Miracle-dz/UniFAR-FTUs huggingface dataset:
The determinants of carboxyl pKa values in turkey ovomucoid third domain

A computational methodology for protein pKa predictions, based on ab initio quantum mechanical treatment of part of the protein and linear Poisson–Boltzmann equation treatment of the bulk solvent, is presented. The method is used to predict and interpret the pKa values of the five carboxyl residues (Asp7, Glu10, Glu19, Asp27, and Glu43) in the serine protease inhibitor turkey ovomucoid third domain. All the predicted pKa values are within 0.5 pH units of experiment, with a root‐mean‐square deviation of 0.31 pH units. We show that the decreased pKa values observed for some of the residues are primarily due to hydrogen bonds to the carboxyl oxygens. Hydrogen bonds involving amide protons are shown to be particularly important, and the effect of hydrogen bonding is shown to be nonadditive. Hydrophobic effects are also shown to be important in raising the pKa. Interactions with charged residues are shown to have relatively little effect on the carboxyl pKa values in this protein, in general agreement with experiment. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Brain-Derived Neurotrophic Factor Promotes Vasculature-Associated Migration of Neuronal Precursors toward the Ischemic Striatum

Stroke induces the recruitment of neuronal precursors from the subventricular zone (SVZ) into the ischemic striatum. In injured areas, de-routed neuroblasts use blood vessels as a physical scaffold to their migration, in a process that resembles the constitutive migration seen in the rostral migratory stream (RMS). The molecular mechanism underlying injury-induced vasculature-mediated migration of neuroblasts in the post-stroke striatum remains, however, elusive. Using adult mice we now demonstrate that endothelial cells in the ischemic striatum produce brain-derived neurotrophic factor (BDNF), a neurotrophin that promotes the vasculature-mediated migration of neuronal precursors in the RMS, and that recruited neuroblasts maintain expression of p75NTR, a low-affinity receptor for BDNF. Reactive astrocytes, which are widespread throughout the damaged area, ensheath blood vessels and express TrkB, a high-affinity receptor for BDNF. Despite the absence of BDNF mRNA, we observed strong BDNF immunolabeling in astrocytes, suggesting that these glial cells trap extracellular BDNF. Importantly, this pattern of expression is reminiscent of the adult RMS, where TrkB-expressing astrocytes bind and sequester vasculature-derived BDNF, leading to the entry of migrating cells into the stationary phase. Real-time imaging of cell migration in acute brain slices revealed a direct role for BDNF in promoting the migration of neuroblasts to ischemic areas. We also demonstrated that cells migrating in the ischemic striatum display higher exploratory behavior and longer stationary periods than cells migrating in the RMS. Our findings suggest that the mechanisms involved in the injury-induced vasculature-mediated migration of neuroblasts recapitulate, at least partially, those observed during constitutive migration in the RMS.
Course of Graves Disease in Interferon-Treated Patients With Chronic Hepatitis C Virus Infection and in Uninfected Patients

Background The development of thyroid antibodies and the alteration of thyroid function are the most common disorders associated with interferon alfa therapy in individuals with chronic hepatitis C (CHC). In this study, we compared the course of Graves disease (GD) between patients diagnosed with CHC and treated with interferon alfa and uninfected patients. Methods We retrospectively analyzed data from 39 GD patients (15 men and 24 women, group 1) affected by CHC and treated with interferon alfa and from 43 uninfected GD patients (19 men and 24 women, group 2) who were seen at our institution from 1999 to 2011. All GD patients were treated with methimazole (MMI). Daily dose of MMI, duration of MMI therapy, and remission rate were evaluated in both groups. Results The daily dose of MMI was found to be lower in group 1 as compared with group 2 (9.74 ± 5.94 mg/d vs 14.12 ± 8.64 mg/d in group 1 vs group 2, respectively, P < 0.01). In addition, the duration of MMI treatment was found to be lower in group 1 as compared with group 2 (13.98 ± 13.0 months vs 38.86 ± 27.13 months in group 1 vs group 2, respectively; P < 0.01). The remission rate from GD was higher in the patients of group 1 in comparison with the patients of group 2 (87.17 % vs 48.86% in group 1 vs group 2, respectively, P < 0.005). Conclusion Altogether, our data demonstrate a more favorable course of GD in the patients with CHC treated with interferon alfa compared with GD occurring in the patients without CHC.
Agents with dycotomic goals which generate a rank-size distribution

Many explanations have been proposed for the rank-size rule or power law in city size distribution based on a probabilistic process [4]. These explanations are usually opposed to that proposed by Zipf [11] who explained the rank-size rule as the result of the application of the principle of least eﬀort. In his opinion, by using this principle, it is possible to ﬁnd an equilibrium between the two opposite forces of diversiﬁcation and of uniﬁcation. In fact, because the main components of the system are resources, people and products, the ﬁrst force brings people near to resources, and the latter brings products near to people. Even these notions are simple, and are accepted in the spatial economic ﬁeld [5] it is not clear how a rank-size rule can be derived from it[2]. In this paper I will show how a rank-size distribution can be generated by using multiagent interaction which uses a probabilistic law to obtain opposing goals that correspond to uniﬁcation and diversiﬁcation forces. This paper is divided in two sections: the ﬁrst section presents a model based on agents pursuing opposite goals; the second discusses the model in relation to the previously proposed models.
HUMOR IN THE BRIEFING ROOM

This article explores the strategic uses of humor in the police organization. Based upon a year-long ethnographic study of one suburban police department, we examine four types of humor characteristics of the work relations among patrol officers: jocular aggression, audience degradation, diffusion of danger/tragedy, and normative neutralization. Humor allows for a wide range of creative expressions by which specific ideas, attitudes, and behaviors may be tested. Through humor, patrol officers relate and interpret work experiences to reinforce their own perspective of policing. Institutionalized humorous communication also contributes to the maintenance of organizational relationships.
Toll-Like Receptor 2-Dependent NF-κB Activation Is Involved in Nontypeable Haemophilus influenzae-Induced Monocyte Chemotactic Protein 1 Up-Regulation in the Spiral Ligament Fibrocytes of the Inner Ear

ABSTRACT Inner ear dysfunction secondary to chronic otitis media (OM), including high-frequency sensorineural hearing loss or vertigo, is not uncommon. Although chronic middle ear inflammation is believed to cause inner ear dysfunction by entry of OM pathogen components or cytokines from the middle ear into the inner ear, the underlying mechanisms are not well understood. Previously, we demonstrated that the spiral ligament fibrocyte (SLF) cell line up-regulates monocyte chemotactic protein 1 (MCP-1) expression after treatment with nontypeable Haemophilus influenzae (NTHI), one of the most common OM pathogens. We hypothesized that the SLF-derived MCP-1 plays a role in inner ear inflammation secondary to OM that is responsible for hearing loss and dizziness. The purpose of this study was to investigate the signaling pathway involved in NTHI-induced MCP-1 up-regulation in SLFs. Here we show for the first time that NTHI induces MCP-1 up-regulation in the SLFs via Toll-like receptor 2 (TLR2)-dependent activation of NF-κB. TLR2−/−- and MyD88−/−-derived SLFs revealed involvement of TLR2 and MyD88 in NTHI-induced MCP-1 up-regulation. Studies using chemical inhibitors and dominant-negative constructs demonstrated that it is mediated by the IκKβ-dependent IκBα phosphorylation and NTHI-induced NF-κB nuclear translocation. Furthermore, we demonstrated that the binding of NF-κB to the enhancer region of MCP-1 is involved in this up-regulation. In addition, we have identified a potential NF-κB motif that is responsive and specific to certain NTHI molecules or ligands. Further studies are necessary to reveal specific ligands of NTHI that activate host receptors. These results may provide us with new therapeutic strategies for prevention of inner ear dysfunction secondary to chronic middle ear inflammation.
Playing hide-and-seek: searching for the use of self in reflective social work practice

With the increasing awareness of power and privilege in current theorizing, social workers are increasingly called upon to engage in critical self-reflection and develop strategies of reflective use of self in their practice. However, despite this call the use of self is disappearing from social work curricula. This paper presents an overview of findings from a small qualitative study exploring the use of self among reflective social work practitioners. In-depth collegial conversations were used to generate data. Narrative and discourse analysis were used to interpret the data. Findings are nuanced and textured reflecting the diversity of participants’ worldviews.
System level assessment of motor control through patterned microstimulation in the superior colliculus

We are immersed in an environment full of sensory information, and without much thought or effort we can produce orienting responses to appropriately react to different stimuli. This seemingly simple and reflexive behavior is accomplished by a very complicated set of neural operations, in which motor systems in the brain must control behavior based on populations of sensory information. The oculomotor or saccadic system is particularly well studied in this regard. Within a visual environment consisting of many potential stimuli, we control our gaze with rapid eye movements, or saccades, in order to foveate visual targets of interest. A key sub-cortical structure involved in this process is the superior colliculus (SC). The SC is a structure in the midbrain which receives visual input and in turn projects to lower-level areas in the brainstem that produce saccades. Interestingly, microstimulation of the SC produces eye movements that match the metrics and kinematics of naturally-evoked saccades. As a result, we explore the role of the SC in saccadic motor control by manually introducing distributions of activity through neural stimulation. Systematic manipulation of microstimulation patterns were used to characterize how ensemble activity in the SC is decoded to generate eye movements. Specifically, we focused on three different facets of saccadic motor control. In the first study, we examine the effective influence of microstimulation parameters on behavior to reveal characteristics of the neural mechanisms underlying saccade generation. In the second study, we experimentally verify the predictions of computational algorithms that are used to describe neural mechanisms for saccade generation. And in the third study, we assess where neural mechanisms for decoding occur within the oculomotor network in order to establish the order of operations necessary for saccade generation. The experiments assess different aspects of saccadic motor control, which collectively, reveal properties and mechanisms that contribute to the comprehensive understanding of signal processing in the oculomotor system.
Manipulated Outcome Expectations and Competitive Performance in Motor Tasks with Gradually Increasing Difficulty

The aim of this study was to examine whether outcome expectations can be generalized from one defined task to other tasks. A deception paradigm was employed in which outcome expectations were manipulated. High, low, or medium expectations toward performing five tasks, which gradually increased in complexity and shared a common skill, were manipulated. Ninety adult males were randomly assigned to manipulation groups. A within-subjects repeated measures ANOVA indicated that those manipulated by medium expectations showed elevated perceptions of outcome expectations. Their performance, however, was superior only in the two tasks most similar in complexity to the initial task. On the less similar tasks, the differences among the groups were insignificant. A generalization effect can therefore be demonstrated on outcome expectations and performance to a certain degree of task complexity. Implications of the superior performance of participants manipulated to produce medium outcome expectations are discussed.
Delayed onset and recurrent Alcaligenes xylosoxidans keratitis.

Alcaligenes xylosoxidans (formerly Achromobacter xylosoxidans) is an opportunistic aerobic gram-negative rod that is oxidase positive and nonlactose fermenting. It may be confused with other gram-negative bacteria such as Pseudomonas aeruginosa (1). The organism was first described and named in 1971 by Yabuuchi and Ohyama (2), who isolated the organism from purulent ear discharge of seven patients. It is frequently found in moist areas of hospitals and is resistant to many antimicrobial agents (3). Alcaligenes xylosoxidans is a transient colonizer of human gastrointestinal or respiratory tract in patients with cystic fibrosis (4). Its mode of transmission is often unknown, although it frequently involves exposure of debilitated patients to contaminated fluids or medical solutions (1,5,6). It has caused bacteremia, urinary tract infections, meningitis, wound infections, pneumonia, and peritonitis (6). To our knowledge, only five cases of A. xylosoxidans keratitis have been reported (Table 1). We report a case of posttraumatic A. xylosoxidans keratitis that recurred after apparent resolution.
Adaptation to Complex Pictures: Exposure to Emotional Valence Induces Assimilative Aftereffects

Aftereffects have been documented for a variety of perceptual categories spanning from body gender to facial emotion, thus becoming an important tool in the study of high-level vision and its neural bases. We examined whether the perceived valence of a complex scene is subject to aftereffects, by observing the participants’ evaluation of the valence of a test picture preceded by a different picture. For this study, we employed an adaptation paradigm with positive and negative images used as adapters, and positive, negative, and neutral images used as tests. Our results show that adaptation to complex emotional pictures induces assimilative aftereffects: participants judged neutral tests more positively following positive adapters and more negatively following negative adapters. This depended on the prolonged adaptation phase (10 s), as the results of a second experiment, in which adapters lasted for 500 ms, did not show aftereffects. In addition, the results show that assimilative aftereffects of negative and positive adapters also manifested themselves on non-neutral (negative and positive) targets, providing evidence that the global emotional content of complex pictures is suitable to induce assimilative aftereffects.
THE ROLE OF DOMOIC ACID IN ABORTION AND PREMATURE PARTURITION OF CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS) ON SAN MIGUEL ISLAND, CALIFORNIA

Domoic acid is a glutaminergic neurotoxin produced by marine algae such as Pseudo-nitzschia australis. California sea lions (Zalophus californianus) ingest the toxin when foraging on planktivorous fish. Adult females comprise 60% of stranded animals admitted for rehabilitation due to acute domoic acid toxicosis and commonly suffer from reproductive failure, including abortions and premature live births. Domoic acid has been shown to cross the placenta exposing the fetus to the toxin. To determine whether domoic acid was playing a role in reproductive failure in sea lion rookeries, 67 aborted and live-born premature pups were sampled on San Miguel Island in 2005 and 2006 to investigate the causes for reproductive failure. Analyses included domoic acid, contaminant and infectious disease testing, and histologic examination. Pseudo-nitzschia spp. were present both in the environment and in sea lion feces, and domoic acid was detected in the sea lion feces and in 17% of pup samples tested. Histopathologic findings included systemic and localized inflammation and bacterial infections of amniotic origin, placental abruption, and brain edema. The primary lesion in five animals with measurable domoic acid concentrations was brain edema, a common finding and, in some cases, the only lesion observed in aborted premature pups born to domoic acid–intoxicated females in rehabilitation. Blubber organochlorine concentrations were lower than those measured previously in premature sea lion pups collected in the 1970s. While the etiology of abortion and premature parturition was varied in this study, these results suggest that domoic acid contributes to reproductive failure on California sea lion rookeries.
The Emergence of Hybrid Organizational Forms: Combining Identity-Based Service Provision and Political Action

After the 1960s, women, Blacks, and other ethnic groups mapped political objectives onto a more traditional form of voluntary association, along with investing in direct political protest and advocacy for civil and social rights. One result was the development of a hybrid organizational form that combines advocacy and service provision as its core identity and thus faces distinctive environmental uncertainties and boundary conditions. This article provides a community ecology framework for analyzing the development of the service/advocacy organizational form. The author argues that hybrid forms of organization, by expanding the resource infrastructure and legitimacy available to identity-based organizations, play a critical role in anchoring the continued viability of identity-based service organizations under newly politicized conditions. Data are drawn from a study of national women’s and racial and ethnic minority organizations since 1955.
Semiautomated analysis of Doppler images for quantification of changes in mitral inflow pattern during parabolic flight

To study changes in left ventricular (LV) mitral inflow induced by gravitational stresses, and evaluate the effects due to different postures, we performed transthoracic Doppler imaging during parabolic flights on 7 normal subjects (mean age/spl square/SD, 46/spl plusmn/5 years) in standing upright and resting position. To detect Doppler velocity profiles, a semiautomatically procedure based on local image properties, was applied. Then, LV inflow parameters were automatically computed and their modifications according to different gravity conditions were found: in standing, LV diastolic rapid filling parameters were significantly affected (E-wave peak, cm/s: from 54.7/spl plusmn/11.1 at 1G to 85.8/spl plusmn/12.1 at 0G; E-wave integral, cm: from 6.6/spl plusmn/1.7 at 1G to 13.1/spl plusmn/3.2 at 0G; E/A integral ratio, a.u.: from 1.4/spl plusmn/7 at 1G to 2.5/spl plusmn/8 at 0G), while late diastolic filling parameters were preserved (A-wave peak, cm/s: from 48.8/spl plusmn/3.6 at 1G to 55.3/spl plusmn/11.3 at 0G). No changes were noted while subjects were in supine resting.
Popeye Domain Containing 1 (Popdc1/Bves) Is a Caveolae-Associated Protein Involved in Ischemia Tolerance

Popeye domain containing1 (Popdc1), also named Bves, is an evolutionary conserved membrane protein. Despite its high expression level in the heart little is known about its membrane localization and cardiac functions. The study examined the hypothesis that Popdc1 might be associated with the caveolae and play a role in myocardial ischemia tolerance. To address these issues, we analyzed hearts and cardiomyocytes of wild type and Popdc1-null mice. Immunoconfocal microscopy revealed co-localization of Popdc1 with caveolin3 in the sarcolemma, intercalated discs and T-tubules and with costameric vinculin. Popdc1 was co-immunoprecipitated with caveolin3 from cardiomyocytes and from transfected COS7 cells and was co-sedimented with caveolin3 in equilibrium density gradients. Caveolae disruption by methyl-β-cyclodextrin or by ischemia/reperfusion (I/R) abolished the cellular co-localization of Popdc1 with caveolin3 and modified their density co-sedimentation. The caveolin3-rich fractions of Popdc1-null hearts redistributed to fractions of lower buoyant density. Electron microscopy showed a statistically significant 70% reduction in caveolae number and a 12% increase in the average diameter of the remaining caveolae in the mutant hearts. In accordance with these changes, Popdc1-null cardiomyocytes displayed impaired [Ca+2]i transients, increased vulnerability to oxidative stress and no pharmacologic preconditioning. In addition, induction of I/R injury to Langendorff-perfused hearts indicated a significantly lower functional recovery in the mutant compared with wild type hearts while their infarct size was larger. No improvement in functional recovery was observed in Popdc1-null hearts following ischemic preconditioning. The results indicate that Popdc1 is a caveolae-associated protein important for the preservation of caveolae structural and functional integrity and for heart protection.
SPRY2 loss enhances ErbB trafficking and PI3K/AKT signalling to drive human and mouse prostate carcinogenesis

Loss of SPRY2 and activation of receptor tyrosine kinases are common events in prostate cancer (PC). However, the molecular basis of their interaction and clinical impact remains to be fully examined. SPRY2 loss may functionally synergize with aberrant cellular signalling to drive PC and to promote treatment‐resistant disease. Here, we report evidence for a positive feedback regulation of the ErbB‐PI3K/AKT cascade by SPRY2 loss in in vitro as well as pre‐clinical in vivo models and clinical PC. Reduction in SPRY2 expression resulted in hyper‐activation of PI3K/AKT signalling to drive proliferation and invasion by enhanced internalization of EGFR/HER2 and their sustained signalling at the early endosome in a PTEN‐dependent manner. This involved p38 MAPK activation by PI3K to facilitate clathrin‐mediated ErbB receptor endocytosis. Finally, in vitro and in vivo inhibition of PI3K suppressed proliferation and invasion, supporting PI3K/AKT as a target for therapy particularly in patients with PTEN‐haploinsufficient‐, low SPRY2‐ and ErbB‐expressing tumours. In conclusion, SPRY2 is an important tumour suppressor in PC since its loss drives the PI3K/AKT pathway via functional interaction with the ErbB system.
Engagement and avoidance in support staff working with people with intellectual disability and challenging behaviour: A multiple-case study†

Abstract Background Challenging behaviour of clients influences emotional wellbeing of staff; this in turn affects levels of staff engagement and avoidance within interactions with clients. The main goal of this study was to investigate to what extent levels of staff engagement and staff avoidance are related to challenging and desirable client behaviours and clients' initiatives for contact. Method Participants were 8 support staff and 3 clients. Staff and client behaviours were measured within moments of interaction in natural settings using systematic observational data. Results The results showed that general levels of staff engagement, avoidance, and client behaviours seem to be related. However, individual, sequential analyses do not support these relationships. Conclusions Future research should take a more individual and intrapersonal view of staff behaviour and staff–client interaction into account, in order to obtain a detailed and realistic image of individual patterns in interactions between support staff and clients.