Miracle-dz/UniFAR-FTUs huggingface dataset:
The human platelet proteome mapped by peptide‐centric proteomics: A functional protein profile

Several studies have been published in which holistic approaches were used to characterise the proteome and transcriptome of human platelets. The key intent being that a deeper understanding of the normal and aberrant physiological functions of platelets can only be achieved if most biomolecular building blocks are mapped. Here we present the application of recently developed novel technologies that overcome some of the shortcomings of gel‐based proteomics. Central in our approach is the so‐called combined fractional diagonal chromatography (COFRADIC)‐technology in which sets of representative peptides are sorted in a diagonal RP chromatographic system through a specific modification of their side chain. In this study we combined three different COFRADIC sorting techniques to analyse the proteome of human platelets. Methionyl, cysteinyl and amino terminal peptides were isolated and analysed by MS/MS. Merging the peptide identifications obtained after database searching resulted in a core set of 641 platelet proteins, which comprises the largest set identified today. In comparison to previously published platelet proteomes, we identified 404 novel platelet proteins containing a high number of hydrophobic membrane proteins and hypothetical proteins. Furthermore we discuss the observed characteristics and potential benefits of each of the different COFRADIC technologies for proteome analysis and highlight important issues that need to be considered when searching sequence databases using data obtained in peptide‐centric, non‐gel proteomics studies.
Inhibition of Digestive α-Amylases from Chilo Suppressalis Walker (Lepidoptera: Crambidae) by a Proteinaceous Extract of Citrullus Colocynthis L. (Cucurbitaceae)

The striped rice-stem borer, Chilo suppressalis (Walker) is one of the most important pest of rice worldwide. In this study, a proteinaceous extract from Citrullus colocynthis L. shows various degrees of inhibition to digestive α-amylases of C. suppressalis. Digestive α-amylases of larvae were inhibited by different concentrations (approximately 50%) of C. colocynthis amylase inhibitor (CCAI). One of the isozymes totally disappeared and the sharpness of another decreased on native-PAGE electrophoresis. The pH dependency of inhibition revealed that the enzyme was inhibited in a wide range of pH from 7-10, and the optimal pH of the enzyme occurred in lepidopteran larvae. The highest inhibition of α-amylase by CCAI was observed at 25°C; the temperature near the optimal temperature of amylolytic activity. A time-course experiment demonstrated that enzymatic activity was the highest, 30 min after the onset of the experiment, when the highest inhibition occurred. The enzyme kinetic studies using Lineweaver-Burk analysis, revealed a mixed inhibition of CCAI on α-amylase activity. The current study is the first basic one using α-amylase inhibitor against C. suppres- salis. This study opens the way for transgenic rice varieties containing inhibitors.
AZGP-1 Immunohistochemical Marker in Prostate Cancer: Potential Predictive Marker of Biochemical Recurrence in Post Radical Prostatectomy Specimens

One of the major challenges in prostate cancer research is to identify prognostic/predictive factors to distinguish aggressive disease from indolent one. To select prognostic/predictive markers of postoperative biochemical recurrence (BCR) that could be easily performed in daily pathology practice, the expression of 6 immunohistochemical markers including zinc-&agr;-2-glycoprotein (AZGP-1), hCAP-D3, mucin 1, vimentin, E-cadherin, and ERG was assessed in a tissue microarray of 400 radical prostatectomy specimens. The expression levels were correlated with clinicopathologic factors and BCR. During the median follow-up period of 55 months, BCR occurred in 70 cases (17.5%). Low expression of AZGP-1 was noted in 76 cases (19.0%), whereas high expression of hCAP-D3, mucin 1, vimentin, and ERG was observed in 205 (51.3%), 81 (20.3%), 33 (8.3%), and 58 (14.5%) cases, respectively. Aberrant E-cadherin expression was noted in 29 cases (7.3%). By univariate analysis, BCR was associated with low expression of AZGP-1, high expression of hCAP-D3, and aberrant expression of E-cadherin. By multivariate analysis, only AZGP-1 remained an independent immunohistochemical factor, in addition to age, preoperative serum prostate-specific antigen level, Gleason score, tumor stage, and resection margin status. These results show that AZGP-1, hCAP-D3, and E-cadherin are potentially useful immunohistochemical markers to predict BCR, and that AZGP-1 can be used as an independent prognostic marker of aggressive prostate cancer.
On the mechanism of alkylphosphocholine (APC)-induced apoptosis in tumour cells

Abstract Alkylphosphocholines (APCs) represent a new and very encouraging class of antitumour agents that have also been shown to induce apoptosis in tumour cells, but their exact mode of action has still not been elucidated. The APC compound presented here, S-1-O-phosphocholine-2-N-acetyl-octadecane (S-NC-2) induces apoptosis in a variety of cancer cells. To define the molecular requirements for S-NC-2-induced apoptosis, activation of caspase-8 and -3 and the cleavage of death substrates, such as poly(ADP-ribose) polymerase (PARP), were investigated in Jurkat, BJAB, SKW6.4 and K562 cells. The signalling pathway seems to be initiated at the death receptor level. Cells that are defective in Fas-receptor signalling (e.g., FADDdn BJAB), as well as cells lacking the Fas receptor (K562), were resistant to S-NC-2 treatment. Furthermore, the treatment of Jurkat cells with S-NC-2 resulted in the clustering of death receptor molecules and co-localisation of the Fas receptor with caveolin, a marker for lipid rafts. In addition, the involvement of mitochondria was detected, since S-NC-2 induces the breakdown of the mitochondrial membrane potential. Overexpression of the anti-apoptotic protein Bcl-2 prevented the loss of ΔΨm in type II (Jurkat) but not in type I cells (SKW6.4). Moreover, cleavage of Bid was found, which points to a possible linkage between the receptor-dependent and the mitochondrial pathways.
CORE-COLLAPSE SUPERNOVAE MISSED BY OPTICAL SURVEYS

We estimate the fraction of core-collapse supernovae (CCSNe) that remain undetected by optical SN searches due to obscuration by large amounts of dust in their host galaxies. This effect is especially important in luminous and ultraluminous infrared galaxies, which are locally rare but dominate the star formation at redshifts of z ∼ 1–2. We perform a detailed investigation of the SN activity in the nearby luminous infrared galaxy Arp 299 and estimate that up to 83% of the SNe in Arp 299 and in similar galaxies in the local universe are missed by observations at optical wavelengths. For rest-frame optical surveys we find the fraction of SNe missed due to high dust extinction to increase from the average local value of ∼19% to ∼38% at z ∼ 1.2 and then remain roughly constant up to z ∼ 2. It is therefore crucial to take into account the effects of obscuration by dust when determining SN rates at high redshift and when predicting the number of CCSNe detectable by future high-z surveys such as LSST, JWST, and Euclid. For a sample of nearby CCSNe (distances 6–15 Mpc) detected during the last 12 yr, we find a lower limit for the local CCSN rate of 1.5+0.4− 0.3 × 10−4 yr−1 Mpc−3, consistent with that expected from the star formation rate. Even closer, at distances less than ∼6 Mpc, we find a significant increase in the CCSN rate, indicating a local overdensity of star formation caused by a small number of galaxies that have each hosted multiple SNe.
Learning and Computational Neuroscience: Foundations of Adaptive Networks

"Learning and Computational Neuroscience" presents recent advances in understanding the brain processes underlying learning and memory, including neural systems analyses of dynamic circuit interactions in the brain and computational models capable of describing simple forms of learning and performance. Its principal aim is to show how each approach is related to and benefits the other, providing a powerful strategy for understanding cognitive processes.Michael Gabriel is Professor of Psychology at the University of Illinois. John Moore is Professor of Psychology and Associate Professor of Computer and Information Science at the University of Massachusetts at Amherst.Contributors: Michael Gabriel and John Moore. Joseph E. LeDoux, Bruce S. Kapp, Amy Wilson, Jeffrey P. Pascoe, William Supple, Paul J. Whalen, Norman W. Weinberger, John H. Ashe, Raju Metherate, David M. Diamond, Jon S. Bakin, J. Michael Cassady. Nestor A. Schmajuk. Malcolm W. Brown. Theodore W. Berger, German Barri onuevo, Steven P. Levitan, Donald N. Krieger, Robert J. H. Sclabassi. Neil E. Berthier, Diana E. J. Blazis. E. James Kehoe. John E. Desmond. A. Harry Klopf, James S. Morgan. Richard S. Sutton, Andrew G. Barto. Christopher J. C. H. Watkins.
Improving Care Transitions: Current Practice and Future Opportunities for Pharmacists

During the past decade, patient safety issues during care transitions have gained greater attention at both the local and national level. Readmission rates to U.S. hospitals are high, often because of poor care transitions. Serious adverse drug events (ADEs) caused by an incomplete understanding of changes in complex drug regimens can be an important factor contributing to readmission rates. This paper describes the roles and responsibilities of pharmacists in ensuring optimal outcomes from drug therapy during care transitions. Barriers to effective care transitions, including inadequate communication, poor care coordination, and the lack of one clinician ultimately responsible for these transitions, are discussed. This paper also identifies specific patient populations at high risk of ADEs during care transitions. Several national initiatives and newer care transition models are discussed, including multi‐ and interdisciplinary programs with pharmacists as key members. Among their potential roles, pharmacists should participate on medical rounds where available, perform medication reconciliation and admission drug histories, apply their knowledge of drug therapy to anticipate and resolve problems during transitions, communicate changes in drug regimens between providers and care settings, assess the appropriateness and patient understanding of drug regimens, promote adherence, and assess health literacy. In addition, this paper identifies barriers and ongoing challenges limiting greater involvement of pharmacists from different practice settings during care transitions. Professional degree programs and residency training programs should increase their emphasis on pharmacists' roles, especially as part of interdisciplinary teams, in improving patient safety during care transitions in diverse practice settings. This paper also recommends that Accreditation Council for Pharmacy Education (ACPE) standards include specific language regarding the exposure of students to issues regarding care transitions and that students have several opportunities to practice the skills needed for effective care transitions. Moreover, reimbursement mechanisms that permit greater pharmacist involvement in providing medication assistance to patients going through care transitions should be explored. Although health information technology offers the potential for safer care transitions, pharmacists' use of information technology must be integrated into the national initiatives for pharmacists to be effectively involved in care transitions. This paper concludes with a discussion about the importance of recognizing and addressing health literacy issues to promote patient empowerment during and after care transitions.
A Practical Guide to Making Patient Assignments in Acute Care

Charge nurses have integral roles in healthcare organizations. Making patient assignments is an important charge nurse role that lacks theoretical support and practical guidelines. Based on a concept analysis of the charge nurse role, the author looks at a theory-gap analysis regarding how patient assignments are made and proposes a framework to guide the process of patient assignments.
Contrasting effects of an ultraviolet B and an ultraviolet A tanning lamp on interleukin‐6, tumour necrosis factor‐α and intercellular adhesion molecule‐1 expression

Background Recent studies have demonstrated that a tanning lamp emitting predominantly ultraviolet (UV) A induces significant yields of the type of potentially mutagenic DNA damage that are associated with the onset of skin cancer (i.e. cyclobutane pyrimidine dimers). UV‐induced immunosuppression is also an important event leading to skin cancer.Objectives To the modulation of key immunological molecules following exposure to a broad‐spectrum UVB lamp and a predominantly UVA‐emitting tanning lamp using model in vitro systems.Methods We compared secretion and mRNA expression of interleukin (IL)‐6 and tumour necrosis factor (TNF)‐α in normal human epidermal keratinocytes, and interferon (IFN)‐γ‐induced intracellular adhesion molecule (ICAM)‐1 in normal human fibroblasts irradiated in vitro with a broad‐spectrum UVB lamp or with a Philips ‘Performance’ tanning lamp.Results With broad‐spectrum UVB irradiation, upregulation of IL‐6 and TNF‐α mRNA was detected 6 h after irradiation, and a dose‐dependent increase of cytokines in the supernatants of irradiated cells was found 24 h after irradiation. In contrast, there was no cytokine secretion and little evidence for mRNA upregulation following exposure to a tanning lamp. When cells were exposed first to broad‐spectrum UVB, then the tanning lamp, UVB‐induced cytokine secretion was inhibited, although mRNA levels were upregulated to a level close to that observed with UVB alone. By using a Schott WG 320 nm filter to attenuate the level of UVB relative to UVA emitted by the tanning lamp, the inhibition of cytokine secretion was shown to be associated with UVA exposure. Both UV sources inhibited IFN‐γ‐induced ICAM‐1 mRNA expression in a dose‐dependent fashion. By using a Schott WG 335 nm filter, inhibition of ICAM‐1 mRNA expression by the tanning lamp was shown to be associated with UVB exposure.Conclusions These results suggest that UV sources emitting different levels of UVA and UVB have differential effects on the modulation of different immunoregulatory molecules, and indicate that there are potential interactions between these wavelengths.
Interferon-&ggr; modulates the functional profile of in-vitro-cultured porcine microglia

Microglia are the most important immune cells within the highly specialized environment of the central nervous system. Upon activation, they transform from a resting ‘ramified’ into a fully functional ‘amoeboid’ phenotype with the ability to perform phagocytosis and generate free radicals. A combined flow cytometric assay for the simultaneous measurement of these two functions in porcine microglia in vitro is presented: reactive oxygen species are detected using hydroethidine; phagocytosis is assessed using fluorescein isothiocyanate-labeled latex beads. The combination of these two probes allowed us to distinguish four subpopulations within cultured porcine microglia on the basis of their functional activity. The effect of several exogenous stimuli [phorbol myristate acetate, conditioned medium, interferon &ggr; (IFN-&ggr;)] on the in-vitro functional properties of porcine microglia is investigated using this test. In particular for IFN-&ggr;, a significant modulatory effect on the intracellular reactive oxygen species production and phagocytic activity was observed. This result suggests an alternative role of IFN-&ggr; acting on cultured porcine microglia.
SPATA2 – Keeping the TNF signal short and sweet

In this issue of The EMBO Journal, a multi‐layered global proteome resource, which comprehensively covers TNF‐induced phosphorylation and ubiquitination events as well as receptor interactions, has led to identification of SPATA2 as a novel player that contributes to TNF signalling by interacting with the LUBAC ubiquitin ligase and the CYLD deubiquitylase. Loss of SPATA2 augments transcriptional activation of NF‐κB and limits TNF‐induced necroptosis. A separate screen published in EMBO Reports corroborates these findings by showing that SPATA2 deficiency regulates CYLD activity, TNF‐induced NF‐κB signalling and cell death.
How Polymer Surface Diffusion Depends on Surface Coverage

Measurements are presented of how surface diffusion of flexible polymers at the solid−liquid interface is controlled by surface coverage. Surface coverage is varied over the full range from dilute to saturated surface coverage. The method of measurement is fluorescence correlation spectroscopy (FCS), and the systems are poly(ethylene oxide) (PEG) and dextran adsorbed onto methyl-terminated self-assembled monolayers in buffered aqueous solution. A detailed study of PEG (Mw = 10 800 g mol-1) shows nonmonotonic behavior. The translational diffusion coefficient (D) at first increases with increasing surface concentration, presumably because the number of adsorption sites per molecule decreases as chains switch from pancake to loop−train−tail conformation. Excellent fits to behavior characteristic of a single diffusion process argue against aggregation or crystallization in the adsorbed state. In-situ ellipsometry measurements appear to rule out conformation changes to a hypothetical helical structure, as this.
Interactions of Insula Subdivisions-Based Networks with Default-Mode and Central-Executive Networks in Mild Cognitive Impairment

Interactions between the brain networks and subnetworks are crucial for active and resting cognitive states. Whether a subnetwork can restore the adequate function of the parent network whenever a disease state affects the parent network is unclear. Investigations suggest that the control of the anterior insula-based network (AIN) over the default-mode network (DMN) and central-executive network (CEN) is decreased in individuals with mild cognitive impairment (MCI). Here, we hypothesized that the posterior insula-based network (PIN) attempts to compensate for this decrease. To test this, we compared a group of MCI and normal cognitive individuals. A dynamical causal modeling method has been employed to investigate the dynamic network controls/modulations. We used the resting state functional MRI data, and assessed the interactions of the AIN and of the PIN, respectively, over the DMN and CEN. We found that the greater control of AIN than that of DMN (Wilcoxon rank sum: Z = 1.987; p = 0.047) and CEN (Z = 3.076; p = 0.002) in normal group and the lower (impaired) control of AIN than that of CEN (Z = 8.602; p = 7.816 × 10-18). We further revealed that the PIN control was significantly higher than that of DMN (Z = 6.608; p = 3.888 × 10-11) and CEN (Z = 6.429; p = 1.278 × 10-10) in MCI group where the AIN was impaired, but that control was significantly lower than of DMN (Z = 5.285; p = 1.254 × 10-7) and CEN (Z = 5.404; p = 6.513 × 10-8) in normal group. Finally, the global cognitive test score assessed using Montreal cognitive assessment and the network modulations were correlated (Spearman’s correlation: r = 0.47; p = 3.76 × 10-5 and r = -0.43; p = 1.97 × 10-4). These findings might suggest the flexible functional profiles of AIN and PIN in normal aging and MCI.
DDAVP, thromboelastography, and uremia.

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Tandem Queues with Planned Inventories

This paper explores a natural generalization of the classic tandem-queue model, designed specifically to represent make- to-stock production processes. In such systems, intermediate and finished goods can be produced and stored in advance of demand. We consider the simplest version of the model, where demand is a Poisson process, and the unit production times are exponentially distributed. We propose and test a tractable approximation scheme. The approximation appears to be quite accurate.
Genetic parameters for spiral-grain angle in two 19-year-old clonal Norway spruce trials

Spiral grain was measured for all annual rings on wood discs taken at a single sampling height from two 19-year-old (field age) Nor- way spruce (Picea abies (L.) Karst. ) clonal trials. In both trials, the mean grain angle reached a maximum inclination to the left at ring number 4, followed by a monotonic decrease towards a right-handed inclination. Clonal means of mean grain angle of rings 3 to 15 ranged from 0.5 to 4.7 degrees and from -0.2 to 5.3 degrees in the two trials, respectively. The broad-sense heritability of mean grain angle was 0.42 in both trials and the slope of the radial grain-angle development showed heritabilities varying between 0.26 and 0.40. Estimates of genotypic correlations in- dicated that clones with a high grain angle in the inner rings tended to have a more rapid development towards a straight angle in the following rings. Selection based on any of the rings in the interval from ring numbers 5 to 10 was most efficient in decreasing the average grain spirality at the sampling level considered.
Variational principles for relativistic smoothed particle hydrodynamics

In this paper we show how the equations of motion for the smoothed particle hydrodynamics (SPH) method may be derived from a variational principle for both non-relativistic and relativistic motion when there is no dissipation. Because the SPH density is a function of the coordinates the derivation of the equations of motion through variational principles is simpler than in the continuum case where the density is defined through the continuity equation. In particular, the derivation of the general relativistic equations is more direct and simpler than that of Fock. The symmetry properties of the Lagrangian lead immediately to the familiar additive conservation laws of linear and angular momentum and energy. In addition, we show that there is an approximately conserved quantity which, in the continuum limit, is the circulation.
Comparative genomic hybridization analysis on male breast cancer

The spectrum of genetic alterations in primary male breast cancer is not well established. We analyzed chromosomal imbalances in 39 tumor samples from primary male breast cancer by comparative genomic hybridization (CGH) and correlated CGH findings with clinicopathological factors. Chromosomal gains were most frequent at 1q (46%), 8q (46%), 16p (36%), 17q (36%), Xq (28%), 20q (26%) and Xp (18%). Losses were most commonly observed at 8p (36%), 16q (28%), 13q (28%), 6q (18%), 11q (18%) and 22q (18%). Gains at 16p, 20q and Xq and losses at 13q correlated significantly with higher degree of cytogenetic complexity. Significant associations with clinicopathological factors were observed for +8q and −16q with larger tumor size and −16q with lower proliferative activity and lower grade of malignancy. A comparison with reported CGH data from female breast cancer showed a similar pattern of chromosomal imbalances, including +1q, −8p, +8q, −13q, +16p, −16q, +17q and +20q. Our results indicate that male breast cancer shares a common pattern of imbalances with female breast cancer, suggesting that similar genetic events may underlie the development and progression of male and female breast cancer. © 2005 Wiley‐Liss, Inc.