Miracle-dz/UniFAR-FTUs huggingface dataset:
The 4-coumarate:CoA ligase gene family in Arabidopsis thaliana comprises one rare, sinapate-activating and three commonly occurring isoenzymes

4-Coumarate:CoA ligase (4CL; EC 6.2.1.12) has a pivotal role in the biosynthesis of plant secondary compounds at the divergence point from general phenylpropanoid metabolism to several major branch pathways. In Arabidopsis thaliana, we have identified a previously undetected, fourth and final member of the At4CL gene family. The encoded enzyme, At4CL4, exhibits the rare property of efficiently activating sinapate, besides the usual 4CL substrates (4-coumarate, caffeate, and ferulate), indicating a distinct metabolic function. Phylogenetic analysis suggests an early evolutionary and functional divergence of three of the four gene family members, At4CL2-4, whereas At4CL1 appears to have originated much later by duplication of its structurally and functionally closest relative, At4CL2. Various characteristics shared by all known plant 4CL genes, as well as by the encoded proteins, define and delimit the At4CL gene family and distinguish it from the closely related family of “At4CL-like” genes.
Structures and interface mapping of the TIR domain-containing adaptor molecules involved in interferon signaling

Significance Toll/interleukin-1 receptor (TIR) homology domains mediate the downstream signaling of Toll-like receptors (TLRs), but the molecular mechanism of the signal transduction is elusive on the structural basis. Here, we determined the structures of TIR domain-containing adaptor molecule (TICAM) 1 and TICAM-2 TIR domains and demonstrated their homotypic and heterotypic interaction surfaces. Both TICAM-1 and TICAM-2 TIR domains form a BB-loop–mediated homodimer. The dimerization of TICAM-2 TIR presents an interaction surface for TICAM-1 TIR. The present result is consistent with the notion that the BB-loop mutant is dominant negative and that dimerization of upstream TIRs is crucial for recruiting downstream TIRs. Homotypic and heterotypic interactions between Toll/interleukin-1 receptor (TIR) domains in Toll-like receptors (TLRs) and downstream adaptors are essential to evoke innate immune responses. However, such oligomerization properties present intrinsic difficulties in structural studies of TIR domains. Here, using BB-loop mutations that disrupt homotypic interactions, we determined the structures of the monomeric TIR domain-containing adaptor molecule (TICAM)-1 and TICAM-2 TIR domains. Docking of the monomeric structures, together with yeast two hybrid-based mutagenesis assays, reveals that the homotypic interaction between TICAM-2 TIR is indispensable to present a scaffold for recruiting the monomeric moiety of the TICAM-1 TIR dimer. This result proposes a unique idea that oligomerization of upstream TIR domains is crucial for binding of downstream TIR domains. Furthermore, the bivalent nature of each TIR domain dimer can generate a large signaling complex under the activated TLRs, which would recruit downstream signaling molecules efficiently. This model is consistent with previous reports that BB-loop mutants completely abrogate downstream signaling.
Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with curative treatment of colorectal liver metastases: an updated systematic review

ABSTRACT Introduction: We aimed to assess the efficacy and safety of delivering intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with curative treatment of colorectal liver metastases. Areas covered: A comprehensive literature search using PubMed was conducted to screen for eligible records. Studies evaluating colorectal surgery and intraperitoneal chemotherapy combined with curative treatment of liver metastases were included. We excluded duplicate publications. Sixty-seven full-text papers were assessed and six papers were finally included. The overall survival in the included studies ranged from 6–49 months. Five-year survival ranged from 18%-28%, three-year survival ranged from 22%-42% and two-year survival ranged from 34%-78%. Survival was lower in patients with liver metastases and peritoneal carcinomatosis (PC) than those with PC alone in the majority of studies. Expert commentary: This review poses questions rather than presenting answers. The heterogeneity of survival data suggests the possible benefit of this aggressive treatment approach in selected patients. Standardization of the technique used for intraperitoneal chemotherapy instillation, agent used as well as the systemic chemotherapy and targeted therapy type and duration through prospective controlled trials is required to provide an evidence of a higher strength to support or prohibit this treatment strategy.
Social media based 3D modeling and visualization

Social Media is a very rich source of up-to-date localized information. In recent years, image collections from photo sharing websites (e.g. Flicker) have been effectively used for 3D reconstruction of objects, buildings and even cities [? ]. While 3D reconstruction techniques are highly improved in terms of accuracy, performance, and parallelism [? , ? ] there are still means to utilize the up-to-date information available from public social sharing websites such as Twitter and Instagram for continuous refinement of the 3D models and information visualization. Our emphasis is on utilizing the information for detecting and refining the changes in the scene, adding new structures and visualizing saliency/popularity information in 3D (See Figure 1).
Full wafer redistribution and wafer embedding as key technologies for a multi-scale neuromorphic hardware cluster

Together with the Kirchhoff-Institute for Physics the Fraunhofer IZM has developed a full wafer redistribution and embedding technology as base for a large-scale neuromorphic hardware system. The paper will give an overview of the neuromorphic computing platform at the Kirchhoff-Institute for Physics and the associated hardware requirements which drove the described technological developments. In the first phase of the project standard redistribution technologies from wafer level packaging were adapted to enable a high density reticle-to-reticle routing on 200 mm CMOS wafers. Neighboring reticles were interconnected across the scribe lines with an 8 μm pitch routing based on semi-additive copper metallization which was photo defined by full field mask aligning equipment. Passivation by photo sensitive benzocyclobutene (BCB) was used to enable a second intra-reticle routing layer. Final IO pads of nickel with flash gold were generated on top of each reticle. For final electrical connection the wafers were placed into mechanical fixtures and the IOs of all reticles were touched by elastomeric connectors. With that concept neuromorphic systems based on full wafers could be assembled and tested. The fabricated high density inter-reticle routing revealed a very high yield of larger than 99.9 %. In order to allow an upscaling of the system size to a large number of wafers with feasible effort a full wafer embedding concept for printed circuit boards was developed and proven in the second phase of the project. The wafers were thinned to 250 μm and laminated with additional prepreg layers and copper foils into a core material. A 200 mm circular cut was done into the core material and the inner prepreg layers to create the required clearance for the wafer. After lamination of the PCB panel the reticle IOs of the embedded wafer were accessed by micro via drilling, copper electroplating, lithography and subtractive etching of the PCB wiring structure. The created wiring with 50 μm line width enabled an access of the reticle IOs on the embedded wafer as well as a board level routing. The panels with the embedded wafers were subsequently stressed with up to 1000 thermal cycles between 0 °C and 100 °C and have shown no severe failure formation over the cycle time.
Pervasive domestication of defective prophages by bacteria

Significance Several molecular systems with important adaptive roles have originated from the domestication of integrated phages (prophages). However, the evolutionary mechanisms and extent of prophage domestication remain poorly understood. In this work, we detected several hundred prophages originating from common integration events and described their dynamics of degradation within their hosts. Surprisingly, we observed strong conservation of the sequence of most vertically inherited prophages, including selection for genes encoding phage-specific functions. These results suggest pervasive domestication of parasites by the bacterial hosts. Because prophages account for a large fraction of bacterial genomes, phage domestication may drive bacterial adaptation. Integrated phages (prophages) are major contributors to the diversity of bacterial gene repertoires. Domestication of their components is thought to have endowed bacteria with molecular systems involved in secretion, defense, warfare, and gene transfer. However, the rates and mechanisms of domestication remain unknown. We used comparative genomics to study the evolution of prophages within the bacterial genome. We identified over 300 vertically inherited prophages within enterobacterial genomes. Some of these elements are very old and might predate the split between Escherichia coli and Salmonella enterica. The size distribution of prophage elements is bimodal, suggestive of rapid prophage inactivation followed by much slower genetic degradation. Accordingly, we observed a pervasive pattern of systematic counterselection of nonsynonymous mutations in prophage genes. Importantly, such patterns of purifying selection are observed not only on accessory regions but also in core phage genes, such as those encoding structural and lysis components. This suggests that bacterial hosts select for phage-associated functions. Several of these conserved prophages have gene repertoires compatible with described functions of adaptive prophage-derived elements such as bacteriocins, killer particles, gene transfer agents, or satellite prophages. We suggest that bacteria frequently domesticate their prophages. Most such domesticated elements end up deleted from the bacterial genome because they are replaced by analogous functions carried by new prophages. This puts the bacterial genome in a state of continuous flux of acquisition and loss of phage-derived adaptive genes.
A simple method for simultaneous interphase-metaphase chromosome analysis in biodosimetry.

PURPOSE To find a simple protocol for measuring chromosome damage both in G1 and in G2/M chromosomes, to overcome problems related to low mitotic index and cell-cycle alterations in biodosimetric tests. MATERIALS AND METHODS The protocol is based on the use of calyculin A to induce premature chromosome condensation in human peripheral blood lymphocytes in different phases of the cell cycle. Chromosome exchanges were measured by fluorescence in situ hybridization (chromosomes 2 and 4) in lymphocytes from four different donors. Cells were exposed to 4Gy X-rays and the results were compared to aberrations in M phase (colcemid block) and G0 (premature chromosome condensation induced by fusion to mitotic hamster cells). RESULTS Treatment with calyculin A produced a high fraction of chromosome condensation in different phases of the cell cycle. Cells in G1 and G2/M could be scored simultaneously for biodosimetry by chromosome painting. The condensation index was 5-20 times higher than the mitotic index (colcemid alone). The calyculin A treatment did not produce a significant increase in the background of chromosomal aberrations or modify the yield of chromosomal aberrations scored after exposure to X-rays. CONCLUSIONS Induction of chromosome condensation by calyculin A is a powerful biodosimetric tool, which provides a high number of spreads for analysis and overcomes problems related to poor in vitro growth or cell-cycle alterations.
Evolutionary algorithm for path planning in mobile robot environment

An evolutionary algorithm is discussed for the path planning problem in mobile robot environment, which may contain a number of unknown obstacles. The evolutionary algorithm searches for paths in the entire, continuous free space. It unifies off-line and on-line planning processes and provides high safety measures without requiring complete information about the obstacles sensed. <<ETX>>
Caregiver Burden and Depression in Mild Cognitive Impairment

Little is known about contributors to burden and depression in caregivers of patients with mild cognitive impairment (MCI) even though these patients experience cognitive, emotional, and behavioral changes. We examined caregiver burden and depression in 43 caregivers for patients with MCI as well as their associations with patients’ neuropsychological status and behavioral symptoms. Almost 30% of caregivers reported clinically significant burden, whereas <5% reported significant depression. Increased caregiver burden was associated with greater disinhibited behaviors by patients, whereas increased caregiver depressive symptoms were associated with greater disinhibited behaviors as well as instrumental activity of daily living (ADL) impairments. Caregiver burden and depression were not associated with patients’ neuropsychological performance. Results suggest these caregivers would benefit from interventions addressing both practical methods to provide ADL assistance and behavioral methods to address inappropriate behaviors in patients in the predementia stages.
On the procurement and pricing of reactive power service in the electricity market environment

Many kinds of ancillary services must be provided in the new electricity market environment, and reactive power service is among the most critical ones. First, the management and procurement of reactive power service are outlined, followed by a brief analysis of associated procurement mechanisms and a summary about current practices in several operating electricity markets. Then, the theoretical basis and characteristics of spot pricing are clarified, and two methods based on spot pricing and power flow tracing respectively analyzed. Finally, some problems not well solved in reactive power pricing are clarified and future research areas prospected.
Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years

Diabetic gastroparesis is a disorder that occurs in both type 1 and type 2 diabetes. It is associated with considerable morbidity among these patients and with the resultant economic burden on the health system. It is primarily a disease seen in middle-aged women, although the increased predisposition in women still remains unexplained. Patients often present with nausea, vomiting, bloating, early satiety and abdominal pain. The pathogenesis of this complex disorder is still not well understood but involves abnormalities in multiple interacting cell types including the extrinsic nervous system, enteric nervous system, interstitial cells of Cajal (ICCs), smooth muscles and immune cells. The primary diagnostic test remains gastric scintigraphy, although other modalities such as breath test, capsule, ultrasound, MRI and single photon emission CT imaging show promise as alternative diagnostic modalities. The mainstay of treatment for diabetic gastroparesis has been antiemetics, prokinetics, nutritional support and pain control. In recent years, gastric stimulation has been used in refractory cases with nausea and vomiting. As we better understand the pathophysiology, newer treatment modalities are emerging with the aim of correcting the underlying defect. In this review, what has been learned about diabetic gastroparesis in the past 5 years is highlighted. The epidemiology, pathogenesis, diagnosis and treatment of diabetic gastroparesis are reviewed, focusing on the areas that are still controversial and those that require more studies. There is also a focus on advances in our understanding of the cellular changes that underlie development of diabetic gastroparesis, highlighting new opportunities for targeted treatment.
Changes in atmospheric chemistry and crop health: A review

The concentrations of atmospheric compounds such as greenhouse gases, heavy metals and trace gas air pollutants have rapidly changed. Many of these compounds interact with agricultural systems and influence crop performance, both directly by affecting growth and quality or indirectly by altering the plant’s ability to cope with other abiotic and biotic stresses. Some atmospheric compounds have little or no discernible impact on the environment; others reach levels that exceed thresholds for damage to crops. In this review, we analyse the literature on airborne species that directly impact crop growth and health. In Europe and North America emissions of SO2, NOx and heavy metals have declined during the past decades and are currently not considered as a major threat to crops. By contrast, air pollutant emissions have been increasing in rapidly growing regions of Asia, Africa and Latin America. Ozone is the most phytotoxic of the common air pollutants. The widespread distribution of O3 already presents a risk to crop growth and health in many regions of the world. It is concluded that the continuous increase in background O3 concentrations will pose a critical threat to future world food security. Interactions with both biotic and abiotic factors must be taken into account in assessing risks of air pollutants in the field. There is evidence that these indirect effects could be more important under certain circumstances than the direct effects of air pollutants on plants. The parallel rapid increase in atmospheric CO2 concentrations accompanied by climate change has two major implications: (1) a possible benefit to crop growth by direct stimulation of photosynthesis and by mitigation of gaseous air pollutants and water stress; and (2) a threat to crop production due to an enhancement of crop quality losses.
System-level performance evaluation of ultra-dense networks for 5G

Ultra dense network (UDN) is a promising technology enabling high power and spectrum efficiencies for future wireless systems such as 5th generation (5G) wireless networks. Regarding the importance of UDN, in this paper we investigate the performance of small cell networks with different small cell base station (SBS) densities via using a system-level simulation platform and some real traffic data provided by China Mobile Research Institute. We first build a practical distribution model for SBSs and then construct practical small cell deployment scenarios considering many practical limitations. After that, network throughputs with different transmission powers and densities of SBSs are simulated. In addition, the performance of cell edge users is also evaluated. Numerical results demonstrate that PPP model still provides an accurate model for constructing unplanned tiers even when many practical limitations are taken into account.
A comparative study on Helicobacter pylori infection in peptic ulcer disease patients with or without previous eradication therapy.

BACKGROUND/AIMS Although H. pyloric eradication therapy is indicated for peptic ulcer patients, the prevalence of H. pylori infection may be different between patients with active or chronic (scarred) peptic ulcers. This study aimed to compare the prevalence of H. pylori infection in active and chronic peptic ulcer patients with or without previous H. pyloric eradication therapy. METHODOLOGY Both non-invasive (13C or 14C urea breath test) and invasive methods (rapid urease test and histology) were used to detect H. pylori. From Dec. 2002 to Jan. 2003, 153 patients with 63% male were enrolled in this study. Fifty-six patients who previously received H. pyloric eradication therapy were enrolled as treated patients, and 97 patients who did not receive therapy were enrolled as untreated patients. RESULTS H. pylori infection rate was still high in untreated patients even when duodenal ulcer had been scarred (96% in active duodenal ulcer and 63% in scarred duodenal ulcer). In treated patients, H. pyloric infected rates were very low when peptic ulcers were scarred (0% in scarred gastric ulcer, 4% in scarred duodenal ulcer and 0% in both scarred ulcers). CONCLUSIONS H. pyloric eradication therapy is indicated for untreated patients even when endoscopic examination revealed chronic scarred duodenal ulcer.
Activation of toll-like receptors 2 and 4 by gram-negative periodontal bacteria.

BACKGROUND/AIMS Periodontitis is a chronic infectious disease associated with a gram-negative subgingival microflora. Bacterial components stimulate, among other receptors, Toll-like receptor (TLR) 2 and/or TLR4. Accumulating evidence indicates that both qualitatively and quantitatively distinct immune responses result from the triggering of TLR2 as compared to TLR4 triggering. The aim was to study the interaction of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Tannerella forsythensis, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum and Veillonella parvula with TLR2 and TLR4. We investigated all known serotypes (K(-), K1-K6) of P. gingivalis and A. actinomycetemcomitans serotype a-e strains for their potency to stimulate cytokine production. METHODS Human embryonic kidney (HEK) cells, stably transfected with CD14, CD14-TLR2, or CD14-TLR4 and whole blood were stimulated with bacterial sonicates. Cytokine production (interleukin-6, -8, -10 and -12) was measured in the supernatant by enzyme-linked immunosorbent assay. RESULTS All test bacteria stimulated HEK-CD14-TLR2, but only A. actinomycetemcomitans and V. parvula stimulated HEK-CD14-TLR4. No differences were found in the activation of HEK-CD14-TLR2/4, or cytokine production in whole blood between serotypes of P. gingivalis and A. actinomycetemcomitans. CONCLUSION Gram-negative periodontal bacteria predominantly stimulated TLR2, which may be of importance for the Th1/Th2 cell orientation of the immune response in periodontitis.