gebhart/patrepeval huggingface dataset:
A Web Tool for Generating High Quality Machine-readable Biological Pathways (2017)

PathWhiz is a web server built to facilitate the creation of colorful, interactive, visually pleasing pathway diagrams that are rich in biological information. The pathways generated by this online application are machine-readable and fully compatible with essentially all web-browsers and computer operating systems. It uses a specially developed, web-enabled pathway drawing interface that permits the selection and placement of different combinations of pre-drawn biological or biochemical entities to depict reactions, interactions, transport processes and binding events. This palette of entities consists of chemical compounds, proteins, nucleic acids, cellular membranes, subcellular structures, tissues, and organs. All of the visual elements in it can be interactively adjusted and customized. Furthermore, because this tool is a web server, all pathways and pathway elements are publicly accessible. This kind of pathway "crowd sourcing" means that PathWhiz already contains a large and rapidly growing collection of previously drawn pathways and pathway elements. Here we describe a protocol for the quick and easy creation of new pathways and the alteration of existing pathways. To further facilitate pathway editing and creation, the tool contains replication and propagation functions. The replication function allows existing pathways to be used as templates to create or edit new pathways. The propagation function allows one to take an existing pathway and automatically propagate it across different species. Pathways created with this tool can be "re-styled" into different formats (KEGG-like or text-book like), colored with different backgrounds, exported to BioPAX, SBGN-ML, SBML, or PWML data exchange formats, and downloaded as PNG or SVG images. The pathways can easily be incorporated into online databases, integrated into presentations, posters or publications, or used exclusively for online visualization and exploration. This protocol has been successfully applied to generate over 2,000 pathway diagrams, which are now found in many online databases including HMDB, DrugBank, SMPDB, and ECMDB.
IL-2 augments the therapeutic efficacy of adoptively transferred B cells which directly kill tumor cells via the CXCR4/CXCL12 and perforin pathways (2016)

We previously reported that antitumor B cells directly kill tumor cells via the Fas/FasL pathway and are regulated by IL-10. In this study, we defined additional mechanisms involved in B cell antitumor immunity. Administration of IL-2 significantly augmented the therapeutic efficacy of adoptively transferred tumor-draining lymph node (TDLN) B cells which express IL- 2R. Culture supernatant of purified B splenocytes harvested from the mice that received adoptive transfer of 4T1 TDLN B cells plus IL-2 administration produced larger amounts of IgG which bound to 4T1, resulting in 4T1 lysis. Furthermore, we detected CXCR4 expression on 4T1 TDLN B cells, and 4T1 tumor cells produced its ligand CXCL12. Transwell experiments demonstrated the chemoattraction of CXCR4-expressing 4T1 TDLN B cells towards CXCL12- producing 4T1 cells. Blockade of CXCR4 using a CXCR4-specific inhibitor, AMD3100, significantly reduced the killing of 4T1 tumor cells by 4T1 TDLN B cells. Blockade of FasL and CXCR4 concurrently inhibited B cell-mediated direct killing of tumor cells in an additive manner, indicating that both Fas/FasL and CXCL12/CXCR4 pathways are involved in the direct killing of 4T1 cells by 4T1 TDLN B cells. TDLN B cells produced perforin. Additional transwell experiments showed that effector B cells could directly kill tumor cells in cell-cell contact via the Fas/FasL and CXCR4/CXCL12 pathways as well as perforin, while without cell contact, perforin secreted by B cells led to tumor cell cytotoxicity. These findings underscore the diversity of function by which B cells can play an important role in the host immune response to tumor.
Manipulation of Pancreatic Stem Cells for Cell Replacement Therapy (2000)

The demonstration of the existence of tissue-specific adult stem cells has had a great impact on our understanding of stem cell biology and its application in clinical medicine. Their existence has revolutionized the implications for the treatment of many degenerative diseases characterized by either the loss or malfunction of discrete cell types. However, successful exploitation of this opportunity requires that we have sufficient know-how of stem cell manipulation. Because stem cells are the founders of virtually all tissues during embryonic development, we believe that understanding the cellular and molecular mechanisms of embryogenesis and organogenesis will ultimately serve as a platform to identify factors and conditions that regulate stem cell behavior. Discovery of stem cell regulatory factors will create potential pharmaceutical opportunities for treatment of degenerative diseases, as well as providing critical knowledge of the processes by which stem cells can be expanded in vitro, differentiated, and matured into desired functional cells for implantation into humans. A well-characterized example of this is the hematopoietic system where the discovery of erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF), which regulate hematopoietic progenitor cell behavior, have provided significant clinical success in disease treatment as well as providing important insights into hematopoiesis. In contrast, little is known about the identity of pancreatic stem cells, the focus of this review. Recent reports of the potential existence of pancreatic stem cells and their utility in rescuing the diabetic state now raise the same possibilities of generating insulin-producing beta cells as well as other cell types of the pancreatic islet from a stem cell. In this review, we will focus on the potential of these new developments and how our understanding of pancreas development can help design strategies and approaches by which a cell replacement therapy can be implemented for the treatment of insulin-dependent diabetes which is manifested by the loss of beta cells in the pancreas.
Wear mechanisms of PcBN tools when machining AISI 316L (2021)

This paper investigates the machinability of AISI 316L stainless steel without and with NMI treatment, when machined with three different PcBN tool grades: low cBN content (50% vol.), medium (65% vol.) and high (90% vol.). The NMI treatment consisted of resulfurized and Ca-treated steels with two different Si/Al ratio. The tool materials were evaluated in terms of tool life, showing the best performance for the medium cBN content grade. Results showed that the crater wear has a more significant effect on the tool performance than the standard wear criteria of maximum flank wear. The worn tools were examined using scanning electron microscopy (SEM), focused ion beam (FIB) and transmission electron microscopy (TEM). In most cases, the crater exhibited three distinct regions from the edge to the end of the contact zone: the plateau, middle crater, and the upper region. Plateau and crater region displayed tool protective layer (TPL), consisting mostly of Al, Si, Mg and Ca-oxides; and some dimples in the tool from preferential wear of cBN grains. In the upper region of the best performing material, a ~1.5 μm thick TPL of mostly MnCr2O4 spinel was found, a result of the transfer of Mn- and Cr-rich oxide NMIs found in this material or oxidation of workpiece material, during the machining process.
Cyclin-dependent kinase inhibitor p27 as a mediator of the G1-S phase block induced by 1,25-dihydroxyvitamin D3 in HL60 cells. (1996)

Progression of mammalian cells through G1 is controlled by the concerted action of protein kinases, the activities of which are modulated in both positive (cyclins) and negative [cyclin-dependent kinase inhibitors (CDIs)] manners by families of regulatory proteins. In differentiation of leukemia cells, a G1 arrest is a common, if not invariable, occurence and takes place after the appearance of markers of monocytic differentiation in human leukemia HL60 cells treated with 1,25 dihydroxyvitamin D3 (1,25D3) at low to moderately high concentrations (F. Zhang et al., Cell Proliferation 27: 643-654, 1994). In the present study, we investigated the protein levels of several G1 regulatory proteins that are potential mediators of the 1,25D3-induced G1 block. During the first 24 h of exposure to a high concentration (4 x 10(-7) M) of 1,25D3, no increase was noted in the immunodetectable levels of cyclins D1 or E, or CDIs p16Ink4, p21Cip1/Waf1, or p27Kip1, even though monocytic differentiation markers were evident, and a prolongation of G1 was noted. After 48 h of exposure 4 x 10(-7) M to 1,25D3, a G1 to S-phase block progressively increased in parallel with the abundance of the p27Kip1 CDI. A transient increase in p21Cip1/Waf1 was noted only at 48 hr. The increase in p27Kip1 protein level was dependent on the concentration of 1,25D3 and was accompanied by an increase in cyclin D and E proteins, which normally peak in mid-G1 and at the G1 to S-phase transition, respectively. These results indicate that p27Kip1 protein is a strong candidate for the cell cycle regulator that blocks the entry into the S-phase in 1,25D3-treated HL60 cells.
[Evaluation of a newly discovered LDL receptor mutation (exon 10, GAC>AAC, D271N, "FH Graz-1") in familial hypercholesterolemia-- a familystudy]. (1999)

Heterozygous familial hypercholesterolemia (FH, prevalence 1:500) is a major cause of early atherosclerotic disease. Little is known about possible co-factors influencing individual patient's risk. We investigated this question in a large family carrying a new LDL-receptor-mutation. Genetic analysis of all exons of the LDL-receptor gene in the index case using polymerase chain reaction (PCR) and Denaturing Gradient Gel Electrophoresis (DGGE) revealed a previously unknown mutation in exon 10 (GAC > ACC, D471N, "FH Graz-1"). Investigation of 21 family members (15 females, 6 males), aged 17 to 86 years, revealed 9 female and 4 male carriers of the mutation. 7 female carriers aged 17 to 58 years show no clinical signs of macrovascular disease. An 86-year old female patient, who was asymptomatic until 85, recently suffered a transient cerebral ischemic attack. All these females were normotensive. The only hypertensive 76-year old patient (ex-smoker with a history of 15 pack years) suffers from angina pectoris. 2 male carriers of the mutation (32 and 38 years old) are asymptomatic. A 65-year old patient suffers from cardiovascular disease. A 49-year old patient had a coronary artery bypass graft after a myocardial infarction at the age of 37. Additionally he has a history of bilateral thrombendarterectomy of the carotid arteries and suffers from bilateral peripheral artery disease. This patient also carries the apoE-genotype 4/3, which might be responsible for his poor response to stain therapy, and needs extracorporal lipid elimination (LDL-C > 200 mg/dl under drug therapy). Both of his daughters are homozygous for the apoE-allele 3 and and responded well to stain therapy. Genetic analysis in patients with FH assures diagnosis, but is not sufficient to determine the individual patient's risk. A precise clinical examination remains the gold standard for individual risk evaluation.
P3‐279: COGNITION AND LOW VISION: COGEVIS (2018)

Visual impairment, defined as visual acuity of 20/40 or less in the best corrected better seeing-eye, affects over 280 million people worldwide. However, to this day, no cognitive screening test exist to assess neuropsychological function in this population, accounting for the visual deficiency which usually affects classical neuropsychological tests' results. We evaluated the cognitive status of visually impaired patients aged 60 years old and above referred to low vision rehabilitation (LVR) based on a standard comprehensive cognitive battery and a new evaluation tool, named the COGEVIS, conceived to be used in patients with severe visual deficits. Thirty eight individuals, 17 women and 21 men with a mean age of 70.3 +/- 1.3 years and mean visual acuity of 0.12 +/- 0.02, were recruited over a one-year period (Fig 1). Sixty-three percent of participants had normal cognitive status (Table 1). Cognitive impairment was diagnosed in 37.5 % of participants. The COGEVIS score cut-off point to screen for cognitive impairment was 24 (maximum score of 30) with a sensitivity of 66.7% and a specificity of 95% (Fig 2). Evaluation following 4 months of visual rehabilitation showed an improvement of Instrumental Activities of Daily Living (p=0.004), National Eye Institute Visual Functioning Questionnaire (p=0.035) and Montgomery–Åsberg Depression Rating Scale (p=0.037). Distribution of the participants according to cognitive status (A) or visual status (B). AD: Alzheimer's disease, LBD: Lewy body dementia, MCI: mild cognitive impairment. Receiving operating characteristics (ROC) curve of the COGEVIS to diagnose cognitive impairment. AUC: Area under the curve. A yellow line is drawn at a 45 degree angle tangent to the ROC Curve. This marks a good cutoff point under the assumption that false negatives and false positives have similar costs. In this case, a COGEVIS below 24 yielded a sensitivity of 66.7 % and a specificity of 94.7 %. This study introduces a new short test to screen for cognitive impairment in visually impaired patients.
Nanoscopic-Confinement Effects on Local Dynamics (2000)

The segmental dynamics of 1.5-2.0 nm polymer films confined between parallel solid surfaces is investigated with dielectric spectroscopy in polymer/silicate intercalated nanocomposites. The confinement effect is evident by the observation of a mode, much faster than the bulk-polymer alpha relaxation and exhibiting much weaker temperature dependence. This is discussed in relation to either the interlayer spacing restricting the cooperative volume of the alpha relaxation or to the dominance of the more mobile interphase regions as predicted by simulations; the data qualitatively support the former.
Pulmonary Mycobacterial Infections and TLRs (2012)

Mycobacterium tuberculosis expresses molecular motifs that are potent TLR agonists, targeting especially TLR2, and resulting in rapid activation of cells of the innate immune system. The control of experimental acute M. tuberculosis infection seems rather independent of the presence of TLRs, as is the induction of adaptive immunity to mycobacteria, while long term control of chronic infection might be more TLR dependent. Conversely, some molecules produced by M. tuberculosis can modulate the host innate TLR mediated responses. Control of M. tuberculosis infection depends on a balance between the host recognition of the pathogen and activation of both innate and adaptive immune responses, and immune evasion strategies developed by the bacteria.
NIMG-59. VALIDATION OF QUANTITATIVE VESSEL SIZE IMAGING (VSI) IN HUMAN GLIOMAS USING IMAGE-GUIDED STEREOTACTIC BIOPSIES (2018)

Angiogenesis is critical for brain tumor development and malignant transformation1, influencing both prognosis and response to therapy. The vessel size imaging (VSI) 2 is a quantitative technique that estimates the mean diameter of vessels by using multi-echo spin-and-gradient-echo (SAGE) dynamic susceptibility contrast (DSC) perfusion MRI. In the current study, we compared rCBV and VSI maps to histology-equivalent estimates of vessel density and vessel diameter in high grade glioma patients, using stereotactic image-guided biopsies. A total of 26 image-guided biopsies were obtained in 11 glioma patients (7 grade III and 4 glioblastoma). MRI examinations were acquired prior to surgery on a 3T MRI, including multi-echo SAGE DSC perfusion (2x gradient echo, 1x asymmetric echo, and 1x spin-echo). One to three biopsy targets (5mm radius) were defined and stereotactically biopsied. Relative cerebral blood volume (rCBV) was calculated3 using DSC data from a single gradient echo. VSI was quantified as VSIm= 0.867(ADC.rCBV)^(1/2)((R_2^*)/R_2^(3/2)) where ADC is the apparent diffusion coefficient (mm2/s), R2* and R2 are transverse relaxation rates. Histologically estimates of VSIHisto. were obtained as previously modelized.4 Our results suggest that no differences exist in vessel density and VSI from histology between grade III and IV. Indeed, ADC, rCBV and VSI are similar within targets for those grades. We observed a significant correlation between rCBV and vessel density (r=0.42, p=0.032) but not between rCBV and VSIHisto.. Interestingly, VSIMRI was independent of vessel density but highly correlated with VSIHisto. MR measures of VSI exhibit a strong relationship to histological measures of vessel diameter in high grade glioma and that independently of blood volume and vessel density. References: 1 Digernes et al. JCBFM 2017. DOI: 10.1177/0271678X17694187 2 Kiselev et al. MRM 2005. DOI: 10.1002/mrm.20383 3 Leu et al. JMRI 2016. DOI: 10.1002/jmri.25227 4 Tropres et al. MRI 2004 DOI: 10.1002/mrm.20017
Efficient detection of eye movements in video image sequences (2000)

A system for automatic detection of eye movements in medical applications is presented. It is designed to register exactly the dynamic motions of human eyes. In principle, the system runs independently of specific applications and may be used for different medical diagnoses. The method for motion analysis is applied to video image sequences of the retina recorded by a scanning laser ophthalmoscope (SLO). A modified block-matching algorithm has been developed for tracking the ocular fundus in the SLO sequences. The image processing strategies implemented provide high reliability of the motion detection which is used to process off-line. Several modifications have been developed in order to take into account the video quality of the SLO sequences. Additionally, some improvements have been implemented to increase the speed of the software. The system includes a phase of automatic motion detection followed by a subsequent phase of manual quality control. In this latter phase, an efficient tool for error detection and correction guarantees high quality and security of movement detection, which is of great importance in clinical applications.
Urinary tract infections (1989)

Recent advances have led to a renewed interest in urinary tract infections in females. First, current research has reassessed the previously used definition of infection as a positive culture with ≥ 100,000 colonies per ml. Norden and Kass1 originally defined a positive culture as ≥ 105 colonies per ml because they found a 96% predictability of a third positive culture if the 2 previous cultures were positive. However, their studies primarily involved pregnant women who were asymptomatic at the time of culture and were not known to be at high risk for recurrent disease. Other authors2,3 reported that symptomatic disease is often associated with colony counts of less than 105 colonies per ml. These studies have thus led to reconsideration of the best way to define infection microbiologically. The roles of new pathogens such as Chlamydia trachomatis, herpes simplex virus (HSV), and Staphylococcus saprophytics have also been demonstrated in recent studies.
Supplementary Figure Legends 1-6 from Epigallocatechin-gallate Suppresses Tumorigenesis by Directly Targeting Pin1 (2023)

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Identification of a Potent and Orally Active Non-peptide C5a Receptor Antagonist (2002)

The anaphylatoxin C5a is a potent chemotactic factor for neutrophils and other leukocytes, and functions as an important inflammatory mediator. Through a high capacity screening followed by chemical optimization, we identified a novel non-peptide C5a receptor antagonist, N-[(4-dimethylaminophenyl)methyl]-N-(4-isopropylphenyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-1- carboxamide hydrochloride (W-54011). W-54011 inhibited the binding of (125)I-labeled C5a to human neutrophils with a K(i) value of 2.2 nm. W-54011 also inhibited C5a-induced intracellular Ca(2+) mobilization, chemotaxis, and generation of reactive super oxide species in human neutrophils with IC(50) values of 3.1, 2.7, and 1.6 nm, respectively. In C5a-induced intracellular Ca(2+) mobilization assay with human neutrophils, W-54011 did not show agonistic activity at up to 10 microm and shifted rightward the concentration-response curves to C5a without depressing the maximal responses. Examination on the species specificity of W-54011 revealed that it was able to inhibit C5a-induced intracellular Ca(2+) mobilization in neutrophils of cynomolgus monkeys and gerbils but not mice, rats, guinea pigs, rabbits, and dogs. In gerbils, oral administration of W-54011 (3-30 mg/kg) inhibited C5a-induced neutropenia in a dose-dependent manner. The present report is the first description of an orally active non-peptide C5a receptor antagonist that could contribute to the treatment of inflammatory diseases mediated by C5a.
Body Mass Index and Non-Hodgkin's Lymphoma Survival in an Ethnically Diverse Population: The Multiethnic Cohort Study. (2014)

Introduction:
Obesity increases the risk of death from several malignancies including breast and colon cancer. However, for non-Hodgkin's lymphoma (NHL), the association between pre-diagnostic body mass index (BMI) and survival is unclear. We examined the association between pre-diagnostic BMI overall and NHL-specific survival in the Multiethnic Cohort (MEC) study of African Americans, Native Hawaiians, Japanese Americans, Latinos, and Caucasians.
MECP2 genomic structure and function: insights from ENCODE (2008)

MECP2, a relatively small gene located in the human X chromosome, was initially described with three exons transcribing RNA from which the protein MeCP2 was translated. It is now known to have four exons from which two isoforms are translated; however, there is also evidence of additional functional genomic structures within MECP2, including exons potentially transcribing non-coding RNAs. Accompanying the recognition of a higher level of intricacy within MECP2 has been a recent surge of knowledge about the structure and function of human genes more generally, to the extent that the definition of a gene is being revisited. It is timely now to review the published and novel functional elements within MECP2, which is proving to have a complexity far greater than was previously thought.
An improved PCM heat storage technology utilizing metal foam (2010)

Having a uniform temperature for electronics is part of thermal management in order to avoid hot spots and reduce thermal stresses in electronic systems. In many applications, thermal energy storage is required to receive, store, and subsequently release heat. The major disadvantage of phase change materials (PCMs) is their low thermal conductivities, which drastically slows the phase change process and causes a wide temperature range within PCMs. Metal foams possess thermal conductivities that are an order of magnitude higher than PCMs, and can be imbedded in PCMs. The random internal structure and high porosity of metal foam enhance and accelerate the phase change process without significantly reducing PCMs' heat storage capacity. Unlike traditional PCM systems, the distribution of the foam ligaments in PCMs makes the melting and solidification processes more uniform and less dependent on the location inside PCMs. In this paper, the performance of a PCM combined with aluminum foam storage system is investigated experimentally. Transient temperatures were measured at strategic locations in the PCM-foam matrix to assess the phase change process. The pure PCM was also tested separately to serve as a base case. The results established the significant phase change process enhancements in terms of time and temperature uniformity.