Miracle-dz/UniFAR-FTUs huggingface dataset:
Two pools of IRE1α in cardiac and skeletal muscle cells

The endoplasmic reticulum (ER) plays a central role in cellular stress responses via mobilization of ER stress coping responses, such as the unfolded protein response (UPR). The inositol‐requiring 1α (IRE1α) is an ER stress sensor and component of the UPR. Muscle cells also have a well‐developed and highly subspecialized membrane network of smooth ER called the sarcoplasmic reticulum (SR) surrounding myofibrils and specialized for Ca2+ storage, release, and uptake to control muscle excitation‐contraction coupling. Here, we describe 2 distinct pools of IRE1α in cardiac and skeletal muscle cells, one localized at the perinuclear ER and the other at the junctional SR. We discovered that, at the junctional SR, calsequestrin binds to the ER luminal domain of IRE1α, inhibiting its dimerization. This novel interaction of IRE1α with calsequestrin, one of the highly abundant Ca2+ handling proteins at the junctional SR, provides new insights into the regulation of stress coping responses in muscle cells. —Wang, Q. , Groenendyk, J., Paskevicius, T. , Qin, W. , Kor, K. C. , Liu, Y. , Hiess, F. , Knollmann, B. C. , Chen, S. R. W. , Tang, J., Chen, X. ‐Z. , Agellon, L. B. , Michalak, M. Two pools of IRE1α in cardiac and skeletal muscle cells. FASEB J. 33, 8892–8904 (2019). www.fasebj. org
Cone Beam Computed Tomography in Oral and Maxillofacial Surgery: An Evidence-Based Review

Cone Beam Computed Tomography (CBCT) is a valuable imaging technique in oral and maxillofacial surgery (OMS) that can help direct a surgeon’s approach to a variety of conditions. A 3-dimensional analysis of head and neck anatomy allows practitioners to plan appropriately, operate with confidence, and assess results post-operatively. CBCT imaging has clear indications and limitations. CBCT offers the clinician 3-dimensional and multi-planar views for a more accurate diagnosis and treatment without the financial burden and radiation exposure of conventional computed tomography (CT) scans. Furthermore, CBCT overcomes certain limitations of 2-dimensional imaging, such as distortion, magnification, and superimposition. However, CBCT lacks the detailed depiction of soft tissue conditions for evaluation of pathologic conditions, head and neck infections, and temporomandibular joint (TMJ) disc evaluation. This review evaluates the evidence-based research supporting the application of CBCT in the various fields of oral and maxillofacial surgery, including dentoalveolar surgery, dental implants, TMJ, orthognathic surgery, trauma, and pathology, and will assess the value of CBCT in pre-operative assessment, surgical planning, and post-operative analysis when applicable. Additionally, the significant limitations of CBCT and potential areas for future research will be discussed.
Correlative Confocal Raman and Scanning Probe Microscopy in the Ionically Active Particles of LiMn2O4 Cathodes

In this contribution, a correlative confocal Raman and scanning probe microscopy approach was implemented to find a relation between the composition, lithiation state, and functional electrochemical response in individual micro-scale particles of a LiMn2O4 spinel in a commercial Li battery cathode. Electrochemical strain microscopy (ESM) was implemented both at a low-frequency (3.5 kHz) and in a high-frequency range of excitation (above 400 kHz). It was shown that the high-frequency ESM has a significant cross-talk with topography due to a tip-sample electrostatic interaction, while the low-frequency ESM yields a response correlated with distributions of Li ions and electrochemically inactive phases revealed by the confocal Raman microscopy. Parasitic contributions into the electromechanical response from the local Joule heating and flexoelectric effect were considered as well and found to be negligible. It was concluded that the low-frequency ESM response directly corresponds to the confocal Raman microscopy data. The analysis implemented in this work is an important step towards the quantitative measurement of diffusion coefficients and ion concentration via strain-based scanning probe microscopy methods in a wide range of ionically active materials.
Relationship of causative organism and time to infection among children with cerebrospinal fluid shunt infection.

OBJECTIVEInfection is a common complication of cerebrospinal fluid (CSF) shunts, occurring in 6%-20% of children. Although studies are limited, Staphylococcus aureus is thought to cause more rapid and aggressive infection than coagulase-negative Staphylococcus (CONS) or gram-negative organisms. The authors' objective was to evaluate the relationship between the causative organisms of CSF shunt infection and the timing of infection.METHODSThe authors performed a retrospective cohort study of children who underwent CSF shunt placement at a tertiary care children's hospital over a 9-year period and subsequently developed a CSF shunt infection. The primary predictor variable was the causative organism recovered from CSF culture, characterized as S. aureus, CONS, or gram-negative organisms. The primary outcome was time to infection, defined as the number of days from most recent shunt intervention to the diagnosis of the infection. The association between causative organism and time to infection was visualized using Kaplan-Meier curves, and statistical comparisons were made using nonparametric Kruskal-Wallis tests.RESULTSAmong 103 children in whom a CSF shunt infection developed, the causative organism was CONS in 57 (55%), S. aureus in 19 (18%), and gram-negative organisms in 9 (9%). The median time to infection did not differ (p = 0.81) for infections caused by CONS (20 days, IQR 11-40), S. aureus (26 days, IQR 12-95), and gram-negative organisms (23 days, IQR 17-34). CONCLUSIONSNo significant difference in time to infection based on the causative organism was observed among children with a CSF shunt infection.
Multilayer architecture microfluidic network array for combinatorial drug testing on 3D-cultured cells

In vitro testing of drug compounds on cell models during the drug development process represents an indispensable step in the initial screening process. Although drug testing on three-dimensional (3D) cultured cells may provide a more accurate prediction of drug efficacy, it is relatively costly and time-consuming to perform compared with conventional 2D cultures due to the thick z-axis of the 3D models. In this study, we have presented a microfluidic platform with integrated pneumatic valves for producing a thin-gel 3D cell culture-based combinatorial drug screening array (3D-μCDS array). The multilayer architecture and microfluidic layout has a smaller device footprint than a single-layer microfluidic channel arrangement, making it well suited to scaling up for high-throughput combinatorial drug screening on 3D cell model. We performed 8 × 8 combination drug screening experiments with the device using two anti-cancer drugs (doxorubicin and paclitaxel) on MDA-MB-231 and MCF-7 breast cancer cell lines for demonstration. Our results indicate that our 3D-μCDS array device allows the successful screening of multiple drug combinations while reducing the operation time and the number of sample/reagents required, making it an ideal tool for general combinatorial drug screening, as well as for applications using valuable tissues and clinical samples.
Agile development: It's only natural

A significant number of software development methods have been published over the last 40 years that purport to be properly based on empirical, adaptive and collaborative development. All suggest, some by name, rapid development; bringing systems to production rapidly and at lower cost. The latest manifestation of these methods is Agile Development. This paper pursues the idea that in normal, everyday life people inevitably and invariably behave in this manner; empirical, adaptive and collaborative. Their behaviour is entirely based on empirical observation of the immediate circumstances and conditions, they adapt their behaviour according to these empirical observations, and they usually need to and indeed do, collaborate with others to achieve their ends. This thinking appears to be well supported in management literature, and by influential thinkers, historically. The thesis is also that every activity that people undertake can be reasonably defined as a project. Everyday activities such as going to work, visiting the supermarket, having dinner in a restaurant with friends are examples of the myriad activities undertaken by individuals, groups and families in the natural course of their lives. To achieve success in even these usual and commonplace activities requires planning, and the activities are carried out using empirical experience to adapt their behaviour as necessary, and is almost always done in cooperation and collaboration with others. The question must arise as to why Agile Development of computer software systems is still considered as a secondary, probably second-rate and even damaging and unworkable approach to software development when these development approaches are so embedded with ideas of empirical planning, adaptive project management and collaborative behaviour. They're only natural!
Regulation of Thymus Size by Competition for Stromal Niches among Early T Cell Progenitors1

Thymic T cell production is characterized by differentiating waves of non-self-renewing, bone marrow-derived progenitors. The factors constraining new progenitor recruitment, intrathymic precursor expansion, and thymus size remain enigmatic, but are believed to be controlled by a feedback loop responding to lymphoid cellularity and competition for stromal niches. In this study, we show that competition for stromal niches does occur, but is solely limited to cells at the early CD4−8− precursor stages of differentiation. The overall size of the organ is determined both by this limitation on early precursor expansion, and by a second, cell-intrinsic limit on expansion of progenitor cells transiting to the CD4+8+ stage. Together with asymmetric use of marrow-derived progenitors to reconstitute the intrathymic pool, these processes facilitate continuous generation of new T cells while maintaining a relatively stable organ size.
Rapid Eye Movement Sleep Percentage and Duration in Posttraumatic Stress Disorder Vary Dynamically and Inversely With Indices of Sympathetic Activation During Sleep and Sleep Fragmentation.

ABSTRACT Posttraumatic stress disorder (PTSD) is associated with activation of the brain fear circuitry. Studies of sleep in PTSD provide a unique window into the relation or connection of sleep physiology and autonomic activation. Serial level 3 home sleep apnea tests (HSATs) (10 HSATs over 1 month) in a patient who was medication free, had PTSD, and had refused positive airway pressure therapy, revealed both percentage of rapid eye movement (REM) sleep (mean ± standard deviation [SD]: 19.88% ± 10.11%; range 1.94% to 35.01%) and REM sleep duration (minutes) (mean ± SD: 73.08 ± 48.24; range 3.49- 151.59) varied markedly over the 10 HSATs. Both percentage of REM sleep and REM sleep duration correlated negatively with sleep onset latency (r = -.661, P = .037 and r = -.748, P = .013, respectively) and the mean pulse rate during sleep (r = -.667, P = .035 and r = -.771, P = .009, respectively), and positively with sleep efficiency (r = .824, P = .003 and r = .922, P < .001, respectively) and percentage of stage N3 sleep (r = .784, P = .007 and r = .734, P = .016, respectively), an index of parasympathetic tone during sleep. These empirical findings suggest a previously unreported inverse relation of REM sleep with sleep fragmentation and sympathetic activation.
A Communication and configuration controller for NoC based reconfigurable data flow architecture

While Network-on-Chip aspects such as topologies, routing strategies or Quality-of-Service have been largely studied, the mapping of real applications on distributed NoC-based architecture is still an open issue. In this paper, we address this issue for complex reconfigurable data-flow applications. We introduce the concept of Communication and Configuration Controller (CCC) which interacts both with the usual Network Interface and the IP core structure. The proposed CCC is a programmable template-based architecture, which provides solutions to manage reconfiguration flows, data synchronizations and global control signaling. An implementation of the CCC is presented, and its performances in a 65nm technology are discussed through a concrete telecommunication application.
Loss of SMAD4 protein expression in gastrointestinal and extra‐gastrointestinal carcinomas

SMAD4 (DPC4) is a tumour suppressor gene that is dysregulated in various tumour types, particularly pancreaticobiliary and gastrointestinal carcinomas. Corresponding loss of protein expression has been reported in approximately 50% of pancreatic and 25% of colonic adenocarcinomas. In the evaluation of carcinoma of unknown primary site, immunohistochemical loss of SMAD4 expression is often used to suggest pancreaticobiliary origin, but there are limited data on the spectrum of SMAD4 expression in carcinomas of other sites. This study evaluates the frequency of SMAD4 loss in a large cohort of carcinomas from diverse anatomical sites.
Characteristic Scales of Initial Density and Velocity Fields

For the initial fields of the density contrast and peculiar velocity, we theoretically calculate the ‘differential’ and ‘integral’ length scales, i.e., statistical measures that respectively characterize the small- and large-scale fluctuations of a random field. These length scales and the associated mass scales explain the length and mass scales observed for (1) halos of young galaxies at z & 5, (2) halos of galaxies at z � 0, and (3) the largest structures in the galaxy distribution at z � 0. We thereby discuss that such observed scales are fossil imprints of the characteristic scales of the initial fields. Subject Index: 464, 469 Since structures of the Universe are formed from gravitational instability of the initial fluctuations, some characteristics of the structures are traced back to those of the initial fluctuations. This should be especially the case for the characteristics determined in the linear or quasi-linear stage of the structure formation. Both the stages are described with the initial peculiar velocity v by the first-order Lagrangian perturbation. 1),2) The linear stage is also described with the initial density contrast δ by the first-order Eulerian perturbation. 2),3) The characteristics of the initial fields of the density contrast δ and peculiar velocity v are studied here. Since these fields are random, we use statistical measures that have been developed to characterize turbulent random fields. 4) Specifically, for the first time, the ‘differential’ and ‘integral’ length scales are used to characterize the initial fields. We calculate the length scales and associated mass scales. They are compared with the scales observed for galaxies and their large-scale distribution, in order to explore the fossil imprints of the initial fluctuations among these structures. §2. Basic framework 2.1. Cosmological parameters For the cosmological parameters, we assume their standard values: the Hubble constant H0 =7 0 km s −1 Mpc −1 (h =0 .7), the matter density Ωm =0 . 14h −2 ,t he baryon density Ωb =0 . 023h −2 , and the temperature of the cosmic microwave background TCMB =2 . 73 K. 5) The matter density Ωm is dominated by the cold dark matter so that the structure formation proceeds from small to large scales.
The Problem of Emergence

Darwin’s question about the origin of species is worth posing and exploring as much in the social sciences as it was in biology. Human organizations, like living organisms, have evolved throughout history, with new organizational forms emerging and transforming in various settings: new types of banks and banking in the history of capitalism; new types of research organizations and research in the history of science; new types of political organizations and nations in the history of state formation. All of these examples are discussed in this book. the histories of economies and polities are littered with new organizational forms that never existed before. in biological language, this emergence of new organizational forms is the puzzle of speciation. We economists, political scientists, and sociologists have many theories about how to choose alternatives, once these swim into our field of vision. But our theories have little to say about the invention of new alternatives in the first place. new ideas, new practices, new organizational forms, new people must enter from off the stage of our imaginary before our analyses can begin. Darwin asked the fundamental question, but our concepts are like those of Darwin before Mendel and Watson and crick. We understand selection and equilibrium, but we do not understand the emergence of what we choose or of who we are. our analytical shears are sharp, but the life forces pushing things up to be trimmed elude us. novelty almost by definition is hard to understand. something is not genuinely new if it already exists in our current practice or imagination. the terms innovation and invention, as we use them in this book, mean the construction of something neither present nor anticipated by anyone in the population. We do not mean that planned incremental improvement on what already exists is not possible—quite the opposite. this type of learning occurs far more often than does the production of genuine novelty. the conundrum for both researchers and participants is that logical cognition, no matter how useful for refinement and improvement, is unlikely to be a fundamental process for generating novelty, because logic can only use axioms that are already there. the literature on “organizational innovation” is voluminous, but that literature largely focuses on learning,1 search,2 and diffusion3 and often uses patents as indicators.4 the term innovation in organization theory refers to products and ideas, never to the emergence of organizational actors per se.5 social science studies processes of innovation, so defined, but mainly by abstracting
Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the In Vivo Activity as a BCRP Inhibitor: Preparation and In Vitro/In Vivo Characterization

LW6 (3-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-4-hydroxy-benzoic acid methyl ester) is a potent inhibitor of drug efflux by the breast cancer resistance protein (BCRP). However, its poor aqueous solubility leads to low bioavailability, which currently limits in vivo applications. Therefore, the present study aimed to develop ternary solid dispersion (SD) formulations in order to enhance the aqueous solubility and dissolution rate of LW6. Various SDs of LW6 were prepared using a solvent evaporation method with different drug/excipient ratios. The solubility and dissolution profiles of LW6 in different SDs were examined, and F8-SD which is composed of LW6, poloxamer 407, and povidone K30 at a weight ratio of 1:5:8 was selected as the optimal SD. The structural characteristics of F8-SD were also examined using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM). In the acidic to neutral pH range, F8-SD achieved rapid dissolution with a drug release of 76–81% within 20 min, while the dissolution of pure LW6 was negligible. The XRPD patterns indicated that F8-SD probably enhanced the solubility and dissolution of LW6 by changing the drug crystallinity to an amorphous state, in addition to the solubilizing effect of the hydrophilic carriers. Furthermore, F8-SD significantly improved the oral bioavailability of topotecan, which is a BCRP substrate, in rats. The systemic exposure of topotecan was enhanced approximately 10-fold by the concurrent use of F8-SD. In conclusion, the ternary SD formulation of LW6 with povidone K30 and poloxamer 407 appeared to be effective at improving the dissolution and in vivo effects of LW6 as a BCRP inhibitor.
Revisiting the Immune Trypanolysis Test to Optimise Epidemiological Surveillance and Control of Sleeping Sickness in West Africa

Background Because of its high sensitivity and its ease of use in the field, the card agglutination test for trypanosomiasis (CATT) is widely used for mass screening of sleeping sickness. However, the CATT exhibits false-positive results (i) raising the question of whether CATT-positive subjects who are negative in parasitology are truly exposed to infection and (ii) making it difficult to evaluate whether Trypanosoma brucei (T.b.) gambiense is still circulating in areas of low endemicity. The objective of this study was to assess the value of the immune trypanolysis test (TL) in characterising the HAT status of CATT-positive subjects and to monitor HAT elimination in West Africa. Methodology/Principal Findings TL was performed on plasma collected from CATT-positive persons identified within medical surveys in several West African HAT foci in Guinea, Côte d'Ivoire and Burkina Faso with diverse epidemiological statuses (active, latent, or historical). All HAT cases were TL+. All subjects living in a nonendemic area were TL−. CATT prevalence was not correlated with HAT prevalence in the study areas, whereas a significant correlation was found using TL. Conclusion and Significance TL appears to be a marker for contact with T.b. gambiense. TL can be a tool (i) at an individual level to identify nonparasitologically confirmed CATT-positive subjects as well as those who had contact with T.b. gambiense and should be followed up, (ii) at a population level to identify priority areas for intervention, and (iii) in the context of HAT elimination to identify areas free of HAT.
Use of LTE for the Interoperability between Different Generations of Wireless Communication

This paper looks potential approaches to interoperability as well as inter-technology mobility using Long Term Evolution (LTE) between different generations of wireless communication. Focus is given on how these approaches can be used in interoperable service deployment, access technology integration, service continuity and smooth migration to LTE by maximizing the use of legacy networks coverage. One of the most important interoperability criterions is the handover latency. Using NCTUNS6 simulator it is shown that LTE (4G) provides less handover latency in comparison to that of other generations of wireless communication system for homogeneous environment.
Coxsackievirus B3 Responds to Polyamine Depletion via Enhancement of 2A and 3C Protease Activity

Polyamines are small positively-charged molecules abundant in eukaryotic cells that are crucial to RNA virus replication. In eukaryotic cells, polyamines facilitate processes such as transcription, translation, and DNA replication, and viruses similarly rely on polyamines to facilitate transcription and translation. Whether polyamines function at additional stages in viral replication remains poorly understood. Picornaviruses, including Coxsackievirus B3 (CVB3), are sensitive to polyamine depletion both in vitro and in vivo; however, precisely how polyamine function in picornavirus infection has not been described. Here, we describe CVB3 mutants that arise with passage in polyamine-depleted conditions. We observe mutations in the 2A and 3C proteases, and we find that these mutant proteases confer resistance to polyamine depletion. Using a split luciferase reporter system to measure protease activity, we determined that polyamines facilitate viral protease activity. We further observe that the 2A and 3C protease mutations enhance reporter protease activity in polyamine-depleted conditions. Finally, we find that these mutations promote cleavage of cellular eIF4G during infection of polyamine-depleted cells. In sum, our results suggest that polyamines are crucial to protease function during picornavirus infection. Further, these data highlight viral proteases as potential antiviral targets and highlight how CVB3 may overcome polyamine-depleting antiviral therapies.