gebhart/patrepeval huggingface dataset:
Parametric hidden Markov models for gesture recognition (1999)

A method for the representation, recognition, and interpretation of parameterized gesture is presented. By parameterized gesture we mean gestures that exhibit a systematic spatial variation; one example is a point gesture where the relevant parameter is the two-dimensional direction. Our approach is to extend the standard hidden Markov model method of gesture recognition by including a global parametric variation in the output probabilities of the HMM states. Using a linear model of dependence, we formulate an expectation-maximization (EM) method for training the parametric HMM. During testing, a similar EM algorithm simultaneously maximizes the output likelihood of the PHMM for the given sequence and estimates the quantifying parameters. Using visually derived and directly measured three-dimensional hand position measurements as input, we present results that demonstrate the recognition superiority of the PHMM over standard HMM techniques, as well as greater robustness in parameter estimation with respect to noise in the input features. Finally, we extend the PHMM to handle arbitrary smooth (nonlinear) dependencies. The nonlinear formulation requires the use of a generalized expectation-maximization (GEM) algorithm for both training and the simultaneous recognition of the gesture and estimation of the value of the parameter. We present results on a pointing gesture, where the nonlinear approach permits the natural spherical coordinate parameterization of pointing direction.
The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases. (1990)

Acetylation of Ser-530 of sheep prostaglandin endoperoxide (PGG/H) synthase by aspirin causes irreversible inactivation of the cyclooxygenase activity of the enzyme. To determine the catalytic function of the hydroxyl group of Ser-530, we used site-directed mutagenesis to replace Ser-530 with an alanine. Cos-1 cells transfected with expression vectors containing the native (Ser-530) or mutant (Ala-530) cDNAs for sheep PGG/H synthase expressed comparable cyclooxygenase and hydroperoxidase activities. Km values for arachidonate (8 microM) and ID50 values for reversible inhibition by the cyclooxygenase inhibitors, flurbiprofen (5 microM), flufenamate (20 microM), and aspirin (20 mM), were also the same for both native and mutant PGG/H synthases; however, only the native enzyme was irreversibly inactivated by aspirin. Thus, the "active site" Ser-530 of PGG/H synthase is not essential for catalysis or substrate binding. Apparently, acetylation of native PGG/H synthase by aspirin introduces a bulky sidechain at position 530 which interferes with arachidonate binding. In related studies, a cDNA for mouse PGG/H synthase was cloned and sequenced. A sequence of 35 residues with Ser-530 at the midpoint was identical in the two proteins. Thus, Ser-530 does lie in a highly conserved region, probably involved in cyclooxygenase catalysis. Sequence comparisons of mouse and sheep PGG/H synthase also provided information about the heme-binding site of the enzyme. The sheep HYPR sequence (residues 274-277), which had been proposed to form a portion of the distal heme-binding site, is not conserved in the mouse PGG/H synthase, suggesting that this region is not the distal heme-binding site. One sequence, TIWLREHNRV (residues 303-312 of the sheep enzyme), is very closely related to the sequence TLW(L)LREHNRL common to thyroid peroxidase and myeloperoxidase. The histidine in this latter sequence is the putative axial heme ligand of these peroxidases. We suggest that the histidine (His-309) of sheep PGG/H synthase sequence is the axial heme ligand of this enzyme.
Alzheimer's disease-like pathological features in transgenic mice expressing the APP intracellular domain (2009)

The hypothesis that amyloid-beta (Abeta) peptides are the primary cause of Alzheimer's disease (AD) remains the best supported theory of AD pathogenesis. Yet, many observations are inconsistent with the hypothesis. Abeta peptides are generated when amyloid precursor protein (APP) is cleaved by presenilins, a process that also produces APP intracellular domain (AICD). We previously generated AICD-overexpressing transgenic mice that showed abnormal activation of GSK-3beta, a pathological feature of AD. We now report that these mice exhibit additional AD-like characteristics, including hyperphosphorylation and aggregation of tau, neurodegeneration and working memory deficits that are prevented by treatment with lithium, a GSK-3beta inhibitor. Consistent with its potential role in AD pathogenesis, we find AICD levels to be elevated in brains from AD patients. The in vivo findings that AICD can contribute to AD pathology independently of Abeta have important therapeutic implications and may explain some observations that are discordant with the amyloid hypothesis.
The ADNP Derived Peptide, NAP Modulates the Tubulin Pool: Implication for Neurotrophic and Neuroprotective Activities (2012)

Microtubules (MTs), key cytoskeletal elements in living cells, are critical for axonal transport, synaptic transmission, and maintenance of neuronal morphology. NAP (NAPVSIPQ) is a neuroprotective peptide derived from the essential activity-dependent neuroprotective protein (ADNP). In Alzheimer's disease models, NAP protects against tauopathy and cognitive decline. Here, we show that NAP treatment significantly affected the alpha tubulin tyrosination cycle in the neuronal differentiation model, rat pheochromocytoma (PC12) and in rat cortical astrocytes. The effect on tubulin tyrosination/detyrosination was coupled to increased MT network area (measured in PC12 cells), which is directly related to neurite outgrowth. Tubulin beta3, a marker for neurite outgrowth/neuronal differentiation significantly increased after NAP treatment. In rat cortical neurons, NAP doubled the area of dynamic MT invasion (Tyr-tubulin) into the neuronal growth cone periphery. NAP was previously shown to protect against zinc-induced MT/neurite destruction and neuronal death, here, in PC12 cells, NAP treatment reversed zinc-decreased tau-tubulin-MT interaction and protected against death. NAP effects on the MT pool, coupled with increased tau engagement on compromised MTs imply an important role in neuronal plasticity, protecting against free tau accumulation leading to tauopathy. With tauopathy representing a major pathological hallmark in Alzheimer's disease and related disorders, the current findings provide a mechanistic basis for further development. NAP (davunetide) is in phase 2/3 clinical trial in progressive supranuclear palsy, a disease presenting MT deficiency and tau pathology.
A Carboxyl-terminal Extension of the Zinc Finger Domain Contributes to the Specificity and Polarity of Peroxisome Proliferator-activated Receptor DNA Binding (1998)

Heterodimers of the peroxisome proliferator-activated receptors (PPAR) and the retinoid X receptors (RXR) recognize response elements (PPREs) that exhibit the consensus sequence 5'-A(A/T)CT(A/G)GGNCAAAG(G/T)TCA-3'. The consensus PPRE includes both a 5'-extension and a direct repeat (DR1) comprised of two canonical core recognition sequences (underlined) for nuclear receptor zinc fingers separated by a single nucleotide spacer. The extended binding site recognized by PPARs is very similar to sites that bind monomers of the nuclear receptors Rev-ErbA and ROR suggesting that the latter could bind to PPREs and affect gene transcription. However, Rev-ErbA and ROR bind weakly to naturally occurring PPREs relative to the consensus binding site, and significant effects on PPARalpha transactivation of a CYP4A6-Z reporter were not observed. In contrast, PPAR/RXR heterodimers bind to a DR2 element containing the conserved 5'-extended sequence that is recognized by dimers of RORalpha or Rev-ErbA. PPARalpha/RXRalpha positively regulate transcription from this element, and co-expression of Rev-ErbA blocks this effect. The nuclear receptors NGFI-B and ROR utilize a carboxyl-terminal extension (CTE) of the zinc finger DNA binding domain in their interactions with the 5'-extension of a single zinc finger-binding site. DNA binding domains (DBD) of PPARs alpha, delta, and gamma that contain the zinc finger motif and a CTE display binding to core recognition sequences that is dependent on the 5'-extended sequence found in PPREs. Unlike DBDs of other nuclear receptors that form heterodimers with RXR, the PPAR-DBDs did not exhibit cooperative binding with the DBD of RXR and exhibit the opposite polarity for binding to the direct repeat motif. In contrast to the corresponding DBD of RXR, the PPAR-DBDs bind as monomers to a single extended binding site as well as to the consensus PPRE. A chimera linking the zinc finger domain of RXRalpha to the CTE from PPARalpha bound to a single extended binding site indicating a functional role for the CTE of PPARs in extended binding site recognition.
Rational Pathway Engineering of Type I Fatty Acid Synthase Allows the Biosynthesis of Triacetic Acid Lactone from d-Glucose in Vivo (2004)

Metabolic pathway engineering is a powerful tool to synthesize structurally diverse and complex chemicals via genetic manipulation of multistep catalytic systems involved in cell metabolism. Here, we report the rational design of a fatty acid biosynthetic pathway, Brevibacterium ammoniagenes fatty acid synthase B (FAS-B), that allows the microbial synthesis of triacetic acid lactone (TAL) from an inexpensive feedstock, d-glucose. TAL can be chemically converted to phloroglucinol, which is a core structure for the synthesis of various high value bioactive compounds and energetic compounds such as 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). Synthesis of phloroglucinol from d-glucose using this combined biological and chemical synthesis may offer significant advantages over the current phloroglucinol manufacture, including environmental friendliness and reduction in the cost of phloroglucinol. More importantly, it represents a novel strategy for the benzene-free synthesis of aromatic chemicals.
Differences in the synthesis and kinetics of release of interleukin 1α, interleukin 1β and tumor necrosis factor from human mononuclear cells (1989)

Cell-associated and secreted interleukin 1 alpha (IL 1 alpha), IL 1 beta and tumor necrosis factor alpha (TNF-alpha), produced by human mononuclear cells (MNC) in vitro in response to lipopolysaccharide, were measured by radioimmunoassay. After 18 h of incubation, total production of IL 1 alpha in medium containing 1% heat-inactivated serum was two-to-three times higher than IL 1 beta. However, in the presence of 1% serum and 5% fresh plasma, IL 1 alpha and IL 1 beta were produced in similar amounts. Independent of the culture conditions, 90% of the IL 1 alpha remained cell associated whereas 80% of IL 1 beta was extracellular. The kinetics of production and release of IL 1 alpha, beta and TNF-alpha were also studied. IL 1 alpha and TNF-alpha reached maximal levels within 6 h of stimulation, whereas IL 1 beta reached maximal levels between 12 and 16 h. IL 1 alpha remained primarily cell associated (80%) for the first 24 h. After 48 h, extracellular IL 1 alpha exceeded cell-associated levels. IL 1 beta was primarily secreted (80%), appearing in the extracellular fluid within 6 h. TNF-alpha appeared in the extracellular fluid within 1 h of incubation, with less than 10% cell associated at any time during the 48 h of incubation. Although the three cytokines share many biological activities, this study provides evidence that MNC IL 1 alpha is predominantly a cell-associated cytokine acting on a cell-cell basis, whereas IL 1 beta and TNF-alpha are secreted as paracrine mediators.
Participation of lymphocyte subpopulations in the pathogenesis of experimental murine cerebral malaria (1996)

We determined the requirement for selected lymphocyte subsets and cytokines in the pathogenesis of experimental murine cerebral malaria (CM) by using gene-targeted knockout and mAb-suppressed mice. Plasmodium berghei ANKA infection induced CM in A 0/0 mice, which lack expression of surface MHC class II glycoproteins and consequently express a severe and chronic reduction in numbers of CD4+ T cells. However, when A 0/0 mice, which are on a C57BL/6 x 129 genetic background, or immune-intact C57BL/6 controls treated with anti-CD4 mAb were infected, none developed CM. The latter finding confirms an earlier report that CD4+ T cells are required for CM to occur and additionally indicates that the reduced numbers of CD4+ T cells present in A 0/0 mice are sufficient for CM development. Neither the recently described CD4+, NK1.1+ T cell subset shown to be present in A 0/0 mice nor traditional NK cells seem to be required for the induction of CM because A 0/0 and C57BL/6 mice severely depleted of both NK1.1+ populations with mAb developed CM as readily as did normal Ig-treated controls. Deficiency of Th1-associated cytokines (IFN-gamma or IL-2) in mice by gene-targeted disruptions completely inhibited CM development, whereas the lack of Th2-associated cytokines (IL-4 or IL-10) did not prevent this disease. Our observation that B cell-deficient JHD and microMT mice developed CM provides evidence that neither B cells, their products, nor B cell Ag presentation are a requisite for CM pathology. We further observed that neither beta 2m 0/0 knockout mice, which lack CD8+ alpha beta T cells, nor C57BL/6 mice depleted of CD8+ T cells with anti-CD8 mAb treatment developed CM, leading us to conclude that CD8+ T cells are also crucial for the development of CM.
Interleukin 6 as a therapeutic target in systemic-onset juvenile idiopathic arthritis (2003)

This review will provide the evidences of the relation between the imbalance of interleukin 6 homeostasis and systemic-onset juvenile idiopathic arthritis. Also reviewed will be the author's recent trials of anti interleukin 6 receptor antibody, named temporally as MRA, for children with acute systemic disease intractable to long-term, high-dose, corticosteroid therapy. MRA would be a therapeutic modality for children with systemic-onset juvenile idiopathic arthritis intractable to high-dose corticosteroids.
Iodine 125‐labeled mesenchymal–epithelial transition factor binding peptide‐click‐cRGDyk heterodimer for glioma imaging (2011)

In our previous study, mesenchymal-epithelial transition factor (c-Met)-binding peptides (cMBP) had been readily radiolabeled with radioactive iodide for glioma imaging because of five histidine amino acids. However, iodinated cMBP showed relatively unfavorable in vivo kinetics. For this reason, we tried to design dual peptide ligands that would be advantageous in recognizing both c-Met receptor and integrin α(v) β(3) . A cMBP-click-cRGDyk (cyclic Arg-Gly-Asp-Tyr-Lys) heterodimer was synthesized from mini polyethylene glycol-conjugated cMBP-3 glycine (GGG)-a single name of amino acids (SC) (Ser-Cys) and cRGDyk through a click (1 + 3 cycloaddition), and then labeled with iodine 125 (I-125) via histidine in the cMBP and tyrosine in the cRGDyk. The receptor-binding characteristics and tumor-targeting efficacy of cMBP-click-cRGDyk were tested in vitro and in vivo. A cMBP-click-cRGDyk had comparable integrin α(v) β(3) -binding affinity with cRGDyk. The results of the biodistribution of (125) I-cMBP-click-cRGDyk at 4 h showed higher tumor-to-blood, tumor-to-liver, and tumor-to-muscle ratios: 10.07, 6.76, and 11.12, compared to 2.34, 1.99, and 5.18 of (125) I-cMBP-GGG-SC, respectively. U87MG tumor xenografts could be visualized by single photon emission computed tomography (SPECT)/CT using (125) I-cMBP-click-cRGDyk and also image contrast and overall quality were improved compared to (125) I-cMBP-GGG-SC. As the results of in vivo inhibition using free cRGDyk or cMBP-GGG-SC indicated, the tumoral uptake of (125) I-cMBP-click-cRGDyk decreased. This finding means that (125) I-cMBP-click-cRGDyk was specifically uptaken by integrin α(v) β(3) and the c-Met receptor. Although imaging quality was improved, additional experiments are needed to acquire significant image-quality improvement.
Designing Antisense Oligonucleotides (2005)

Antisense oligonucleotides have been used for a number of years to modify the expression of specific genes both in vivo and in vitro (Scanlon et al., 1995). The most potent mode of antisense activity is through RNase H–mediated degradation of RNA (Figure 1). The RNase H– endonuclease specifically cleaves RNA only when it is hybridized as a heteroduplex with DNA. In general, oligonucleotides that cannot invoke RNase H pathways are 10–100 fold less potent than RNase H–activating oligonucleotides of identical sequence.
Primary Study On Fabrication Of High Performance Dental ZrO_2 Ceramics Restoration. (2004)

Objective: In this paper, the technology route of fabricating high performance dental restoration via partial sintering-CAD/CAM-full sintering three steps method was primarily studied, where Y 2O 3-stabilized tetragonal zirconia polycrystal (Y-TZP) nanometer crystalline powder was used as raw material. Methods:First,Partial sintered Y-TZP blank was manufactured by molded shape at 25MPa, sintered at low temperature. Second,The initial dental framework was obtained by machining the blank on dental CAD/CAM system. Third,the ultimate high performance dental restoration was obtained by full sintered the initial dental framework. Results:To fabricate a dental crown, the machining time of partial sintered ceramic blank was equal to the machine anticipation time. The full sintered Y-TZP had excellent mechanical properties, with bending strength of 710 MPa, fracture toughness of 4.77 MPa·m 1/2 . During full sintering process, the shrinkages of dental crown in different spatial dimensions were equality and uniformity. The dental crown had verisimilitude configuration, and had no crack on surface. Conclusion: Y-TZP can be used as a new promising ceramics to fabricate molars crowns and bridges, because their strength are 3-5 times stronger than those of current dental ceramics. The technology route of partial sintering- CAD/CAM- full sintering three steps method is also a feasible simple way to fabricate high performance dental restoration.
Magic state parity-checker with pre-distilled components (2018)

Magic states are eigenstates of non-Pauli operators. One way of suppressing errors present in magic states is to perform parity measurements in their non-Pauli eigenbasis and postselect on even parity. Here we develop new protocols based on non-Pauli parity checking, where the measurements are implemented with the aid of pre-distilled multiqubit resource states. This leads to a two step process: pre-distillation of multiqubit resource states, followed by implementation of the parity check. These protocols can prepare single-qubit magic states that enable direct injection of single-qubit axial rotations without subsequent gate-synthesis and its associated overhead. We show our protocols are more efficient than all previous comparable protocols with quadratic error reduction, including the protocols of Bravyi and Haah.
Semliki Forest virus vectors: efficient vehicles for in vitro and in vivo gene delivery (2001)

Rapidly generated high-titer Semliki Forest virus (SFV) vectors can infect numerous mammalian cell lines and primary cell cultures, and result in high levels of transgene expression. SFV-based expression of transmembrane receptors has been characterized by specific ligand-binding activity and functional responses. Adaptation of the SFV technology for mammalian suspension cultures has allowed the production of hundreds of milligrams of recombinant receptor for purification and structural studies. The same SFV stock solutions used for the infection of mammalian cells in culture have also been successfully applied for efficient transgene expression in organotypic hippocampal slices, as well as in vivo in rodent brain.
Fluoroquinolones: antimicrobial agents of the 90’s. (1994)

The development of fluoroquinolones in early 1980s was a breakthrough in the treatment of infectious diseases. The basic structure of fluoroquinolone consists of quinolone carboxylic acid. The modifications at various positions in structure have resulted in a series of potent compounds having wide spectrum of activity which includes gram negative and gram positive organisms, mycobacterium, chlamydia etc. They act by selective inhibition of bacterial DNA gyrase enzyme. These compounds have proved their utility in the treatment of various infections viz., U.T.I, acute bacterial diarrhoea1 diseases, gonorrhoea, chanchroid, S.typhi infection and various other systemic infections. They also have good prophylactic role in surgery and in immunocompromised patients. Compared to other antimicrobial agents, resistance to fluoroquinolones is not common and in addition, they have fewer and mild side effects like g.i.t disturbances (most frequent), mild CNS reactions (headache, dizziness, sleepiness) and hypersensitivity reactions. The bioavailability of fluoroquinolones is decreased with concomitant administration of antacids, iron salts, ranitidine and pirenzipine. Some of the fluoroquinolones (ciprofloxacin, enoxacin) significantly raise the plasma levels of theophylline and caffeine. Although a large number of fluoroquinolones have been developed in the recent past, yet there is need for compounds which have broader spectrum of activity, higher potency, better CNS/CSF penetration and better patient tolerability.
Efficacy of depatuxizumab mafodotin (ABT-414) monotherapy in patients with EGFR-amplified, recurrent glioblastoma: results from a multi-center, international study (2017)

Depatux-m monotherapy displayed frequent but mostly Grade 1/2 ocular toxicities. A PFS6 of 28.8% was observed in this rGBM population, warranting further study.
Radiative forcing of climate by hydrochlorofluorocarbons and hydrofluorocarbons (1995)

We measure infrared absorption spectra of 18 hydrochlorofluorocarbons and hydrofluorocarbons, seven of which do not yet appear in the literature. The spectra are used in a narrowband model of the terrestrial infrared radiation to calculate radiative forcing and global warming potentials. We investigate the sensitivity of the radiative forcing to the absorption spectrum temperature dependence, halocarbon vertical profile, stratospheric adjustment, cloudiness, spectral overlap, and latitude, and we make some recommendations for the reporting of radiative forcings that would help to resolve discrepancies between assessments. We investigate simple methods of estimating instantaneous radiative forcing directly from a molecule's absorption spectrum and we present a new method that agrees to within 0.3% with our narrowband model results.
Activity recognition from accelerometer data (2005)

Activity recognition fits within the bigger framework of context awareness. In this paper, we report on our efforts to recognize user activity from accelerometer data. Activity recognition is formulated as a classifica-tion problem. Performance of base-level classifiers and meta-level classifiers is compared. Plurality Voting is found to perform consistently well across different set-tings.
Automatic Analysis of Single-Channel Sleep EEG: Validation in Healthy Individuals (2007)

Our results establish the face validity and convergent validity of ASEEGA for single-channel sleep analysis in healthy individuals. ASEEGA appears as a good candidate for diagnostic aid and automatic ambulant scoring.