Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrative Analysis of Brain Region-specific Shank3 Interactomes for Understanding the Heterogeneity of Neuronal Pathophysiology Related to SHANK3 Mutations

Recent molecular genetic studies have identified 100s of risk genes for various neurodevelopmental and neuropsychiatric disorders. As the number of risk genes increases, it is becoming clear that different mutations of a single gene could cause different types of disorders. One of the best examples of such a gene is SHANK3, which encodes a core scaffold protein of the neuronal excitatory post-synapse. Deletions, duplications, and point mutations of SHANK3 are associated with autism spectrum disorders, intellectual disability, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Nevertheless, how the different mutations of SHANK3 can lead to such phenotypic diversity remains largely unknown. In this study, we investigated whether Shank3 could form protein complexes in a brain region-specific manner, which might contribute to the heterogeneity of neuronal pathophysiology caused by SHANK3 mutations. To test this, we generated a medial prefrontal cortex (mPFC) Shank3 in vivo interactome consisting of 211 proteins, and compared this protein list with a Shank3 interactome previously generated from mixed hippocampal and striatal (HP+STR) tissues. Unexpectedly, we found that only 47 proteins (about 20%) were common between the two interactomes, while 164 and 208 proteins were specifically identified in the mPFC and HP+STR interactomes, respectively. Each of the mPFC- and HP+STR-specific Shank3 interactomes represents a highly interconnected network. Upon comparing the brain region-enriched proteomes, we found that the large difference between the mPFC and HP+STR Shank3 interactomes could not be explained by differential protein expression profiles among the brain regions. Importantly, bioinformatic pathway analysis revealed that the representative biological functions of the mPFC- and HP+STR-specific Shank3 interactomes were different, suggesting that these interactors could mediate the brain region-specific functions of Shank3. Meanwhile, the same analysis on the common Shank3 interactors, including Homer and GKAP/SAPAP proteins, suggested that they could mainly function as scaffolding proteins at the post-synaptic density. Lastly, we found that the mPFC- and HP+STR-specific Shank3 interactomes contained a significant number of proteins associated with neurodevelopmental and neuropsychiatric disorders. These results suggest that Shank3 can form protein complexes in a brain region-specific manner, which might contribute to the pathophysiological and phenotypic diversity of disorders related to SHANK3 mutations.
Forward Anonymity-Preserving Secure Remote Authentication Scheme

Dynamic ID-based authentication solves the ID-theft problem by changing the ID in each session instead of using a fixed ID while performing authenticated key exchanges between communicating parties. User anonymity is expected to be maintained and the exchanged key kept secret even if one of the long-term keys is compromised in the future. However, in the conventional dynamic ID-based authentication scheme, if the server’s long-term key is compromised, user anonymity can be broken or the identities of the users can be traced. In addition, these schemes are vulnerable to replay attacks, in which any adversary who captures the authentication message can retransmit it, and eventually cause the legitimate user to be denied service. This paper proposes a novel dynamic ID-based authentication scheme that preserves forward anonymity as well as forward secrecy and obviates replay attacks.
Optogenetics and Translational Medicine

Optogenetics has proven useful for understanding basic neurobiology and may next serve as a therapeutic modality in the clinic. Optogenetic tools enable light-mediated control of cellular excitability and signaling in vivo. By manipulating biological processes, scientists can determine the roles played by these processes in intact biological systems, such as the brain. Such cellular-level control has greatly affected basic science. Here, we discuss how optogenetic tools might be translated into clinical impact through identification of new molecular and circuit-level targets and provide temporally precise interventions for defined biochemical or cellular events.
Crystal structure of (2,4-di-tert-butyl-6-{[(6,6′-dimethyl-2′-oxido-1,1′-biphenyl-2-yl)imino]methyl}phenolato-κ3 O,N,O′)bis(propan-2-olato-κO)titanium(IV)

In the mononuclear TiIV title complex, [Ti(C29H33NO2)(C3H6O)2], the TiNO4 coordination polyhedron comprises an N-atom and two O-atom donors from the dianionic Schiff base ligand and two O-atom donors from monodentate isopropoxide anions. The stereochemistry is distorted trigonal–bipyramidal with the N-donor in an elongated axial site [Ti—N = 2.2540 (17) Å], the O-donors having normal Ti—O bond lengths [1.7937 (14) Å (axial)–1.8690 (14) Å]. In the crystal, C—H⋯π interactions link molecules into centrosymmetric dimers.
Heparin but not citrate anticoagulation of blood preserves platelet function for prolonged periods

Summary. Background: Current guidelines state that platelet aggregation studies should be conducted within 4 h of venepuncture because of the decline in sensitivity to platelet agonists. This constrains studies of platelet activity in clinical situations where samples need to be transported or there are unavoidable delays prior to assessment. Objectives: The aim of the present study was to compare systematically the responses of platelets stored in the presence of either citrate or heparin, the two most widely used anti‐coagulants, using a range of standard techniques. Methods: Blood was taken from healthy volunteers and either assessed immediately or stored at ambient temperature (18–25 °C) for 24 h. Platelet reactivity to a range of agonists was determined by a combination of 96‐well plate techniques; light transmission aggregometry, thrombi adhesion, ATP and ADP release, and TxA2 release; by whole blood aggregometry; and by PFA‐100. Results and conclusions: Testing using 96‐well plate techniques allowed for the simultaneous measurement of responses to multiple concentrations of multiple agonists. The responses of platelets from blood anti‐coagulated with heparin were predominantly preserved in all assays after 24 h storage, whereas, responses of platelets stored in blood anti‐coagulated with citrate were greatly diminished. Consequently, anti‐coagulation with heparin, but not citrate, preserves platelet responses for up to 24 h as determined by a range of techniques.
New n-well fabrication techniques based on 2D process simulation

For submicron device technology, 2D process modeling is essential. The need for shallow junctions and control of lateral dimensions of well and oxide isolation regions require well-characterized processes. This paper presents results obtained with SUPREM-IV which show fully numerical 2D coupled diffusion for both point defects and dopant atoms. Based on comparison of experimental results and parameter extraction for surface kinetic coefficients of point defects, SUPREM-IV is used to design a new n-well process with 37% reduction of the lateral well dimension. For dopant diffusion, the role of coupled point defects (interstitials and vacancies) and dopants are shown to give a unique result based on extracted surface recombination rates (1) and experimental data.
Short selling activity and waiting games

The paper studies the reaction of informed investors to the presence of short sellers in the market. We find that other informed investors break down their trades across more brokers when short sellers are active. Consequently, they turn to more unfamiliar brokers and end up bearing higher trading costs. This behavior can lead to a slowdown of information impounding. Consistent with this conjecture, we find that prices are less efficient when short selling occurs in stocks that are intermediated by more brokers. These findings suggest that competition among brokers may in fact reduce price efficiency, if informed traders use it to hide their information.
Construction of Vector for Functional Analysis of the Intrinsically Bent DNA in the ACE3 Replicator from Drosophila melanogaster

DNA replication is a crucial process for species survival, nevertheless it is not clear which factors define origin selection in multicellular eukaryotes. Developmental gene amplification systems, such as the one described during ovarian follicles development in Drosophila melanogaster, are useful tools for studying of DNA replication process in these organisms. We previously described that the well characterized third chromosome amplified domain of D. melanogater displays three intrinsically bent DNA sites: b1, localized at an amplification control element (ACE3), b2 and b3, both localized at the preferential origin ori-β. This proposal aimed to construct a Drosophila transformation vector, which contains a short deletion at the ACE3, in order to reduce the intrinsically bent DNA site b1, and analyze the functional role of this site in the gene amplification process. Through a series of cloning steps, we obtained a Big Parent vector derivative, containing a deletion at the positions 176-180 bp, inside the ACE3. The generation of a Drosophila transformation vector displays a reduced intrinsically bent DNA site in the third chromosome amplified domain, it will allow the analysis of the functional role of this curvature in developmental gene amplification, providing new insights on replication initiation in D. melanogaster and the function of intrinsically bent DNA sites.
Wideband VCO With Simultaneous Switching of Frequency Band, Active Core, and Varactor Size

As the tuning range of integrated LC-VCOs increases, it becomes difficult to co-design the active negative resistance core and the varactor size optimally for the complete frequency range. The presented VCO design solves this by adjusting the size of the negative resistance transistors with a switched active core, with the additional benefit that this reduces parasitics and hence allows to achieve better phase noise and an even higher tuning range. Also the VCO gain variations are counteracted by employing an analog varactor that can change in size. The implementation in 0.13-mum CMOS shows a tuning range from 3.1 to 5.2 GHz, with a power consumption varying accordingly from 7.7 to 2.1 mA from a 1.2 V supply. The measured phase noise is -118 dBc/Hz at 1 MHz from a 4-GHz carrier.
Pituitary growth hormone network responses are sexually dimorphic and regulated by gonadal steroids in adulthood

There are well-recognized sex differences in many pituitary endocrine axes, usually thought to be generated by gonadal steroid imprinting of the neuroendocrine hypothalamus. However, the recognition that growth hormone (GH) cells are arranged in functionally organized networks raises the possibility that the responses of the network are different in males and females. We studied this by directly monitoring the calcium responses to an identical GH-releasing hormone (GHRH) stimulus in populations of individual GH cells in slices taken from male and female murine GH-eGFP pituitary glands. We found that the GH cell network responses are sexually dimorphic, with a higher proportion of responding cells in males than in females, correlated with greater GH release from male slices. Repetitive waves of calcium spiking activity were triggered by GHRH in some males, but were never observed in females. This was not due to a permanent difference in the network architecture between male and female mice; rather, the sex difference in the proportions of GH cells responding to GHRH were switched by postpubertal gonadectomy and reversed with hormone replacements, suggesting that the network responses are dynamically regulated in adulthood by gonadal steroids. Thus, the pituitary gland contributes to the sexually dimorphic patterns of GH secretion that play an important role in differences in growth and metabolism between the sexes.
Domain Structure of the NRIF3 Family of Coregulators Suggests Potential Dual Roles in Transcriptional Regulation

ABSTRACT The identification of a novel coregulator for nuclear hormone receptors, designated NRIF3, was recently reported (D. Li et al., Mol. Cell. Biol. 19:7191–7202, 1999). Unlike most known coactivators, NRIF3 exhibits a distinct receptor specificity in interacting with and potentiating the activity of only TRs and RXRs but not other examined nuclear receptors. However, the molecular basis underlying such specificity is unclear. In this report, we extended our study of NRIF3-receptor interactions. Our results suggest a bivalent interaction model, where a single NRIF3 molecule utilizes both the C-terminal LXXIL (receptor-interacting domain 1 [RID1]) and the N-terminal LXXLL (RID2) modules to cooperatively interact with TR or RXR (presumably a receptor dimer), with the spacing between RID1 and RID2 playing an important role in influencing the affinity of the interactions. During the course of these studies, we also uncovered an NRIF3-NRIF3 interaction domain. Deletion and mutagenesis analyses mapped the dimerization domain to a region in the middle of NRIF3 (residues 84 to 112), which is predicted to form a coiled-coil structure and contains a putative leucine zipper-like motif. By using Gal4 fusion constructs, we identified an autonomous transactivation domain (AD1) at the C terminus of NRIF3. Somewhat surprisingly, full-length NRIF3 fused to the DNA-binding domain of Gal4 was found to repress transcription of a Gal4 reporter. Further analyses mapped a novel repression domain (RepD1) to a small region at the N-terminal portion of NRIF3 (residues 20 to 50). The NRIF3 gene encodes at least two additional isoforms due to alternative splicing. These two isoforms contain the same RepD1 region as NRIF3. Consistent with this, Gal4 fusions of these two isoforms were also found to repress transcription. Cotransfection of NRIF3 or its two isoforms did not relieve the transrepression function mediated by their corresponding Gal4 fusion proteins, suggesting that the repression involves a mechanism(s) other than the recruitment of a titratable corepressor. Interestingly, a single amino acid residue change of a potential phosphorylation site in RepD1 (Ser28 to Ala) abolishes its transrepression function, suggesting that the coregulatory property of NRIF3 (or its isoforms) might be subjected to regulation by cellular signaling. Taken together, our results identify NRIF3 as an interesting coregulator that possesses both transactivation and transrepression domains and/or functions. Collectively, the NRIF3 family of coregulators (which includes NRIF3 and its other isoforms) may play dual roles in mediating both positive and negative regulatory effects on gene expression.
Open‐Label, Single‐Dose Pharmacokinetic Study of Modafinil Tablets: Influence of Age and Gender in Normal Subjects

An open‐label, single‐center, single‐dose, parallel‐group study was performed in healthy young males and females as well as healthy elderly males to examine the influence of age and gender on the pharmacokinetics of modafinil following administration of a single 200 mg oral dose. Twelve subjects were enrolled in each of the following three groups: young males, young females, and elderly males. Each fasted (overnight) subject received 2 × 100 mg modafinil tablets. Blood and urine samples were collected at various times up to 72 hours postdose for the determination of plasma and urine levels of modafinil as well as the acid and sulfone metabolites. The plasma concentrations of the individual isomers, d‐ and l‐modafinil, were also determined. Pharmacokinetic parameters were determined by noncompartmental methods. Modafinil was well tolerated at a single oral dose of 200 mg. The most commonly reported adverse events were headache, fever, pharyngitis, and asthenia. There were no clinically meaningful differences with respect to the incidence rate of treatment‐emergent adverse events among the young female, young male, and old male groups. Modafinil was rapidly absorbed after oral dosing and slowly cleared (t1/2 ∼ 11–14 hr) from the body. Modafinil acid was the major urinary metabolite, which accounted for 35% to 60% of the dose. Results from this study indicated that there were age and gender effects on modafinil clearance processes. In this regard, the clearance rate of modafinil in males decreased with age while young females cleared modafinil at a faster rate than young males. Stereospecific pharmacokinetics of modafinil were also demonstrated. The d‐modafinil was eliminated three times faster than the l‐modafinil.
Childhood adversities as predictors of incident coronary heart disease and cerebrovascular disease

Background Studies suggest that childhood adversities are important determinants of various types of later illnesses as well as poor health behaviour. However, few large-scale prospective studies have examined the associations between childhood adversities and cardiovascular disease. Objective To investigate whether childhood adversities are associated with increased risk of incident cardiovascular disease Design and setting Participants were 23 916 men and women in four age groups (20–24, 30–34, 40–44, and 50–54 years) from the Health and Social Support study, a longitudinal study on a random sample representative of the Finnish population. Data from national health registers on coronary heart disease and cerebrovascular disease during a mean follow-up of 6.9 years were linked to survey responses on childhood adversities. Cox proportional hazard models were adjusted for age group and potential mediators (education, health risk behaviours, diabetes and depression). Results There was a significant linear trend between the number of childhood adversities and disease end points in women. The risk of incident cardiovascular disease was threefold among women exposed concurrently to three types of childhood adversities (financial difficulties, interpersonal conflicts and longstanding illness of a family member). Among men, increased risk was observed only among those with longstanding illness of a family member (HR=1.44; 95% CI 1.06 to 1.96). Conclusions In this prospective population-based sample, childhood adversities were associated with a significantly increased risk of objectively verified cardiovascular disease, especially among women but to a lesser extent among men. More studies with prospective settings are needed to confirm the association and possible mechanisms.
A new tumor promoter, dihydroteleocidin b, enhances cell growth and the production of murine leukemia virus by fibroblasts

The effects of tumor promoters on the expression of murine leukemia virus (MuLV) were studied in tissue culture. Dihydroteleocidin B, an indole alkaloid, recently found to be a tumor promoter, enhanced not only the production of Moloney MuLV (M‐MuLV) by a mouse fibroblast cell line, C3H2K, persistently infected with M‐MuLV, but also growth of the C3H2K cells. The production of infectious M‐MuLV by M‐MuLV‐infected C3H2K cells that had been treated with dihydroteleocidin B for 1‐7 days was four or five times higher than that of control cells. C3H2K cells grew faster and became stationary at higher cell densities in the presence of dihydroteleocidin B than in its absence. The tumor‐promoting phorbol esters phorbol‐12, 13‐didecanoate and 12‐O‐tetradecanoylphorbol‐13‐acetate also enhanced the production of M‐MuLY, but their effects were not so strong as that of dihydroteleocidin B. These tumor promoters, however, did not induce production of endogenous MuLV in C3H2K or K‐BALB cells.
An assessment of the ability of a silver-releasing device to prevent bacterial contamination of urethral catheter drainage systems.

OBJECTIVE To investigate the ability of a silver-releasing device to protect the catheterized bladder from infection by blocking the ascending migration of bacteria from contaminated urine-drainage bags. MATERIALS AND METHODS A simple physical model of the catheterized bladder and drainage system was used with the device located in the drainage-tube just below the sampling port. Urine was supplied to the model at 1.0 mL/min and the drainage bag was contaminated with Pseudomonas aeruginosa, Escherichia coli and Proteus mirabilis. Over 10 days, urine from the bag, catheter sampling-port and bladder were examined for contamination. RESULTS Bacteriological analysis showed that the mean time for test organisms to reach the sampling ports of four different control bag systems ranged from 5.7 to 7.7 days. Urine from the sampling ports of the test systems incorporating the silver device remained sterile for 10 days. The device also prevented the growth of the large populations of bacteria (10(8) colony-forming units per mL) that occurred in the control bags. While scanning electron microscopy showed the formation of bacterial biofilm throughout the control drainage systems, no bacterial colonization was visible on the surfaces of the test systems. Chemical analysis established that the devices consistently generated concentrations of silver in urine ranging from 1.0 to 2.0 micrograms/mL. CONCLUSION The incorporation of the silver-releasing device into the drainage systems produced an antibacterial barrier which protected the catheterized bladder from intraluminal contamination for at least 10 days. These in vitro tests suggest a useful role for the device in controlling infection in patients undergoing short-term indwelling bladder catheterization.
Historical evidence based trust management strategy against black hole attacks in MANET

Distributed, self-organized and infrastructure-independent nature of MANET makes it vulnerable to various kinds of attacks. Among them, a threat caused by black hole attack is more prominent. A trust management scheme is a common way to detect and isolate the compromised nodes while a cryptography mechanism shows a failure facing to inner attacks. The previous work proposed two simple models along with trust computation methods to filter out black hole nodes using the benevolent ones and achieved better performance against pure black hole attacks. In this study, a method to prevent gray hole attack, one kind of black hole attack, which is more cunning and clandestine attack is proposed. The neighbour observing model based on watchdog concept is focused on the direct trust value (DTV) to detect single black hole attack. Historical evidence is also taken into consideration against gray hole attacks. Moreover, the neighbour recommendation model that companied with indirect trust value (ITV) is used to detect the cooperative black hole attacks. On the other hand, the proposed method tries to balance the trust values from different neighbour nodes to mitigate the damage by their deceiving. The simulation results demonstrate the advantages of proposed method by punishing malicious actions to prevent the camouflage and deception in the attack.
High resolution dual-channel SAR-system for airborne applications

The airborne monitoring of scenes using unmanned or small piloted aircrafts is becoming increasingly important. Several types of airborne sensors - in the electro-optical, infrared or millimeter wave spectrum - are available for the different platforms. Beside the all-weather suitability of the sensors, the deployment scenarios, often demand for the ability to look through dust clouds, smoke, or fog. The only sensor, which is capable to cope with such environmental restrictions and, at the same time, to deliver high-resolution images, is the synthetic aperture radar (SAR). In this paper, we present the extension of the well-established MIRANDA-35 SAR system with a second receiving channel for polarimetric and interferometric applications. The applied frontend upgrades and the configuration for airborne SAR with the MIRANDA system are described. Furthermore, we present the design of a newly constructed slotted waveguide antenna for cross-polarization. The first polarimetric measurement results conclude the paper and demonstrate the capabilities of the dual-channel Ka-band sensor.