Miracle-dz/UniFAR-FTUs huggingface dataset:
C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK)—endogenous negative regulators of Src-family protein kinases

C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are endogenous inhibitors of the Src-family protein tyrosine kinases (SFKs). Since constitutive activation of SFKs contributes to cancer formation and progression, to prevent excessive activation of SFKs, their activity in normal cells is kept at the basal level by CSK and CHK. CSK and CHK inactivate SFKs by specifically phosphorylating a consensus tyrosine (called YT) near their C-termini. Upon phosphorylation, the phospho-YT engages in intramolecular interactions that lock the SFK molecule in an inactive conformation. SFKs are anchored to the plasma membrane, while CSK and CHK are localized predominantly in the cytosol. To inhibit SFKs, CSK and CHK need to translocate to the plasma membrane. Recruitment of CSK and CHK to the plasma membrane is mediated by the binding of their SH2, SH3 and/or kinase domains to specific transmembrane proteins, G-proteins and adaptor proteins located near the plasma membrane. For CSK, membrane recruitment often accompanies activation. CSK and CHK employ two types of direct interactions with SFKs to achieve efficient YT phosphorylation: (i) short-range interactions involving binding of the active sites of CSK and CHK to specific residues near YT, (ii) long-range non-catalytic interactions involving binding of SFKs to motifs located distally from the active sites of CSK and CHK. The interactions between CSK and SFKs are transient in nature. Unlike CSK, CHK binds tightly to SFKs to form stable protein complexes. The binding is non-catalytic as it is independent of YT. More importantly, the tight binding alone is sufficient to completely inhibit SFKs. This non-catalytic inhibitory binding represents a novel mechanism employed by CHK to inhibit SFKs. Given that SFKs are implicated in cancer development, compounds mimicking the non-catalytic inhibitory mechanism of CHK are potential anti-cancer therapeutics.
A 60 Year-Old Man with AIDS and Pneumonia

1 Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Disease, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 2 Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Disease, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 3 Virology Research Center, National Research Institute of Tuberculosis and Lung Disease, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Damping-factor-control frequency compensation technique for low-voltage low-power large capacitive load applications

Frequency compensation techniques for multiple-stage amplifiers are becoming increasingly important as cascode configuration is not applicable to low-voltage design. Nested Miller compensation (NMC) is commonly used to stabilize multiple-stage amplifiers. However, the bandwidth of an NMC amplifier is poor. Several topologies such as multi-path nested Miller compensation (MNMC) and nested Gm-C compensation (NGCC) have been proposed to enhance the bandwidth. When compared to an NMC amplifier, MNMC can increase the bandwidth by approximately a factor of two while NGCC can further improve the stability of the amplifier. Nevertheless, the bandwidth enhancement by the two topologies is not sufficient for high-speed applications especially to drive large capacitive loads, such as the error amplifier in a low-voltage low-dropout regulator in portable electronic devices. A topology called damping-factor-control frequency compensation (DFCFC) for three-stage amplifiers significantly increases the bandwidth and improves the transient response of the amplifiers.
Formation of the complex of bovine papillomavirus E1 and E2 proteins is modulated by E2 phosphorylation and depends upon sequences within the carboxyl terminus of E1.

The 68-kDa bovine papillomavirus (BPV) type 1 replication protein E1 and the 48-kDa transactivator protein E2 form a complex that specifically binds DNA [Mohr, I.J., Clark, R. , Sun, S. , Androphy, E.J., MacPherson, P. & Botchan, M.R. (1990) Science 250, 1694-1699]. We have confirmed this observation and shown that the E1-E2 complex binds to DNA fragments that contain the BPV plasmid maintenance sequence 1 and a site for the initiation of bidirectional BPV DNA synthesis. The E1 protein was found to bind preferentially to non- or underphosphorylated species of E2, suggesting that the phosphorylation state of E2 modulates the association of the two proteins. Replication-deficient E1 mutants with single amino acid substitutions and deletions in the carboxyl terminus failed to interact with E2, indicating that a region in the E1 carboxyl terminus is required for E1 to interact with E2. Our results suggest that the replication deficiency of some E1 mutants reflects their inability to associate with E2.
Generation of free radicals from freshly fractured silica dust. Potential role in acute silica-induced lung injury.

Data presented here indicate that freshly fractured silica exhibits surface characteristics and biologic reactivity distinct from aged silica, and on this basis we propose that these surface features may lead to enhanced manifestations of lung injury. Grinding of silica produces approximately 10(18) Si and Si-O (silicon-based) radicals per gram of dust on the particulate surface which are characterized by an electron spin resonance (ESR) spectrum centered around g = 2.0015. These silicon-based radicals react with aqueous media to produce OH radicals, which are demonstrable using a DMPO spin trap. The concentration of silicon-based radicals in silica decreases with aging in air and exhibits a half-life of approximately 30 h, whereas its ability to generate OH radicals in aqueous solution decreases with a half-life of approximately 20 h. However, on storage in aqueous media, the concentration of silicon-based radicals and the dust's ability to generate OH radicals decrease significantly within a few minutes. Freshly ground silica is also more biologically reactive than aged silica, because freshly crushed silica activates a greater respiratory burst in alveolar macrophages than aged silica, i.e., storage of ground dust in air decreases silica-induced superoxide anion secretion, hydrogen peroxide release, and NBT reduction by 25%, 68%, and 43%, respectively. Furthermore, compared to aged silica, freshly ground silica exhibits a greater cytotoxic effect on cellular membrane integrity, i.e., a 1.5-fold increase in LDH release from macrophages, a 36-fold increase in hemolytic activity, and a three-fold increase in the ability to induce lipid peroxidation. (ABSTRACT TRUNCATED AT 250 WORDS)
Importin‐7 mediates glucocorticoid receptor nuclear import and is impaired by oxidative stress, leading to glucocorticoid insensitivity

Some patients with severe inflammatory disease fail to respond to glucocorticoids, and oxidative stress contributes to this insensitivity. Importin receptors are associated with nuclear translocation of the glucocorticoid receptor (GR), which is essential for glucocorticoid function. We hypothesized that importin‐7 is central to GR nuclear translocation and glucocorticoid sensitivity. We investigated the effects of importin‐7 siRNA on fluticasone propionate (FP)‐induced GR nuclear localization and suppression of IL‐1β‐induced CXCL8 and the effects of hydrogen peroxide (H2O2) plus IL‐1β costimulation on importin‐7 expression, function, and glucocorticoid responsiveness in a human macrophagecell line (U937). H2O2 significantly reduced FP‐induced GR nuclear localization (3.4±0.51‐ vs. 5.7±0.85‐fold increase, P<0.05) and suppression of IL‐1β‐induced CXCL8 (62.3±2.3 vs. 85.1±7.0%, P<0.05). Knockdown of importin‐7 by 38.4 ± 11.5% (compared with control siRNA) significantly reduced FP‐mediated GR nuclear localization (3.5±0.5‐ vs. 5.7±0.85‐fold increase, P<0.05) and suppression of IL‐1β‐induced CXCL8 expression (40.2±16.1 vs. 68.4±3.0%, P<0.05). H2O2 plus IL‐1β had no direct effect on importin‐7 but caused a significant loss (61.2±12.6% compared with baseline) of nuclear RanGTP, an essential cofactor for importin‐7‐mediated nuclear import of cargo proteins. The importin‐7 complex is essential for glucocorticoid function, and the expression of its cofactor RanGTP is reduced during oxidative stress‐induced glucocorticoid insensitivity. —Hakim, A. , Barnes, P. J., Adcock, I. M. , Usmani, O. S. Importin‐7 mediates glucocorticoid receptor nuclear import and is impaired by oxidative stress, leading to glucocorticoid insensitivity. FASEB J. 27, 4510–4519 (2013). www.fasebj. org
REVIEW - A reference data set for retinal vessel profiles

This paper describes REVIEW, a new retinal vessel reference dataset. This dataset includes 16 images with 193 vessel segments, demonstrating a variety of pathologies and vessel types. The vessel edges are marked by three observers using a special drawing tool. The paper also describes the algorithm used to process these segments to produce vessel profiles, against which vessel width measurement algorithms can be assessed. Recommendations are given for use of the dataset in performance assessment. REVIEW can be downloaded from http://ReviewDB.lincoln. ac.uk.
The treatment of kala-azar during pregnancy.

BACKGROUND Kala-azar in pregnant women is difficult to treat because for them the two commonly used drugs, sodium stibogluconate and pentamidine, are not considered safe. We assessed the effect of amphotericin B on pregnancy, on the foetus and kala-azar. METHODS Five pregnant women were administered amphotericin B at a dose of 1 mg/kg body weight daily starting with 0.5 mg/kg body weight till a total dose of 20 mg/kg body weight was given. The progress of pregnancy was monitored ultrasonographically and the mothers and children were followed for six months. RESULTS All the 5 women were cured of the disease and there was no harmful effect on the children. CONCLUSION Amphotericin B cures kala-azar during pregnancy with no harmful effects on the foetus.
A broadband dual-polarization patch array

A 2 × 1 patch array with broadband and dual-polarization features is proposed. The element antenna is a stacked slot-coupled patch. Its axially symmetric configuration is aimed to provide similar radiation performances in both polarizations. The projected application is to serve as the base station antenna of an outdoor small cell. To meet the operation needs, the two radiating elements are placed in a linear configuration to elevate the gain performance. The −10 dB bandwidth of the antenna array extends from 1.7 to 2.65 GHz, which covers several LTE bands. The measured isolation between two orthogonal ports is 25 dB. Performance features such as good impedance matching, high gain, and good cross-polarization discrimination are verified via simulated and measured results.
Hippocampal circuitry complicates analysis of long‐term potentiation in mossy fiber synapses

Much of the current interest in the hippocampus concerns a rapid and persistent form of synaptic plasticity, called long‐term potentiation (LTP), that is a candidate substrate for some of the mnemonic functions of this structure. There are at least two kinds of LTP in the hippocampus. One form is found at the synapse between the mossy fibers of the granule cells and the pyramidal neurons of the CA3 region. Attempts to examine the mechanism underlying this form of LTP have yielded contradictory conclusions. The authors show how the complex circuitry of the dentate gyrus and adjacent hippocampus may have caused the contradictions. To overcome problems introduced by the circuitry, a specific set of procedures and criteria for evoking and identifying mossy fiber responses is proposed. Use of these or similar procedures and criteria will improve the design and interpretation of experiments on mossy fiber LTP and allow more informative comparisons among species and brain regions and across laboratories.
Protection of microbial dihydrofolate reductase against inactivation by pronase.

The dihydrofolate reductase of Escherichia coli is rapidly and irreversibly inactivated in the presence of the proteolytic enzyme Pronase. However, the reductase is almost completely protected when dihydrofolate, NADP, NADPH, or N 5 -formyltetrahydrofolate are present at saturating concentrations. NAD, NADH, 2-amino-4-hydroxy-6hydroxymethyl dihydropteridine, p -aminobenzoylglutamate, amid glutamate were all ineffective in this regard. On the other hand, NAD did not accelerate the inactivation of E. coli dihydrofolate reductase by Pronase. Certain small-molecule, heterocyclic inhibitors of dihydrofolate reductase were also excellent protective agents when added at 30 times the concentration needed for 50% inhibition of the reductase. Surprisingly, at this same concentration certain other inhibitors with equal or better capacity for binding to the reductase failed to show any protective activity. The structural requirements for protection were explored, and some possible implications of the findings are discussed.
Investigating the feasibility of classifying breast microcalcifications using photon‐counting spectral mammography: A simulation study

Purpose A dual‐energy material decomposition method using photon‐counting spectral mammography was investigated as a non‐invasive diagnostic approach to differentiate between Type I calcifications, consisting of calcium oxalate dihydrate or weddellite compounds that are more often associated with benign lesions, and Type II calcifications containing hydroxyapatite that are predominantly associated with malignant tumors. Methods The study was carried out by numerical simulation to assess the feasibility of the proposed approach. A pencil‐beam geometry was modeled, and the total number of x‐rays transported through a breast embedded with microcalcifications of different types and sizes were simulated by a one‐pixel detector. Material decomposition using two energy bins was then applied to characterize the simulated calcifications into hydroxyapatite and weddellite using maximum‐likelihood estimation, taking into account the polychromatic source, and the energy dependent attenuation. Simulation tests were carried out for different dose levels, energy windows and calcification sizes for multiple noise realizations. Results The results were analyzed using receiver operating characteristic (ROC) analysis. Classification between Type I and Type II calcifications achieved by analyzing a single microcalcification showed moderate accuracy. However, simultaneously analyzing several calcifications within the cluster provided area under the ROC curve of greater than 99% for radiation dose greater than 4.8 mGy mean glandular dose. Conclusion Simulation results indicated that photon‐counting spectral mammography with dual energy material decomposition has the potential to be used as a non‐invasive method for discrimination between Type I and Type II microcalcifications that can potentially improve early breast cancer diagnosis and reduce the number of negative breast biopsies. Additional studies using breast specimens and clinical data should be performed to further explore the feasibility of this approach.
Energy Efficiency Tradeoff in Interference Channels

Interference is one of the major obstacles to improving the performance in wireless communication systems. As the ever-growing data traffic is carried over extremely dense networks, how to deal with interference becomes even more relevant. In this paper, we investigate a network with N pairs of users transmitting on the same channel simultaneously from the energy efficiency (EE) perspective. For such an interference network, we aim to address two issues: what is the EE tradeoff between users and how to design energy-efficient resource allocation scheme? To answer these two questions, we formulate a non-concave multi-objective optimization problem (MOOP) to investigate the EE tradeoff, taking into account the minimum data rate requirement of each user. The weighted Tchebycheff method is utilized to solve the MOOP by converting it into a single-objective optimization problem, which is then solved by the Dinkelbach method and the concave-convex procedure method. Based on the above, a power control algorithm is developed for the interference network to achieve at least a local optimum. The proposed algorithm is compared with the orthogonal bandwidth sharing, where each user orthogonally shares the whole bandwidth without interfering each other. In this scenario, the weighted Tchebycheff and the Dinkelbach methods are also utilized to develop the optimal bandwidth allocation and power control algorithm. The performance of the proposed algorithms is verified by numerical results, which show that it is better to share the bandwidth orthogonally rather than non-orthogonally if the interference between each user pair is stronger than a given threshold.
Do all roads lead to Rome? Routes to metastasis development

Metastasis, the life‐threatening aspect of cancer, is a systemic disease process. Considerable progress has been made in recent years regarding how tumor cells circulating in the blood and lymphatic systems interact with and extravasate into secondary sites, and what determines whether these disseminated tumors cells survive, remain dormant or go on to form macrometastases. New insights into the routes that tumor cells take once leaving the primary tumor have emerged. Novel concepts regarding early seeding of metastases coupled to parallel progression, self‐seeding of primary tumors by circulating tumor cells and the induction of premetastatic niches in distant organs by primary tumors have come to the fore. The perceived role of the lymphatic system in determining patterns of metastasis formation in distant organs has been reassessed. Together these new insights have the potential to offer new therapeutic options. In particular, the regulation of tumor cell dormancy emerges as a key event in metastasis formation, and therapeutic control of dormancy holds the promise of rendering cancer a chronic rather than life‐threatening disease.
Thermodynamics of electrical noise : a frequency-domain inequality for linear networks

This paper addresses the frequency-domain characterization of electrical noise in linear time-invariant distributed networks. A new general inequality is derived. The flow of noise power from one source to another through a lossless coupling network is shown to obey a relation analogous to the second law of thermodynamics. The noise sources can be essentially any stationary random processes; in particular they need not be Gaussian and need not represent thermal noise. In this sense the inequality is quite general. Proofs are based on standard techniques from the theory of linear circuits and random signals; thermodynamic concepts are used only for motivation and interpretation.
Forgetting our facts: the role of inhibitory processes in the loss of propositional knowledge.

Seven experiments are reported that show that retrieving facts from long-term memory is accomplished, in part, by inhibitory processes that suppress interfering facts. When asked to repeatedly retrieve a recently learned proposition (e.g., recalling The actor is looking at the tulip, given cues such as Actor looking t__), subjects experienced a recall deficit for related facts (e.g., The actor is looking at the violin) on a recall test administered 15 min later. Importantly, this retrieval-induced forgetting was shown to generalize to other facts in which the inhibited concepts took part (e.g., The teacher is lifting the violin), replicating a finding observed by M. C. Anderson and B. A. Spellman (1995) with categorical stimuli. These findings suggest a critical role for suppression in models of propositional retrieval and implicate the mere retrieval of what we know as a source of forgetting of factual knowledge.
A bi-directional electrochemically driven micro liquid dosing system with integrated sensor/actuator electrodes

In this contribution a micro liquid dosing system is presented, which allows bi-directional manipulation of fluids (i.e. pushing out and pulling in of liquids) by the electrochemical generation and removal of gas bubbles. Bi-directionality is obtained by reversal of the actuation current thereby causing the earlier produced gasses to react back to water. This reduction of gas volume actively pulls liquid back into the system. The electrochemical actuator electrodes have been specially designed to perform the simultaneous measurement of conductivity, via which the total amount of gas can be estimated. As this amount equals the total dosed volume of liquid, dispensed volumes can be determined on-line during experiments.
Characterization of Ischemic Changes in Small Bowel After Normothermic Regional Perfusion: Potential to Consider Small Bowel Grafts from DCD Donors?

D after circulatory death (DCD) has been proven to be a useful source of organs when transplant waiting list requirements cannot be met by donations after brain death (DBD). DCD intestinal grafts are currently not regarded suitable for small bowel transplantation, due to dismal results in an animal model of DCD intestinal transplantation. DCD donors constitute up to 40% of the donor pool in countries that have adopted the use of DCD organs next to DBD, and are the sole source of postmortem organs in societies where the concept of brain death has not been accepted in organ donation. Normothermic regional perfusion (NRP) is a new technique that involves a period of in situ extracorporealmembrane oxygenation and aims to reverse deleterious effects of warm ischemia and to increase organ yield inDCDdonors (Figure 1A). Pilot results forNRP in liver, kidney, and pancreas transplantation are encouraging. Strikingly, in our experience of NRP, we noted vital bowel sustaining normal peristalsis throughout these procedures, and we hypothesize that NRP may potentially enable DCD small bowel transplantation. In a DCD donor, procurement of liver and kidneys with abdominal NRP and simultaneous cold perfusion of lungs was performed (approved byNovel Therapeutics Committee of Queen Elizabeth Hospital Birmingham, UK). Consent