Miracle-dz/UniFAR-FTUs huggingface dataset:
An immunohistochemical and stereological analysis of PSI‐induced nigral neuronal degeneration in the rat

Systemic administration of the proteasomal inhibitor I (PSI) to rats was reported to cause progressive nigral dopaminergic neuronal loss but this is disputed. A major controversy centres over the use of manual counting of tyrosine hydroxylase (TH) positive neurons at the level of third cranial nerve as opposed to employing systematic stereological analysis of cell loss in the entire substantia nigra (SN). To provide a method of marking SN neurones independent of protein expression, fluorogold™ (FG) was stereotaxically injected bilaterally into the striatum of male Wistar rats to retrogradely label nigral dopaminergic neurons. After 1 week, animals were treated with six doses of PSI (8 mg/kg, s.c.) or its vehicle (dimethyl sulphoxide) on alternate days over a 2‐week period. Five weeks after the last treatment, PSI‐treated animals showed decreased spontaneous locomotor activity and reduced TH positive SN cell number at the level of the third cranial nerve compared to control rats. Manual cell counting showed loss of FG‐labelled SN neurones at this level, with a subpopulation of surviving neurons displaying abnormal morphology. Manual counting of all FG‐labelled cells in the entire SN also showed regional PSI‐induced loss of neurones with both normal and compromised morphology. Stereological optical fractionator estimates of total FG‐labelled cell number confirmed the manual cell counting data both at the level of the third cranial nerve and throughout the entire SN. These findings confirm that PSI does cause a persistent nigral dopaminergic neuronal loss. The reason for the lack of reproducibility between laboratories requires further investigation. We suggest that a failure to distinguish between TH‐positive neurones with normal and abnormal morphology following PSI administration contributes to equivocal results.
Dynamics of phosphodiester synthesis by DNA ligase

Ligases are essential actors in DNA replication, recombination, and repair by virtue of their ability to seal breaks in the phosphodiester backbone. Ligation proceeds through a nicked DNA-adenylate intermediate (AppDNA), which must be sealed quickly to avoid creating a potentially toxic lesion. Here, we take advantage of ligase-catalyzed AMP-dependent incision of a single supercoiled DNA molecule to observe the step of phosphodiester synthesis in real time. An exponentially distributed number of supercoils was relaxed per successful incision-resealing event, from which we deduce the torque-dependent ligation probability per DNA swivel. Premature dissociation of ligase from nicked DNA-adenylate accounted for ≈10% of the observed events. The ability of ligase to form a C-shaped protein clamp around DNA is a key determinant of ligation probability per turn and the stability of the ligase-AppDNA intermediate. The estimated rate of phosphodiester synthesis by DNA ligase (400 s−1) is similar to the high rates of phosphodiester synthesis by replicative DNA polymerases.
Sliding perspectives: dissociating ownership from self-location during full body illusions in virtual reality

Bodily illusions have been used to study bodily self-consciousness and disentangle its various components, among other the sense of ownership and self-location. Congruent multimodal correlations between the real body and a fake humanoid body can in fact trigger the illusion that the fake body is one's own and/or disrupt the unity between the perceived self-location and the position of the physical body. However, the extent to which changes in self-location entail changes in ownership is still matter of debate. Here we address this problem with the support of immersive virtual reality. Congruent visuotactile stimulation was delivered on healthy participants to trigger full body illusions from different visual perspectives, each resulting in a different degree of overlap between real and virtual body. Changes in ownership and self-location were measured with novel self-posture assessment tasks and with an adapted version of the cross-modal congruency task. We found that, despite their strong coupling, self-location and ownership can be selectively altered: self-location was affected when having a third person perspective over the virtual body, while ownership toward the virtual body was experienced only in the conditions with total or partial overlap. Thus, when the virtual body is seen in the far extra-personal space, changes in self-location were not coupled with changes in ownership. If a partial spatial overlap is present, ownership was instead typically experienced with a boosted change in the perceived self-location. We discussed results in the context of the current knowledge of the multisensory integration mechanisms contributing to self-body perception. We argue that changes in the perceived self-location are associated to the dynamical representation of peripersonal space encoded by visuotactile neurons. On the other hand, our results speak in favor of visuo-proprioceptive neuronal populations being a driving trigger in full body ownership illusions.
Effect of Saline Environment on the Strength of Reinforced Concrete Beams

This paper presents the experimental results of tests carried out to investigate the influence of parameters such as w/c ratio, curing condition and surface bar coating on the shear and bending strengths of fifteen reinforced concrete beams under severe saline environmental conditions. Sodium chloride was used as an additive and an aqueous solution for chloride introduction. The effectiveness of coating the surface of reinforcing steel bar with a paint to protect it against corrosion in concrete was also evaluated. Results show that after 500 days of soaking in the chloride solution the beams undergone considerable deterioration. Significant reduction in shear and flexural strength of reinforced concrete beams due to concrete degradation and steel corrosion especially when sodium chloride was used as an additive. The results indicate that the use of paint-coated reinforcing steel bars in reinforced concrete beams can be helpful to protect the reinforcement against corrosion under saline environment.
Playing with the Social Network: Social Cohesion in Resettled and Non-Resettled Communities in Cambodia

Mutual aid among villagers in developing countries often is the sole possibility to insure against economic shocks. By using field laboratory experiments in Cambodian villages we study social cohesion in newly resettled and established communities which are both part of a land distribution project. All participants signed up voluntarily for the project, share comparable socio-demographic attributes and have similar preexisting network ties. We use a version of the solidarity game to identify the effect of a voluntary resettlement program on the willingness to help fellow villagers after an income shock. The voluntary resettled players only transfer between 41 % and 57 % of the amount the non-resettled players transfer to an anonymous community member. The solidarity differences are not only driven by lower expectations that the others would also help but are based on more selfish preferences among resettled farmers. Our findings are relevant for resettlement policies, because recipients might have to get additional compensation and formal insurance against the negative social consequences of resettlement until social cohesion is eventually re-established.
Information Technology Capital, Managerial Human Capital, and Firm Performance: An Empirical Investigation

Information technology (IT) business value study has maintained its prosperity for years suggesting that this topic is both theoretically intriguing and pragmatically important in the IT community. Recently information systems (IS) researchers have shifted their attention to the various macroand micro-level contingencies that can affect the value of IT. In the present study the authors particularly examine an important firm-level contingency imposed by the firm’s managerial human capital, manifested by a set of managerial characteristics such as tenure, the level of education, and IT knowledge of the top manager. Employing a dataset of 771 Chinese non-state-owned firms, this paper investigates the interactions between these characteristics and IT capital with regard to their impact on firm performance. The regression results show that not only are the main effects of IT capital and managerial human capital significant, but also their interactions affect firm performance positively in certain industry contexts. In particular, the moderating effects of managerial human capital on IT business value are significant in a subsample of service firms. This is not surprising given that service firms tend to be more information intensive. To the authors’ knowledge, it is the first paper that simultaneously examines IT capital together with managerial human capital. The findings of this paper enrich the IT business value literature and provide some useful insights to the firm managers regarding IT management.
Enriching Complex Networks with Word Embeddings for Detecting Mild Cognitive Impairment from Speech Transcripts

Mild Cognitive Impairment (MCI) is a mental disorder difficult to diagnose. Linguistic features, mainly from parsers, have been used to detect MCI, but this is not suitable for large-scale assessments. MCI disfluencies produce non-grammatical speech that requires manual or high precision automatic correction of transcripts. In this paper, we modeled transcripts into complex networks and enriched them with word embedding (CNE) to better represent short texts produced in neuropsychological assessments. The network measurements were applied with well-known classifiers to automatically identify MCI in transcripts, in a binary classification task. A comparison was made with the performance of traditional approaches using Bag of Words (BoW) and linguistic features for three datasets: DementiaBank in English, and Cinderella and Arizona-Battery in Portuguese. Overall, CNE provided higher accuracy than using only complex networks, while Support Vector Machine was superior to other classifiers. CNE provided the highest accuracies for DementiaBank and Cinderella, but BoW was more efficient for the Arizona-Battery dataset probably owing to its short narratives. The approach using linguistic features yielded higher accuracy if the transcriptions of the Cinderella dataset were manually revised. Taken together, the results indicate that complex networks enriched with embedding is promising for detecting MCI in large-scale assessments.
Joint non-linear ranging and affine synchronization basis for a network of mobile nodes

Synchronization and localization are critical challenges for the coherent functioning of a wireless network of mobile nodes. In this paper, a novel joint non-linear range and affine time model is presented based on two way time stamp exchanges, extending an existing affine time-range model. For a pair of nodes, a closed form pairwise least squares solution is proposed for estimating pairwise range parameters, namely relative range, range rate and rate of range rate between the nodes, in addition to estimating the clock skews and the clock offsets. Extending these pair wise solutions to network wide ranging and clock synchronization, we present a central data fusion based global least squares solution. Furthermore, a new Constrained Cramer Rao Bound (CCRB) is derived for the joint time-range model and the proposed algorithms are shown to approach the theoretical limits asymptotically.
The Construction of A Strategic Issue: Issue Selling as A Narrative Process

For the past 30 years, the issue-selling movement has uncovered the vast repertoire of actions by which ‘sellers’ persuade a decision-maker that an issue is strategic. While these works have a rational and teleological conception of this phenomenon, implying that the strategic scope of the issue is given ex ante, other research in strategy shows that such scope is a social and discursive construction based on interactions between various actors. This article proposes a model of issue selling as an emergent narrative process. Based on a qualitative survey of 42 middle managers, using semistructured interviews, we show this process starts with a phase of incremental elaboration, in which the seller informally shares narrative fragments with a network of actors, followed by a phase of interpretation, in which the seller formally presents his or her narrative to a decision-maker, coherently articulating previously collected narrative fragments. We also show that the passage between these two phases is allowed by what we call the ‘strategic construction’ of the narrative. These results help to show that issue selling is a less solitary and rational process than previous work suggests.
Beta-Catenin Expression in Pediatric Fibroblastic and Myofibroblastic Lesions: A Study of 100 Cases

Nuclear immunoreactivity for β-catenin is a useful adjunct for diagnosis of adult desmoid-type fibromatoses, many of which exhibit mutations within the APC/β-catenin (Wnt) pathway. Pediatric fibromatoses represent a heterogeneous group of lesions that are diagnostically challenging, especially on biopsy. We studied β-catenin expression in a variety of pediatric fibroblastic and myofibroblastic lesions. Immunohistochemical nuclear expression of β-catenin was assessed in 100 tumors. High-level expression of β-catenin was found in 42% of usual-type or deep fibromatoses (21 of 50). Such expression was not seen in any of the other lesions, including fibrous hamartoma of infancy (0 of 18), juvenile hyaline fibromatosis (0 of 7), infantile digital fibromatosis (0 of 6), myofibromatosis (0 of 5), lipofibromatosis (0 of 4), calcifying aponeurotic fibroma (0 of 3), palmar-plantar fibromatosis (0 of 2), fibromatosis colli (0 of 1), or torticollis (0 of 1). High-level β-catenin staining is seen in deep “adult-type” fibromatoses occurring in children, although to a lesser frequency than in adult fibromatoses. This indicates that a subset of deep fibromatoses in childhood shares similar mechanisms of tumorigenesis with those in adults. β-catenin is not expressed in other common pediatric fibroblastic and myofibroblastic lesions, and the Wnt pathway does not appear to play a role in their pathogenesis.
What are we waiting for? Factors influencing completion times in an academic and peripheral emergency department.

BACKGROUND A long completion time in the Emergency Department (ED) is associated with higher morbidity and in-hospital mortality. A completion time of more than four hours is a frequently used cut-off point. Mostly, older and sicker patients exceed a completion time of four hours on the ED. The primary aim was to examine which factors currently contribute to overcrowding and a time to completion of more than four hours on the EDs of two different hospitals, namely: the VU Medical Center (VUmc), an academic level 1 trauma centre and the St. Antonius Hospital, a large community hospital in Nieuwegein. In addition, we compared the differences between these hospitals. METHODS In this observational study, the time steps in the process of diagnosing and treatment of all patients visiting the EDs of the two hospitals were measured for four weeks. Patients triaged as Emergency Severity Index (ESI) category 2/3 or Manchester Triage System (MTS) orange/yellow were followed more closely and prospectively by researchers for detailed information in the same period from 12.00-23.00 hrs. RESULTS In the VUmc, 89% of the patients had a completion time of less than four hours. The average completion time (n = 2262) was 2:10 hours, (median 1:51 hours, range: 0:05-12:08). In the St. Antonius Hospital, 77% of patients had a completion time shorter than four hours (n = 1656). The average completion time in hours was 2:49 (n = 1655, median 2:34, range: 0:08-11:04). In the VUmc, a larger percentage of ESI 1, 2 and 3 patients did not achieve the 4-hour target (14%, 20% and 19%) compared with ESI 4 and 5 patients (2.7% and 0%), p < 0.001. At the St. Antonius Hospital, a greater percentage of orange and yellow categorised patients exceeded four hours on the ED (32% and 28%) compared with red (8%) and green/blue (13%), p < 0.001. For both hospitals there was a significant dependency between exceeding four hours on the ED and the following: whether a consultation was performed (p < 0.001), the number of radiology tests performed (p < 0.001), and an age above 65 years. CONCLUSION Factors leading to ED stagnation were similar in both hospitals, namely old age, treatment by more than one speciality and undergoing radiological tests. Uniform remedial measures should be taken on a nationwide level to deal with these factors to reduce stagnation in the EDs.
TIM3 Checkpoint Inhibition Fails to Prolong Survival in Ovarian Cancer-Bearing Mice

Simple Summary Ovarian cancer still ranks as the deadliest gynecological malignancy worldwide. In this research, we aimed to evaluate the potential of anti-TIM3, a relatively novel checkpoint inhibitor, for the treatment of ovarian cancer. Our preclinical studies showed no improvement of survival in ovarian cancer-bearing mice after anti-TIM3 treatment. Additionally, we found no significant immunological changes induced by this therapy in treated mice. However, changing the order of combination treatment with anti-TIM3 and chemotherapy influenced the outcome in mice. Further preclinical studies are required to find and optimize ovarian cancer treatment approaches. Abstract Immune checkpoint inhibitor (ICI) therapy has proven revolutionary in the treatment of some cancers. However, ovarian cancer remains unresponsive to current leading ICIs, such as anti-PD1 or anti-PD-L1. In this article, we explored the potential of an upcoming checkpoint molecule, T-cell immunoglobulin and mucin domain 3 (TIM3), for the treatment of ovarian cancer using a syngeneic orthotopic mouse model (ID8-fLuc). Besides therapeutic efficacy, we focused on exploring immune changes in tumor tissue and peritoneal fluid. Our results showed no improvement in survival in ovarian cancer-bearing mice after anti-TIM3 treatment when used as monotherapy nor when combined with anti-PD1 or standard-of-care chemotherapy (carboplatin/paclitaxel). This was reflected in the unaltered immune infiltration in treated mice compared to control mice. Altering the order of drug administration within the combination treatment altered the survival results, but did not result in a survival benefit over chemotherapy alone. These findings highlight the need for further preclinical studies to find beneficial treatment schemes and combination therapies for ovarian cancer.
The Human Immunodeficiency Virus Type 1 Promoter Contains a CATA Box Instead of a TATA Box for Optimal Transcription and Replication

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) transcriptional promoter contains a single polymorphism in the TATA box. Most subtypes contain the sequence TATAAGC, but subtype E and some recombinant AG strains have the sequence TAAAAGC. Based on mutagenesis studies of cellular RNA polymerase II (pol II) promoters, it has been proposed that the subtype E TATA box is nonfunctional due to the T-to-A substitution at the critical position 3. By means of transcription and virus replication assays, we demonstrate that the true TATA box motif within the viral long terminal repeat (LTR) promoter starts two nucleotides further upstream. Because of this realignment, subtype E has the sequence CATAAAA and all other subtypes have the sequence CATATAA. The polymorphism therefore has shifted from position 3 to position 5 and is no longer incompatible with efficient transcription according to rules determined for cellular pol II promoters. In addition, through sensitive competition experiments, we demonstrate that the CATA box of subtypes B and E can be improved for replication by the mutations 1T and 5T, respectively. The fact that the fitness of both subtype LTRs can be increased by specific point mutations in the CATA box suggests that the transcriptional promoter of HIV-1 is fine-tuned towards a suboptimal level of replication. However, this replication rate may be optimal in the in vivo context of an infected individual.
Genome-Wide Detection of Small Regulatory RNAs in Deep-Sea Bacterium Shewanella piezotolerans WP3

Shewanella are one of the most abundant Proteobacteria in the deep-sea and are renowned for their versatile electron accepting capacities. The molecular mechanisms involved in their adaptation to diverse and extreme environments are not well understood. Small non-coding RNAs (sRNAs) are known for modulating the gene expression at transcriptional and posttranscriptional levels, subsequently playing a key role in microbial adaptation. To understand the potential roles of sRNAs in the adaptation of Shewanella toward deep-sea environments, here an in silico approach was utilized to detect the sRNAs in the genome of Shewanella piezotolerans WP3, a piezotolerant and psychrotolerant deep-sea iron reducing bacterium. After scanning 3673 sets of 5′ and 3′ UTRs of orthologous genes, 209 sRNA candidates were identified with high confidence in S. piezotolerans WP3. About 92% (193 out of 209) of these putative sRNAs belong to the class trans-encoded RNAs, suggesting that trans-regulatory RNAs are the dominant class of sRNAs in S. piezotolerans WP3. The remaining 16 cis-regulatory RNAs were validated through quantitative polymerase chain reaction. Five cis-sRNAs were further shown to act as cold regulated sRNAs. Our study provided additional evidence at the transcriptional level to decipher the microbial adaptation mechanisms to extreme environmental conditions.
Flow Features of the Near Wake of the Australian Boobook Owl (Ninox boobook) During Flapping Flight Suggest an Aerodynamic Mechanism of Sound Suppression for Stealthy Flight

Synopsis The mechanisms associated with the ability of owls to fly silently have been the subject of scientific interest for many decades and may be relevant to bio-inspired design to reduce noise of flapping and non-flapping flying devices. Here, we characterize the near wake dynamics and the associated flow structures produced during flight of the Australian boobook owl (Ninox boobook). Three individual owls were flown at 8 ms−1 in a climatic avian wind tunnel. The velocity field in the wake was sampled at 500 Hz using long-duration high-speed particle image velocimetry (PIV) while the wing kinematics were imaged simultaneously using high speed video. The time series of velocity maps that were acquired over several consecutive wingbeat cycles enabled us to characterize the wake patterns and to associate them with the phases of the wingbeat cycle. We found that the owl wake was dramatically different from other birds measured under the same flow conditions (i.e., western sandpiper, Calidris mauri and European starling, Sturnus vulgaris). The near wake of the owl did not exhibit any apparent shedding of organized vortices. Instead, a more chaotic wake pattern was observed, in which the characteristic scales of vorticity (associated with turbulence) are substantially smaller in comparison to other birds. Estimating the pressure field developed in the wake shows that owls reduce the pressure Hessian (i.e., the pressure distribution) to approximately zero. We hypothesize that owls manipulate the near wake to suppress the aeroacoustic signal by controlling the size of vortices generated in the wake, which are associated with noise reduction through suppression of the pressure field. Understanding how specialized feather structures, wing morphology, or flight kinematics of owls contribute to this effect remains a challenge for additional study.