Speech Interpolation: Principles and Performance Characterization (1982)

The BPA (block priority assignment) system combines the principle of speech interpolation with waveform coding methods for the active speech signal. Coding with variable wordlength permits adapting the demand of the <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N</tex> speech sources to the capacity of the channel. The system emphasized in this paper not only varies the bits per source according to the number of active talkers, but also assigns the number of bits to the source that needs it most based on estimates of the SNR over the block. When ADPCM and DSI are combined to give a 4:1 compression ratio over standard PCM (data rate 16 kbits/s) no distortions are audible. The influence of transmission errors and the use of various waveform coders is considered.
Coupled InP quantum-dot InGaP quantum well InP–InGaP–In(AlGa)P–InAlP heterostructure diode laser operation (2001)

Data are presented showing that a p–n InP–In0.5Ga0.5P–In0.5(Al0.3Ga0.2)P–In0.5Al0.5P quantum-dot (QD) heterostructure diode, with an auxiliary ∼20 Å InGaP quantum well (QW) coupled via an In(AlGa)P barrier (∼20 Å) to the single layer of QDs to aid carrier collection, has a steeper current–voltage characteristic than the case of a similar diode with no auxiliary QW. The p–n InP+InGaP QD+QW diode is capable of 300 K visible-spectrum QD laser operation, while the single-layer InP QD diode (single QD layer) saturates at low current (≲1 mA) and does not exhibit stimulated emission.
Towards New Uses of Botulinum Toxin as a Novel Therapeutic Tool (2011)

The uses of botulinum toxin in the fields of neurology, ophthalmology, urology, rehabilitation medicine and aesthetic applications have been revolutionary for the treatment of patients. This non-invasive therapeutic has continually been developed since first discovered in the 1970s as a new approach to what were previously surgical treatments. As these applications develop, so also the molecules are developing into tools with new therapeutic properties in specific clinical areas. This review examines how the botulinum toxin molecule is being adapted to new therapeutic uses and also how new areas of use for the existing molecules are being identified. Prospects for future developments are also considered.
Atu027, a Liposomal Small Interfering RNA Formulation Targeting Protein Kinase N3, Inhibits Cancer Progression (2008)

We have previously described a small interfering RNA (siRNA) delivery system (AtuPLEX) for RNA interference (RNAi) in the vasculature of mice. Here we report preclinical data for Atu027, a siRNA-lipoplex directed against protein kinase N3 (PKN3), currently under development for the treatment of advanced solid cancer. In vitro studies revealed that Atu027-mediated inhibition of PKN3 function in primary endothelial cells impaired tube formation on extracellular matrix and cell migration, but is not essential for proliferation. Systemic administration of Atu027 by repeated bolus injections or infusions in mice, rats, and nonhuman primates results in specific, RNAi-mediated silencing of PKN3 expression. We show the efficacy of Atu027 in orthotopic mouse models for prostate and pancreatic cancers with significant inhibition of tumor growth and lymph node metastasis formation. The tumor vasculature of Atu027-treated animals showed a specific reduction in lymph vessel density but no significant changes in microvascular density.
Native-oxide stripe-geometry AlxGa1−xAs-GaAs quantum well heterostructure lasers (1991)

Data are presented on the room-temperature continuous (cw) operation of native-oxide single-stripe AlxGa1−xAs-GaAs quantum well heterostructure (QWH) lasers. The device quality native oxide is produced by the conversion of high Al composition AlxGa1−xAs (x∼0.8) confining layers via H2O vapor oxidation (400 °C) in a N2 carrier gas. The 10-μm-wide cw 300 K QWH lasers, which are fabricated by simplified processing, have excellent spectral quality and have been operated to powers in excess of 100 mW per facet.
Dynamic IPC/clock rate optimization (1998)

Current microprocessor designs set the functionality and clock rate of the chip at design time based on the configuration that achieves the best overall performance over a range of target applications. The result may be poor performance when running applications whose requirements are not well-matched to the particular hardware organization chosen. We present a new approach called Complexity-Adaptive Processors (CAPs) in which the IPC/clock rate tradeoff can be altered at runtime to dynamically match the changing requirements of the instruction stream. By exploiting repeater methodologies used increasingly in deep sub-micron designs, CAPs achieve this flexibility with potentially no cycle time impact compared to a fixed architecture. Our preliminary results in applying this approach to on-chip caches and instruction queues indicate that CAPs have the potential to significantly outperform conventional approaches on workloads containing both general-purpose and scientific applications.
Predominance of T lymphocytes in pancreatic islets and spleen of pre-diabetic non-obese diabetic (NOD) mice: a longitudinal study. (1985)

We examined sequential changes in the subsets of mononuclear cells infiltrating the pancreatic islets and splenic lymphocytes in pre-diabetic non-obese diabetic (NOD) mice, an animal model for type I diabetes, using immunofluorescent techniques. In the pancreas, a predominant infiltration by activated T lymphocytes, including helper inducer and cytotoxic suppressor T cells, was observed in the early stage of insulitis. Natural killer cells were also detected in the lesions. Immunoglobulin bearing cells tended to increase in number with the progression of insulitis. T lymphocytes were localized close to islet cells, while immunoglobulin bearing cells appeared adjacent to blood vessels and around T cell clusters. Immunoglobulin deposition or Ia expression on islet cells was not observed. The percentage of splenic T lymphocytes was markedly increased in the initial stage of insulitis as compared with control ICR mice and this elevated proportion of T cells continued throughout the observation period. As for splenic T cell subsets, cytotoxic suppressor T cells were increased in NOD mice. These results suggest that T lymphocytes play an important role in the initiation of insulitis long before the onset of overt diabetes. Moreover, NOD mice seem to have characteristic immunological features different from the BB rat or a reported case with human type I diabetes.
The Roles of Auxin Response Factor Domains in Auxin-Responsive Transcription (2003)

Auxin response factors (ARFs) are transcription factors that bind to TGTCTC auxin response elements in promoters of early auxin response genes. ARFs have a conserved N-terminal DNA binding domain (DBD) and in most cases a conserved C-terminal dimerization domain (CTD). The ARF CTD is related in amino acid sequence to motifs III and IV found in Aux/IAA proteins. Just C terminal to the DBD, ARFs contain a nonconserved region referred to as the middle region (MR), which has been proposed to function as a transcriptional repression or activation domain. Results with transfected protoplasts reported here show that ARFs with Q-rich MRs function as activators, whereas most, if not all other ARFs, function as repressors. ARF DBDs alone are sufficient to recruit ARFs to their DNA target sites, and auxin does not influence this recruitment. ARF MRs alone function as activation or repression domains when targeted to reporter genes via a yeast Gal4 DBD, and auxin does not influence the potency of activation or repression. ARF CTDs, along with a Q-rich MR, are required for an auxin response whether the MRs plus CTDs are recruited to a promoter by an ARF DBD or by a Gal4 DBD. The auxin response is mediated by the recruitment of Aux/IAA proteins to promoters that contain a DNA binding protein with a Q-rich MR and an attached CTD.
Role of single-qubit decoherence time in adiabatic quantum computation (2009)

We have studied numerically the evolution of an adiabatic quantum computer in the presence of a Markovian Ohmic environment by considering Ising spin-glass systems with up to 20 qubits independently coupled to this environment via two conjugate degrees of freedom. The required computation time is demonstrated to be of the same order as that for an isolated system and is not limited by the single-qubit decoherence time ${T}_{2}^{\ensuremath{\ast}}$, even when the minimum gap is much smaller than the temperature and decoherence-induced level broadening. For small minimum gap, the system can be described by an effective two-state model coupled only longitudinally to environment.
Targeted cellular immunotherapy with bifunctional antibodies. (1991)

Linking an antitumor cell antibody with an antilymphocyte antibody produces a bifunctional antibody that can redirect T lymphocytes to lyse tumor cells. Bifunctional antibodies that bypass the normal specificity of the T cell antigen receptor can, theoretically, retarget all of a cancer patient's cytotoxic T lymphocytes to kill tumor cells. Studies have demonstrated that bifunctional antibodies redirect effector cells to lyse human tumor cells in vitro and neutralize human tumor xenografts in animal models. Several different effector cell populations have been studied and many different human tumors have been targeted for lysis. Current research goals include the improvement of methods for the preparation of antibody reagents and the enhancement of cellular trafficking to tumors.
Heritable Targeted Inactivation of Myostatin Gene in Yellow Catfish (Pelteobagrus fulvidraco) Using Engineered Zinc Finger Nucleases (2011)

Yellow catfish (Pelteobagrus fulvidraco) is one of the most important freshwater aquaculture species in China. However, its small size and lower meat yield limit its edible value. Myostatin (MSTN) is a negative regulator of mammalian muscle growth. But, the function of Mstn in fish remains elusive. To explore roles of mstn gene in fish growth and create a strain of yellow catfish with high amount of muscle mass, we performed targeted disruption of mstn in yellow catfish using engineered zinc-finger nucleases (ZFNs). Employing zebrafish embryos as a screening system to identify ZFN activity, we obtained one pair of ZFNs that can edit mstn in yellow catfish genome. Using the ZFNs, we successfully obtained two founders (Founder July29-7 and Founder July29-8) carrying mutated mstn gene in their germ cells. The mutated mstn allele inherited from Founder July29-7 was a null allele (mstn(nju6)) containing a 4 bp insertion, predicted to encode function null Mstn. The mutated mstn inherited from Founder July29-8 was a complex type of mutation (mstn(nju7)), predicted to encode a protein lacking two amino acids in the N-terminal secretory signal of Mstn. Totally, we obtained 6 mstn(nju6/+) and 14 mstn(nju7/+) yellow catfish. To our best knowledge, this is the first endogenous gene knockout in aquaculture fish. Our result will help in understanding the roles of mstn gene in fish.
Loss of differentiation control in transformed 3T3 T proadipocytes. (1993)

Nontransformed 3T3 T mesenchymal/proadipocyte stem cells can be readily induced to differentiate, yet previous work has shown that 3T3 T cells that are spontaneously or virally transformed not only lose their normal growth control mechanisms but also lose the ability to differentiate. Loss of growth control can be due to autocrine mechanisms in some transformed cells, but the mechanisms involved in disrupting differentiation control are poorly understood. Our goal is to further define the growth and differentiation defects that arise in neoplastically transformed cells and the mechanisms underlying those defects. For example, exogenous transforming growth factor beta and tumor necrosis factor, both of which are secreted aberrantly by some tumor cells, are known inhibitors of different steps of the normal 3T3 T adipocyte differentiation process, suggesting a potential role as autocrine factors in disrupting differentiation of transformed 3T3 T cells. In the current study we transformed 3T3 T cells in vitro with chemical or UV irradiation treatment in order to determine if the acquisition of the transformed phenotype after these treatments is also associated with loss of differentiation control as it is with spontaneously or virally transformed cells. Four chemically and two UV-treated 3T3 T cell lines were isolated from type III foci and all have been found to be tumorigenic in syngeneic animals and to have lost the ability to differentiate. Relative to the parental cell line the differentiation abilities of the transformed clones ranged from 0 to less than 5%. In this regard, we also analyzed the normal and aberrant expression of three growth factors and differentiation inhibitors in transformed cells. Both transforming growth factor alpha and beta were found to be expressed in non-transformed 3T3 T cells as determined by Northern blot analyses. In addition, both were found to be down-regulated during differentiation of 3T3 T cells. Transformed/differentiation-defective 3T3 T cells expressed varied levels of transforming growth factor alpha and beta. Three of the new transformed clones expressed particularly high levels of transforming growth factor alpha. Very low levels of tumor necrosis factor expression were found in the normal cells and the transformed cells appeared to express tumor necrosis factor at similar levels. In contrast, none of the transformed cells expressed any of the differentiation-specific genes tested (lipoprotein lipase, glycerol-3-phosphate dehydrogenase, etc.). Even a transformed clone which could undergo growth arrest but not morphological differentiation expressed no differentiation-specific genes. Together, these data suggest that neoplastic transformation in general disrupts differentiation control.(ABSTRACT TRUNCATED AT 400 WORDS)
Studies of membrane-associated and soluble (secreted) lymphotoxin in human lymphokine-activated T-killer cells in vitro. (1992)

The expression, release, and cytolytic activity of membrane-associated lymphotoxin was examined in cultures of phytohemagglutinin-P (PHA-P) and interleukin 2 (IL-2)-stimulated human T-lymphokine-activated killer (T-LAK) cells in vitro. Lymphotoxin (LT/TNF-beta) was identified on the membrane of T-LAK cells using flow cytometry. The membrane form of LT (mLT) is detected not only on T-LAK cells but also on LT-secreting human B-cell lymphoid cell lines, RPMI 1788 and Raji, but not on U937 or K562 cells. Maximum expression of mLT on T-LAK cells and the secretion of LT into the supernatant depended on the concentration of IL-2. Expression of mLT on T-LAK cells was reduced by stimulation with PHA-P; however, supernatant LT levels greatly increased. Both expression of mLT and release of soluble LT was reduced after incubation of T-LAK cells with actinomycin D (ActD) or cycloheximide (CHx). Paraformaldehyde-fixed T-LAK cells caused cytolysis of WEHI 164 cells in vitro, which was blocked by anti-LT but not anti-TNF antibody. These data support the concept that mLT may be an intermediate form to secreted LT, and that the mLT form is cytolytically active.
Role of Adult Mesenchymal Stem Cells in Bone Tissue Engineering Applications: Current Status and Future Prospects (2005)

Mesenchymal stem cells (MSCs) have been demonstrated as an attractive cell source for tissue-engineering applications because of their ability to be easily isolated and expanded from adult bone marrow aspirates and their versatility for pluripotent differentiation into mesenchymal tissues. This review highlights advances and progress in bone reconstruction techniques for both the repair of site-specific bone defects and the attenuation of musculoskeletal disease symptoms associated with osteoporosis and osteogenesis imperfecta. Despite the enormous potential benefits of MSCs within these approaches, conventional tissue culture methods limit the clinical utility of these cells because of the gradual loss of both their proliferative and differentiation potential during ex vivo expansion. Novel strategies to overcome these limitations are discussed including cultivation in the presence of basic fibroblastic growth factor 2, induction of ectopotic telomerase expression, and ex vivo expansion on various collagenous biomaterials. In addition, this review also outlines mechanistic theories on the potential role of MSC-extracellular matrix interactions in mediating the retention of MSC proliferative and differentiation capacity after ex vivo expansion on collagenous biomaterials.
Stroma-Contact Prevents Loss of Hematopoietic Stem Cell Quality During Ex Vivo Expansion of CD34+ Mobilized Peripheral Blood Stem Cells (1998)

Stroma-supported long-term cultures (LTC) allow estimation of stem cell quality by simultaneous enumeration of hematopoietic stem cell (HSC) frequencies in a graft using the cobblestone area forming cell (CAFC) assay, and the ability of the graft to generate progenitors in flask LTC (LTC-CFC). We have recently observed that the number and quality of mobilized peripheral blood stem cells (PBSC) was low in patients having received multiple rounds of chemotherapy. Moreover, grafts with low numbers of HSC and poor HSC quality had a high probability to cause graft failure upon their autologous infusion. Because ex vivo culture of stem cells has been suggested to present an attractive tool to improve hematological recovery or reduce graft size, we have studied the possibility that such propagation may affect stem cell quality. In order to do so, we have assessed the recovery of different stem cell subsets in CD34+ PBSC after a 7-day serum-free liquid culture using CAFC and LTC-CFC assays. A numerical expansion of stem cell subsets was observed in the presence of interleukin-3 (IL-3), stem cell factor, and IL-6, while stroma-contact, stromal soluble factors, or combined addition of FLT3-ligand and thrombopoietin improved this parameter. In contrast, ex vivo culture severely reduced the ability of the graft to produce progenitors in LTC while stromal soluble factors partly abrogated this quality loss. The best conservation of graft quality was observed when the PBSC were cultured in stroma-contact. These data suggest that ex vivo propagation of PBSC may allow numerical expansion of various stem cell subsets, however, at the expense of their quality. In addition, cytokine-driven PBSC cultures require stroma for optimal maintenance of graft quality.
Quantitative Control of Adaptive Cardiac Hypertrophy by Acetyltransferase p300 (2008)

Small increments in p300 are necessary and sufficient to drive myocardial hypertrophy, possibly through acetylation of MEF2 and upstream of signals promoting phosphorylation or nuclear export of histone deacetylases. We propose that induction of myocardial p300 content is a primary rate-limiting event in the response to hemodynamic loading in vivo and that p300 availability drives and constrains adaptive myocardial growth. Specific reduction of p300 content or activity may diminish stress-induced hypertrophy and forestall the development of heart failure.
The myth of consumerism in the NHS (1997)

In the last of her series of articles, Kate Phillips looks at patients as consumers
Anticodon Sequence Mutants of Escherichia coli Initiator tRNA:  Effects of Overproduction of Aminoacyl-tRNA Synthetases, Methionyl-tRNA Formyltransferase, and Initiation Factor 2 on Activity in Initiation (2003)

Anticodon sequence mutants of Escherichia coli initiator tRNA initiate protein synthesis with codons other than AUG and amino acids other than methionine. Because the anticodon sequence is, in many cases, important for recognition of tRNAs by aminoacyl-tRNA synthetases, the mutant tRNAs are aminoacylated in vivo with different amino acids. The activity of a mutant tRNA in initiation in vivo depends on (i) the level of expression of the tRNA, (ii) the extent of aminoacylation of the tRNA, (iii) the extent of formylation of the aminoacyl-tRNA to formylaminoacyl-tRNA (fAA-tRNA), and (iv) the affinity of the fAA-tRNA for the initiation factor IF2 and the ribosome. Previously, using E. coli overproducing aminoacyl-tRNA synthetases, methionyl-tRNA formyltransferase, or IF2, we identified the steps limiting the activity in initiation of mutant tRNAs aminoacylated with glutamine and valine. Here, we have identified the steps limiting the activity of mutant tRNAs aminoacylated with isoleucine and phenylalanine. The combined results of experiments involving a variety of initiation codons (AUG, UAG, CAG, GUC, AUC, and UUC) provide support to the hypothesis that the ribosome.fAA-tRNA complex can act as an intermediate in initiation of protein synthesis. Comparison of binding affinities of various fAA-tRNAs (fMet-, fGln-, fVal-, fIle-, and fPhe-tRNAs) to IF2 using surface plasmon resonance supports the idea that IF2 can act as a carrier of fAA-tRNA to the ribosome. Other results suggest that the C1xA72 base pair mismatch, unique to eubacterial and organellar initiator tRNAs, may also be important for the binding of fAA-tRNA to IF2.
Quantification of atherosclerotic plaque components using in vivo MRI and supervised classifiers (2006)

In this work we aimed to study the possibility of using supervised classifiers to quantify the main components of carotid atherosclerotic plaque in vivo on the basis of multisequence MRI data. MRI data consisting of five MR weightings were obtained from 25 symptomatic subjects. Histological micrographs of endarterectomy specimens from the 25 carotids were used as a standard of reference for training and evaluation. The set of subjects was divided in a training set (12 subjects) and an evaluation set (13 subjects). Four different classifiers and two human MRI readers determined the percentages of calcified tissue, fibrous tissue, lipid core, and intraplaque hemorrhage on the subject level for all subjects in the evaluation set. Quantification of the relatively small amounts of calcium could not be done with statistical significance by either the classifiers or the MRI readers. For the other tissues a simple Bayesian classifier (Bayes) performed better than the other classifiers and the MRI readers. All classifiers performed better than the MRI readers in quantifying the sum of hemorrhage and lipid proportions. The MRI readers overestimated the hemorrhage proportions and tended to underestimate the lipid proportions. In conclusion, this pilot study demonstrates the benefits of algorithmic classifiers for quantifying plaque components.