gebhart/patrepeval huggingface dataset:
A 45nm CMOS neuromorphic chip with a scalable architecture for learning in networks of spiking neurons (2011)

Efforts to achieve the long-standing dream of realizing scalable learning algorithms for networks of spiking neurons in silicon have been hampered by (a) the limited scalability of analog neuron circuits; (b) the enormous area overhead of learning circuits, which grows with the number of synapses; and (c) the need to implement all inter-neuron communication via off-chip address-events. In this work, a new architecture is proposed to overcome these challenges by combining innovations in computation, memory, and communication, respectively, to leverage (a) robust digital neuron circuits; (b) novel transposable SRAM arrays that share learning circuits, which grow only with the number of neurons; and (c) crossbar fan-out for efficient on-chip inter-neuron communication. Through tight integration of memory (synapses) and computation (neurons), a highly configurable chip comprising 256 neurons and 64K binary synapses with on-chip learning based on spike-timing dependent plasticity is demonstrated in 45nm SOI-CMOS. Near-threshold, event-driven operation at 0.53V is demonstrated to maximize power efficiency for real-time pattern classification, recognition, and associative memory tasks. Future scalable systems built from the foundation provided by this work will open up possibilities for ubiquitous ultra-dense, ultra-low power brain-like cognitive computers.
Thermodynamics of protein destabilization in live cells (2015)

Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a β-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37 °C but with a conspicuous twist: While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components, acting preferentially on the unfolded ensemble. This points to a model where the in vivo influence on protein behavior is case specific, determined by the individual protein's interplay with the functionally optimized "interaction landscape" of the cellular interior.
Loss of TRAIL-Receptors Is a Recurrent Feature in Pancreatic Cancer and Determines the Prognosis of Patients with No Nodal Metastasis after Surgery (2013)

This is a first report on the prognostic significance of TRAIL-receptors expression in pancreatic cancer showing that TRAIL-R2 might represent a prognostic marker for patients with early stage disease. In addition, our data suggest that loss of membrane-bound TRAIL-receptors could represent a molecular mechanism for therapeutic failure upon administration of TRAIL-receptors-targeting antibodies in pancreatic cancer. This hypothesis should be evaluated in future clinical trials.
Comparison of circulating CA15-3 and carcinoembryonic antigen levels in patients with breast cancer. (1986)

An immunoradiometric assay (IRMA) has been used to determine circulating levels of the breast cancer-associated antigen, CA15-3. Of 1,050 normal control subjects, serum from 99 (9.4%) had CA15-3 antigen levels greater than 22 U/mL, while that from 58 (5.5%) and 14 (1.3%) had levels greater than 25 U/mL and 30 U/mL, respectively. In contrast, 115 of 158 patients (73%) with metastatic breast cancer had CA15-3 levels greater than 22 U/mL. Thirteen of 26 patients (50%) with only local metastases, 27 of 34 (79%) of those with only bone metastases, and 20 of 24 (83%) with hepatic metastases had CA15-3 levels greater than 22 U/mL. Furthermore, nine of 31 patients (29%) with primary breast cancer had CA15-3 levels greater than 22 U/mL. CA15-3 and carcinoembryonic antigen (CEA) levels were compared for the same patient population. Significantly more patients with metastatic breast cancer had elevated CA15-3 levels than had elevated CEA levels (P less than .001). Furthermore, the CA15-3 IRMA was more sensitive than the CEA assay in patients with only bone metastases, as well as those with only local metastases. Significantly more patients with primary carcinoma of the breast also had elevated CA15-3 than had elevated CEA levels (P less than .02). CA15-3 levels were greater than 22 U/mL in patients with nonmalignant conditions, including five of 25 patients (20%) with benign breast diseases, and 23 of 52 patients (44%) with benign liver diseases. Furthermore, CA15-3 levels were also greater than 22 U/mL in 24 of 54 patients (44%) with gastrointestinal (GI) malignancies, 12 of 17 patients (71%) with bronchogenic carcinoma, and 29 of 44 patients (66%) with epithelial ovarian carcinoma. Serial CA15-3 levels correlated with clinical disease course. Nineteen of 21 patients (91%) with tumor progression had at least a 25% increase in CA15-3 levels. Conversely, seven of nine patients (78%) with tumor regression had at least a 50% decrease in CA15-3 levels. Among 27 patients with stable disease, 16 (59%) had levels that did not vary by more than +/- 25% of the original CA15-3 levels. These results indicate that the CA15-3 antigen is a sensitive marker for the evaluation and monitoring of patients with breast cancer.
A review of melt extrusion additive manufacturing processes: I. Process design and modeling (2014)

Purpose – The purpose of this paper is to systematically and critically review the literature related to process design and modeling of fused deposition modeling (FDM) and similar extrusion-based additive manufacturing (AM) or rapid prototyping processes. Design/methodology/approach – A systematic review of the literature focusing on process design and mathematical process modeling was carried out. Findings – FDM and similar processes are among the most widely used rapid prototyping processes with growing application in finished part manufacturing. Key elements of the typical processes, including the material feed mechanism, liquefier and print nozzle; the build surface and environment; and approaches to part finishing are described. Approaches to estimating the motor torque and power required to achieve a desired filament feed rate are presented. Models of required heat flux, shear on the melt and pressure drop in the liquefier are reviewed. On leaving the print nozzle, die swelling and bead cooling are considered. Approaches to modeling the spread of a deposited road of material and the bonding of polymer roads to one another are also reviewed. Originality/value – To date, no other systematic review of process design and modeling research related to melt extrusion AM has been published. Understanding and improving process models will be key to improving system process controls, as well as enabling the development of advanced engineering material feedstocks for FDM processes.
Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon (2010)

Vancomycin, metronidazole, and the bacteriocin lacticin 3147 are active against a wide range of bacterial species, including Clostridium difficile. We demonstrate that, in a human distal colon model, the addition of each of the three antimicrobials resulted in a significant decrease in numbers of C. difficile. However, their therapeutic use in the gastrointestinal tract may be compromised by their broad spectrum of activity, which would be expected to significantly impact on other members of the human gut microbiota. We used high-throughput pyrosequencing to compare the effect of each antimicrobial on the composition of the microbiota. All three treatments resulted in a decrease in the proportion of sequences assigned to the phyla Firmicutes and Bacteroidetes, with a corresponding increase in those assigned to members of the Proteobacteria. One possible means of avoiding such "collateral damage" would involve the application of a narrow-spectrum antimicrobial with specific anti-C. difficile activity. We tested this hypothesis using thuricin CD, a narrow-spectrum bacteriocin produced by Bacillus thuringiensis, which is active against C. difficile. The results demonstrated that this bacteriocin was equally effective at killing C. difficile in the distal colon model but had no significant impact on the composition of the microbiota. This offers the possibility of developing a targeted approach to eliminating C. difficile in the colon, without collateral damage.
Characterization of human Gadd45, a p53-regulated protein. (1994)

GADD45 (growth arrest and DNA damage) is a DNA-damage-inducible gene regulated in part by the tumor suppressor p53. A role in negative growth control has recently been suggested based on significant (more than 75%) reduction of colony formation following over expression of Gadd45. To better understand the role of Gadd45, we have developed specific rabbit and murine antibodies raised against the human recombinant protein. Using these antibodies, we have found that in ML-1 cells Gadd45 is predominantly a nuclear protein. MyD118, a protein induced by terminal differentiation sharing 57% homology with Gadd45, does not cross-react with any of the antibodies produced. As expected, the induction of Gadd45 protein by ionizing radiation (IR) was also found to be dependent on a wild type p53 phenotype. Interestingly, WI-L2-NS, a human lymphoid cell line, showed very high basal levels of Gadd45 mRNA and protein in addition to a high constitutive level of a mutated p53 protein. In this cell line, the high levels of GADD45 did not inhibit cellular growth in spite of the fact that no mutations were found in GADD45 sequence. These results indicate that some cell line(s) can tolerate high levels of Gadd45 and abrogate its growth suppression function.
Secure remote access to an Internet Web server (1999)

We address the problem of secure remote access to a site's internal Web server from outside the firewall. The goal is to give authorized users access to sensitive information, while protecting the information from others. We implemented our solution using a one-time password scheme for client authentication and secure socket layer (SSL) for confidentiality. Our main design considerations were security, performance, ease of use, availability, and scale. We were further constrained by the desire to leave our firewall and local infrastructure unchanged.
Elucidation of the Biosynthesis of Eicosapentaenoic Acid in the Microalga Porphyridium cruentum (II. Studies with Radiolabeled Precursors) (1997)

In the course of the study of the biosynthesis of the fatty acid eicosapentaenoic acid (EPA) in the microalga Porphyridium cruentum, cells were pulse-labeled with various radiolabeled fatty acid precursors. Our data show that the major end products of the biosynthesis are EPA-containing galactolipids of a eukaryotic and prokaryotic nature. The prokaryotic molecular species contain EPA and arachidonic acid at the sn-1 position and C16 fatty acids, mainly 16:0, at the sn-2 positions, whereas in the eukaryotic species both positions are occupied by EPA or arachidonic acid. However, we suggest that both the eukaryotic and prokaryotic molecular species are formed in two pathways, [omega]6 and [omega]3, which involve cytoplasmic and chloroplastic lipids. In the [omega]6 pathway, cytoplasmic 18:2-phosphatidylcholine (PC) is converted to 20:4[omega]6-PC by a sequence that includes a [delta]6 desaturase, an elongation step, and a [delta]5 desaturase. In the minor [omega]3 pathway, 18:2-PC is presumably desaturated to 18:3[omega]3, which is sequentially converted by the enzymatic sequence of the [omega]6 pathway to 20:5[omega]3-PC. The products of both pathways are exported, as their diacylglycerol moieties, to the chloroplast to be galactosylated into their respective monogalactosyldiacylglycerol molecular species. The 20:4[omega]6 in both eukaryotic and prokaryotic monogalactosyldiacylglycerol can be further desaturated to EPA by a chloroplastic [delta]17 ([omega]3) desaturase.
A simple method for generating single-stranded DNA probes labeled to high activities (1990)

Journal Article A simple method for generating single-stranded DNA probes labeled to high activities Get access M. Espelund, M. Espelund Division of General Genetics, University of OsloPO Box 1031, Blindern, N-0315 Oslo 3, Norway Search for other works by this author on: Oxford Academic PubMed Google Scholar R.A.Prentice Stacy, R.A.Prentice Stacy Division of General Genetics, University of OsloPO Box 1031, Blindern, N-0315 Oslo 3, Norway Search for other works by this author on: Oxford Academic PubMed Google Scholar K.S. Jakobsen K.S. Jakobsen * Division of General Genetics, University of OsloPO Box 1031, Blindern, N-0315 Oslo 3, Norway *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 20, 25 October 1990, Pages 6157–6158, https://doi.org/10.1093/nar/18.20.6157 Published: 25 October 1990 Article history Received: 31 August 1990 Published: 25 October 1990
Mapping and Engineering Functional Domains of the Assembly-Activating Protein of Adeno-associated Viruses (2018)

Adeno-associated viruses (AAVs) encode a unique assembly-activating protein (AAP) within their genomes that is essential for capsid assembly. Studies to date have focused on establishing the role of AAP as a chaperone that mediates the stability, nucleolar transport, and assembly of AAV capsid proteins. Here, we map structure-function correlates of AAP using secondary structure analysis, followed by deletion and substitutional mutagenesis of specific domains, namely, the N-terminal hydrophobic region (HR), conserved core (CC), proline-rich region (PRR), threonine/serine-rich region (T/S), and basic region (BR). First, we establish that the centrally located PRR and T/S are flexible linker domains that can either be deleted completely or replaced by heterologous functional domains that enable ancillary functions such as fluorescent imaging or increased AAP stability. We also demonstrate that the C-terminal BR domains can be substituted with heterologous nuclear or nucleolar localization sequences that display various abilities to support AAV capsid assembly. Further, by replacing the BR domain with immunoglobulin (IgG) Fc domains, we assessed AAP complexation with AAV capsid subunits and demonstrate that the hydrophobic region (HR) and the conserved core (CC) in the AAP N terminus are the sole determinants for viral protein (VP) recognition. However, VP recognition alone is not sufficient for capsid assembly. Our study sheds light on the modular structure-function correlates of AAP and provides multiple approaches to engineer AAP that might prove useful toward understanding and controlling AAV capsid assembly.<b>IMPORTANCE</b> Adeno-associated viruses (AAVs) encode a unique assembly-activating protein (AAP) within their genomes that is essential for capsid assembly. Understanding how AAP acts as a chaperone for viral assembly could help improve efficiency and potentially control this process. Our studies reveal that AAP has a modular architecture, with each module playing a distinct role and can be engineered for carrying out new functions.
Temporal study of the activity of matrix metalloproteinases and their endogenous inhibitors during wound healing (1996)

The restoration of functional connective tissue is a major goal of the wound healing process. This regenerative event requires the deposition and accumulation of collagenous and noncollagenous matrix molecules as well as the remodelling of extracellular matrix (ECM) by matrix metalloproteinases (MMPs). In this study, we have utilized substrate gel electrophoresis, radiometric enzyme assays, and Western blot analyses to determine the temporal pattern of appearance and activity of active and latent MMPs and their inhibitors during the entire healing process in a partial thickness wound model. Through the use of substrate gel electrophoresis, we studied the appearance of proteolytic bands whose molecular weight was consistent with their being members of the MMP family of enzymes. Proteolytic bands whose molecular weight is consistent with both the active and latent forms of MMP-2 (72 kDa, Type IV gelatinase) were detected in wound fluid of days 1-7 after wounding. The number of active MMP-2 species detectable in wound fluid was greatest during days 4-6 after wounding. The most prominent proteolytic band detected each day migrated with a molecular weight consistent with it being the latent form of MMP-9 (92 kDa, Type V pro-collagenase). In contrast to MMP-2, the active form of this enzyme was never detected. The presence of MMP-1 (interstitial collagenase) was detected by immunoblot in the wound fluid from days 1-6 post-injury. Using a radiometric enzyme assay for collagenase inhibitory activity we have also determined the time course of activity of endogenous matrix metalloproteinase inhibitors. We have correlated these data to the known cellular events occurring in the wound during this time period as well. This study establishes a prototypical pattern of MMP appearance in normal wound healing. It may also provide potential intervention sites for the therapeutic use of inhibitors of aberrant MMP activities which characterize chronic wounds.
Formation of protein micelles from amphiphilic membrane proteins. (1978)

The membrane penicillinase (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6) from Bacillus licheniformis, the Semliki Forest virus spike proteins, and the Sendai virus glycoproteins have each been isolated as soluble protein aggregates that are virtually free of lipid and detergent. The sedimentation coefficients of the complexes were 18 S, 29 S, and 43 S, respectively. Mixed aggregates containing both the virus glycoproteins and the penicillinase could also be formed. Such protein micelles may serve a number of useful purposes in membrane research.
Implementation of road traffic signs detection based on saliency map model (2008)

In this paper, we proposed a new road traffic sign detection model based on human-like selective attention mechanism for implementing interactive workload manager system. Since the road traffic sign boards have dominant color contrast against backgrounds, we consider the color opponents and its edge information with center surround difference and normalization as a pre-processing, which is effective to intensify the sign board color characteristics as well as reduce background noise influence. After constructing the road traffic sign saliency map using the edge and color feature maps, the candidate road traffic sign regions are selected by local maximum energy searching with entropy maximization algorithm to find suitable size of the sign board areas. Computational experiment results show that the proposed model can successfully detect a road traffic sign board.
Analysis of resolution limitation of integral photography (1998)

The resolution limitation of integral photography (IP) is analyzed. Estimating the resolution of IP measured at the viewpoint, we derive the optimum width of the aperture or lens. It is shown that the resolution of aperture-plate IP is lower than conventional two-dimensional displays, even with an optimum design. When the ideal lens is utilized, however, lens-array IP can provide a three-dimensional display that is free from any discontinuous change of images that occur with the observer’s movement and with the same resolution that conventional two-dimensional displays feature.
Increased protein kinase C activity is linked to reduced insulin receptor autophosphorylation in liver of starved rats. (1990)

Phosphorylation of the insulin receptor beta-subunit on serine/threonine residues by protein kinase C reduces both receptor kinase activity and insulin action in cultured cells. Whether this mechanism regulates insulin action in intact animals was investigated in rats rendered insulin-resistant by 3 days of starvation. Insulin-stimulated autophosphorylation of the partially purified hepatic insulin receptor beta-subunit was decreased by 45% in starved animals compared to fed controls. This autophosphorylation defect was entirely reversed by removal of pre-existing phosphate from the receptor with alkaline phosphatase, suggesting that increased basal phosphorylation on serine/threonine residues may cause the decreased receptor tyrosine kinase activity. Tryptic removal of a C-terminal region of the receptor beta-subunit containing the Ser/Thr phosphorylation sites similarly normalized receptor autophosphorylation. To investigate which kinase(s) may be responsible for such increased Ser/Thr phosphorylation in vivo, protein kinase C and cAMP-dependent protein kinase A in liver were studied. A 2-fold increase in protein kinase C activity was found in both cytosol and membrane extracts from starved rats as compared to controls, while protein kinase A activity was diminished in the cytosol of starved rats. A parallel increase in protein kinase C was demonstrated by immunoblotting with a polyclonal antibody which recognizes several protein kinase C isoforms. These findings suggest that in starved, insulin-resistant animals, an increase in hepatic protein kinase C activity is associated with increased Ser/Thr phosphorylation which in turn decreases autophosphorylation and function of the insulin receptor kinase.
Effects of Systemic Demethylchlortetracycline on Human Cutaneous Microflora (1969)

The aerobic flora of the axilla and forehead of 20 normal human subjects was studied through a 3-week course of 600 mg of demethylchlortetracycline daily and a 3-week follow-up. In general in the axilla, an initial fall in bacterial density was followed by recovery in numbers due to the proliferation of resistant coagulase-negative cocci and diminution of the lipophilic diphtheroid group of bacteria within 1 week of treatment. During the remainder of the treatment period, the flora was essentially stable in both density and composition. In the follow-up phase, the initial flora was slowly re-established but resistant cocci persisted for more than 3 weeks. On the forehead the fall in density was slower and recovery during treatment was incomplete. Resistant coagulase-negative cocci became dominant and persisted through the follow-up phase. In two individuals, temporary colonization of the axilla by Staphylococcus aureus was seen.
Silver-Mediated Trifluoromethoxylation of Aryl Stannanes and Arylboronic Acids (2011)

A silver-mediated cross-coupling of trifluoromethoxide with aryl stannanes and arylboronic acids to give aryl trifluoromethyl ethers is reported. This is the first report of a transition-metal-mediated C(aryl)-OCF(3) bond formation.