gebhart/patrepeval huggingface dataset:
Characterization of the purified vitamin K-dependent gamma-glutamyl carboxylase. (1993)

Vitamin K-dependent carboxylase, purified from bovine liver, has properties similar to those reported for the carboxylase activity present in crude, solubilized microsomes. The purified carboxylase was found to possess the vitamin K epoxidase activity, believed to be essential for vitamin K-dependent carboxylation, but did not contain vitamin K epoxide reductase activity. Kinetic studies of the carboxylase done under defined conditions were complicated by the non-Michaelis-Menten kinetic behavior observed for reactions with two of the enzymes substrates, FLEEL and vitamin K1 hydroquinone. Initial rate experiments with the substrate FLEEL demonstrated behavior consistent with substrate inhibition and gave half-maximal activity at 1 mM FLEEL. Experiments with the substrate vitamin K1 hydroquinone also displayed non-Michaelis-Menten kinetics, as maximal activity was reached prematurely in relation to behavior at lower concentrations. Half-maximal activity was observed at 35 microM vitamin K1 hydroquinone. Initial rate experiments with varying NaH14CO3 concentration displayed Michaelis-Menten kinetics and gave a Km(app) of 0.29 mM. At cosubstrate concentrations chosen to obtain near-maximal activity, initial rate studies with varying NaH14CO3 concentration indicated a kcat near 1.0 s-1. Removal of the fourth substrate, oxygen, resulted in the loss of more than 99% of carboxylase activity. The sulfhydryl reagent N-ethylmaleimide inhibited carboxylase irreversibly, as did the anticoagulant warfarin.
Frequency analysis of human primitive haematopoietic stem cell subsets using a cobblestone area forming cell assay. (1994)

Stroma-dependent long-term bone marrow cultures (LTBMC) assay the ability of primitive haematopoietic stem cells (HSC) for long-term production of clonable progenitors. We have developed a limiting dilution type LTBMC assay allowing frequency analysis of transiently repopulating HSC and long-term culture initiating cells (LTC-IC) without the necessity to replate large numbers of wells. Normal or 5-FU-treated Ficoll bone marrow cells (BMC), or BMCs sorted on CD34 or HLA-DR expression, or Rh123 retention, (input range 40-70,000 CFU-GM/BFU-E/10(5) cells) were plated at limiting dilution on unirradiated adherent layers formed by a novel murine preadipose cell line (FBMD-1). The percentage of wells with at least one phase-dark haematopoietic clone (cobblestone area, CA) beneath the stromal layer was weekly determined for at least 8 weeks, and CA-forming cell (CAFC) frequencies were calculated using Poisson statistics. Parallel LTBMCs of the same samples were weekly assessed for supernate CFU-GM/BFU-E production. Weekly addition of rhIL-3 with rhG-CSF supported a high average clonogenic output per CA and dramatically increased CA size, but did not significantly alter the apparent CAFC frequency. The generation of CFU-GM per CA was constant over a period of 6 weeks with weekly means of eight normal BM samples, ranging between 5-16. At week 6 the mean CAFC frequency was 29 (1 SEM, 8.8)/10(5). Early appearing CAFC were highly sensitive to 5-FU, and were contained over the full Rh123 and HLA-DR fluorescence profile of CD34pos cells, whereas CAFC week 5-8 were predominantly contained in the CD34pos Rh123dull HLA-DRlow fraction in agreement with previously reported LTC-IC characteristics. In conclusion, the CAFC assay enumerates LTC-IC using a direct visual endpoint and allows study of LTC-IC heterogeneity with respect to progenitor cell generation per stem cell clone in various haematologic diseases.
Generation in vivo of peptide-specific cytotoxic T cells and presence of regulatory T cells during vaccination with hTERT (class I and II) peptide-pulsed DCs (2009)

Addition of IFN-alpha to ex vivo monocyte-derived DCs, did not significantly enhance peptide-specific T cell responses in vivo, compared with TNF-alpha alone. Class II cognate help significantly augments peptide-specific T cell responses. Clinically favourable responses were seen in patients with low levels of circulating T regs.
Thyrotropin releasing hormone (TRH) may preserve pancreatic islet cell function: potential role in the treatment of diabetes mellitus. (2007)

Thyrotropin Releasing Hormone (TRH), first identified in the hypothalamus as a regulator of the Pituitary-Thyroid axis, has also been found in the beta-cell of the pancreas co-localised with insulin. The significance of this association is emphasised by the report that the TRH knock-out (KO) mouse is hyperglycemic. These findings have led to speculation that TRH may have a physiologic role in the regulation of carbohydrate metabolism. To understand better the role of TRH in the pancreas, TRH was administered to rats rendered diabetic from streptozotocin damage to the islets of Langerhans. This resulted in almost complete normalisation of the profound hyperglycemia. TRH is capable of reversing Diabetes Mellitus (DM) in an experimental animal model, possibly by promoting neogenesis of beta cells through induction of adult stem cells in the pancreas. These studies point to a potential therapeutic role for TRH in the treatment of DM in man.
Critical care performance measurement: The time has come for all* (2006)

Critical Care Medicine, Medicine and Pharmacy and Therapeutics, University of Pittsburgh Schools of Medicine and Pharmacy, Pittsburgh, PA Dr. Sirio has consulted for Cerner Corporation.
Systolic and diastolic blood pressures as predictors of coronary heart disease mortality in the Whitehall study. (1985)

Systolic and diastolic blood pressures were compared as predictors of death due to coronary heart disease using data on the 10 year mortality outcome from the 18 403 male civil servants, aged 40-64, in the Whitehall study. There were 727 deaths due to coronary heart disease. At entry to the study the systolic pressure in these men was significantly higher than the diastolic pressure, and a standardised index of relative risk for death from coronary heart disease was greater for systolic blood pressure. After adjustment for age the top quintile of systolic pressure (greater than 151 mm Hg) identified 5% more men at risk of death from coronary heart disease than for the top diastolic quintile (greater than 95 mm Hg). The findings suggested that clinicians should pay more attention to systolic levels as a criterion for making diagnostic and therapeutic decisions.
Primary Surface Rupture Associated with the Mw 7.1 16 October 1999 Hector Mine Earthquake, San Bernardino County, California (2002)

The M w 7.1 Hector Mine earthquake occurred within the Mojave Desert portion of the eastern California shear zone and was accompanied by 48 km of dextral surface rupture. Complex northward rupture began on two branches of the Lavic Lake fault in the northern Bullion Mountains and also propagated southward onto the Bullion fault. Lesser amounts of rupture occurred across two right steps to the south. Surface rupture was mapped using postearthquake, 1:10,000-scale aerial photography. Field mapping provided additional detail and more than 400 fault-rupture observations; of these, approximately 300 measurements were used to characterize the slip distribution. En echelon surface rupture predominated in areas of thick alluvium, whereas in the bedrock areas, rupture was more continuous and focused within a narrower zone. Measured dextral offsets were relatively symmetrical about the epicentral region, with a maximum displacement of 5.25 ± 0.85 m.[*][1] Vertical slip was a secondary component and was variable, with minor west-side-down displacements predominating in the Bullion Mountains. Field and aerial photographic evidence indicates that most of the faults that ruptured in 1999 had had prior late-Quaternary displacement, although only limited sections of the rupture show evidence for prior Holocene displacement.

 [1]: #fn-1
Biomedical Stretchable Sytems using MID Based Stretchable Electronics Technology (2007)

In order to fit human body, flexibility, or even better stretchability is requested for biomedical systems like implants or smart clothes. A stretchable electronic technology has been developed. This can provide highly stretchable interconnections fully compatible with PCB technologies. In order to prove the feasibility of complex biomedical systems like inner body implants or wearable systems, a variety of stretchable systems has been designed from sensor to power source systems.
Error estimation for lattice methods of stage self-calibration (1997)

For more than a dozen years now, stage self-calibration methods have been proposed for ameliorating overlay alignment problems. The idea is that a stage, calibrated to an accurate Cartesian standard, can reduce butting errors and, in mix-and-match, eliminate the need to force all line-of-duty lithography tools to conform to an identically distorted standard, with all of the re-adjustments and bookkeeping that entails. For all of their promise, there are important issues that must be resolved before self-calibration strategies can be trusted. The major problem is the determination of rigorously established error bounds - self-calibration procedures can be useful only if they assuredly improve the accuracy of the machines they are used to calibrate. However, in a previous paper the author has shown that a basic operation in so-called lattice methods of self-calibration procedures, namely rotation of a symmetric artifact, leads to an unstable set of equations, raising the question whether such procedures can possibly yield improved accuracy. This paper addresses that problem explicitly and thereby demonstrates a method for deriving the needed error bounds. The example used is a rotationally symmetric (regular) polygon. For the purpose of exposition, qualitative algebraic, not numeric, results are emphasized, but the method can be applied to produce the necessary numbers for general calibration lattices. The method can be applied to error estimation for practical stage self-calibration.
Heterogeneous Photocatalysis: Recent Advances and Applications (2013)

Semiconductor heterogeneous photocatalysis, the subject of this review, is a versatile, low-cost and environmentally benign treatment technology for a host of pollutants. These may be of biological, organic and inorganic in origin within water and air. The efficient and successful application of photocatalysis demands that the pollutant, the catalyst and source of illumination are in close proximity or contact with each other. The ability of advanced oxidation technology to remove low levels of persistent organic pollutants as well as microorganisms in water has been widely demonstrated and, progressively, the technology is now being commercialized in many areas of the world including developing nations. This review considers recent developments in the research and application of heterogeneous semiconductor photocatalysis for the treatment of low-level concentrations of pollutants in water and air using titanium dioxide as a “model” semiconductor. The review considers charge transport characteristics on the semiconductor surface, photocatalyst reactor design and organic degradation mechanistic pathways. The effects of photoreactor operating parameters on the photocatalytic process are discussed in addition to mineralization and disinfection kinetics.
Breast cancer risk associated with genotypic polymorphism of the mitosis‐regulating gene Aurora‐A/STK15/BTAK (2005)

Aneuploidy, an abnormal number of chromosomes, is relatively common and occurs early in breast cancer development. This observation supports a breast tumorigenic contribution of mechanisms responsible for maintaining chromosome number stability in which centrosomes play an essential role. We therefore speculated that the Aurora-A/STK15/BTAK gene, implicated in the regulation of centrosome duplication, may be associated with breast tumorigenesis. To test this hypothesis, we conducted a case-control study of 709 primary breast cancer patients and 1,972 healthy controls, examining single-nucleotide polymorphisms (SNPs), including a suggested functional Phe31Ile SNP, in Aurora-A. We were also interested in knowing whether any association between Aurora-A and breast cancer was modified by reproductive risk factors reflecting susceptibility to estrogen exposure. Our hypothesis is that, since estrogen is known to promote breast cancer development via its mitogenic effect leading to malignant proliferation on breast epithelium and since Aurora-A is involved in regulating mitosis, the discovery of a joint effect between the Aurora-A genotype and reproductive risk factors on cancer risk might yield valuable clues to the association of breast tumorigenesis with estrogen. Support for this hypothesis came from the following observations. (i) Two SNPs in Aurora-A were significantly associated with breast cancer risk (p < 0.05). (ii) Haplotype analyses, based on different combinations of multiple SNPs in Aurora-A, revealed a strong association with breast cancer risk; interestingly, the genotypic distribution of the suggested functional Phe31Ile SNP was not significantly different between breast cancer patients and controls, but the specific haplotype containing the putative at-risk Ile allele was more common in patients. (iii) This association between risk and putative high-risk genotypes was stronger and more significant in women thought to be more susceptible to estrogen, i.e., those with a longer interval between menarche and first full-term pregnancy. (iv) The protective effect conferred by a history of full-term pregnancy was significant only in women with a putative low-risk genotype of Aurora-A. Our study provides new findings supporting the mutator role of Aurora-A in breast cancer development, suggesting that breast cancer could be driven by genomic instability associated with variant Aurora-A, the tumorigenic contribution of which could be enhanced as a result of increased mitosis due to estrogen exposure.
Microvascular and Macrovascular Complications of Diabetes (2008)

Diabetes is a group of chronic diseases characterized by hyperglycemia. Modern medical care uses a vast array of lifestyle and pharmaceutical interventions aimed at preventing and controlling hyperglycemia. In addition to ensuring the adequate delivery of glucose to the tissues of the body, treatment of diabetes attempts to decrease the likelihood that the tissues of the body are harmed by hyperglycemia.

The importance of protecting the body from hyperglycemia cannot be overstated; the direct and indirect effects on the human vascular tree are the major source of morbidity and mortality in both type 1 and type 2 diabetes. Generally, the injurious effects of hyperglycemia are separated into macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke) and microvascular complications (diabetic nephropathy, neuropathy, and retinopathy). It is important for physicians to understand the relationship between diabetes and vascular disease because the prevalence of diabetes continues to increase in the United States, and the clinical armamentarium for primary and secondary prevention of these complications is also expanding.

### Diabetic retinopathy

Diabetic retinopathy may be the most common microvascular complication of diabetes. It is responsible for ∼ 10,000 new cases of blindness every year in the United States alone.1 The risk of developing diabetic retinopathy or other microvascular complications of diabetes depends on both the duration and the severity of hyperglycemia. Development of diabetic retinopathy in patients with type 2 diabetes was found to be related to both severity of hyperglycemia and presence of hypertension in the U.K. Prospective Diabetes Study (UKPDS), and most patients with type 1 diabetes develop evidence of retinopathy within 20 years of diagnosis.2,3 Retinopathy may begin to develop as early as 7 years before the diagnosis of diabetes in patients with type 2 diabetes.1 There are several proposed pathological mechanisms by which diabetes may lead …
Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes (2018)

Interleukin-2 (IL-2) is a cytokine required for effector T cell expansion, survival, and function, especially for engineered T cells in adoptive cell immunotherapy, but its pleiotropy leads to simultaneous stimulation and suppression of immune responses as well as systemic toxicity, limiting its therapeutic use. We engineered IL-2 cytokine-receptor orthogonal (<i>ortho</i>) pairs that interact with one another, transmitting native IL-2 signals, but do not interact with their natural cytokine and receptor counterparts. Introduction of <i>ortho</i>IL-2Rβ into T cells enabled the selective cellular targeting of <i>ortho</i>IL-2 to engineered CD4<sup>+</sup> and CD8<sup>+</sup> T cells in vitro and in vivo, with limited off-target effects and negligible toxicity. <i>Ortho</i>IL-2 pairs were efficacious in a preclinical mouse cancer model of adoptive cell therapy and may therefore represent a synthetic approach to achieving selective potentiation of engineered cells.
Prediction of the Risk of Myocardial Infarction from Polymorphisms in Candidate Genes (2002)

Determination of the genotypes of the connexin 37, plasminogen-activator inhibitor type 1, and stromelysin-1 genes may prove reliable in predicting the genetic risk of myocardial infarction and might thus contribute to the primary prevention of this condition.
Transactivator of transcription–tagged cell cycle and apoptosis regulatory protein-1 peptides suppress the growth of human breast cancer cells in vitro and in vivo (2007)

Abstract Deregulated signaling by the epidermal growth factor receptor family of proteins is encountered in human malignancies including breast cancer. Cell cycle and apoptosis-regulatory protein-1 (CARP-1), a novel, perinuclear phosphoprotein, is a regulator of apoptosis signaling by epidermal growth factor receptors. CARP-1 expression is diminished in human breast cancers, and correlates inversely with human breast cancer grades which could be attributed to increased methylation. The expression of CARP-1, on the other hand, interferes with the ability of human breast cancer cells to invade through the matrigel-coated membranes, to form colonies in the soft agar, and to grow as s.c. tumors in severe combined immunodeficiency (SCID) mice. To test whether CARP-1 is a suppressor of human breast cancer growth, we generated transactivator of transcription (TAT)–tagged CARP-1 peptides. Treatment of human breast cancer cells with affinity purified, TAT-CARP-1 1–198, 197–454, and 896–1150 peptides caused inhibition of human breast cancer cell proliferation and elevated apoptosis. In contrast, TAT-tagged enhanced green fluorescent protein or CARP-1 (1–198Y192/F) peptide failed to inhibit cell proliferation or induce apoptosis. Apoptosis by CARP-1 peptides, with the exception of CARP-1 (1–198Y192/F), involves the activation of p38 stress-activated protein kinase and caspase-9. Moreover, administration of TAT-CARP-1 (1–198), but not TAT-tagged enhanced green fluorescent protein or TAT-CARP-1 (1–198Y192/F), inhibits growth of human breast cancer cell–derived tumor xenografts in SCID mice. We conclude that CARP-1 is a suppressor of human breast cancer growth, and its expression is diminished in tumors, in part, by methylation-dependent silencing. [Mol Cancer Ther 2007;6(5):1661–72]
Synthesis and Photopolymerization of Thiol‐Modified Triazine‐Based Monomers and Oligomers for the Use in Thiol‐Ene‐Based Dental Composites (2014)

Thiol‐ene photopolymerizations combine the unique features of step‐growth reactions and photoinitiated polymerizations, so that they experience a growing interest for applications such as coatings or dental restoratives. Most studies have making use of a relatively flexible ester and the hydrolytically labile derivative pentaerythritoltetra(3‐mercaptopropionate) ( PETMP ) as the thiol component in common. In this study, the performance of hydrolytically stable 1,3,5‐tris(3‐mercaptopropyl)‐1,3,5‐triazine‐2,4,6‐trione ( 4a ), 1,3,5‐tris(2‐methyl‐3‐mercapto‐propyl)‐1,3,5‐triazine‐2,4,6‐trione ( 4b ), and oligomers thereof in thiol‐ene photopolymerizations is investigated. The oligomers are prepared via thiol‐Michael or thiol‐isocyanate additions by using 4a and suitable diacrylates or diisocyanates containing a rigid core structure. Compared with PETMP , the thiol derivative 4a shows better flexural strength and modulus of elasticity in thiol‐ene photopolymerizations with 1,3,5‐triallyl‐1,3,5‐triazine‐2,4,6‐trione ( TATATO ) as the‐ene derivative. This phenomenon becomes especially evident after storage in water at 37 °C for 24 h. Furthermore, the performance regarding the flexural strength, the Young's modulus of elasticity, the polymerization shrinkage stress of 4a , and the polyadducts thereof in dental filling composites is evaluated and discussed. image
A Fully Digital 8$\,\times\,$16 SiPM Array for PET Applications With Per-Pixel TDCs and Real-Time Energy Output (2013)

An 8 × 16 pixel array based on CMOS small-area silicon photomultipliers (mini-SiPMs) detectors for PET applications is reported. Each pixel is 570 × 610 μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> in size and contains four digital mini-SiPMs, for a total of 720 SPADs, resulting in a full chip fill-factor of 35.7%. For each gamma detection, the pixel provides the total detected energy and a timestamp, obtained through two 7-b counters and two 12-b 64-ps TDCs. An adder tree overlaid on top of the pixel array sums the sensor total counts at up to 100 Msamples/s, which are then used for detecting the asynchronous gamma events on-chip, while also being output in real-time. Characterization of gamma detection performance with an 3 × 3 × 5 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> LYSO scintillator at 20°C is reported, showing a 511-keV gamma energy resolution of 10.9% and a coincidence timing resolution of 399 ps.
MEMS for Watches (2004)

In order to make new mechanical watch movements possible as well as adding new functions to wristwatches, MEMS, W-LIGA, and silicon micromachining have become indispensable technologies in the watch industries. Examples presented here are deep reactive ion etching (DRIE) of silicon gears, SU-8 based UV-LIGA and MEMS based pressure and magnetic sensors. This article provides a brief overview of some recent commercialized technologies in Switzerland.
High frequency of point mutations clustered within the adenosine triphosphate–binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance (2002)

Point mutations were found in the adenosine triphosphate (ATP) binding region of BCR/ABL in 12 of 18 patients with chronic myeloid leukemia (CML) or Ph-positive acute lymphoblastic leukemia (Ph(+) ALL) and imatinib resistance (defined as loss of established hematologic response), but they were found in only 1 of 10 patients with CML with imatinib refractoriness (failure to achieve cytogenetic response). In 10 of 10 patients for whom samples were available, the mutation was not detected before the initiation of imatinib therapy. Three mutations (T315I, Y253H, and F317L present in 3, 1, and 1 patients, respectively) have a predicted role in abrogating imatinib binding to BCR/ABL, whereas 3 other mutations (E255K, G250E, and M351T, present in 4, 2, and 2 patients, respectively) do not. Thus we confirm a high frequency of mutations clustered within the ATP-binding region of BCR/ABL in resistant patients. Screening may allow intervention before relapse by identifying emerging mutations with defined impacts on imatinib binding. Certain mutations may respond to higher doses of imatinib, whereas other mutations may mandate switching to another therapeutic strategy.