gebhart/patrepeval huggingface dataset:
Dietary Supplements and Military Divers: A Synopsis for Undersea Medical Officers (2004)

Abstract : The variety, availability, sales and use of dietary supplements (DS) remain poorly understood by the mainstream medical community, but the potential for use and abuse of DS cannot be taken lightly by undersea medical officers (UMO). Despite the indisputable pharmacologic effects many of these over-the-counter (OTC) products exert, the use of DS is generally overlooked by clinicians. DS information is not covered in much depth, if at all, in medical education, and physicians are not trained in this area. As such, many may feel uncomfortable with their lack of familiarity regarding the ever-increasing supplement pharmacopoeia. Peer-reviewed scientific research and evidenced-based information are often limited. Moreover, because the general public and active duty community perceive these natural substances as harmless, the products often do not come to the attention of physicians at all. Less than half of all users of DS consult a physician or a practitioner about alternative products (Aeromed) Whereas the literature on DS use is limited, research specific to use of DS under extreme environments is even sparser: virtually no studies have been conducted in hyperbaric/ undersea environments. Due to the physiologic and psychological challenges of these extreme environments, military and civilian restrictions on the use of most medications in aviation and diving are quite specific and very strict. Because DS are not regulated by the Food and Drug Administration (FDA) as drugs, specifics regarding their use have not been addressed in diving regulations. To date, US Navy divers are not required to disclose their use of supplements, nor has it been common practice for UMOs or civilian equivalents to inquire about such use. However, considerable risks are expected with the use of many DS that are currently marketed. The safety and efficacy of most DS are not known for environments encountered routinely by the military diver.
Accurate low-cost methods for performance evaluation of cache memory systems (1988)

Trace-driven simulation is a simple way of evaluating cache memory systems with varying hardware parameters. But to evaluate realistic workloads, simulating even a few million addresses is not adequate and such large scale simulation is impractical from the consideration of space and time requirements. New methods of simulation based on statistical techniques are proposed for decreasing the need for large trace measurements and for predicting true program behavior. In the method, sampling techniques are applied while collecting the address trace from a workload. This drastically reduces the space and time needed to collect the trace. New simulation techniques are developed to use the sample data not only to predict the mean miss rate of the cache, but also to provide an empirical estimate of its actual distribution. Finally, a new concept of primed cache is introduced to simulate large caches by the sampling-based method.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Role of Mitogen-activated Protein Kinases and c-Jun/AP-1 trans-Activating Activity in the Regulation of Protease mRNAs and the Malignant Phenotype in NIH 3T3 Fibroblasts (1999)

Ras activates a multitude of downstream activities with roles in cellular proliferation, invasion and metastasis, differentiation, and programmed cell death. In this work we have evaluated the requirement of extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinase kinase (JNKK), and c-Jun/AP-1 activities in transformation and extracellular matrix invasion of ras oncogene expressing NIH 3T3 fibroblasts by expressing stable mutant genes that constitutively inhibit these activities. Whereas the inhibition of ERK activity reverts the transformed and invasive phenotype, the inhibition of the JNK pathway and AP-1 trans-activating activities by JNKK[K129R] and c-Jun(TAM67) had no effect on the ability of the ras oncogene-expressing cells to grow in soft agar or invade Matrigel basement membrane. Thus an elevated JNK activity and/or c-Jun/AP-1 trans-activating activity are not absolute requirements for ras transformation or invasion through basement membrane, and the dependence on AP-1 activity for transformation is cell-specific. However, inhibition of JNK kinase (JNKK) in ras-transformed cells with normally elevated JNK activity switches the protease-dependent invasive phenotype from a urokinase plasminogen activator (uPA)-dependent to a cathepsin L (CL)-dependent invasive phenotype. Conversely, treatment of ras-transformed cells of low constitutive JNK activity with the JNK stimulator, anisomycin, converts the protease mRNA levels from those characteristic of a CL-dependent to a uPA-dependent phenotype. These protease phenotypes can be duplicated in untransformed NIH 3T3 cells that express platelet-derived growth factor receptors and m1 muscarinic receptors that selectively stimulate the ERK or JNK pathways, respectively. It is concluded that high ERK activity is required for both protease phenotypes, whereas the JNK pathway and c-Jun/AP-1 activity are not required for transformation but regulate a switch between uPA and CL protease phenotypes in both transformed and untransformed cells. In ras-transformed NIH 3T3 fibroblasts, the uPA- and CL-dependent protease phenotypes are redundant in their ability to invade through basement membrane.
Synthesis of veratramine (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of veratramineWilliam Summer. Johnson, Hendrik A. P. DeJongh, Charles E. Coverdale, John William. Scott, and Urs. BurckhardtCite this: J. Am. Chem. Soc. 1967, 89, 17, 4523–4524Publication Date (Print):August 1, 1967Publication History Published online1 May 2002Published inissue 1 August 1967https://pubs.acs.org/doi/10.1021/ja00993a049https://doi.org/10.1021/ja00993a049research-articleACS PublicationsRequest reuse permissionsArticle Views553Altmetric-Citations36LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
PTPN11 (Protein-Tyrosine Phosphatase, Nonreceptor-Type 11) Mutations in Seven Japanese Patients with Noonan Syndrome (2002)

Noonan syndrome is an autosomal dominant disorder defined by short stature, delayed puberty, and characteristic dysmorphic features. Tartaglia et al. (Nature Genetics, 29:465–468) have recently shown that gain-of-function mutations in the gene PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) cause Noonan syndrome in roughly half of patients that they examined. To further explore the relevance of PTPN11 mutations to the pathogenesis of Noonan syndrome, we analyzed the PTPN11 gene in 21 Japanese patients. Mutation analysis of the 15 coding exons and their flanking introns by denaturing HPLC and direct sequencing revealed six different heterozygous missense mutations (Asp61Gly, Tyr63Cys, Ala72Ser, Thr73Ile, Phe285Ser, and Asn308Asp) in seven cases (six sporadic and one familial). The mutations clustered either in the N-Src homology 2 domain or in the protein-tyrosine phosphatase domain. The clinical features of the mutation-positive and mutation-negative patients were comparable. The results provide further support to the notion that PTPN11 mutations are responsible for the development of Noonan syndrome in a substantial fraction of patients and that relatively infrequent features of Noonan syndrome, such as sensory deafness and bleeding diathesis, can also result from mutations of PTPN11.
Development of a Haptic Training Simulation for the Administration of Dental Anaesthesia based upon Accurate Anatomical Data (2014)

In the dental curriculum, the initial administration of local anaesthesia injection on live patients is critical and students may experience a high degree of anxiety. Low self-confidence often caused by insufficient knowledge of anatomy has been repeatedly reported as one of the major causes. In this paper, we focus on the development of a haptic training system based upon an accurate anatomical model, which aims to encourage self-paced learning of the practical skills that are required in such procedures and to increase students' self-confidence. We first present the workflow we have considered to develop an accurate anatomical model of the human head and neck and introduce a Virtual Reality-based application commissioned by NHS Education for Scotland to support the learning of the anatomy in a safe and repeatable manner. Finally, we describe the functionalities of the haptic training system and discuss further developments with regard to existing research outcomes.
A Reduced Complexity Transmitter for UF-OFDM (2015)

UF-OFDM is a promising 5G waveform candidate, close to CP-OFDM, but with better spectral properties. Efficient receiver implementations exist, which are close to CP-OFDM in terms of complexity. The UF-OFDM multi-carrier modulator, on the other hand, still has no efficient solution in the literature up to now. This paper addresses this problem and presents a novel frequency domain generation method for UF-OFDM, where overlapping subbands are superimposed. Our approach can bring down UF-OFDM multi-carrier modulator complexity almost as low as a factor of 2 above CP-OFDM, with a negligible approximation error. Thus the required efficient transmitter implementation is delivered by this paper's solution, ready to be used in hardware implementations.
Production of transgenic sheep with growth‐regulating genes (1989)

Pronuclei of fertilized sheep ova were injected with fusion genes consisting of the mouse metallothionein-I promotor/regulator ligated to either the structural gene for bovine growth hormone (mMTbGH) or to a minigene for human growth hormone-releasing factor (mMThGRF). From a total of 842 sheep ova injected with mMTbGH and transferred into recipient ewes, 47 lambs were born. Two of the lambs were transgenic with mMTbGH, and both had bGH mRNA present in liver, kidney, and gut. In one lamb, plasma growth hormone was as high as 700 ng/ml. From a total of 435 sheep ova injected with mMThGRF and transferred to recipients, 54 lambs were born and 9 fetuses were collected. Nine of the 63 had integrated the mMThGRF gene. One of the nine had high concentrations of immunoassayable hGRF in its plasma and high variable plasma concentrations of ovine growth hormone. The lamb that expressed the hGRF gene did not release GH in response to an hGRF challenge. Four of five fetal offspring of a nonexpressing mMThGRF transgenic ram also contained the mMThGRF gene and, like the sire, failed to express the gene as determined by either liver hGRF mRNA or by plasma hGRF. Growth of the single transgenic lamb expressing hGRF was similar to control lambs. These studies demonstrate efficient introduction of genes into the sheep genome and indicate that transgenes are expressed and heritable.
Development of a combined intravascular ultrasound and photoacoustic imaging system (2006)

Intravascular ultrasound (IVUS) imaging has emerged as an imaging technique to evaluate coronary artery diseases including vulnerable plaques. However, in addition to the morphological characteristics provided by IVUS imaging, there is a need for functional imaging capability that could identify the composition of vulnerable plaques. Intravascular photoacoustic (IVPA) imaging, in conjunction with clinically available IVUS imaging, may be such a technique allowing vulnerable plaque characterization and differentiation. We have developed an integrated intravascular ultrasound and photoacoustic imaging system to visualize clinically relevant structural and functional properties of the coronary arteries. The performance of the combined IVUS and IVPA imaging system was evaluated through images of arterial phantoms. Experiments were performed using high frequency IVUS imaging catheters operating at 20 MHz, 30 MHz and 40 MHz. The IVPA imaging was successful in highlighting inclusions based on differential optical absorption while these lesions did not have sufficient contrast in the IVUS images. Finally, initial IVUS and IVPA imaging studies were performed on ex vivo samples of a rabbit artery using the 40 MHz IVUS imaging catheter. Results of the above studies demonstrate the feasibility of combining intravascular ultrasound and photoacoustic imaging and suggest clinical utility of the developed imaging system in interventional cardiology.
Simple and selective method for aldehydes (RCHO) .fwdarw. (E)-haloalkenes (RCH:CHX) conversion by means of a haloform-chromous chloride system (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSimple and selective method for aldehydes (RCHO) .fwdarw. (E)-haloalkenes (RCH:CHX) conversion by means of a haloform-chromous chloride systemK. Takai, K. Nitta, and K. UtimotoCite this: J. Am. Chem. Soc. 1986, 108, 23, 7408–7410Publication Date (Print):November 1, 1986Publication History Published online1 May 2002Published inissue 1 November 1986https://pubs.acs.org/doi/10.1021/ja00283a046https://doi.org/10.1021/ja00283a046research-articleACS PublicationsRequest reuse permissionsArticle Views9474Altmetric-Citations689LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Combination chemotherapy in vitro exploiting glutamine metabolism of human glioma and medulloblastoma. (1985)

The human glioma-derived cell line D-54 MG and the human medulloblastoma-derived cell line TE-671 have been shown to be sensitive in culture to the pharmacological interference with glutamine metabolism by acivicin, 6-diazo-5-oxo-L-norleucine, and methionine sulfoximine. Using as a guide the multiple contributions of glutamine to the biosynthesis of proteins, purines, and pyrimidines, we now have identified six additional antimetabolites active against these lines in vitro at clinically relevant concentrations. The 50% growth-inhibitory levels of the drugs against D-54 MG in 6-day continuous exposure experiments were: L-asparaginase, 0.057 IU/ml; 5-fluorouracil, 0.5 micrograms/ml; 6-mercaptopurine, 0.8 micrograms/ml; actinomycin D, 0.0007 micrograms/ml; N-phosphonacetyl-L-aspartic acid, 2.3 micrograms/ml; and 5-azacytidine, 0.2 micrograms/ml (3-day exposure. The corresponding 50% growth-inhibitory values in TE-671 were: L-asparaginase, 0.54 IU/ml; 5-fluorouracil, 1.5 micrograms/ml; 6-mercaptopurine, 4.7 micrograms/ml; actinomycin D, 0.00044 micrograms/ml; N-phosphonacetyl-L-aspartic acid, 4.5 micrograms/ml; and 5-azacytidine, 0.49 micrograms/ml. Dipyridamole up to 10 micrograms/ml was inactive against both lines. The isobologram method was used to evaluate the effectiveness of several two-drug combinations which were biochemically designed. The sums of the optimal fractional inhibitory concentrations for the pairs were: acivicin plus L-asparaginase, 0.14; acivicin plus methionine sulfoximine, 0.40; 6-diazo-5-oxo-L-norleucine plus methionine sulfoximine, 0.60; acivicin plus 6-mercaptopurine, 1.0, all in TE-671; and acivicin plus 5-fluorouracil, 0.79, in D-54 MG. Our findings suggest that an antimetabolite regimen exploiting glutamine sensitivity might improve the chemotherapy of some human gliomas and medulloblastomas.
Osteosarcoma Models: From Cell Lines to Zebrafish (2012)

High-grade osteosarcoma is an aggressive tumor most commonly affecting adolescents. The early age of onset might suggest genetic predisposition; however, the vast majority of the tumors are sporadic. Early onset, most often lack of a predisposing condition or lesion, only infrequent (<2%) prevalence of inheritance, extensive genomic instability, and a wide histological heterogeneity are just few factors to mention that make osteosarcoma difficult to study. Therefore, it is sensible to design and use models representative of the human disease. Here we summarize multiple osteosarcoma models established in vitro and in vivo, comment on their utilities, and highlight newest achievements, such as the use of zebrafish embryos. We conclude that to gain a better understanding of osteosarcoma, simplification of this extremely complex tumor is needed. Therefore, we parse the osteosarcoma problem into parts and propose adequate models to study them each separately. A better understanding of osteosarcoma provides opportunities for discovering and assaying novel effective treatment strategies."Sometimes the model is more interesting than the original disease"PJ Hoedemaeker (1937-2007).
Coupling between elastic strain and interstitial fluid flow: ramifications for poroelastic imaging (2006)

We study the effects of interstitial fluid flow and interstitial fluid drainage on the spatio-temporal response of soft tissue strain. The motivation stems from the ability to measure in vivo strain distributions in soft tissue via elastography, and the desire to explore the possibility of using such techniques to investigate soft tissue fluid flow. Our study is based upon a mathematical model for soft tissue mechanics from the literature. It is a simple generalization of biphasic theory that includes coupling between the fluid and solid phases of the soft tissue, and crucially, fluid exchange between the interstitium and the local microvasculature. We solve the mathematical equations in two dimensions by the finite element method (FEM). The finite element implementation is validated against an exact analytical solution that is derived in the appendix. Realistic input tissue properties from the literature are used in conjunction with FEM modelling to conduct several computational experiments. The results of these lead to the following conclusions: (i) different hypothetical flow mechanisms lead to different patterns of strain relaxation with time; (ii) representative tissue properties show fluid drainage into the local microvasculature to be the dominant flow-related stress/strain relaxation mechanism; (iii) the relaxation time of strain in solid tumours due to drainage into the microvasculature is on the order of 5–10 s; (iv) under realistic applied pressure magnitudes, the magnitude of the strain relaxation can be as high as approximately 0.4% strain (4000 microstrains), which is well within the range of strains measurable by elastography.
Measurement of very long‐chain fatty acids, phytanic and pristanic acid in plasma and cultured fibroblasts by gas chromatography (1995)

Two methods are described, both currently used in our laboratory, for the quantitative analysis of very long-chain fatty acids, phytanic acid and pristanic acid in plasma and cultured fibroblasts by gas-liquid chromatography. The first method is based on the procedure developed by Moser and Moser (1991) and the second is based on the method of Onkenhout and colleagues (1989), which is an application of the original method of Lepage and Roy for plasma and fibroblasts. A survey is given of the concentrations of very long-chain fatty acids, pristanic and phytanic acid in plasma and fibroblasts from control subjects and all patients investigated so far in our laboratory.
Transient Expression of Cellular Polypyrimidine-Tract Binding Protein Stimulates Cap-Independent Translation Directed by Both Picornaviral and Flaviviral Internal Ribosome Entry Sites In Vivo (2000)

The regulation of cap-independent translation directed by the internal ribosome entry sites (IRESs) present in some viral and cellular RNAs is poorly understood. Polypyrimidine-tract binding protein (PTB) binds specifically to several viral IRESs. IRES-directed translation may be reduced in cell-free systems that are depleted of PTB and restored by reconstitution of lysates with recombinant PTB. However, there are no data concerning the effects of PTB on IRES-directed translation in vivo. We transfected cells with plasmids expressing dicistronic transcripts in which the upstream cistron encoded PTB or PTB deletion mutants (including a null mutant lacking amino acid residues 87 to 531). The downstream cistron encoded a reporter protein (chloramphenicol acetyltransferase [CAT]) under translational control of the poliovirus IRES which was placed within the intercistronic space. In transfected BS-C-1 cells, transcripts expressing wild-type PTB produced 12-fold more reporter protein than similar transcripts encoding the PTB null mutant. There was a 2.4-fold difference in CAT produced from these transcripts in HeLa cells, which contain a greater natural abundance of PTB. PTB similarly stimulated CAT production from transcripts containing the IRES of hepatitis A virus or hepatitis C virus in BS-C-1 cells and Huh-7 cells (37- to 44-fold increase and 5 to 5.3-fold increase, respectively). Since PTB had no quantitative or qualitative effect on transcription from these plasmids, we conclude that PTB stimulates translation of representative picornaviral and flaviviral RNAs in vivo. This is likely to reflect the stabilization of higher ordered RNA structures within the IRES and was not observed with PTB mutants lacking RNA recognition motifs located in the C-terminal third of the molecule.