gebhart/patrepeval huggingface dataset:
Representation of a Function by Its Line Integrals, with Some Radiological Applications (1963)

A method is given of finding a real function in a finite region of a plane given its line integrals along all straight lines intersecting the region. The solution found is applicable to three problems of interest for precise radiology and radiotherapy: (1) the determination of a variable x-ray absorption coefficient in two dimensions; (2) the determination of the distribution of positron annihilations when there is an inhomogeneous distribution of the positron emitter in matter; and (3) the determination of a variable density of matter with constant chemical composition, using the energy loss of charged particles in the matter.
Dopamine D1 Receptor‐mediated Facilitation of GABAergic Neurotransmission in the Rat Strioentopeduncular Pathway and its Modulation by Adenosine A1 Receptor‐mediated Mechanisms (1996)

By using in vivo microdialysis it was found that one of the main functions of striatal dopamine D1 receptors is to selectively facilitate GABAergic neurotransmission in the 'direct' strioentopeduncular pathway. D1 receptors localized in the entopeduncular nucleus were also found to facilitate GABA release. However, results obtained from in vivo microdialysis, in vivo electrochemistry, immunohistochemistry and confocal laser microscopy suggested that entopeduncular D1 receptors could only be activated under pharmacological conditions. Adenosine A1 receptors were found to antagonistically modulate the D1-mediated regulation of the strioentopeduncular pathway. Furthermore, using in situ hybridization D1 and A1 receptors were shown to be colocalized in medium-sized striatal neurons. These results show that the strioentopeduncular neuron is a main locus for adenosine-dopamine interactions in the brain.
Crystallographic analysis of Thr‐200 → His human carbonic anhydrase II and its complex with the substrate, HCO (1993)

A complex of carbonic anhydrase (CA) with one of its substrates, bicarbonate, has been studied crystallographically. Human isoenzyme II was mutated at position 200 from threonine to histidine, which results in higher affinity for bicarbonate. The HCO3- ion binds in the active site to the zinc ion as a pseudo-bidentate ligand which gives the metal a coordination geometry between tetrahedral and trigonal bipyramide. The water/hydroxide normally bound with tetrahedral coordination to the zinc is probably replaced by the OH group of the bicarbonate ion. The importance of residues Thr-199 and Glu-106 in controlling the binding orientation of HCO3- is discussed as well as the catalytic mechanism. Both the complex as well as the uncomplexed mutant were studied at 1.9 A resolution.
Production of Multicistronic HIV-1 Based Lentiviral Vectors (2009)

In the last decade lentiviral gene transfer vectors have gained significant place both in basic science and gene therapy applications. A number of gene transfer applications would benefit from vectors capable of expressing multiple genes. This chapter focuses on production of bicistronic and tricistronic lentiviral vectors based on the internal ribosomal entry site (IRES) sequence of encephalomyocarditis virus (EMCV) and/or foot-and-mouth disease virus (FMDV) cleavage factor 2A. Multigene vectors produced high titer viral particles and were able to simultaneously express two or three transgenes in transduced cells. The level of expression of individual transgenes varied depending on the transgene itself, its position within the construct, the total number of transgenes expressed, the strategy used for multigene expression, and the number of copies of proviral insertions.
Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease. (1997)

This study confirms that many of the phenomena with which C reactive protein is associated, are also associated with serum levels of cytokine, which may be the mechanism.
Dopamine-1 Receptor Coupling Defect in Renal Proximal Tubule Cells in Hypertension (1999)

The ability of the dopamine-1 (D1)-like receptor to stimulate adenylyl cyclase (AC) and phospholipase C (PLC), inhibit sodium transport in the renal proximal tubule (RPT), and produce natriuresis is attenuated in several rat models of hypertension. Since the inhibitory effect of D1-like receptors on RPT sodium transport is also reduced in some patients with essential hypertension, we measured D1-like receptor coupling to AC and PLC in cultures of human RPT cells from normotensive (NT) and hypertensive (HT) subjects. Basal cAMP concentrations were the same in NT (n=6) and HT (n=4). However, the D1-like receptor agonist fenoldopam increased cAMP production to a greater extent in NT (maximum response=67+/-1%) than in HT (maximum response=17+/-5%), with a potency ratio of 105. Dopamine also increased cAMP production to a greater extent in NT (32+/-3%) than in HT (14+/-3%). The fenoldopam-mediated increase in cAMP production was blocked by SCH23390 (a D1-like receptor antagonist) and by antisense D1 oligonucleotides in both HT and NT, indicating action at the D1 receptor. The stimulatory effects of forskolin and parathyroid hormone-related protein of cAMP accumulation were not statistically different in NT and HT, indicating receptor specificity and an intact G-protein/AC pathway. The fenoldopam-stimulated PLC activity was not impaired in HT, and the primary sequence and expression of the D1 receptor were the same in NT and HT. However, D1 receptor serine phosphorylation in the basal state was greater in HT than in NT and was not responsive to fenoldopam stimulation in HT. These studies demonstrate the expression of D1 receptors in human RPT cells in culture. The uncoupling of the D1 receptor in both rats (previously described) and humans (described here) suggests that this mechanism may be involved in the pathogenesis of hypertension; the uncoupling may be due to ligand-independent phosphorylation of the D1 receptor in hypertension.
Flipping bits in memory without accessing them: An experimental study of DRAM disturbance errors (2014)

Memory isolation is a key property of a reliable and secure computing system-an access to one memory address should not have unintended side effects on data stored in other addresses. However, as DRAM process technology scales down to smaller dimensions, it becomes more difficult to prevent DRAM cells from electrically interacting with each other. In this paper, we expose the vulnerability of commodity DRAM chips to disturbance errors. By reading from the same address in DRAM, we show that it is possible to corrupt data in nearby addresses. More specifically, activating the same row in DRAM corrupts data in nearby rows. We demonstrate this phenomenon on Intel and AMD systems using a malicious program that generates many DRAM accesses. We induce errors in most DRAM modules (110 out of 129) from three major DRAM manufacturers. From this we conclude that many deployed systems are likely to be at risk. We identify the root cause of disturbance errors as the repeated toggling of a DRAM row's wordline, which stresses inter-cell coupling effects that accelerate charge leakage from nearby rows. We provide an extensive characterization study of disturbance errors and their behavior using an FPGA-based testing platform. Among our key findings, we show that (i) it takes as few as 139K accesses to induce an error and (ii) up to one in every 1.7K cells is susceptible to errors. After examining various potential ways of addressing the problem, we propose a low-overhead solution to prevent the errors.
Deacetylase Inhibition in Haematological Malignancies – Advanced T-cell Lymphoma, Hodgkin’s Lymphoma, Multiple Myeloma, Acute Myelogenous Leukaemia and Myelodysplastic Syndrome (2010)

One of the groups of novel targeted drugs that has been most extensively studied in the last few years are histone deacetylase inhibitors (HDACis). These compounds inhibit the deacetylation induced by deacetylase (DACs) in both histone and non-histone proteins, resulting in an antitumour effect. The first HDACi to obtain approval by the US Food and Drug Administration (FDA) for an oncological indication was vorinostat for the treatment of cutaneous T-cell lymphoma (CTCL). Other HDACis have also shown activity in this disease. The activity of these agents in monotherapy in highly refractory Hodgkin’s lymphoma (HL) patients also shows clear therapeutic potential. Regarding acute myeloid leukaemia (AML), myelodysplastic syndrome (MDS) and multiple myeloma (MM), the antitumour activity in monotherapy, despite showing hints of activity, has been limited; however, based on pre-clinical studies, some combinations with other novel or well-established agents, such as anthracyclins or 5-azacytidine in the case of AML/MDS or with bortezomib or lenalidomide for MM, are ongoing, with promising signs of activity. Therefore, the use of these agents alone or in combination with other treatments seems to be an attractive approach for patients with haematological malignancies.
CXCR3 and IFN Protein-10 in Pneumocystis Pneumonia (2006)

We have previously shown that Tc1 CD8(+) T cells have in vitro and in vivo effector activity against Pneumocystis (PC) infection in mice. Because these cells have preferential expression of CXCR3, we investigated whether CXCR3 was required for host defense activity against PC. Mice deficient in CXCR3 but CD4(+) T cell intact, showed an initial delay but were able to clear the infectious challenge, indicating that CXCR3 signaling is not essential for clearance of PC. CD4-depleted mice had lower levels of monokine induced by IFN-gamma, IFN protein-10 (IP-10), and IFN-inducible T cell alpha-chemoattractant at day 7 of infection and are permissive to PC infection. Overexpression of IP-10 in the lungs by adenoviral gene transfer did not accelerate clearance of infection in control mice but accelerated clearance by day 28 in mice depleted of CD4(+) T cells. This effect was associated with increased recruitment of CD8(+) T to the lungs with higher CXCR3(+) expression levels and enhanced IFN-gamma secretion upon in vitro activation compared with control mice. These results indicate that the CXCR3 chemokines are part of the host defense response to PC, and that IP-10 can direct Tc1 CD8(+) T cell recruitment to the lungs and contribute to host defense against PC even in the absence of CD4(+) T cells.
Peptide and protein antigens require distinct antigen-presenting cell subsets for the priming of CD4+ T cells. (1995)

Priming of naive CD4+ T cells to Ag requires an antigen-presenting cell (APC) that can take up the Ag and present peptide bound to MHC class II molecules. We have used both in vivo and in vitro approaches to demonstrate that the APC used to prime naive CD4+ T cells depends on the initial form in which an Ag is administered. Although Ag delivered as a peptide was presented most efficiently to CD4+ T cells by DC, these APC were poor at priming to a protein form of the same Ag. In contrast, the presence of B cells was a requisite for priming to protein Ag.
Effect of CD154-CD40 interactions on collagen production by fibroblasts (2001)

We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA). An indirect immunofluorescence test and rat oesophagus substrate was used for the detection and quantification of AKA antibodies in patients sera. Overall 33/60 patients with JIA had sera positive for AKA (55 %, P = 0,0001) ranging from 1:10 to 1:160 dilutions. Following idiopathic arthritis of childhood classification criteria AKA occurred in 2/7 patients with systemic disease (28,6 %), in 13/30 patients with RF negative polyarthritis (43,3 %, P = 0,008) and in 15/18 RF positive polyarthritis (83,3 %, P = 0,000002). AKA were also found in a small cohort of patients with oligoarthritis (1/3) and psoriatic arthritis (2/2). AKA positivity occurred in 3/26 healthy controls at a 1:20 dilution. The presence of AKA was correlated as well as with the severity of the disease. Our study revealed that AKA was present overall in 18/29 patients (62%) with severe JIA and in 12/26 patients (46,2 %) with non-severe disease, however this did not reach statistical significance (P = 0,18). We also observed that AKA remained positive regardless of disease activity. AKA were detectable in 55,6 % patients with active JIA and in 48,6 % patients in the complete or near remission.
COX-2-Derived Prostacyclin Confers Atheroprotection on Female Mice (2004)

Female gender affords relative protection from cardiovascular disease until the menopause. We report that estrogen acts on estrogen receptor subtype alpha to up-regulate the production of atheroprotective prostacyclin, PGI2, by activation of cyclooxygenase 2 (COX-2). This mechanism restrained both oxidant stress and platelet activation that contribute to atherogenesis in female mice. Deletion of the PGI2 receptor removed the atheroprotective effect of estrogen in ovariectomized female mice. This suggests that chronic treatment of patients with selective inhibitors of COX-2 could undermine protection from cardiovascular disease in premenopausal females.
A Novel Robotic Platform for Laser-Assisted Transurethral Surgery of the Prostate (2014)

Benign prostatic hyperplasia (BPH) is the most common pathology afflicting ageing men. The gold standard for the surgical treatment of BPH is transurethral resection of the prostate. The laser-assisted transurethral surgical treatment of BPH is recently emerging as a valid clinical alternative. Despite this, there are still some issues that hinder the outcome of laser surgery, e.g., distal dexterity is strongly reduced by the current endoscopic instrumentation and contact between laser and prostatic tissue cannot be monitored and optimized. This paper presents a novel robotic platform for laser-assisted transurethral surgery of BPH. The system, designed to be compatible with the traditional endoscopic instrumentation, is composed of a catheter-like robot provided with a fiber optic-based sensing system and a cable-driven actuation mechanism. The sensing system allows contact monitoring between the laser and the hypertrophic tissue. The actuation mechanism allows steering of the laser fiber inside the prostatic urethra of the patient, when contact must be reached. The design of the proposed robotic platform along with its preliminary testing and evaluation is presented in this paper. The actuation mechanism is tested in in vitro experiments to prove laser steering performances according to the clinical requirements. The sensing system is calibrated in experiments aimed to evaluate the capability of discriminating the contact forces, between the laser tip and the prostatic tissue, from the pulling forces exerted on the cables, during laser steering. These results have been validated demonstrating the robot's capability of detecting sub-Newton contact forces even in combination with actuation.
Leptin Improves Insulin Resistance and Hyperglycemia in a Mouse Model of Type 2 Diabetes (2005)

Leptin has metabolic effects on peripheral tissues including muscle, liver, and pancreas, and it has been successfully used to treat lipodystrophic diabetes, a leptin-deficient state. To study whether leptin therapy can be used for treatment of more common cases of type 2 diabetes, we used a mouse model of type 2 diabetes (MKR mice) that show normal leptin levels and are diabetic due to a primary defect in both IGF-I and insulin receptors signaling in skeletal muscle. Here we show that leptin administration to the MKR mice resulted in improvement of diabetes, an effect that was independent of the reduced food intake. The main effect of leptin therapy was enhanced hepatic insulin responsiveness possibly through decreasing gluconeogenesis. In addition, the reduction of lipid stores in liver and muscle induced by enhancing fatty acid oxidation and inhibiting lipogenesis led to an improvement of the lipotoxic condition. Our data suggest that leptin could be a potent antidiabetic drug in cases of type 2 diabetes that are not leptin resistant.
Synthesis of labeled acrylamide and N‐methylolacrylamide (NMA): 15N‐acrylamide, 13C‐NMA, 15N‐NMA, and 13C,15N‐NMA (2005)

Abstract Labeled derivatives of N ‐methylolacrylamide (NMA) including 15 N‐NMA, 13 C‐NMA, and 13 C, 15 N‐NMA were synthesized and purified. A required chemical precursor, 15 N‐acrylamide, was also prepared. Reported methods for synthesizing unlabeled analogs are noted, and modifications to these methods for achieving the labeled materials are specified. Monomers were examined via 1 H, 13 C, and 15 N nuclear magnetic resonance (NMR) spectroscopy. Peak assignments and coupling constants are reported for each compound. To our knowledge, this is the first reported publication on the preparation and characterization of 13 C‐NMA, 15 N‐NMA, 13 C, 15 N‐NMA, and 15 N‐acrylamide. Copyright © 2005 John Wiley &amp; Sons, Ltd.
A trivalent subunit antigen glycoprotein vaccine as immunotherapy for genital herpes in the guinea pig genital infection model (2017)

An estimated 417 million people worldwide ages 15 to 49 are infected with herpes simplex virus type 2 (HSV-2), the most common cause of genital ulcer disease. Some individuals experience frequent recurrences of genital lesions, while others only have subclinical infection, yet all risk transmitting infection to their intimate partners. A vaccine was developed that prevents shingles, which is a recurrent infection caused by varicella-zoster virus (VZV), a closely related member of the Herpesviridae family. The success of the VZV vaccine has stimulated renewed interest in a therapeutic vaccine for genital herpes. We have been evaluating a trivalent subunit antigen vaccine for prevention of genital herpes. Here, we assess the trivalent vaccine as immunotherapy in guinea pigs that were previously infected intravaginally with HSV-2. The trivalent vaccine contains HSV-2 glycoproteins C, D, and E (gC2, gD2, gE2) subunit antigens administered with CpG and alum as adjuvants. We previously demonstrated that antibodies to gD2 neutralize the virus while antibodies to gC2 and gE2 block their immune evasion activities, including evading complement attack and inhibiting activities mediated by the IgG Fc domain, respectively. Here, we demonstrate that the trivalent vaccine significantly boosts ELISA titers and neutralizing antibody titers. The trivalent vaccine reduces the frequency of recurrent genital lesions and vaginal shedding of HSV-2 DNA by approximately 50% and almost totally eliminates vaginal shedding of replication-competent virus, suggesting that the trivalent vaccine is a worthy candidate for immunotherapy of genital herpes.
An efficient algorithm for virtual topology reconfiguration in WDM optical ring networks (2002)

Wavelength-division multiplexed (WDM) networks using wavelength routing are emerging to be the right choice for the future transport networks. In a WDM-based transport network, the optical layer provides circuit-switched lightpath services to the client layer such as IP, SONET, and ATM. The set of lightpaths in the optical layer defines the virtual topology. Since the optical switches (cross-connects) are reconfigurable, the virtual topology can be reconfigured in accordance with the changing traffic demand pattern at the client layer in order to optimize the network performance. On the other hand, changing the virtual topology can be disruptive to the network since the traffic at each node must be buffered or re-routed while the topology is being reconfigured. We develop a reconfiguration algorithm to reduce the cost of virtual topology reconfiguration in WDM optical ring networks. The algorithm is based on the concept of splitting and merging existing lightpaths, together with cost-benefit analysis to reduce the network reconfiguration cost. Our objective is to reduce the number of lightpaths that need to be reconfigured, while ensuring that the network congestion is low. The performance of the algorithm is verified through simulation experiments.
PhoneStation, moving the telephone onto the virtual desktop (1993)

PhoneStation is a system that provides a Sun Microsystems SPARCstation with complete control over an ordinary telephone line. It consists of a telephone line interface unit with loop control and touch tone detection, a suite of supporting software libraries that include digital signal processing for call progress monitoring, text-to-speech conversion, telephone line control, and PhoneScript, a high level procedural language that uses TCL for building interactive based application.
HUMAN BOCAVIRUS, A NEWLY DISCOVERED PARVOVIRUS OF THE RESPIRATORY TRACT (2008)

Human Bocavirus is a newly discovered parvovirus. This virus is the fourth most frequently detected virus among symptomatic children with respiratory infection. Human Bocavirus is present worldwide and is a probable cause of symptomatic respiratory infection, although Koch's postulates are not all fulfilled. In this article, we propose an overview of the main clinical data about this virus, two years after its discovery. In addition, we discuss some hypotheses about its tropism for the lung in young children.
Epoxides and Soluble Epoxide Hydrolase in Cardiovascular Physiology (2012)

Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites that importantly contribute to vascular and cardiac physiology. The contribution of EETs to vascular and cardiac function is further influenced by soluble epoxide hydrolase (sEH) that degrades EETs to diols. Vascular actions of EETs include dilation and angiogenesis. EETs also decrease inflammation and platelet aggregation and in general act to maintain vascular homeostasis. Myocyte contraction and increased coronary blood flow are the two primary EET actions in the heart. EET cell signaling mechanisms are tissue and organ specific and provide significant evidence for the existence of EET receptors. Additionally, pharmacological and genetic manipulations of EETs and sEH have demonstrated a contribution for this metabolic pathway to cardiovascular diseases. Given the impact of EETs to cardiovascular physiology, there is emerging evidence that development of EET-based therapeutics will be beneficial for cardiovascular diseases.
Proteinase-mediated cell signalling: targeting proteinase-activated receptors (PARs) by kallikreins and more (2006)

Serine proteinases, like trypsin, can play a hormone-like role by triggering signal transduction pathways in target cells. In many respects these hormone-like actions of proteinases can now be understood in terms of the pharmacodynamics of the G protein-coupled 'receptor' responsible for the cellular actions of thrombin (proteinase-activated receptor-1, or PAR1). PAR1, like the other three members of this receptor family (PAR2, PAR3 and PAR4), has a unique mechanism of activation involving the proteolytic unmasking of an N-terminally tethered sequence that can activate the receptor. The selective activation of each PAR by short synthetic peptides representing these sequences has demonstrated that PAR1, PAR2 and PAR4 play important roles in regulating physiological responses ranging from vasoregulation and cell growth to inflammation and nociception. We hypothesise that the tissue kallikreins may regulate signal transduction via the PARs. Although PARs can account for many of their biological actions, kallikreins may also cause effects by mechanisms not involving the PARs. For instance, trypsin activates the insulin receptor and thrombin can act via a mechanism involving its non-catalytic domains. Based on the data we summarise, we propose that the kallikreins, like thrombin and trypsin, must now be considered as important 'hormonal' regulators of tissue function.