gebhart/patrepeval huggingface dataset:
Non-Fc-Mediated Mechanisms Are Involved in Clearance of Amyloid-βIn Vivoby Immunotherapy (2002)

Transgenic (Tg) mouse models overexpressing amyloid precursor protein (APP) develop senile plaques similar to those found in Alzheimer's disease in an age-dependent manner. Recent reports demonstrated that immunotherapy is effective at preventing or removing amyloid-beta deposits in the mouse models. To characterize the mechanisms involved in clearance, we used antibodies of either IgG1 (10d5) or IgG2b (3d6) applied directly to the brains of 18-month-old Tg2576 or 20-month-old PDAPP mice. Both 10d5 and 3d6 led to clearance of 50% of diffuse amyloid deposits in both animal models within 3 d. Fc receptor-mediated clearance has been shown to be important in an ex vivo assay showing antibody-mediated clearance of plaques by microglia. We now show, using in vivo multiphoton microscopy, that FITC-labeled F(ab')2 fragments of 3d6 (which lack the Fc region of the antibody) also led to clearance of 45% of the deposits within 3 d, similar to the results obtained with full-length 3d6 antibody. This result suggests that direct disruption of plaques, in addition to Fc-dependent phagocytosis, is involved in the antibody-mediated clearance of amyloid-beta deposits in vivo. Dense-core deposits that were not cleared were reduced in size by approximately 30% with full-length antibodies and F(ab')2 fragments 3 d after a topical treatment. Together, these results indicate that clearance of amyloid deposits in vivo may involve, in addition to Fc-dependent clearance, a non-Fc-mediated disruption of plaque structure.
Improved Synthesis of ADAM10 Inhibitor GI254023X (2010)

This upscaled synthesis, free of diastereomeric intermediates, ensures single-batch identity, thus warranting its reproducibility in further biological investigations.
Technological progresses in monoclonal antibody production systems (2009)

Monoclonal antibodies (mAbs) have become vitally important to modern medicine and are currently one of the major biopharmaceutical products in development. However, the high clinical dose requirements of mAbs demand a greater biomanufacturing capacity, leading to the development of new technologies for their large-scale production, with mammalian cell culture dominating the scenario. Although some companies have tried to meet these demands by creating bioreactors of increased capacity, the optimization of cell culture productivity in normal bioreactors appears as a better strategy. This review describes the main technological progresses made with this intent, presenting the advantages and limitations of each production system, as well as suggestions for improvements. New and upgraded bioreactors have emerged both for adherent and suspension cell culture, with disposable reactors attracting increased interest in the last years. Furthermore, the strategies and technologies used to control culture parameters are in constant evolution, aiming at the on-line multiparameter monitoring and considering now parameters not seen as relevant for process optimization in the past. All progresses being made have as primary goal the development of highly productive and economic mAb manufacturing processes that will allow the rapid introduction of the product in the biopharmaceutical market at more accessible prices.
PML is induced by oncogenicrasand promotes premature senescence (2000)

Oncogenic ras provokes a senescent-like arrest in human diploid fibroblasts involving the Rb and p53 tumor suppressor pathways. To further characterize this response, we compared gene expression patterns between ras-arrested and quiescent IMR90 fibroblasts. One of the genes up-regulated during ras-induced arrest was promyelocytic leukemia (PML) protein, a potential tumor suppressor that encodes a component of nuclear structures known as promyelocytic oncogenic domains (PODs). PML levels increased during both ras-induced arrest and replicative senescence, leading to a dramatic increase in the size and number of PODs. Forced PML expression was sufficient to promote premature senescence. Like oncogenic ras, PML increased the levels of p16, hypophosphorylated Rb, phosphoserine-15 p53, and expression of p53 transcriptional targets. The fraction of Rb and p53 that colocalized with PML markedly increased during ras-induced arrest, and expression of PML alone forced p53 to the PODs. E1A abolished PML-induced arrest and prevented PML induction and p53 phosphorylation in response to oncogenic ras. These results imply that PML acts with Rb and p53 to promote ras-induced senescence and provide new insights into PML regulation and activity.
An eye for an eye: A single camera gaze-replacement method (2010)

The camera in video conference systems is typically positioned above, or below, the screen, causing the gaze of the users to appear misplaced. We propose an effective solution to this problem that is based on replacing the eyes of the user. This replacement, when done accurately, is enough to achieve a natural looking video. At an initialization stage the user is asked to look straight at the camera. We store these frames, then track the eyes accurately in the video sequence and replace the eyes, taking care of illumination and ghosting artifacts. We have tested the system on a large number of videos demonstrating the effectiveness of the proposed solution.
Rice seed priming (2005)

This article 'Rice seed priming' appeared in the International Rice Research Notes series, created by the International Rice Research Institute (IRRI) to expedite communication among scientists concerned with the development of improved technology for rice and rice-based systems. The series is a mechanism to help scientists keep each other informed of current rice research findings. The concise scientific notes are meant to encourage rice scientists to communicate with one another to obtain details on the research reported.
Formal verification made easy (1997)

Formal verification (FV) is considered by many to be complicated and to require considerable mathematical knowledge for successful application. We have developed a methodology in which we have added formal verification to the verification process without requiring any knowledge of formal verification languages. We use only finite-state machine notation, which is familiar and intuitive to designers. Another problem associated with formal verification is state-space explosion. If that occurs, no result is returned; our method switches to random simulation after one hour without results, and no effort is lost. We have compared FV against random simulation with respect to development time, and our results indicate that FV is at least as fast as random simulation. FV is superior in terms of verification quality, however, because it is exhaustive.
Type 1 T-regulatory cells: their role in the control of immune responses1 (2003)

The induction of tolerance is essential for the maintenance of immune homeostasis, for the prevention of autoimmune diseases, and to achieve transplantation tolerance. To induce tolerance, the immune system uses several mechanisms, including the deletion of autoreactive T cells, the induction of anergy, and active suppression of autoimmune responses. The mechanisms of thymic deletion and anergy of autoreactive T cells are well characterized, whereas active suppression by T-regulatory (Tr) cells, which has recently emerged as an essential component of the immune response to induce peripheral tolerance, is less well understood. Results from seminal studies by a number of laboratories have renewed interest in CD4+ T cells with regulatory properties. Although many aspects of the mechanisms by which these cells exert their effects have still to be elucidated, it is well established that T-regulatory cells suppress immune responses by means of cell-to-cell interactions or the production of interleukin (IL)-10, transforming growth factor (TGF)-beta, or both. Type-1 Tr (Tr1) cells are defined by their ability to produce high levels of IL-10 and TGF-beta. Tr1 cells specific for a variety of antigens arise in vivo but may also differentiate from naive CD4+ T cells in the presence of IL-10 in vitro. Tr1 cells have a low proliferative capacity. Tr1 cells suppress naive and memory T-helper type 1 or 2 responses by means of production of IL-10 and TGF-beta. Further characterization of Tr1 cells at the molecular level will define their mechanisms of action and clarify their relationship with other subsets of Tr cells. The use of Tr1 cells to identify novel targets for the development of new therapeutic agents, and as a cellular therapy to modulate peripheral tolerance, can be foreseen.
Suppression of Graft Coronary Artery Disease by a Brief Treatment With a Selective εPKC Activator and a δPKC Inhibitor in Murine Cardiac Allografts (2004)

An epsilonPKC activator and a deltaPKC inhibitor together reduced GCAD. Clinically, these PKC isozyme regulators may be useful for organ preservation and prevention of ischemia-reperfusion injury and graft coronary artery disease in cardiac transplantation.
A Formalization of the Security Features of Physical Functions (2011)

Physical attacks against cryptographic devices typically take advantage of information leakage (e.g., side-channels attacks) or erroneous computations (e.g., fault injection attacks). Preventing or detecting these attacks has become a challenging task in modern cryptographic research. In this context intrinsic physical properties of integrated circuits, such as Physical(ly) Unclonable Functions~(PUFs), can be used to complement classical cryptographic constructions, and to enhance the security of cryptographic devices. PUFs have recently been proposed for various applications, including anti-counterfeiting schemes, key generation algorithms, and in the design of block ciphers. However, currently only rudimentary security models for PUFs exist, limiting the confidence in the security claims of PUF-based security primitives. A useful model should at the same time (i) define the security properties of PUFs abstractly and naturally, allowing to design and formally analyze PUF-based security solutions, and (ii) provide practical quantification tools allowing engineers to evaluate PUF instantiations. In this paper, we present a formal foundation for security primitives based on PUFs. Our approach requires as little as possible from the physics and focuses more on the main properties at the heart of most published works on PUFs: robustness (generation of stable answers), unclonability (not provided by algorithmic solutions), and unpredictability. We first formally define these properties and then show that they can be achieved by previously introduced PUF instantiations. We stress that such a consolidating work allows for a meaningful security analysis of security primitives taking advantage of physical properties, becoming increasingly important in the development of the next generation secure information systems.
Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. (1999)

Recent evidence suggests that tumor cells may release DNA into the circulation, which is enriched in the serum and plasma, allowing detection of ras and p53 mutations and microsatellite alterations in the serum DNA of cancer patients. We examined whether aberrant DNA methylation might also be found in the serum of patients with non-small cell lung cancer. We tested 22 patients with non-small cell lung cancer using methylation-specific PCR, searching for promoter hypermethylation of the tumor suppressor gene p16, the putative metastasis suppressor gene death-associated protein kinase, the detoxification gene glutathione S-transferase P1, and the DNA repair gene O6-methylguanine-DNA-methyltransferase. Aberrant methylation of at least one of these genes was detected in 15 of 22 (68%) NSCLC tumors but not in any paired normal lung tissue. In these primary tumors with methylation, 11 of 15 (73%) samples also had abnormal methylated DNA in the matched serum samples. Moreover, none of the sera from patients with tumors not demonstrating methylation was positive. Abnormal promoter methylation in serum DNA was found in all tumor stages. Although these results need to be confirmed in larger studies and in other tumor types, detection of aberrant promoter hypermethylation of cancer-related genes in serum may be useful for cancer diagnosis or the detection of recurrence.
Synthesis and neuroleptic activity of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles (1985)

The synthesis of a series of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles is described. The neuroleptic activity of the series was evaluated by utilizing the climbing mice assay and inhibition of [3H]spiroperidol binding. Structure-activity relationships were studied by variation of the substituent on the benzisoxazole ring with concomitant variation of four different 1-piperidinyl substituents. Maximum neuroleptic activity was realized when there was a 6-fluoro substituent on the benzisoxazole ring. The 1-piperidinyl substituent appeared less significant, although in most cases, the (1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)propyl group imparted maximum potency. The most potent compound in both assays was 6-fluoro-3-[1-[3-(1,3-dihydro-2-oxo-2H-benzimidazol-1-yl) propyl]-4-piperidinyl]-1,2-benzisoxazole (11b).
DNA glycosylases in the base excision repair of DNA (1997)

A wide range of cytotoxic and mutagenic DNA bases are removed by different DNA glycosylases, which initiate the base excision repair pathway. DNA glycosylases cleave the N-glycosylic bond between the target base and deoxyribose, thus releasing a free base and leaving an apurinic/apyrimidinic (AP) site. In addition, several DNA glycosylases are bifunctional, since they also display a lyase activity that cleaves the phosphodiester backbone 3' to the AP site generated by the glycosylase activity. Structural data and sequence comparisons have identified common features among many of the DNA glycosylases. Their active sites have a structure that can only bind extrahelical target bases, as observed in the crystal structure of human uracil-DNA glycosylase in a complex with double-stranded DNA. Nucleotide flipping is apparently actively facilitated by the enzyme. With bacteriophage T4 endonuclease V, a pyrimidine-dimer glycosylase, the enzyme gains access to the target base by flipping out an adenine opposite to the dimer. A conserved helix-hairpin-helix motif and an invariant Asp residue are found in the active sites of more than 20 monofunctional and bifunctional DNA glycosylases. In bifunctional DNA glycosylases, the conserved Asp is thought to deprotonate a conserved Lys, forming an amine nucleophile. The nucleophile forms a covalent intermediate (Schiff base) with the deoxyribose anomeric carbon and expels the base. Deoxyribose subsequently undergoes several transformations, resulting in strand cleavage and regeneration of the free enzyme. The catalytic mechanism of monofunctional glycosylases does not involve covalent intermediates. Instead the conserved Asp residue may activate a water molecule which acts as the attacking nucleophile.
A feature definition language for bridging solids and features (1993)

Article A feature definition language for bridging solids and features Share on Authors: Timo Laakko View Profile , Martti Mäntylä View Profile Authors Info & Claims SMA '93: Proceedings on the second ACM symposium on Solid modeling and applicationsJune 1993 Pages 333–342https://doi.org/10.1145/164360.164464Online:01 June 1993Publication History 10citation369DownloadsMetricsTotal Citations10Total Downloads369Last 12 Months5Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Discovery and biological characterization of potent myeloid cell leukemia‐1 inhibitors (2016)

Comp. 2: 5IEZ; Comp. 5: 5IF4.
Inflammation and Atherosclerosis (2002)

Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an ongoing inflammatory response. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and, ultimately, the thrombotic complications of atherosclerosis. These new findings provide important links between risk factors and the mechanisms of atherogenesis. Clinical studies have shown that this emerging biology of inflammation in atherosclerosis applies directly to human patients. Elevation in markers of inflammation predicts outcomes of patients with acute coronary syndromes, independently of myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker C-reactive protein, prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors. Moreover, certain treatments that reduce coronary risk also limit inflammation. In the case of lipid lowering with statins, this anti-inflammatory effect does not appear to correlate with reduction in low-density lipoprotein levels. These new insights into inflammation in atherosclerosis not only increase our understanding of this disease, but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance.
Estrogen Therapy in Postmenopausal Women (1998)

There are plausible biological mechanisms by which estrogen might lead to improved cognition, reduced risk for dementia, or improvement in the severity of dementia. Studies conducted in women, however, have substantial methodologic problems and have produced conflicting results. Large placebo-controlled trials are required to address estrogen's role in prevention and treatment of Alzheimer disease and other dementias. Given the known risks of estrogen therapy, we do not recommend estrogen for the prevention or treatment of Alzheimer disease or other dementias until adequate trials have been completed.
Hepatitis B core antigen synthesised in Escherichia coli: its use for antibody screening in patients attending a clinic for sexually transmitted diseases (1984)

Hepatitis B core antigen (HBcAg) synthesised in Escherichia coli by recombinant DNA techniques was compared with HBcAg prepared from infected liver tissue. The two antigens were used in radioimmunoassays (RIA) to detect antibody to HBcAg (anti-HBc) in sera from patients attending a clinic for sexually transmitted diseases. Out of 2151 sera tested, 260 were anti-HBc positive with both HBcAg preparations but seven were positive with the liver-derived antigen alone. Reasons for these discrepant results are discussed. The slight loss of sensitivity of the anti-HBc RIA using E. coli HBcAg was not considered significant when compared with the potential advantages of a synthetic antigen. The presence of other hepatitis B markers in the 267 anti-HBc positive sera was determined: 25 contained HBsAg, 220 anti-HBs and, of the 22 that were HBsAg/anti-HBs negative, 12 contained anti-HBe. In the 10 remaining sera, anti-HBc was the only hepatitis B marker that could be found.
Performance evaluation of public-key certificate revocation system with balanced hash tree (2003)

A new method for updating certificate revocation trees (CRT) is proposed. Efficient revocation of public-key certificates is a current issue in public-key infrastructure because a traditional certificate revocation list uses a large amount of bandwidth. A certificate revocation tree is a hash tree of revoiced certificates and reduces a bandwidth consumption up to O(log(n)). In this paper, an implementation of certificate revocation tree with S-expression is presented and the performance of the system is evaluated in terms of communication and computational costs. To update a CRT, we have two algorithms; (1) random insertion-a new certificate to be revoiced is just inserted into the existing tree and (2) balancing updating-balances CRT every time a new certificate is added.
Geometric Entangling Gates in Decoherence-Free Subspaces with Minimal Requirements (2009)

We introduce a new strongly driven dispersive atom-cavity interaction and develop a new scheme for implementing the nontrivial entangling gates for two logical qubits in decoherence-free subspaces (DFSs). Our scheme combines the robust advantages of DFS and the geometric phase. Moreover, only two neighboring physical qubits, which encode a logical qubit, are required to undergo the collective dephasing in our scheme.
Orexin A (hypocretin 1) injected into hypothalamic paraventricular nucleus and spontaneous physical activity in rats (2004)

In humans, nonexercise activity thermogenesis (NEAT) increases with positive energy balance. The mediator of the interaction between positive energy balance and physical activity is unknown. In this study, we address the hypothesis that orexin A acts in the hypothalamic paraventricular nucleus (PVN) to increase nonfeeding-associated physical activity. PVN-cannulated rats were injected with either orexin A or vehicle during the light and dark cycle. Spontaneous physical activity (SPA) was measured using arrays of infrared activity sensors and night vision videotaped recording (VTR). O(2) consumption and CO(2) production were measured by indirect calorimetry. Feeding behavior was assessed by VTR. Regardless of the time point of injection, orexin A (1 nmol) was associated with dramatic increases in SPA for 2 h after injection (orexin A: 6.27 +/- 1.95 x 10(3) beam break count, n = 24; vehicle: 1.85 +/- 1.13 x 10(3), n = 38). This increase in SPA was accompanied by compatible increase in O(2) consumption. Duration of feeding was increased only when orexin A was injected in the early light phase and accounted for only 3.5 +/- 2.5% of the increased physical activity. In a dose-response experiment, increases in SPA were correlated with dose of orexin A linearly up to 2 nmol. PVN injections of orexin receptor antagonist SB-334867 were associated with decreases in SPA and attenuated the effects of PVN-injected orexin A. Thus orexin A can act in PVN to increase nonfeeding-associated physical activity, suggesting that this neuropeptide might be a mediator of NEAT.