gebhart/patrepeval huggingface dataset:
Towards a comprehensive simulation model of malaria epidemiology and control (2008)

Planning of the control of Plasmodium falciparum malaria leads to a need for models of malaria epidemiology that provide realistic quantitative prediction of likely epidemiological outcomes of a wide range of control strategies. Predictions of the effects of control often ignore medium- and long-term dynamics. The complexities of the Plasmodium life-cycle, and of within-host dynamics, limit the applicability of conventional deterministic malaria models. We use individual-based stochastic simulations of malaria epidemiology to predict the impacts of interventions on infection, morbidity, mortality, health services use and costs. Individual infections are simulated by stochastic series of parasite densities, and naturally acquired immunity acts by reducing densities. Morbidity and mortality risks, and infectiousness to vectors, depend on parasite densities. The simulated infections are nested within simulations of individuals in human populations, and linked to models of interventions and health systems. We use numerous field datasets to optimise parameter estimates. By using a volunteer computing system we obtain the enormous computational power required for model fitting, sensitivity analysis, and exploration of many different intervention strategies. The project thus provides a general platform for comparing, fitting, and evaluating different model structures, and for quantitative prediction of effects of different interventions and integrated control programmes.
ChemInform Abstract: THE TERT.‐BUTYLDIMETHYLSILYL (TBDMS) GROUP AS A PROTECTING GROUP IN DEOXYNUCLEOSIDES (1974)

Abstract TBDMS‐chlorid reagiert in Gegenwart von Imidazol in DMF bei 35°C selektiv mit den Hydroxylgruppen von Nucleosiden, wie z.B. (I), zu Gemischen aus den entsprechenden Mono‐ und Diderivaten (II)‐(IV), wobei im Falle der Desoxynucleoside (I) insbesondere die 5′‐Derivate (II) gebildet werden.
Sorghum Expressed Sequence Tags Identify Signature Genes for Drought, Pathogenesis, and Skotomorphogenesis from a Milestone Set of 16,801 Unique Transcripts (2005)

Improved knowledge of the sorghum transcriptome will enhance basic understanding of how plants respond to stresses and serve as a source of genes of value to agriculture. Toward this goal, Sorghum bicolor L. Moench cDNA libraries were prepared from light- and dark-grown seedlings, drought-stressed plants, Colletotrichum-infected seedlings and plants, ovaries, embryos, and immature panicles. Other libraries were prepared with meristems from Sorghum propinquum (Kunth) Hitchc. that had been photoperiodically induced to flower, and with rhizomes from S. propinquum and johnsongrass (Sorghum halepense L. Pers.). A total of 117,682 expressed sequence tags (ESTs) were obtained representing both 3' and 5' sequences from about half that number of cDNA clones. A total of 16,801 unique transcripts, representing tentative UniScripts (TUs), were identified from 55,783 3' ESTs. Of these TUs, 9,032 are represented by two or more ESTs. Collectively, these libraries were predicted to contain a total of approximately 31,000 TUs. Individual libraries, however, were predicted to contain no more than about 6,000 to 9,000, with the exception of light-grown seedlings, which yielded an estimate of close to 13,000. In addition, each library exhibits about the same level of complexity with respect to both the number of TUs preferentially expressed in that library and the frequency with which two or more ESTs is found in only that library. These results indicate that the sorghum genome is expressed in highly selective fashion in the individual organs and in response to the environmental conditions surveyed here. Close to 2,000 differentially expressed TUs were identified among the cDNA libraries examined, of which 775 were differentially expressed at a confidence level of 98%. From these 775 TUs, signature genes were identified defining drought, Colletotrichum infection, skotomorphogenesis (etiolation), ovary, immature panicle, and embryo.
High-quality volume rendering using texture mapping hardware (1998)

Wt present a method Jor volume rendering of regular grids cclhic~h takes advantage of <?D texture mapping hardware currc,rhlly available on graphics workstations.
X-Ray Crystal Structures of Human Immunodeficiency Virus Type 1 Protease Mutants Complexed with Atazanavir (2007)

Atazanavir, which is marketed as REYATAZ, is the first human immunodeficiency virus type 1 (HIV-1) protease inhibitor approved for once-daily administration. As previously reported, atazanavir offers improved inhibitory profiles against several common variants of HIV-1 protease over those of the other peptidomimetic inhibitors currently on the market. This work describes the X-ray crystal structures of complexes of atazanavir with two HIV-1 protease variants, namely, (i) an enzyme optimized for resistance to autolysis and oxidation, referred to as the cleavage-resistant mutant (CRM); and (ii) the M46I/V82F/I84V/L90M mutant of the CRM enzyme, which is resistant to all approved HIV-1 protease inhibitors, referred to as the inhibitor-resistant mutant. In these two complexes, atazanavir adopts distinct bound conformations in response to the V82F substitution, which may explain why this substitution, at least in isolation, has yet to be selected in vitro or in the clinic. Because of its nearly symmetrical chemical structure, atazanavir is able to make several analogous contacts with each monomer of the biological dimer.
DNA binding by the herpes simplex virus type 1 ICP4 protein is necessary for efficient down regulation of the ICP0 promoter (1989)

The herpes simplex virus type 1 ICP4 and ICP0 polypeptides are immediate-early proteins that positively and negatively regulate expression of other viral genes in trans. ICP4 has recently been shown to bind DNA bearing the consensus sequence 5'-ATCGTCNNNN(T/C)CG(A/G)C-3', present upstream of a number of viral genes. To test the hypothesis that this DNA-binding activity is involved in ICP4-mediated gene regulation, site-specific mutagenesis was employed to mutate the version of this sequence in the promoter of the ICP0 gene. The mutation eliminated detectable binding of ICP4 to the promoter as measured in vitro by a gel electrophoresis band shift assay. The ability of the mutated ICP0 promoter to direct synthesis of a reporter gene was also investigated in a transient transfection assay. Whereas ICP4 was found to transactivate the wild-type ICP0 promoter two- to threefold, the mutated promoter was transactivated seven- to ninefold. In assays containing the ICP0 transactivator gene, ICP4 down regulated the wild-type promoter far more efficiently than the mutated promoter. Finally, both the wild-type and mutated ICP0 promoters exhibited a similar response to ICP4 in transfections that included a vector expressing the viral transactivator protein VP16. These experiments suggest that the sequence-specific DNA-binding activity of ICP4 is an essential element of its role as a negative regulator of gene expression.
Leech salivary gland extract from Haementeria officinalis, a potent inhibitor of cyclophosphamide- and radiation-induced artificial metastasis enhancement. (1984)

Studies were designed to determine whether salivary gland extract (SGE) from the leech Haementeria officinalis could inhibit enhancement of lung tumor colonization induced by pretreatment of mice with cyclophosphamide (CY) or local thoracic irradiation (LTI). Tumor nodules in the lung were generated by i.v. injections of T241 sarcoma and FSA fibrosarcoma cells into syngeneic C57BL/6 and C3Hf/Kam mice, respectively. CY (200 mg/kg) was given i.p. 1 or 4 days prior to i.v. injection of tumor cells. In other mice, a single dose of 1000 rads of LTI was given 1 day before tumor cells. Three i.v. or i.p. injections of SGE at doses of 600 to 800 micrograms of protein per injection given at 2-hr intervals between 2 hr before and 4 hr after CY, LTI, or tumor cell injection strongly inhibited and, in some cases, abolished the artificial metastasis enhancing effect of CY and LTI. SGE was similarly effective in inhibiting the enhancement of lung colonization when given before or after cytotoxic agents. Using [125I]iododeoxyuridine-labeled tumor cells, it was observed that SGE did not affect the initial lodgement of tumor cells in the lung, but it greatly facilitated their subsequent release from the lung. In normal mice, the SGE was active when given on the day or 1 day before but not when given 4 days before tumor cells. The antimetastatic effect of SGE was ascribed to its anti-platelet-aggregating, anticoagulant, and antiproteolytic enzyme activities.
Control of gastric emptying by regulatory peptides. (1988)

The rate of gastric emptying is controlled by humoral and nerval factors. When glucose, fat, or amino come into contact with the duodenal mucosa inhibitory mechanisms decrease the fundic pressure and thereby slow the gastric emptying of nutrients. Among the various peptides, so far investigated, gastrin inhibits the emptying rate, however, this effect is only seen at unphysiological high concentrations. Cholecystokinin, on the other hand, is able to decrease the delivery of glucose to the duodenum at physiological concentrations. Also secretin exerts an inhibitory effect on gastric emptying. The peptide YY which is released from the ileum and colon after ingestion of carbohydrates or fat and which inhibits gastric acid secretion also reduces the amount of food emptied from the stomach. This inhibitory effect was achieved by doses which are within the physiological range. The neuropeptide vasoactive intestinal polypeptide (VIP) and the enkephalins are both able to retard the gastric emptying. Some of these effects, especially of VIP, are mediated by noncholinergic, non-adrenergic inhibitory vagal nerves. Stimulation of gastric emptying is seen with motilin and somatostatin. The effect of motilin is a direct one, whereas the effect of somatostatin is probably due to inhibition of regulatory peptides which in turn inhibit the emptying in the sense of a feedback. So far, these peptides which are responsible for the inhibitory effect of gastric emptying following the presence of carbohydrates in the duodenum, have not yet been elucidated. The rate of glucose delivery to the duodenum determines the shape of the blood glucose curve and either directly via the blood glucose or indirectly via the release of insulinotropic gut hormones, also the amount of insulin secreted.
Identification of an Oligodeoxynucleotide Sequence Motif That Specifically Inhibits Phosphorylation by Protein Tyrosine Kinases (1997)

Protein tyrosine kinases (PTKs) have central roles in cellular signal transduction. We have identified a sequence motif (CGT[C]GA) in phosphorothioate-modified oligodeoxynucleotides (ODNs) that specifically inhibits the enzymatic activity of recombinant or immunoprecipitated PTK in vitro. Hexamer ODNs containing this motif block both substrate and autophosphorylation of at least four different PTKs but have no apparent effect on the enzymatic activity of a serine/threonine protein kinase. These data suggest possible new applications for ODNs and have implications for the design and interpretation of experiments using antisense or triplex ODNs.
Probabilistic Modeling for Face Orientation Discrimination: Learning from Labeled and Unlabeled Data (1998)

This paper presents probabilistic modeling methods to solve the problem of discriminating between five facial orientations with very little labeled data. Three models are explored. The first model maintains no inter-pixel dependencies, the second model is capable of modeling a set of arbitrary pair-wise dependencies, and the last model allows dependencies only between neighboring pixels. We show that for all three of these models, the accuracy of the learned models can be greatly improved by augmenting a small number of labeled training images with a large set of unlabeled images using Expectation-Maximization. This is important because it is often difficult to obtain image labels, while many unlabeled images are readily available. Through a large set of empirical tests, we examine the benefits of unlabeled data for each of the models. By using only two randomly selected labeled examples per class, we can discriminate between the five facial orientations with an accuracy of 94%; with six labeled examples, we achieve an accuracy of 98%. 1
80 nm ultra-wideband erbium-doped silica fibre amplifier (1997)

The authors demonstrate a two band architecture for an ultra-wideband erbium-doped silica fibre amplifier with a record optical bandwidth of 80 nm. To obtain a low noise figure and high output power, the two bands share a common first gain section and have distinct second gain sections.
The Inhibition of Fibroblast Growth Factor-2 Export by Cardenolides Implies a Novel Function for the Catalytic Subunit of Na+,K+-ATPase (1998)

Basic fibroblast growth factor (FGF-2) is one of a select group of proteins that can exit cells through an alternate, endoplasmic reticulum/Golgi apparatus independent exocytic pathway. This alternate pathway has been termed protein export. In an attempt to better understand this process, we have identified a family of related compounds, "cardenolides," that inhibit FGF-2 export. The cardenolides inhibit FGF-2 export in a time and concentration dependent fashion. Inhibition of FGF-2 export is specific in that the cardenolides have no effect on conventional protein secretion as measured by their inability to block release of the secreted protein human chorionic gonadotropin-alpha. Because cardenolides are known to inhibit ion transport activity mediated by Na+,K+-ATPase, we investigated whether there are functional interactions between FGF-2 and their only known molecular target: the alpha-subunit of Na+, K+-ATPase. Export of FGF-2 from COS-1 cells is selectively inhibited when co-transfected with expression vectors encoding the alpha-subunit and FGF-2. Moreover, antibodies to the alpha-subunit specifically co-immunoprecipitate FGF-2 along with the alpha-subunit while conversely, antibodies to FGF-2 specifically co-immunoprecipitate the alpha-subunit along with FGF-2. Finally, the ion transporting activities of the Na+,K+-ATPase can be uncoupled from protein export. Varying the external concentration of K+ has little effect on export of FGF-2. Taken together, these data: 1) identify a novel activity for cardenolides; 2) suggest a previously unknown role for the alpha-subunit of Na+, K+-ATPase in FGF-2 export; and 3) raise the possibility that the alpha-subunit itself may be an integral component of this alternate exocytic pathway mediating translocation of cytosolic FGF-2 to the cell surface.
Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. (1976)

A single cell clonal line which responds reversibly to nerve growth factor (NGF) has been established from a transplantable rat adrenal pheochromocytoma. This line, designated PC12, has a homogeneous and near-diploid chromosome number of 40. By 1 week's exposure to NGF, PC12 cells cease to multiply and begin to extend branching varicose processes similar to those produced by sympathetic neurons in primary cell culture. By several weeks of exposure to NGF, the PC12 processes reach 500-1000 mum in length. Removal of NGF is followed by degeneration of processes within 24 hr and by resumption of cell multiplication within 72 hr. PC12 cells grown with or without NGF contain dense core chromaffin-like granules up to 350 nm in diameter. The NGF-treated cells also contain small vesicles which accumulate in process varicosities and endings. PC12 cells synthesize and store the catecholamine neurotransmitters dopamine and norepinephrine. The levels (per mg of protein) of catecholamines and of the their synthetic enzymes in PC12 cells are comparable to or higher than those found in rat adrenals. NGF-treatment of PC12 cells results in no change in the levels of catecholamines or of their synthetic enzymes when expressed on a per cell basis, but does result in a 4- to 6-fold decrease in levels when expressed on a per mg of protein basis. PC12 cells do not synthesize epinephrine and cannot be induced to do so by treatment with dexamethasone. The PC12 cell line should be a useful model system for neurobiological and neurochemical studies.
BAY X1005, a new selective inhibitor of leukotriene synthesis: pharmacology and pharmacokinetics. (1993)

The enantiomer BAY X1005 [(R)-2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl acetic acid] potently inhibits LTB4 synthesis in isolated PMNL of various species (IC50 mumol/l, human 0.22, rat 0.026, mouse 0.039) and LTC4 synthesis in mouse macrophages (IC50 0.021 mumol/l). Due to high protein binding the in vitro potency for LTB4 synthesis inhibition in whole blood is lowered to 17 mumol/l as determined by RIA. BAY X1005 is selective for the 5-lipoxygenase pathway leaving 12-HETE and HHT unaltered, as determined in human whole blood. After oral application BAY X1005 inhibits edema formation and myeloperoxidase activity in the arachidonate-induced mouse ear inflammation test (ED50 48.7 and 7.9, respectively). Oral activity in the rat ex vivo is found in whole blood for LTB4 synthesis inhibition (ED50 11.8 mg/kg p.o.). BAY X1005 demonstrates a high bioavailability (f 86%) with a Cmax of 13 mg/l and t1/2 of 3.5 h in the rat at 10 mg/kg p.o. Thus, the pharmacodynamic, pharmacokinetic profile and safety aspects of the leukotriene synthesis inhibitor BAY X1005 allow testing in man for its therapeutic potential in inflammatory and allergic diseases.
Head-mounted display with mid-air tactile feedback (2015)

Virtual and physical worlds are merging. Currently users of head-mounted displays cannot have unobtrusive tactile feedback while touching virtual objects. We present a mid-air tactile feedback system for head-mounted displays. Our prototype uses the focus of a modulated ultrasonic phased array for unobtrusive mid-air tactile feedback generation. The array and the hand position sensor are mounted on the front surface of a head-mounted virtual reality display. The presented system can enhance 3D user interfaces and virtual reality in a new way.
Ischemia of the Endolymphatic Sac (1992)

A decrease in vascular density in the endolymphatic sac was suspected as a factor in the pathogenesis of endolymphatic hydrops in Meniere's disease. The present study was undertaken to explore this possibility by cutting the posterior meningeal artery and the sigmoid sinus above and below the external aperture of the vestibular aqueduct or by incision of the dura adjacent to the sinus in 18 guinea pigs. The lesions in the sac were greater in the segmental ablation of the artery and sinus and were consistently associated with the development of endolymphatic hydrops. Among the lesions shown in the sac epithelia, the intermediate portion was most often and most severely affected with a decrease in rugose formation and a flattening of the tall epithelial cells or replacement of epithelial cells by squamous type cells. A high correlation between the lesions in the intermediate portion and occurrence of hydrops suggests that the intermediate portion plays a greater role in the pathogenesis of endolymphatic hydrops. The sac luminal precipitates known to be increased in human Meniere's cases were decreased or absent in this study, which suggests that the increased amount is unlikely to be the cause of endolymphatic hydrops. The evidence supports the hypothesis that these substances are secreted by the endolymphatic sac. The limited sensory cell lesions seen in the cochleae and saccules are likely to be due to a temporary vascular ischemia and endolymphatic hydrops.
Skin-derived antileucoproteases (SKALPs): characterization of two new elastase inhibitors from psoriatic epidermis (1990)

Elastase inhibiting activity (EIA) was demonstrated in the epidermis from lesions and in psoriatic scale, whereas normal epidermis did not contain significant EIA. Two new elastase inhibitors were partially purified and characterized using psoriatic scale as a source. The two species (approximate molecular weights 10 and 20 kDa) were shown to be stable, and high-affinity inhibitors of human leucocyte elastase (Ki less than 10(-10) M). No activity against human cathepsin G could be demonstrated. Cultured human keratinocytes were shown to contain EIA activity similar to that found in psoriatic scale. EIA could also be demonstrated in human epidermis following the induction of an experimental inflammatory response by sellotape-stripping. We propose the acronym SKALP (skin-derived antileucoprotease) as a name for these new proteinase inhibitors.
Increased Expression of Tissue Plasminogen Activator and Its Inhibitor and Reduced Fibrinolytic Potential of Human Endothelial Cells Cultured in Elevated Glucose (1992)

In diabetic patients, elevated plasma levels of t-PA and PAI-1 accompany impaired fibrinolysis. To identify mechanisms for these abnormalities, we examined whether vascular endothelial cells exposed to high glucose upregulate t-PA and PAI-1 production and whether ambient PA activity is decreased concomitantly. In 17 cultures of human umbilical vein endothelial cells grown to confluency in 30 mM glucose, the t-PA antigen released to the medium in 24 h was (median) 52 ng/10(6) cells (range 10-384) and the PAI-1 antigen was 872 ng/10(6) cells (range 217-2074)--both greater (P less than 0.02) than the amounts released by paired control cultures grown in 5 mM glucose--29 ng/10(6) cells (range 7.5-216) and 461 ng/10(6) cells (range 230-3215), respectively. In the presence of high glucose, the steady-state levels of t-PA and PAI-1 mRNAs were increased correspondingly (median 142 and 183% of control, respectively, P less than 0.05); high glucose per se and hypertonicity contributed to the upregulation in additive fashion. The PA activity of conditioned medium from cultures exposed to high glucose was 0.4 IU/ml (range 0.2-0.6), which was significantly lower (P less than 0.02) than the PA activity of control medium (0.5 IU/ml, range 0.2-0.9). No difference was observed when comparing the PA activities of acidified conditioned media, expected to be depleted of inhibitors. Thus, high glucose coordinately upregulates endothelial t-PA and PAI-1 expression through effects exerted at the pretranslational level and enhanced by even mild degrees of hypertonicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Precise Data Locality Optimization of (2002)

A significant source for enhancing application performance and for reducing power consumption in embedded processor applications is to improve the usage of the memory hierarchy. In this paper, a temporal and spatial locality optimization framework of nested loops is proposed, driven by parameterized cost functions. The considered loops can be imperfectly nested. New data layouts are propagated through the connected references and through the loop nests as constraints for optimizing the next connected reference in the same nest or in the other ones. Unlike many existing methods, special attention is paid to TLB (Translation Lookaside Buffer) effectiveness since TLB misses can take from tens to hundreds of processor cycles. Our approach only considers active data, that is, array ele- ments that are actually accessed by a loop, in order to prevent useless memory loads and take advantage of storage compression and temporal locality. Moreover, the same data transformation is not necessar- ily applied to a whole array. Depending on the referenced data subsets, the transformation can result in different data layouts for a same array. This can significantly improve the performance since a priori incompatible references can be simultaneously optimized. Finally, the process does not only consider the innermost loop level but all levels. Hence, large strides when control returns to the enclosing loop are avoided in several cases, and better optimization is provided in the case of a small index range of the innermost loop.