Miracle-dz/UniFAR-FTUs huggingface dataset:
The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1

Continuous regeneration of digestive enzyme (zymogen)-secreting chief cells is a normal aspect of stomach function that is disrupted in precancerous lesions (e.g. metaplasias, chronic atrophy). The cellular and genetic pathways that underlie zymogenic cell (ZC) differentiation are poorly understood. Here, we describe a gene expression analysis of laser capture microdissection purified gastric cell populations that identified the bHLH transcription factor Mist1 as a potential ZC regulatory factor. Our molecular and ultrastructural analysis of proliferation, migration and differentiation of the gastric unit in Mist1-/- and control mice supports a model whereby wild-type ZC progenitors arise as neck cells in the proliferative (isthmal) zone of the gastric unit and become transitional cells (TCs) with molecular and ultrastructural characteristics of both enzyme-secreting ZCs and mucus-secreting neck cells as they migrate to the neck-base zone interface. Thereafter, they rapidly differentiate into mature ZCs as they enter the base. By contrast, Mist1-/- neck cells differentiate normally, but ZCs in the mature, basal portion of the gastric unit uniformly exhibit multiple apical cytoplasmic structural abnormalities. This defect in terminal ZC differentiation is also associated with markedly increased abundance of TCs, especially in late-stage TCs that predominantly have features of immature ZCs. Thus, we present an in vivo system for analysis of ZC differentiation, present molecular evidence that ZCs differentiate from neck cell progenitors and identify Mist1 as the first gene with a role in this clinically important process.
Electroencephalogram–Electromyography Coupling Analysis in Stroke Based on Symbolic Transfer Entropy

The coupling strength between electroencephalogram (EEG) and electromyography (EMG) signals during motion control reflects the interaction between the cerebral motor cortex and muscles. Therefore, neuromuscular coupling characterization is instructive in assessing motor function. In this study, to overcome the limitation of losing the characteristics of signals in conventional time series symbolization methods, a variable scale symbolic transfer entropy (VS-STE) analysis approach was proposed for corticomuscular coupling evaluation. Post-stroke patients (n = 5) and healthy volunteers (n = 7) were recruited and participated in various tasks (left and right hand gripping, elbow bending). The proposed VS-STE was employed to evaluate the corticomuscular coupling strength between the EEG signal measured from the motor cortex and EMG signal measured from the upper limb in both the time-domain and frequency-domain. Results showed a greater strength of the bi-directional (EEG-to-EMG and EMG-to-EEG) VS-STE in post-stroke patients compared to healthy controls. In addition, the strongest EEG–EMG coupling strength was observed in the beta frequency band (15–35 Hz) during the upper limb movement. The predefined coupling strength of EMG-to-EEG in the affected side of the patient was larger than that of EEG-to-EMG. In conclusion, the results suggested that the corticomuscular coupling is bi-directional, and the proposed VS-STE can be used to quantitatively characterize the non-linear synchronization characteristics and information interaction between the primary motor cortex and muscles.
Inactivation of Lgt Allows Systematic Characterization of Lipoproteins from Listeria monocytogenes

ABSTRACT Lipoprotein anchoring in bacteria is mediated by the prolipoprotein diacylglyceryl transferase (Lgt), which catalyzes the transfer of a diacylglyceryl moiety to the prospective N-terminal cysteine of the mature lipoprotein. Deletion of the lgt gene in the gram-positive pathogen Listeria monocytogenes (i) impairs intracellular growth of the bacterium in different eukaryotic cell lines and (ii) leads to increased release of lipoproteins into the culture supernatant. Comparative extracellular proteome analyses of the EGDe wild-type strain and the Δlgt mutant provided systematic insight into the relative expression of lipoproteins. Twenty-six of the 68 predicted lipoproteins were specifically released into the extracellular proteome of the Δlgt strain, and this proved that deletion of lgt is an excellent approach for experimental verification of listerial lipoproteins. Consequently, we generated Δlgt ΔprfA double mutants to detect lipoproteins belonging to the main virulence regulon that is controlled by PrfA. Overall, we identified three lipoproteins whose extracellular levels are regulated and one lipoprotein that is posttranslationally modified depending on PrfA. It is noteworthy that in contrast to previous studies of Escherichia coli, we unambiguously demonstrated that lipidation by Lgt is not a prerequisite for activity of the lipoprotein-specific signal peptidase II (Lsp) in Listeria.
Memory Latency E ects in Decoupled ArchitecturesLizyamma

Decoupled computer architectures partition the memory access and execute functions in a computer program and achieve high performance by exploiting the ne{grain paral-lelism between the two. These architectures make use of an access processor to perform the data fetch ahead of demand by the execute process and hence are often less sensitive to memory access delays than conventional architectures. Past performance studies of de-coupled computers used memory systems that are interleaved or pipelined, and in those studies latency eeects were partially hidden due to interleaving. A detailed simulation study of the latency eeects in decoupled computers is under-taken in this paper. Decoupled architecture performance is compared to single processors with caches. The memory latency sensitivity of cache based uniprocessors and decoupled systems is studied. Simulations are performed to determine the signiicance of data caches in a decoupled architecture. It is observed that decoupled architectures can reduce the peak memory bandwidth requirement, but not the total bandwidth, whereas data caches can reduce the total bandwidth by capturing locality. It may be concluded that despite their capability to partially mask the eeects of memory latency, decoupled architectures still need a data cache.
Expérience des réformes et transformation de l’ethos de service public dans l’administration publique québécoise

Les reformes ayant cours dans l’administration publique quebecoise, dans le mouvement du Nouveau Management Public, confrontent deux systemes de valeurs et proposent un changement de culture qui met au defi l’ethos de service public traditionnel. Ces transformations affectent la construction identitaire des gestionnaires dont les roles et fonctions s’en trouvent fortement alteres par les injonctions qui leur sont adressees d’etre les porteurs (leaders) du changement aupres de leur personnel. Dans cette recherche, basee sur des entretiens biographiques, la construction identitaire et ses tensions sont etudiees sous l’angle de la subjectivite, dans une dialectique mettant en rapport l’experience des sujets-acteurs et la dynamique sociale, culturelle et institutionnelle. L’analyse tente de comprendre comment ces gestionnaires parviennent a composer avec leur role de courroie dans l’articulation de cette reforme « generique » a leur contexte organisationnel specifique, d’etre aussi des impulseurs de changement, imputables de leurs unites administratives, alors qu’ils en subissent les tensions et paradoxes. Et enfin comment preservent-ils leur engagement et celui de leurs personnels envers l’action publique, meme lorsque celle-ci, telle qu’elle s’en trouve transformee, confronte leurs valeurs, leur conception du service public et leurs convictions ?
Tilted Implants for Full-Arch Rehabilitations in Completely Edentulous Maxilla: A Retrospective Study

Purpose. The aims of this study were to assess the treatment outcome of immediately loaded full-arch fixed bridges anchored to both tilted and axially placed implants in the edentulous maxilla and to evaluate the incidence of biological and prosthetic complications. Materials and Methods. Thirty-four patients (18 women and 16 men) were included in the study. Each patient received a maxillary full-arch fixed bridge supported by two axial implants and two distal tilted implants. A total of 136 implants were inserted. Loading was applied within 48 hours of surgery and definitive restorations were placed 4 to 6 months later. Patients were scheduled for followup at 6, 12, 18, and 24 months and annually up to 5 years. At each followup plaque level and bleeding scores were assessed and every complication was recorded. Results. The overall follow-up range was 12 to 73 months (mean 38.8 months). No implant failures were recorded to date, leading to a cumulative implant survival rate of 100%. Biological complications were recorded such as alveolar mucositis (11.8% patients), peri-implantitis (5.9% patients), and temporomandibular joint pain (5.9% patients). The most common prosthetic complications were the fracture or detachment of one or multiple acrylic teeth in both the temporary (20.6% patients) and definitive (17.7% patients) prosthesis and the minor acrylic fractures in the temporary (14.7% patients) and definitive (2.9% patients) prosthesis. Hygienic complications occurred in 38.2% patients. No patients' dissatisfactions were recorded. Conclusions. The high cumulative implant survival rate indicates that this technique could be considered a viable treatment option. An effective recall program is important to early intercept and correct prosthetic and biologic complications in order to avoid implant and prosthetic failures.
Measuring the Moment-to-Moment Variability of Tinnitus: The TrackYourTinnitus Smart Phone App

Tinnitus, the phantom perception of sound without a corresponding external sound, is a frequent disorder which causes significant morbidity. So far there is no treatment available that reliably reduces the tinnitus perception. The research is hampered by the large heterogeneity of tinnitus and the fact that the tinnitus perception fluctuates over time. It is therefore necessary to develop tools for measuring fluctuations of tinnitus perception over time and for analyzing data on single subject basis. However, this type of longitudinal measurement is difficult to perform using the traditional research methods such as paper-and-pencil questionnaires or clinical interviews. Ecological momentary assessment (EMA) represents a research concept that allows the assessment of subjective measurements under real-life conditions using portable electronic devices and thereby enables the researcher to collect longitudinal data under real-life conditions and high cost efficiency. Here we present a new method for recording the longitudinal development of tinnitus perception using a modern smartphone application available for iOS and Android devices with no costs for the users. The TrackYourTinnitus (TYT) app is available and maintained since April 2014. A number of 857 volunteers with an average age of 44.1 years participated in the data collection between April 2014 and February 2016. The mean tinnitus distress at the initial measurement was rated on average 13.9 points on the Mini-Tinnitus Questionnaire (Mini-TQ; max. 24 points). Importantly, we could demonstrate that the regular use of the TYT app has no significant negative influence on the perception of the tinnitus loudness nor on the tinnitus distress. The TYT app can therefore be proposed as a safe instrument for the longitudinal assessment of tinnitus perception in the everyday life of the patient.
The unique games conjecture, integrality gap for cut problems and embeddability of negative type metrics into l/sub 1/

In this paper, we disprove the following conjecture due to Goemans (1997) and Linial (2002): "Every negative type metric embeds into with constant distortion. " We show that for every /spl delta/ > 0, and for large enough n, there is an n-point negative type metric which requires distortion at-least (log log n) /sup 1/6-/spl delta// to embed into l/sub 1/. Surprisingly, our construction is inspired by the Unique Games Conjecture (UGC) of Khot (2002), establishing a previously unsuspected connection between PCPs and the theory of metric embeddings. We first prove that the UGC implies super-constant hardness results for (non-uniform) sparsest cut and minimum uncut problems. It is already known that the UGC also implies an optimal hardness result for maximum cut (2004). Though these hardness results depend on the UGC, the integrality gap instances rely "only" on the PCP reductions for the respective problems. Towards this, we first construct an integrality gap instance for a natural SDP relaxation of unique games. Then, we "simulate" the PCP reduction and "translate"the integrality gap instance of unique games to integrality gap instances for the respective cut problems! This enables us to prove a (log log n) /sup 1/6-/spl delta// integrality gap for (nonuniform) sparsest cut and minimum uncut, and an optimal integrality gap for maximum cut. All our SDP solutions satisfy the so-called "triangle inequality" constraints. This also shows, for the first time, that the triangle inequality constraints do not add any power to the Goemans-Williamson's SDP relaxation of maximum cut. The integrality gap for sparsest cut immediately implies a lower bound for embedding negative type metrics into l/sub i/. It also disproves the non-uniform version of Arora, Rao and Vazirani's Conjecture (2004), asserting that the integrality gap of the sparsest cut SDP, with the triangle inequality constraints, is bounded from above by a constant.
Preservation of Antigen-Specific Functions of αβ T Cells and B Cells Removed from Hematopoietic Stem Cell Transplants Suggests Their Use As an Alternative Cell Source for Advanced Manipulation and Adoptive Immunotherapy

Hematopoietic stem cell transplantation is standard therapy for numerous hematological diseases. The use of haploidentical donors, sharing half of the HLA alleles with the recipient, has facilitated the use of this procedure as patients can rely on availability of a haploidentical donor within their family. Since HLA disparity increases the risk of graft-versus-host disease, T-cell depletion has been used to remove alloreactive lymphocytes from the graft. Selective removal of αβ T cells, which encompass the alloreactive repertoire, combined with removal of B cells to prevent EBV-related lymphoproliferative disease, proved safe and effective in clinical studies. Depleted αβ T cells and B cells are generally discarded as by-products. Considering the possible use of donor T cells for donor lymphocyte infusions or for generation of pathogen-specific T cells as mediators of graft-versus-infection effect, we tested whether cells in the discarded fractions were functionally intact. Response to alloantigens and to viral antigens comparable to that of unmanipulated cells indicated a functional integrity of αβ T cells, in spite of the manipulation used for their depletion. Furthermore, B cells proved to be efficient antigen-presenting cells, indicating that antigen uptake, processing, and presentation were fully preserved. Therefore, we propose that separated αβ T lymphocytes could be employed for obtaining pathogen-specific T cells, applying available methods for positive selection, which eventually leads to indirect allodepletion. In addition, these functional T cells could undergo additional manipulation, such as direct allodepletion or genetic modification.
International Journal of Molecular Sciences the Honolulu Liver Disease Cluster at the Medical Center: Its Mysteries and Challenges

In 2013, physicians at the Honolulu Queen's Medical Center (QMC) noticed that seven liver disease patients reported the use of OxyELITE Pro (OEP), a widely consumed dietary supplement (DS). Assuming a temporal association between OEP use and disease, they argued that OEP was the cause of this mysterious cluster. Subsequent reexamination, however, has revealed that this QMC cohort is heterogeneous and not a cluster with a single agent causing a single disease. It is heterogeneous because patients used multiple DS's and drugs and because patients appeared to have suffered from multiple liver diseases: liver cirrhosis, liver failure by acetaminophen, hepatotoxicity by non-steroidal antiinflammatory drugs (NSAIDs), resolving acute viral hepatitis by hepatitis B virus (HBV), herpes simplex virus (HSV), and varicella zoster virus (VZV), and suspected hepatitis E virus (HEV). Failing to exclude these confounders and to consider more viable diagnoses, the QMC physicians may have missed specific treatment options in some of their patients. The QMC physicians unjustifiably upgraded their Roussel Uclaf Causality Assessment Method (RUCAM) causality scores so that all patients would appear to be " probable " for OEP. However, subsequent RUCAM reassessments by our group demonstrated a lack of causality for OEP in the evaluated QMC cases. The QMC's questionable approaches explain the extraordinary accumulation of suspected OEP cases at the QMC in Hawaii as single place, whereas similar cohorts were not published by any larger US liver center, substantiating that the problem is with the QMC. In this review article, we present and discuss new case data and critically evaluate upcoming developments of problematic regulatory assessments by the US Centers for Disease Control and Prevention (CDC), the Hawaii Department of Health (HDOH), and the Food and Drug Administration (FDA), as based on invalid QMC conclusions, clarifying now also basic facts and facilitating constructive discussions.
Boundaries of the Firm: Evidence from the Banking Industry

Agency theory implies that asset ownership and decision authority are complements. Using 1998 data from Texas commercial banks, we test whether the likelihood of local ownership of bank offices increases with the importance of granting local managers greater decision authority (for example, due to location or customer base). Our empirical evidence is consistent with this hypothesis. It suggests that complementarities between strategy and organizational structure can foster differentiation among firms in terms of location, customers, and products. It also supports the growing view that small locally-owned banks have a comparative advantage over large banks within specific environments.
Occurrence and Fate of the Pharmaceutical Drug Diclofenac in Surface Waters: Rapid Photodegradation in a Lake

The pharmaceutical drug diclofenac (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid) was detected in rivers and lakes in Switzerland. The data strongly suggest inputs of diclofenac from human medical use via wastewater treatment plants. Interestingly, the concentrations in a major tributary to a lake (Greifensee) were significantly higher (up to 370 ng/L) than those in the outflow of this lake (up to 12 ng/L). It is estimated that more than 90% of the diclofenac entering the lake is eliminated in the lake, most likely by photolytic degradation. Diclofenac was not detected in the sediments of the lake, and in a laboratory experiment, it showed negligible adsorption onto sediment particles. Incubation of lake water, fortified with diclofenac, showed no degradation in the dark, suggesting minimal chemical and biological degradation. However, when the fortified water was exposed to sunlight, rapid photodegradation was observed with a (pseudo) first-order kinetic and a half-life of less than 1 h (October and 4.
Experimentally based topology models for E. coli inner membrane proteins

Membrane protein topology predictions can be markedly improved by the inclusion of even very limited experimental information. We have recently introduced an approach for the production of reliable topology models based on a combination of experimental determination of the location (cytoplasmic or periplasmic) of a protein's C terminus and topology prediction. Here, we show that determination of the location of a protein's C terminus, rather than some internal loop, is the best strategy for large‐scale topology mapping studies. We further report experimentally based topology models for 31 Escherichia coli inner membrane proteins, using methodology suitable for genome‐scale studies.
NRP-1 Receptor Expression Mismatch in Skin of Subjects with Experimental and Diabetic Small Fiber Neuropathy

The in vivo cutaneous nerve regeneration model using capsaicin is applied extensively to study the regenerative mechanisms and therapeutic efficacy of disease modifying molecules for small fiber neuropathy (SFN). Since mismatches between functional and morphological nerve fiber recovery are described for this model, we aimed at determining the capability of the capsaicin model to truly mimic the morphological manifestations of SFN in diabetes. As nerve and blood vessel growth and regenerative capacities are defective in diabetes, we focused on studying the key regulator of these processes, the neuropilin-1 (NRP-1)/semaphorin pathway. This led us to the evaluation of NRP-1 receptor expression in epidermis and dermis of subjects presenting experimentally induced small fiber neuropathy, diabetic polyneuropathy and of diabetic subjects without clinical signs of small fiber neuropathy. The NRP-1 receptor was co-stained with CD31 vessel-marker using immunofluorescence and analyzed with Definiens® technology. This study indicates that capsaicin application results in significant loss of epidermal NRP-1 receptor expression, whereas diabetic subjects presenting small fiber neuropathy show full epidermal NRP-1 expression in contrast to the basal expression pattern seen in healthy controls. Capsaicin induced a decrease in dermal non-vascular NRP-1 receptor expression which did not appear in diabetic polyneuropathy. We can conclude that the capsaicin model does not mimic diabetic neuropathy related changes for cutaneous NRP-1 receptor expression. In addition, our data suggest that NRP-1 might play an important role in epidermal nerve fiber loss and/or defective regeneration and that NRP-1 receptor could change the epidermal environment to a nerve fiber repellant bed possibly through Sem3A in diabetes.
Measurement of mechanical properties of bone material in vitro by ultrasound reflection: Methodology and comparison with ultrasound transmission

An ultrasound reflection technique was designed and implemented to study the mechanical properties of bone material. The technique uses the fact that an ultrasound beam produced in water undergoes total internal reflection off a bone sample at a critical angle formally related to the velocity of a pressure wave in bone. When the plane of scattering is rotated around the normal to the sample surface, the critical angle varies with a periodic dependence dictated by the intrinsic symmetry of the bone structure at the point being examined.