Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted unlabeled multiple reaction monitoring analysis of cell markers for the study of sample heterogeneity in isolated rat brain cortical microvessels

Liquid chromatography coupled to tandem mass spectrometry‐based targeted absolute protein quantification (in fmol of the analyte protein per μg of total protein) is employed for the molecular characterization of the blood–brain barrier using isolated brain microvessels. Nevertheless, the heterogeneity of the sample regarding the levels of different cells co‐isolated within the microvessels and bovine serum albumin (BSA) contamination (from buffers) are not always evaluated. We developed an unlabeled targeted liquid chromatography coupled to tandem mass spectrometry method to survey the levels of endothelial cells (ECs), astrocytes, and pericytes, as well as BSA contaminant in rat cortical microvessels. Peptide peak identities were evaluated using a spectral library and chromatographic parameters. Sprague–Dawley rat microvessels obtained on three different days were analyzed with this method complemented by an absolute quantification multiple reaction monitoring method for transporter proteins P‐gp, Bcrp, and Na+/K+ ATPase pump using stable isotope labeled peptides as internal standard. Inter‐day differences in the cell markers and BSA contamination were observed. Levels of cell markers correlated positively between each other. Then, the correlation between cell marker proteins and transporter proteins was evaluated to choose the best EC marker protein for protein quantification normalization. The membrane protein Pecam‐1 showed a very high correlation with the EC‐specific transporter P‐gp (Pearson product‐moment correlation coefficient (r) > 0.89) and moderate to high with Bcrp (r ≥ 0.77), that can be found also in pericytes and astrocytes. Therefore, Pecam‐1 was selected as a marker for the normalization of the quantification of the proteins of endothelial cells.
Kinesin motor activation: Microtubules pull the switches

Within the teeming interior of the cell, many molecular machines drive the essential processes of life. These nanomachines use cellular fuel—ATP—and, as also ought to be true for everyday macromachines, fuel efficiency is paramount. Thus the cell’s nanomachines have evolved to use ATP only when they can couple it to essential work. A study published in PNAS (1) provides unprecedented detail of how one family of cytoskeleton-based nanomachines—the microtubule-tracking kinesins—achieves such fuel efficiency.
LIFE OR DEATH BY EEG.

The bioelectric activity of the living brain is silenced by anoxia which soon produces cerebral death. Respirators and heart stimulators can maintain the look of life in the face of death while agonizing and expensive prolongation of false hope continues for all concerned. When the brain is so compromised, the EEG can signal the point of no return, although the cardiovascular system continues to respond to supportive therapy that produces a respectable ECG. Supportive efforts should be continued only so long as the brain shares physiological response together with heart and lungs. Adequate experience has been analyzed to show that competent application and interpretation of the EEG should gain medical approval for legal pronouncement of human death.
Graphene mediated domain formation in exchange coupled graphene/Co3O4(111)/Co(0001) trilayers

Graphene grown directly on Co3O4(111)/Co(0001) by molecular beam epitaxy exhibits extrinsic p-type doping, as demonstrated by photoemission and conductivity measurements. Trilayer heterostructures of graphene/Co3O4(111)/Co(0001) reveal an unconventional magneto-optical Kerr hysteresis with vanishing remanence for temperatures up to 400 K. Magnetic force microscopy measurements demonstrate that the vanishing remanence is due to a complex domain state, indicating substrate-induced graphene spin polarization. The domain formation of the Co magnetization is in strong contrast to the magnetic behavior of Co in Co/Co3O4 bilayers. This suggests that the Co3O4 interlayer mediates the variable Co magnetization and induced graphene spin polarization, with possible retroaction of graphene on the Co film.
On reverberation and cross-correlation estimates of the size of the broad-line region in active galactic nuclei

It is known that the dependence of the emission-line luminosity of a typical cloud in the active galactic nuclei (AGN) broad-line regions (BLRs) upon the incident flux of ionizing continuum can be non-linear. We study how this non-linearity can be taken into account in estimating the size of the BLR by means of the ‘reverberation’ methods. We show that the BLR size estimates obtained by cross-correlation of emission-line and continuum light curves can be much (up to an order of magnitude) less than the values obtained by reverberation modelling. This is demonstrated by means of numerical cross-correlation and reverberation experiments with model continuum flares and emission-line transfer functions and by means of practical reverberation modelling of the observed optical spectral variability of NGC 4151. The time behaviour of NGC 4151 in the Hα and Hβ lines is modelled on the basis of the observational data by Kaspi et al. and the theoretical BLR model by Shevchenko. The values of the BLR parameters are estimated that allow to judge on the size and physical characteristics of the BLR. The small size of the BLR, as determined by the cross-correlation method from the data of Kaspi et al., is shown to be an artefact of this method. So, the hypothesis that the BLR size varies in time is not necessitated by the observational data.
Hypoxia-Induced Developmental Delays of Inhibitory Interneurons Are Reversed by Environmental Enrichment in the Postnatal Mouse Forebrain

Infants born premature experience hypoxic episodes due to immaturity of their respiratory and central nervous systems. This profoundly affects brain development and results in cognitive impairments. We used a mouse model to examine the impact of hypoxic rearing (9.5–10.5% O2) from postnatal day 3 to 11 (P3–P11) on GABAergic interneurons and the potential for environmental enrichment to ameliorate these developmental abnormalities. At P15 the numbers of cortical interneurons expressing immunohistochemically detectable levels of parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide were decreased in hypoxic-reared mice by 59%, 32%, and 38%, respectively, compared with normoxic controls. Hypoxia also decreased total GABA content in frontal neocortex by 31%. However, GAD67-EGFP knock-in mice reared under hypoxic conditions showed no changes in total number of GAD67-EGFP+ cells and no evidence of increased interneuron death, suggesting that the total number of interneurons was not decreased, but rather, that hypoxic-rearing decreased interneuron marker expression in these cells. In adulthood, PV and SST expression levels were decreased in hypoxic-reared mice. In contrast, intensity of reelin (RLN) expression was significantly increased in adult hypoxic-reared mice compared with normoxic controls. Housing mice in an enriched environment from P21 until adulthood normalized phenotypic interneuron marker expression without affecting total interneuron numbers or leading to increased neurogenesis. Our data show that (1) hypoxia decreases PV and SST and increases RLN expression in cortical interneurons during postnatal cortical development and (2) enriched environment has the capacity to normalize the interneuron abnormalities in cortex.
Effectiveness of a low-frequency sports-specific resistance and plyometric training programme: the case of an elite junior badminton player

This intervention aimed to improve Badminton-specific functional performance of an elite under-19 player (18 years) via a single-weekly resistance and plyometric training (RPT) session for 8-weeks. The athlete’s ‘response-to’ and ‘withdrawal-from’ the RPT were assessed. The athlete (stature: 1.77 m, mass: 81.5 kg) completed the RPT intervention throughout a competitive season. Performance testing was conducted at; baseline, post-intervention (8-weeks) and after withdrawal-from the RPT (16-weeks). Jump height and throwing distance were assessed via countermovement jump (CMJ), standing long-jump (SLJ) and one-arm (1-MBT) and two-arm (2-MBT) medicine-ball throws respectively. Speed and agility were assessed by 5 m and 10 m sprints and ‘sideways’ and ‘four-corner’ tests respectively. A positive change from baseline to post-intervention (8-weeks) was observed in: CMJ (+0.07 m), SLJ (+0.13 m), 1-MBT (+2.25 m) and 2-MBT (+0.26 m). Observed changes in speed and agility were minimal. At the 16-weeks, small declines in CMJ, SLJ, 1-MBT and 2-MBT (0.04 m, 0.04 m, 0.52 m and 0.05 respectively) existed. Small improvements in 5 and 10 m sprint times (-0.12 s to -0.09 s) and side-ways agility were observed (-0.11 s to -0.39 s), possibly explained by conditioning effects of training and competition. An 8-week Badminton-specific RPT programme provided favourable increases in jumps and MB throws. However, such positive changes were not sustained following the withdrawal period.
Asymptotics of resonances induced by point interactions

We consider the resonances of the self-adjoint three-dimensional Schr\"odinger operator with point interactions of constant strength supported on the set $X = \{ x_n \}_{n=1}^N$. The size of $X$ is defined by $V_X = \max_{\pi\in\Pi_N} \sum_{n=1}^N |x_n - x_{\pi(n)}|$, where $\Pi_N$ is the family of all the permutations of the set $\{1,2,\dots,N\}$. We prove that the number of resonances counted with multiplicities and lying inside the disc of radius $R$ behaves asymptotically linear $\frac{W_X}{\pi} R + \mathcal{O}(1)$ as $R \to \infty$, where the constant $W_X \in [0,V_X]$ can be seen as the effective size of $X$. Moreover, we show that there exist configurations of any number of points such that $W_X = V_X$. Finally, we construct an example for $N = 4$ with $W_X < V_X$, which can be viewed as an analogue of a quantum graph with non-Weyl asymptotics of resonances.
Connectionist multivariate density-estimation and its application to speech synthesis

Autoregressive models factorize a multivariate joint probability distribution into a product of one-dimensional conditional distributions. The variables are assigned an ordering, and the conditional distribution of each variable modelled using all variables preceding it in that ordering as predictors. Calculating normalized probabilities and sampling has polynomial computational complexity under autoregressive models. Moreover, binary autoregressive models based on neural networks obtain statistical performances similar to that of some intractable models, like restricted Boltzmann machines, on several datasets. The use of autoregressive probability density estimators based on neural networks to model real-valued data, while proposed before, has never been properly investigated and reported. In this thesis we extend the formulation of neural autoregressive distribution estimators (NADE) to real-valued data; a model we call the real-valued neural autoregressive density estimator (RNADE). Its statistical performance on several datasets, including visual and auditory data, is reported and compared to that of other models. RNADE obtained higher test likelihoods than other tractable models, while retaining all the attractive computational properties of autoregressive models. However, autoregressive models are limited by the ordering of the variables inherent to their formulation. Marginalization and imputation tasks can only be solved analytically if the missing variables are at the end of the ordering. We present a new training technique that obtains a set of parameters that can be used for any ordering of the variables. By choosing a model with a convenient ordering of the dimensions at test time, it is possible to solve any marginalization and imputation tasks analytically. The same training procedure also makes it practical to train NADEs and RNADEs with several hidden layers. The resulting deep and tractable models display higher test likelihoods than the equivalent one-hidden-layer models for all the datasets tested. Ensembles of NADEs or RNADEs can be created inexpensively by combining models that share their parameters but differ in the ordering of the variables. These ensembles of autoregressive models obtain state-of-the-art statistical performances for several datasets. Finally, we demonstrate the application of RNADE to speech synthesis, and
How enhanced molecular ions in Cold EI improve compound identification by the NIST library.

RATIONALE Library-based compound identification with electron ionization (EI) mass spectrometry (MS) is a well-established identification method which provides the names and structures of sample compounds up to the isomer level. The library (such as NIST) search algorithm compares different EI mass spectra in the library's database with the measured EI mass spectrum, assigning each of them a similarity score called 'Match' and an overall identification probability. Cold EI, electron ionization of vibrationally cold molecules in supersonic molecular beams, provides mass spectra with all the standard EI fragment ions combined with enhanced Molecular Ions and high-mass fragments. As a result, Cold EI mass spectra differ from those provided by standard EI and tend to yield lower matching scores. However, in most cases, library identification actually improves with Cold EI, as library identification probabilities for the correct library mass spectra increase, despite the lower matching factors. METHODS This research examined the way that enhanced molecular ion abundances affect library identification probability and the way that Cold EI mass spectra, which include enhanced molecular ions and high-mass fragment ions, typically improve library identification results. It involved several computer simulations, which incrementally modified the relative abundances of the various ions and analyzed the resulting mass spectra. RESULTS The simulation results support previous measurements, showing that while enhanced molecular ion and high-mass fragment ions lower the matching factor of the correct library compound, the matching factors of the incorrect library candidates are lowered even more, resulting in a rise in the identification probability for the correct compound. CONCLUSIONS This behavior which was previously observed by analyzing Cold EI mass spectra can be explained by the fact that high-mass ions, and especially the molecular ion, characterize a compound more than low-mass ions and therefore carries more weight in library search identification algorithms. These ions are uniquely abundant in Cold EI, which therefore enables enhanced compound characterization along with improved NIST library based identification.
The Use of Agonistic Anti-CD40 Therapy in Treatments for Cancer

Agonistic anti-CD40 antibody is a potent stimulator of anti-tumor immune responses due to its action on both immune and tumor cells. It has the ability to “precondition” dendritic cells, allowing them to prime effective cytotoxic T-cell responses. Thus, anti-CD40 antibody provides an ideal therapy for combination with traditional cancer treatments (i.e., chemotherapy, surgery) in order to elicit immune-mediated anti-tumor effects. This review summarizes the mechanisms of action of agonistic anti-CD40, the use of mouse models to investigate its effects and combinations with other therapies in vivo, and current clinical trials combining humanized anti-CD40 antibody with chemotherapy and/or other immunotherapies.
Use of PCR-Based Mycobacterium tuberculosis Genotyping To Prioritize Tuberculosis Outbreak Control Activities

ABSTRACT Genotypic analysis of Mycobacterium tuberculosis isolates is increasingly applied in direct support of tuberculosis outbreak control activities. This is facilitated by PCR-based strain typing methods that enable the genotypic characterization of samples containing small numbers of M. tuberculosis cells. By using DNA extracted directly from primary diagnostic cultures, PCR-based methods were applied to a tuberculosis outbreak investigation and to surveillance in King County, Washington. In the outbreak investigation, five epidemiologically linked M. tuberculosis isolates had a unique pattern at mycobacterial interspersed repeating unit (MIRU) loci 10 and 23 when the pattern was compared to the patterns in a local MIRU locus database. In order to quickly identify new cases involving this strain (termed SBRI10), targeted genotyping at these two loci was performed with cultures from epidemiologically associated tuberculosis cases. Isolates with the characteristic genotypes at loci 10 and 23 were further analyzed by use of a 12-locus MIRU panel and by repetitive-unit-sequence-based PCR (rep-PCR). Between May 2004 and January 2005, 82 cases were screened, of which 14 were identified for further analysis and 13 were confirmed to be infected with SBRI10. Between September 2005 and August 2006, surveillance universal genotyping was performed by using the 12-locus MIRU panel with DNA from primary diagnostic enrichment cultures. A total of 161 samples were submitted for analysis, and 156 were successfully typed. Fifty-one cases formed 18 presumptive clusters by MIRU locus typing. Of these, 30 cases were confirmed to be members of 11 clusters by rep-PCR. Presumptive genotypic data were available rapidly, sometimes within 2 weeks of diagnosis. In this fashion, PCR-based genotyping provided data that can be used to prioritize disease control activities.
Quality Control and Complication Screening Programme of Chinese Medicinal Drugs at the First German Hospital of Traditional Chinese Medicine - A Retrospective Analysis

Background: The use of drugs derived from plants is a cornerstone of Traditional Chinese Medicine (TCM). Yet, too little is known about risk and safety of Chinese medicinal drugs (CMD). Therefore, the TCM hospital Bad Kötzting has developed a quality control and complication screening programme in order to ensure a safe administration of TCM drugs to their patients. Methods: All Chinese medicinal drugs delivered to the hospital between September 1, 2012 and December 31, 2013 entered the quality control program and were screened for microbial contamination, aflatoxin, pesticides and heavy metals. A routinely applied complication screening programme monitored liver enzymes in all patients. Case causality assessment by CIOMS scale and identification of admitted herbs were conducted. Additionally, side effects of patients were identified by a routinely performed web-based documentation system. Results: In 5 of 23 investigated samples (21.7%) the initial testing showed microbial contamination (2), pesticide (2) and heavy metals (1). The drugs were tested for authenticity and adulterations, respectively. All 994 patients (mean age 52.6 years; 72.6% female) admitted were available for analysis. 448 (45.1%) of all patients reported having perceived at least one side effect of treatment. They experienced mainly gastrointestinal symptoms (13.6%), neurovegetative symptoms (10.8 %), temporary deteriorations of pain (8.8%), diarrhoea (5.9%), nausea (1.6%) and vomiting (0.5%). Further, 6 patients with a more than 2-fold elevation (compared to maximum normal value or elevated admission values) of ALT were found in the systematic laboratory control with a non-conclusive causality assessment for TCM-drugs. Conclusion: Approximate incidence rates and analysed drugs associated with liver damage revealed a low rate of liver injury. Patients should be informed of the gastrointestinal symptoms caused by and potential hepatotoxicity of TCM herbs.
PaperID: A Technique for Drawing Functional Battery-Free Wireless Interfaces on Paper

We describe techniques that allow inexpensive, ultra-thin, battery-free Radio Frequency Identification (RFID) tags to be turned into simple paper input devices. We use sensing and signal processing techniques that determine how a tag is being manipulated by the user via an RFID reader and show how tags may be enhanced with a simple set of conductive traces that can be printed on paper, stencil-traced, or even hand-drawn. These traces modify the behavior of contiguous tags to serve as input devices. Our techniques provide the capability to use off-the-shelf RFID tags to sense touch, cover, overlap of tags by conductive or dielectric (insulating) materials, and tag movement trajectories. Paper prototypes can be made functional in seconds. Due to the rapid deployability and low cost of the tags used, we can create a new class of interactive paper devices that are drawn on demand for simple tasks. These capabilities allow new interactive possibilities for pop-up books and other papercraft objects.
Molecular characterization of Xenopus lamin LIV reveals differences in the lamin composition of sperms in amphibians and mammals

Lamins are nuclear intermediate filament proteins. They are involved in most nuclear activities and are essential for retaining the mechano-elastic properties of the nucleus. Somatic cells of vertebrates express lamins A, B1, and B2 while lamin LIII, a major component of the amphibian oocyte lamina is absent in mammals. The organization of the lamina of germ cells differs significantly from that of somatic cells. Mammalian spermatogenic cells express two short lamins, C2 and B3, that are splice isoforms of lamin A and B2, respectively. Here we identify the previously described Xenopus lamin LIV as splice variant of the lamin LIII gene. LIV contains 40 extra residues in coil 2A of the rod domain, which results in altered assembly properties. Xenopus lamin LIV and mammalian B3 assemble into short structures rather than into long IF-like filaments. Expression of lamin LIV is restricted to male germ cells suggesting that it might be the functional equivalent of mammalian lamin B3. We provide evidence that lamins C2 and B3 are restricted to the mammalian lineage and describe the lamin composition of Xenopus sperm. Our results show that the evolution of germ cell-specific lamins followed separate and distinctly different paths in amphibians and mammals.
Assessment of teamwork during structured interdisciplinary rounds on medical units.

BACKGROUND Interdisciplinary rounds (IDR) provide a means to assemble hospital team members and improve collaboration. Little is known about teamwork during IDR. OBJECTIVE To evaluate and characterize teamwork during IDR. DESIGN Cross-sectional observational study. SETTING Six medical units which had implemented structured interdisciplinary rounds (SIDR). MEASUREMENTS We adapted the Observational Teamwork Assessment for Surgery (OTAS) tool, a behaviorally anchored rating scale shown to be reliable and valid in surgical settings. OTAS provides scores ranging from 0 to 6 (0 = problematic behavior; 6 = exemplary behavior) across 5 domains (communication, coordination, cooperation/backup behavior, leadership, and monitoring/situational awareness) and for prespecified subteams. Two researchers conducted direct observations using the adapted OTAS tool. RESULTS We conducted 7-8 independent observations for each unit (total = 44) and 20 joint observations. Inter-rater reliability was excellent at the unit level (Spearman's rho = 0.75), and good across domains (rho = 0.53-0.68) and subteams (rho = 0.53-0.76) with the exception of the physician subteam, for which it was poor (rho = 0.35). Though teamwork scores were generally high, we found differences across units, with a median (interquartile range [IQR]) 4.5 (3.9-4.9) for the lowest and 5.4 (5.3-5.5) for the highest performing unit (P < 0.01). Domain scores differed, with leadership receiving the lowest (median [IQR] = 5.0 [4.6-5.3]), and cooperation/backup behavior and monitoring/situational awareness receiving highest scores (median [IQR] = 5.4 [5.0-5.5] and 5.4 [5.0-5.7]). Differences across subteams were of borderline significance (P = 0.05). CONCLUSIONS The adapted OTAS instrument demonstrated acceptable reliability for assessing teamwork during SIDR across units, domains, and most subteams. Variation in performance suggests a need to improve consistency of teamwork and emphasizes the importance of leadership.