gebhart/patrepeval huggingface dataset:
Design for effective thermalization of junctions for quantum coherence (2001)

We present a design for effectively isolating low-dissipation superconducting tunnel junctions without causing excessive heating. In order to obtain a long decoherence time in macroscopic quantum coherence experiments, it will be essential to make high impedance connections to the junction. In our design, the connections are made by thin-film resistors. To prevent excessive heating, we divide the resistors into many short sections, each of which is heat-sunk to small metal banks. We rely on electron diffusion to carry the heat out of the resistors and into the banks. We calculate the resulting temperature profile in the resistors and discuss the effect on the decoherence time of the junction.
Treatment with anti‐CR3 antibodies ED7 and ED8 suppresses experimental allergic encephalomyelitis in Lewis rats (1993)

Experimental allergic encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS). Among the leukocytes which infiltrate the CNS during EAE, numerous macrophages are present. These macrophages are thought to play a crucial role in the generation of tissue damage and attendant neurological deficits. The mechanism by which the macrophages migrate across the blood-brain barrier is not yet clear. Membrane proteins involved in macrophage adherence to the endothelium include the CD11b/CD18 integrin, also known as the type 3 complement receptor (CR3). In this study we show that two monoclonal antibodies (mAb) ED7 and ED8 are directed against rat CR3. In addition, these mAb reduce recruitment of myelomonocytic cells towards thioglycollate induced peritonitis by 15-33%. This indicates that both ED7 and ED8 interfere with an epitope on CR3, which is involved in recruitment of phagocytes towards inflammatory lesions. Intravenous injection of ED7 and ED8 suppressed clinical signs of EAE. MRC OX-42, which also recognizes CR3, did not reduce thioglycollate-induced phagocyte recruitment into the peritoneum, and had no effect on EAE. These findings suggest that CR3 plays a role in the recruitment of macrophages towards the inflamed CNS of EAE animals, and confirm the role of macrophages in the generation of clinical signs of EAE. Involvement of CR3 in other phagocyte immune functions during EAE is discussed.
Intronic Alus Influence Alternative Splicing (2008)

Examination of the human transcriptome reveals higher levels of RNA editing than in any other organism tested to date. This is indicative of extensive double-stranded RNA (dsRNA) formation within the human transcriptome. Most of the editing sites are located in the primate-specific retrotransposed element called Alu. A large fraction of Alus are found in intronic sequences, implying extensive Alu-Alu dsRNA formation in mRNA precursors. Yet, the effect of these intronic Alus on splicing of the flanking exons is largely unknown. Here, we show that more Alus flank alternatively spliced exons than constitutively spliced ones; this is especially notable for those exons that have changed their mode of splicing from constitutive to alternative during human evolution. This implies that Alu insertions may change the mode of splicing of the flanking exons. Indeed, we demonstrate experimentally that two Alu elements that were inserted into an intron in opposite orientation undergo base-pairing, as evident by RNA editing, and affect the splicing patterns of a downstream exon, shifting it from constitutive to alternative. Our results indicate the importance of intronic Alus in influencing the splicing of flanking exons, further emphasizing the role of Alus in shaping of the human transcriptome.
Power Reduction of Functional Units Considering Temperature and Process Variations (2008)

Continuous technology scaling has resulted in an increase in both, the power density as well as the variation in device dimensions (process variations) of the manufactured processors. Both power density and process variations have a significant impact on the leakage power. Therefore, power optimization techniques should be sensitive to the variation in leakage power due to both temperature as well as process variations. Operation to functional units binding mechanism (OFBM) is the mechanism to dynamically issue operations to functional units (FUs) in superscalar processors. We propose a leakage-aware OFBM (LA-OFBM), which is both temperature and process variation aware. Our experimental results demostrate that LA-OFBM reduces the mean and standard deviation of the total energy consumption of ALUs by 18%, and 46% respectively, as compared to the traditional OFBM, without any performance penalty.
Isolation of a peptide transport-deficient mutant of yeast (1978)

A peptide transport mutant of a leucine-lysine auxotroph of Saccharomyces cerevisiae (strain Z1-2D) was isolated on the basis of its resistance to L-ethionyl-L-alanine. The mutant, designated Z1-2D Etar, did not utilize di- and tripeptides containing leucine or lysine although it contained peptidases which released the required amino acids from these substrates. S. cerevisiae Z1-2D Etar did not accumulate radioactivity from [14C]glycyl-L-leucine under conditions identical to those in which the parent took up the label from this dipeptide. These results indicate that the mutant lacks the cellular mechanism to transport peptides to the site of the peptidase activity and that di- and tripeptides share a common mode of entry into yeast.
Contribution of CpG motifs to the immunogenicity of DNA vaccines (1997)

We previously showed that bacterial DNA contains immunostimulatory motifs consisting of unmethylated CpG dinucleotides flanked by two 5' purines and two 3' pyrimidines. These motifs rapidly trigger an innate immune response, characterized by the production of IL-6, IL-12, and IFN-gamma. Since DNA vaccines are constructed from plasmids of bacterial DNA, we examined whether CpG motifs present in these plasmids contributed to the immunogenicity of DNA vaccines. In vitro experiments showed that DNA plasmids induced production of the same cytokines stimulated by bacterial DNA, an effect eliminated by DNase treatment. In vivo experiments showed that the immunogenicity of a DNA vaccine was significantly reduced by methylating its CpG motifs and was significantly increased by coadministering exogenous CpG-containing DNA. These findings support the conclusion that CpG motifs in the plasmid backbone of DNA vaccines play an important role in the induction of Ag-specific immunity.
Cancer immunotherapy: The past, the present and the future (2003)

One of the most controversial issues in immunology for over a century has been whether an effective immune response can be elicited against malignant tumours. Whether the immunology community has believed cancer immunotherapy is feasible or impossible has been largely determined by the prevailing immunological paradigms at that time. In fact, during the last 110 years it is possible to trace at least five dramatic fluctuations in attitude towards cancer immunotherapy. It now appears, however, that overwhelming evidence is available to support the view that both the innate and adaptive immune responses can recognize and eliminate tumours. On the other hand, it remains to be seen if these immune responses can be harnessed to control cancer as, at the time of diagnosis, many tumours have already been immunoselected to be highly resistant to immune elimination. Based on these observations it is argued that immunotherapy approaches, other than the generation of tumour-specific cytotoxic T lymphocytes, must be explored. Alternative strategies include recruiting tumouricidal myeloid cells into tumours, generating antiangiogenic immune responses and directing innate immunity to hypoxia-induced ligands on tumour cells.
HIV-1 DNA predicts disease progression and post-treatment virological control (2014)

In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials.
Interleukin-2 Signaling and the Maintenance of Self-Tolerance (2001)

IL-2 plays an important and complex role in the immune system, serving as a growth factor, a differentiation factor, and a regulator of cell death. It shares many of these functions with other cytokines such as IL-15, which complicates the interpretation of the IL-2-deficient phenotype. Nonetheless, it is clear that a major indispensable role of IL-2 signaling, at least in mice, is to limit the number of activated T cells in the periphery after exposure to self- or environmental antigens. Although we still do not understand the mechanism by which this occurs, there emerge several general conclusions that provide a foundation for future work on this issue. The autoimmune phenotype associated with IL-2 deficiency results from the dysregulated activity of thymus-derived TCR alpha beta CD4+ and/or CD8+ T cells. The process requires an initial antigenic stimulus (e.g., from intestinal flora or self-antigens), but can then spread to naive bystander T cells by an undefined mechanism. A key observation is that neighboring T cells with intact IL-2 signaling can suppress the dysregulated activity of IL-2- or IL-2R-deficient T cells in a dominant manner, indicating that IL-2-based immune regulation is a systemic rather than cell autonomous property. The IL-2R signal responsible for maintaining homeostasis is not dependent on either the Shc or Stat5 pathways, therefore AICD, which is Stat5-dependent in vitro, cannot be the critical mechanism. Finally, expression of the IL-2R in the thymus and not the periphery appears sufficient to suppress the autoimmune phenotype, suggesting that IL-2 signaling may be required for some aspect of thymocyte selection and/or differentiation that has so far gone undetected. These observations can be combined into a unified model wherein IL-2 signaling is required for the development of a regulatory T-cell subset that serves to terminate antigen-induced responses of TCR alpha beta T cells. On the other hand, the role of IL-2 in the maintenance of self-tolerance could be multifaceted, with no single model accounting for all experimental findings. Of note, most of our knowledge regarding IL-2 signaling and tolerance has come from studies of knockout mice. Conceptually, it is important to remember that the function of a molecule such as IL-2 is not simply the inverse of the phenotype seen when that molecule is absent, since necessity and sufficiency are not always coupled in physiological processes. In this regard, perhaps new insights into this important issue can be gained by better defining when and where IL-2 signaling normally occurs in wild-type animals and the functional status of the T cells involved.
A non-iterative algorithm for obtaining multi-pulse excitation for linear-predictive speech coders (2005)

Many commercial applications of vocoders require good-quality speech reproduction at moderate bit-rates and at low cost. Multi-pulse-excited linear prediction provides excellent quality of speech reproduction at moderate bit-rates. An analysis-by-synthesis method for deriving the multi-pulse excitation sequence is described in [1]. It employs minimization of the spectrally-weighted energy in the synthesis error signal. The complexity of this method is judged to render it unsuitable for low-cost implementation at present. A modified algorithm is derived, exploiting the time-domain behaviour of the spectral weighting function. The modified algorithm has been used to implement a 7.2 kbits/s real-time vocoder on a double Eurosize circuit board (160mm × 233.4mm).
International Study to Predict Optimized Treatment for Depression (iSPOT-D), a randomized clinical trial: rationale and protocol (2011)

International Study to Predict Optimised Treatment - in Depression (iSPOT-D) ClinicalTrials.gov Identifier: NCT00693849. URL: http://clinicaltrials.gov/ct2/show/NCT00693849?term=International+Study+to+Predict+Optimized+Treatment+for+Depression&rank=1
Decoy Administration of NF- κ B into the Subarachnoid Space for Cerebral Angiopathy (1998)

Subarachnoid hemorrhage (SAH), encephalitis, meningitis, and autoimmune diseases sometimes lead to cerebral angiopathy, characterized specifically by narrowing of vessels, morphological changes in the structure of vessel walls, and a concomitant decrease in cerebral blood flow. Many patients also develop delayed ischemic neurological deficits. Thus, preventing vascular reactions is of paramount importance in treating SAH. Although cerebral vasospasm has some relationship with the inflammatory reaction of major cerebral vessels against the autologous blood, and many trials have attempted to prevent angiopathy after SAH, an effective treatment has not yet been established. The purpose of this article is to evaluate the preventive effect of nuclear factor KB (NF-kappaB) decoy oligo-DNA after SAH; since NF-kappaB is closely related to inflammation. In the rabbit angiopathy model after SAH, we evaluated the effectiveness of the decoy oligo-DNA using the angiographic (digital subtraction angiography) and histological (hematoxylin-eosin and Masson's trichrome staining) methods. Moreover, a gel-shift assay for NF-kappaB was also performed in order to evaluate the activity of NF-kappaB. We describe a new concept for treating cerebral angiopathy after SAH and for successfully inhibiting cerebral vasospasm and morphological changes in vessel walls in a rabbit model. In this treatment, we used synthetic double-strand oligo-DNA with a high affinity for transcription factor NF-kappaB, and cationic liposome complex administered through the cerebrospinal fluid.
Institutional Responses to #MeToo Claims: #VaticanToo, #KavanaughToo, and the Stumbling Block of Scandal (2019)

participants in the Legal Forum's #MeToo Symposium and the Oxford Reputation Symposium, and for the
Permanent Pervenous Atrial Pacing from the Coronary Vein (1970)

Permanent pervenous atrial pacing from the coronary vein has been attempted in 14 patients. Several types of arrhythmias including symptomatic bradycardia, "bradytachy" syndrome, and refractory ventricular tachyarrhythmia-fibrillation have been successfully treated with pervenous atrial pacing in 10 patients for 1 to 30 mo. Longterm atrial pacing was unsuccessful in four patients; in two of these four this was due to high atrial pacing thresholds. To date there has been no evidence of pacemaker perforation or pacemaker-induced coronary vein thrombosis. It is concluded that permanent pervenous atrial pacing from the coronary vein is a reliable method of atrial pacing without resorting to thoracotomy.
Sensitive and Convenient Detection of microRNAs Based on Cascade Amplification by Catalytic DNAzymes (2012)

On target: We have developed two cascade amplification strategies that combine duplex specific nuclease (DSN) amplicon with either G-quadruplex-based DNA peroxidase or 8-17 DNAzyme amplicon for miRNA detection. In this way, sensitive and convenient detection of miRNAs was achieved. In the DNA peroxidase-based system, a visual color change could be observed in the presence of target miRNAs (see scheme).
Organic LEDs: Sky‐Blue Organic Light Emitting Diode with ≈37% External Quantum Efficiency Using Thermally Activated Delayed Fluorescence from Spiroacridine‐Triazine Hybrid (Adv. Mater. 32/2016) (2016)

Extremely efficient blue organic electroluminescence with external quantum efficiency of 37% with a conventional planar device structure is reported by K.-T. Wong, C.-C. Wu, and co-workers on page 6976. Such a high efficiency is realized by thermally activated delayed fluorescence emitters based on spiroacridine–triazine hybrids, which simultaneously possess nearly 100% photoluminescence quantum yield and strongly horizontally oriented emitting dipoles.
Six-Degree-of-Freedom Haptic Rendering in Virtual Teleoperation (2008)

Six-degree-of-freedom (6-DoF) haptic rendering of the telerobotic operation method using virtual joint coupling (VJC) is proposed. This algorithm couples six joints of a virtual robot with those of a 6-DoF haptic device based on a spring-damper model to render force and torque feedback to a user and drive the virtual robot in the teleoperation simulation. Our rigid body dynamics is decoupled from the haptic rendering loop with an open dynamic simulation library Open Dynamics Engine, which runs at a lower update rate, thereby alleviating computation demand and improving the stability of the system. To illustrate the role of haptics and physically based simulation in teleoperation, a path-following experiment with virtual constraints is carried out. An experiment of virtual assembly, in which a user performs assembly tasks by means of manipulation of a gripper mounted at the end of a virtual robot, is also implemented to verify the VJC algorithm.
Thermodynamics of protein cross-links (1978)

The thermal transitions of native lysozyme and a well-characterized cross-linked derivative of lysozyme [Imoto, T., and Rupley, J. A. (1973), J. Mol. Biol. 80, 657] have been studied in 1.94 M guanidine hydrochloride at pH 2. The observed increase in the melting temperature from 32.4 degrees C for native lysozyme to 61.8 degrees C for the cross-linked derivative corresponds to a calculated 5.2 kcal/mol increase in the free energy of denaturation. This free-energy change is attributed to the decreased entropy of the unfolded polypeptide chain following introduction of a cross-link and is shown to compare well with theoretical predictions. The possibility that an introduction of a cross-link could also affect the enthalpy of an unfolded protein was investigated. The heats of reduction of bovine serum albumin and lysozyme by dithioerythritol in 6 M guanidine hydrochloride were determined and compared to that for the model peptide, oxidized glutathione. The near identity of the observed heats was taken as evidence that the introduction of cross-links into a random-coil protein does not, in general, introduce strain.
Production of glycoprotein vaccines in Escherichia coli (2010)

The presented data demonstrate that glycosylated proteins can be produced in recombinant E. coli at a larger scale. The described methodologies constitute an important step towards cost-effective in vivo production of conjugate vaccines, which in future may be used for combating severe infectious diseases, particularly in developing countries.
Alteration in the IL‐2 signal peptide affects secretion of proteins in vitro and in vivo (2004)

Modification of the IL-2 signal peptide augments protein secretion both in vitro and in vivo. As a result, optimizing the signal peptide should be considered for increasing the therapeutic levels of secreted proteins.
Applications of carbonic anhydrase inhibitors and activators in therapy (2002)

Inhibitors and activators of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) have a large number of applications in therapy. Many types of such new derivatives have been reported recently, together with their potential applications as antiglaucoma, anticancer and anti-osteoporosis agents or for the management of a variety of neurological disorders, among others. Furthermore, some CA isozymes seem to be valuable markers of tumour progression in a variety of tissues and organs. The CA activators, although not clinically exploited up to now, seem to constitute a new revolutionary approach for the treatment of Alzheimer's disease and other neurodegenerative disorders in need of memory therapy. Recent progress in all these areas, as well as in the characterisation of new such enzymes/isozymes isolated in many organisms/tissues and their detailed catalytic/inhibition mechanisms are, reviewed in the present paper.
Intranasal immunogenicity and adjuvanticity of site-directed mutant derivatives of cholera toxin (1997)

Genetically modified derivatives of cholera toxin (CT), harboring a single amino acid substitution in and around the NAD binding cleft of the A subunit, were isolated following site-directed mutagenesis of the ctxA gene. Two mutants of CT, designated CTS106 (with a proline-to-serine change at position 106) and CTK63 (with a serine-to-lysine change at position 63), were found to have substantially reduced ADP-ribosyltransferase activity and toxicity; CTK63 was completely nontoxic in all assays, whereas CTS106 was 10(4) times less toxic than wild-type CT. The mucosal adjuvanticity and immunogenicity of derivatives of CT were assessed by intranasal immunization of mice, with either ovalbumin or fragment C of tetanus toxin as a bystander antigen. Mice immunized with wild-type CT produced both local (immunoglobulin A in mucosal washes) and systemic immune responses to both CT and bystander antigens. CTS106 showed good local and systemic responses to bystander proteins and to itself. Interestingly, mice immunized with the nontoxic derivative of CT, CTK63, generated weak immune responses to the bystander antigens which were similar to those achieved when CT B subunit was used as an adjuvant. In parallel experiments, an equivalent nontoxic mutant of the Escherichia coli heat-labile enterotoxin, LTK63 (with a serine-to-lysine change at position 63), was tested (9). In contrast to CTK63, LTK63 was found to be more immunogenic and a better intranasal adjuvant than recombinant heat-labile enterotoxin B subunit or CTK63. This information, together with data on immunoglobulin subclass responses, suggests that although highly homologous, CT and heat-labile enterotoxin should not be considered biologically identical in terms of their ability to act as intranasal adjuvants.