gebhart/patrepeval huggingface dataset:
A Comparison Between the Minimal Model and the Glucose Clamp in the Assessment of Insulin Sensitivity Across the Spectrum of Glucose Tolerance (1994)

An insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis was compared with the glucose clamp in 11 subjects with normal glucose tolerance (NGT), 20 with impaired glucose tolerance (IGT), and 24 with non-insulin-dependent diabetes mellitus (NIDDM). The insulin sensitivity index (SI) was calculated from FSIGTT using 22- and 12-sample protocols (SI(22) and SI(12), respectively). Insulin sensitivity from the clamp was expressed as SI(clamp) and SIP(clamp). Minimal model parameters were similar when calculated with SI(22) and SI(12). SI could not be distinguished from 0 in approximately 50% of diabetic patients with either protocol. SI(22) correlated significantly with SI(clamp) in the whole group (r = 0.62), and in the NGT (r = 0.53), IGT (r = 0.48), and NIDDM (r = 0.41) groups (P < 0.05 for each). SI(12) correlated significantly with SI(clamp) in the whole group (r = 0.55, P < 0.001) and in the NGT (r = 0.53, P = 0.046) and IGT (r = 0.58, P = 0.008) but not NIDDM (r = 0.30, P = 0.085) groups. When SI(22), SI(clamp), and SIP(clamp) were expressed in the same units, SI(22) was 66 +/- 5% (mean +/- SE) and 50 +/- 8% lower than SI(clamp) and SIP(clamp), respectively. Thus, minimal model analysis of the insulin-modified FSIGTT provides estimates of insulin sensitivity that correlate significantly with those from the glucose clamp. The correlation was weaker, however, in NIDDM. The insulin-modified FSIGTT can be used as a simple test for assessment of insulin sensitivity in population studies involving nondiabetic subjects. Additional studies are needed before using this test routinely in patients with NIDDM.
An OS-based alternative to full hardware coherence on tiled CMPs (2008)

The interconnect mechanisms (shared bus or crossbar) used in current chip-multiprocessors (CMPs) are expected to become a bottleneck that prevents these architectures from scaling to a larger number of cores. Tiled CMPs offer better scalability by integrating relatively simple cores with a lightweight point-to-point interconnect. However, such interconnects make snooping impractical and, thus, require alternative solutions to cache coherence. This paper proposes a novel, cost-effective mechanism to support shared-memory parallel applications that forgoes hardware maintained cache coherence. The proposed mechanism is based on the key ideas that mapping of lines to physical caches is done at the page level with OS support and that hardware supports remote cache accesses. It allows only some controlled migration and replication of data and provides a sufficient degree of flexibility in the mapping through an extra level of indirection between virtual pages and physical tiles. We evaluate the proposed tiled CMP architecture on the Splash-2 scientific benchmarks and ALPBench multimedia benchmarks against one with private caches and a distributed directory cache coherence mechanism. Experimental results show that the performance degradation is as little as 0%, and 16% on average, compared to the cache coherent architecture across all benchmarks for 16 and 32 processors.
Insulin gene therapy from design to beta cell generation (2012)

Despite the fact that insulin injection can protect diabetic patients from developing diabetes-related complications, recent meta-analyses indicate that rapid and long-acting insulin analogues only provide a limited benefit compared with conventional insulin regarding glycemic control. As insulin deficiency is the main sequel of type-1 diabetes (T1D), transfer of the insulin gene-by-gene therapy is becoming an attractive treatment modality even though T1D is not caused by a single genetic defect. In contrast to human insulin and insulin analogues, insulin gene therapy targets to supplement patients not only with insulin but also with C-peptide. So far, insulin gene therapy has had limited success because of delayed and/or transient gene expression. Sustained insulin gene expression is now feasible using current gene-therapy vectors providing patients with basal insulin coverage, but management of postprandial hyperglycaemia is still difficult to accomplish because of the inability to properly control insulin secretion. Enteroendocrine cells of the gastrointestinal track (K cells and L cells) may be ideal targets for insulin gene therapy, but cell-targeting difficulties have limited practical implementation of insulin gene therapy for diabetes treatment. Therefore, recent gene transfer technologies developed to generate authentic beta cells through transdifferentiation are also highlighted in this review.
Regulation of theOct-4gene by nuclear receptors (1994)

To unravel the network of transcription factors established during development it is important to understand how genes specifically expressed during embryogenesis are regulated. Oct-4 is a transcription factor whose expression is associated with an undifferentiated cell phenotype in the early mouse embryo and is downregulated when such cells differentiate. An enhancer in the upstream region of Oct-4 has previously been reported as being sufficient to mediate the cell-type specific expression and RA-dependent down-regulation in EC cells, although the enhancer contains no retinoic acid receptor (RAR) binding sites. Here we report the identification of promoter elements important for the regulation of the Oct-4 gene in EC cells. A region of the proximal Oct-4 promoter contains an overlapping set of regulatory elements including a high affinity binding site for Sp1 and three direct repeats of an AGGTCA-like sequence with either +1 or 0 spacing. Binding and transient transfection assays reveal that Oct-4 is subject to negative regulation by different members of the steroid-thyroid hormone receptor superfamily. Specifically, important roles for ARP-1 and RAR in Oct-4 expression are indicated.
Proximal Tubule-Specific Deletion of the NHE3 (Na + /H + Exchanger 3) in the Kidney Attenuates Ang II (Angiotensin II)-Induced Hypertension in Mice (2019)

The present study directly tested the hypothesis that the NHE3 (Na<sup>+</sup>/H<sup>+</sup> exchanger 3) in the proximal tubules of the kidney is required for the development of Ang II (angiotensin II)-induced hypertension using PT-Nhe3<sup>-/-</sup> (proximal tubule-specific NHE3 knockout) mice. Specifically, PT-Nhe3<sup>-/-</sup> mice were generated using the SGLT2-Cre/Nhe3<sup>loxlox</sup> approach, whereas Ang II-induced hypertension was studied in 12 groups (n=5-12 per group) of adult male and female wild-type (WT) and PT-Nhe3<sup>-/-</sup> mice. Under basal conditions, systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were significantly lower in male and female PT-Nhe3<sup>-/-</sup> than WT mice (P<0.01). A high pressor, 1.5 mg/kg per day, intraperitoneal or a slow pressor dose of Ang II, 0.5 mg/kg per day, intraperitoneal for 2 weeks significantly increased systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure in male and female WT mice (P<0.01), but the hypertensive response to Ang II was markedly attenuated in male and female PT-Nhe3<sup>-/-</sup> mice (P<0.01). Ang II impaired the pressure-natriuresis response in WT mice, whereas proximal tubule-specific deletion of NHE3 improved the pressure-natriuresis response in Ang II-infused PT-Nhe3<sup>-/-</sup> mice (P<0.01). AT<sub>1</sub> receptor blocker losartan completely blocked Ang II-induced hypertension in both WT and PT-Nhe3<sup>-/-</sup> mice (P<0.01). However, inhibition of nitric oxide synthase with L-N<sup>G</sup>-Nitroarginine methyl ester had no effect on Ang II-induced hypertension in WT or PT-Nhe3<sup>-/-</sup> mice (not significant). Furthermore, Ang II-induced hypertension was significantly attenuated by an orally absorbable NHE3 inhibitor AVE0657. In conclusion, NHE3 in the proximal tubules of the kidney may be a therapeutical target in hypertension induced by Ang II or with increased NHE3 expression in the proximal tubules.
Discontinuity Meshing for Complex Environments (1998)

Throughout this thesis, there is an underlying assumption that the quality of a computer graphics image is important. This thesis reports research into computer image synthesis for obtaining this quality. The
Gain flattening fibre filters using phase-shiftedlong period fibre gratings (1998)

The transmission characteristics of phase-shifted long period gratings (LPGs) are examined theoretically by a combination of coupled-mode theory and transfer matrix formulation. It is shown that the transmission spectrum of such a grating can be significantly controlled by the phase shift which allows the shape of the spectrum to be tailored to meet the requirements of many kinds of gain flattening. By choosing the phase shift and the index change appropriately, a phase-shifted LPG is designed to flatten the spectrum of an Er:silica superfluorescent fibre source.
Recombinat hormones: Structure-function relationship of recombinant follicle stimulating hormone (Puregon®) (1996)

After separation by means of preparative isoelectrofocusing, the isohormones of a Chinese hamster ovary (CHO)-derived recombinant follicle stimulating hormone (rFSH, Puregon) were characterized with respect to structural and functional features. A carbohydrate analysis revealed that rFSH isohormones with a low isoelectric point (pl) have a high sialic acid/galactose ratio and are rich in tri- and tetra-antennary N-linked carbohydrate chains in comparison with the high pl isohormones. The relative basic isohormones exhibit receptor binding activity and intrinsic bioactivity 2-3-fold higher than the relative acidic isohormones. However, due to their lower clearance rate these acidic isohormones displayed a 20-fold higher in-vivo bioactivity in the rat. A comparison of the isohormone profile of rFSH and urinary FSH (Metrodin) revealed that rFSH contains about 2-fold more basic isohormones with pl > or = 4.7 and 2-fold less acidic isohormones with pl < 4.1. In-vitro studies showed that the receptor binding affinity and intrinsic bioactivity of both FSH preparations are similar. Also the in-vivo efficacy and the pharmacokinetic behaviour of rFSH and urinary FSH in the rat were similar, which is not surprising since both preparations were compared in terms of in-vivo bioactivity calibrated in the rat Steelman-Pohley assay. However, in dogs the bioavailability of rFSH was lower than that of urinary FSH, which is in agreement with the higher percentage of relative basic isohormones in rFSH. This suggests that the pharmacokinetic behaviour of FSH in rats and dogs is different, which is supported by the much longer elimination half-life of rFSH and urinary FSH in dogs (27.9 and 30.4 h respectively) compared with rats (11.4 and 10.4 h respectively) for rFSH and urinary FSH respectively. The observed differences in pharmacokinetic behaviour in dogs and rats indicate that the rat Steelman-Pohley assay might not be a valid model for the prediction of the FSH bioactivity in species other than rat.
A Mesenchymal Stromal Cell Gene Signature for Donor Age (2012)

Human aging is associated with loss of function and regenerative capacity. Human bone marrow derived mesenchymal stromal cells (hMSCs) are involved in tissue regeneration, evidenced by their capacity to differentiate into several lineages and therefore are considered the golden standard for cell-based regeneration therapy. Tissue maintenance and regeneration is dependent on stem cells and declines with age and aging is thought to influence therapeutic efficacy, therefore, more insight in the process of aging of hMSCs is of high interest. We, therefore, hypothesized that hMSCs might reflect signs of aging. In order to find markers for donor age, early passage hMSCs were isolated from bone marrow of 61 donors, with ages varying from 17-84, and clinical parameters, in vitro characteristics and microarray analysis were assessed. Although clinical parameters and in vitro performance did not yield reliable markers for aging since large donor variations were present, genome-wide microarray analysis resulted in a considerable list of genes correlating with human age. By comparing the transcriptional profile of aging in human with the one from rat, we discovered follistatin as a common marker for aging in both species. The gene signature presented here could be a useful tool for drug testing to rejuvenate hMSCs or for the selection of more potent, hMSCs for cell-based therapy.
Low-Delay Singing Voice Alignment to Text. (1999)

In this paper we present some ideas and preliminary results on how to move phoneme recognition techniques from speech to the singing voice to solve the low-delay alignment problem. The work focus mainly on searching the most appropriate Hidden Markov Model (HMM) architecture and suitable input features for the singing voice, and reducing the delay of the phonetic aligner without reducing its accuracy.
Microbiological degradation of the herbicide dicamba (1995)

Pseudomonas paucimobilis was isolated from a consortium which was capable of degrading dicamba (3,6-dichloro-2-methoxybenzoic acid) as the sole source of carbon. The degradation of dicamba by P. paucimobilis and the consortium was examined over a range of substrate concentration, temperature, and pH. In the concentration range of 100-2000 mg dicamba L-1 (0.5-9.0 mM), the degradation was accompanied by a stoichiometric release of 2 mol of Cl- per mol of dicamba degraded. The cultures had an optimum pH 6.5-7.0 for dicamba degradation. Growth studies at 10 degrees C, 20 degrees C, and 30 degrees C yielded activation energy values in the range of 19-36 kcal mol-1 and an average of Q10 value of 4.0. Compared with the pure culture P. paucimobilis, the consortium was more active at the lower temperature.
Next-generation Sequencing-based genomic profiling: Fostering innovation in cancer care? (2017)

We identified a high prevalence of gene alterations using an next-generation sequencing test. Although some benefit was associated with the matched therapy, most of the patients had disease progression as the best response, indicating the limited biological potential and unclear clinical relevance of this practice.
Studying the recruitment of Sp1 to the β-globin promoter with an in vivo method: Protein position identification with nuclease tail (PIN*POINT) (1998)

Transcription is thought to be regulated by recruitment of transcription factors, adaptors, and certain enzymes to cis-acting elements through protein-DNA interactions and protein-protein interactions. To better understand transcription, a method with the capability to detect in vivo recruitment of these individual proteins will be essential. Toward this end, we use a previously undescribed in vivo method that we term protein position identification with nuclease tail (PIN*POINT). In this method, a fusion protein composed of a chosen protein linked to a nonsequence-specific nuclease is expressed in vivo, and the binding of the protein to DNA is made detectable by the nuclease-induced cleavage near the binding site. In this article, we used the technique protein position identification with nuclease tail to study the effect of the beta-globin locus control region (LCR) and promoter elements on the recruitment of transcription factor Sp1 to the beta-globin promoter. We present evidence that the hypersensitive sites of the LCR synergistically enhance the recruitment of a multimeric Sp1 complex to the beta-globin promoter and that this may be accomplished by protein-protein interactions with proteins bound to the LCR, the upstream activator region, and, possibly, general transcription factors bound near the "TATA" box.
Vaccination against Marek’s Disease (1986)

Marek’s disease is a serious lymphoproliferative disease of the fowl which affects most organs and tissues but has an unusual predilection for peripheral nerves. The disease varies in severity ranging in extremes from the chronic disease, in which peripheral nerve involvement and paralytic signs are the most conspicuous features, to an acute fulminating disease in which multiple and diffuse lympho-mata are present. Prior to the development and wide use of vaccines for the control of the disease, it was of great economic importance to the poultry industry throughout the world. In the acute form mortality of 30% of a flock was common, and in some cases mortality reached over 50%.
Gene-Expression Profiling in Differentiated Thyroid Cancer – a Viable Strategy for the Practice of Genomic Medicine? (2005)

Thyroid neoplasias have been largely ignored as an active field of investigation due to the overall favorable prognosis of differentiated nonmedullary thyroid cancers. However, differentiated thyroid cancers have the highest estimated annual percentage increase in incidence amongst all cancer sites. Furthermore, no significant progress has been made to improve survival, especially for advanced disease. Compounding the problem, there remains a lack of highly accurate preoperative markers or molecular-based predictive models to differentiate benign from malignant follicular neoplasias, thus we continue to rely upon surgery for diagnostic purposes in this subset of patients. Therefore, new approaches are necessary to identify potential novel diagnostic, prognostic and therapeutic algorithms, which would not only allow accurate early diagnosis but also personalized patient management, with clinical management and surveillance tailored according to the genetic signature of the patient. The advent of modern genomic technologies, such as global gene-expression profiling, may begin to provide the data required for the evidence-based practice of genomic medicine as it relates to thyroid neoplasia. However, it is already clear that genomic technology alone is insufficient to fully achieve this vision.
Chemical Synthesis and Characterization of α-N-Octanoyl and Other α-N-Acyl Colistin Nonapeptide Derivatives (1973)

Eight α-N-acyl colistin nonapeptide derivatives including three aliphatic, four aromatic and one alicyclic derivatives were synthesized by the reaction of colistin nonapeptide with corresponding acid chlorides. This acylation reaction was carried out under the condition kept restrictedly at pH 5,0 in order to introduce an acyl group only to α-amino group but not to γ-amino group existing in a colistin nonapeptide molecule. Synthetic method and several physico-chemical natures of these acyl colistin nonapeptide derivatives are given in this paper. All of the acylated derivatives thus synthesized exhibited characteristic antimicrobial activities. Antimicrobial spectra were substantially based upon a gram-negative type and not so much altered by chemical structures of acyl groups which were considerably differentiated from each other such as cyclic or chain form. Thus, more possible response of carbon size than its structure to the antimicrobial effectiveness was inferred. In spite of almost no toxicity and feeble antimicrobial activity of colistin nonapeptide itself, these acylated colistin nonapeptide derivatives showed a toxicity against mice at a dose of 16.9~70 mg/kg in LD50, which, however, was inferior to the toxicity of colistin sulfate, possibly correspondent to their much weaker antimicrobial activities, as a whole. Hence, it seems likely that acyl part of these acylated colistin nonapeptide derivatives including that of colistin is seriously responsible for the biological activities.
Nonstationary filtering for removal of signal dependent noise in reconstructions from projections (2003)

The authors discuss a way to improve transmission tomograms in the presence of large density data variations and low photon dosage. They present a design for nonstationary filters that exploits the detectability of high-density regions in the object to match filters to local noise properties. The design of each filter is formulated as a least-squares optimization problem, with linear equality and inequality constraints that protect the resolution of detail while minimizing noise power in the reconstruction. Experimental results show reconstructions in whitened noise of power equivalent to those of conventional convolution backprojection, but with significantly better resolution.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo (2007)

Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. We have recently shown that hematopoietic malignant cells including those from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) aberrantly expressed Aurora A and B kinases, and ZM447439, a potent inhibitor of Aurora kinases, effectively induced growth arrest and apoptosis of a variety of leukemia cells. The present study explored the effect of AZD1152, a highly selective inhibitor of Aurora B kinase, on various types of human leukemia cells. AZD1152 inhibited the proliferation of AML lines (HL-60, NB4, MOLM13), ALL line (PALL-2), biphenotypic leukemia (MV4-11), acute eosinophilic leukemia (EOL-1), and the blast crisis of chronic myeloid leukemia K562 cells with an IC50 ranging from 3 nM to 40 nM, as measured by thymidine uptake on day 2 of culture. These cells had 4N/8N DNA content followed by apoptosis, as measured by cell-cycle analysis and annexin V staining, respectively. Of note, AZD1152 synergistically enhanced the antiproliferative activity of vincristine, a tubulin depolymerizing agent, and daunorubicin, a topoisomerase II inhibitor, against the MOLM13 and PALL-2 cells in vitro. Furthermore, AZD1152 potentiated the action of vincristine and daunorubicin in a MOLM13 murine xenograft model. Taken together, AZD1152 is a promising new agent for treatment of individuals with leukemia. The combined administration of AZD1152 and conventional chemotherapeutic agent to patients with leukemia warrants further investigation.
Role of the dsdC activator in regulation of D-serine deaminase synthesis (1978)

The activator of the D-serine deaminase operon, the product of the dsdC gene, has been partially purified. It is reasonably stable to routine purification procedures in the presence of its ligand D-serine, but not in its absence. It loses activity upon dialysis in amino acid-free buffer, but activity is completely restored upon readdition of D-serine. It apparently functions purely as an activator, no repressor function could be demonstrated at suboptimal D-serine concentration. It is a transcriptional control element. The time required for in vitro transcription of D-serine deaminase mRNA, nearly 4 min, is similar to that for beta-galactosidase. Since the beta-galactosidase monomer is a much protein, this is surprisingly long.
ClearBoard (1992)

This paper introduces a novel shared drawing medium called ClearBoard. It realizes (1) a seamless shared drawing space and (2) eye contact to support realtime and remote collaboration by two users. We devised the key metaphor: “talking through and drawing on a transparent glass window” to design ClearBoard. A prototype of ClearBoard is implemented based on the “Drafter-Mirror” architecture. This paper first reviews previous work on shared drawing support to clarify the design goals. We then examine three methaphors that fulfill these goals. The design requirements and the two possible system architectures of ClearBoard are described. Finally, some findings gained through the experimental use of the prototype, including the feature of “gaze awareness”, are discussed.