Miracle-dz/UniFAR-FTUs huggingface dataset:
Peptides derived from lupin proteins confer potent protection against oxidative stress.

BACKGROUND Lupin seeds are rich in proteins, which are utilized in the food industry. There is an increased interest in lupin research due to its association with health-related benefits, such as reduction of hypertension and hyperglycemia. However, studies on the peptides derived from lupin proteins are rare. RESULTS Lupin protein hydrolysates (LPHs) were prepared by proteolysis using alcalase, trypsin and pepsin, respectively. All the hydrolysates demonstrated higher antioxidant and angiotensin I-converting enzyme (ACE) inhibitory activities compared to lupin proteins. The hydrolysates were fractionated into three fractions based on molecular weight (MW), and the peptides with MW < 3 kDa (LPH3) had the highest antioxidant and ACE inhibitory activities compared to other fractions. Cell model study revealed that LPH3 fraction had the highest protection against the generation of reactive oxygen species in HepG2 cells, which was associated with increased activities of superoxide dismutase and glutathione peroxidase through upregulation of SOD1, GPX1, GCLM, SLC7A11 and SRXN1 expression. CONCLUSIONS The analysis of amino acid composition indicated that the peptides were characterized with high content of hydrophobic amino acids, which may be responsible for the greatest antioxidant activity. This study highlights the promising potential of lupin peptides as a functional ingredient in healthy foods. © 2018 Society of Chemical Industry.
SFT-4/Surf4 control ER export of soluble cargo proteins and participate in ER exit site organization

Lipoproteins regulate the overall lipid homeostasis in animals. However, the molecular mechanisms underlying lipoprotein trafficking remain poorly understood. Here, we show that SFT-4, a Caenorhabditis elegans homologue of the yeast Erv29p, is essential for the endoplasmic reticulum (ER) export of the yolk protein VIT-2, which is synthesized as a lipoprotein complex. SFT-4 loss strongly inhibits the ER exit of yolk proteins and certain soluble cargo proteins in intestinal cells. SFT-4 predominantly localizes at ER exit sites (ERES) and physically interacts with VIT-2 in vivo, which suggests that SFT-4 promotes the ER export of soluble proteins as a cargo receptor. Notably, Surf4, a mammalian SFT-4 homologue, physically interacts with apolipoprotein B, a very-low-density lipoprotein core protein, and its loss causes ER accumulation of apolipoprotein B in human hepatic HepG2 cells. Interestingly, loss of SFT-4 and Surf4 reduced the number of COPII-positive ERES. Thus, SFT-4 and Surf4 regulate the export of soluble proteins, including lipoproteins, from the ER and participate in ERES organization in animals.
Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment

Background: Oxidative stress is one of the causative factors in the pathogenesis of neuro-degenerative diseases including mild cognitive impairment (MCI) and dementia. We previously reported that molecular hydrogen (H2) acts as a therapeutic and preventive antioxidant. Objective: We assess the effects of drinking H2-water (water infused with H2) on oxidative stress model mice and subjects with MCI. Methods: Transgenic mice expressing a dominant-negative form of aldehyde dehydrogenase 2 were used as a dementia model. The mice with enhanced oxidative stress were allowed to drink H2-water. For a ran-domized double-blind placebo-controlled clinical study, 73 subjects with MCI drank ~300 mL of H2-water (H2-group) or placebo water (control group) per day, and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores were determined after 1 year. Results: In mice, drinking H2-water decreased oxidative stress markers and suppressed the decline of memory impairment and neurodegeneration. Moreover, the mean lifespan in the H2-water group was long-er than that of the control group. In MCI subjects, although there was no significant difference between the H2- and control groups in ADAS-cog score after 1 year, carriers of the apolipoprotein E4 (APOE4) geno-type in the H2-group were improved significantly on total ADAS-cog score and word recall task score (one of the sub-scores in the ADAS-cog score). Conclusion: H2-water may have a potential for suppressing dementia in an oxidative stress model and in the APOE4 carriers with MCI.
Drosophila Dosage Compensation Loci Associate with a Boundary-Forming Insulator Complex

ABSTRACT Chromatin entry sites (CES) are 100- to 1,500-bp elements that recruit male-specific lethal (MSL) complexes to the X chromosome to upregulate expression of X-linked genes in male flies. CES contain one or more ∼20-bp GA-rich sequences called MSL recognition elements (MREs) that are critical for dosage compensation. Recent studies indicate that CES also correspond to boundaries of X-chromosomal topologically associated domains (TADs). Here, we show that an ∼1,000-kDa complex called the late boundary complex (LBC), which is required for the functioning of the Bithorax complex boundary Fab-7, interacts specifically with a special class of CES that contain multiple MREs. Mutations in the MRE sequences of three of these CES that disrupt function in vivo abrogate interactions with the LBC. Moreover, reducing the levels of two LBC components compromises MSL recruitment. Finally, we show that several of the CES that are physically linked to each other in vivo are LBC interactors.
Safety, Tolerability, and Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Pediatric Patients

ABSTRACT The safety, tolerability, and pharmacokinetics of the liposomal formulation of amphotericin B (L-AMB) were evaluated in 40 immunocompromised children and adolescents. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study with 10 to 13 patients in each of the four dosage cohorts. Each cohort received daily dosages of 2.5, 5.0, 7.5, or 10 mg of amphotericin B in the form of L-AMB per kg of body weight. Neutropenic patients between the ages of 1 and 17 years were enrolled to receive empirical antifungal therapy or treatment of documented invasive fungal infections. The pharmacokinetic parameters of L-AMB were measured as those of amphotericin B by high-performance liquid chromatography and calculated by noncompartmental methods. There were nine adverse-event-related discontinuations, four of which were related to infusions. Infusion-related side effects occurred for 63 (11%) of 565 infusions, with 5 patients experiencing acute infusion-related reactions (7.5- and 10-mg/kg dosage levels). Serum creatinine levels increased from 0.45 ± 0.04 mg/dl to 0.63 ± 0.06 mg/dl in the overall population (P = 0.003), with significant increases in dosage cohorts receiving 5.0 and 10 mg/kg/day. At the higher dosage level of 10 mg/kg, there was a trend toward greater hypokalemia and vomiting. The area under the concentration-time curve from 0 to 24 h (AUC0–24) values for L-AMB on day 1 increased from 54.7 ± 32.9 to 430 ± 566 μg · h/ml in patients receiving 2.5 and 10.0 mg/kg/day, respectively. These findings demonstrate that L-AMB can be administered to pediatric patients at dosages similar to those for adults and that azotemia may develop, especially in those receiving ≥5.0 mg/kg/day.
The Pedaling Technique of Elite Endurance Cyclists: Changes with Increasing Workload at Constant Cadence

A pedal dynamometer recorded changes in pedaling technique (normal and tangential components of the applied force, crank orientation, and pedal orientation) of 14 elite male 40-km time trialists who rode at constant cadence as the workload increased from similar to an easy training ride to similar to a 40-km competition. There were two techniques for adapting to increased workload. Seven subjects showed no changes in pedal orientation, and predominantly increased the vertical component of the applied force during the downstroke as the workload increased. In addition to increasing the vertical component during the downstroke, the other subjects also increased the toe up rotation of the pedal throughout the downstroke and increased the horizontal component between 0° and 90°. A second finding was that negative torque about the bottom bracket during the upstroke usually became positive (propulsive) torque at the high workload. However, while torque during the upstroke did reduce the total positive work requi.
Emergency Department Provider Perspectives on Benzodiazepine-Opioid Coprescribing: A Qualitative Study.

OBJECTIVE Benzodiazepines and opioids are prescribed simultaneously (i.e., "coprescribed") in many clinical settings, despite guidelines advising against this practice and mounting evidence that concomitant use of both medications increases overdose risk. This study sought to characterize the contexts in which benzodiazepine-opioid coprescribing occurs and providers' reasons for coprescribing. METHODS We conducted focus groups with emergency department (ED) providers (resident and attending physicians, advanced practice providers, and pharmacists) from three hospitals using semistructured interviews to elicit perspectives on benzodiazepine-opioid coprescribing. Discussions were audio-recorded and transcribed. We performed qualitative content analysis of the resulting transcripts using a consensual qualitative research approach, aiming to identify priority categories that describe the phenomenon of benzodiazepine-opioid coprescribing. RESULTS Participants acknowledged coprescribing rarely and reluctantly and often provided specific discharge instructions when coprescribing. The decision to coprescribe is multifactorial, often isolated to specific clinical and situational contexts (e.g., low back pain, failed solitary opioid therapy) and strongly influenced by a provider's beliefs about the efficacy of combination therapy. The decision to coprescribe is further influenced by a self-imposed pressure to escalate care or avoid hospital admission. When considering potential interventions to reduce the incidence of coprescribing, participants opposed computerized alerts but were supportive of a pharmacist-assisted intervention. Many providers found the process of participating in peer discussions on prescribing habits to be beneficial. CONCLUSIONS In this qualitative study of ED providers, we found that benzodiazepine-opioid coprescribing occurs in specific clinical and situational contexts, such as the treatment of low back pain or failed solitary opioid therapy. The decision to coprescribe is strongly influenced by a provider's beliefs and by self-imposed pressure to escalate care or avoid admission.
Does Religiosity Predict Suicidal Behavior

Research was reviewed on whether self-report measures of religiosity were a protective factor against suicidal behaviors. It was found that scores on Francis’s measure of religiosity was negatively associated with non-lethal suicidal behavior (ideation and attempts), a protective effect. Similarly, it was found that intrinsic religiosity (but not extrinsic religiosity) was negatively associated with non-lethal suicidal behaviors. However, these associations were weak. Research is needed on the issue whether counselors can use their patients’ religiosity to reduce the risk of dying by suicide.
Ultraviolet Radiation Inhibits Mammary Carcinogenesis in an ER-Negative Murine Model by a Mechanism Independent of Vitamin D3

Three decades ago, the Garlands postulated that vitamin D3 produced in the skin by ultraviolet radiation (UVR)-induced conversion of 7-dehydrocholesterol to pre-D3 has anticancer effects, thus triggering more than 9,500 publications on D3 and cancer. Here, we report that UVR treatment of transgenic mice of the well-established C3(1)/SV40 Tag mammary cancer model significantly inhibits both autochthonous carcinogenesis and allograft tumor growth, but in contrast neither dietary nor topical D3 influences mammary carcinogenesis in this specific mouse model. Furthermore, UVR's inhibitory effects occur irrespective of whether or not the treatment increases circulating D3 in the mice. The inhibitory effect of UVR on autochthonous tumors occurs at or before the stage of ductal carcinoma in situ. Our studies indicate clearly that UVR can exert D3-independent anticancer effects in C3(1)/SV40 Tag mice. Therefore, supplemental D3 may not mimic all possible beneficial effects of UVR, and uncovering non–D3-mediated mechanisms of UVR tumor inhibition may lead to novel strategies for cancer prevention. Cancer Prev Res; 11(7); 383–92. ©2018 AACR.
Locomotion System for a Mobile Robot on Magnetic Wheels With Both Axial and Circumferential Mobility and With Only an 8-mm Height for Generator Inspection With the Rotor Still Installed

This paper describes the locomotion system for a miniature climbing robot on magnetic wheels for inspecting large generator stators (>;1 m in diameter, >;10 MW, and installed in thermal power plants) with the rotor still installed. Due to its compact mechanical design, it is able to pass through narrow entrance gaps down to 9 mm. In comparison to previous designs, it is not only able to drive on axial paths on the stator but also switch to circumferential paths as well. This enhances the application scope to generators with internal obstacles and facilitates the future system integration toward fully autonomous scans. For the axial movement, the robot uses an adapted magnetic-wheeled drive unit from the previous generation. The circumferential paths are realized with inchworm locomotion (also called “frame walking”). This paper concludes with the test results and provides an outlook on future improvements and extensions toward a full robotic system.
Hodgkin lymphoma cell lines: to separate the wheat from the chaff

Abstract Characteristic components of Hodgkin lymphoma (HL) tissue are the mono- or multinucleated Hodgkin-Reed-Sternberg (HRS) cells. Given the challenges of isolating these rare malignant cells and the difficulty in culturing cells from patients, many investigators have tried to establish cell lines in efforts to develop cellular tools for in vitro studies. A limited number of HL cell lines exist and have provided valuable insights into HL pathobiology. A literature survey indicated that 35 cell lines derived from HL patients have been published. To determine whether all these alleged HL cell lines hold up to scrutiny, we examined the available data and also put some of these cell lines to the test of hierarchical clustering, providing additional information regarding assignment to cell line type and tissue derivation. Hierarchical clustering separated the bona fide (classical) HL cell lines completely from cell lines derived from other lymphoma categories and proved conclusively that HL cell lines represent a distinct entity, irrespective of the cellular origin of the HRS cells. We conclude by pointing out the need for an intensified search for new cell culture avenues in order to develop a new generation of informative HL cell lines covering more widely the spectrum of HL stages and subtypes.
Dynein Regulators Are Important for Ecotropic Murine Leukemia Virus Infection

ABSTRACT During the early steps of infection, retroviruses must direct the movement of the viral genome into the nucleus to complete their replication cycle. This process is mediated by cellular proteins that interact first with the reverse transcription complex and later with the preintegration complex (PIC), allowing it to reach and enter the nucleus. For simple retroviruses, such as murine leukemia virus (MLV), the identities of the cellular proteins involved in trafficking of the PIC in infection are unknown. To identify cellular proteins that interact with the MLV PIC, we developed a replication-competent MLV in which the integrase protein was tagged with a FLAG epitope. Using a combination of immunoprecipitation and mass spectrometry, we established that the microtubule motor dynein regulator DCTN2/p50/dynamitin interacts with the MLV preintegration complex early in infection, suggesting a direct interaction between the incoming viral particles and the dynein complex regulators. Further experiments showed that RNA interference (RNAi)-mediated silencing of either DCTN2/p50/dynamitin or another dynein regulator, NudEL, profoundly reduced the efficiency of infection by ecotropic, but not amphotropic, MLV reporters. We propose that the cytoplasmic dynein regulators are a critical component of the host machinery needed for infection by the retroviruses entering the cell via the ecotropic envelope pathway. IMPORTANCE Retroviruses must access the chromatin of host cells to integrate the viral DNA, but before this crucial event, they must reach the nucleus. The movement through the cytoplasm—a crowded environment where diffusion is slow—is thought to utilize retrograde transport along the microtubule network by the dynein complex. Different viruses use different components of this multisubunit complex. We found that the preintegration complex of murine leukemia virus (MLV) interacts with the dynein complex and that regulators of this complex are essential for infection. Our study provides the first insight into the requirements for retrograde transport of the MLV preintegration complex.
Lumbar facet injection for the treatment of chronic piriformis myofascial pain syndrome: 52 case studies

Background and aims The aim of this study was to demonstrate the effectiveness of lumbar facet joint injection for piriformis myofascial pain syndrome. Methods Fifty-two patients with chronic myofascial pain in the piriformis muscle each received a lumbar facet injection into the ipsilateral L5–S1 facet joint region, using the multiple insertion technique. Subjective pain intensity, trunk extension range, and lumbar facet signs were measured before, immediately after, and 2 weeks after injection. Thirty-six patients received follow-up for 6 months. Results Immediately after the injection, 27 patients (51.9%) had complete pain subsidence, 19 patients (36.5%) had pain reduction to a tolerable level, and only 6 patients (11.5%) had no pain relief to a tolerable level. Mean pain intensity was reduced from 7.4±0.9 to 1.6±2.1 after injection (P<0.01). This effectiveness lasted for 2 weeks in 49 patients (94.2%), and lasted for approximately 6 months in 35 (97.2%) of 36 patients. The mean range of motion increased from 13.4±6.8 degrees to 22.1±6.0 degrees immediately after injection, and further increased 2 weeks and 6 months later. Immediately after injection, 45 patients (86.5%) had no facet sign. In addition, 90.4% and 94.4% of patients had no facet sign after 2 weeks and after 6 months, respectively. Conclusions It is important to identify the possible cause of piriformis myofascial pain syndrome. If this pain is related to lumbar facet lesions, lumbar facet joint injection can immediately suppress piriformis myofascial pain symptoms. This effectiveness may last for at least 6 months in most patients. This study further supports the importance of eliminating the underlying etiological lesion for complete and effective relief of myofascial pain syndrome.
Dorsoventral and Proximodistal Hippocampal Processing Account for the Influences of Sleep and Context on Memory (Re)consolidation: A Connectionist Model

The context in which learning occurs is sufficient to reconsolidate stored memories and neuronal reactivation may be crucial to memory consolidation during sleep. The mechanisms of context-dependent and sleep-dependent memory (re)consolidation are unknown but involve the hippocampus. We simulated memory (re)consolidation using a connectionist model of the hippocampus that explicitly accounted for its dorsoventral organization and for CA1 proximodistal processing. Replicating human and rodent (re)consolidation studies yielded the following results. (1) Semantic overlap between memory items and extraneous learning was necessary to explain experimental data and depended crucially on the recurrent networks of dorsal but not ventral CA3. (2) Stimulus-free, sleep-induced internal reactivations of memory patterns produced heterogeneous recruitment of memory items and protected memories from subsequent interference. These simulations further suggested that the decrease in memory resilience when subjects were not allowed to sleep following learning was primarily due to extraneous learning. (3) Partial exposure to the learning context during simulated sleep (i.e., targeted memory reactivation) uniformly increased memory item reactivation and enhanced subsequent recall. Altogether, these results show that the dorsoventral and proximodistal organization of the hippocampus may be important components of the neural mechanisms for context-based and sleep-based memory (re)consolidations.
Deep Reinforcement Learning from Human Preferences

For sophisticated reinforcement learning (RL) systems to interact usefully with real-world environments, we need to communicate complex goals to these systems. In this work, we explore goals defined in terms of (non-expert) human preferences between pairs of trajectory segments. We show that this approach can effectively solve complex RL tasks without access to the reward function, including Atari games and simulated robot locomotion, while providing feedback on less than one percent of our agent's interactions with the environment. This reduces the cost of human oversight far enough that it can be practically applied to state-of-the-art RL systems. To demonstrate the flexibility of our approach, we show that we can successfully train complex novel behaviors with about an hour of human time. These behaviors and environments are considerably more complex than any that have been previously learned from human feedback.
Bacterial growth efficiency in lakewater cultures

Batch cultures of natural bacterial assemblages from 3 lakes were used to measure bacterial growth efficiency (BGE) from increments in biomass and oxygen uptake. As could be expected from previous results and a logist~c growth model, the growth efficiency vaned anlong experiments and changed over time in relation to growth phases. During each experiment a maximum efficiency (range from 38 to 76%), which often coincided with maximum growth rate, could be identified. However, a significant relationship between efficiency and growth rate was not present and 2 cases of high efficiency during the apparent stationary phase were observed. Calculations of BGE by averaging procedures like linear regression of biomass increase and oxygen uptake versus time or end-point data at an apparent stationary phase most often resulted in low efficiency estimates. The maximum BGE values were on average 1.6 to 1.8 times hlgher than values calculated from regressions. We suggest to ident~fy the maximum value in future measurements of BGE to avoid an underestimation of BGE. These findings are discussed in relation to in situ growth efficiency.
Epidemiology and Characteristics of Cervical Spine Injury in Patients Presenting to a Regional Emergency Department

Purpose This study aims to establish the demographics and characteristics of patients with cervical spine injury (CSI) in an Irish cohort presenting to a regional emergency department. Methods We performed a retrospective analysis of the medical records of patients who underwent cervical spine computed tomography (CT) scans following trauma from January 2013 to July 2016. We looked at the mechanism of injury, mode of arrival to the emergency department, triage category, correlation between examination, and site of CSI and neurological status. Results Over the study period, 808 patients underwent CT scans of the cervical spine for potential CSI. The incidence of CSI in our cohort was 9.4% (n = 76). Approximately 70% (n = 53) were men. Falls (53%) and motor vehicle accidents (29%) were noted to be the more common mechanisms of injury in this cohort. The C2 region was the most common location for CSI. Only 7% (n = 5) of patients had documented neurology. Conclusion This study demonstrates the epidemiology and characteristics of CSI presenting in an Irish cohort. The incidence of CSI was found to be 9.4% with a male preponderance and falls being the most common cause of trauma.