gebhart/patrepeval huggingface dataset:
Spinally delivered nociceptin/orphanin FQ reduces flinching behaviour in the rat formalin test (1997)

The aims of this study were to investigate the dose-dependent effects of spinally delivered nociceptin (0.3, 1, 3.3 and 10 nmol) on flinching behaviour in the rat formalin test and whether these effects were influenced by the concomitant systemic administration of naloxone (3 mg/kg, i.p.). The effect of the highest nociceptin dose differed statistically from vehicle, 0.3 and 1 nmol nociceptin. Following the administration of 1, 3.3 or 10 nmol nociceptin mean total flinches decreased dose-dependently. The effects of 10 nmol nociceptin were not reversed by a high dose of naloxone. We observed a decrease in flinching behaviour with intrathecally to the lumbar enlargement delivered nociceptin and conclude that nociceptin has antinociceptive effects in the rat formalin test.
Update on pancreatic intraepithelial neoplasia. (2008)

Pancreatic intraepithelial neoplasia (PanIN) is a histologically well-defined precursor to invasive ductal adenocarcinoma of the pancreas. PanINs are remarkably common lesions, particularly in the elderly population. Molecular studies have helped establish the progression of PanIN to invasive cancer, and recently genetically engineered mouse models have been generated that recapitulate the entire spectrum of lesions from precursor to invasive pancreatic cancer. Some PanIN lesions produce lobulocentric atrophy of the pancreatic parenchyma, and, when multifocal, this lobulocentric atrophy may be detectable using currently available imaging techniques such as endoscopic ultrasound. The association of acinar-ductal metaplasia with PanIN lesions has led some to hypothesize that PanINs develop from acinar cells that undergo acinar-ductal metaplasia.
Molecular interactions between wheat and cereal aphid (Sitobion avenae): Analysis of changes to the wheat proteome (2011)

Aphids are major insect pests of cereal crops, acting as virus vectors as well as causing direct damage. The responses of wheat to infestation by cereal aphid (Sitobion avenae) were investigated in a proteomic analysis. Approximately, 500 protein spots were reproducibly detected in the extracts from leaves of wheat seedlings after extraction and 2-DE. Sixty-seven spots differed significantly between control and infested plants following 24 h of aphid feeding, with 27 and 11 up-regulated, and 8 and 21 down-regulated, in local or systemic tissues, respectively. After 8 days, 80 protein spots differed significantly between control and aphid treatments with 13 and 18 up-regulated and 27 and 22 down-regulated in local or systemic tissues, respectively. As positive controls, plants were treated with salicylic acid or methyl jasmonate; 81 and 37 differentially expressed protein spots, respectively, were identified for these treatments. Approximately, 50% of differentially expressed protein spots were identified by PMF, revealing that the majority of proteins altered by aphid infestation were involved in metabolic processes and photosynthesis. Other proteins identified were involved in signal transduction, stress and defence, antioxidant activity, regulatory processes, and hormone responses. Responses to aphid attack at the proteome level were broadly similar to basal non-specific defence and stress responses in wheat, with evidence of down-regulation of insect-specific defence mechanisms, in agreement with the observed lack of aphid resistance in commercial wheat lines.
Mammalian homolog of Drosophila retinal degeneration B rescues the mutant fly phenotype. (1997)

Mutations in the Drosophila rdgB gene, which encodes a transmembrane phosphatidylinositol transfer protein (PITP), cause a light-enhanced retinal degeneration. Cloning of mammalian rdgB orthologs (mrdgB) reveal predicted proteins that are 39% identical to rdgB, with highest homology in the N-terminal PITP domain (62%) and in a region near the C terminus (65%). The human mrdgB gene spans approximately 12 kb and maps to 11q13.1, a locus where several retinal diseases have also been mapped. Murine mrdgB maps to a syntenic region on the proximal region of chromosome 19. MrdgB is specifically expressed in the retina and brain. In the retina, MrdgB protein is localized to photoreceptor inner segments and the outer and inner plexiform layers. Expression of murine mrdgB in mutant flies fully rescues both the rdgB-dependent retinal degeneration and abnormal electroretinogram. These results suggest the existence of similarities between the invertebrate and mammalian retina that were not previously appreciated and also identify mrdgB as a candidate gene for retinal diseases that map to 11q13.1.
Kinetic profiling of novel spirobenzo-oxazinepiperidinone derivatives as equilibrative nucleoside transporter 1 inhibitors (2023)

Abstract Evaluation of kinetic parameters of drug-target binding, k on , k off , and residence time (RT), in addition to the traditional in vitro parameter of affinity is receiving increasing attention in the early stages of drug discovery. Target binding kinetics emerges as a meaningful concept for the evaluation of a ligand’s duration of action and more generally drug efficacy and safety. We report the biological evaluation of a novel series of spirobenzo-oxazinepiperidinone derivatives as inhibitors of the human equilibrative nucleoside transporter 1 (hENT1, SLC29A1). The compounds were evaluated in radioligand binding experiments, i.e. , displacement, competition association, and washout assays, to evaluate their affinity and binding kinetic parameters. We also linked these pharmacological parameters to the compounds’ chemical characteristics, and learned that separate moieties of the molecules governed target affinity and binding kinetics. Among the 29 compounds tested, 28 stood out with high affinity and a long residence time of 87 min. These findings reveal the importance of supplementing affinity data with binding kinetics at transport proteins such as hENT1.
Systemic lupus erythematosus in mice, spontaneous and induced, is associated with autoimmunity to the C-terminal domain of p53 that recognizes damaged DNA (2000)

The tumor suppressor molecule p53 features a regulatory domain at the C terminus that recognizes damaged DNA. Since damaged DNA might be involved in activating anti-DNA autoantibodies, we tested whether autoimmunity to the C terminus of p53 might mark murine systemic lupus erythematosus (SLE). We now report that MRL / MpJ-Fas(lpr) mice, which spontaneously develop SLE, produce antibodies both to the C terminus of p53 and to a monoclonal antibody (PAb-421) that binds the p53 C terminus. Anti-idiotypic antibodies to PAb-421 (sampled as monoclonal antibodies) could also bind DNA. Thus, the PAb-421 antibody mimics DNA, and the anti-idiotypic antibody to PAb-421 mimics the p53 DNA-binding site. This mimicry was functional; immunization of BALB / c mice to PAb-421 induced anti-DNA antibodies and antibodies to the C terminus of p53, and most of the mice developed an SLE-like disease. Immunization of C57BL / 6 mice to PAb-421 induced antibodies to p53, but not to its C-terminal domain. The C57BL / 6 mice also did not develop anti-DNA antibodies or the SLE-like disease. Thus, network autoimmunity to the domain of p53 that recognizes damaged DNA can be a pathogenic feature in SLE in genetically susceptible strains of mice.
Microarray analysis of multiple candidate genes and associated plasma proteins for nephropathy secondary to type 2 diabetes among Chinese individuals (2009)

Our preliminary observations suggest that common haplotypes from NOX4 and endothelin-1 SNP correlated with plasma Cu/Zn SOD and C-terminal pro-endothelin-1 concentrations, respectively, and might have conferred diabetic nephropathy susceptibility. Common NOS1 and rare NOX1 variants also revealed a suggestive association with diabetic nephropathy. Future studies to validate our observation are needed.
A Value Token Transfer Protocol (VTTP) for Decentralized Finance (2020)

We present Value Token Transfer Protocol (VTTP), a decentralized finance protocol for exchange of value or tokens within and between participating blockchain networks, fiat bank accounts and fiat wallets. The protocol allows intra-chain or inter-chain transfers of cryptocurrencies or tokens. VTTP works in both client-server and peer-to-peer models. The protocol comprises receiving from a client a transfer request to transfer value in a form of a cryptocurrency or a token, determining if the transfer request is intra-chain or inter-chain, transmitting to the client a response to the transfer request, the response comprising a raw transaction, receiving from the client a response to the raw transaction wherein a private key of a user is used to sign the raw transaction, defining a signed transaction, verifying a signature of the signed transaction and broadcasting the signed transaction to the sending and receiving blockchain networks.
Surgically induced unilateral pulmonary hypertension: time-related analysis of a new experimental model (2003)

The lung exposed to systemic pressure and oxygenation develops irreversible vascular lesions typical of pulmonary vascular obstructive disease. The lung exposed to increased flow shows only mild elevation of the arterial pressure, remains responsive to oxygen vasodilatation, and displays normal histology.
1.6Tb/s Transmission Feasibility Employing IM/DD for Datacentre Networks (2020)

We demonstrate the feasibility of an aggregate data-rate of 1.6Tb/s using 200Gb/s per lane. Eight O-band wavelengths carrying 112GBd PAM4 are employed to demonstrate transmission over 2km of SSMF at the HD-FEC threshold of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$1.75\times 10^{-3}$</tex> .
Nilotinib Significantly Alters CSF Biomarkers and Increases Endogenous Dopamine in Open-Label Phase I Clinical Trial in Parkinsons Disease with Dementia and Lewy Body Dementia (I1.009) (2016)

Objectives: To examine the effects of Nilotinib on CSF biomarkers in PD with dementia and LBD patients. Background: PD involves death of dopamine producing neurons in the Substantia Nigra pars compacta. Alpha-Synuclein accumulation into Lewy bodies (LBs) is the pathological hallmark of Synucleinopathies. As PD progresses, p-Tau and beta-amyloid (Abeta) pathologies coincide with the onset of dementia. Pre-clinical data indicate that the tyrosine kinase Abl (Abelson) inhibitor Nilotinib penetrates the brain and induces autophagic clearance of alpha-Synuclein, p-Tau and Abeta. Design and methods: Nilotinib is FDA-approved for the treatment of chronic myeloid leukemia (CML) at 800mg oral dose twice daily. To examine the effects of lower doses (<50[percnt] of CML dose) of Nilotinib on safety and efficacy, we randomized 12 participants with late stage (Hoehn and Yahr 3-5) PD with dementia (PDD) and Lewy body dementia (LBD) into 150mg (N=6) or 300mg (N=6) groups, who received oral daily doses of Nilotinib for 6 months. Results: The results indicate that Nilotinib prevents the loss of alpha-Synuclein in CSF, and decreases it in the plasma. Nilotinib significantly increases CSF HVA levels, suggesting an increase in central dopamine stores despite reduction of L-Dopa replacement therapy. Furthermore, our results demonstrate that Nilotinib peaks in human CSF at 2 hours and inhibits Abl, indicating direct target engagement. Nilotinib significantly reduced CSF levels of p-Tau231 and pTau181 and Abeta42/40 levels, in agreement with pre-clinical evidence suggesting autophagic protein clearance. Nilotinib also significantly reduced markers of neuronal death, including CSF neuron specific enolase (NSE) and S100B. A number of neurotrophic factors were also altered in the CSF after 6 months of Nilotinib treatment. Conclusions: These results indicate that Nilotinib is a potential disease-modifying therapy in neurodegenerative diseases, and provide strong feasibility for multicenter, randomized, placebo-controlled, double blind trials in early dementia and Parkinsonism.
60Gb/s waveguide-coupled O-band GeSi quantum-confined Stark effect electro-absorption modulator (2021)

We report O-band GeSi quantum-confined Stark effect waveguide-coupled electro- absorption modulator with 50GHz bandwidth. Static extinction ratio of 5.2dB, insertion loss of 7.6dB and 60Gb/s NRZ-OOK operation are shown for a 2V swing.
Effect of Human Recombinant VWF Administration on Plasma ADAMTS13 Activities in Non-Human Primates and Rabbits (2008)

Abstract Von Willebrand factor (VWF) is composed of a series of multimers, the sizes of which are regulated by the plasma metalloprotease ADAMTS13. Reports suggest that a transient increase in VWF levels, triggered for instance by DDAVP treatment, will result in a decrease in ADAMTS13 activity. This phenomenon is widely believed to be due to ADAMTS13 being exhausted when confronted with an excess of substrate. Treating patients who have type 3 von Willebrand disease with a recombinant human von Willebrand factor (rVWF) that has not yet been exposed to ADAMTS13 might thus cause a drop in ADAMTS13 levels. We therefore tested whether a rise in VWF concentrations to supraphysiological levels caused by administration of rVWF could influence endogenous ADAMTS13 levels in animal models. Various doses of human rVWF (300, 600, and 1200 RCo IU/kg BW) were injected into rabbits and cynomolgus monkeys and plasma samples were collected at a range of time points. As expected, VWF antigen rose sharply in a dose-dependent manner (~25 IU/ml VWF:Ag for the highest dose, 15 min after injection) and then declined gradually (~7 IU/ml VWF:Ag for the highest dose, 18 hours after injection). When these samples were tested for ADAMTS13 activity using the FRETS assay, no relevant changes were observed throughout the entire test period in the rabbit or in the monkey samples, indicating that rVWF, even at high doses, did not compromise ADAMTS13 activity. Both rabbit and cynomolgus ADAMTS13 recognized human rVWF as the specific cleavage products were detectable by electrophoresis at all doses administered. These animal studies thus indicate that an excess of intravenously administered rVWF leading to supraphysiological levels does not exhaust ADAMTS13.
Syndecan expression regulates cell morphology and growth of mouse mammary epithelial tumor cells. (1992)

S115 mouse mammary epithelial cells lose their epithelial morphology and become tumorigenic when exposed to steroids. We have recently reported that testosterone exposure results in the suppression of syndecan expression, suggesting that this cell surface proteoglycan may influence S115 cell phenotype. We now report that a similar suppression and morphological response of S115 cells can be achieved by glucocorticoid exposure. We introduced into S115 cells an exogenous gene construct containing the full-length human syndecan cDNA under the control of a glucocorticoid-inducible retroviral promoter, in order to study the effect of syndecan expression on S115 cell behavior. Glucocorticoid-induced re-expression of syndecan in S115 cells restored an epithelial phenotype, while control transfectants and parental S115 cells exhibited an altered, nonepithelial phenotype. Moreover, the S115 cells expressing exogenous syndecan revealed a reduced ability to form colonies in soft agar. Therefore, the maintenance of epithelial morphology and normal growth of S115 cells are dependent on syndecan expression.
Diagnosing infeasibilities in network flow problems (1994)

We consider the problem of finding a feasible flow in which each node i has a supply b(i), and each arc has a lower bound of 0 on flow and an upper bound uij. It is well known that this feasibility problem can be transformed into a maximum flow problem. It is also well known that there is no feasible flow if and only if there is a subset S of nodes such that the sum of the supplies of the nodes of S exceeds the capacity of the arcs emanating from S. Such a set S is called a &amp;amp;quot;witness to the infeasibility &amp;amp;quot; of the network flow problem. In the case that there are many different witnesses for an infeasible problem, a small cardinality witness may be preferable in practice because it is generally easier for the user to assimilate, and may provide more guidance to the user on how to identify the cause of the infeasibility. Here we show that the problem of finding a minimum cardinality witness is NP-hard. We also consider minimal witnesses, that is, a witness S such that no proper subset of S is also a witness. The primary contribution of this paper is an algo-rithm for determining minimal witnesses whose running time is comparable to solving a single maximum flow problem.
Abstract 2133: In pursuit of MCL-1 inhibitors with improved therapeutic window for the treatment of hematological malignancies: Discovery of JNJ-4355 (2022)

Abstract Appropriate control of cell death is a fundamental biological process which is frequently dysregulated during tumor development and therapeutic resistance. Apoptosis is a form of regulated cell death initiated by either the extracellular environment (extrinsic) or following internal cellular damage (intrinsic). It is controlled by the BCL-2 family which includes anti-apoptotic regulators like BCL-2, BCL-XL and MCL-1 that bind and sequester various pro-apoptotic BH3-only proteins (BIM, BAD, BID, NOXA, PUMA, etc.), and the pro-apoptotic effectors (BAK, BAX, etc.) responsible for mitochondrial pore formation and MOMP (mitochondrial outer membrane permeabilization). MOMP results in intermembrane space protein release, leading to caspase activation in an irreversible path to programmed cell death. Of the anti-apoptotic regulators, MCL-1 is one of the most frequently and highly amplified genes in human cancers such as myeloid leukemia making it a compelling therapeutic target. Since BCL-2 proteins interact through protein-protein interactions, they have long been elusive targets. The success of selective BCL-2 protein inhibitor Venetoclax in the treatment of various hematological cancers, however spurred interest in MCL-1 as an oncology target. Using structure-based drug design, major breakthroughs were made in the development of MCL-1 inhibitors, with several candidates entering clinical studies in the past five years. JNJ-4355, a highly potent 1,4-indolyl macrocycle (MCL-1 Ki = 18 pM, Cell (MOLP8) AC50 = 8.7 nM) was optimized to address shortcomings from first generation MCL-1 inhibitors: it has improved physicochemical properties (CHI LogD7.4 = 2.35, EPSA = 151 Å2), resulting in greatly improved equilibrium solubility (3.14 mM in buffer pH 7) and reduced protein binding (99.93%). JNJ-4355 showed promising in vitro potency data in cancer cell lines and AML patient-derived samples (cell killing AC50 0.29-75 nM in 25/27 evaluable samples). In vivo MCL-1:BAK complex disruption was confirmed in a mouse MOLM13 (AML) xenograft. Efficacy was demonstrated in a mouse MOLP8 (multiple myeloma) xenograft resulting in complete tumor regression after a single IV dose of JNJ-4355. Citation Format: Frederik J. Rombouts, Lento William, Ingrid Velter, Ann Vos, Aldo Peschiulli, Reuillon Tristan, Maria Dominguez Blanco, Matthieu Jouffroy, Lisa McQueen, Helena Steyvers, Mariette Bekkers, Cristina Altrocchi, Beth Pietrak, Seong Joo Koo, Lawrence Szewczuk, David Walker, Kathryn Packman, Ruud Bueters, Petra Vinken, Amy Johnson, Ricardo Attar, Ulrike Philippar. In pursuit of MCL-1 inhibitors with improved therapeutic window for the treatment of hematological malignancies: Discovery of JNJ-4355 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2133.
Stiffness Model of Single-Geared Joint with 3D-Printed Link in Robot Arm (2023)

For saving energy in industrial robots, we aim to establish a method for constructing lightweight robot components using metals and resins. Most gears and link parts in current industrial robots are made of metal. It is necessary to use resin in robot components to reduce their weight. However, resins are generally less stiff and can reduce performance. Link parts were made from metal or resin, and the stiffness of the robot arm in the axial and rotational directions was measured. Based on the experimental results, a stiffness model for the joint and link is proposed and the potential of a 3D-printed link in industrial robots is shown.
New Insights Into the Interactions Between T-Cell Costimulatory Blockade and Conventional Immunosuppressive Drugs (2002)

The widespread view that calcineurin inhibitors abrogate the effects of T-cell costimulatory blockade should be revisited. Sufficient costimulatory blockade and synergy induced by CD154 blockade and rapamycin promote allograft tolerance and prevent chronic rejection.
I/O Braid (2018)

We introduce I/O Braid, an interactive textile cord with embedded sensing and visual feedback. I/O Braid senses proximity, touch, and twist through a spiraling, repeating braiding topology of touch matrices. This sensing topology is uniquely scalable, requiring only a few sensing lines to cover the whole length of a cord. The same topology allows us to embed fiber optic strands to integrate co-located visual feedback. We provide an overview of the enabling braiding techniques, design considerations, and approaches to gesture detection. These allow us to derive a set of interaction techniques, which we demonstrate with different form factors and capabilities. Our applications illustrate how I/O Braid can invisibly augment everyday objects, such as touch-sensitive headphones and interactive drawstrings on garments, while enabling discoverability and feedback through embedded light sources.
Genotypic Comparison between Streptococcus suis Isolated from Pigs and Humans in Thailand (2020)

<i>Streptococcus suis</i> is a zoonotic pathogen of economic significance to the swine industry. The number of infected cases is increasing in humans worldwide. In this study, we determined the prevalence and diversity of <i>S. suis</i> carriage in slaughterhouse pigs in Phayao province, Thailand, where an outbreak occurred in 2007. The overall <i>S. suis</i> carriage rate was 35.2% among slaughterhouse pigs. The prevalence rates of serotypes 2 and 14 (the major serotypes infected in humans) were 6.7% and 2.6%, respectively. In both serotypes, 70.4% of isolates of serotypes 2 and 14 revealed sequence types and pulsotypes identical to human isolates in Thailand. It is suggested that pathogenic strains of <i>S. suis</i> are a risk factor for occupational exposure to pigs or the consumption of raw pork products. Food safety, hygiene, and health education should be encouraged to reduce the risk group.
WLAN visual sensor networking (2002)

This paper presents a discussion on constructing a wireless ad hoc network using unattended ground visual sensors. The IEEE 802.11 WLAN standard is used to implement a single-hop ad hoc network because of its simplicity. The bandwidth allocation and traffic control between visual sensors is coordinated by the Medium Access Control (MAC) protocol. A ground visual sensor tower is designed for the networking purpose with specially designed video compression, power management, and network module to achieve maximum thoroughput