gebhart/patrepeval huggingface dataset:
Molecular basis of odor coding in the malaria vector mosquito Anopheles gambiae (2010)

A systematic functional analysis across much of the conventional Anopheles gambiae odorant receptor (AgOR) repertoire was carried out in Xenopus oocytes using two-electrode, voltage-clamp electrophysiology. The resulting data indicate that each AgOR manifests a distinct odor-response profile and tuning breadth. The large diversity of tuning responses ranges from AgORs that are responsive to a single or small number of odorants (specialists) to more broadly tuned receptors (generalists). Several AgORs were identified that respond robustly to a range of human volatiles that may play a critical role in anopheline host selection. AgOR responses were analyzed further by constructing a multidimensional odor space representing the relationships between odorants and AgOR responses. Within this space, the distance between odorants is related to both chemical class and concentration and may correlate with olfactory discrimination. This study provides a comprehensive overview of olfactory coding mechanisms of An. gambiae that ultimately may aid in fostering the design and development of olfactory-based strategies for reducing the transmission of malaria and other mosquito-borne diseases.
Early T‐cell responses in tuberculosis immunity (2008)

Tuberculosis (TB) has plagued mankind for millennia yet is classified as an emerging infectious disease, because its prevalence in the human population continues to increase. Immunity to TB depends critically on the generation of effective CD4(+) T-cell responses. Sterile immunity has not been achieved through vaccination, although early T-cell responses are effective in controlling steady-state infection in the lungs. Although such early T-cell responses are clearly protective, the initiation of the Mycobacterium tuberculosis (Mtb) T-cell response occurs much later than is the case following other aerogenic infections. This fact suggests that there is a critical period, before the activation of the T-cell response, in which Mtb is able to establish infection. An understanding of the factors that regulate early T-cell activation should, therefore, lead to better control of the disease. This review discusses recent work that has investigated the early development of T-cell immunity following Mtb infection in the mouse.
The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins (2016)

Genomics, epigenomics, transcriptomics, proteomics and metabolomics efforts rapidly generate a plethora of data on the activity and levels of biomolecules within mammalian cells. At the same time, curation projects that organize knowledge from the biomedical literature into online databases are expanding. Hence, there is a wealth of information about genes, proteins and their associations, with an urgent need for data integration to achieve better knowledge extraction and data reuse. For this purpose, we developed the Harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins from over 70 major online resources. We extracted, abstracted and organized data into ∼72 million functional associations between genes/proteins and their attributes. Such attributes could be physical relationships with other biomolecules, expression in cell lines and tissues, genetic associations with knockout mouse or human phenotypes, or changes in expression after drug treatment. We stored these associations in a relational database along with rich metadata for the genes/proteins, their attributes and the original resources. The freely available Harmonizome web portal provides a graphical user interface, a web service and a mobile app for querying, browsing and downloading all of the collected data. To demonstrate the utility of the Harmonizome, we computed and visualized gene-gene and attribute-attribute similarity networks, and through unsupervised clustering, identified many unexpected relationships by combining pairs of datasets such as the association between kinase perturbations and disease signatures. We also applied supervised machine learning methods to predict novel substrates for kinases, endogenous ligands for G-protein coupled receptors, mouse phenotypes for knockout genes, and classified unannotated transmembrane proteins for likelihood of being ion channels. The Harmonizome is a comprehensive resource of knowledge about genes and proteins, and as such, it enables researchers to discover novel relationships between biological entities, as well as form novel data-driven hypotheses for experimental validation.Database URL: http://amp.pharm.mssm.edu/Harmonizome.
Ventricular Remodeling After Infarction and the Extracellular Collagen Matrix (2003)

Bodh I. Jugdutt, MD L eft ventricular (LV) remodeling after myocardial in- farction (MI) contributes significantly to LV dilation and dysfunction, and disability and death. Two paradigms, pertinent to antiremodeling therapy after MI (Figure Paradigm 1, LV remodeling is a major mechanism for disability and death, 1,2 has received a great deal of attention. In contrast, paradigm 2, remodeling of the extracellular collagen matrix (ECCM) plays a major role in LV remodeling, A host of clinical trials showed that angiotensin-converting enzyme (ACE) inhibitors (ACE-Is) with or without aldosterone antagonists, angiotensin II (AngII) type 1 (AT 1 ) receptor blockers (ARBs), -adrenergic blockers or reperfusion improve outcome in survivors of MI. 8 -10 Concurrent evidence has underscored the importance of preserving the ECCM during healing after MI. 2-7 However, the antifibrotic action of ACE-Is, aldosterone antagonists and ARBs on ECCM in the infarct zone (IZ) and noninfarct zone (NIZ), Nevertheless, excessive ECCM, as in dilated ischemic cardiomyopathy after remote MI, 14,15 can contribute to LV diastolic dysfunction and poor outcome, 6 suggesting that antifibrotic drugs that target excess ECCM might be a logical therapeutic approach. This review focuses on the role of the ECCM in the evolution of LV remodeling after MI and the potential impact of therapies that target the ECCM.
Modulation of opioid analgesia by agmatine (1996)

Administered alone, agmatine at doses of 0.1 or 10 mg/kg is without effect in the mouse tailflick assay. However, agmatine enhances morphine analgesia in a dose-dependent manner, shifting morphine's ED50 over 5-fold. A far greater effect is observed when morphine is given intrathecally (9-fold shift) than after intracerebroventricular administration (2-fold). In contrast to the potentiation of morphine analgesia, agmatine (10 mg/kg) has no effect on morphine's inhibition of gastrointestinal transit. delta-Opioid receptor-mediated analgesia also is potentiated by agmatine, but kappa1-receptor-mediated (U50,488H; trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetemide) and kappa3-opioid receptor-mediated (naloxone benzoylhydrazone) analgesia is not significantly enhanced by any dose of agmatine tested in this acute model. In chronic studies, agmatine at a low dose (0.1 mg/kg) which does not affect morphine analgesia acutely prevents tolerance following chronic morphine dosing for 10 days. A higher agmatine dose (10 mg/kg) has a similar effect. Agmatine also blocks tolerance to the delta-opioid receptor ligand [D-Pen2,D-Pen5]enkephalin given intrathecally, but not to the kappa3-opioid receptor agonist naloxone benzoylhydrazone. Despite its inactivity on kappa1-opioid analgesia in the acute model, agmatine prevents kappa1-opioid receptor-mediated tolerance. These studies demonstrate the dramatic interactions between agmatine and opioid analgesia and tolerance.
Energy and Execution Time Analysis of a Software-based Trusted Platform Module (2007)

Trusted platforms have been proposed as a promising approach to enhance the security of general-purpose computing systems. However, for many resource-constrained embedded systems, the size and cost overheads of a separate trusted platform module (TPM) chip are not acceptable. One alternative is to use a software-based TPM (SW-TPM), which implements TPM functions using software that executes in a protected execution domain on the embedded processor itself. However, since many embedded systems have limited processing capabilities and are battery-powered, it is also important to ensure that the computational and energy requirements for SW-TPMs are acceptable. In this work, an evaluation of the energy and execution time overheads for a SW-TPM implementation on a Sharp Zaurus PDA was performed. The execution time and energy required by each TPM command was characterized through actual measurements on the target platform. In addition, the overheads of using SW-TPM in the context of various end applications, including trusted boot of the Linux operating system (OS), secure file storage, secure VoIP client, and secure Web browser was also evaluated. Furthermore, it was observed that for most TPM commands, the overheads are primarily due to the use of 2048-bit RSA operations that are performed within SW-TPM. In order to alleviate SW-TPM overheads, the use of elliptic curve cryptography (ECC) as a replacement for the RSA algorithm specified in the trusted computing group (TCG) standards was evaluated. Experiments indicate that this optimization can significantly reduce SW-TPM overheads (an average of 6.51times execution time reduction and 6.75times energy consumption reduction for individual TPM commands, and an average of 10.25times execution time reduction and 10.75times energy consumption reduction for applications). This work demonstrates that ECC-based SW-TPMs are a viable approach to realizing the benefits of trusted computing in resource-constrained embedded systems
Intercarrier interference in MIMO OFDM (2002)

In this paper, we examine multicarrier transmission over time-varying channels. We first develop a model for such a transmission scheme and focus particularly on multiple-input multiple output (MIMO) orthogonal frequency division multiplexing (OFDM). Using this method, we analyze the impact of time variation within a transmission block (time variation could arise both from Doppler spread of the channel and from synchronization errors). To mitigate the effects of such time variations, we propose a time-domain approach. We design ICI-mitigating block linear filters, and we examine how they are modified in the context of space-time block-coded transmissions. Our approach reduces to the familiar single-tap frequency-domain equalizer when the channel is block time invariant. Channel estimation in rapidly time-varying scenarios becomes critical, and we propose a scheme for estimating channel parameters varying within a transmission block. Along with the channel estimation scheme, we also examine the issue of pilot tone placement and show that in time-varying channels, it may be better to group pilot tones together into clumps that are equispaced onto the FFT grid; this placement technique is in contrast to the common wisdom for time-invariant channels. Finally, we provide numerical results illustrating the performance of these schemes, both for uncoded and space-time block-coded systems.
Phosphotyrosine‐Protein‐Phosphatases and Human Reproduction: An Association between Low Molecular Weight Acid Phosphatase (ACPl) and Spontaneous Abortion (1996)

ACP1 (low molecular weight acid phosphatase) genetic polymorphism has been studied in 173 women with a history of two or more consecutive spontaneous abortions and in 1508 control subjects, including 482 normal pregnant women. The proportion of carriers of ACP1*C allele (*A/ *C, *B/*C) in women with a history of repeated spontaneous abortion is lower than in normal pregnant women and other control groups. Women with repeated spontaneous abortion show a specific decrease of ACP1 S isoform concentration as compared to normal pregnant women. The other component of ACP1 activity, the F isoform, does not show a significant difference between the two groups. The data suggest that women with ACP1 genotypes showing a high concentration of S isoform are relatively 'protected' against spontaneous abortion. Preliminary analysis of a sample of 352 normal puerperae along with their newborn babies supports this hypothesis.
Adherence of Staphylococcus epidermidis to fibrin-platelet clots in vitro mediated by lipoteichoic acid (1990)

The adherence of two strains of Staphylococcus epidermidis to human fibrin-platelet clots in vitro was investigated. Both strains were noncapsulated, nonhemagglutinating, and nonslime producers. Binding was not related to surface charge, carbohydrate profile, or hydrophobicity of the bacteria. Adherence was reduced four- to sixfold (P less than 0.001) on pretreatment of bacteria with lipase, while neuraminidase, trypsin, phospholipase C, and sodium periodate did not alter their binding. Pretreatment of bacteria with substances known to bind lipoteichoic acid (LTA), such as human albumin and anti-LTA antibodies, also resulted in a fourfold (P less than 0.001) reduction in adherence. Prior incubation of clots with free LTA, but not with deacylated LTA, produced a fourfold (P less than 0.001) decrease in the adherence of homologous and heterologous strains of S. epidermidis. A similar reduction was also observed when LTAs derived from Staphylococcus aureus and Streptococcus pyogenes were used. These data provide evidence that the lipid moiety of LTA has a central role in the adherence of S. epidermidis to fibrin-platelet clots in vitro.
Rapid and protracted phases of retinal ganglion cell loss follow axotomy in the optic nerve of adult rats (1993)

To investigate the short- and long-term effects of axotomy on the survival of central nervous system (CNS) neurons in adult rats, retinal ganglion cells (RGCs) were labelled retrogradely with the persistent marker diI and their axons interrupted in the optic nerve (ON) by intracranial crush 8 or 10 mm from the eye or intraorbital cut 0.5 or 3 mm from the eye. Labelled RGCs were counted in flat-mounted retinas at intervals from 2 weeks to 20 months after axotomy. Two major patterns of RGC loss were observed: (1) an initial abrupt loss that was confined to the first 2 weeks after injury and was more severe when the ON was cut close to the eye; (2) a slower, persistent decline in RGC densities with one-half survival times that ranged from approximately 1 month after intraorbital ON cut to 6 months after intracranial ON crush. A small population of RGCs (approximately 5%) survived for as long as 20 months after intraorbital axotomy. The initial loss of axotomized RGCs presumably results from time-limited perturbations related to the position of the ON injury. A persistent lack of terminal connectivity between RGCs and their targets in the brain may contribute to the subsequent, more protracted RGC loss, but the differences between intraorbital cut and intracranial crush suggest that additional mechanisms are involved. It is unclear whether the various injury-related processes set in motion in both the ON and the retina exert random effects on all RGCs or act preferentially on subpopulations of these neurons.
Geometrical information extraction from laser speckle pattern images using texture analysis (2006)

In this paper, the statistical properties of speckle pattern are investigated from the point of view of computer texture analysis, and a measurement method of an object surface roughness and the object surface displacement is subsequently put forward. In the geometrical information extraction technique, the speckle pattern images are taken by a very simple configuration of setup consisting of a laser and a CCD camera. Surface roughness and displacement information is extracted based on the energy feature characterization of the grey level co-occurrence matrices of the speckle pattern images. Our experimental results show that surface roughness and displacement contained in surface speckle pattern images have a good relationship with their energy feature. By means of a set of standard surface specimens with different roughness, the relation curve is readily calibrated. Then the surface roughness of an object surface made by same material and manufactured by the same way as the standard specimens can be evaluated from a single speckle pattern image taken from the surface. Similarly, the surface displacement can also be obtained from a single speckle pattern image. The easily implemented method can be used in-process surface roughness and displacement measurement.
Intracellular accumulation, subcellular distribution, and efflux of tilmicosin in chicken phagocytes (1998)

Tilmicosin is a semi-synthetic macrolide antibiotic, currently approved for veterinary use in cattle and swine respiratory disease, and is in development for use in poultry mycoplasma air sacculitis. In order to provide an understanding of clinical efficacy, the in vitro interaction of tilmicosin with three types of chicken phagocytes (MQ-NCSU macrophages, monocyte-macrophages, and heterophils) was evaluated. After incubation with radiolabeled tilmicosin, uptake was determined and expressed as the ratio of the cellular (Cc) to the extracellular (Ce) drug concentration (Cc:Ce). Tilmicosin was avidly accumulated by heterophils (Cc: Ce 138 at 4 h incubation vs 32 and 66, respectively, in MQ-NCSU and monocyte-macrophages) with 61 to 88% localized in the lysosomes. Uptake was dependent on cell viability, temperature, and pH, but was not influenced by metabolic inhibitors. However, phagocytosis of Pasteurella multocida and lipopolysaccharide exposure increased tilmicosin uptake by the chicken phagocytes. Upon removal of extracellular tilmicosin, 50% of the intracellular tilmicosin was effluxed within the first 30 min, but after 4 h of incubation in antibiotic-free medium, 30% remained cell-associated. Opsonized P. multocida significantly enhanced the release of tilmicosin from all three types of chicken phagocytes. Tilmicosin uptake was observed to increase lysosomal enzyme (acid phosphatase, lysozyme, avidin, and beta-glucuronidase) production. Finally, neutrophils were shown to transport and efflux bioactive tilmicosin in a test system measuring both neutrophil chemotaxis under agarose and a bioassay measuring inhibition of bacterial growth in the presence of antibiotic in agar. These in vitro observations of cellular pharmacology suggest a complex interaction between phagocytes and tilmicosin that contribute to clinical efficacy.
The Importance of Conformation in the Ozonolysis of Acetals (1972)

Six gauche conformations are theoretically possible for an acetal function and only three of them are reactive toward ozone. Each oxygen of the acetal function must have an electron pair orbital oreitned antiperiplanar to the C—H bond in order to be reactive toward ozone.
Neurons, astrocytes, and oligodendrocytes of the rat cerebral cortex originate from separate progenitor cells: an ultrastructural analysis of clonally related cells (1993)

The diverse array of neurons and glia in the mammalian cerebral cortex arises from proliferating cells of the ventricular zone that surrounds the lateral ventricles of the developing brain. A fundamental but unresolved question is whether the individual cells of the ventricular zone are committed to producing progeny of only one particular phenotype or whether they generate progeny of more than one phenotype. We have begun to address this question by asking if individual cells of the ventricular zone generate exclusively neurons or glia at the onset of cortical neurogenesis in the rat. To assess the phenotypes of cells derived from a common progenitor cell, retroviral-mediated gene transfer was used to introduce the reporter gene, Escherichia coli beta-galactosidase, into ventricular zone cells at embryonic day 15 or 16. We used histochemistry to reveal beta-galactosidase-expressing cells in the mature rat cerebral cortex. Isolated clusters of beta-galactosidase-expressing cells, presumably clones, were identified in serial sections. Since the histochemical reaction product is electron dense, each cell could be examined at the ultrastructural level and assigned definitively to one of the major classes of cells in the cerebral cortex on the basis of well-established morphological criteria. This approach overcomes the problems of cell type identification encountered with light microscopy, where it is not always possible to distinguish between different cell phenotypes. We found that virtually all clones contained cells of exclusively one type: either all astrocytes, all oligodendrocytes, or all neurons. Furthermore, each particular cell type exhibited a different pattern and intensity of staining. The neuronal clones, with one exception, were composed of either all pyramidal cells (projection neurons), or all nonpyramidal cells (interneurons). The size and composition of neuronal clones did not seem related to their position in the cerebral cortex. Collectively, our observations indicate that separate progenitor cells exist for pyramidal neurons, nonpyramidal neurons, astrocytes, and oligodendrocytes. The striking phenotypic homogeneity in the clones arising from individual progenitor cells suggests that by the onset of cortical neurogenesis, at least some lineage restrictions have already occurred among the precursor cell population. Thus, our results suggest that lineage may play a pivotal role in determining some of the functionally important phenotypic attributes of cells in the cerebral cortex.
Tensions in the Role of the IMF and Directions for Reform (2005)

While the International Monetary Fund (IMF) has evolved considerably since its foundation 60 years ago, the past few years have brought fresh challenges. This paper discusses four key areas in which developments have led to a rethinking of the institution's role: the emerging market financial crises, the changing role of conditionality, the phenomenon of prolonged use, and the search for a clearer role in low-income countries. In response to these challenges, important reforms have been undertaken to strengthen the institution's effectiveness, but important tensions remain unresolved. The paper discusses the implications for the governance of the institution.
Hyaluronan in human cerebrospinal fluid (1996)

We studied the concentration of hyaluronan in cerebrospinal fluid (CSF) in various diseases and attempted to define its reference interval. A radioassay utilizing cartilage proteins with affinity for hyaluronan was used in determining the concentration of 200 lumbar and 27 ventricular CSF specimens and 11 brain cyst fluids. Molecular weight distributions were determined by gel chromatography and localization in brain tissue by histochemistry. The hyaluronan level of lumbar CSF showed an increase with age; comparatively healthy children had (mean +/- SD) 50 +/- 41 micrograms/L (n = 40) and adults 166 +/- 77 micrograms/L (n = 9); i.e. significantly different values. The highest level was recorded in a patient with meningitis (> 8000 micrograms/L). More than 4000 micrograms/ L was noted in a patient with tumour metastasis in the cerebellum. Significantly elevated levels were especially found with spinal stenosis, head injury and cerebral infarction, but also in inflammatory medical disorders, hydrocephalus and encephalitis. We found no significant increase in multiple sclerosis and some other neurological diseases. Ventricular CSF of adults contained significantly less hyaluronan (53 +/- 73 micrograms/L; n = 16) than lumbar CSF. Hyaluronan in cyst fluids varied from 31 to 25,000 micrograms/L. Weight average molecular weight of hyaluronan in CSF was 2.9-3.0 x 10(5) and in brain tumour cyst fluid 2.4 x 10(6). In search for the origin of hyaluronan in CSF it was found that its concentration in the choroid plexus and leptomeninges was low, but that hyaluronan was accumulated in the superficial layer of the cerebral cortex. Continued screening for hyaluronan in CSF may be valuable in cases of inflammatory diseases, tumours and obstruction to CSF flow.