Miracle-dz/UniFAR-FTUs huggingface dataset:
μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve

Voltage-gated sodium channels (VGSCs) are important for action potentials. There are seven major isoforms of the pore-forming and gate-bearing α-subunit (NaV1) of VGSCs in mammalian neurons, and a given neuron can express more than one isoform. Five of the neuronal isoforms, NaV1.1, 1.2, 1.3, 1.6, and 1.7, are exquisitely sensitive to tetrodotoxin (TTX), and a functional differentiation of these presents a serious challenge. Here, we examined a panel of 11 μ-conopeptides for their ability to block rodent NaV1.1 through 1.8 expressed in Xenopus oocytes. Although none blocked NaV1.8, a TTX-resistant isoform, the resulting “activity matrix” revealed that the panel could readily discriminate between the members of all pair-wise combinations of the tested isoforms. To examine the identities of endogenous VGSCs, a subset of the panel was tested on A- and C-compound action potentials recorded from isolated preparations of rat sciatic nerve. The results show that the major subtypes in the corresponding A- and C-fibers were NaV1.6 and 1.7, respectively. Ruled out as major players in both fiber types were NaV1.1, 1.2, and 1.3. These results are consistent with immunohistochemical findings of others. To our awareness this is the first report describing a qualitative pharmacological survey of TTX-sensitive NaV1 isoforms responsible for propagating action potentials in peripheral nerve. The panel of μ-conopeptides should be useful in identifying the functional contributions of NaV1 isoforms in other preparations.
The Effects of Muscle Strength Responsiveness to Periodized Resistance Training on Resistin, Leptin, and Cytokine in Elderly Postmenopausal Women

Abstract Prestes, J, Nascimento, DdC, Neto, IVS, Tibana, RA, Shiguemoto, GE, Perez, SEA, Botero, JP, Schoenfeld, BJ, and Pereira, GB. The effects of muscle strength responsiveness to periodized resistance training on resistin, leptin, and cytokine in elderly postmenopausal women. J Strength Cond Res 32(1): 113–120, 2018—The aim of this study was to evaluate muscle strength responsiveness and to determine whether interleukin 4 (IL-4), leptin, and resistin would be affected by the individual pattern of response to a resistance training (RT) periodization program. Twenty-six elderly postmenopausal women participated in the present study (mean age = 62.57 ± 6.69 years and body mass index = 28.09 ± 4.83 kg·m−2). Four-month longitudinal training program was performed consisting of 2 whole-body sessions per week with increasing intensity and decreasing volume by using 6–14 repetitions maximum (RM). Two acute whole-body RT sessions (before and after chronic training) were also performed comprising 3 sets of 12–14RM. The responsiveness was determined based on their relative muscle strength gains in 45° leg press. High responders were defined as relative muscle strength gains ≥32% and low responders <32% (n = 13 in each group). Muscle strength increased by a higher amount in the high-responsive group as compared with the low-responsive group in the 45° leg press and bench press, whereas muscle strength increased for both groups when compared with pretraining evaluation (p = 0.001). Low responders displayed higher plasma leptin levels when compared with high responders at baseline (p = 0.001), and after 16 weeks of training, leptin levels were significantly lower when compared with baseline (pretraining period). Both groups displayed a decrease in baseline resistin values after 16 weeks of RT, but only a statistically simple main effect was observed for low responders. In addition, there were no effect of time and no significant interaction between the responsiveness and time on IL-4 concentration. In conclusion, RT is effective in improving upper and lower limb muscle strength in elderly women, with higher magnitudes of increase seen for those classified as high responders. Resistin and leptin displayed a decrease over time, regardless of responsiveness classification.
Social Inhibition in Immersive Virtual Environments

We assessed the utility of using immersive virtual environment (IVE) technology for social psychological research by attempting to replicate two classic social influence effects. Specifically, we sought to replicate the classic social facilitation/inhibition effects wherein individuals' performance on a task is affected by the presence of others. Within an IVE, participants mastered one of two tasks and subsequently performed the mastered or nonmastered task either alone or in the presence of a virtual human audience whom they were led to believe were either computer-controlled agents or human-controlled avatars. Those performing in the presence of avatars demonstrated classic social inhibition performance impairment effects relative to those performing alone or in the presence of agents. We discuss important elements involved in the experience of social influence within immersive virtual environments.
The effect of laryngeal mask airway insertion on the position of the internal jugular vein

A high‐quality ultrasound system (Dyasonics Prisma) was used to study the effect of laryngeal mask airway insertion and cuff inflation on the position and relations of the internal jugular vein in eight healthy young patients undergoing elective surgery. On insertion of the laryngeal mask, with the cuff pre‐inflated with 10 ml of air, some minor movement was discernible in the larynx. Neither the larynx nor surrounding structures changed significantly in position. However, on full inflation of the laryngeal mask cuff there was a more noticeable movement of the larynx, which visibly distended in an anterior direction. The mean anterior displacement was 0.8 cm (range 0.6–1.1 cm). There was no significant lateral displacement of the carotid artery or internal jugular vein and there was no significant compression of these structures. We conclude that in the presence of a laryngeal mask airway fixed landmarks such as the sternal notch and angle of the jaw should be used to identify the likely position of the internal jugular vein. Difficulty in cannulation may be experienced if the mobile laryngeal structures are used as landmarks.
Collingwood's Dialectic of History

When Collingwood's The Idea of History was published posthumously in 1946, it brought to critical notice an issue which had been almost completely ignored by English-speaking philosophers, although it was increasingly plaguing reflective historians: is history an autonomous mode of knowledge, or is it an imperfectly developed version of the kind of inquiry more securely practiced in the successful natural sciences? Collingwood gave a definite answer to this question, and one which, if not authoritative, was at least reasoned and provocative. Yet the essays collected as "Epilegomena" in The Idea of History are in fact very difficult to understand and elucidate, although the full extent of their difficulty is concealed by the grace of their style and the often compelling quality of the obiter dicta so often quoted from them. It is notable that advocates as well as critics of Collingwood's views have focused their attention on The Idea of History, perhaps with side glances at his Autobiography of 1939.1 Nevertheless, as I propose to argue, it is virtually impossible to arrive at an adequate interpretation of Collingwood's idea of history from The Idea of History itself. There are at least four main reasons for the almost universal failure to recognize this. First, the seven essays were written at different times for different audiences and were never revised as a whole. This is an especial difficulty where anything like a systematic theory is at issue. While Collingwood did have a systematic
Ketoprofen Pharmacokinetics in the Elderly: Influence of Rheumatic Disease, Renal Function, and Dose

An age‐related accumulation of ketoprofen due to a reduced clearance has been reported in the elderly. Other studies have not observed these changes in the kinetics of unchanged ketoprofen, but have reported increased plasma levels and reduced urinary excretion of conjugated ketoprofen. The authors examined the effects of dose, renal function, and the presence of arthritis on the stereoselective kinetics of ketoprofen in five nonarthritic and six arthritic elderly subjects. There was a significant difference in renal function (CLCr, mL/min; arthritic, 71.8 ± 12.3, nonarthritic, 91.4 ± 11.1), but not in age or weight between the two groups. Subjects received 50 mg and then 150 mg enteric‐coated racemic ketoprofen, and plasma and urine samples were collected for 24 hours. No significant differences in CL/F, area under the curve (AUC), half‐life (t1/2), time to reach peak concentration (tmax), or maximum peak plasma concentration (Cmax) were found between groups or between doses, and values were similar to those previously reported in young adults. Urinary ketoprofen conjugate (S:R) ratio was 1.6 ± . 25 and 1.65 ± . 27 for arthritic and nonarthritic subjects. Greater amounts of conjugated ketoprofen enantiomers were present in the plasma of the arthritic compared with nonarthritic subjects. Renal clearance of ketoprofen conjugates exhibited stereoselectivity (R > S), and was decreased in the arthritic group. Significant changes in the kinetics of unchanged ketoprofen was not found to occur in elderly subjects in the presence or absence of rheumatic disease or moderate renal impairment. Dosage adjustments in the elderly based on age alone may not be necessary.
Configural Features in the Context of Upright and Inverted Faces

When faces are turned upside down, recognition is known to be severely disrupted. This effect is thought to be due to disruption of configurai processing. Recently, Leder and Bruce (2000, Quarterly Journal of Experimental Psychology A 53 513–536) argued that configural information in face processing consists at least partly of locally processed relations between facial elements. In three experiments we investigated whether a local relational feature (the interocular distance) is processed differently in upside-down versus upright faces. In experiment 1 participants decided in which of two sequentially presented photographic faces the interocular distance was larger. The decision was more difficult in upside-down presentation. Three different conditions were used in experiment 2 to investigate whether this deficit depends upon parts of the face beyond the eyes themselves; displays showed the eye region alone, the eyes and nose, or the eyes and nose and mouth. The availability of additional features did not interact with the inversion effect which was observed strongly even when the eyes were shown in isolation. In experiment 3 all eyes were turned upside down in the inverted face condition as in the Thatcher illusion (Thompson, 1980 Perception 9 483–484). In this case no inversion effect was found. These results are in accordance with an explanation of the face-inversion effect in which the disruption of configural facial information plays the critical role in memory for faces, and in which configural information corresponds to spatial information that is processed in a way which is sensitive to local properties of the facial features involved.
5′ Processing of tRNA Precursors Can Be Modulated by the Human La Antigen Phosphoprotein

ABSTRACT Eukaryotic precursor (pre)-tRNAs are processed at both ends prior to maturation. Pre-tRNAs and other nascent transcripts synthesized by RNA polymerase III are bound at their 3′ ends at the sequence motif UUUOH [3′ oligo(U)] by the La antigen, a conserved phosphoprotein whose role in RNA processing has been associated previously with 3′-end maturation only. We show that in addition to its role in tRNA 3′-end maturation, human La protein can also modulate 5′ processing of pre-tRNAs. Both the La antigen’s N-terminal RNA-binding domain and its C-terminal basic region are required for attenuation of pre-tRNA 5′ processing. RNA binding and nuclease protection assays with a variety of pre-tRNA substrates and mutant La proteins indicate that 5′ protection is a highly selective activity of La. This activity is dependent on 3′ oligo(U) in the pre-tRNA for interaction with the N-terminal RNA binding domain of La and interaction of the C-terminal basic region of La with the 5′ triphosphate end of nascent pre-tRNA. Phosphorylation of La is known to occur on serine 366, adjacent to the C-terminal basic region. We show that this modification interferes with the La antigen’s ability to protect pre-tRNAi Met from 5′ processing either by HeLa extract or purified RNase P but that it does not affect interaction with the 3′ end of pre-tRNA. These findings provide the first evidence to indicate that tRNA 5′-end maturation may be regulated in eukaryotes. Implications of triphosphate recognition is discussed as is a role for La phosphoprotein in controlling transcriptional and posttranscriptional events in the biogenesis of polymerase III transcripts.
Role of Toxin Functional Domains in Anthrax Pathogenesis

ABSTRACT We investigated the role of the functional domains of anthrax toxins during infection. Three proteins produced by Bacillus anthracis, the protective antigen (PA), the lethal factor (LF), and the edema factor (EF), combine in pairs to produce the lethal (PA+LF) and edema (PA+EF) toxins. A genetic strategy was developed to introduce by allelic exchange specific point mutations or in-frame deletions into B. anthracis toxin genes, thereby impairing either LF metalloprotease or EF adenylate cyclase activity or PA functional domains. In vivo effects of toxin mutations were analyzed in an experimental infection of mice. A tight correlation was observed between the properties of anthrax toxins delivered in vivo and their in vitro activities. The synergic effects of the lethal and edema toxins resulted purely from their enzymatic activities, suggesting that in vivo these toxins may act together. The PA-dependent antibody response to LF induced by immunization with live B. anthracis was used to follow the in vivo interaction of LF and PA. We found that the binding of LF to PA in vivo was necessary and sufficient for a strong antibody response against LF, whereas neither LF activity nor binding of lethal toxin complex to the cell surface was required. Mutant PA proteins were cleaved in mice sera. Thus, our data provide evidence that, during anthrax infection, PA may interact with LF before binding to the cell receptor. Immunoprotection studies indicated that the strain producing detoxified LF and EF, isogenic to the current live vaccine Sterne strain, is a safe candidate for use as a vaccine against anthrax.
Potential of Nanofiltration for Phosphate Removal from Wastewater

Experimental investigations were conducted to evaluate the performance of nanofiltration for tertiary level phosphate removal from wastewater. A flat sheet type Desal-5 thin film nanofiltration membrane in a plate and frame module, was used. The influence of pressure, initial feed concentration, competing compounds, on nanofiltration performance were determined. The experimental study range of pressure and concentration were 400–1000 kPa and 2–10 mg l−1 P respectively and ammonium sulphate was used as the competing compound. Results showed that phosphorus removal efficiency for nanofiltration is high (>95%) and it can produce an effluent containing less than 0.1 mg l−1 P as a tertiary level treatment. Higher pressure and concentration showed positive response, while presence of competing compound showed negative response on phosphorus rejection. A numerical equation relating osmotic pressure and permeate flux has also been developed based on the experimental results.
Adjunctive treatment of manic agitation with lorazepam versus haloperidol: a double-blind study.

BACKGROUND While lithium is effective in treating the majority of bipolar patients during a manic episode, the addition of neuroleptic during the early phase of treatment has been common clinical practice in inpatient settings. In an earlier open study, we demonstrated the utility of the short-acting benzodiazepine lorazepam as an adjunct to lithium for the clinical management of manic agitation. METHOD We now present data from a randomized, double-blind clinical study of lorazepam versus haloperidol in 20 hospitalized patients with a DSM-III-R diagnosis of bipolar disorder who were being treated concomitantly with lithium. Patients were rated using the Mania Rating Scale, Brief Psychiatric Rating Scale, Physician Global Impression Scale, and side effects scales. Data were analyzed using standard group comparisons and survival analysis. RESULTS There was no evidence for a significant difference between the two treatment groups in the magnitude of or time to response (5.0 +/- .82 days for haloperidol; 6.5 +/- .93 days for lorazepam). Of the patients who were terminated from the protocol early, nonresponse was the primary reason in the lorazepam group while side effects were the reason in the haloperidol group. CONCLUSION Lorazepam may offer an efficacious and safe alternative to haloperidol as an adjunctive treatment to lithium in the clinical management of the early phase of manic agitation in a subgroup of bipolar patients.
Pain Beliefs and Readiness to Change Among Adolescents With Chronic Musculoskeletal Pain and Their Parents Before an Initial Pain Clinic Evaluation

Objectives:To understand relationships between pain-related beliefs and readiness to change among treatment-seeking adolescents with chronic musculoskeletal pain and their parents. Methods:A total of 102 adolescent-parent dyads were recruited at the time of initial evaluation at a multidisciplinary pain management clinic. Dyads completed self-report measures to assess pain, catastrophizing, endorsement of a biopsychosocial perspective of pain, and readiness to change/motivation to adopt a self-management approach to pain coping. Results:Agreement between adolescent-parent dyad reports of pain catastrophizing and readiness to change was found; however, adolescents were less likely to view pain as “affected by feelings and emotions” than parents. The hypothesis that greater pain catastrophizing would be correlated with less readiness to change was partially supported. Adolescent and parents who reported lower levels of endorsement of a biopsychosocial perspective were less willing to adopt a self-management approach to pain coping. Endorsement of a biopsychosocial perspective of pain aligned with readiness to change stages more consistently for parents. Discussion:This study documents initial relationships among pain catastrophizing, biopsychosocial perspectives of pain, and readiness to engage in a self-management approach to pain coping for adolescents with chronic pain and their parents. Although agreement exists between dyads regarding catastrophizing and readiness to change, differences were noted in biopsychosocial perspective and dominant readiness to change stage before an initial pain clinic encounter. Findings are considered in terms of future research to advance knowledge regarding the role these factors may play in treatment adherence and outcomes.
1 Deciding for Others Reduces Loss Aversion *

We study risk taking on behalf of others, both with and without potential losses. A large-scale incentivized experiment is conducted with subjects randomly drawn from the Danish population. On average, decision makers take the same risks for other people as for themselves when losses are excluded. In contrast, when losses are possible, decisions on behalf of others are more risky. Using structural estimation, we show that this increase in risk stems from a decrease in loss aversion when others are affected by their choices.
Peak External Photocurrent Quantum Efficiency Exceeding 100% via MEG in a Quantum Dot Solar Cell

An experimental solar cell productively uses an extra fraction of high-energy light typically lost as heat. Multiple exciton generation (MEG) is a process that can occur in semiconductor nanocrystals, or quantum dots (QDs), whereby absorption of a photon bearing at least twice the bandgap energy produces two or more electron-hole pairs. Here, we report on photocurrent enhancement arising from MEG in lead selenide (PbSe) QD-based solar cells, as manifested by an external quantum efficiency (the spectrally resolved ratio of collected charge carriers to incident photons) that peaked at 114 ± 1% in the best device measured. The associated internal quantum efficiency (corrected for reflection and absorption losses) was 130%. We compare our results with transient absorption measurements of MEG in isolated PbSe QDs and find reasonable agreement. Our findings demonstrate that MEG charge carriers can be collected in suitably designed QD solar cells, providing ample incentive to better understand MEG within isolated and coupled QDs as a research path to enhancing the efficiency of solar light harvesting technologies.
Major depressive disorder as a co-morbid diagnosis in schizophrenia versus the diagnosis of schizoaffective disorder – depressed type

The purpose of this article is to focus on the importance of depressive symptoms in patients suffering from schizophrenia, and the dilemma posed by hierarchical classification methods, which exclude co-morbid diagnoses such as Major Depressive Disorder in patients with schizophrenia. The question arises that if Major Depressive Disorder is only categorized under the diagnosis of Schizoaffective Disorder (depressed type), are we able to recognize these symptoms promptly and treat them sufficiently? The duration of the substantial period of depressed mood referred to in the DSM IV TR criteria for Schizoaffective Disorder is unspecified. We suggest that one should only allocate the latter diagnosis if the substantial period is that of one third or more of the whole duration of the illness. Identification of the optimal cutoff point can generate further hypothesis testing research and refinement of the diagnostic model. It is not only important to refine the diagnosis, but it is even more important to detect these symptoms and treat promptly and effectively. According to the latest literature, the best possible treatment for depression in schizophrenia appears to be the combination of a second-generation antipsychotic and cognitive psychotherapy.
Unitary study on evoked activity of callosal neurons and its effect on pyramidal tract cell activity on cats.

Microelectrode experiments were made on two kinds of cortical cells in the cat, each identified by antidromic stimulation. First, recordings were made from callosal neurons, and these were studied by radial nerve stimulation. Second, recordings were made from pyramidal tract cells (P. T. cells), and the effects of corpus callosum stimulation on the activities of P. T. cells were studied. All studies were carried out in the pericruciate cortex. The following results were obtained;1) Out of 20 cells identified as callosal neurons, 12 were fired by single stimuli delivered to the superficial radial nerve. The latency of the discharge ranged from 12 to 20msec.2) Single stimuli to the corpus callosum produced long lasting inhibitory effects on P. T. cells. The inhibitory effect seemed to start with a latency of 20 to 30msec. Though with most cells the effect was purely inhibitory (table 1), on rare occasions a transitory excitation preceded the inhibition.3) In a few successful intracellular recordings from P. T. cells, a marked hyperpolarization of the membrane was observed to occur when firing was inhibited.