gebhart/patrepeval huggingface dataset:
Extended Duration Vascular Endothelial Growth Factor Inhibition in the Eye: Failures, Successes, and Future Possibilities (2018)

Vascular endothelial growth factor (VEGF) plays a pivotal role in the development of neovascularization and edema from several common chorioretinal vascular conditions. The intravitreally injected drugs (aflibercept, bevacizumab, conbercept, pegaptanib, and ranibizumab) used to treat these conditions improve the visual acuity and macular morphology in most patients. Monthly or bimonthly injections were administered in the phase III pivotal trials but physicians usually individualize therapy with <i>pro re nata</i> (PRN) or treat and extend regimens. Despite these lower frequency treatment regimens, frequent injections and clinic visits are still needed to produce satisfactory outcomes. Newly developed drugs and refillable reservoirs with favorable pharmacokinetic profiles may extend durations of action and require fewer office visits. However, we have learned from previous experiences that the longer durations of action seen in strategically designed phase III trials often do not translate to less frequent injections in real-life clinical practice. Unfortunately, long-acting therapies that produce soluble VEGF receptors (encapsulated cell technology and adenovirus injected DNA) have failed in phase II trials. The development of longer duration therapies remains a difficult and frustrating process, and frequent drug injections are likely to remain the standard-of-care for years to come.
RNA apatamers for yeast ribosomal protein L32 have a conserved purine-rich internal loop. (1997)

Two in vitro selection experiments were conducted to determine the RNA sequence requirements for binding ribosomal protein L32 (RPL32) from Saccharomyces cerevisiae. To preserve the wild-type stem-internal loop-stem fold, only a limited portion of the RNA comprising the internal loop region was randomized. Most of the selected RNAs have secondary structures similar to that of the wild-type, and four purines on both sides of the internal loop are highly conserved. Indeed, a pair of 5'-GA-3' dinucleotides is found in all but one of the stem-loop-stem L32 aptamers and these conserved purines may contact the protein directly or form a necessary RNA secondary or tertiary structure. These aptamers have a potential G:U pair bordering the loop adjacent to the conserved GAs, but a cytidine replaces a phylogenetically conserved adenosine at one loop position in many of the selected RNAs. In model RNAs, the cytidine-bearing variant binds protein slightly more strongly than does the wild-type RNA. That the seven-member, 2 + 5 internal loop is important for protein binding is reinforced by the finding that the position, but not the size, of the loop is variable. A minority of the RNA aptamers has three consecutive uridines and may fold into a similar structure, but with the internal loop inverted.
Distinctive characteristics of bronchial reticular basement membrane and vessel remodelling in chronic obstructive pulmonary disease (COPD) and in asthma: they are not the same disease (2012)

The characteristics of Rbm remodelling are quite different in asthma and COPD.
Dnmt3a Is a Haploinsufficient Tumor Suppressor in CD8+ Peripheral T Cell Lymphoma (2016)

DNA methyltransferase 3A (DNMT3A) is an enzyme involved in DNA methylation that is frequently mutated in human hematologic malignancies. We have previously shown that inactivation of Dnmt3a in hematopoietic cells results in chronic lymphocytic leukemia in mice. Here we show that 12% of Dnmt3a-deficient mice develop CD8+ mature peripheral T cell lymphomas (PTCL) and 29% of mice are affected by both diseases. 10% of Dnmt3a+/- mice develop lymphomas, suggesting that Dnmt3a is a haploinsufficient tumor suppressor in PTCL. DNA methylation was deregulated genome-wide with 10-fold more hypo- than hypermethylated promoters and enhancers, demonstrating that hypomethylation is a major event in the development of PTCL. Hypomethylated promoters were enriched for binding sites of transcription factors AML1, NF-κB and OCT1, implying the transcription factors potential involvement in Dnmt3a-associated methylation. Whereas 71 hypomethylated genes showed an increased expression in PTCL, only 3 hypermethylated genes were silenced, suggesting that cancer-specific hypomethylation has broader effects on the transcriptome of cancer cells than hypermethylation. Interestingly, transcriptomes of Dnmt3a+/- and Dnmt3aΔ/Δ lymphomas were largely conserved and significantly overlapped with those of human tumors. Importantly, we observed downregulation of tumor suppressor p53 in Dnmt3a+/- and Dnmt3aΔ/Δ lymphomas as well as in pre-tumor thymocytes from 9 months old but not 6 weeks old Dnmt3a+/- tumor-free mice, suggesting that p53 downregulation is chronologically an intermediate event in tumorigenesis. Decrease in p53 is likely an important event in tumorigenesis because its overexpression inhibited proliferation in mouse PTCL cell lines, suggesting that low levels of p53 are important for tumor maintenance. Altogether, our data link the haploinsufficient tumor suppressor function of Dnmt3a in the prevention of mouse mature CD8+ PTCL indirectly to a bona fide tumor suppressor of T cell malignancies p53.
A new spontaneous fission mode for {sup 252}Cf: Hyperdeformation, cluster radioactivity, new levels (1995)

Direct measurements of yields and neutron multiplicities were made for Sr-Nd, Zr-Ce, Mo-Ba, Ru-Xe, and Pd-Te from {gamma}-ray coincidence studies in spontaneous fission of {sup 252}Cf. Strong enhancement of the 7-10 {nu} emission channels is seen in the Mo-Ba data. Unfolding the Mo-Ba data revealed a new fission mode associated with the enhanced {nu} yields with much lower total kinetic energy going by {sup 108}Mo-{sup 144}Ba, {sup 107}Mo- {sup 145}Ba, and/or {sup 106}Mo-{sup 146}Ba. Analysis indicates one or more of {sup 144,145,146}Ba are hyperdeformed with 3:1 axis ratio. Theoretical calculations predict a third minimum in the PES for {sup 252}Cf with {beta}{sub 2} {approximately} 0.9 and {beta}{sub 3} {approximately} 0.7. Zero neutron emission channels, a new form of cluster radioactivity, are seen in 8 and 7 correlated pairs in SF of {sup 252}Cf and {sup 242}Pu, respectively, with the odd-odd zero neutron channel yields strongly enhanced as predicted for cluster radioactivity. New level structures and isotopes include new octupole deformations, identical bands and other structures.
Safe Trajectory Generation for Complex Urban Environments Using Spatio-Temporal Semantic Corridor (2019)

Planning safe trajectories for autonomous vehicles in complex urban environments is challenging since there are numerous semantic elements (such as dynamic agents, traffic lights, and speed limits) to consider. These semantic elements may have different mathematical descriptions, such as obstacle, constraint, and cost. It is non-trivial to tune the effects from different combinations of semantic elements for a stable and generalizable behavior. In this letter, we propose a novel unified spatio-temporal semantic corridor (SSC) structure, which provides a level of abstraction for different types of semantic elements. The SSC consists of a series of mutually connected collision-free cubes with dynamical constraints posed by the semantic elements in the spatio-temporal domain. The trajectory generation problem then boils down to a general quadratic programming formulation. Thanks to the unified SSC representation, our framework can generalize to any combination of semantic elements. Moreover, our formulation provides a theoretical guarantee that the entire trajectory is safe and constraint-satisfied, by using the convex hull and hodograph properties of piecewise Bézier curve parameterization. We also release the code of our method to accommodate benchmarking.
Developmental regulation of IL-4, IL-2, and IFN-gamma production by murine peripheral T lymphocytes. (1993)

Lymph node T cells from naive, 4-day-old neonatal mice resemble activated adult T cells in that they produce low levels of IL-2 but high levels of IL-4 in response to anti-CD3 stimulation in vitro. Herein, we show that the capacity for high level IL-4 production is rapidly lost in the early postnatal period. A decline is first evident at 5 days postbirth. By 6 days postbirth, T cells secrete IL-4 at low levels, similar to those produced by T cells from naive, adult animals. In contrast, the acquisition of high, adultlike IL-2 or IFN-gamma production does not occur until approximately 6 wk of life. Thus, the loss of high level IL-4 production and the acquisition of high level IL-2 and IFN-gamma production are distinct developmental events, occurring at widely separated intervals. There are two phases in the transition to adultlike IL-2 production. In the early neonatal period, the underproduction of IL-2 appears to be due to a combination of intrinsic nonresponsiveness to CD3-mediated stimulation and the production of a soluble inhibitor of IL-2 production. The inhibitory activity required the presence of IL-4 because neutralizing anti-IL-4 antibody completely eliminated inhibition. Moreover, experiments using rIL-4 showed that IL-4 alone was sufficient to dramatically inhibit IL-2 production by T cells from naive, adult animals in a primary stimulation. Between 4 to 5 days and 6 wk of life, the underproduction of IL-2 and IFN-gamma appears to result solely from a lowered responsiveness of the T cells. Thus, the progression to adultlike lymphokine production involves a combination of changes in the types of lymphokines produced and in the magnitude of the response to activation signals.
General Formulation of Drillstring Under Large Deformation and Its Use in BHA Analysis (1986)

ABSTRACT The paper presents the basic formulations adopted in a 3-D BHA program called DIDRILSM*, for drillstring deformation under general static downhole loadings. These formulations account for large deformation effects, and have been simplified for fast solution using the finite difference method, while retaining second order terms. An explicit formula for the bit side force is presented. In addition to previously demonstrated effects of WOB, TOB, and borehole curvatures on the bit side force, this paper demonstrates some non-linear effects on the bit side force, which increase with large deformations, mainly due to increased borehole curvatures. For 2-D borehole with less than 5°/100′ curvature, the nonlinear effects on the bit side forces are in general small. The nonlinear effects are seen to be insensitive to WOB, TOB, and hole clearance for the examples considered. Effects due to these latter variables on the local force/moment distributions may be more pronounced.
Driving with Diabetes in the Future: In-Vehicle Medical Monitoring (2010)

The motor car is a ubiquitous feature of modern life, and most of us spend significant amounts of time in a car, behind the wheel. Driving a vehicle requires complex coordination of cognitive, motor, and sensory skills. All of these aspects can be affected adversely by diabetes per se, with hypoglycemia being the main concern for people with diabetes who drive. Here we introduce the concept of using the motor vehicle as a device to collect and deliver physiological and clinical information, which, in turn, may enable more people to drive more safely by reducing the chances of medical mishaps behind the wheel. This is particularly relevant for people living with diabetes who are at risk from a number of medical conditions that have the potential to have an impact on safe driving. The development of in-vehicle medical monitoring presents a new opportunity for novel collaborations between two industries, which have safety as a core value.
An improved synthesis of pyrroles from <i>N‐p</i>‐toluenesulfonylglycine esters and α,β‐unsaturated aldehydes and ketones (1991)

Abstract N‐p ‐Toluenesulfonylglycine esters 2 condensed with α,β ‐unsaturated carbonyl compounds 1 in the presence of the non‐nucleophilic base DBU to give hydroxypyrrolidines 3 . Dehydration with phosphorus oxychloride‐pyridine, followed by DBU mediated elimination of p ‐toluenesulfinic acid, gave a series of synthetically useful pyrrole‐2‐carboxylates 5 .
Tribulosin suppresses apoptosis via PKC epsilon and ERK1/2 signaling pathway during hypoxia/reoxygenation in neonatal rat ventricular cardiac myocytes (2011)

Tribulosin (tigogenin 3-O-β-D-xylopyranosyl(1-2)-[β-D-xylopyranosyl (1-3)]-β-D-glucopyranosyl (1-4)-[a-L-rhamnopyranosyl(1-2)]-β-D-galactopyranoside), a component of gross saponins of Tribulus terrestris, has been shown to produce cytoprotective effects in heart. Yet, the precise mechanisms are not fully understood. We examined the mechanisms of tribulosin on myocardial protection. Ventricular myocytes were isolated from the heart of neonatal rats and were exposed to 3 h of hypoxia followed by 2 h reoxygenation. Apoptosis was induced by hypoxia/reoxygenation (H/R), and the expression of protein kinase C epsilon (PKCϵ) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured neonatal rat cardiac myocytes was detected. The results indicated that treatment with tribulosin in the culture medium protected cardiac myocytes against apoptosis induced by H/R. PKCϵ and ERK1/2 expression increased after pretreated with tribulosin. In the presence of PKCϵ inhibitor co-treated with tribulosin, the expression of ERK1/2 was decreased in H/R cardiac myocytes. While preconditioned with PD98059, ERK1/2 inhibitor, no effects on the expression of PKCϵ were detected. Tribulosin has protective effects on cardiac myocytes against apoptosis induced by H/R injury via PKCϵ and ERK1/2 signaling pathway.
Constituents of <i>Nauclea</i><i>diderrichii</i>. Part VII. Synthesis of nauclederine, naucleonine, and naucleonidine; spectroscopic evidence for the structures of 3α-dihydrocadambine and two other constituents (1976)

Evidence is advanced concerning the structures of six N. diderrichii alkaloids, based on synthetic and spectroscopic studies. The synthesis of nauclederine, 2, provides support for the structural assignment made earlier. Synthesis has shown that the structures previously assigned to the alkaloids designated ND-305B and ND-363C are incorrect; this, however, has led to revised structures (19 and 20) for these alkaloids, now named naucleonine and naucleonidine, respectively, and these have been established by synthesis. Based on this study and an examination of data obtained previously, a tentative proposal is made for the structure 21 of another constituent of the plant, designated ND-363B. Spectroscopic studies have allowed a structure 22 to be advanced for the glycosidic alkaloid, which was shown to be identical with the alkaloid 3α-dihydrocadambine obtained by Brown and Fraser. Based on this study and a reexamination of data reported previously, structure 25 is tentatively proposed for another constituent of the plant, designated ND-370.
Frustrated Alzheimer’s researchers seek better lab mice (2018)

Several projects are trying to develop animal models that more closely mimic how the brain disease affects people. Several projects are trying to develop animal models that more closely mimic how the brain disease affects people.
Task assignment optimization in geographically distributed data centers (2017)

Recent advance in geo-distributed systems has made distributed data processing possible, where tasks are decomposed into subtasks, deployed into multiple data centers and run in parallel. Compared to conventional approaches that process every task in a single datacenter resulting in high latency and large data aggregation, the geo-distributed cloud systems provide a highly available and more economic platform. However, distributed application (task) execution introduces extra cost and latency as data need to be exchanged between data centers. In addition, task dependency and diverse task constraints make it even more challenging to choose an appropriate task assignment strategy. In this paper, we discuss a task assignment problem in geographically distributed cloud systems. In light of growing demand from big data processing and storage, we consider data intensive tasks where a task often requires significant computing resources and its input data typically located in multiple data centers. By taking the distributed input, task dependency, heterogeneous pricing scheme, and resource constraints into account, we aim to optimize the performance when deploying tasks in geo-graphically distributed data centers. A heuristic algorithm is presented to provide an approximate solution to the proposed NP-hard problem. We perform an extensive simulation study to evaluate the performance of our solution under various settings. The simulation results demonstrate that our approach can outperform the state-of-the-art strategies, and achieve significant reduction in cost and latency.
Preparation of IgA‐deficient platelets (1990)

The IgA-deficient patient presents a difficult transfusion problem, particularly if he or she has previously been immunized and has formed IgA antibodies. Blood components from IgA-deficient donors may be used safely but are often not accessible to transfusion facilities. A satisfactory red cell component may be obtained by standard freezing and washing methods. There is no comparable platelet concentrate that uniformly affords protection against anti-IgA-mediated reactions. A method has been developed for the preparation of an IgA-deficient platelet concentrate by washing with citrate-buffered saline. Platelets prepared in this manner were transfused successfully to an IgA-deficient patient with a history of anaphylaxis related to transfusion. It was further demonstrated that the removal of IgA is enhanced if platelets are washed within 48 hours of collection. When platelets were stored for more than 48 hours, similar washing techniques resulted in significantly higher levels of IgA in the platelets washed with either buffered (p = 0.004) or unbuffered (p = 0.0002) saline. Platelets washed with unbuffered saline (pH 4.5-5.5) contained substantially more IgA than did platelets washed in a similar manner with citrate-buffered saline (pH 6.5-6.8) (p = 0.001).
Pneumocystis cariniiPneumonia in patients with solid tumors without acquired immune deficiency syndrome (1991)

Pneumocystis carinii pneumonia (PCP) developed in two patients with solid tumors without acquired immune deficiency syndrome (AIDS). In patients with neoplastic solid tumors, as in those with hematologic malignancies, Pneumocystis is a possible cause of pneumonia. Management protocols evaluating pulmonary infiltrates in this patient population must include tests for PCP.
Microbial diversity drives multifunctionality in terrestrial ecosystems (2016)

Despite the importance of microbial communities for ecosystem services and human welfare, the relationship between microbial diversity and multiple ecosystem functions and services (that is, multifunctionality) at the global scale has yet to be evaluated. Here we use two independent, large-scale databases with contrasting geographic coverage (from 78 global drylands and from 179 locations across Scotland, respectively), and report that soil microbial diversity positively relates to multifunctionality in terrestrial ecosystems. The direct positive effects of microbial diversity were maintained even when accounting simultaneously for multiple multifunctionality drivers (climate, soil abiotic factors and spatial predictors). Our findings provide empirical evidence that any loss in microbial diversity will likely reduce multifunctionality, negatively impacting the provision of services such as climate regulation, soil fertility and food and fibre production by terrestrial ecosystems.
Cationic rare-earth metal SALEN complexes (2008)

Complexes (Salpren(tBu,tBu))Y[N(SiHMe2)2](thf) and (SALEN(tBu,tBu))La[N(SiHMe2)2](thf) (SALEN(tBu,tBu) = Salcyc(tBu,tBu) and Salpren(tBu,tBu)) were prepared from Ln[N(SiHMe2)2]3(thf)2 and H2SALEN(tBu,tBu). The yttrium complex was characterized by X-ray crystallography revealing intrinsic solid-state structural features: the metal centre is displaced by 1.05 angstroms from the [N2O2] least squares plane of a highly bent Salpren(tBu,tBu) ligand (angle(Ph,Ph) dihedral angle of 80.4(1) degrees ) and is coordinated asymmetrically by the silylamide ligand exhibiting one significant Y---(HSi) beta-agostic interaction (Y-N1-Si1, 106.90(9) degrees; Y---Si1, 3.2317(6) angstroms). Complexes (SALEN(tBu,tBu))Ln[N(SiHMe2)2](thf)n (n = 1, Sc; n = 2, Y, La) react with ammonium tetraphenylborate to form the ion pairs [(SALEN(tBu,tBu))Ln(thf)n][BPh4]. The cationisation was proven by X-ray crystal structure analyses of [(Salpren(tBu,tBu))Sc(thf)2][B(C6H5)4].2(thf) and [(Salpren(tBu,tBu))Ln(thf)3][B(C6H5)4].4(thf) (Ln = Y, La), showing an octahedral and pentagonal-bipyramidal coordination geometry, respectively.
An Investigation of Phosphorus Transient Diffusion in Silicon Below the Solid Solubility Limit and at a Low Implant Energy (1994)

Transient diffusion of ion‐implanted phosphorus under nonoxidizing conditions is studied for P doses of at 20 keV. The annealing steps [rapid thermal anneal (RTA) or furnace anneal (FA)] are carried out in an ambient at 950 or 1050°C. A "kink" is observed in secondary ion mass spectroscopy (SIMS) profiles for both RTA and FA runs. A significant enhanced diffusion is observed in the concentration regime below the kink. In addition, from the SIMS profiles it appears that phosphorus atoms in the surface region tend to pile up at the interface. Phosphorus diffusion is modeled using a previously reported empirical model for boron and arsenic diffusion.1 Activation energies and other model coefficients have been fit based on the RTA data only, and then applied to both RTA and FA diffusions. The long preannealing cycle in FA runs has been accounted for in simulations. A comparison of simulations, SIMS, SRP, and electrical measurements shows that phosphorus concentration above the kink (i.e., phosphorus pileup) is immobile. Further, phosphorus pileup appears to be active in the high dose samples, but inactive in the low dose ones. This deactivation is believed to be due to the formation of some type of phosphorus‐vacancy complex in the vacancy‐rich region at the surface.
Pantheism and enlightenment : the state of the debate (2007)

International audience
Fabric organization of the subendothelium of the human brain artery by polarized-light microscopy. (1991)

The thickened subendothelium of brain arteries that is characteristic of atherosclerosis was assessed for the directional organization of the two main birefringent components, smooth muscle cells and collagen. Thirty-three arteries from 16 autopsy cases were pressure fixed at 30, 60, 110, and 200 mm Hg, sectioned at a thickness of 7 microns , and stained with silver impregnation to enhance tissue birefringence. The intended focus of the study was on muscle organization, but it also included the collagen among the cells because of the coalignment of the two tissues and their similar staining properties for polarized-light microscopy. The birefringent medial fabric at all pressures was circumferentially oriented, with a mean deviation of the 33 sections of 1.4 degrees from circumferential with an average circular standard deviation of 3.5 degrees, thereby showing remarkable coherence. In contrast, the subendothelium showed great variability both in thickness and in organization. Many arteries had no measurable subendothelium, and others had as much as 100%, with some atherosclerotic lesions as much as 300% of the medial width. Measurements from the subendothelium revealed a helical arrangement of tissue, often divided into separate regions, with a balance of left- and right-handed helical components and generally with lower pitch angles in the layers adjacent to the lumen. The average circular standard deviation within individual subendothelial layers was 14.5 degrees.