gebhart/patrepeval huggingface dataset:
Inhibition of Calcium Oxalate Monohydrate Crystal Growth in High and Low Ionic Strength Solutions (1998)

The effect of additives on the kinetics of growth of calcium oxalate monohydrate crystals has been studied. Conductivity and potentiometry measurements have been compared. Growth rates were calculated from precipitate curves by a cubic spline method. An approach consisting on the calculation of rate constants and orders of reaction from logarithmic plots of growth rate versus supersaturation has been followed to study crystal growth kinetics. This method revealed that the presence of additives is causing not only a decrease on the rate constant but an increase on the order of reaction as well. The effect of additives (EDTA, citrate and phytate) was considerably weaker in high ionic strength media. Phytate produced a complete blockage of crystal growth in concentrations as low as 2 × 10—6 mole/L in both methods.
Type 1 Parathyroid Hormone Receptor Expression Level Modulates Renal Tone and Plasma Renin Activity in Spontaneously Hypertensive Rat (2002)

These studies examine whether PTHrP(1-36), a vasodilator, modulates BP and renal vascular resistance (RVR) in spontaneously hypertensive rat (SHR). Within the kidney of normotensive rats, PTHrP(1-36) was enriched in vessels. In vessels of SHR, PTHrP was upregulated by 40% and type 1 PTH receptor (PTH1R) was downregulated by 65% compared with normotensive rats. To investigate the role of endogenous PTHrP in the regulation of BP and RVR, SHR were subjected to somatic human (h)PTH1R gene delivery. Three weeks after a single intravenous injection of pcDNA1.1 plasmid containing the hPTH1R gene under the control of the cytomegalovirus promoter, hPTH1R mRNA was detected in all of the main organs. Within the kidney, the transgene was enriched in vessels. In the isolated perfused kidney, RVR was reduced by 23% and PTHrP(1-36)-induced vasodilation, which is depressed in SHR, was restored and a vasoconstrictory response to PTH(3-34), a PTH1R antagonist, was revealed. These effects were not observed in control SHR treated with empty plasmid. BP remained unchanged, and plasma renin activity increased by 60%. Thus, in SHR renal vessels, a reduced number of PTH1R contributes to the high RVR, despite the higher expression of vasodilatory PTHrP. Moreover, these studies provide evidence for a direct link between the density of PTH1R and plasma renin activity, which might be responsible for the absence of effect of PTH1R gene delivery on BP in SHR. Overall, PTHrP significantly contributes to the homeostasis of renal and systemic hemodynamics in SHR.
Natural Genetic Competence in Bacillus subtilis Natto OK2 (2000)

ABSTRACT We isolated a Bacillus subtilis natto strain, designated OK2, from a lot of commercial fermented soybean natto and studied its ability to undergo natural competence development using a comG-lacZ fusion at the amyE locus. Although transcription of the late competence genes was not detected in the B. subtilis natto strain OK2 during competence development, these genes were constitutively transcribed in the OK2 strain carrying either the mecA or the clpC mutation derived from B. subtilis 168. In addition, both OK2 mutants exhibited high transformation frequencies, comparable with that observed for B. subtilis 168. Moreover, as expected from these results, overproduction of ComK derived from strain 168 in strain OK2 resulted in a high transformation frequency as well as in induction of the late competence genes. These results clearly indicated that ComK produced in both the mecA and clpC mutants of strain OK2 (ComK OK2 ) could activate the transcription of the whole set of late competence genes and suggested that ComK OK2 was not activated in strain OK2 during competence development. We therefore sequenced the comS gene of OK2 and compared it with that of 168. The comS OK2 had a single-base change, resulting in the replacement of Ser (strain 168) by Cys (strain OK2) at position 11.
350-OR: The Oral Disposition Index (ODI) Predicts Type 1 Diabetes (T1D) in Autoantibody-Positive (Ab+) Individuals (2022)

The ODI is a measure of β-cell function accounting for insulin sensitivity. ODI has primarily been studied in adults and shown to be inversely predictive of type 2 diabetes (T2D) ; however, little is known about ODI’s prediction of T1D. We thus used data from Ab+ Trialnet Pathway to Prevention (PTP) and Diabetes Prevention Trial Type 1 (DPT-1) cohorts (relatives of T1D patients) to study this. Data were analyzed from 33PTP participants: age (mean±SD) 15.8±12.1 yrs; BMI 21.1±13.1 kg/m2; 50.1% female, and 2from DPT-1: age 14.8±10.0 yrs; BMI 21.8±6.1 kg/m2; 51.2% female. Insulin measures at baseline included insulin sensitivity [ (1/Fasting Insulin) ; 1/FI) ], β-cell function [C-peptide index: (30 min C-pep-0 min C-pep) / (30 min glucose-0 min glucose) ], and ODI [ (1/FI) x (C-peptide Index) ]. Spearman correlations of C-peptide Index vs. 1/FI were r=-0.47 (p&amp;lt;0.001) in PTP, and r=-0.22 (p=0.001) in DPT-1. The figure shows cumulative incidence curves according to ODI quartiles (Q) for progression to T1D in both PTP and DPT-1. The diagnosis of T1D was inversely related to ODI, with Q4 vs. Q1 hazard ratios and 95% CIs of [0.13 (0.10, 0.16) , p=0.006] for PTP and of [0.13 (0.06, 0.29) , p=0.002] for DPT-1. In conclusion, ODI is inversely predictive of T1D among Ab+ individuals. Thus, as with predicting T2D, insulin sensitivity should be taken into account when β-cell function is used to predict T1D in Ab+ populations. Disclosure H.M.Ismail: n/a. D.D.Cuthbertson: None. M.J.Redondo: Advisory Panel; Provention Bio, Inc. L.M.Jacobsen: None. M.A.Atkinson: None. J.Sosenko: None. Diabetes prevention trial type 1: n/a. Type 1 diabetes trialnet: n/a. Funding NIH
EFFECTS OF CALCIUM SUPPLEMENTATION ON BONE MINERAL DENSITY (BMD) IN PREMENOPAUSAL WOMEN RUNNERS (1992)

Weltman, A. FACSM; Snead, D. B.; Weltman, J. Y.; Evans, W. S.; Teates, C. D.; Veldhuls, J. D.; Rogol, A. D. FACSM Author Information
Design, Synthesis, and Biological Evaluation of a Novel VEGFR-2 Inhibitor Based on a 1,2,5-Oxadiazole-2-Oxide Scaffold with MAPK Signaling Pathway Inhibition (2022)

Over the past few decades, the development of broad-spectrum anticancer agents with anti-angiogenic activity has witnessed considerable progress. In this study, a new series of pyrazolo[3,4-d]pyrimidines based on a phenylfuroxan scaffold were designed, synthesized, and evaluated, in terms of their anticancer activities. NCI-60 cell one-dose screening revealed that compounds 12a–c and 14a had the best MGI%, among the tested compounds. The target fluorinated compound 12b, as the most active one, showed better anticancer activity compared to the reference drug sorafenib, with IC50 values of 11.5, 11.6, and 13 µM against the HepG-2, A2780CP, and MDA-MB-231 cell lines, respectively. Furthermore, compound 12b (IC50 = 0.092 µM) had VEGFR-2-inhibitory activity comparable to that of the standard inhibitor sorafenib (IC50 = 0.049 µM). Furthermore, the ability of compound 12b in modulating MAPK signaling pathways was investigated. It was found to decrease the level of total ERK and its phosphorylated form, as well as leading to the down-regulation of metalloproteinase MMP-9 and the over-expression of p21 and p27, thus leading to subG1 cell-cycle arrest and, thus, the induction of apoptosis. Additionally, compound 12b decreased the rate of wound healing in the absence of serum, in comparison to DMSO-treated cells, providing a significant impact on metastasis inhibition. The quantitative RT-PCR results for E-cadherin and N-cadherin showed lower expression of the neuronal N-cadherin and increased expression of epithelial E-cadherin, indicating the ability of 12b to suppress metastasis. Furthermore, 12b-treated HepG2 cells expressed a low level of anti-apoptotic BCL-2 and over-expressed proapoptotic Bax genes, respectively. Using the DAF-FM DA fluorescence probe, compound 12b produced NO intracellularly as efficiently as the reference drug JS-K. In silico molecular docking studies showed a structural similarity through an overlay of 12b with sorafenib. Interestingly, the drug-likeness properties of compound 12b met the expectations of Pfizer’s rule for the design of new drug candidates. Therefore, this study presents a novel anticancer lead compound that is worthy of further investigation and activity improvement.
Hybrid exceptional point and its dynamical encircling in a two-state system (2018)

Hybrid exceptional points (HEPs) are non-Hermitian degeneracies that exhibit different dispersion relations (e.g., linear or square-root) along different directions in the parameter space. Here, we show that a two-state system consisting of coupled ferromagnetic waveguides applied with a bias magnetic field can support the presence of a HEP. A configuration is designed to dynamically encircle the HEP, showing a nonchiral behavior due to the unique topological structure of energy surfaces around the HEP. This is in contrast to the chiral dynamics found when an exceptional point is encircled dynamically. We performed numerical simulations and microwave experiments to demonstrate the topological transition enabled by the HEP in the proposed system.
Electronic discharge summaries. (2005)

Timely completion of Discharge Summaries is a requirement of high quality care. We developed a system for writing electronic Discharge Summaries. DSUM Writer has generated 2464 of 7349 total summaries (34%) and has paid for itself during its first 8 weeks in production. DSUM Writer is a component of a suite of tools (eNote) for electronic physician documentation used to support clinical care, billing and narrative analysis research.
Enantioselective recognition of amino acids by chiral peptido-calix[4]arenes and thiacalix[4]arene (2009)

International audience
Validation of SleepMinder as non-contact device for sleep-disordered breathing and periodic limb movement (2015)

<b>Background:</b> Recent studies found that the non-contact type IV screening device SleepMinder (ResMed Sensor Technologies, Dublin, Ireland) detects sleep-disordered breathing (SDB) with high diagnostic accuracy in cohorts suspected of obstructive sleep apnoea (OSA). However, it was reported that in patients with periodic limb movement (PLM) Sleepminder overestimates the apnoea-hypopnoea index (AHI). <b>Aims and objectives:</b> We aimed to overcome this limitation by introducing the novel sleep disorder index (SDI) which is the sum of the AHI and the period limb movement index (PLMI). This study tested the hypothesis whether using the SDI is associated with high diagnostic accuracy for detecting SDB and/or PLM. <b>Methods:</b> Between January 2011 and December 2013 we studied a mixed cohort of 57 patients (31 OSA, 19 PLM). The easy-to-use device SleepMinder emits a very low electromagnetic radiation and detects body movement by measuring the Doppler effect. We interpreted the device-generated movement index as the SDI and validated the diagnostic accuracy against simultaneous application of PSG. <b>Results:</b> The SDI of SleepMinder correlated well with the sum of AHI and PLMI derived from PSG (r=0.79, p=0.01). For PSG-SDI cut-off ≥15/h, sensitivity was 92.2% and specificity was 95.8%. We found a positive predictive value of 97.2% and a negative predictive value of 95.8%. Positive likelihood ratio was 23.3 and negative likelihood ratio was 0.03. <b>Conclusions:</b> The non-contact type IV screening device SleepMinder detects accurately the combination of the sleep disorders SDB and/or PLM. Thus, this easy-to-use method provides a high pre-test probability for further specific, diagnostic testing.
Data from The ERBB4/HER4 Intracellular Domain 4ICD Is a BH3-Only Protein Promoting Apoptosis of Breast Cancer Cells (2023)

&lt;div&gt;Abstract&lt;p&gt;ERBB4/HER4 (referred to here as ERBB4) is a unique member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. In contrast to the other three members of the EGFR family (i.e., EGFR, ERBB2/HER2/NEU, and ERBB3), which are associated with aggressive forms of human cancers, ERBB4 expression seems to be selectively lost in tumors with aggressive phenotypes. Consistent with this observation, we show that ERBB4 induces apoptosis when reintroduced into breast cancer cell lines or when endogenous ERBB4 is activated by a ligand. We further show that ligand activation and subsequent proteolytic processing of endogenous ERBB4 results in mitochondrial accumulation of the ERBB4 intracellular domain (4ICD) and cytochrome &lt;i&gt;c&lt;/i&gt; efflux, the essential and committed step of mitochondrial regulated apoptosis. Our results indicate that 4ICD is functionally similar to BH3-only proteins, proapoptotic members of the BCL-2 family required for initiation of mitochondrial dysfunction through activation of the proapoptotic multi-BH domain proteins BAX/BAK. Similar to other BH3-only proteins, 4ICD cell-killing activity requires an intact BH3 domain and 4ICD interaction with the antiapoptotic protein BCL-2, suppressed 4ICD-induced apoptosis. Unique among BH3-only proteins, however, is the essential requirement of BAK but not BAX to transmit the 4ICD apoptotic signal. Clinically, cytosolic but not membrane ERBB4/4ICD expression in primary human breast tumors was associated with tumor apoptosis, providing a mechanistic explanation for the loss of ERBB4 expression during tumor progression. Thus, we propose that ligand-induced mitochondrial accumulation of 4ICD represents a unique mechanism of action for transmembrane receptors, directly coupling a cell surface signal to the tumor cell mitochondrial apoptotic pathway. (Cancer Res 2006; 66(12): 6412-20)&lt;/p&gt;&lt;/div&gt;
Energy Management Policies for Harvesting-Based Wireless Sensor Devices with Battery Degradation (2013)

Energy Harvesting Wireless Sensor Devices are increasingly being considered for deployment in sensor networks, due to their demonstrated advantages of prolonged lifetime and autonomous operation. However, irreversible degradation mechanisms jeopardize battery lifetime, calling for intelligent management policies, which minimize the impact of these phenomena while guaranteeing a minimum Quality of Service (QoS). This paper explores a mathematical characterization of these devices, focusing on the interplay between the battery discharge policy and the irreversible degradation of the storage capacity. We propose a stochastic Markov chain framework, suitable for policy optimization, which captures the degradation status of the battery. We present a general result of Markov chains, which exploits the timescale separation between the communication time-slot of the device and the battery degradation process, and enables an efficient optimization. We show that this model fits well the behavior of real batteries for what concerns their storage capacity degradation over time. We demonstrate that a degradation-aware policy significantly improves the lifetime of the sensor compared to "greedy" policies, while guaranteeing the minimum required QoS. Finally, a simple heuristic policy, which never discharges the battery below a given threshold, is shown to achieve near-optimal performance in terms of battery lifetime.
The processing, characterization, and properties of fly ash based geopolymer concrete (2012)

Abstract. In recent years, attempts to increase the utilization of fly ash as a replacement for ordinary Portland cement (OPC) in concrete have increased in significance. Geopolymer concrete does not need the presence of Portland cement as a binder. Instead, an activating geopolymer can be utilized with an alkaline activator. Moreover, the use of fly ash is more environmentally friendly due to the reduced CO2 emissions and costs compared to OPC, which requires the burning of large quantities of fuel and the decomposition of limestone and can result in significant CO2 emissions. The compressive strength increases with the optimum NaOH molarity, fly ash/ alkaline activator ratio, Na2SiO3/NaOH ratio used, and curing process handled. Fly ash-based geopolymer also provides superior performance givens its better resistance to aggressive environments compared to normal concrete. This paper summarizes the current knowledge about the properties and characteristics of fly ash-based geopolymer by reviewing previous research work. 1.
SMAD1 Deficiency in Either Endothelial or Smooth Muscle Cells Can Predispose Mice to Pulmonary Hypertension (2013)

A deficiency in bone morphogenetic protein receptor type 2 (BMPR2) signaling is a central contributor in the pathogenesis of pulmonary arterial hypertension (PAH). We have recently shown that endothelial-specific Bmpr2 deletion by a novel L1Cre line resulted in pulmonary hypertension. SMAD1 is one of the canonical signal transducers of the BMPR2 pathway, and its reduced activity has been shown to be associated with PAH. To determine whether SMAD1 is an important downstream mediator of BMPR2 signaling in the pathogenesis of PAH, we analyzed pulmonary hypertension phenotypes in Smad1-conditional knockout mice by deleting the Smad1 gene either in endothelial cells or in smooth muscle cells using L1Cre or Tagln-Cre mouse lines, respectively. A significant number of the L1Cre(+);Smad1 (14/35) and Tagln-Cre(+);Smad1 (4/33) mutant mice showed elevated pulmonary pressure, right ventricular hypertrophy, and a thickening of pulmonary arterioles. A pulmonary endothelial cell line in which the Bmpr2 gene deletion can be induced by 4-hydroxy tamoxifen was established. SMAD1 phosphorylation in Bmpr2-deficient cells was markedly reduced by BMP4 but unaffected by BMP7. The sensitivity of SMAD2 phosphorylation by transforming growth factor-β1 was enhanced in the Bmpr2-deficient cells, and the inhibitory effect of transforming growth factor-β1-mediated SMAD2 phosphorylation by BMP4 was impaired in the Bmpr2-deficient cells. Furthermore, transcript levels of several known transforming growth factor-β downstream genes implicated in pulmonary hypertension were elevated in the Bmpr2-deficient cells. Taken together, these data suggest that SMAD1 is a critical mediator of BMPR2 signaling pertinent to PAH, and that an impaired balance between BMP4 and transforming growth factor-β1 may account for the pathogenesis of PAH.
The GIST paradigm: lessons for other kinase‐driven cancers (2010)

Gastrointestinal stromal tumour (GIST) is the most common sarcoma of the intestinal tract, known to be notoriously refractory to conventional chemotherapy or radiation. It is an ideal solid tumour model to apply our understanding from aberrant signal transduction to drug development, since nearly all tumours have a mutation in the KIT or, less often, the PDGFRA or BRAF genes. The constitutively activated KIT and PDGFRA oncoproteins serve as crucial diagnostic and therapeutic targets. The discovery of oncogenic KIT activation as a central mechanism of GIST pathogenesis suggested that inhibiting or blocking KIT signalling might be the milestone in the targeted therapy of GISTs. Indeed, imatinib mesylate inhibits KIT kinase activity and represents the front-line drug for the treatment of unresectable and advanced GISTs, achieving a partial response or stable disease in about 80% of patients with metastatic GIST. KIT mutation status has a significant impact on treatment response, emerging in recent years as a leading paradigm for genotype-driven targeted therapy. In this review, parallels with other models in oncology that share their addiction to a particular mutationally activated kinase are contrasted. A better understanding of oncogene addiction as a common theme across tumours of diverse histologies underlies the clinical success of targeting such kinases with several selective kinase inhibitors. Also remarkable is the similarity displayed in the mechanisms of drug failure after a successful but temporary clinical response to kinase inhibition. Reactivation of the same oncogenic kinase, often by acquisition of second site mutations, is another emerging paradigm of secondary resistance in these tumour models. The complexity of polyclonal resistance in imatinib-resistant patients argues that single next-generation kinase inhibitors will not be beneficial in all mutant clones. Other broad therapeutic strategies could include combination of kinase inhibitors with targeting KIT downstream targets, such as PI3-K or MAPK/MEK inhibitors.
Response, Survival, and Long-Term Toxicity After Therapy With the Radiolabeled Somatostatin Analogue [90Y-DOTA]-TOC in Metastasized Neuroendocrine Cancers (2011)

This study documents the long-term outcome of [(90)Y-DOTA]-TOC treatment in a large cohort. Response to [(90)Y-DOTA]-TOC is associated with longer survival. Somatostatin receptor imaging is predictive for both survival after [(90)Y-DOTA]-TOC treatment and occurrence of renal toxicity.
Gender dependence of normal myocardial perfusion distributions using the XACT imaging system (2010)

1741 Objectives A new solid-state SPECT imaging system employing a respiratory motion matched, ultra-low dose CT-based attenuation correction (AC) has shown improved radiotracer uniformity in the normal myocardium compared to uncorrected (NC) reconstructions. The purpose of this study was to investigate the differences in the radiotracer distribution in normal myocardium as a function of gender with and without AC. Methods We evaluated 70 randomly selected patients (35M, 35F) with a pre-test likelihood of Results NC gender databases were significantly different in 4 of 9 segments (basal and distal anterior, p Conclusions XACT AC distributions in males and females approach equivalence in this pilot population. Further evaluation with a larger population will more clearly define the significance of these findings with the expectation that gender independence with XACT AC is achievable
Myeloid-Derived Suppressor Cells Are Involved in Lysosomal Acid Lipase Deficiency–Induced Endothelial Cell Dysfunctions (2014)

The underlying mechanisms that lysosomal acid lipase (LAL) deficiency causes infiltration of myeloid-derived suppressor cells (MDSCs) in multiple organs and subsequent inflammation remain incompletely understood. Endothelial cells (ECs), lining the inner layer of blood vessels, constitute barriers regulating leukocytes transmigration to the site of inflammation. Therefore, we hypothesized that ECs are dysfunctional in LAL-deficient (lal(-/-)) mice. We found that Ly6G(+) cells transmigrated more efficiently across lal(-/-) ECs than wild-type (lal(+/+)) ECs, which were associated with increased levels of PECAM-1 and MCP-1 in lal(-/-) ECs. In addition, lal(-/-) ECs showed enhanced migration and proliferation, decreased apoptosis, but impaired tube formation and angiogenesis. lal(-/-) ECs also suppressed T cell proliferation in vitro. Interestingly, lal(-/-) Ly6G(+) cells promoted in vivo angiogenesis (including a tumor model), EC tube formation, and proliferation. Finally, the mammalian target of rapamycin (mTOR) pathway was activated in lal(-/-) ECs, and inhibition of mTOR reversed EC dysfunctions, including decreasing Ly6G(+) cell transmigration, delaying migration, and relieving suppression of T cell proliferation, which was mediated by decreasing production of reactive oxygen species. Our results indicate that LAL regulates EC functions through interaction with MDSCs and modulation of the mTOR pathway, which may provide a mechanistic basis for targeting MDSCs or mTOR to rejuvenate EC functions in LAL deficiency-related diseases.