gebhart/patrepeval huggingface dataset:
Hierarchical evolution of neural networks (2002)

In most applications of neuro-evolution, each individual in the population represents a complete neural network. Recent work on the SANE system, however, has demonstrated that evolving individual neurons often produces a more efficient genetic search. This paper demonstrates that while SANE can solve easy tasks very quickly, it often stalls in larger problems. A hierarchical approach to neuro-evolution is presented that overcomes SANE's difficulties by integrating both a neuron-level exploratory search and a network-level exploitive search. In a robot arm manipulation task, the hierarchical approach outperforms both a neuron-based search and a network-based search.
DNS-based Detection of Scanning Worms in an Enterprise Network. (2005)

Worms are arguably the most serious security threat facing the Internet. Seeking a detection technique that is both sufficiently efficient and accurate to enable automatic containment of worm propagation at the network egress points, we propose a new technique for the rapid detection of worm propagation from an enterprise network. It relies on the correlation of Domain Name System (DNS) queries with outgoing connections from an enterprise network. Improvements over existing scanning worm detection techniques include: (1) the possibility to detect worm propagation after only a single infection attempt; (2) the capacity to detect zero-day worms; and (3) a low false positive rate. The precision of this first-mile detection technique supports the use of automated containment and suppression strategies to stop fast scanning worms before they leave the network boundary. We believe that this technique can be applied with the same precision to identify other forms of malicious behavior within an enterprise network including: mass-mailing worms, network reconnaissance activity, and covert communications. Currently, it is unclear if our DNS-based detector will work for all network protocols. In some network environments, the DNS detection technique may need to be used as a secondary input to a more sophisticated anomaly detector.
Secure capabilities for a petabyte-scale object-based distributed file system (2005)

Recently, the Network-Attached Secure Disk (NASD) model has become a more widely used technique for constructing large-scale storage systems. However, the security system proposed for NASD assumes that each client will contact the server to get a capability to access one object on a server. While this approach works well in smaller-scale systems in which each file is composed of a few objects, it fails for large-scale systems in which thousands of clients make accesses to a single file composed of thousands of objects spread across thousands of disks. The file system we are building, Ceph, distributes files across many objects and disks to distribute load and improve reliability. In such a system, the metadata server cluster will sometimes see thousands of open requests for the same file within seconds. To address this bottleneck, we propose new authentication protocols for object-based storage systems in which a sequence of fixed-size objects comprise a file and flash crowds are likely. We qualitatively evaluated the security and risks of each protocol, and, using traces of a scientific application, compared the overhead of each protocol. We found that, surprisingly, a protocol using public key cryptography incurred little extra cost while providing greater security than a protocol using only symmetric key cryptography.
PointNet: Deep Learning on Point Sets for 3D Classification and Segmentation (2016)

Point cloud is an important type of geometric data structure. Due to its irregular format, most researchers transform such data to regular 3D voxel grids or collections of images. This, however, renders data unnecessarily voluminous and causes issues. In this paper, we design a novel type of neural network that directly consumes point clouds and well respects the permutation invariance of points in the input. Our network, named PointNet, provides a unified architecture for applications ranging from object classification, part segmentation, to scene semantic parsing. Though simple, PointNet is highly efficient and effective. Empirically, it shows strong performance on par or even better than state of the art. Theoretically, we provide analysis towards understanding of what the network has learnt and why the network is robust with respect to input perturbation and corruption.
Phase II, randomized, multicenter, comparative study of peginterferon–α–2a (40 kD) (Pegasys®)versusinterferon α-2a (Roferon®-A) in patients with treatment-naïve, chronic-phase chronic myelogenous leukemia (2007)

The efficacy and safety of peginterferon-alpha-2a (40 kD) (PEG-IFNalpha-2a), 450 microg once weekly, versus IFNalpha-2a, 9 MIU once daily, for 12 months, was evaluated in a Phase II study in IFN-naïve patients with chronic-phase, Philadelphia-chromosome-positive CML. At the end of the treatment, complete hematological response was observed in 66.2% (47/71) and 45.2% (33/73) of the PEG-IFNalpha-2a group and IFNalpha-2a groups, respectively (p = 0.009), and major cytogenetic response occurred in 35.2% and 17.8%, respectively (p = 0.016). PEG-IFNalpha-2a was at least as effective as IFNalpha-2a overall, including progression-free survival at the end of treatment, and overall survival after 30 months of follow-up. Adverse events necessitated fewer withdrawals but more dose adjustments in the PEG-IFNalpha-2a group compared with the IFNalpha-2a group (11%versus 23%, and 84.5%versus 65.8%, respectively). In conclusion, PEG-IFNalpha-2a (40 kD), 450 microg once weekly, compared with IFNalpha-2a, 9 MIU once daily, resulted in higher rates of hematologic and cytogenetic response and greater overall survival.
Rapid diagnosis of tuberculosis and multidrug resistance with the microscopic observation drug susceptibility assay in Ecuador. (2010)

A collaborative project was established between the Alli Causai Foundation in Ambato, Ecuador, and the University of Genoa, Italy, to introduce the microscopic observation drug susceptibility (MODS) assay for the rapid identification of Mycobacterium tuberculosis in Ecuador. A total of 507 samples were evaluated during a 10-month period, and DNA was extracted from each isolate and sent to Genoa for confirmatory molecular analysis. M. tuberculosis was identified in 45 samples by MODS, and drug resistance was observed in approximately 21% of the isolates, with four multidrug-resistant strains detected in two patients.
An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulation (2006)

Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness among the elderly in Western countries. Genetic factors, age, cigarette smoking, nutrition, and exposure to light have been identified as AMD risk factors. In this study, we investigated the association between ApoE C112R/R158C single nucleotide polymorphisms (which determine the E2, E3, and E4 isoforms) and age-related macular degeneration (AMD), and the mechanism underlying the association. Genomic DNA was extracted from 133 clinically screened controls, 94 volunteers with a younger mean age, 120 patients with advanced AMD, and 40 archived ocular AMD slides for single nucleotide polymorphism typing. The effects of recombinant ApoE isoforms on CCL2 (a chemokine), CX3CR1 (a chemokine receptor), and VEGF (a cytokine) expression in cultured human retinal pigment epithelium (RPE) cells were tested and serum cholesterol profiles of the clinically screened subjects were analyzed. ApoE112R (E4) distribution differed significantly between AMD patients and controls. ApoE112R allele frequency was 10.9% in the AMD group when compared with 16.5% in the younger controls and 18.8% in the clinically screened controls. The pathologically diagnosed archived AMD cases had the lowest allele frequency of 5%. No significant differences in ApoE158C (E2) distribution were observed among the groups. A meta-analysis of 8 cohorts including 4,289 subjects showed a strong association between AMD and 112R, but not 158C. In vitro studies found that recombinant ApoE suppresses CCL2 and VEGF expression in RPE cells. However, the E4 isoform showed more suppression than E3 in both cases. These results further confirm the association between ApoE112R and a decreased risk of AMD development. The underlying mechanisms may involve differential regulation of both CCL2 and VEGF by the ApoE isoforms.
Use of CpG oligodeoxynucleotides as immune adjuvants (2004)

Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs directly stimulate human B cells and plasmacytoid dendritic cells (pDCs), thereby promoting the production of T helper 1 (Th1) and pro-inflammatory cytokines and the maturation/activation of professional antigen-presenting cells. These activities enable CpG ODNs to act as immune adjuvants, accelerating and boosting antigen-specific immune responses by 5-500-fold. These effects are optimized by maintaining close physical contact between the CpG DNA and the immunogen. Animal challenge models establish that protective immunity can be accelerated and magnified by coadministering CpG DNA with vaccines. Ongoing clinical studies indicate that CpG ODNs are safe and well tolerated when administered as adjuvants to humans, and in some cases, they increase vaccine-induced immune responses.
Ligand‐Free Iron/Copper Cocatalyzed Alkynylation Coupling Reactions (2008)

Abstract Ligand‐free iron/copper cocatalyzed cross‐coupling reactions of aryl halides with terminal alkynes were carried out to provide the corresponding coupling products in good yields (up to 99%). Noteworthy is that this low‐cost, effective and environmentally friendly protocol was the first to be employed in alkynylation couplings.
Bacterial lipopolysaccharide transforms mesangial into proliferative lupus nephritis without interfering with processing of pathogenic immune complexes in NZB/W mice. (1990)

Systemic lupus erythematosus is a multifactorial systemic disease in which genetic, immunologic, hormonal, and environmental factors may contribute to disease pathogenesis. Bacterial products (eg, bacterial lipopolysaccharide [LPS]) induce a lupuslike disease in normal mice and trigger an early and accelerated form of lupus nephritis in NZB/W mice. To investigate whether the mechanism by which LPS accelerates nephritis in the NZB/W mice involves interference with processing of immune complexes (IC), we administered LPS to NZB/W mice for 5 weeks and probed the kinetics of removal, liver uptake, and organ localization of a subsaturating dose of radiolabeled IC (2.5 mg of bovine serum albumin-antibovine serum albumin). Control NZB/W mice received vehicle (saline) alone. In NZB/W exposed to LPS, features of polyclonal B-cell activation (PBA) were enhanced, anti-DNA antibodies were raised, and a proliferative glomerulonephritis developed that was associated with renal insufficiency and substantial proteinuria. This LPS-accelerated nephritis could not be attributed to altered complement concentration, to altered blood cell carrier function, to delayed removal of pathogenic (large-sized) ICs from the circulation, to impaired liver uptake of ICs, or to enhanced localization of ICs in kidney. The findings indicate that transformation of nephritis is probably the result of LPS-induced PBA, that defective processing of pathogenic IC is not a contributory factor to nephritis, and that mechanisms other than passive renal localization of circulating ICs must be operative.
Identification of Two Amino Acids in Activin A That Are Important for Biological Activity and Binding to the Activin Type II Receptors (1999)

Activins are members of the transforming growth factor-beta family of growth and differentiation factors. In this paper, we report the results of a structure-function analysis of activin A. The primary targets for directed mutagenesis were charged, individual amino acids located in accessible domains of the protein, concentrating on those that differ from transforming growth factor-beta2, the x-ray crystal structure of which is known. Based on the activities of the recombinant activin mutants in two bioassays, 4 out of 39 mutant proteins (D27K, K102A, K102E, and K102R) produced in a vaccinia virus system were selected for further investigation. After production in insect cells and purification of these four mutants to homogeneity, they were studied in bioassays and in cross-linking experiments involving transfected receptor combinations. Mutant D27K has a 2-fold higher specific bio-activity and binding affinity to an ActRIIA/ALK-4 activin receptor complex than wild type activin, whereas mutant K102E had no detectable biological activity and did not bind to any of the activin receptors. Mutant K102R and wild type activin bound to all the activin receptor combinations tested and were equipotent in bioassays. Our results with the Lys-102 mutants indicate that the positive charge of amino acid 102 is important for biological activity and type II receptor binding of activins.
Multiple Mechanisms of Cytokine Action in Neurodegenerative and Psychiatric States: Neurochemical and Molecular Substrates (2005)

Neuroinflammatory processes appear to play a fundamental role in the pathology associated with a number of neurodegenerative and psychiatric conditions. In this respect, the immunocompetent brain microglia and peripheral macrophages release a host of proinflammatory cytokines that not only modulate immunological processes but also influence neuronal functioning and even survival. For instance, alterations of the cytokines, tumor necrosis factor-alpha, as well as several of the interferons and interleukins have been associated with Parkinson's disease (PD) and clinical depression. Importantly, anti-inflammatory treatments that block these cytokines may impart protection against behavioural pathology and neuronal damage in animal models of PD and depression involving exposure to environmental toxins and stressors, respectively. The present review highlights the involvement of inflammatory cells and cytokines in depression and PD and explores some of the potential cellular and molecular mechanisms through which the immunotransmitters affect neuronal functioning. Attention is also devoted to the possibility that cytokines may sensitize neuroinflammatory pathways that, in turn, favour long-term pathology.
Low-Dose Cyclophosphamide Synergizes with Dendritic Cell-Based Immunotherapy in Antitumor Activity (2010)

Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor's offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide. Proportions of regulatory T cells and the cytotoxic T cell functions at different stages of disease were analyzed. We found that low-dose cyclophosphamide induced beneficial immunomodulatory effects by preventing the induction of Tregs, and as a consequence, cytotoxic T cell function was no longer affected. Addition of cyclophosphamide improved immunotherapy leading to an increased median and overall survival. Future studies are needed to address the usefulness of this combination treatment for mesothelioma patients.
Non-Fullerene-Acceptor-Based Bulk-Heterojunction Organic Solar Cells with Efficiency over 7% (2015)

A novel perylene bisimide (PBI) dimer-based acceptor material, SdiPBI-S, was developed. Conventional bulk-heterojunction (BHJ) solar cells based on SdiPBI-S and the wide-band-gap polymer PDBT-T1 show a high power conversion efficiency (PCE) of 7.16% with a high open-circuit voltage of 0.90 V, a high short-circuit current density of 11.98 mA/cm(2), and an impressive fill factor of 66.1%. Favorable phase separation and balanced carrier mobilites in the BHJ films account for the high photovoltaic performance. The results demonstrate that fine-tuning of PBI-based materials is a promising way to improve the PCEs of non-fullerene BHJ organic solar cells.
Direct reverse transcription-PCR on oligo(dT)-immobilized polypropylene microplates after capturing total mRNA from crude cell lysates (1998)

To simplify gene expression analysis, oligo(dT)-immobilized polypropylene microplates were used serially to capture mRNA, synthesize cDNA, and amplify specific genes. The amounts of immobilized oligonucleotide, hybridized mRNA, and synthesized cDNA were quantified fluorometrically using either Yoyo-1 or AttoPhos. The immobilized oligonucleotides captured approximately 40-55% of mRNA directly from crude cell lysates. Hybridized mRNA was then amplified by one-step reverse transcription (RT)-PCR with rTth polymerase or two-step PCR with initial cDNA synthesis followed by PCR, where the latter exhibited more sensitivity. In two-step RT-PCR, microplates can be reused for multiple PCRs with the same or different primer sets because synthesized cDNA was covalently attached to the plates at its 5' end. We believe this microplate may be acceptable as a platform for various mRNA expression analyses, including basic research, drug screening, and molecular toxicology, as well as for molecular pathological diagnostics.
Design and application of data interchange formats (DIFs) for improving interoperability in SBA (2012)

Data Interchange Formats(DIFs) can enhance interoperability of physically distributed organizations in Simulation Based Acquisition(SBA) process by being used as a template for exchanging information in Distributed Product Descriptions(DPDs) directly without data format interchange among different acquisition tools. In this paper, we propose a framework for developing DIF and demonstrate its validity by using XML-based implementation. Specifically, we show that Solid Edge CAD file can be converted to XML-based DIF file using the neutral format and to Robcad CAD file, while keeping the shape information as well as kinematics, axis, the surface information. Based on this work, we can increase the possibility to provide interoperability in Integrated Collaborative Environment(ICE) based SBA.
Homer: Passion in the Iliad (2005)

European literature begins with the word μηνιν (mênin). This is the accusative singular form of a Greek noun usually translated as “wrath”, “anger” or “rage”, but also connoting “bane” or “malice”. “The wrath sing, goddess, of Peleus’ son Achilles, that deadly anger which heaped up a myriad sorrows upon the Achaeans”: these are the first two lines of the Iliad, a formulaic oral composition probably of the later eighth century BC.1 These two lines, rather than the poem’s title, announce its theme and disclose its quality. This is the story not of the fall of Troy (Ilium), but of Achilles’ passion. The poem does not offer a sequential account of the Greek (Achaean) expedition to recover Helen from the Trojans, but represents the emotions and behaviour of Achilles and the other leading characters of the war in relation to a single illuminative episode in it.
Adenylate cyclase toxin (CyaA) of Bordetella pertussis. Evidence for the formation of small ion-permeable channels and comparison with HlyA of Escherichia coli. (1994)

The interaction between the adenylate cyclase toxin (CyaA) of Bordetella pertussis and lipid was studied using the lipid bilayer assay. The addition of CyaA to the aqueous phase bathing lipid bilayer membranes composed of different lipids resulted in the increase of the membrane conductance. This increase was rather small for membranes formed of pure lipids as compared with lipid mixtures such as asolectin. The toxin formed in asolectin membranes small transient ion-permeable channels with a single-channel conductance of 27 pS in 1 M KCl, which is considerably smaller than that of the alpha-hemolysin (HlyA) of Escherichia coli (1500 pS). Experiments with different salts suggested that the CyaA-induced channels were exclusively cation-selective because of negative charges localized at the channel mouth. The single-channel conductance of channels initiated by CyaA was independent of whether the toxin was purified from B. pertussis or from recombinant E. coli. However, the channel-forming activity of the CyaA expressed in B. pertussis was substantially higher than that of the recombinant toxin. Experiments with mutant forms of CyaA suggested that both the activation of CyaA by CyaC and the hemeolytic part of the toxin, but not the repeats and the cyclase activity, are required for channel formation in lipid bilayer membranes.
Effects of the Stationary Phase and the Solvent on the Stereodynamics of biphep Ligands Quantified by Dynamic Three‐Column HPLC (2012)

Dynamics and kinetics in a single stroke: The stereodynamics of the tropos-chiral diphosphine biphep and its 3,3′-dialkoxy analogues were investigated by enantioselective dynamic HPLC (DHPLC) and a novel three-column approach, in with the dynamics and kinetics of the interconversion were examined in a single experimental setup (see scheme). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
NVP-AUY922: a small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models (2008)

NVP-AUY922 is a potent small molecule HSP90 inhibitor showing significant activity against breast cancer cells in cellular and in vivo settings. On the basis of its mechanism of action, preclinical activity profile, tolerability, and pharmaceutical properties, the compound recently has entered clinical phase I breast cancer trials.
Real-time stochastic rasterization on conventional GPU architectures (2010)

This paper presents a hybrid algorithm for rendering approximate motion and defocus blur with precise stochastic visibility evaluation. It demonstrates---for the first time, with a full stochastic technique---real-time performance on conventional GPU architectures for complex scenes at 1920×1080 HD resolution. The algorithm operates on dynamic triangle meshes for which per-vertex velocity or corresponding vertices from the previous frame are available. It leverages multisample antialiasing (MSAA) and a tight space-time-aperture convex hull to efficiently evaluate visibility independently of shading. For triangles whose motion crosses the camera plane, we present a novel 2D bounding box algorithm that we conjecture is conservative. The sampling algorithm further reduces sample variance within primitives by integrating textures according to ray differentials in time and aperture.