Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute and Persistent Suppression of Preproenkephalin mRNA Expression in the Striatum Following Developmental Hypoxic‐Ischemic Injury

Abstract: The striatum is vulnerable to hypoxic‐ischemic injury during development. In a rodent model of perinatal hypoxia‐ischemia, it has been shown that striatal neurons are not uniformly vulnerable. Cholinergic neurons and NADPH‐diaphorase‐positive neurons are relatively spared. However, it is unknown what classes of striatal neurons are relatively sensitive. One of the major classes of striatal neurons uses enkephalin as a neurotransmitter. We have studied the effect of early hypoxic‐ischemic injury on this class of neurons using a quantitative solution hybridization assay for preproenkephalin mRNA in conjunction with in situ hybridization. Hypoxia‐ischemia results in an early (up to 24 h) decrease in striatal preproenkephalin mRNA, which is shown by in situ hybridization to occur mainly in the dorsal portion of the striatum. By 14 days, whole striatal preproenkephalin mRNA and total enkephalin‐containing peptide levels are normal. However, at 14 days, in situ hybridization reveals that regions of complete preproenkephalin mRNA‐positive neuron loss remain in the dorsal region. Normal whole striatal levels are due to an up‐regulation of preproenkephalin mRNA expression in the ventrolateral region of the injured striatum. Given the important role that the enkephalin‐containing striatal efferent projection plays in regulating motor function, its relative loss may be important in the chronic disturbances of motor control observed in brain injury due to developmental hypoxic‐ischemic injury.
Comparison of Human Immunodeficiency Virus Type 1 Pr55Gag and Pr160Gag-Pol Processing Intermediates That Accumulate in Primary and Transformed Cells Treated with Peptidic and Nonpeptidic Protease Inhibitors

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) produces two polyproteins, Pr55Gag and Pr160Gag-Pol, that are cleaved into mature functional subunits by the virally encoded protease. Drugs that inhibit this protease are an important part of anti-HIV therapy. We studied the ordered accumulation of Gag and Gag-Pol processing intermediates by variably blocking the protease with HIV-1 protease inhibitors (PIs). Variable protease inhibition caused accumulation of a complex pattern of processing intermediates, which was the same after incubating HIV-1-infected cells with increasing concentrations of either one of the peptidomimetic inhibitors indinavir, saquinavir (SQV), ritonavir (RTV), nelfinavir, and SC-52151 or one of the nonpeptidomimetic inhibitors DMP450, DMP323, PNU-140135, and PNU-109112 for 3 days. The patterns of Gag and Gag-Pol processing intermediate accumulation were nearly identical when the following were compared: cell- versus virion-associated proteins, HIV-1-infected transformed cell lines versus primary human peripheral blood mononuclear cells (PBMCs) and HIV-1MN versus HIV-1IIIB virus strains. RTV was a more potent inhibitor of p24 production in PBMCs than SQV by approximately 7-fold, whereas SQV was a more potent inhibitor in transformed cells than RTV by approximately 30-fold. Although the antiretroviral potency of HIV-1 PIs may change as a function of cell type, the polyprotein intermediates that accumulate with increasing drug concentrations are the same. These results support sequential processing of Gag and Gag-Pol polyproteins by the HIV-1 protease and may have important implications for understanding common cross-resistance pathways.
Vascular Endothelial Growth Factor (VEGF) Concentration Is Underestimated by Enzyme-Linked Immunosorbent Assay in the Presence of Anti-VEGF Drugs.

PURPOSE Commercially available enzyme-linked immunosorbent assay (ELISA) kits are often used to monitor vascular endothelial growth factor (VEGF) levels in exudative age-related macular degeneration. To test their accuracy, this study performed measurements using the ELISA kits in the presence of anti-VEGF drugs. METHODS The concentrations of bevacizumab, pegaptanib, or ranibizumab at 28 days and aflibercept at 28 and 56 days after an injection were estimated based on previous pharmacokinetic studies. Vascular endothelial growth factor concentrations were measured with two widely used VEGF ELISA kits in the presence of anti-VEGF drugs or control mouse immunoglobulin G (IgG). The monocyte chemotactic protein-1 (MCP-1) ELISA kit was used as a non-VEGF ELISA control kit. RESULTS The concentrations of aflibercept, bevacizumab, pegaptanib, and ranibizumab were estimated at 0.14 to 7.2, 4.9, 8.6, and 0.11 to 1.1 μg/mL, respectively. ELISA underestimated the VEGF concentration 2- to 100-fold lower in the presence of an anti-VEGF drug, except for pegaptanib, at all VEGF concentrations tested (7.8-1500 pg/mL). Vascular endothelial growth factor at 1000 pg/mL was measured as 92, 150, and 170 pg/mL in the presence of aflibercept (7.2 μg/mL), bevacizumab (4.9 μg/mL), and ranibizumab (1.1 μg/mL), respectively (all P < 0.0001), and the measured VEGF concentration decreased proportionately by 90% to 92% with aflibercept, 85% to 94% with bevacizumab, and 83% to 99% with ranibizumab. The control mouse IgG did not interfere with the measurement of VEGF. Ranibizumab did not affect the measurements with MCP-1 ELISA. CONCLUSIONS Investigators should exercise caution when interpreting measurements of VEGF ELISA in patients being treated with an anti-VEGF drug.
Performance comparison of top N recommendation algorithms

In traditional recommender systems, services/items are recommended to the user based on the initial ratings while the results comes from the predicted rating values are not considered which further refers to top N recommendations. In top N recommendation algorithms, recommendation process is further enhanced by predicting the missing ratings where the basic objective is to find the items that might be interest of a user. Performance comparison and evaluation of different top N recommendation algorithms is quite challenging for large datasets where selection of an appropriate algorithm can help to improve the recommendation process by predicting missing ratings. Therefore, in this paper we analyse and evaluate the 6 different top N recommendation algorithms using accuracy metrics such as precision and recall on Movie-lense 100K dataset from the Group-lens. Our main finding is the selection of Top N recommendation algorithm that perform significantly better than other recommender algorithms in pursuing the top-N recommendation process.
Virtual Network Functions instantiation on SDN switches for policy-aware traffic steering

Software-Defined Networking (SDN) provides the capability to steer traffic in a network to lower the management cost. Network Function Virtualization (NFV) gives the chance to implement network functions at the right time and the right place to increase operation flexibility. Together SDN and NFV show the potential to create an agile system with a low operations cost and a high customer satisfaction. However, the combination of SDN with NFV results in the redundant packet forwarding traffic inside SDN in order to forward packets based on the deployed network functions for a service chain. Besides, it also increase the computation requirement of a controller for possible packet header modifications and flow states management. In this paper, we propose to implement network functions on SDN switches to lower the traffic inside of SDN and the computation requirement of a SDN controller. We create network function modules for open virtual switches and make those functions to be managed by a controller with an algorithm to streamline the implemented service chains. Our results show that the proposed system can reduce about 2/3 of current network traffic compared to the current solutions without the modification of forwarding tables and packets.
Organization and Function of the YsiA Regulon of Bacillus subtilis Involved in Fatty Acid Degradation*

The organization and function of the Bacillus subtilis YsiA regulon involved in fatty acid degradation were investigated. Northern and primer extension analyses indicated that this regulon comprises five operons, i.e. lcfA-ysiA-B-etfB-A, ykuF-G, yhfL, yusM-L-K-J, and ywjF-acdA-rpoE. YusJ and AcdA, YsiB and YusL, and YusK presumably encode acyl-CoA dehydrogenases, 3-hydroxyl-CoA dehydrogenase/enoyl-CoA hydratase complexes, and acetyl-CoA C-acyltransferase, respectively, which are directly involved in the fatty acid β-oxidation cycle. In addition, LcfA and YhfL are likely to encode long chain acyl-CoA ligases. On gel retardation and footprinting analyses involving the purified YsiA protein, we identified cis-sequences for YsiA binding (YsiA boxes) in the promoter regions upstream of ysiA, ykuF, yusL, yhfL, and ywjF, the equilibrium dissociation constants (Kd) for YsiA binding being 20, 21, 37, 43, and 65 nm, respectively. YsiA binding was specifically inhibited by long chain acyl-CoAs with 14–20 carbon atoms, acyl-CoAs with 18 carbon atoms being more effective; out of long chain acyl-CoAs tested, monounsaturated oleoyl-CoA, and branched chain 12-metyltetradecanoyl-CoA were most effective. These in vitro findings were supported by the in vivo observation that the knock-out of acyl-CoA dehydrogenation through yusJ, etfA, or etfB disruption resulted in YsiA inactivation, probably because of the accumulation of long chain acyl-CoAs in the cells. Furthermore, the disruption of yusL, yusK, yusJ, etfA, etfB, or ykuG affected the utilization of palmitic acid, a representative long chain fatty acid. Based on this work, ysiA, ysiB, ykuF, ykuG, yhfL, yusM, yusL, yusK, yusJ, and ywjF can be renamed fadR, fadB, fadH, fadG, lcfB, fadM, fadN, fadA, fadE, and fadF.
Geometrically based preconditioner for the Fast Multipole Method using rooftop basis functions and Galerkin testing procedure

The EFIE formulation has been adopted in the FMM-Fast Fourier Transform (FFT) code [7], using a restarted GMRES solver. The first tested geometry consists on a hollow cylinder (1.6λ radius, 3.2λ height) and two λ/2-length dipoles modeled employing wire basis functions. These dipoles are set at a λ/4 distance from the cylinder wall spaced 90°. The estimation of the mutual admittance provided by a reference Method of Moments (MoM) code, non-preconditioned FMM-FFT and preconditioned FMM-FFT approaches is shown in Figure 1. The non-preconditioned result comes up slowly to the reference solution without reaching it after the allowed number of iterations. A better agreement is achieved in a few iterations with the preconditioned solution. In order to give more insight on the preconditioner behavior, it has been evaluated an error measure of the current coefficients regarding to MoM solution. With an analogous aim than for rw in (3), this error has been weighted by L to express all the terms in Amperes, independently of the basis function type. It has been obtained an error of 1% with the preconditioned method, better than the 6% for the non-preconditioned solution. [htpb] Both original and weighted residues of equation (3) are plotted in Figure 2. It illustrates clearly the chaotic behavior of the original residue in contrast to the smooth curves obtained using the weighting procedure. It may be appreciated that a better convergence is obtained for the preconditioned method and that the weighted residue is more correlated with the actual situation reflected in Figure 1.
Experience in Monitoring Gentamicin Therapy during Treatment of Serious Gram-Negative Sepsis

This paper reports our experience in monitoring gentamicin therapy during the treatment of 68 episodes of serious Gram-negative sepsis in 65 hospital patients. Most of the patients had major underlying disease. Of those who were adequately treated (peak serum concentrations of 5 μg/ml or more in 72 hours for septicaemia, urinary tract infection, and wound infection; and 8 μg/ml or more at some time during the course of treatment for pneumonia) 84% (46 out of 55) were cured. These serum concentrations could be achieved only by starting with a regimen of 5 mg/kg/day in three divided doses in all adult patients, subsequent dosage being determined by the results of rapid serum assay. The incidence of nephrotoxicity and symptomatic ototoxicity was no greater than in previous series. The main reason for assaying serum gentamicin is to ensure that an adequate dosage is achieved as soon as possible. In patients with impaired renal function or receiving prolonged high dosage assays also serve to guard against an excessive accumulation of gentamicin and an increased risk of toxicity.
Applying proximity rank join model into location-based services

Joining objects from different web sources and returning top-k combinations is a research topic with much attention. Such techniques could be used in location based scenarios, which for one example, help plan a wonderful night by finding a good combination of hotel, restaurant and theater. Challenge to such techniques is that in a good combination, each individual object should be good enough and, of equal or even greater importance, subject to some given criteria, such as within a given range and close to each other. Proximity rank join method is one way to settle this problem. It takes advantage of sorted access of inputs, does not rely on specialize data structures to determine spatial closeness, and has efficient pull and bound strategies to avoid reading too much inputs before finding the top-k answers. In this paper, we propose a detailed scheme using the proximity rank join model that is optimized for location based purposes. It will be shown that our scheme indeed reflects user's desire better and outperform the naïve Euclidean distance scheme.
Chronic exposure to free fatty acids or high glucose induces apoptosis in rat pancreatic islets: possible role of oxidative stress.

We investigated the effect of a chronic exposure to high levels of free fatty acid (FFA; 2 mmol/L oleate/palmitate 2:1) or glucose (16.7 mmol/L) on islet cell apoptosis. Apoptosis was detected using 4 different methods: (1) cell staining with annexin-V fluorescien isothiocyanate (FITC) conjugate and propidium iodide (PI); (2) quantification of cytoplasmatic DNA fragments by an enzyme-linked immunosorbent assay (ELISA); (3) assay of caspase 3 activity; and (4) TdT-mediated dUTP nick-end labeling (TUNEL). Islet cells were also costained with an anti-insulin antibody to identify apoptotic beta cells. We also evaluated by reverse-transcriptase polymerase chain reaction (RT-PCR) the expression of bax, bcl-2, and caspas 3, genes involved in apoptosis. In islets cultured for 7 days in the presence of high FFA or for 3 days in the presence of high glucose levels, we observed: (1) a 2- to 3-fold increase of apoptotic cells conjugated with annexin-V FITC and PI; (2) a 4- to 6-fold increase of cytoplasmatic DNA fragments; (3) a 3- to 4-fold increase of caspase 3 activity; and (4) a significant increase of insulin positive apoptotic cells as detected with the TUNEL method. RT-PCR analysis indicated in islets exposed to high FFA or glucose levels an increase of bax (proapoptotic gene), a reduction of bcl-2 (antiapoptotic gene), and a slight (although not significant) increase in caspase 3 expression. Western blot analysis also showed an increase of Bax protein levels in islets exposed to high FFA or glucose. The simultaneous presence of both metabolic abnormalities did not further increase the amount of apoptotic cells, although the time-course of the cellular damage induced by FFA was accelerated by the contemporary presence of high glucose. To elucidate the mechanism by which FFA and glucose may induce pancreatic beta-cell damage, we examined whether nicotinamide prevents apoptosis in pancreatic islets cultured for 7 days with high FFA or for 3 days with high glucose. Nicotinamide was able to prevent beta-cell damage by significantly reducing apoptosis in both experimental conditions. Also, the increase of Bax protein level was prevented by nicotinamide. These data indicate that chronic exposure to elevated FFA or glucose levels increases apoptosis in rat pancreatic islets and these cytotoxic effects could be mediated by oxidative stress. This may contribute to the beta-cell failure that occurs in most in type 2 diabetic patients few years after clinical diabetes onset.
Vection during Conflicting Multisensory Information about the Axis, Magnitude, and Direction of Self-Motion

We examined the vection induced by consistent and conflicting multisensory information about self-motion. Observers viewed displays simulating constant-velocity self-motion in depth while physically oscillating their heads left–right or back–forth in time with a metronome. Their tracked head movements were either ignored or incorporated directly into the self-motion display (as an added simulated self-acceleration). When this head oscillation was updated into displays, sensory conflict was generated by simulating oscillation along: (i) an orthogonal axis to the head movement; or (ii) the same axis, but in a non-ecological direction. Simulated head oscillation always produced stronger vection than ‘no display oscillation’—even when the axis/direction of this display motion was inconsistent with the physical head motion. When head-and-display oscillation occurred along the same axis: (i) consistent (in-phase) horizontal display oscillation produced stronger vection than conflicting (out-of-phase) horizontal display oscillation; however, (ii) consistent and conflicting depth oscillation conditions did not induce significantly different vection. Overall, orthogonal-axis oscillation was found to produce very similar vection to same-axis oscillation. Thus, we conclude that while vection appears to be very robust to sensory conflict, there are situations where sensory consistency improves vection.
Addressing Conceptual Gaps in Big Data Research Ethics: An Application of Contextual Integrity

The rise of big data has provided new avenues for researchers to explore, observe, and measure human opinions, activities, and interactions. While scholars, professional societies, and ethical review boards have long-established research ethics frameworks to ensure the rights and welfare of the research subjects are protected, the rapid rise of big data-based research generates new challenges to long-held ethical assumptions and guidelines. This article discloses emerging conceptual gaps in relation to how researchers and ethical review boards think about privacy, anonymity, consent, and harm in the context of big data research. It closes by invoking Nissenbaum’s theory of “privacy as contextual integrity” as a useful heuristic to guide ethical decision-making in big data research projects.
Where and How to Search for Evidence in the Education Literature: The WHEEL

An awareness of how and where to search the education literature, and how to appraise it is essential to be a teacher scholar (an academic who takes a scholarly approach to teaching), to develop high quality education research, and to perform the scholarship of teaching and learning. Most pharmacy faculty scholars do not receive training in searching the education literature. Thus, a framework for searching the education literature is needed. The framework presented here on where and how to search for evidence in the education literature, referred to as the WHEEL for teaching, is meant to serve as a guide for faculty members in conducting comprehensive and exhaustive literature searches for the publication of scholarship of teaching and learning projects, educational research, or approaching one's teaching in a scholarly manner. Key resources to search and methods for searching the education literature are listed and described.
Overlapping Specificities of Base Excision Repair, Nucleotide Excision Repair, Recombination, and Translesion Synthesis Pathways for DNA Base Damage in Saccharomyces cerevisiae

ABSTRACT The removal of oxidative damage from Saccharomyces cerevisiae DNA is thought to be conducted primarily through the base excision repair pathway. The Escherichia coliendonuclease III homologs Ntg1p and Ntg2p are S. cerevisiae N-glycosylase-associated apurinic/apyrimidinic (AP) lyases that recognize a wide variety of damaged pyrimidines (H. J. You, R. L. Swanson, and P. W. Doetsch, Biochemistry 37:6033–6040, 1998). The biological relevance of theN-glycosylase-associated AP lyase activity in the repair of abasic sites is not well understood, and the majority of AP sites in vivo are thought to be processed by Apn1p, the major AP endonuclease in yeast. We have found that yeast cells simultaneously lacking Ntg1p, Ntg2p, and Apn1p are hyperrecombinogenic (hyper-rec) and exhibit a mutator phenotype but are not sensitive to the oxidizing agents H2O2 and menadione. The additional disruption of the RAD52 gene in the ntg1 ntg2 apn1 triple mutant confers a high degree of sensitivity to these agents. The hyper-rec and mutator phenotypes of the ntg1 ntg2 apn1 triple mutant are further enhanced by the elimination of the nucleotide excision repair pathway. In addition, removal of either the lesion bypass (Rev3p-dependent) or recombination (Rad52p-dependent) pathway specifically enhances the hyper-rec or mutator phenotype, respectively. These data suggest that multiple pathways with overlapping specificities are involved in the removal of, or tolerance to, spontaneous DNA damage in S. cerevisiae. In addition, the fact that these responses to induced and spontaneous damage depend upon the simultaneous loss of Ntg1p, Ntg2p, and Apn1p suggests a physiological role for the AP lyase activity of Ntg1p and Ntg2p in vivo.
Identification of Amino Acid Residues Critical for Aggregation of Human CC Chemokines Macrophage Inflammatory Protein (MIP)-1α, MIP-1β, and RANTES

Human CC chemokines macrophage inflammatory protein (MIP)-1α, MIP-1β, and RANTES (regulated on activation normal T cell expressed) self-associate to form high-molecular mass aggregates. To explore the biological significance of chemokine aggregation, nonaggregating variants were sought. The phenotypes of 105 hMIP-1α variants generated by systematic mutagenesis and expression in yeast were determined. hMIP-1α residues Asp26and Glu66 were critical to the self-association process. Substitution at either residue resulted in the formation of essentially homogenous tetramers at 0.5 mg/ml. Substitution of identical or analogous residues in homologous positions in both hMIP-1β and RANTES demonstrated that they were also critical to aggregation. Our analysis suggests that a single charged residue at either position 26 or 66 is insufficient to support extensive aggregation and that two charged residues must be present. Solution of the three-dimensional NMR structure of hMIP-1α has enabled comparison of these residues in hMIP-1β and RANTES. Aggregated and disaggregated forms of hMIP-1α, hMIP-1β, and RANTES generally have equivalent G-protein-coupled receptor-mediated biological potencies. We have therefore generated novel reagents to evaluate the role of hMIP-1α, hMIP-1β, and RANTES aggregation in vitro and in vivo. The disaggregated chemokines retained their human immunodeficiency virus (HIV) inhibitory activities. Surprisingly, high concentrations of RANTES, but not disaggregated RANTES variants, enhanced infection of cells by both M- and T-tropic HIV isolates/strains. This observation has important implications for potential therapeutic uses of chemokines implying that disaggregated forms may be necessary for safe clinical investigation.