Miracle-dz/UniFAR-FTUs huggingface dataset:
Iminohydantoin lesion induced in DNA by peracids and other epoxidizing oxidants.

The oxidation of guanine to 5-carboxamido-5-formamido-2-iminohydantoin (2-Ih) is shown to be a major transformation in the oxidation of the single-stranded DNA 5-mer d(TTGTT) by m-chloroperbenzoic acid (m-CPBA) and dimethyldioxirane (DMDO) as a model for peracid oxidants and in the oxidation of the 5-base pair duplex d[(TTGTT). (AACAA)] with DMDO. 2-Ih has not been reported as an oxidative lesion at the level of single/double-stranded DNA or at the nucleoside/nucleotide level. The lesion is stable to DNA digestion and chromatographic purification, suggesting that 2-Ih may be a stable biomarker in vivo. The oxidation products have been structurally characterized and the reaction mechanism has been probed by oxidation of the monomeric species dGuo, dGMP, and dGTP. DMDO selectively oxidizes the guanine moiety of dGuo, dGMP, and dGTP to 2-Ih, and both peracetic and m-chloroperbenzoic acids exhibit the same selectivity. The presence of the glycosidic bond results in the stereoselective induction of an asymmetric center at the spiro carbon to give a mixture of diastereomers, with each diastereomer in equilibrium with a minor conformer through rotation about the formamido C-N bond. Labeling studies with [(18)O(2)]-m-CPBA and H(2)(18)O to determine the source of the added oxygen atoms have established initial epoxidation of the guanine 4-5 bond with pyrimidine ring contraction by an acyl 1,2-migration of guanine carbonyl C6 to form a transient dehydrodeoxyspiroiminodihydantoin followed by hydrolytic ring-opening of the imidazolone ring. Consistent with the proposed mechanism, no 8-oxoguanine was detected as a product of the oxidations of the oligonucleotides or monomeric species mediated by DMDO or the peracids. The 2-Ih base thus appears to be a pathway-specific lesion generated by peracids and possibly other epoxidizing agents and holds promise as a potential biomarker.
A fast implementation method for the FFBP algorithm

A fast implementation method for the fast factorized back-projection (FIM-FFBP) algorithm is proposed to focus high-resolution spotlight synthetic aperture radar (SAR) data. Different from the original FFBP utilizing two-dimensional image-domain interpolation for sub-aperture fusion, FIM-FFBP finishes the image fusion using chirp-z transform and circular shifting. FIM-FFBP yields enhanced efficiency over the nearest interpolation with 4 times upsampling based FFBP, and keeps the high precision simultaneously. Real-data experiment verifies the efficiency superiorities of the FIM-FFBP.
Characterization of lactoferrin oil-in-water emulsions and their stability in recombined milk

Emulsions were prepared with 20% soy oil and different concentrations of lactoferrin, and tested at pH values from 3 to 7·5. The stability of the emulsions decreased as the pH got closer to the isoelectric point of the protein. A concentration of 1% lactoferrin was determined to be sufficient to provide full coverage of the emulsion droplets. Lactoferrin-stabilized emulsions were then prepared in water at pH 6·6 and their behaviour when added to reconstituted milk was studied. It was observed that lactoferrin emulsions were stable when reconstituted in milk, but they showed aggregation when diluted in milk serum alone. The destabilization was caused by shielding of the charges on the surface of the oil droplets. Stabilization in milk occurred due to interactions at the interface with other soluble proteins. In fact, when β-lactoglobulin or sodium caseinate were added to the serum, stability of the emulsion droplets was restored, indicating that these proteins were able to adsorb at the interface and aid in the stabilization. Since ζ-potential measurements did not show significant overall charge on the emulsion droplets, this suggests that the stabilization forces are not only electrostatic in nature, but that there are other mechanisms at play.
Patch-based anisotropic diffusion scheme for fluorescence diffuse optical tomography—part 1: technical principles

Fluorescence diffuse optical tomography (fDOT) provides 3D images of fluorescence distributions in biological tissue, which represent molecular and cellular processes. The image reconstruction problem is highly ill-posed and requires regularisation techniques to stabilise and find meaningful solutions. Quadratic regularisation tends to either oversmooth or generate very noisy reconstructions, depending on the regularisation strength. Edge preserving methods, such as anisotropic diffusion regularisation (AD), can preserve important features in the fluorescence image and smooth out noise. However, AD has limited ability to distinguish an edge from noise. In this two-part paper, we propose a patch-based anisotropic diffusion regularisation (PAD), where regularisation strength is determined by a weighted average according to the similarity between patches around voxels within a search window, instead of a simple local neighbourhood strategy. However, this method has higher computational complexity and, hence, we wavelet compress the patches (PAD-WT) to speed it up, while simultaneously taking advantage of the denoising properties of wavelet thresholding. The proposed method combines the nonlocal means (NLM), AD and wavelet shrinkage methods, which are image processing methods. Therefore, in this first paper, we used a denoising test problem to analyse the performance of the new method. Our results show that the proposed PAD-WT method provides better results than the AD or NLM methods alone. The efficacy of the method for fDOT image reconstruction problem is evaluated in part 2.
Preventive and Abortive Strategies for Stimulation Based Control of Epilepsy: A Computational Model Study

Epilepsy is a condition in which periods of ongoing normal EEG activity alternate with periods of oscillatory behavior characteristic of epileptic seizures. The dynamics of the transitions between the two states are still unclear. Computational models provide a powerful tool to explore the underlying mechanisms of such transitions, with the purpose of eventually finding therapeutic interventions for this debilitating condition. In this study, the possibility to postpone seizures elicited by a decrease of inhibition is investigated by using external stimulation in a realistic bistable neuronal model consisting of two interconnected neuronal populations representing pyramidal cells and interneurons. In the simulations, seizures are induced by slowly decreasing the conductivity of GABA[Formula: see text] synaptic channels over time. Since the model is bistable, the system will change state from the initial steady state (SS) to the limit cycle (LS) state because of internal noise, when the inhibition falls below a certain threshold. Several state-independent stimulations paradigms are simulated. Their effectiveness is analyzed for various stimulation frequencies and intensities in combination with periodic and random stimulation sequences. The distributions of the time to first seizure in the presence of stimulation are compared with the situation without stimulation. In addition, stimulation protocols targeted to specific subsystems are applied with the objective of counteracting the baseline shift due to decreased inhibition in the system. Furthermore, an analytical model is used to investigate the effects of random noise. The relation between the strength of random noise stimulation, the control parameter of the system and the transitions between steady state and limit cycle are investigated. The study shows that it is possible to postpone epileptic activity by targeted stimulation in a realistic neuronal model featuring bistability and that it is possible to stop seizures by random noise in an analytical model.
Milk Ejection Bursts of Supraoptic Oxytocin Neurones during Bilateral and Unilateral Suckling in the Rat

Extracellular recordings of the electrical activity of oxytocin neurones were made from the supraoptic nuclei (SON) of lactating rats, and the milk‐ejection bursts and the background activity of oxytocin neurones were investigated during unilateral and bilateral suckling. When application of pups was limited to the nipples on either the same side (ipsilateral suckling) or the side opposite (contralateral suckling) to the oxytocin neurone recorded, the burst amplitude and background firing rate were significantly (P<0.05) lower and the inter‐burst interval was significantly (P<0.05) longer than during bilateral suckling. Furthermore, the burst amplitude was significantly (P<0.05) lower during ipsilateral suckling than during contralateral suckling. The majority of the oxytocin neurones showed a gradual increase in the burst amplitude during bilateral (88.9%) and contralateral (77.3%) suckling, but during ipsilateral suckling only 40% of the neurones did. The inter‐burst interval became shorter with the progress of the milk ejection reflex during any mode of suckling. Three pairs of oxytocin neurones recorded simultaneously from both SON were successfully tested for the effect of bilateral and unilateral suckling on the electrical activity, and the results showed the same direction of change in the burst amplitude, background activity and burst interval as shown in single side recordings. These findings indicate that the burst amplitude mainly depends on the amount of afferent suckling signals arising from the nipples on the side opposite to the recording side, and that there may exist bilateral summation centres coordinating with the synchronization mechanism of milk‐ejection bursts of oxytocin neurones.
NO-induced modulation of calcium-oscillations in pulmonary vascular smooth muscle.

The effect of the nitric oxide (NO) donor sodium nitroprusside (SNP) on both [Ca(2+)](i)and mechanical activity was studied in the rat isolated pulmonary artery (RPA). In freshly isolated myocytes loaded with 1 microM indo-lacetoxymethyl ester for 30 min, short (40-60 s) application of ATP (100 microM) or ET-1 (0.1 microM) induced 3-6 cyclic rises in [Ca(2+)](i)(Ca-oscillations) of decreasing amplitude. Preincubation of cells with SNP (10-250 microM) for 10 min had no effect on the resting [Ca(2+)](i)value, but progressively abolished the oscillations. A similar effect was obtained with 8-bromo-cGMP (100-500 microM). SNP (0.001-100 microM) concentration-dependently relaxed ATP (10 mM, n = 4) and ET-1 (0.1 microM, n = 4)-precontracted RPA. 1H-[1,2,4]oxadiazolol [4,3,-a]quinoxalin-1-one (ODQ, 10 microM), a potent inhibitor of the cytosolic guanylyl cyclase, fully reversed the effect of SNP on ATP-induced [Ca(2+)](i)oscillations as well as on ATP-precontracted RPA. In contrast, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H8, 10 microM), a potent inhibitor of cGMP-dependent protein kinase (PKG), did not alter the effect of SNP. Caffeine (5 mM) induced only one transient [Ca(2+)](i)-increase (n = 24), the amplitude of which was altered neither by SNP nor by 8-bromo-cGMP. Our results show that the relaxing effect of NO in RPA is related, at least in part, to its action on the Ca-signalling pathway. NO interacts with inositol trisphosphate pathway without interacting with the ryanodine-sensitive receptor. Finally, the effect of NO involves an increase in cGMP but appears independent of activation of PKG.
Borderline Personality Disorder, Exposure to Interpersonal Trauma, and Psychiatric Comorbidity in Urban Primary Care Patients

Objective: Few data are available on interpersonal trauma as a risk factor for borderline personality disorder (BPD) and its psychiatric comorbidity in ethnic minority primary care populations. This study aimed to examine the relation between trauma exposure and BPD in low-income, predominantly Hispanic primary care patients. Method: Logistic regression was used to analyze data from structured clinical interviews and self-report measures (n = 474). BPD was assessed with the McLean screening scale. Trauma exposure was assessed with the Life Events Checklist (LEC); posttraumatic stress disorder (PTSD) was assessed with the Lifetime Composite International Diagnostic Interview, other psychiatric disorders with the SCID-I, and functional impairment with items from the Sheehan Disability Scale and Social Adjustment Scale Self-Report (SAS-SR). Results: Of the 57 (14%) patients screening positive for BPD, 83% reported a history of interpersonally traumatic events such as sexual and physical assault or abuse. While interpersonal trauma experienced during adulthood was as strongly associated with BPD as interpersonal trauma experienced during childhood, noninterpersonal trauma was associated with BPD only if it had occurred during childhood. The majority (91%) of patients screening positive for BPD met criteria for at least one current DSM-IV Axis I diagnosis and exhibited significant levels of functional impairment. Conclusion: Increased awareness of BPD in minority patients attending primary care clinics, high rates of exposure to interpersonal trauma, and elevated risk for psychiatric comorbidity in this population may enhance physicians' understanding, treatment, and referral of BPD patients.
Mid-Infrared Grating Couplers for Silicon-on-Sapphire Waveguides

Theoretical and experimental results of mid-infrared (mid-IR) gratings for coupling between transverse-electric (TE)/transverse-magnetic (TM) mode silicon-on-sapphire (SOS) waveguides and zirconium, barium, lanthanum, aluminum, and sodium fluoride (ZBLAN) fibers are presented. The shallow-etched uniform grating, full-etched subwavelength grating, and apodized grating are analyzed theoretically. TE mode shallow-etched apodized gratings with coupling efficiency of 80.6% and TM mode full-etched apodized subwavelength gratings with coupling efficiency of 39.6% are predicted at the wavelength of 2.75 by finite-difference time-domain (FDTD) simulation. An co-doped ZBLAN fiber laser is set up to be used as a mid-IR light source at 2.75 . Coupling efficiencies of 32.6% and 11.6% to TE mode and TM mode SOS waveguides, respectively, were obtained experimentally with uniform grating couplers. The dependence of coupling efficiency on etch depth, grating period, fill factor, and incident angle are also studied.
Enhancement of treatment adherence among patients with bipolar disorder.

OBJECTIVE Because about one-third of persons with bipolar illness take less than 30 percent of their medication and because nonadherence is associated with rehospitalization and suicide, the literature was searched to identify controlled studies of enhancement of treatment adherence among persons with bipolar disorder. METHODS Studies published up to October 2003 were evaluated. Those selected for review were controlled trials that used samples of adults with a diagnosis of bipolar disorder and that measured adherence to either mood-stabilizing medication or psychotherapy. Information was extracted on the diagnostic composition and size of the study group, the type and duration of the intervention, the method of measuring adherence, and outcomes. RESULTS Eleven studies met inclusion criteria. Although the literature on enhancing treatment adherence among persons with bipolar disorder is limited, the existing data are promising and demonstrate development over time in our understanding of how best to manage this illness. Interventions that have been shown to be effective include interpersonal group therapy, cognitive-behavioral therapy, group sessions for partners of persons with bipolar disorder, and patient and family psychoeducation. Effective therapies occur in the context of long-term management of illness that incorporates a good understanding of medications and their risks and benefits as well as education about illness awareness and self-management. The majority of effective therapies feature an interactional component between patients and their care providers or therapists. CONCLUSIONS Adherence to treatment for bipolar disorder may be enhanced by interventions that address issues of appropriately taking medications to manage illness. For optimum outcomes, promotion of adherence must be integrated into the medication management of bipolar illness.
Tomography, Adjoint Methods, Time-Reversal, and Banana-Doughnut Kernels

SUMMARY We draw connections between seismic tomography, adjoint methods popular in climate and ocean dynamics, time-reversal imaging and finite-frequency ‘banana-doughnut’ kernels. We demonstrate that Frechet derivatives for tomographic and (finite) source inversions may be obtained based upon just two numerical simulations for each earthquake: one calculation for the current model and a second, ‘adjoint’, calculation that uses time-reversed signals at the receivers as simultaneous, fictitious sources. For a given model, m, we consider objective functions χ(m) that minimize differences between waveforms, traveltimes or amplitudes. For tomographic inversions we show that the Frechet derivatives of such objective functions may be written in the generic form , where δ ln m=δm/m denotes the relative model perturbation. The volumetric kernel Km is defined throughout the model volume V and is determined by time-integrated products between spatial and temporal derivatives of the regular displacement field s and the adjoint displacement field s†; the latter is obtained by using time-reversed signals at the receivers as simultaneous sources. In waveform tomography the time-reversed signal consists of differences between the data and the synthetics, in traveltime tomography it is determined by synthetic velocities, and in amplitude tomography it is controlled by synthetic displacements. For each event, the construction of the kernel Km requires one forward calculation for the regular field s and one adjoint calculation involving the fields s and s†. In the case of traveltime tomography, the kernels Km are weighted combinations of banana-doughnut kernels. For multiple events the kernels are simply summed. The final summed kernel is controlled by the distribution of events and stations. Frechet derivatives of the objective function with respect to topographic variations δh on internal discontinuities may be expressed in terms of 2-D kernels Kh and Kh in the form , where Σ denotes a solid-solid or fluid-solid boundary and ΣFS a fluid–solid boundary, and ∇Σ denotes the surface gradient. We illustrate how amplitude anomalies may be inverted for lateral variations in elastic and anelastic structure. In the context of a finite-source inversion, the model vector consists of the time-dependent elements of the moment-density tensor m(x, t). We demonstrate that the Frechet derivatives of the objective function χ may in this case be written in the form , where e† denotes the adjoint strain tensor on the finite-fault plane Σ. In the case of a point source this result reduces further to the calculation of the time-dependent adjoint strain tensor e† at the location of the point source, an approach reminiscent of an acoustic time-reversal mirror. The theory is illustrated for both tomographic and source inversions using a 2-D spectral-element method.
Potential role of skeletal muscle glucose metabolism on the regulation of insulin secretion

Pancreatic beta cells sense glucose flux and release as much insulin as required in order to maintain glycaemia within a narrow range. Insulin secretion is regulated by many factors including glucose, incretins, and sympathetic and parasympathetic tones among other physiological factors. To identify the mechanisms linking obesity‐related insulin resistance with impaired insulin secretion represents a central challenge. Recently, it has been argued that a crosstalk between skeletal muscle and the pancreas may regulate insulin secretion. Considering that skeletal muscle is the largest organ in non‐obese subjects and a major site of insulin‐ and exercise‐stimulated glucose disposal, it appears plausible that muscle might interact with the pancreas and modulate insulin secretion for appropriate peripheral intracellular glucose utilization. There is growing evidence that muscle can secrete so‐called myokines that can have auto/para/endocrine actions. Although it is unclear in which direction they act, interleukin‐6 seems to be a possible muscle‐derived candidate protein mediating such inter‐organ communication. We herein review some of the putative skeletal muscle‐derived factors mediating this interaction. In addition, the evidence coming from in vitro, animal and human studies that support such inter‐organ crosstalk is thoroughly discussed.
Hyperforin Blocks Neutrophil Activation of Matrix Metalloproteinase-9, Motility and Recruitment, and Restrains Inflammation-Triggered Angiogenesis and Lung Fibrosis

Hyperforin (Hyp), a polyphenol-derivative of St. John's wort (Hypericum perforatum), has emerged as key player not only in the antidepressant activity of the plant but also as an inhibitor of bacteria lymphocyte and tumor cell proliferation, and matrix proteinases. We tested whether as well as inhibiting leukocyte elastase (LE) activity, Hyp might be effective in containing both polymorphonuclear neutrophil (PMN) leukocyte recruitment and unfavorable eventual tissue responses. The results show that, without affecting in vitro human PMN viability and chemokine-receptor expression, Hyp (as stable dicyclohexylammonium salt) was able to inhibit in a dose-dependent manner their chemotaxis and chemoinvasion (IC50 = 1 μM for both); this effect was associated with a reduced expression of the adhesion molecule CD11b by formyl-Met-Leu-Phe-stimulated neutrophils and block of LE-triggered activation of the gelatinase matrix metalloproteinase-9. PMN-triggered angiogenesis is also blocked by both local injection and daily i.p. administration of the Hyp salt in an interleukin-8-induced murine model. Furthermore, i.p. treatment with Hyp reduces acute PMN recruitment and enhances resolution in a pulmonary bleomycin-induced inflammation model, significantly reducing consequent fibrosis. These results indicate that Hyp is a powerful anti-inflammatory compound with therapeutic potential, and they elucidate mechanistic keys.
Dual-Layered MIMO Transmission for Increased Bandwidth Efficiency

A dual-layered downlink transmission scheme is proposed for intrinsically amalgamating multiple-input-multiple-output (MIMO) spatial multiplexing (SMX) with spatial modulation (SM). The proposed scheme employs a classic SMX transmission that is known to offer superior bandwidth efficiency (BE) compared with SM. We exploit receive-antenna-based SM (RSM) on top of this transmission as an enhancement of the BE. The RSM here is applied to the combined spatial and power-level domain not by activating and deactivating the RAs but rather by choosing between two power levels {P1, P2} for the received symbols in these antennas. In other words, the combination of symbols received at a power level P1 carries information in the spatial domain in the same manner as the combination of nonzero elements in the receive symbol vector carries information in the RSM transmission. This allows for the coexistence of RSM with SMX, and the results show increased BE for the proposed scheme compared with both SMX and SM. To characterize the proposed scheme, we carry out a mathematical analysis of its performance, and we use this to optimize the ratio between P1 and P2 for attaining the minimum error rates. Our analytical and simulation results demonstrate significant BE gains for the proposed scheme compared with conventional SMX and SM.