gebhart/patrepeval huggingface dataset:
Real-time computer accompaniment (1990)

Now that real-time computer music systems are relatively portable and affordable, it has become common to use them in live performance. Unfortunately, most computer music systems offer little more than a tape recorder in terms of their abilities to interact with live musicians. Computer accompaniment was designed to go beyond this “tape recorder” model of human-computer interaction. Computer accompaniment is a process in which a computer “listens” to a live musician, follows along in a score, and synchronizes an “accompaniment” score with the live player. A system has been implemented that can reliably accompany a live musician in spite of tempo changes and wrong notes. Input is acoustic for instruments that produce a single tone (monophonic) and via mechanical sensors for keyboard input. The talk will focus on the pattern matching used to follow the score and on tempo adjustment techniques used to produce a musical accompaniment.
Investigation of the Structure–Activity Relationships of Psilocybin Analogues (2020)

The 5-HT<sub>2A</sub> receptor is thought to be the primary target for psilocybin (4-phosphoryloxy-<i>N</i>,<i>N</i>-dimethyltryptamine) and other serotonergic hallucinogens (psychedelic drugs). Although a large amount of experimental work has been conducted to characterize the pharmacology of psilocybin and its dephosphorylated metabolite psilocin (4-hydroxy-<i>N</i>,<i>N</i>-dimethyltryptamine), there has been little systematic investigation of the structure-activity relationships (SAR) of 4-substituted tryptamine derivatives. In addition, structural analogs of psilocybin containing a 4-acetoxy group, such as 4-acetoxy-<i>N</i>,<i>N</i>-dimethyltryptamine (4-AcO-DMT), have appeared as new designer drugs, but almost nothing is known about their pharmacological effects. To address the gap of information, studies were conducted with 17 tryptamines containing a variety of symmetrical and asymmetrical <i>N</i>,<i>N</i>-dialkyl substituents and either a 4-hydroxy or 4-acetoxy group. Calcium mobilization assays were conducted to assess functional activity at human and mouse 5-HT<sub>2</sub> subtypes. Head-twitch response (HTR) studies were conducted in C57BL/6J mice to assess 5-HT<sub>2A</sub> activation <i>in vivo</i>. All of the compounds acted as full or partial agonists at 5-HT<sub>2</sub> subtypes, displaying similar potencies at 5-HT<sub>2A</sub> and 5-HT<sub>2B</sub> receptors, but some tryptamines with bulkier <i>N</i>-alkyl groups had lower potency at 5-HT<sub>2C</sub> receptors and higher 5-HT<sub>2B</sub> receptor efficacy. In addition, <i>O</i>-acetylation reduced the <i>in vitro</i> 5-HT<sub>2A</sub> potency of 4-hydroxy-<i>N</i>,<i>N</i>-dialkyltryptamines by about 10- to 20-fold but did not alter agonist efficacy. All of the compounds induce head twitches in mice, consistent with an LSD-like behavioral profile. In contrast to the functional data, acetylation of the 4-hydroxy group had little effect on HTR potency, suggesting that <i>O</i>-acetylated tryptamines may be deacetylated <i>in vivo</i>, acting as prodrugs. In summary, the tryptamine derivatives have psilocybin-like pharmacological properties, supporting their classification as psychedelic drugs.
HERV-K: The Biologically Most Active Human Endogenous Retrovirus Family (1996)

The human genome contains a wide variety of endogenous retrovirus-like sequences. The human endogenous retrovirus type K (HERV-K) family comprises 30-50 members per haploid genome in humans and is highly conserved in Old World monkeys and apes. Some proviruses are displaying open reading frames (ORF) with coding capacity for viral particles. HERV-K sequences most likely code for the previously described human teratocarcinoma-derived virus (HTDV) and correlated expression of HERV-K Gag has been demonstrated by immunoelectron microscopy studies. Protease, but not yet reverse transcriptase (RT), enzymatic activity was demonstrated for recombinant HERV-K proteins. However, an ultrasensitive RT assay revealed specific polymerase activity associated with the HTDV particles. HERV-K transcription is specifically regulated by viral long terminal repeats and RNA is expressed at low steady-state levels in a variety of human tissues and tumours. In teratocarcinoma cell lines, HERV-K is highly expressed in a complex pattern showing full-length as well as subgenomic envelope (env) and two alternatively spliced small transcripts. The doubly spliced 1.8-kb mRNA codes for cORF protein which resembles Rev of HIV-1 and is located in the nucleolus. In addition, the cORF sequence acts as a leader and is essential for effective expression of glycosylated HERV-K Env protein. Although HERV-K sequences code for all necessary retroviral proteins, infectious particles could not yet be demonstrated. The putative implication of HERV sequences in pathophysiological processes, for example, testicular malignancies, remains to be elucidated.
Profile of romosozumab and its potential in the management of osteoporosis (2017)

Increased understanding of bone biology has led to the discovery of several unique signaling pathways that regulate bone formation and resorption. The Wnt signaling pathway plays a significant role in skeletal development, adult skeletal homeostasis, and bone remodeling. Sclerostin is an inhibitor of the Wnt signaling pathway. Romosozumab, a humanized monoclonal antibody that binds to sclerostin, prevents sclerostin from exerting this inhibitory effect. Therefore, in the presence of romosozumab, the Wnt signaling pathway is activated leading to bone formation and bone mineral density gain. Clinical studies of romosozumab have shown that this agent is one of the most potent bone anabolic agents in development to date. Romosozumab does not act solely as an anabolic agent, but rather, it has effects on increasing bone formation as well as reducing bone resorption. In the clinical studies, patients tolerated romosozumab well with no major safety signals reported. In a Phase III study, romosozumab as compared to placebo has been shown to reduce vertebral fractures by 73% after 1 year of treatment. Sequential therapy with romosozumab for 1 year followed by denosumab in the second year reduced vertebral fractures by 75% as compared to the group that received placebo for 1 year and denosumab in the second year. Romosozumab holds significant potential, by a novel mechanism of action, to expand our ability to treat osteoporosis. More studies are needed to determine the ideal setting in which romosozumab may be used to optimize osteoporosis treatment.
Reductive metabolism of the hypoxia marker pimonidazole is regulated by oxygen tension independent of the pyridine nucleotide redox state (1998)

2-Nitroimidazoles, such as pimonidazole, are reduced in cells with low oxygen tension and are, therefore, used as hypoxia markers. However, the effect of the pyridine nucleotide redox state on pimonidazole reduction is not known. Therefore, livers from fed or fasted rats were perfused with oxygen-saturated buffer containing pimonidazole (400 microM) in the presence and absence of an inhibitor of the mitochondrial respiratory chain, potassium cyanide; these treatments were used to modulate the mitochondrial and cytosolic pyridine nucleotide redox states. Pimonidazole-induced increases in oxygen uptake over basal values were as follows: fed, 15.1 +/- 2.4; fasted, 4.2 +/- 0.8; fed + KCN, 32.1 +/- 0.9; fasted + KCN, 0.2 +/- 0.2 micromol x g(-1) x h(-1). However, if NADPH was added in excess, microsomal oxygen uptake due to oxidative metabolism of pimonidazole was independent of treatment. These results indicate that pimonidazole-stimulated O2 uptake, due predominantly to N-oxidation and glucuronidation, is dependent on the NADPH redox state. In contrast, reduced pimonidazole adducts, detected immunochemically, accumulated in pericentral regions in liver. Increasing the NADH redox state by inhibiting the mitochondrial respiratory chain with KCN decreased protein-bound pimonidazole adducts. Concomitantly, the average O2 tension of the liver was increased at least 30%. However, KCN had no effect on total pimonidazole adducts detected by ELISA, although both cytosolic (lactate/pyruvate) and mitochondrial (3-hydroxybutyrate/acetoacetate) NADH redox states were elevated by at least a factor of eight. These results indicate that, unlike oxidative metabolism, the pyridine nucleotide redox state does not determine the rate of reductive metabolism of pimonidazole. Instead, the cellular oxygen tension regulates this process. Therefore, even in cases where the supply of reducing equivalents is increased (e.g., ethanol metabolism), accumulation of the reduced bound product of pimonidazole is oxygen dependent in liver.
Expression characteristics of the human CD97 antigen (1997)

Molecules whose expression is increased upon stimulation on leukocyte populations are of considerable interest because insights into their structure and function extend knowledge of the intracellular and intercellular events that accompany cellular activation. One such molecule is CD97, a cell surface antigen that is rapidly upregulated upon activation on lymphocytes. Increasing CD97 levels on peripheral blood lymphocytes (PBL) induced by different stimuli were found to be largely independent on de novo RNA and protein synthesis during the early stage of activation. Thus, inhibition of CD97 surface expression by cycloheximide was not noticeable or insignificant for 15 min to 4 h after stimulation. Furthermore, a fraction of intracellular CD97 decreased within 2 h suggesting redistribution of CD97 protein. Later, de novo protein synthesis apparently contributes to the induction of high CD97 surface density and inhibition by cycloheximide was more pronounced. Upregulation of CD97 on PBL involves protein kinase C-, tyrosine protein kinase- and Ca2+-dependent intracellular pathways. The effect on CD97 surface expression of the phorbol ester, phorbol 12-myristate 13-acetate (PMA), is different in PBL and Jurkat T cells. Whereas it stimulated after 22 h strong CD97 increase on PBL it suppressed CD97 expression on Jurkat T cells. CD97 expression, which is strong and constitutive on myelo-monocytic cells, is shown to be not leukocyte-restricted. Thus, CD97 transcripts were found in most of the investigated nonhematopoietic cell types and CD97 protein was detected on the cell surface at low amount. In a previous report, sequence data of a CD97 cDNA suggested a protein homologous to the secretin receptor superfamily and consisting of 722 amino acids with 8 potential glycosylation sites. According to this finding, glycoproteins displaying apparent molecular weights in the region of 70-85 kDa were detected in all investigated cell types. These molecules may represent differentially glycosylated and sialylated molecular forms of the same polypeptide. The findings support the notion that CD97 is broadly distributed and possesses a differentially regulated expression behavior on leukocytes and non-hematopoietic cells.
Sampling Properties of the Spectrum and Coherency of Sequences of Action Potentials (2001)

The spectrum and coherency are useful quantities for characterizing the temporal correlations and functional relations within and between point processes. This article begins with a review of these quantities, their interpretation, and how they may be estimated. A discussion of how to assess the statistical significance of features in these measures is included. In addition, new work is presented that builds on the framework established in the review section. This work investigates how the estimates and their error bars are modified by finite sample sizes. Finite sample corrections are derived based on a doubly stochastic inhomogeneous Poisson process model in which the rate functions are drawn from a low-variance gaussian process. It is found that in contrast to continuous processes, the variance of the estimators cannot be reduced by smoothing beyond a scale set by the number of point events in the interval. Alternatively, the degrees of freedom of the estimators can be thought of as bounded from above by the expected number of point events in the interval. Further new work describing and illustrating a method for detecting the presence of a line in a point process spectrum is also presented, corresponding to the detection of a periodic modulation of the underlying rate. This work demonstrates that a known statistical test, applicable to continuous processes, applies with little modification to point process spectra and is of utility in studying a point process driven by a continuous stimulus. Although the material discussed is of general applicability to point processes, attention will be confined to sequences of neuronal action potentials (spike trains), the motivation for this work.
Chemical Studies of Histone Acetylation (1974)

The activity of a calf thymus histone deacetylase was tested on histone F2A1 and derivative peptides prepared by cyanogen bromide cleavage, chymotryptic digestion, and solid phase peptide synthesis. Enzyme assays were based on the release of radioactively labeled acetate from the substrates. The large fragment (residues 1 to 84) derived by CNBr treatment and the NH2-terminal sequence (residues 1 to 37) prepared by chymotryptic digestion were both active as substrates for the deacetylase. The enzyme failed to remove acetyl groups from a smaller synthetic peptide (residues 15 to 21) encompassing the major site of acetylation at Lys16.
Cellular levels of class 1 and class 3 aldehyde dehydrogenases and certain other drug-metabolizing enzymes in human breast malignancies. (1997)

Molecular determinants of cellular sensitivity to cyclophosphamide, long the mainstay of chemotherapeutic regimens used to treat metastatic breast cancer, include class 1 and class 3 aldehyde dehydrogenases (ALDH-1 and ALDH-3, respectively), which catalyze the detoxification of this agent. Thus, interindividual variation in the activity of either of these enzymes in breast cancers could contribute to the wide variation in clinical responses that are obtained when such regimens are used to treat these malignancies. Consistent with this notion, ALDH-1 levels in primary and metastatic breast malignancies were found to range from 1-276 and 8-160 mIU/g tissue, respectively, and those of ALDH-3 range from 1-242 and 6-97 mIU/g tissue, respectively. ALDH-1 and ALDH-3 levels in normal breast tissue predicted the levels of these enzymes in primary and metastatic breast malignancies present in the same individuals. Confirming and extending the observations of others, levels of glutathione, a molecular determinant of cellular sensitivity to various DNA cross-linking agents including cyclophosphamide, and of DT-diaphorase, glutathione S-transferases, and cytochrome P450 1A1, each of which is known to catalyze the detoxification/toxification of one or more anticancer agents (although not of cyclophosphamide), also varied widely in primary and metastatic breast malignancies. Given the wide range of ALDH-1, ALDH-3, and glutathione levels that were observed in malignant breast tissues, measurement of their levels in normal breast tissue and/or primary breast malignancies prior to the initiation of chemotherapy is likely to be of value in predicting the therapeutic potential, or lack thereof, of cyclophosphamide in the treatment of metastatic breast cancer, thus providing a rational basis for the design of individualized therapeutic regimens when treating this disease.
Vertebrate mRNAs with a 5'-terminal pyrimidine tract are candidates for translational repression in quiescent cells: characterization of the translational cis-regulatory element. (1994)

The translation of mammalian ribosomal protein (rp) mRNAs is selectively repressed in nongrowing cells. This response is mediated through a regulatory element residing in the 5' untranslated region of these mRNAs and includes a 5' terminal oligopyrimidine tract (5' TOP). To further characterize the translational cis-regulatory element, we monitored the translational behavior of various endogenous and heterologous mRNAs or hybrid transcripts derived from transfected chimeric genes. The translational efficiency of these mRNAs was assessed in cells that either were growing normally or were growth arrested under various physiological conditions. Our experiments have yielded the following results: (i) the translation of mammalian rp mRNAs is properly regulated in amphibian cells, and likewise, amphibian rp mRNA is regulated in mammalian cells, indicating that all of the elements required for translation control of rp mRNAs are conserved among vertebrate classes; (ii) selective translational control is not confined to rp mRNAs, as mRNAs encoding the naturally occurring ubiquitin-rp fusion protein and elongation factor 1 alpha, which contain a 5' TOP, also conform this mode of regulation; (iii) rat rpP2 mRNA contains only five pyrimidines in its 5' TOP, yet this mRNA is translationally controlled in the same fashion as other rp mRNAs with a 5' TOP of eight or more pyrimidines; (iv) full manifestation of this mode of regulation seems to require both the 5' TOP and sequences immediately downstream; and (v) an intact translational regulatory element from rpL32 mRNA fails to exert its regulatory properties even when preceded by a single A residue.
The functional domains of coagulation factor VIII:C. (1986)

A lack of factor VIII:C, manifested as a bleeding disorder due to the absence of clot formation, is known as hemophilia A, an X chromosome-linked inherited disease afflicting 1-2 males/10,000. To determine the minimum functional domain(s) essential for factor VIII:C activity, we have expressed the amino-terminal (92-kDa) and carboxyl-terminal (80-kDa) proteolytic cleavage products as individual, secreted polypeptides in monkey cells without the 909-residue central region. We have found that neither terminal domain alone is able to promote coagulation in factor VIII:C-deficient plasma. However, when the 92- and 80-kDa peptides are co-expressed, clotting activity is readily detected. Thus, these two chains alone constitute an active or activatable complex. The central domain is required neither for activity nor for the assembly of an active complex from two chains expressed in trans. These results suggest that a truncated derivative of factor VIII:C may be useful in coagulation therapy.
Multiple People Tracking by Lifted Multicut and Person Re-identification (2017)

Tracking multiple persons in a monocular video of a crowded scene is a challenging task. Humans can master it even if they loose track of a person locally by re-identifying the same person based on their appearance. Care must be taken across long distances, as similar-looking persons need not be identical. In this work, we propose a novel graph-based formulation that links and clusters person hypotheses over time by solving an instance of a minimum cost lifted multicut problem. Our model generalizes previous works by introducing a mechanism for adding long-range attractive connections between nodes in the graph without modifying the original set of feasible solutions. This allows us to reward tracks that assign detections of similar appearance to the same person in a way that does not introduce implausible solutions. To effectively match hypotheses over longer temporal gaps we develop new deep architectures for re-identification of people. They combine holistic representations extracted with deep networks and body pose layout obtained with a state-of-the-art pose estimation model. We demonstrate the effectiveness of our formulation by reporting a new state-of-the-art for the MOT16 benchmark. The code and pre-trained models are publicly available.
Differentiation and Expansion of T Cells with Regulatory Function from Human Peripheral Lymphocytes by Stimulation in the Presence of TGF-β (2005)

T cells with immunoregulatory function have been described in human and mouse systems. In both systems these cells can be differentiated either in the thymus or from peripheral T cells. To date, more progress has been made in the study of murine regulatory T cells, because it has been very difficult to isolate human regulatory T cells of sufficient purity and in sufficient numbers to permit detailed examinations of their biochemistry. We report in this study that human T cells with regulatory function can be differentiated in vitro from naive (CD4(+)CD45RA(+)) cord blood or peripheral T cells by stimulation with anti-CD3 and anti-CD28 in the presence of TGF-beta. Cells derived in this manner express a surface phenotype (CD25(+), CD122(+), HLA-DR(+), glucocorticoid-induced TNF receptor-related gene(+), CD103(+), CTLA-4(+)) described for human and mouse regulatory T cells and express protein and message for the transcription factor forkhead/winged helix transcription factor (FOXP3). They produce primarily TGF-beta and IL-10, with lesser amounts of IFN-gamma and IL-13, when stimulated through their TCRs and are capable of inhibiting cytokine production and proliferation by stimulated naive T cells. Unlike Th1 and Th2 cells, these TGF-beta-derived regulatory T cells do not appear to be dependent on the protein kinase Ctheta; pathway of NF-kappaB activation for Ag-induced responses.
Localisation of glutamate receptors in the substantia nigra pars compacta of the monkey. (1997)

The distribution of ionotropic glutamate receptor subunits GluR1, GluR2/3 and NMDAR1, and meta-botropic receptor mGluR1 alpha was studied in the monkey substantia nigra. High levels of immunoreactivity to GluR1, GluR2/3 and NMDAR1, and moderate levels of immunoreactivity to mGluR1 alpha were observed in the substantia nigra pars compacta. GluR1 and GluR2/3 were mostly in cell bodies and larger stem dendrites, whilst NMDAR1 and mGluR1 alpha were present on medium sized and small dendrites, respectively. The substantia nigra receives glutamatergic afferents from the subthalamic nucleus and the frontal cortex. Overactivity of the subthalamic nucleus, coupled with high levels of glutamate receptors on the neurons in the pars compacta, could predispose these neurons to excitotoxic injury, and could contribute to the development of Parkinson's disease.
Patterning of active organic materials by direct transfer for organic electronic devices (2005)

We demonstrate the localized patterning of organic thin films based on direct material transfer from a stamp to a substrate. This process, based on van der Waals bonding between contacting organic films, extends the range of application of patterning via stamping to devices where the active organic materials must be locally deposited on the substrate. A mechanical analysis combined with finite element numerical simulations successfully describes the details of the material transfer process over substrate irregularities and step edges. To demonstrate local patterning, we fabricate an array of organic light-emitting devices, showing that the organic-organic interface formed by the transfer process does not significantly affect device performance. This technique expands the application of a unique attribute of organic materials—the ability to compositionally pattern materials to locally modify, or optimize a device function or property within the substrate plane.