gebhart/patrepeval huggingface dataset:
Split Multi-link Trunking (SMLT) (2008)

This document describes Split Multi-link Trunking (SMLT) for bridged
and routed networks. SMLT enables topologies with upstream node
redundancy for increased reliability of Layer 2 link aggregation
subnetworks based on [IEEE 802.3ad] and router redundancy based on
VRRP [RFC3768]. SMLT is an improvement over Multi-Link Trunking
(MLT), a method of link aggregation that allows multiple Ethernet
links to be aggregated together, and handled as a single logical
trunk. MLT can be realized via many different link aggregation
mechanisms. Several methods of MLT are in use today; one example is
[IEEE 802.3ad]. SMLT is MLT with links of a link-aggregation group
connected to ports on two different devices (e.g. SMLT client and
aggregation device). Unlike MLT, at least one end of a link-aggregated
group is dual-homed to two different SMLT aggregation devices. In many
cases those devices act as bridges (switches) as well as L3 routers
(Routing Switches). These two redundant SMLT aggregation devices can
share one or more VRRP routing instances; for that SMLT-VRRP extends
the VRRP functionality to an active-active router concept, where both
SMLT aggregation device route traffic for a common VRRP-ID, thus load
balancing traffic not only for L2 but also for L3.
Acute myeloid leukemia targets for bispecific antibodies (2017)

Despite substantial gains in our understanding of the genomics of acute myelogenous leukemia (AML), patient survival remains unsatisfactory especially among the older age group. T cell-based therapy of lymphoblastic leukemia is rapidly advancing; however, its application in AML is still lagging behind. Bispecific antibodies can redirect polyclonal effector cells to engage chosen targets on leukemia blasts. When the effector cells are natural-killer cells, both antibody-dependent and antibody-independent mechanisms could be exploited. When the effectors are T cells, direct tumor cytotoxicity can be engaged followed by a potential vaccination effect. In this review, we summarize the AML-associated tumor targets and the bispecific antibodies that have been studied. The potentials and limitations of each of these systems will be discussed.
PARP14 Controls the Nuclear Accumulation of a Subset of Type I IFN–Inducible Proteins (2018)

The enzymes of the poly-ADP-ribose polymerase (PARP) superfamily control many relevant cellular processes, but a precise understanding of their activities in different physiological or disease contexts is largely incomplete. We found that transcription of several <i>Parp</i> genes was dynamically regulated upon murine macrophage activation by endotoxin. PARP14 was strongly induced by several inflammatory stimuli and translocated into the nucleus of stimulated cells. Quantitative mass spectrometry analysis showed that PARP14 bound to a group of IFN-stimulated gene (ISG)-encoded proteins, most with an unknown function, and it was required for their nuclear accumulation. Moreover, PARP14 depletion attenuated transcription of primary antiviral response genes regulated by the IFN regulatory transcription factor 3, including <i>Ifnb1</i>, thus reducing IFN-β production and activation of ISGs involved in the secondary antiviral response. In agreement with the above-mentioned data, PARP14 hindered <i>Salmonella typhimurium</i> proliferation in murine macrophages. Overall, these data hint at a role of PARP14 in the control of antimicrobial responses and specifically in nuclear activities of a subgroup of ISG-encoded proteins.
O-linked glycoproteins of the nuclear pore complex interact with a cytosolic factor required for nuclear protein import. (1992)

Mediated import of proteins into the nucleus requires cytosolic factors and can be blocked by reagents that bind to O-linked glycoproteins of the nuclear pore complex. To investigate whether a cytosolic transport factor directly interacts with these glycoproteins, O-linked glycoproteins from rat liver nuclear envelopes were immobilized on Sepharose beads via wheat germ agglutinin or specific antibodies. When rabbit reticulocyte lysate (which provides cytosolic factors required for in vitro nuclear import) was incubated with the immobilized glycoproteins, the cytosol was found to be inactivated by up to 80% in its ability to support mediated protein import in permeabilized mammalian cells. Inactivation of the import capacity of cytosol, which was specifically attributable to the glycoproteins, involves stoichiometric interactions and is likely to involve binding and depletion of a required factor from the cytosol. This factor is distinct from an N-ethylmaleimide-sensitive receptor for nuclear localization sequences characterized recently since it is insensitive to N-ethylmaleimide. Cytosol inactivation is suggested to be caused by at least two proteins of the glycoprotein fraction, although substantial capacity for inactivation can be attributed to protein bound by the RL11 antibody, consisting predominantly of a 180-kD glycosylated polypeptide. Considered together, these experiments identify a novel cytosolic factor required for nuclear protein import that directly interacts with O-linked glycoproteins of the pore complex, and provide a specific assay for isolation of this component.
Cholesteryl ester analogs inhibit cholesteryl ester but not triglyceride transfer catalyzed by the plasma cholesteryl ester‐triglyceride transfer protein (1990)

A lipid transfer protein complex (LTC), purified from human plasma by immunoaffinity chromatography, catalyzed the interlipoprotein transfer of cholesteryl esters (CE) and triglycerides (TG). The CE transfer activity of LTC was governed by the structure of the CE. Incubation of LTC with long chain CE both activated and stabilized LTC. Short chain CE also enhanced the CE and TG transfer activity of LTC during the initial time of incubation. However, LTC's incubation with short chain CE induced a subsequent and time-dependent loss of CE transfer activity without concomitant loss of TG transfer activity. The data indicate that the CE and TG transfer activity of LTC can be regulated independently.
Validación Española de Maudsley y Adicction profile (MAP) (2004)

RESUMEN
Se realizo un estudio con el objetivo de determinar la fiabilidad de la entrevista MAP (Maudsley Addiction Profile). La muestra incluye 646 pacientes con una media de 36 anos de edad, (79% hombres y 21% mujeres) tratados por problemas con el alcohol (39%) y otras drogas (61%). Las entrevistas MAP fueron realizadas por mas de 60 entrevistadores de ambos sexos, personal clinico e investigador. Se calcularon coeficientes de correlacion y coeficientes kappa. La mayoria de estos estimadores muestran una fiabilidad test ? retest y estabilidad temporal aceptables o satisfactorias, con valores cercanos o superiores a 0,80, apoyando la fiabilidad de la mayor parte de la informacion obtenida. El sexo del entrevistado, tipo de entrevistador y sustancia principal (alcohol o drogas) no afectan sustancialmente
a la fiabilidad del MAP.

Palabras clave: Fiabilidad, resultados, tratamiento, abuso de drogas.
ERBB-2 overexpression confers PI 3′ kinase-dependent invasion capacity on human mammary epithelial cells (2000)

Amplification and overexpression of ERBB-2 in human breast cancer is thought to play a significant role in the progression of the disease; however, its precise role in the aetiology of altered phenotypes associated with human breast cancer is unknown. We have previously shown that exogenous overexpression of ERBB-2 conferred growth factor independence on human mammary epithelial cells. In this study, we show that ERBB-2 overexpression also causes the cells to acquire other characteristics exhibited by human breast cancer cells, such as anchorage-independent growth and invasion capabilities. ERBB-2-induced invasion is dependent on fibronectin and correlates with the down-regulation of cell surface alpha4 integrin. In addition ERBB-2 co-immunoprecipitates with focal adhesion kinase (FAK) in these cells. We have also shown, by use of exogenously expressed PTEN and by treatment with the PI3'-kinase inhibitor LY294002, that ERBB-2-induced invasion is dependent on the PI3'-kinase pathway; however, PTEN does not dephosphorylate FAK in these cells.
Predicting fracture swarms — the influence of subcritical crack growth and the crack-tip process zone on joint spacing in rock (2004)

Abstract Swarms or clusters represent an exception to the widely accepted idea that fracture spacing in sedimentary rock should be proportional to mechanical layer thickness. Experimental studies and static stress analysis do not provide adequate explanation for fracture swarm occurrence. The problem is re-examined numerically, accounting for the dynamics of pattern development for large populations of layer-confined fractures. Two crucial aspects of this model are: (1) the inclusion of three-dimensional effects in calculating mechanical interaction between simultaneously propagting fractures; and (2) the use of a subcritical crack-propagation rule, where propagation velocity during stable growth scales with the crack-tip stress intensity factor. Three regimes of fracture spacing are identified according to the magnitude of the subcritical index of the fracturing material. For low subcritical index material ( n = 5) numerous fractures propagate simultaneously throughout a body resulting in irregular spacing that is, on average, much less than layer thickness. For intermediate subcritical index ( n = 20) one fracture propagates at a time, fully developing its stress shadow and resulting in a pattern with regular spacing proportional to layer thickness. For high subcritical index cases ( n = 80) fractures propagate in a fashion analogous to a process zone, leaving a fracture pattern consisting of widely spaced fracture clusters.
Grippers for the Micro Assembly Containing Shape Memory Actuators and Sensors (1997)

Shape memory alloys (SMA) show a high ratio of work capacity per material volume. This makes the application of SMA especially useful in micron-sized systems. The development of robotic grippers is one important prerequisite for the successful automation of the assembly of micro systems. Therefore the SMA may also play a role, for example, as actuators in micron-sized grippers. This paper presents the development of micron-sized grippers. Due to a special relation between the electrical resistance and the shape change of a NiTi-wire the actuator may also be used simultaneously as a sensor. Besides these functional properties a superelastic SMA may be used for structural purposes, i.e. as solid-state flexure hinges. The sensoric features of binary and ternary NiTi-based alloys are investigated using different Ti50Nijo.xC~x alloys with 0 c X i 25 at-%. Besides the chemical composition the functional properties are affected by the thermo-mechanical treatment (TMT). Different TMT of Ti5$Ji50.xC~x alloys and their influence on the functional properties are compared. The effect of the TMT on the amount and the stability of the shape memory effect has to be taken into account if the optimum alloy and condition for the use in grippers for micro assembly are investigated. The function and the properties of the developped gripping devices are demonstrated by prototypes.
The role of cysteine oxidation in the thermal inactivation of T4 lysozyme (1987)

Wild-type T4 lysozyme contains unpaired cysteine residues at positions 54 and 97. To investigate the role these residues play in the thermal inactivation of the wild-type, we constructed a double mutant with these cysteines replaced with valine and serine. This molecule, T4 lysozyme (C54V/C97S), is more stable than the wild-type to inactivation at 70 degrees C at pH 6.5 and 8.0. Guanidine hydrochloride reactivation experiments and SDS-PAGE on the inactivated products show that the wild-type is susceptible to varying degrees of oxidative damage, depending on buffer conditions, while the cysteine-minus mutant inactivates only by other pathways. The products of thermal, oxidative inactivation of the wild-type are disulfide-linked oligomers. The dependence of inactivation rate on temperature suggests that the formation of these aggregates depends on prior thermal unfolding of the T4 lysozyme molecule.
Activity of bortezomib, a proteasome inhibitor, in breast cancer cells: Association with negative estrogen receptor and IKK/NF-κB expression (2005)

3169 Background: We reported that bortezomib (Velcade), a proteasome inhibitor, suppressed cell growth and induced apoptosis to varying extents (IC50 range, 4nM to 1000 nM) in a panel of breast cancer cells (Codony et al, Proc AACR 2004). Notably, bortezomib effects were unrelated to EGFR/HER2 expression. Here we addressed whether estrogen receptor (ER) and IκB kinase (IKK)/nuclear factor (NF)-κB expression were related to bortezomib effects and also studied the relation between these two systems in breast cancer. Methods: Proteasome activity was measured by fluorogenic proteasome assay. Expression of ER, IKKs (α, β and NEMO), NF-κB (p65, p50, p52, RelB and c-Rel) and IκB (α, β and ε) subunits were assayed by WB. Ductal breast carcinoma in situ (DCIS) and infiltrating carcinoma specimens were assayed by IHC for ER and p65 expression. p65NF-κB nuclear staining was interpreted as an activated form of NF-κB. Results: ER-positive cell lines were relatively bortezomib resistant (MCF7, IC50 100 nM; BT474, IC50 1000 nM) while ER-negative cells were generally more sensitive (SKBR3, IC50 4 nM; MDA-MB-468, IC50 4 nM; MDA-MB-231, IC50 6 nM; MDA-MB-453, IC50 100 nM). ER-positive cell lines expressed all the assayed proteins of the IKK/NF-κB system while ER-negative cell lines lacked one or more elements of IKK/NF-κB. ER-negative SK-BR-3 cells were 200-fold more sensitive than ER-positive BT-474 cells; however bortezomib inhibited proteasome activity similarly in both cells. SKBR3 cells overexpressed c-Rel and RelB while had low levels of IKK-α, IκB-α and IκB-β. In clinical specimens, normal breast showed mainly weak p65NF-κB cytoplasmic staining and occasional faint nuclear staining. DCIS had strong and diffuse cytoplasmic p65NF-κB staining. Twelve out of 14 (86%) ER-negative infiltrating breast cancers exhibited p65NF-κB activation (i.e. nuclear staining), whereas only 2 out of 6 (33%) ER-positive specimens had p65NF-κB activation (p=0.037). Conclusions: An ER-negative status, coupled with a dysregulated IKK/NF-κB system, were linked to a greater antitumor effect of bortezomib. In vivo data further establishs that ER-negative breast cancers have commonly activated NF-κB. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Millennium Millennium
Value of Fibrosis Markers for Staging Liver Fibrosis in Patients With Precirrhotic Alcoholic Liver Disease (2008)

In alcoholic patients, various markers have limited value in predicting and diagnosing the stages of fibrosis compared to liver biopsy. Thus, further prospective studies are required to better define the usefulness of each marker or their combination which are possibly affected by alcohol metabolism.
Differentiation of liver progenitor cell line to functional organotypic cultures in 3D nanofibrillar cellulose and hyaluronan-gelatin hydrogels (2014)

Physiologically relevant hepatic cell culture models must be based on three-dimensional (3D) culture of human cells. However, liver cells are generally cultured in two-dimensional (2D) format that deviates from the normal in vivo morphology. We generated 3D culture environment for HepaRG liver progenitor cells using wood-derived nanofibrillar cellulose (NFC) and hyaluronan-gelatin (HG) hydrogels. Culture of undifferentiated HepaRG cells in NFC and HG hydrogels induced formation of 3D multicellular spheroids with apicobasal polarity and functional bile canaliculi-like structures, structural hallmarks of the liver tissue. Furthermore, hepatobiliary drug transporters, MRP2 and MDR1, were localized on the canalicular membranes of the spheroids and vectorial transport of fluorescent probes towards the biliary compartment was demonstrated. Cell culture in 3D hydrogel supported the mRNA expression of hepatocyte markers (albumin and CYP3A4), and metabolic activity of CYP3A4 in the HepaRG cell cultures. On the contrary, the 3D hydrogel cultures with pre-differentiated HepaRG cells showed decreasing expression of albumin and CYP3A4 transcripts as well as CYP3A4 activity. It is concluded that NFC and HG hydrogels expedite the hepatic differentiation of HepaRG liver progenitor cells better than the standard 2D culture environment. This was shown as improved cell morphology, expression and localization of hepatic markers, metabolic activity and vectorial transport. The NFC and HG hydrogels are promising materials for hepatic cell culture and tissue engineering.
Dose escalation study of tezacitabine in combination with cisplatin in patients with advanced cancer (2003)

Based on dose-limiting neutropenia and thrombocytopenia at the highest dose level, the recommended Phase II doses are 200 mg/m(2) of tezacitabine and 50 mg/m(2) of cisplatin.
Effect of Magnesium Sulfate Pretreatment and Significance of Matrix Metalloproteinase-1 and Interleukin-6 Levels in Coronary Reperfusion Therapy for Patients with Acute Myocardial Infarction (1999)

Magnesium (Mg) inhibits the influx of calcium in vascular smooth muscle cells. The purposes of this study were to test the hypothesis that an intravenous administration of magnesium might effect the complement response and to determine the effects of a magnesium pretreatment of patients with acute myocardial infarction (AMI) on the incidence of reperfusion injuries. Thirty-eight AMI patients were treated with coronary reperfusion therapy within 6 hours of onset. They were randomly divided into two groups: group pretreated with intravenous magnesium sulfate (0.27 mmol/kg) (magnesium group, n = 19), and nonpretreated controls (placebo group). The reperfusion injuries observed within 1 hour after the coronary reperfusion included arrhythmias, aggravated chest pain, and ST segment elevation in 12-lead electrocardiograms. Coronary recanalization was performed in 36 patients. The incidence of reperfusion arrhythmia was significantly lower in the magnesium group than in the placebo group (17% vs 78%, p<0.001). At the postreperfusion stage, there was a tendency for the degree of ST segment reelevation in the magnesium group lower than in the placebo group (2.5 +/- 2.3 mm vs 4.7 +/- 3.8 mm, p = 0.07). No marked difference was observed in the incidence of chest pain aggravation between the two groups (67% vs 73%, ns). The peak serum levels of interleukin-6 (IL-6) were significantly lower in the magnesium group than those in the placebo group (38.9 +/- 25.0 vs 92.3 +/- 76.5 pg/mL, p = 0.016). The peak serum levels of matrix metalloproteinase-1 (MMP-1) were lower than those in the placebo group (16.2 +/- 4.8 vs 19.7 +/- 9.0 ng/mL, p = 0.09), but the difference was not significant. A positive correlation was observed between the peak MMP-1 values and the peak IL-6 values (r = 0.57, p = 0.001) in all patients. Increased serum ionized Mg2+ may inhibit arrhythmic recurrence and the production of IL-6 and MMP-1 after reperfusion and prevent the increase of myocardial lesions caused by calcium overload on myocytes. The increased IL-6 production may induce MMP-1, leading to tissue organ injury. Pretreatment with magnesium sulfate may protect the myocardium of AMI patients from reperfusion injuries.
Squaring The Circle In The Hyperbolic Disk (2014)

Bolyai ended his 1832 introduction to non-Euclidean geometry with a strategy for constructing regular quadrilaterals (squares) and circles of the same area. In this article, we provide the steps for these constructions in the Poincare disk. We come to the surprising conclusion that Bolyai's strategy of building the circle and square separately is the only way to perform the constructions. That is, we cannot in general construct the square from the circle, nor vice versa.
Inflammation in Parkinsons Diseases and Other Neurodegenerative Diseases: Cause and Therapeutic Implications (2007)

Agents suppressing microglial activation are attracting attention as candidate drugs for neuroprotection in Parkinson s disease (PD): While different mechanisms including environmental toxins and genetic factors initiate neuronal damage in the substantia nigra and striatum in PD, there is unequivocal evidence that activation of neuroinflammatory cells aggravates this neurodegenerative process. It was shown that following an acute exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and other toxins the degenerative process continues for years in absence of the toxin. Reactive microglia has been observed in the substantia nigra of patients with PD, indicating that this inflammatory process might aggravate neurodegeneration. By releasing various kinds of noxious factors such as cytokines or proinflammatory molecules microglia may damage CNS cells. The stimuli triggering microgliosis in Parkinsonian syndromes are unknown so far: However, analysis of neuronal loss in PD patients shows that it is not uniform but that neurons containing neuromelanin (NM) are predominantly involved. We hypothesized that extraneuronal melanin might trigger microgliosis, microglial chemotaxis and microglial activation in PD with subsequent release of neurotoxic mediators. The addition of human NM to microglial cell cultures induced positive chemotactic effects, activated the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappaB) via phosphorylation and degradation of the inhibitor protein kappaB (IkappaB), and led to an upregulation of TNF-alpha, IL-6 and NO. These findings demonstrate a crucial role of NM in the pathogenesis of Parkinson's disease by augmentation of microglial activation, leading to a vicious cycle of neuronal death, exposure of additional neuromelanin and chronification of inflammation. Antiinflammatory drugs may be one of the new approaches in the treatment of PD.
A Common Dominant TLR5 Stop Codon Polymorphism Abolishes Flagellin Signaling and Is Associated with Susceptibility to Legionnaires' Disease (2003)

Although Toll-like receptors (TLRs) are critical mediators of the immune response to pathogens, the influence of polymorphisms in this gene family on human susceptibility to infection is poorly understood. We demonstrated recently that TLR5 recognizes flagellin, a potent inflammatory stimulus present in the flagellar structure of many bacteria. Here, we show that a common stop codon polymorphism in the ligand-binding domain of TLR5 (TLR5392STOP) is unable to mediate flagellin signaling, acts in a dominant fashion, and is associated with susceptibility to pneumonia caused by Legionella pneumophila, a flagellated bacterium. We also show that flagellin is a principal stimulant of proinflammatory cytokine production in lung epithelial cells. Together, these observations suggest that TLR5392STOP increases human susceptibility to infection through an unusual dominant mechanism that compromises TLR5's essential role as a regulator of the lung epithelial innate immune response.