cssi/SciSciGPT-SciSciNet huggingface dataset:
Heterogeneity and ontogenesis of progestin receptors in rabbit lung.

Abstract In order to evaluate the possible role of progesterone in fetal lung development, the presence of specific pulmonary progestin receptors and their ontogenesis were investigated in the rabbit fetus. Scatchard analysis of binding in lung cytosol from 29-day fetuses over a wide range of [ 3 H]-R5020 concentrations indicates the presence of at least two binding sites. One of these sites, type I, is of very high affinity ( K D = 0.12 nM) and low capacity (26fmol per mg protein). The second binding site, type II, is of lower affinity ( K D = 36 nM) and higher capacity (240 fmol per mg protein). These two binding sites can be distinguished by sucrose density gradient centrifugation, the type I component sedimenting at 7.1 S and the type II component sedimenting at 4.5 S. Similar type I and type II sites are present in adult lung cytosol except that the type II binding component in adult lung sediments at 2.8 S rather than 4.5 S. Progesterone and R5020 compete well with [ 3 H]-R5020 for binding to both sites while dexamethasone and cortisol do not compete. Thus the type I and type II binding sites appear to represent specific progestin receptors distinct from transcortin or the glucocorticoid receptor. The concentration of the type I sites increases significantly between the 20th and 29th day of gestation, with a further increase being observed in adult animals. The type II site is not measurable until 26 days of gestation and attains adult levels by day 29. Among a large number of fetal tissues examined, the lung contained the highest concentration of type I progestin receptor sites. Although cortisol and dexamethasone, even at very high concentrations, do not compete with [ 3 H]-R5020 for binding to lung cytosol, the binding of [ 3 H]-dexamethasone is inhibited significantly by nonlabeled progesterone or R5020 and this inhibition appears to be due to dissociation of [ 3 H]-dexamethasone-receptor complexes. These results indicate that, in addition to type I and type II progestin receptor sites, fetal lung cytosol contains a third binding site, type III, which appears to be different from the glucocorticoid receptor site. Occupation of the type III site by progestins interferes with the binding of glucocorticoids to glucocorticoid receptors perhaps by increasing the rate of dissociation of glucoeortieoid-receptor complexes.
The inactivation of succinate dehydrogenase by bromopyruvate.

Abstract 1. 1. Bromopyruvate has been found to be a potent irreversible inhibitor of succinate dehydrogenase (succinate:(acceptor) oxidoreducatase, EC 1.3.99.1). While the kinetics of inactivation show a saturation effect, they do not fit the simple model for an active-site-directed irreversible inhibitor. Instead, a concentration dependent plateau is observed. A similar phenomenon occurs when N- ethylmaleimide is the alkylating agent. Reversible inhibitors and substrates protect succinate dehydrogenase from activation by bromopyruvate and N- ethylmaleimide . Both reagents have similar relative reactivities toward the enzyme and 2-nitro-5-thiolbenzoic acid dianion. 2. 2. The absorption and dithionite bleaching spectra are not greatly affected by the reaction of enzyme with bromopyruvate, but the ability of succinate to bleach is lost. A decrease in hydrogen exchange capacity parallels the decrease in assay activity.
On Frustration Effects in Accident Behavior

Drake (1940) developed the hypothesis that individuals who react more quickly than they perceive are more likely to have accidents than are individuals who perceive more quickly than they react. In addition, several studies suggest the relevance of emotional factors in accidents; however, their precise nature is not indicated. Frustration theory (Maier, 1939) would appear to provide a sufficiently precise approach to fruitful investigation of certain emotional factors and the means for experimental manipulation of relevant factors in Drake's perceptual speed-motor speed ratio hypothesis. Each of 17 male Ss was given approximately 200 trials on an appararus which called for a precise and delicate motor response to a visual problem. Colored dots, 4/4 in. in diameter and 1% in. apart horizontally, were presented in pairs, one pair ac a time. Ss were to discover, by pressing one or the other of two buttons and noting the occurrence or absence with each trial of shock to the right foot, the ordered scheme of stimulus presentation. In addition, Ss were instructed, and given 10 practice trials, that insufficient pressure would fail to turn off a red signal light and that too much would yield shock to the foot. One S discovered the solution and was eliminated from further trials. Data from the remaining 16 Ss indicate that with continued failure to solve the visual problem, (a) "hypotheses" as to the solution tended to become simpler and (b) motor responses, as measured by shock frequency and kymograph recordings, increased in variability and intensity. Nevertheless, the experiment is merely exploratory and cannot be considered a valid test of frustration effects since there was no evidence either from observation or in the data, that the frustration threshold for any S was exceeded. Frustration effects on perception using three-dimensional stimuli must be studied, as must the effects on motor functions, under conditions of exceeded frustration thresholds.
Microstructural analysis of rapid solidification and undercooling in the Al-Ge system

Submicron powders, amorphous films and melt spun ribbons of various Al-Ge alloys have been analyzed to determine the relative roles of undercooling and cooling rate in the production of non-equilibrium structures. All analyses were performed in transmission electron microscopes equipped with energy dispersive x-ray spectrometers. The submicron powders, produced by electro-hydrodynamic atomization, were analyzed in their as-received condition and then annealed and/or melted using the electron beam as a local heating source. Once molten, the liquid droplets were undercooled at different cooling rates by varying the rate of beam obstruction. In this manner, a number of different microstructures were produced. These included metastable crystalline phases and mixed amorphous/crystalline structures. By combining this technique with a microscope heating stage, it was possible to carry out controlled dynamic undercooling experiments and determine phase selection as a function of undercooling and composition. The amorphous films were rapidly heated with the electron beam in the microscope and metastable as well as stable phases were produced. The results of these complementary analyses will be compared and discussed with reference to current models and theories of rapid solidification.
Strengthening of local vital events registration: lessons learnt from a voluntary sector initiative in a district in southern India

Problem Birth and death registration rates are low in most parts of India. Poor registration rates are due to constraints in both the government system (supply-side) and the general population (demand-side). Approach We strengthened vital event registration at the local level within the existing legal framework by: (i) involving a non-profit organization as an interface between the government and the community; (ii) conducting supply-side interventions such as sensitization workshops for government officials, training for hospital staff and building data-sharing partnerships between stakeholders; (iii) monitoring for vital events by active surveillance through lay-informants; and (iv) conducting demand-side interventions such as publicity campaigns, education of families and assistance with registration. Local setting In the government sector, registration is given low priority and there is an attitude of blaming the victim, ascribing low levels of vital event registration to “cultural reasons/ignorance “. In the community, low registration was due to lack of awareness about the importance of and procedures for registration. Relevant changes This initiative helped improve registration of births and deaths at the subdistrict level. Vital event registration was significantly associated with local equity stratifiers such as gender, socioeconomic status and geography. Lessons learnt The voluntary sector can interface effectively between the government and the community to strengthen vital registration. With political support from the government, outreach activities can dramatically improve vital event registration rates, especially in disadvantaged populations. The potential relevance of the data and the data collection process to stakeholders at the local level is a critical factor for success.
Relative GPS Carrier-Phase positioning using particle filters with position samples

In this paper, the problem of precise relative positioning using GPS (Global Positioning System) Carrier-Phase (CP) information is addressed. The unknown cycle ambiguity between GPS satellites and antennas at the moment of receiving the CP signal should be resolved for precise navigation. The sequential Monte Carlo filter approach, called particle filter (PF), is applied to the relative positioning problem which includes the ambiguity resolution problem for the CP nonlinear observation and dynamic equations. The proposed algorithm of GPS CP navigation is based on two main factors. First, even though most existing GPS CP navigation algorithms focus on obtaining the correct integer value among the integer candidates, we directly sample from the three dimensional position space and construct integers consistent with the PF. This allows the PF position estimates to be insensitive to changes of GPS satellites and cycle-slips. Second, the potential large number of samples in position space is handled with the resampling technique in the sequential particle filters. The experimental results show the performance and the advantages of the proposed approach compared to the existing methods.
Stereoselective synthesis of macrocyclic peptides via a dual olefin metathesis and ethenolysis approach

Macrocyclic compounds occupy an important chemical space between small molecules and biologics and are prevalent in many natural products and pharmaceuticals. The growing interest in macrocycles has been fueled, in part, by the design of novel synthetic methods to these compounds. One appealing strategy is ring-closing metathesis (RCM) that seeks to construct macrocycles from acyclic diene precursors using defined transition-metal alkylidene catalysts. Despite its broad utility, RCM generally gives rise to a mixture of E- and Z-olefin isomers that can hinder efforts for the large-scale production and isolation of such complex molecules. To address this issue, we aimed to develop methods that can selectively enrich macrocycles in E- or Z-olefin isomers using an RCM/ethenolysis strategy. The utility of this methodology was demonstrated in the stereoselective formation of macrocyclic peptides, a class of compounds that have gained prominence as therapeutics in drug discovery. Herein, we report an assessment of various factors that promote catalyst-directed RCM and ethenolysis on a variety of peptide substrates by varying the olefin type, peptide sequence, and placement of the olefin in macrocycle formation. These methods allow for control over olefin geometry in peptides, facilitating their isolation and characterization. The studies outlined in this report seek to expand the scope of stereoselective olefin metathesis in general RCM.
Graded representations in behavioral dissociations

Why do people sometimes seem to know things when they are tested in one way, while seeming unaware of this information when tested in a different way? Such task-dependent behaviors, or dissociations, often occur in infants and children, and in adults following brain damage. To explain these dissociations, researchers have posited separable knowledge systems that are differentially tapped by various tasks, develop at different rates and can be selectively impaired. There is an alternative account in which knowledge is viewed as graded in nature. Certain tasks tap weaker representations, while other tasks require stronger representations, leading to dissociations in behavior. The graded representations approach addresses dissociations observed in perception, attention, memory, executive functioning and language, and has implications for the organization, development and impairment of our cognitive systems.
Verified hybrid controllers for automated vehicles

The objective of an automated highway system (AHS) is to increase the safety and throughput of the existing highway infrastructure by introducing traffic automation. AHS is an example of a large scale, multiagent complex dynamical system and is ideally suited for a hierarchical hybrid controller. We discuss the design of safe and efficient hybrid controllers for regulation of vehicles on an AHS. We use game theoretic techniques to deal with the multiagent and multiobjective nature of the problem. The result is a hybrid controller that by design guarantees safety, without the need for further verification. The calculations also provide an upper bound on the performance that can be expected in terms of throughput at various levels of centralization.
Small-molecule costimulatory blockade: organic dye inhibitors of the CD40-CD154 interaction.

Costimulatory blockade is one of the most promising therapeutic targets in autoimmune diseases as well as in transplant recipients, and inhibition of the cluster of differentiation (CD)40–CD154 interaction, which is required for T cell activation and development of an effective immune response, is particularly promising in islet transplant recipients. Here, we report the ability of several small-molecule organic dyes to concentration dependently inhibit this interaction with IC50 values in the low-micromolar range. They were found to be considerably more active in inhibiting this interaction than the tumor necrosis factor (TNF)-R1-TNF-α or B cell-activating factor (BAFF)-R-BAFF interaction, which are members of the same family. They specifically inhibited CD154-induced cell responses in human B cells as well as in THP-1 myeloid cells, which can serve as surrogate dendritic cells, at concentrations well below their cytotoxic concentrations determined in the same cells. Flow cytometry experiments confirmed their ability to inhibit the CD154-induced, but not the Staphylococcus aureus Cowan I- or phorbol 12-myristate 13-acetate-induced increase in the surface expression of CD54, CD40, and major histocompatibility complex class II. Accordingly, these compounds can be useful not only for experimental investigations involving the inhibition of the CD40–CD154 costimulatory interaction but can also provide important structure–activity relationship information and can serve as the starting point of a targeted drug discovery program.
INTERACTIONS BETWEEN ANGIOTENSIN II AND THE SYMPATHETIC NERVOUS SYSTEM IN THE THE LONG-TERM CONTROL OF ARTERIAL PRESSURE

SUMMARY 1. The role of the renin-angiotensin system in long-term control of sympathetic activity and arterial pressure is reviewed. 2. There is evidence that favours a necessary role for the sympathetic nervous system in long-term arterial pressure regulation. First, appropriate changes in sympathetic activity appear to be produced in response to chronic changes in blood volume or blood pressure. Second, prevention of the normal homeostatic decrease in sympathetic activity in response to an increase in sodium intake produces hypertension. 3. Long-term changes in sympathetic activity cannot be mediated by the baroreceptor reflex, because it adapts to sustained changes in pressure. Therefore, an hypothesis is presented that evokes a key role for angiotensin II (AngII) in determining the chronic level of sympathetic activity. The key feature of this model is that the role of AngII is non-adaptive: chronic changes in extracellular fluid volume produce sustained reciprocal changes in AngII, and long-term increases in AngII produce sustained increases in sympathetic activity. 4. Evidence is reviewed that suggests that a lack of the normal suppression in AngII and/or sympathetic activity in response to an increase in sodium intake produces salt-sensitive hypertension.
Developing policy, standard orders, and quality-assurance monitoring for palliative sedation therapy

Purpose The development of a policy, evidence-based standard orders, and monitoring for palliative sedation therapy (PST) is described. Summary Concerns regarding PST at the University of Minnesota Medical Center (UMMC) arose and needed to be addressed in a formal process. A multidisciplinary group consisting of palliative care physicians, nurse practitioners, clinical nurse specialists, and clinical pharmacy specialists reached consensus on the practice model and medications to be used for PST. Major elements of the plan included the development and implementation of an institutional policy for palliative sedation; standard orders for patient care, sedation, and monitoring; education for staff, patients, and patients’ family members; and quality-assurance monitoring. A literature review was performed to identify research and guidelines defining the practice of PST. Policy content includes the use of a standard order set linking patient care, medication administration, the monitoring of sedation, and symptom management. Approval of the policy involved several UMMC committees. An evaluation matrix was used to determine critical areas for PST monitoring and to guide development of a form to monitor quality. A retrospective chart audit using the quality-assurance monitoring form assessed baseline sedation medication and patient outcomes. Assessment of compliance began in the fall of 2008, after the policy and standard orders were approved by the UMMC medical executive committee. In 2008, two cases of PST were monitored using the standardized form. PST cases will be continually monitored and analyzed. Conclusion Development of policy, standard orders, and quality-assurance monitoring for PST required a formal multidisciplinary process. A process-improvement process is critical to defining institutional policy, educational goals, and outcome metrics for PST.
Ethical Conflict and Moral Compromise in Pharmacy

SUMMARYAlthough ethical reasoning and analysis may occasionally resolve or reduce ethical conflict, it cannot eliminate it. Some degree of rationally irreconcilable conflict among conscientious, reasonable individuals is unavoidable in free democratic societies. Under what circumstances, then, and for what reasons may individuals accept a compromise solution to an ethical conflict without compromising (or betraying) their moral integrity? After examining the concept of compromise, I show how and why compromise in ethics may, in some circumstances, be integrity-preserving. I conclude by indicating three ways in which this notion of integrity-preserving compromise may be applicable to the ethics of pharmaceutical care.
Women’s Preference for Masculine Traits Is Disrupted by Images of Male-on-Female Aggression

Women’s preferences for men’s masculinized faces and voices were assessed after women (n=331) were primed with images of male-on-male aggression, male-on-female aggression, pathogens, and neutral scenes. Male-on-male aggression and pathogen primes were associated with increased preference for masculine traits, but the same effect emerged in the neutral condition. We show the increased preference for masculine traits was due to repeated exposure to these traits, not the priming images themselves. Images of male-on-female aggression were an exception; these elicited feelings of disgust and anger appeared to disrupt the preference for masculinized traits. The results suggest women process men’s facial and vocal traits as signals of aggressive potential and lose any preference for these traits with cues indicating men might direct this aggression toward them.
The City Manager Plan, the Latest in American City Government.

Scarcely have we become accustomed to the thought that commission government for American cities, unknown fifteen years ago, has taken a permanent and important place in our municipal development when we hear on all sides discussion of a still newer form called the city manager plan. To judge from present indications it seems not unlikely that the phenomenal spread of the commission form will be repeated in the case of this latest development. It becomes a matter of interest therefore to examine into this innovation in American municipal government and to see what elements of strength and weakness it may show and how it is related to our other forms. If we regard as the essential characteristics of commission government the union of all powers of the city, legislative and administrative, in the hands of a small body of men, each one charged with the responsibility for the proper administration of one of the departments, we may characterize the city manager form by stating that the immediate duty of directing the administration of the city's affairs is imposed upon a single, professional official chosen by the representative body of the city.
Pilot-assisted 16-level QAM for wireless video

This paper presents a twin-class transmission system for narrowband radio access channels suitable for handheld video phone and multimedia portable PC applications. The transmission system is comprised of a hierarchical 16-QAM modulation technique and a channel-coding scheme. The formation of dual-priority transmission is due to differing error resiliencies of the bits that make up a given symbol in a Gray-coded 16-QAM. On this basis, a twin-class pilot-assisted fade-estimation technique that can gracefully reduce the power loss caused by the transmission of pilot overhead is developed. The twin-class 16-QAM system is then used to transport a compressed video bitstream, which is partitioned to match the bit-error sensitivity of the transmitted symbol. The partitioning scheme is based on a separation of the variable-length (VL) coded discrete cosine transform (DCT) coefficients within each DCT block. This partitioning scheme is then applied to split the ITU-T H.263-coded bitstream. The scheme is suitable for constant bit-rate transmission (CBR), where the fraction of bits assigned to each of the two partitions can be adjusted according to the requirements of the unequal error protection scheme employed. The distribution of the VL-coded (VLC) information amongst the two partitions is performed adaptively. Finally, the performance of the partitioning scheme for transmission of video signals using our twin-class 16-QAM transmission system is evaluated under multipath fading conditions.
The Future of Cancer Screening

Lung and ovarian cancers are two of the most common and deadly cancers affecting men and women in the United States. The potential impact of an effective screening modality for early detection of these cancers is enormous. Yet, to date, no screening tool has been proven to reduce mortality in asymptomatic individuals, and no major organization endorses current modalities for screening for these cancers. Novel approaches, potentially relying on genomics and proteomics, may be the future for early detection of these deadly cancers.
Through the Glass Darkly: New Paradigms for Counselors, Courage, and Spirituality in Contemporary Education

This article proposes a paradigm shift in the view of the school counselor role. Evolving from the dualistic mind/body split of traditional physics, counseling has largely focused on problem identification and attempting to fix what is wrong. The new sciences of chaos and complexity invite a more holistic view, with the psychospiritual development of all students seen as an appropriate part of a comprehensive education. School counselors are well placed to mentor the psychospiritual development of all students and to facilitate the presence of spirituality on school sites. Two complementary models, Courage to Teach/Lead and the Ignatian model of Spiritual Discernment are presented with discussion of how their principles and practices might be applied by counselors engaged in this role shift.
Mechanisms of Egg Yolk Formation and Implications on Early Life History of White Perch (Morone americana)

The three white perch (Morone americana) vitellogenins (VtgAa, VtgAb, VtgC) were quantified accurately and precisely in the liver, plasma, and ovary during pre-, early-, mid-, and post-vitellogenic oocyte growth using protein cleavage-isotope dilution mass spectrometry (PC-IDMS). Western blotting generally mirrored the PC-IDMS results. By PC-IDMS, VtgC was quantifiable in pre-vitellogenic ovary tissues and VtgAb was quantifiable in pre-vitellogenic liver tissues however, neither protein was detected by western blotting in these respective tissues at this time point. Immunohistochemistry indicated that VtgC was present within pre-vitellogenic oocytes and localized to lipid droplets within vitellogenic oocytes. Affinity purification coupled to tandem mass spectrometry using highly purified VtgC as a bait protein revealed a single specific interacting protein (Y-box binding protein 2a-like [Ybx2a-like]) that eluted with suramin buffer and confirmed that VtgC does not bind the ovary vitellogenin receptors (LR8 and Lrp13). Western blotting for LR8 and Lrp13 showed that both receptors were expressed during vitellogenesis with LR8 and Lrp13 expression highest in early- and mid-vitellogenesis, respectively. The VtgAa within the ovary peaked during post-vitellogenesis, while VtgAb peaked during early-vitellogenesis in both white perch and the closely related striped bass (M. saxatilis). The VtgC was steadily accumulated by oocytes beginning during pre-vitellogenesis and continued until post-vitellogenesis and its composition varies widely between striped bass and white perch. In striped bass, the VtgC accounted for 26% of the vitellogenin-derived egg yolk, however in the white perch it comprised only 4%. Striped bass larvae have an extended developmental window and these larvae have yolk stores that may enable them to survive in the absence of food for twice as long as white perch after hatch. Thus, the VtgC may play an integral role in providing nutrients to late stage fish larvae prior to the onset of exogenous feeding and its composition in the egg yolk may relate to different early life histories among this diverse group of animals.
The Initial Magdalenian mosaic: New evidence from Urtiaga cave, Guipúzcoa, Spain

Abstract Transitional moments in prehistory are of broad interest in archaeology. Immediately following the Last Glacial Maximum, two technological shifts occurred in SW Europe: in France, at ∼18,000 uncal. BP, an industry characterized by large Solutrean projectiles was replaced by the well-defined Badegoulian industry; a thousand years later in Vasco-Cantabrian Spain, Solutrean technologies were gradually replaced by Magdalenian antler point ( sagaie ) and lithic inset composite weapons. The Solutrean–Magdalenian transition remains ill-defined in Vasco-Cantabria, where very few “transitional” assemblages dating to the c. 17–16,000 uncal. BP interval have been identified, leaving questions as to how the changes occurred and what kinds of relationships existed between French and Spanish groups during this period. Urtiaga cave (Guipuzcoa) Level F (17,050 ± 140 uncal. BP) contributes a new Initial Magdalenian archaeological sample to the discussion of Last Glacial behavioral change during a technological transition. This paper synthesizes the results of a detailed lithic analysis with findings from previous studies of fauna and osseous industry from Urtiaga Level F. Then, the analysis explores Initial Magdalenian organizational behaviors through a series of lithic procurement/mobility models that show dynamic land use in eastern Vasco-Cantabria. Finally, Urtiaga Level F was compared to four other Initial Magdalenian occupations in the region, demonstrating that lithic maintenance—in manufacture, use, and rejuvenation—was a significant factor in how Initial Magdalenian groups organized their landscape-level behavioral strategies. The archaeological assemblages from Urtiaga cave are important contributions to archaeological questions surrounding the Solutrean–Magdalenian transition, providing further evidence for in situ technological change in Vasco-Cantabria. Additionally, the economic analyses discussed in this paper provide new attributes that archaeologists can use to identify Initial Magdalenian sites on the landscape. This study develops a methodological procedure that is broadly applicable to archaeological studies related to prehistoric cultural transitions and to those studies that apply data from collections recovered during the early 20th century to modern interpretive frameworks.
Stenomastigus pseudofranzi sp. n., from South Africa (Staphylinidae, Scydmaeninae)

A new species of the endemic South African genus Stenomastigus Leleup (Staphylinidae, Scydmaeninae, Mastigini), S. pseudofranzi sp. n. is described. Because some morphological structures of the new species highly resemble those of S. franzi Leleup, description of the latter species is supplemented with previously unknown details of the aedeagus (includingthe copulatory piece). Habitus, aedeagi, modified fore legs of males and other diagnostic characters of both species are illustrated.
Familial cancer, emotional distress, and low natural cytotoxic activity in healthy women

Summary Background We investigated the possibility that healthy individuals with a family history of cancer may have lower levels of natural cytotoxic activity and examined the possible contribution of distress-induced immune suppression. Materials and methods Forty-three healthy women, recruited without regard to their family histories of cancer, came to the laboratory on two consecutive days. On each day, subjects completed questionnaires and provided blood samples for assessment of natural cytotoxic activity. Results 1) Women with a history of cancer in one or more first degree relatives had lower levels of natural cytotoxic activity than women without cancer in first degree relatives. 2) There were no differences in demographic, health, or behavioral variables, but we could not rule out differences in emotional distress. 3) Independent of family history, women with higher levels of distress had lower natural cytotoxic activity. 4) When the contribution of this distress-induced immune suppression was statistically removed, natural cytotoxic activity remained lower in women with cancer in first degree relatives. Conclusions These findings raise the possibility that reductions in systemic natural cytotoxic activity, in conjunction with heritable defects in the preneoplastic cell, may contribute to increased cancer risk in individuals with a family history of cancer.
Towards quantitative cutoffs for insomnia: how current diagnostic criteria mischaracterize remission

Abstract Objective Although sleep symptoms of insomnia can be quantified, none of the current diagnostic systems stipulate quantitative cutoffs for sleep-onset latency (SOL) or wake time after sleep onset (WASO). Diagnoses are based instead on idiographic patient reports of "difficulty" falling/staying asleep. Therefore, we examined whether remission of insomnia as per the diagnostic criteria results from a normalization of quantitative sleep disturbance, or if it is simply reflective of tolerance to sleep symptoms. Methods This study involved a yearlong prospective investigation of 649 adults (48.1 ± 11.6 years; 69.3% female) with DSM-5-based insomnia. Participants completed measures of sleep disturbance, perceived sleep-related distress, daytime sleepiness, functional impairment, and workplace productivity at baseline and follow-up one year later. Results A total of 271 participants no longer met the DSM-5-based insomnia criteria at follow-up. However, 66% of these remitters reported ≥31 min of SOL and/or WASO. Daytime impairment in this subgroup of remitters was no different from that among individuals who met the diagnostic criteria at both baseline and follow-up (ie, chronic insomniacs). By contrast, follow-up impairment was significantly lower ( F = 12.3; P Conclusion This is the first study on the long-term course of insomnia based on the newly established DSM-5 criteria. A troubling implication of findings is that a majority of insomniacs stop meeting the diagnostic criteria despite continued sleep disturbance and impairment. "Remission" in these cases is attributable instead to tolerance of sleep symptoms. Incorporating quantitative criteria into current diagnoses may offer a more sensitive assay of treatment needs.
Brief paper: Near optimal smoothing for singularly perturbed linear systems

A two time-scale lower order design is proposed as a near optimal solution to the fixed-interval smoothing problem for systems with slow and fast modes. The slow mode smoothing solution, in the limit as the perturbation parameter @m -> 0, tends to that of the reduced-order problem; and the near optimal fast mode smoother is simply a weighted sum of lower order two time-scale filters. While the near optimal solution affords a significant reduction in computational complexity, the performance degradation, as illustrated in an example, is typically negligible.
Mechanical damage of tympanic membrane in relation to impulse pressure waveform - A study in chinchillas.

Mechanical damage to middle ear components in blast exposure directly causes hearing loss, and the rupture of the tympanic membrane (TM) is the most frequent injury of the ear. However, it is unclear how the severity of injury graded by different patterns of TM rupture is related to the overpressure waveforms induced by blast waves. In the present study, the relationship between the TM rupture threshold and the impulse or overpressure waveform has been investigated in chinchillas. Two groups of animals were exposed to blast overpressure simulated in our lab under two conditions: open field and shielded with a stainless steel cup covering the animal head. Auditory brainstem response (ABR) and wideband tympanometry were measured before and after exposure to check the hearing threshold and middle ear function. Results show that waveforms recorded in the shielded case were different from those in the open field and the TM rupture threshold in the shielded case was lower than that in the open field (3.4 ± 0.7 vs. 9.1 ± 1.7 psi or 181 ± 1.6 vs. 190 ± 1.9 dB SPL). The impulse pressure energy spectra analysis of waveforms demonstrates that the shielded waveforms include greater energy at high frequencies than that of the open field waves. Finally, a 3D finite element (FE) model of the chinchilla ear was used to compute the distributions of stress in the TM and the TM displacement with impulse pressure waves. The FE model-derived change of stress in response to pressure loading in the shielded case was substantially faster than that in the open case. This finding provides the biomechanical mechanisms for blast induced TM damage in relation to overpressure waveforms. The TM rupture threshold difference between the open and shielded cases suggests that an acoustic role of helmets may exist, intensifying ear injury during blast exposure.
What Is Happening in Liberal Education

The very question – what is happening in liberal education, has a contemporaneity – something is happening – now – that represents, for better or worse, a departure from the past. We might lament this departure – what is happening in liberal education – or we might welcome it – what is happening in liberal education – but the question itself suggests a stable concept – liberal education – that is undergoing change.
A method for quantitative estimation of small amounts of D-tubocurarine chloride in plasma.

SummarySmall amounts of D-tubocurarine can be measured in plasma by extraction with ethylene dichloride and reaction with methyl orange. The plasma level for paralysis in rabbits is about 1.2 to 2.2 mg per liter.
Dual Stimuli-Responsive, Rechargeable Micropumps via “Host–Guest” Interactions

We demonstrate a supramolecular approach to the fabrication of self-powered micropumps based on “host–guest” molecular recognition between α- and β-cyclodextrin and trans-azobenzene. Both hydrogels and surface coatings based on host–guest partners were used as scaffolds to devise the micropumps. These soft micropumps are dual stimuli-responsive and can be actuated either by light or by introducing guest molecules. Furthermore, the micropumps can be recharged through reversible host–guest interaction.
In search of an antibody specificity highly predictive of congenital heart block.

Since the relationship of maternal autoimmunity and congenital heart block (CHB) was initially described in the late 1970s, investigators have attempted to identify additional factors associated with its development.1–4 Detection of CHB in the absence of cardiac structural abnormalities predicts the presence of maternal autoantibody responses against the ribonucleoproteins SSA/Ro and SSB/La in >85% of cases.5 CHB is associated with considerable morbidity and mortality, with a 17.5% case fatality rate and approximately 70% requiring permanent pacemaker placement.6 Sustained reversal of third-degree CHB has never been achieved and to date there is no approved medication for treatment or prevention of this disease. Recognising those mothers at increased risk of CHB in an offspring would provide insights into the pathogenesis of disease and help prioritise allocation of screening resources, including intense echocardiographic monitoring. In a recent publication in Lupus Science and Medicine , Tonello et al sought to identify maternal autoantibody profiles conferring high risk for CHB.7 Importantly, all serological evaluations were done during the pregnancies. The …
Physical Activity in Obesity and Diabetes

Type 2 diabetes mellitus (hereafter referred to as “diabetes”) is a common metabolic condition usually secondary to obesity (WHO Physical Activity Fact Sheet: World Health Organization; 2015 [updated Jan 2015; cited 2015 February 18]. Available from: http://www.who.int/mediacentre/factsheets/fs385/en/). In those with obesity and diabetes, sedentary lifestyle is a common finding and is importantly related to the development of cardiovascular morbidities and blood glucose dysregulation. In these individuals, impairments that arise due to obesity and diabetes, also create barriers to being active, setting up a vicious cycle that promotes sedentary behavior. Physical activity (PA) and avoidance of sedentary behaviors are key considerations for disease prevention and management in this population. This chapter will summarize the importance of physical activity interventions in obesity and diabetes, and also provide an overview of current evidence-based recommendations for PA prescription in this population.
Structure-Based Virtual Screening of Commercially Available Compound Libraries

Virtual screening (VS) is an efficient hit-finding tool. Its distinctive strength is that it allows one to screen compound libraries that are not available in the lab. Moreover, structure-based (SB) VS also enables an understanding of how the hit compounds bind the protein target, thus laying ground work for the rational hit-to-lead progression. SBVS requires a very limited experimental effort and is particularly well suited for academic labs and small biotech companies that, unlike pharmaceutical companies, do not have physical access to quality small-molecule libraries. Here, we describe SBVS of commercial compound libraries for Mer kinase inhibitors. The screening protocol relies on the docking algorithm Glide complemented by a post-docking filter based on structural protein-ligand interaction fingerprints (SPLIF).
Nonkeratinizing Squamous Cell Carcinoma In Situ of the Upper Aerodigestive Tract: An HPV-Related Entity

The clinical and pathologic characteristics of human papillomavirus (HPV)-related premalignant lesions in the upper aerodigestive tract have not been adequately studied. There are a few reports of oral cavity HPV-related severe dysplasia with unique morphology (prominent apoptosis/karyorrhexis imparting a ‘bowenoid’ appearance) and a single case report of HPV-related squamous cell carcinoma in situ with nonkeratinizing histology distinct from the ‘bowenoid’ pattern that extensively involved the upper aerodigestive tract. The aim of this study was to characterize the morphologic and clinical features of HPV-related severe dysplasia/carcinoma in situ. All cases of upper aerodigestive tract severe dysplasia/carcinoma in situ (111 cases from 98 patients) at Washington University from July 2012 to March 2015 were categorized into histologic types: keratinizing, nonkeratinizing, mixed or ‘bowenoid’. There were 83 (85 %) patients with keratinizing, 3 (3 %) nonkeratinizing and 12 (12 %) mixed patterns. The previously reported ‘bowenoid’ morphology was not identified. All 3 (100 %) nonkeratinizing and 6 (50 %) mixed cases were p16 and HPV RNA in situ hybridization (RNA ISH) positive (100 % concordance between p16 and RNA ISH). Only 2 of 73 keratinizing cases were p16 positive, 1 of which was also HPV RNA ISH positive (1.4 % of keratinizing cases HPV-related). Thus, nonkeratinizing morphology was a strong predictor of transcriptionally-active HPV in severe dysplasia/carcinoma in situ. HPV-related cases most commonly occurred in the floor of mouth and were frequently extensive (≥4 cm) or unresectable.
Acceleration region measurements in a nested channel Hall thruster

The recent interest from NASA to develop high-powered electric propulsion technologies for cargo and manned missions to Mars has motivated the development of nested channel Hall thrusters at the University of Michigan. In collaboration with the Air Force Research Laboratory (AFRL), the 6-kW X2 nested channel Hall thruster was built and tested at the University of Michigan. Initial characterization of this thruster was completed by Liang.1 This work included measurements of plume properties such as the plasma potential, electron temperature, and plume divergence.1 However, plasma properties within the channel of the thruster have yet to be reported. Further characterization of nested channel thrusters is necessary to validate these designs and improve the fidelity of numerical models.
Pulmonary Embolism Rates Following Total Hip Arthroplasty With Prophylactic Anticoagulation: Some Pulmonary Emboli Cannot Be Avoided

Abstract Background A symptomatic pulmonary embolism (PE) after total joint arthroplasty has been described as a “never event.” Despite potent anticoagulants and improvements in patient care, PE continues to occur following total hip arthroplasty (THA). This study evaluates symptomatic PE rates over time in THA patients enrolled in multicenter randomized clinical trials (RCTs) assessing the efficacy of venous thromboembolism prophylaxis regimens. Methods The MEDLINE and Cochrane Central Register of Controlled Trials were searched to identify clinical trials assessing prophylactic anticoagulation in patients undergoing THA between January 1995 and December 2015. Inclusion criteria consisted of RCTs evaluating prophylactic anticoagulation in patients undergoing THA. A random effect model was used to combine PE rates across studies. Results A total of 21 studies (34,764 patients) were included. Patients were administered low molecular weight heparin (13,590 patients), oral factor Xa inhibitors (6609 patients), oral direct thrombin inhibitors (5965 patients), indirect factors Xa/IIa inhibitors (3444 patients), aspirin (2427 patients), and warfarin (489 patients). Mobile compression was used in 199 patients, and placebo was used in 2041 patients. Across all included studies, the estimated PE rate was 0.21% (95% confidence interval: 0.13%, 0.32%). Between 1997 and 2013, the proportion of PEs did not change in regression analysis. Conclusion Although the PE rate was low, it was consistent throughout the 17 years spanning these RCTs, which excluded patients with significant morbidity. These results suggest that even healthy THA patients receiving aggressive anticoagulation still have a risk for PE, and the “never event” designation requires reassessment.
Anti GD1b/ GD1a Positive Pure Sensory Ataxic Neuronopathy Progressing to Severe Acute Motor Sensory Axonal Neuropathy: An Atypical Presentation of Guillan-Barre Syndrome (P3.140)

Objective:We report an atypical case of pure sensory ataxic neuronopathy(SAN) with predominantly sensory findings, ataxia, and areflexia progressing to severe acute motor and sensory axonal neuropathy (AMSAN). Background:Acute pure SAN is a rare variant of GBS, specifically associated with anti-GD1b antibodies. Progression to AMSAN has not previously been reported. Methods:Case report. Results:A 42 year old female with h/o severe alcohol abuse presented with a 2 week history of gradually progressive bilateral lower extremity pain and numbness. On admission, exam showed nystagmus in all directions of gaze, severe allodynia, burning dysesthesias, impaired light touch, length dependent decrease in vibration sense, temperature and pin prick in the lower extremities with diffuse areflexia. Severe ataxia and dysmetria were also present. Muscle strength although limited by pain, was preserved. She was also noted to have altered mental status with confabulations and her thiamine levels were extremely low. Initial diagnosis was Wernicke’s encephalopathy with severe thiamine deficiency induced painful neuropathy. Lumbar puncture revealed albumino-cytologic dissociation. Electromyography (EMG) and Nerve conduction studies (NCV) revealed severe length dependent pure sensory polyneuropathy of axonal type with normal motor responses. She was diagnosed with pure SAN and received 3 sessions of plasmapheresis but continued to deteriorate clinically, now developing worsening weakness independent of pain which rapidly progressed to quadriplegia. Hospital course was further complicated with sepsis and acute respiratory distress syndrome. She was initiated on intravenous immunoglobulin. Repeat EMG/NCV at this stage revealed severe sensory-motor polyneuropathy with axonal degeneration and active denervation changes in all muscles tested, with absent F waves consistent with severe AMSAN. Anti-GD1b and anti-GD1a antibodies were positive. Patient was subsequently discharged to acute rehabilitation. Conclusions:Our patient demonstrated a pure SAN with preserved motor responses which rapidly progressed to a severe AMSAN. Progression from one rare variant of GBS to another variant is highly atypical. Disclosure: Dr. Rodriguez has nothing to disclose. Dr. Shah has nothing to disclose. Dr. Li has nothing to disclose.
The limited prospects for international tax cooperation

The recent pace of international agreement aimed to reduce tax evasion and avoidance was completely unpredicted prior to the financial crisis. The two targets are often considered to be merely different dimensions of the same problem. This paper argues that the two problems actually involve very different logics, and this holds the key to the prospects for success. The assault on tax evasion confronts a problem that is commonly recognized and admits to amelioration through the increased information sharing that is rapidly, although unevenly, advancing. Attempts to reduce corporate tax avoidance, however, confront ambiguity at every turn. National corporate tax systems differ markedly from each other in rules as well as rates, and agreement necessarily takes place in an ever more competitive international business environment in which national rate and rule setting will remain largely independent. Moreover, increased attention to the international taxation of business seems to have increased rather than dampened unilateral initiatives to advance national gain.