Miracle-dz/UniFAR-FTUs huggingface dataset:
Discrete and Essential Roles of the Multiple Domains of Arabidopsis FHY3 in Mediating Phytochrome A Signal Transduction1[C][W][OA]

Phytochrome A is the primary photoreceptor for mediating various far-red light-induced responses in higher plants. We recently showed that Arabidopsis (Arabidopsis thaliana) FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and FAR-RED-IMPAIRED RESPONSE1 (FAR1), a pair of homologous proteins sharing significant sequence homology to Mutator-like transposases, act as novel transcription factors essential for activating the expression of FHY1 and FHL (for FHY1-like), whose products are required for light-induced phytochrome A nuclear accumulation and subsequent light responses. FHY3, FAR1, and Mutator-like transposases also share a similar domain structure, including an N-terminal C2H2 zinc finger domain, a central putative core transposase domain, and a C-terminal SWIM motif (named after SWI2/SNF and MuDR transposases). In this study, we performed a promoter-swapping analysis of FHY3 and FAR1. Our results suggest that the partially overlapping functions of FHY3 and FAR1 entail divergence of their promoter activities and protein subfunctionalization. To gain a better understanding of the molecular mode of FHY3 function, we performed a structure-function analysis, using site-directed mutagenesis and transgenic approaches. We show that the conserved N-terminal C2H2 zinc finger domain is essential for direct DNA binding and biological function of FHY3 in mediating light signaling, whereas the central core transposase domain and C-terminal SWIM domain are essential for the transcriptional regulatory activity of FHY3 and its homodimerization or heterodimerization with FAR1. Furthermore, the ability to form homodimers or heterodimers largely correlates with the transcriptional regulatory activity of FHY3 in plant cells. Together, our results reveal discrete roles of the multiple domains of FHY3 and provide functional support for the proposition that FHY3 and FAR1 represent transcription factors derived from a Mutator-like transposase(s).
The Effect of Parallel Prototyping on Design Performance, Learning, and Self-Efficacy

Designs often improve with iteration. Does creating and receiving feedback on multiple prototypes in parallel — as opposed to serially — affect outcome, learning, and selfefficacy? Two experiments manipulated whether participants designed prototypes and received feedback in parallel or serial. In the first, participants designed Web advertisements and received descriptive critique on each prototype. As measured by click-through rate and expert ratings, ads created in the Parallel condition significantly outperformed those in the Serial condition. Independent raters found Parallel prototypes to be significantly more divergent. Parallel participants reported a larger increase in task-specific selfconfidence. In post-task interviews, several Serial participants reported negative reactions to critique; no Parallel participants reported this. The second study manipulated Parallel versus Serial for a simple mechanical design task. This study found no significant performance difference between conditions. We discuss differences between the tasks and the implications for understanding when and how parallel prototyping is beneficial.
SpiderStore: Exploiting Main Memory for Efficient RDF Graph Representation and Fast Querying

The constant growth of available RDF data requires fast and ecient querying facilities of graph data. So far, such data sets have been stored by using mapping techniques from graph structures to relational models, secondary memory structures or even complex main memory based models. We present the main memory database SpiderStore which is capable of eciently managing large RDF data sets and providing powerful and fast SPARQL processing facilities. The SpiderStore storage concept aims at storing the graph structure in main memory without performing any complex mappings. Therefore it exploits the natural web-structure of RDF by using fast and random access to main memory. The abandonment of additional mappings or meta-information therefore leads to a signicant performance gain compared to other common RDF stores.
Dopamine Attenuates Prefrontal Cortical Suppression of Sensory Inputs to the Basolateral Amygdala of Rats

The basolateral complex of the amygdala (BLA) plays a significant role in affective behavior that is likely regulated by afferents from the medial prefrontal cortex (mPFC). Studies suggest that dopamine (DA) is a necessary component for production of appropriate affective responses. In this study, prefrontal cortical and sensory cortical [temporal area 3 (Te3)] inputs to the BLA and their modulation by DA receptor activation was examined using in vivosingle-unit extracellular recordings. We found that Te3 inputs are more capable of driving BLA projection neuron firing, whereas mPFC inputs potently elicited firing from BLA interneurons. Moreover, mPFC stimulation before Te3 stimulation attenuated the probability of Te3-evoked spikes in BLA projection neurons, possibly via activation of inhibitory interneurons. DA receptor activation by apomorphine attenuated mPFC inputs, while augmenting Te3 inputs. Additionally, DA receptor activation suppressed mPFC-induced inhibition of Te3-evoked spikes. Thus, the mPFC may attenuate sensory-driven amygdala-mediated affective responses via recruitment of BLA inhibitory interneurons that suppress sensory cortical inputs. In situations of enhanced DA levels in the BLA, such as during stress and after amphetamine administration, mPFC regulation of BLA will be dampened, leading to a disinhibition of sensory-driven affective responses.
Amphiphilic, tri‐block copolymers provide potent, membrane‐targeted neuroprotection

Excitatory amino acid receptor activation and reactive oxygen species production are important mediators of neuronal death following acute brain injury and can lead to loss of membrane integrity. Poloxamer 188 (P188) is an amphiphilic, polyethylene‐polypropylene‐polyethylene copolymer that restores plasma membrane integrity of nonneuronal cells following membrane injury. Here, we demonstrate that P188 provides profound protection of hippocampal and cerebellar neurons following severe excitotoxic and oxidative injury in vitro, through membrane‐targeted mechanisms. Widespread death of cultured hippocampal neurons observed 48 h after N‐methyl‐D‐aspartate (NMDA) exposure was prevented by incubation of neurons in P188 following NMDA. P188 provided similar neuroprotection from kainate, menadione, and tert‐butyl‐hydroperoxide, but not from staurosporine. P188 application did not alter either NMDA receptor function or NMDA‐induced [Ca2+]i increases. Whole‐cell capacitance measurements revealed that P188 application increased cell surface area, consistent with its insertion into the plasma membrane. Following plasma membrane electroporation, P188 arrested loss of intracellular contents, which demonstrated direct restoration of plasma membrane integrity following physical disruption. Measurements of oxidized C11‐BODIPY581/591 fluorescence demonstrated that P188 blocked lipid peroxidation. These observations demonstrate that amphiphilic tri‐block copolymers provide strong, membrane‐targeted neuroprotection and represent a novel approach to the treatment of acute neuronal injury.
Incidence, prognosis, and etiology of end-stage liver disease in patients receiving home total parenteral nutrition.

BACKGROUND Elevations in liver function tests have been reported in patients receiving total parenteral nutrition (TPN). The clinical aspects of end-stage liver disease (ESLD) associated with the prolonged use of home TPN have not been fully clarified. In previous series patients with duodenocolostomies appeared to be at higher risk than persons with some jejunum or ileum remaining in situ. METHODS The records of 42 patients treated with home TPN for more than 1 year were examined. This constituted 283 person-years of home TPN. Patients with duodenocolostomies were examined as a separate group on the basis of the literature experience. RESULTS Six of 42 patients who received chronic home TPN had ESLD with 100% subsequent mortality, at an average of 10.8 +/- 7.1 months after the initial bilirubin elevation. Thirteen of 42 patients had superior mesenteric artery or vein thrombosis (SMT) leading to duodenocolostomy. In 8 of these 13 patients with SMT and underlying inflammatory or malignant disorder, 2 had ESLD. The remaining 5 SMT patients who had only minimal liver enzyme elevation over 13.6 +/- 6.7 (range 3 to 19) years of home TPN were significantly younger (36 +/- 7 years vs 64 +/- 13 years) and did not have underlying inflammation either by clinical diagnosis or as reflected in the high normal serum albumin level (> or = 4.0 g/dL). Despite their extreme short bowel syndrome and long exposure to home TPN, ESLD did not develop. CONCLUSIONS Approximately 15% of patients who receive prolonged TPN have ESLD with a high rate of morbidity and mortality. The combination of chronic inflammation and the short bowel syndrome appears to be necessary for the development of ESLD with prolonged home TPN.
Categorization of COPD patients in Turkey via GOLD 2013 strategy document: ALPHABET study

Objective To determine distribution of COPD assessment categories and physicians’ adherence to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013 strategy in Turkish COPD patients. Methods A total of 1,610 COPD patients (mean [standard deviation] age: 62.6 [9.9] years, 85.7% were males) were included in this multicenter, non-interventional, cross-sectional study. Patients were categorized via GOLD 2013 strategy document. Consistency between reported and re-classified GOLD categories, and measures used for symptom evaluation and exacerbation was analyzed. Results Overall, 41.1% of patients were assigned to GOLD A, while 13.2% were assigned to GOLD C categories. Long-acting beta-2 agonist + long-acting muscarinic antagonist + inhaled corticosteroid regimen was the most common treatment (62.0%). Over-treatment was noted in >70% of GOLD A, B, and C patients. A high consistency between measures of symptom evaluation (Kappa coefficient =0.993, P<0.0001) and a low-moderate consistency between exacerbation risk measures (Kappa coefficient =0.237, P<0.0001) were noted. Conclusion Our findings revealed GOLD A as the most prevalent category in Turkish cohort of COPD patients. Group assignment was altered depending on the chosen measure for symptom and risk assessment. Physician non-adherence to treatment recommendations in GOLD 2013 document leading to over-treatment in patients assigned to GOLD A, B, and C categories was also detected.
How much space is left for a new family of fermions

We perform an exploratory study of the allowed parameter range for the CKM-like mixing of hypothetical quarks of a fourth generation. As experimental constraints we use the tree-level determinations of the 3x3 Cabibbo-Kobayashi-Maskawa (CKM) elements and flavor-changing neutral current (FCNC) processes (K, D, B{sub d}, B{sub s} mixing and the decay b{yields}s{gamma}) under the assumption that the 4x4 CKM matrix is unitary. For the FCNCs we use some simplifying assumptions concerning the QCD corrections. Typically small mixing with the fourth family is favored; contrary to expectation, however, we find that also a quite large mixing with the fourth family is not yet excluded.
Biomechanical Comparison of Ulnar Collateral Ligament Reconstruction Between Palmaris Longus Autograft and Knee Medial Collateral Ligament Allograft

Background: Medial ulnar collateral ligament (mUCL) injury can cause significant pain and alter throwing mechanics. Common autograft options for mUCL reconstruction (UCLR) include the palmaris longus (PL) and hamstring tendons. Allograft use may reduce donor site morbidity and decrease function related to PL autografts. Purpose: To compare varus stability and load to failure between a novel allograft for UCLR—knee medial collateral ligament (kMCL)—and a PL autograft in human donor elbow specimens. Study Design: Controlled laboratory study. Methods: A total of 24 fresh-frozen human elbows were dissected to expose the mUCL. Medial elbow stability was tested with the mUCL intact (native), deficient, and reconstructed utilizing the humeral single-docking technique with either a (1) kMCL allograft (n = 12) or (2) a PL autograft (n = 12). A 3-N·m valgus torque was applied to the elbow, and valgus rotation of the ulna was recorded via motion tracking cameras. The elbow was cycled through a full range of motion 5 times. After kinematic testing, specimens were loaded to failure at 70° of elbow flexion, and failure modes were recorded. Results: The mUCL-deficient elbows demonstrated significantly greater valgus rotation compared with the intact and reconstructed elbows at every flexion angle tested (10°-120°) (P <.001). Both kMCL- and PL-reconstructed elbows exhibited significantly higher mean valgus rotation compared with the intact state between 10° and 40° of flexion (P < .01). There were no significant differences in valgus rotation at any flexion angle between the kMCL and PL graft groups. When loaded to failure, elbows reconstructed with both kMCL and PL grafts failed at similar torque values (18.6 ± 4 and 18.1 ± 3.4 N·m, respectively; P = .765). Conclusion: Fresh-frozen and aseptically processed kMCL allografts demonstrated similar kinematic and failure properties to PL tendon autografts in UCL-reconstructed elbows, although neither graft fully restored kinematics between 10° and 40°. Clinical Relevance: Prepared kMCL ligament allografts may provide a viable graft material when reconstructing elbow ligaments while avoiding the potential complications related to PL autografts— including donor site morbidity.
Systematic review of the prognostic effectiveness of SPECT myocardial perfusion scintigraphy in patients with suspected or known coronary artery disease and following myocardial infarction

ObjectivesIn patients with suspected or known coronary artery disease (CAD), or following myocardial infarction (MI), assessing the degree of ischaemia is important from a prognostic and therapeutic point of view. Single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy (MPS) is a non-invasive technique that allows the presence, location and extent of ischaemia to be determined. The aim of this systematic review was to assess the prognostic effectiveness of SPECT MPS. MethodsWe sought prognostic studies involving SPECT, exercise tolerance testing (ETT) and/or coronary angiography (CA) in people with suspected or known CAD, or following MI. Outcomes included cardiac death, non-fatal MI and revascularization. We searched the following databases: MEDLINE, PREMEDLINE, EMBASE, BIOSIS, Science Citation Index, the Cochrane Library, the Health Management Information Consortium and the Health Technology Assessment Database. ResultsTwenty-one observational studies enrolling 53,762 people reported the general prognostic value of SPECT MPS. In multivariate analysis, SPECT MPS variables yielded both independent and incremental value to combinations of clinical, ETT and angiographic variables in predicting cardiac death or non-fatal MI. Three comparative studies reported lower revascularization rates following a SPECT MPS-CA strategy (6–21%) compared with direct CA (16–44%). Four observational studies enrolling 2106 people reported the prognostic value of SPECT for patients following MI. In multivariate analysis including clinical history, ETT, SPECT MPS and angiographic variables, strategies involving SPECT MPS provided independent and incremental prognostic performance in predicting future cardiac events. ConclusionsSPECT MPS provides important additional information to that from ETT and/or CA that helps to risk-stratify patients with suspected or known CAD or following MI, enabling them to be managed more appropriately. Increasing the use of strategies involving SPECT MPS may identify lower risk patients for whom invasive CA might be avoided.
Quantifying the coevolutionary potential of multistep immune defenses

Coevolutionary models often assume host infection by parasites depends on a single bout of molecular recognition. As detailed immunological studies accumulate, however, it becomes increasingly apparent that the outcome of host–parasite interactions more generally depends on complex multiple step infection processes. For example, in plant and animal innate immunity, recognition steps are followed by downstream effector steps that kill recognized parasites, with the outcome depending on an escalatory molecular arms race. Here, we explore the consequences of such multistep infection processes for coevolution using a genetically explicit model. Model analyses reveal that polymorphism is much greater at recognition loci than effector loci, that host–genotype by parasite–genotype (Gh × Gp) interactions are larger for the recognition step, and that the recognition step contributes more to local adaptation than the effector step. These results suggest that (1) local adaptation is more likely when fitness measures are related to recognition versus downstream effectors, (2) effector loci, while mechanistically important, are less likely to harbor the Gh × Gp variation that fuels coevolution, and (3) recognition loci are better candidates for genomic hotspots of coevolution.
Emerging Metropolis: Politics of planning in Tehran during cold war

The Second World War and its associated political events of a national and global scale brought new circumstances, which was considerably influenced the development processes of Tehran. During World War II, Iran hoped that Washington would keep Britain and the Soviet Union from seizing control of the country's oil fields. In 1951 and 1952 Truman worked with Iranian Prime Minister, though unsuccessfully, to regain some of those lost oil rights for Iran. By the late 1950s and President Kennedy's presidency, he used aid as leverage for social reform. During the early years of 1960's, the Kennedy Administration was urging its allies in the third world to carry out necessary reforms in order to prevent popular discontent and enhance dominant ideology of ‘modernism'. In 1968, a major piece of legislation, the Urban Development and Renewal Act, enabled the municipality to implement Tehran's Comprehensive Plan (TCP 1968), which integrated all the elements of a 1960s' American city such as the separation of functions, highways, suburbs, shopping centers and housing area. The export of these American cities principles can only be understood from the background of the Cold War period, in which the east and west were both competing for cultural colonization of Middle Eastern strategically important cities like Tehran. During this period, the new developments supported by the oil boom of the 1970s, were built in different forms to constitute an expanding metropolis. In 1974, the second "International Congress of Architecture" with the theme of "Toward a Quality of Life" held at Persepolis and brought together all leading world architects and planners to review Iran's progress in its professional response to the challenges posed by increasing oil revenues. This research aims to represent the export of planning as a political means of cultural colonization of Third World during the cold war period.
The genetic code, 8-dimensional hypercomplex numbers and dyadic shifts

The article is devoted to algebraic features of structural phenomena of molecular ensembles of the genetic code. Matrix forms of presentations of the genetic code allow showing deep relations of the genetic code with dyadic shifts and algebras of 8-dimensional hypercomplex numbers. Hadamard matrices and orthogonal systems of Rademacher and Walsh functions, which are well-known formalisms from discrete signal processing, participate in this discovery of hidden structural features of the genetic code. The described results are useful to understand a non- casual character of the genetic code systems, which has a deep algebraic nature. The results lead to new theoretical approaches in the field of algebraic biology.
Cerebral hemodynamics and the aging brain REVIEW

Aging is associated with a number of degenerative changes in the structure and function of blood vessels. Recent studies have examined the impact of age on cerebral hemodynamics and brain structure and function. These studies have shown age related changes in resting cerebral blood flow, cerebral vasoreactivity, cerebral autoregulation, and neurovascular coupling. Studies have also shown that aging is associated with cortical atrophy and cerebral white matter injury. More recent studies have also examined the relationship between age related cerebral hemodynamics and brain structure and function. Cross-sectional studies have shown that both cerebral vasoreactivity and pulsatility index are associated with cerebral white matter injury. Similarly, cerebral vasoreactivity has also been associated with impaired mobility which is known to be a clinical consequence of cerebral white matter injury in the elderly people. Neurovascular coupling has also been associated with slow gait and impaired executive function.
Incretin Receptors for Glucagon-Like Peptide 1 and Glucose-Dependent Insulinotropic Polypeptide Are Essential for the Sustained Metabolic Actions of Vildagliptin in Mice

OBJECTIVE—Dipeptidyl peptidase-4 (DPP4) inhibitors lower blood glucose in diabetic subjects; however, the mechanism of action through which these agents improve glucose homeostasis remains incompletely understood. Although glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) represent important targets for DPP4 activity, whether additional substrates are important for the glucose-lowering actions of DPP4 inhibitors remains uncertain. RESEARCH DESIGN AND METHODS—We examined the efficacy of continuous vildagliptin administration in wild-type (WT) and dual incretin receptor knockout (DIRKO) mice after 8 weeks of a high-fat diet. RESULTS—Vildagliptin had no significant effect on food intake, energy expenditure, body composition, body weight gain, or insulin sensitivity in WT or DIRKO mice. However, glycemic excursion after oral glucose challenge was significantly reduced in WT but not in DIRKO mice after vildagliptin treatment. Moreover, vildagliptin increased levels of glucose-stimulated plasma insulin and reduced levels of cholesterol and triglycerides in WT but not in DIRKO mice. Vildagliptin treatment reduced the hepatic expression of genes important for cholesterol synthesis and fatty acid oxidation, including phospho-mevalonate kinase (Mvk), acyl-coenzyme dehydrogenase medium chain (Acadm), mevalonate (diphospho)decarboxylase (Mvd), and Acyl-CoA synthetase (Acsl1), in WT but not in DIRKO mice. However, vildagliptin also reduced levels of hepatic mRNA transcripts for farnesyl di-phosphate transferase (Fdft1), acetyl coenzyme A acyltransferase 1 (Acaa1), and carnitine palmitoyl transferase 1 (Cpt 1) in DIRKO mice. No direct effect of GLP-1 receptor agonists was detected on cholesterol or triglyceride synthesis and secretion in WT hepatocytes. CONCLUSIONS—These findings illustrate that although GLP-1 and GIP receptors represent the dominant molecular mechanisms for transducing the glucoregulatory actions of DPP4 inhibitors, prolonged DPP4 inhibition modulates the expression of genes important for lipid metabolism independent of incretin receptor action in vivo.