gebhart/patrepeval huggingface dataset:
Exosomes in cancer: small particle, big player (2015)

Exosomes have emerged as a novel mode of intercellular communication. Exosomes can shuttle bioactive molecules including proteins, DNA, mRNA, as well as non-coding RNAs from one cell to another, leading to the exchange of genetic information and reprogramming of the recipient cells. Increasing evidence suggests that tumor cells release excessive amount of exosomes, which may influence tumor initiation, growth, progression, metastasis, and drug resistance. In addition, exosomes transfer message from tumor cells to immune cells and stromal cells, contributing to the escape from immune surveillance and the formation of tumor niche. In this review, we highlight the recent advances in the biology of exosomes as cancer communicasomes. We review the multifaceted roles of exosomes, the small secreted particles, in communicating with other cells within tumor microenvironment. Given that exosomes are cell type specific, stable, and accessible from body fluids, exosomes may provide promising biomarkers for cancer diagnosis and represent new targets for cancer therapy.
Functional significance of renal prostacyclin and thromboxane A2 production in patients with systemic lupus erythematosus. (1985)

We have examined the urinary excretion of stable immunoreactive eicosanoids in 23 female patients with systemic lupus erythematosus (SLE), 16 patients with chronic glomerular disease (CGD), and 20 healthy women. SLE patients had significantly higher urinary thromboxane B2 (TXB2) and prostaglandin (PG) E2 excretion and significantly lower 6-keto-PGF1 alpha than did healthy women. In contrast, CGD patients only differed from controls for having reduced 6-keto-PGF1 alpha excretion. The group of SLE patients with active renal lesions differed significantly from the group with inactive lesions for having a lower creatinine clearance and urinary 6-keto-PGF1 alpha and higher urinary TXB2. Higher urinary TXB2 excretion was associated with comparable platelet TXB2 production in whole blood, undetectable TXB2 in peripheral venous blood, and unchanged urinary excretion of 2,3-dinor-TXB2. A significant inverse correlation was found between urinary TXB2 and creatinine clearance rate (CCr). In contrast, the urinary excretion of 6-keto-PGF1 alpha showed a significant linear correlation with both CCr and para-aminohippurate clearance rate (CPAH). In four SLE and seven CGD patients, inhibition of renal cyclooxygenase activity by ibuprofen was associated with a significant reduction in urinary 6-keto-PGF1 alpha and TXB2 and in both CCr and CPAH. However, the average decrease in both clearances was 50% lower in SLE patients than in CGD patients, when fractionated by the reduction in urinary 6-keto-PGF1 alpha or PGE2 excretion. We conclude that the intrarenal synthesis of PGI2 and TXA2 is specifically altered in SLE. Such biochemical alterations are associated with changes in glomerular hemodynamics and may play a role in the progression of SLE nephropathy.
An eight-channel fiber-optic Bragg grating and stimulated Brillouin sensor system for simultaneous temperature and strain measurements (1999)

An eight channel fiber-optic sensor has been developed to simultaneously measure the strain and temperature independently using fiber Bragg gratings and stimulated Brillouin scattering. The temperature and strain resolution is approximately 1.5/spl deg/C and 20 μ/spl epsiv/, and the spatial resolution for sensing Brillouin scattering is 5 m.
An Apolipoprotein AI Mimetic Peptide:  Membrane Interactions and the Role of Cholesterol, (2004)

The 18-amino acid amphipathic helical peptide Ac-DWFKAFYDKVAEKFKEAF-NH(2) promotes the separation of cholesterol from the phospholipid, resulting in the formation of cholesterol crystallites, even at mole fractions of cholesterol as low as 0.3. The peptide exerts a greater degree of penetration into membranes of pure phosphatidylcholine in the absence of cholesterol than into bilayers of phosphatidylcholine and cholesterol. The circular dichroism spectrum of the peptide in buffer indicates that it self-associates, leading to the formation of structures with higher helical content. However, in the presence of lipid, the peptide remains helical over a larger concentration range. The peptide undergoes a thermal transition on heating. Cholesterol has little effect on the secondary structure of the peptide; however, increased Trp emission intensity in the absence of cholesterol indicates a deeper penetration of the helix upon removal of cholesterol from the membrane. The results with these model systems demonstrate changes in peptide-lipid interactions that may be related to the observed biological properties of this peptide.
In Vitro Determination of Apoptotic Effect of Heparin on Lymphoblasts By Using Flow Cytometric DNA Analysis and Measurements of Caspase-9 Activation and Cytochrome C Level (2011)

Heparin induces apoptosis on peripheral neutrophils, mononuclear cells of the healthy controls, and on lymphoblasts of the patients with acute lymphoblastic leukemia, in vitro. We studied the caspase-9 activity and cytochrome C level as the indicators of the apoptotic effect of heparin on lymphoblasts by the intrinsic pathway of apoptosis. Twenty samples of the patients with acute lymphoblastic leukemia were included in the study. Cytochrome C level and caspase-9 activity were concomitantly determined with the percentage of apoptotic lymphoblasts when incubated in 0, 10, and 20 U/mL heparin concentrations at 0, 1, and 2 hours. The percentages of apoptosis of lymphoblasts at the first hour were higher than those at 0 and 2 hours in 10 and 20 U/mL heparin concentrations, separately (P<0.05). The mean percentage of apoptosis of lymphoblasts in 20 U/mL heparin levels was significantly higher than those in 0 and 10 U/mL heparin levels at 1 and 2 hours (P<0.05). The highest apoptotic effect of heparin on lymphoblasts was determined at the first hour in 20 U/mL heparin concentration. The mean caspase-9 activitity at the first hour was significantly higher than the values at 0 and 2 hours in 10 and 20 U/mL heparin levels, separately (P<0.05). The mean caspase-9 activity in 20 U/mL heparin concentration was significantly higher than values in 0 and 10 U/mL heparin concentrations at 1 and 2 hours (P<0.05). The highest caspase-9 activity was determined in 20 U/mL heparin levels at the first hour. The mean cytochrome C level at the first hour was significantly higher than those at 0 and 2 hours in 10 and 20 U/mL heparin concentrations, separately (P<0.05). The highest cytochrome C level was determined in 20 U/mL heparin concentration at the first hour. We claimed that heparin induces the apoptosis of lymphoblasts by the activation of the intrinsic pathway.
PathMarker: systems for capturing trips (2005)

Central to capturing a trip is knowing where you were, and when you were there. Combining continuous path data with media (path-enhanced media or PEM) offers substantial advantages over the previous approach of tagging individual media with time and location. Prototype systems, collectively called PathMarker, are used for gathering, editing, presenting and browsing PEM. We have developed: (1) a methodology for gathering PEM with off-the-shelf hardware; (2) software for automatic conversion of the raw path data and media into an application independent XML representation; (3) two example PEM applications. The first application provides map-overlaid trip editing, presentation and browsing. The second application provides a 3D immersive environment with digital elevation maps for automatic trip flybys and for browsing. Experience with a number of recorded trips confirms that PathMarker systems seem to capture the essence of a trip.
The Effects of Anesthesia and Hypothermia on Canine Cerebral ATP and Lactate during Anoxia Produced by Decapitation (1970)

ATP and lactate in the canine brain were determined before and during cerebral anoxia induced by decapitation, both at 30 C during halothane anesthesia (0.8 per cent) and at 37 C during four anesthetic circumstances (nitrous oxide, 70 per cent; halothane, 0.8 per cent; halothane, <0.1 per cent; and
A Real-World Perspective on Molecular Design (2016)

We present a series of small molecule drug discovery case studies where computational methods were prospectively employed to impact Roche research projects, with the aim of highlighting those methods that provide real added value. Our brief accounts encompass a broad range of methods and techniques applied to a variety of enzymes and receptors. Most of these are based on judicious application of knowledge about molecular conformations and interactions: filling of lipophilic pockets to gain affinity or selectivity, addition of polar substituents, scaffold hopping, transfer of SAR, conformation analysis, and molecular overlays. A case study of sequence-driven focused screening is presented to illustrate how appropriate preprocessing of information enables effective exploitation of prior knowledge. We conclude that qualitative statements enabling chemists to focus on promising regions of chemical space are often more impactful than quantitative prediction.
Structural Framework for the Protein Kinase Family (1992)

In this review, we have summarized the general structural features of the catalytic subunit of cAMP-dependent protein kinase, emphasizing those features that will very likely be conserved in all members of the protein kinase family. The overall secondary structure of the catalytic core will probably be conserved throughout the catalytic core, as will the active site regions associated with MgATP binding and catalysis. The mechanisms for activation and the role of protein phosphorylation are unique for each kinase. The structure of the catalytic subunit now provides a general framework for modeling other protein kinases. Although this is no substitute for a crystal structure for each protein kinase, this one structure, nevertheless, does provide major insights to the molecular organization of each of these enzymes.
A t-butyloxycarbonyl-modified Wnt5a-derived hexapeptide functions as a potent antagonist of Wnt5a-dependent melanoma cell invasion (2009)

The influential role of Wnt5a in tumor progression underscores the requirement for developing molecules that can target Wnt5a-mediated cellular responses. In the aggressive skin cancer, melanoma, elevated Wnt5a expression promotes cell motility and drives metastasis. Two approaches can be used to counteract these effects: inhibition of Wnt5a expression or direct blockade of Wnt5a signaling. We have investigated both options in the melanoma cell lines, A2058 and HTB63. Both express Frizzled-5, which has been implicated as the receptor for Wnt5a in melanoma cells. However, only the HTB63 cell line expresses and secretes Wnt5a. In these cells, the cytokine, TGFbeta1, controlled the expression of Wnt5a, but due to the unpredictable effects of TGFbeta1 signaling on melanoma cell motility, targeting Wnt5a signaling via TGFbeta1 was an unsuitable strategy to pursue. We therefore attempted to target Wnt5a signaling directly. Exogenous Wnt5a stimulation of A2058 cells increased adhesion, migration and invasion, all crucial components of tumor metastasis, and the Wnt5a-derived N-butyloxycarbonyl hexapeptide (Met-Asp-Gly-Cys-Glu-Leu; 0.766 kDa) termed Box5, abolished these responses. Box5 also inhibited the basal migration and invasion of Wnt5a-expressing HTB63 melanoma cells. Box5 antagonized the effects of Wnt5a on melanoma cell migration and invasion by directly inhibiting Wnt5a-induced protein kinase C and Ca(2+) signaling, the latter of which we directly demonstrate to be essential for cell invasion. The Box5 peptide directly inhibits Wnt5a signaling, representing an approach to anti-metastatic therapy for otherwise rapidly progressive melanoma, and for other Wnt5a-stimulated invasive cancers.
Prognostic relevance of carcinoembryonic antigen and estrogen receptor status in breast cancer patients (1994)

The association between CEA and ER was the most important independent predictor of a subgroup of patients (CEA-negative, ER-positive) with the most favorable prognosis. The results imply that the association of several tumor markers may provide tumor profiles with superior predictive value than a single parameter.
Exploring the Effect of Sequence Length and Composition on Allele-Selective Inhibition of Human Huntingtin Expression by Single-Stranded Silencing RNAs (2014)

Mutant huntingtin (HTT) protein is the cause of Huntington's disease (HD), an incurable neurological disorder. Almost all patients are heterozygous for mutant HTT and approaches that reduce levels of mutant HTT while leaving expression of wild-type HTT intact might be ideal options for therapeutic development. We have developed several allele-selective strategies for silencing HTT, including single-stranded silencing RNAs (ss-siRNAs). ss-siRNAs are oligonucleotides containing chemical modifications that permit action through the RNA interference (RNAi) pathway. Modified ss-siRNAs chosen to test the effects of varying oligomer length, lipid modification, the introduction of mismatched bases, and variation of chemical modification. We find that several modified ss-siRNA are potent and allele-selective inhibitors of HTT expression. An ss-siRNA with three mismatched bases relative to the CAG repeat was an allele-selective inhibitor of HTT expression in the HdhQ175 mouse model. Multiple allele-selective ss-siRNAs provide a wide platform of modifications to draw on for further optimization and therapeutic development. Our data provide insights into how ss-siRNAs can be modified to improve their properties and facilitate the discovery of the lead compounds necessary for further development.
Processing 3D flash LADAR point-clouds in real-time for flight applications (2007)

Ball Aerospace & Technologies Corp. has demonstrated real-time processing of 3D imaging LADAR point-cloud data to produce the industry's first time-of-flight (TOF) 3D video capability. This capability is uniquely suited to the rigorous demands of space and airborne flight applications and holds great promise in the area of autonomous navigation. It will provide long-range, three dimensional video information to autonomous flight software or pilots for immediate use in rendezvous and docking, proximity operations, landing, surface vision systems, and automatic target recognition and tracking. This is enabled by our new generation of FPGA based "pixel-tube" processors, coprocessors and their associated algorithms which have led to a number of advancements in high-speed wavefront processing along with additional advances in dynamic camera control, and space laser designs based on Ball's CALIPSO LIDAR. This evolution in LADAR is made possible by moving the mechanical complexity required for a scanning system into the electronics, where production, integration, testing and life-cycle costs can be significantly reduced. This technique requires a state of the art TOF read-out integrated circuit (ROIC) attached to a sensor array to collect high resolution temporal data, which is then processed through FPGAs. The number of calculations required to process the data is greatly reduced thanks to the fact that all points are captured at the same time and thus correlated. This correlation allows extremely efficient FPGA processing. This capability has been demonstrated in prototype form at both Marshal Space Flight Center and Langley Research Center on targets that represent docking and landing scenarios. This report outlines many aspects of this work as well as aspects of our recent testing at Marshall's Flight Robotics Laboratory.
Distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain: An in situ hybridization study (1996)

The distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide (PACAP) receptor (PACAP-R) was examined in the rat brain, and also in the hypophysis and pineal gland, by in situ hybridization with a specific 35S-labeled riboprobe which was generated from a rat PACAP-R cDNA clone. In the brain, expression of PACAP-R mRNA was most prominent in the periglomerular and granule cells of the olfactory bulb, granule cells of the dentate gyrus, supraoptic nucleus, and area postrema. The expression was also intense in the piriform, cingulate, and retrosplenial cortices, pyramidal cells in CA2, non-pyramidal cells in CA1-CA3, neuronal cells in the hilus of the dentate gyrus, lateral septal nucleus, intercalated amygdaloid nucleus, anterodorsal thalamic nucleus, most of the midline and intralaminar thalamic nuclei, many regions of the hypothalamus, dorsal motor nucleus of the vagus nerve, hypoglossal nucleus, and lateral reticular nucleus. No significant expression was detected in the mitral and tufted cells in the olfactory bulb, pyramidal cells in CA1 and CA3, posterior nuclear group of the thalamus, dorsal lateral geniculate nucleus, and Purkinje, Golgi, and granule cells in the cerebellar cortex. Moderate-to-weak expression was further observed in many other regions of the brain. In the cerebellar cortex, presumed Bergmann glia cells showed moderate expression. In the hypophysis, the expression was moderate in the anterior lobe, and weak to moderate in the posterior lobe; no significant expression was observed in the intermediate lobe. In the pineal gland, the expression was very weak, if any. Thus, the expression of PACAP-R was detected not only on neuronal cells but also on some particular glial cells. The present study has shown, for the first time, the exact site of PACAP-R expression in the brain and hypophysis. Although the functional significance of PACAP and PACAP-R in the brain still remains to be clarified, the present results are considered to provide some direction for future functional studies.
Aggressive Nutritional Support Does Not Prevent Protein Loss Despite Fat Gain in Septic Intensive Care Patients (1987)

It is current clinical practice to give intravenous nutrition (IVN) to critically ill postoperative septic intensive care patients to prevent loss of body protein, although it has not hitherto been possible to confirm this by direct measurement of body composition. Using a neutron activation analysis facility adapted to provide an intensive care environment and tritiated water dilution we directly measured total body water, protein and fat before and after 10 days of IVN (mean daily non-protein energy and amino acid intakes 2,750 kcal and 127 gm) in eight adult intensive care patients. All patients had recovered from the septic shock syndrome but were still ventilator dependent at the start of IVN. Six patients survived to leave hospital. As a group, the patients lost 12.5% of body protein (mean loss 1.5 +/- SE 0.3 kg; p = 0.001) despite a gain in fat (mean 2.2 +/- 0.8 kg; p = 0.026). There were, in addition, large losses of body water in most patients (mean, 6.8 +/- 2.6 kg; p = 0.036). We conclude that substantial losses of body protein occur in critically ill septic patients despite aggressive nutritional support and that further research is urgently required on the fate of infused substrates and the efficacy of alternative nutritional therapies.
Nasal Deposition and Clearance in Man: Comparison of a Bidirectional Powder Device and a Traditional Liquid Spray Pump (2012)

The initial deposition following powder delivery was significantly larger in the ciliated mucosa of the upper and posterior nasal regions, whereas less was deposited in the lower regions. Overall nasal clearance of powder was slower initially, but due to retention in anterior nonciliated regions the overall nasal clearance after spray was slower.
Anaemia of critical illness - implications for understanding and treating rHuEPO resistance (2002)

The prospect of a shortage of blood for transfusions, increasing awareness of the adverse effects of transfusions, and the availability of human recombinant erythropoietin (rHuEPO) have stimulated interest in the pathogenesis of the anaemia of intensive care unit (ICU) patients. As in the anaemia of chronic illness or chronic renal failure (CRF), the anaemia of ICU patients is a multifactorial process. Blood loss, inappropriately low erythropoietin production, reduced red cell lifespan, reduced iron availability, and inhibition of erythropoiesis by cytokines all contribute to the anaemia of critical illness, although the contributions of the various elements differ depending on the disease aetiology. Evidence is accumulating that use of rHuEPO can induce stimulation of erythropoiesis in critical illness, but at doses that are usually several-fold higher than those used to define resistance to rHuEPO in the current guidelines for the management of anaemia in CRF. Available data suggest that these high doses are well tolerated, at least in the short term. These observations, as well as demonstrating the potential benefits of rHuEPO therapy in critically ill patients, have practical implications for non-ICU patients with CRF who do not respond sufficiently to the usual doses of rHuEPO. Although the risk-benefit ratio relationship for very high doses of rHuEPO needs further consideration, demonstration of rHuEPO efficacy in critical illness should result in a re-evaluation of the 'dose-response relationship' for rHuEPO in patients with less acute and severe illness, including CRF patients hyporesponsive to current dosing regimens.
Biomass in the manufacture of industrial products—the use of proteins and amino acids (2007)

The depletion in fossil feedstocks, increasing oil prices, and the ecological problems associated with CO2 emissions are forcing the development of alternative resources for energy, transport fuels, and chemicals: the replacement of fossil resources with CO2 neutral biomass. Allied with this, the conversion of crude oil products utilizes primary products (ethylene, etc.) and their conversion to either materials or (functional) chemicals with the aid of co-reagents such as ammonia and various process steps to introduce functionalities such as -NH2 into the simple structures of the primary products. Conversely, many products found in biomass often contain functionalities. Therefore, it is attractive to exploit this to bypass the use, and preparation of, co-reagents as well as eliminating various process steps by utilizing suitable biomass-based precursors for the production of chemicals. It is the aim of this mini-review to describe the scope of the possibilities to generate current functionalized chemical materials using amino acids from biomass instead of fossil resources, thereby taking advantage of the biomass structure in a more efficient way than solely utilizing biomass for the production of fuels or electricity.
Survival in Men With Nonmetastatic Prostate Cancer Treated With Hormone Therapy: A Quantitative Systematic Review (2007)

This systematic review provides a new baseline for expected DFS and OS in patients treated with hormone therapy for nonmetastatic prostate cancer. Survival in these men may be longer than estimated previously.