Previous Restraint Research Articles

Integrating AlphaFold pLDDT Scores into CABS-flex for enhanced protein flexibility simulations

CABS-flex is a well-established method for fast protein flexibility simulations, offering an effective balance between computational efficiency and accuracy in modeling protein dynamics. To further enhance its predictive capabilities, we propose incorporating AlphaFold's predicted Local Distance Difference Test (pLDDT) scores into CABS-flex simulations. The pLDDT scores, which reflect the confidence of AlphaFold's structural predictions, were integrated with secondary structure information to refine the restraint schemes used in the simulations. We tested this approach on the ATLAS database, which includes molecular dynamics (MD) simulations of nearly 1400 proteins. The results showed improved alignment of flexibility predictions with the MD data compared to previous restraint schemes. The integration of pLDDT scores also offers a new perspective on protein flexibility by incorporating structural confidence into the analysis. This development enhances the utility of CABS-flex for investigating protein dynamics and motion.

Restraint stress potentiates neuropeptide Y-mediated impairment on spatial memory in rats

Memory is the ability to store, retrieve and use information that requires a progressive time-dependent stabilization process known as consolidation to be established. The hippocampus is essential for processing all the information that forms memory, especially spatial memory. Neuropeptide Y (NPY) affects memory, so in this study we investigated the participation and recruitment of NPY receptors during spatial memory consolidation in rats. Using the water maze test, we show that NPY (1 pmol) injected into the dorsal hippocampus impaired memory consolidation and that previous restraint stress (30min) potentiates NPY effects, i.e. further impaired memory consolidation. Using selective antagonists for NPY Y1 and Y2 receptors we demonstrate that both receptors play a key role on spatial memory consolidation. Our data suggest that NPY modulates aversive and adaptive memory formation by NPY receptors activation.

Estimation of thermal stresses in the field test under the restraint method

Abstract The restraint degree of the early-age concrete structure is an important factor for the generation of the thermal stress. When the concrete cannot deform freely as a result of the restrained deformation, the thermal stress, will generate until it increases to the degree that is great enough to affect the service life and safety of the concrete structure. Therefore, a new prediction method based on the time-restraint is proposed in this study. In the field test, a combination of the strain history of the newly cast concrete wall and the linear logarithmic creep model was adopted to calculate the thermal stresses. Compared with the traditional method, the complex structural restraint development can be described by a restraint model. The restraint coefficient of a specified location in the concrete wall changes from complete restraint to non-complete restraint, which can be transformed into a function of restraint coefficient related to the curing age. Compared with previous restraint evaluations, the restraint model reflects the restraint development of early-age concrete structures more authentically. Combined with the new restraint model, the thermal stress can be estimated with the completely restrained stress.

Molecular docking of thiamine reveals similarity in binding properties between the prion protein and other thiamine-binding proteins

Prion-induced diseases are a global health concern. The lack of effective therapy and 100% mortality rates for such diseases have made the prion protein an important target for drug discovery. Previous NMR experimental work revealed that thiamine and its derivatives bind the prion protein in a pocket near the N-terminal loop of helix 1, and conserved intermolecular interactions were noted between thiamine and other thiamine-binding proteins. Furthermore, water-mediated interactions were observed in all of the X-ray crystallographic structures of thiamine-binding proteins, but were not observed in the thiamine-prion NMR study. To better understand the potential role of water in thiamine-prion binding, a docking study was employed using structural X-ray solvent. Before energy minimization, docked thiamine assumed a "V" shape similar to some of the known thiamine-dependent proteins. Following minimization with NMR-derived restraints, the "F" conformation was observed. Our findings confirmed that water is involved in ligand stabilization and phosphate group interaction. The resulting refined structure of thiamine bound to the prion protein allowed the 4-aminopyrimidine ring of thiamine to π-stack with Tyr150, and facilitated hydrogen bonding between Asp147 and the amino group of 4-aminopyrimidine. Investigation of the π-stacking interaction through mutation of the tyrosine residue further revealed its importance in ligand placement. The resulting refined structure is in good agreement with previous experimental restraints, and is consistent with the pharmacophore model of thiamine-binding proteins.

An unexpected increase in restraint duration alters the expression of stress response habituation

While habituation develops to a repeated psychological stressor, manipulating certain parameters of the stress challenge experience may lead to dishabituation of the stress response. In this experiment, we investigated whether the behavioral, endocrine, and neural responses (c-fos mRNA immediate early gene expression) to a psychological stressor (restraint) differ when the duration of the stressor given on the test day violates expectations based on prior stress experience. Rats experienced 10 min of daily restraint on Days 1-4 followed by a challenge with either the same duration (10 min) or a longer duration (30 min) of restraint on Day 5. Rats' behavior was video recorded during the Day 5 restraint episode, and trunk blood and brain tissue were collected 30 min following restraint onset. Struggling behavior was manually scored as active attempts to escape the restraint device. Rats who experienced the same duration of repeated restraint showed a significant decrease of plasma corticosterone (CORT) compared to the 10 min acute restraint group (habituation). In addition, these rats showed decreased active struggling over repeated restraint trials. Conversely, the rats showed an increased CORT response (dishabituation) when they experienced a longer duration of restraint on Day 5 than they had previously. These rats showed a habituated behavioral response during the first 10 min of restraint, however struggling behavior increased once the duration of restraint exceeded the expected duration (with a peak at 12 min). This peak in struggling behavior did not occur during 30 min acute restraint, indicating that the effect was related to the memory of previous restraint experience and not due to a longer duration of restraint. In contrast, these animals showed habituated c-fos mRNA expression in the paraventricular nucleus (PVN), lateral septum (LS), and medial prefrontal cortex (mPFC) in response to the increased stressor duration. Thus, there was a dissociation between c-fos mRNA expression in key stress responsive brain regions and the behavioral and endocrine response to increased stressor duration. This dissociation may have been due to a greater lag time for c-fos mRNA responses to reflect the impact of a dishabituation response. In conclusion, habituation of the endocrine and behavioral stress response occurred when the duration of the stressor matches the previous experience, while dishabituation of the stress response was triggered (with remarkable temporal precision) by an unexpected increase in stress duration.

Facilitating influence of stress on the consolidation of fear memory induced by a weak training: Reversal by midazolam pretreatment

It is well known that an emotionally arousing experience usually results in a robust and persistent memory trace. The present study explored the potential mechanisms involved in the influence of stress on the consolidation of a contextual fear memory in animals subjected to a weak fear training protocol, and whether pretreatment with intra-basolateral amygdala or systemic administration of midazolam (MDZ) prevents the potential stress-induced influence on fear memory formation. A previous restraint session facilitated fear retention, this effect was not due to a sensitized effect of restraint on the footshock experience. MDZ, both systemically or intra-basolateral amygdala infusion prior to the restraint, attenuated the stress-induced promoting influence on fear memory formation. In addition, stress exposure activated the ERK1/2 pathway in basolateral amygdala (BLA) after the weak training procedure but not after the immediate footshock protocol. Similar to our behavioral findings, MDZ attenuated stress-induced elevation of phospho-ERK2 (p-ERK2) in BLA following the acquisition session. Given that the activation of ERK1/2 pathway is essential for associative learning, we propose that stress-induced facilitation of p-ERK2 in BLA is an important mechanism for the promoting influence of stress on the consolidation of contextual fear memory.

Constitutional illusions and anchoring truths: the touchstone of the natural law

Introduction: the anchoring common sense and the puzzles of the law 1. On the novelties of an old constitution: settled principles and unsettling surprises 2. The natural law - again, ever 3. Lochner and the cast of our law 4. The strange case of prior restraint: the Pentagon Papers 5. Near revisited 6. The saga of Frank Snepp and the new regime of previous restraints 7. And yet ... a good word on behalf of the legal positivists 8. Conclusion and afterword.

Training Staff in an Adolescent Inpatient Psychiatric Unit in Positive Approaches to Managing Aggressive and Harmful Behaviour: Does it Improve Confidence and Knowledge?

This study examined the implementation of a model of managing aggressive and harmful behaviour in an adolescent in-patient psychiatric unit. This model, Positive Behaviour Management, replaced a previous model, Control and Restraint, which was considered unsuitable. Both models included the use of physical interventions, and the research into such techniques is considered. The aims of the study were to evaluate the effects of three training courses on staff confidence in managing aggressive behaviour, knowledge about good practice and staff satisfaction with the new model. A multiple baseline design was used to examine change before, during and after the training period, and at one-year follow-up. The study found that staff confidence increased significantly following training but had returned to baseline levels by the time of follow-up. Staff knowledge significantly increased during the study periods but did not appear to be directly linked to the training courses, and was maintained at one-year follow-up. Staff reported significantly higher levels of satisfaction with the new model than with the previous model, which were maintained at follow-up. The findings of the study and the difficulties encountered are discussed in relation to similar findings elsewhere.

Inhibition of restraint stress‐induced neural and behavioural activation by endogenous cannabinoid signalling

The role of endocannabinoid (eCB) signalling in restraint stress-induced neuronal activation was studied. Male mice exposed to 30 min of restraint exhibit increased Fos protein within prefrontal cortex (PFC), lateral septum (LS), nucleus accumbens (Acb) and medial amygdala. SR141716 (2 mg/kg) itself had no effect on Fos but pretreatment with SR141716 significantly potentiated restraint-induced Fos expression in cingulate, LS and Acb. SR141716 also significantly increased the time spent in active escape behaviours during the restraint. In restraint-habituated mice (mice exposed to four previous restraint episodes), the fifth restraint exposure resulted in decreased expression of active escape behaviours compared to the first exposure and only induced Fos protein in the central and medial amygdala. Administration of SR141716 prior to the fifth restraint episode resulted in greater potentiation of restraint-induced Fos induction than the first; significant increases occurred within all regions of PFC examined, LS and Acb. Brain regional eCB content was measured immediately after restraint. N-arachidonylethanolamine content within the amygdala was significantly decreased after both restraint episodes. 2-Arachidonylglycerol content was significantly increased in both the limbic forebrain and amygdala after the fifth restraint but not the first. Restraint had no effect on cerebellar eCB content. These data suggest that eCB activation of CB(1) receptors opposes the behavioural and neuronal responses to aversive stimuli. Because repeated homotypic stress increased both limbic 2-AG and resulted in a greater effect of SR141716 on limbic Fos expression, we hypothesize that increased CB(1) receptor activity contributes to the expression of habituation to homotypic stress.

Psychiatric nurses expressed conflicting feelings in the decision to use physical restraints

(2000) J Adv Nurs 31, 362. Marangos-Frost S, Wells D. . Psychiatric nurses' thoughts and feelings about restraint use: a decision dilemma . . . Feb; . : . –9....

C-fos expression, behavioural, endocrine and autonomic responses to acute social stress in male rats after chronic restraint: modulation by serotonin

The effects in male rats of serotonin depletion (using the neurotoxin 5,7-dihydroxytryptamine) on the cross-sensitization of an acute social stress (defeat by a larger resident male) by previous repeated restraint stress (10 days, 60 min per day) was studied. Previous restraint increased freezing responses during social defeat in sham-operated rats, but this was not observed in those with depleted serotonin (83% or more in different regions of the brain). In contrast, neither heart rate (tachycardia) nor core temperature responses (hyperthermia) were accentuated in previously restrained rats (i.e. neither showed heterotypical sensitization), and neither adapted to repeated restraint (there is a hypothermic core temperature response during restraint). Corticosterone levels, which did adapt, nevertheless did not show accentuated responses to social defeat in previously restrained rats, though samples could only be taken 60 min after defeat. c-fos expression in the central nucleus of the amygdala 60 min after social defeat was increased by previous restraint. No other areas examined in the hypothalamus (e.g., paraventricular nucleus) or brainstem (e.g., solitary nucleus) showed differences related to previous restraint. Serotonin depletion reduced the expression of c-fos in the frontal cortex, lateral preoptic area, medial amygdala, central gray, medial and dorsal raphe, and locus coeruleus after social stress, but this was not altered by previous restraint. These results show that serotonin depletion has selective effects on the cross-sensitization of responses in previously stressed rats to a heterotypical stressor.

Importance of histamine H 2 receptors in restraint-morphine interactions

The effects of the brain-penetrating H2 antagonist zolantidine (ZOL, 3 mg/kg, s.c.) were studied on morphine (MOR, 4 mg/kg, s.c.) antinociception (tail flick test) in the presence and absence of previous restraint stress. Animals were handled for 3 days (to reduce handling stress), restrained for 1 hr or handled on day 4, and tested 24 hrs later. As found previously, restraint enhanced the intensity and duration of MOR antinociception. ZOL potentiated MOR antinociception in handled, non-restrained animals, but inhibited MOR action in restrained animals. In contrast, ZOL had no effects on nociceptive responses in either handled or stressed subjects in the absence of MOR. The data suggest that, in the absence of restraint, brain HA acts at the H2 receptor to inhibit MOR antinociception. In contrast, when an animal has been previously restrained, HA enhances MOR antinociception. Thus, brain HA appears to mediate the restraint-induced potentiation of MOR antinociception. Taken with previous results, the present findings suggest that in the presence of MOR, brain HA can provide bidirectional modulation of nociception. The direction of the modulation seems to depend upon the stress experience of the animal.

Effects of housing, restraint and chronic treatments with mCPP and sertraline on behavioural responses to mCPP.

The effects of pretreatments on behavioural responses to activation of 5-HT1C receptors by m-chlorophenylpiperazine (mCPP) were investigated. The hypo locomotor and anxiogenic effects of mCPP (social interaction test) were influenced neither by previous housing (single versus grouped) nor by restraint (2 h, 24 h previously). In the absence of mCPP, 24 h group housing led to decreased social interaction and the restraint procedure led to significant decreases of feeding and locomotion. The hypophagic effect of mCPP was unaffected by previous restraint. However, chronic pretreatment with mCPP (2.5 mg/kg per day IP x 14) or with the antidepressant 5-HT reuptake inhibitor sertraline (5 mg/kg per day SC x 14) attenuated all three behaviours. The above findings are discussed with respect to published data on effects of pretreatments on responses to the activation of 5-HT1C receptors.

Hippocampal 5-HT receptors and consolidation of stressful memories.

It has been suggested that postsynaptic 5-HT1A receptors in the hippocampus, innervated by 5-HT neurons localized in the median raphe nucleus, mediate adaptive or coping responses to aversive events and that dysfunction of this system is related to symptoms of depression. To test this hypothesis we investigated the expression of c-fos mRNA in animals submitted to immobilization stress. The results showed that c-fos mRNA expression is significantly increased in the dentate gyrus and CA1-CA3 regions of the hippocampus after 30 min of forced restraint, suggesting that this structure is activated during stress. To investigate the role of 5-HT neurotransmission in the hippocampus on adaptation to aversive events we immobilized rats for 2 h and tested them 24 h later in an elevated plus-maze. Our results showed that the previous restraint period decreases exploration of open arms in the maze. This effect was reversed by bilateral microinjection of zimelidine (20 and 100 nmol), a 5-HT re-uptake blocker, or 8-OH-DPAT (3 nmol), a 5-HT1A agonist, into the dorsal hippocampus immediately after restraint. These results are compatible with the idea that postsynaptic 5-HT1A receptors located in the hippocampus participate in the development of tolerance to aversive events.

Homogeneous Structures Subjected to Repeated Structural System Changes

In this paper the creep effects in structures subjected to successive structural system changes are analyzed. The problem is related to structures that develop their structural system from statically determinate to indeterminate, with a gradual increase in the number of redundant restraints introduced at different times. Assuming a linear creep law, the stress redistribution caused by creep in the structure for each stage is evaluated. Writing the compatibility equation at the last restraint introduced, a recurrent formula for the history of redundant reaction is derived. The general solution is proposed as the sum of elastic quantities multiplied by integral terms (which take the creep effects into account) that are the same as the simple case where the additional restraints are introduced all together. The method presented demonstrates that, at all stages, the reaction at the last restraint does not depend on the introduction times of the previous restraints. This reaction is determined by a particular Volterra integral equation solved by numerical procedures of the general method.

Cable Television and Libraries

The cable television industry began to expand greatly in the 1970s as a consequence of several court decisions forcing the Federal Communications Commission to lift its previous restraints. Originally, cable had been seen chiefly as a means to improve reception in isolated areas. Today, however, this same cable has revolutionized what we have come to see on television.

Fundamental Liberties of a Free People. Religion, Speech, Press, Assembly

This is critical rather than technical examination of the freedoms which are analogous with America: freedom of religion, freedom of speech, and others. Konvitz covers such topics as obscene literature, labor dispute picketing, previous restraint, police power, freedom not to speak, etc.

The Meiji Political Novel: A Brief Survey

FROM a purely objective point of view, the study of the political novel in any period of history is useful because of the inherent value of that particular type of novel portrayal of the political ideology of its time and presentation of its authors' political opinions. This is especially true with reference to the political novel in Japan's Meiji era. The Restoration had shifted the balance of power; Western influence was strong; Japan was emerging from her self-imposed seclusion. In the first flush of her breakaway from previous restraints and before new ones could be devised and stringently enforced Japan's political thought as expressed in the literary vehicle specifically designed for it presents perhaps a truer index of the feelings of the literate classes than does the governmental mechanism which was evolved at that time, inasmuch as one of the avowed purposes of a novel is to appeal to its audience, a point not included in Japanese governmental tradition. This being the general trend in the Far East, the most important medium even the only medium through which the articulate could register their objections and their own thoughts has been literature. Certainly one of the most important causes for the Western belief that the Oriental is phlegmatic and mysterious is that so little study has been made of his writings, the only possible channel for his outpourings. Meiji culture saw that collision of the ancient Confucian tradition with the West's spirit of innovation. Oppressed by the old-time political organization, many of the thinking people of Meiji yearned for objectives which perhaps they could not fully comprehend, but which they knew of and wanted because they linked them with the new and wonderful West independence, freedom, equal rights. And it was in Western society, politics, literature, and fine arts that they saw the concrete appearance of their ideals. Therefore, the first literary movement which we see in Meiji,

Previous Restraints upon Freedom of Speech

Previous Restraints upon Freedom of Speech