Miracle-dz/UniFAR-FTUs huggingface dataset:
T‐cell receptor sequences that elicit strong down‐regulation of premature termination codon‐bearing transcripts

The nonsense‐mediated decay (NMD) RNA surveillance pathway detects and degrades mRNAs containing premature termination codons (PTCs). T‐cell receptor (TCR) and immunoglobulin transcripts, which commonly harbor PTCs as a result of programmed DNA rearrangement during normal development, are down‐regulated much more than other known mammalian gene transcripts in response to nonsense codons. Here, we demonstrate that this is not because of promoter or cell type but instead is directed by regulatory sequences within the rearranging VDJ exon and immediately flanking intron sequences of a Vβ8. 1 TCR‐β gene. Insertion of these sequences into a heterologous gene elicited strong down‐regulation (>30‐fold) in response to PTCs, indicating that this region is sufficient to trigger robust down‐regulation. The rearranging Vβ5. 1 exon and the flanking intron sequences from another member of the TCR‐β family also triggered strong down‐regulation, suggesting that down‐regulatory‐promoting elements are a conserved feature of TCR genes. Importantly, we found that the Vβ8. 1 down‐regulatory‐promoting element was position dependent, such that it failed to function when positioned downstream of a PTC. To our knowledge, this is the first class of down‐regulatory elements identified that act upstream of nonsense codons.
Ece1 and Tbx1 define distinct pathways to aortic arch morphogenesis

Pharyngeal arch artery (PAA) remodeling defects account for several cases of congenital heart disease. Mutations in the Endothelin‐1 genetic pathway or Tbx1, a candidate gene for DiGeorge syndrome, cause similar aortic arch defects. Previous research suggests that Tbx1 may trigger diffusible signals from the pharyngeal arches to support the growth of the PAAs that contribute to the mature aortic arch. The demonstration of genetic interaction between Tbx1 and Fgf8 pointed to FGF signaling as a possible candidate. Because Fgf8 interacts with Endothelin‐1 signaling and because Endothelin‐1 signaling interacts with neural crest‐derived cells in the pharyngeal apparatus, we hypothesized that Tbx1 and Endothelin‐1 signaling may contribute to the same pathway required for aortic arch morphogenesis. Therefore, we have analyzed mice mutated for the endothelin converting enzyme (Ece1) or Tbx1 genes and compound mutants. Results show that the two genes have different roles in the remodeling of the PAAs and do not interact. We propose that Tbx1 is required for the formation and early growth and remodeling of the PAAs, whereas Ece1 is necessary for regression of the cranial arch arteries and growth of the most caudal arch arteries. The latter function is likely related to the known role of the Endothelin‐1 pathway in neural crest function. Developmental Dynamics 228:95–104, 2003. © 2003 Wiley‐Liss, Inc.
Immunodiagnosis of histoplasmosis in a compromised host

Three serological tests for the diagnosis of histoplasmosis were compared for sensitivity and specificity in serum from blood bank donors, patients with histoplasmosis, and infected or noninfected immunosuppressed patients. The histoplasmin latex agglutination test was positive in 9% of the normal patients, 33% of the histoplasmosis patients, and 61% of the noninfected immunosuppressed patients. Since the test is prone to many false-positive results in patients with inflammatory diseases or non-Histoplasma infections, it has limited potential as a screening test among compromised patients. Immunodiffusion and counterimmunoelectrophoresis using a mycelial antigen were found to be more sensitive than either test using a combined yeast and mycelial antigen or a pure yeast phase antigen. Counterimmunoelectrophoresis at pH 7.2 proved to be the test of choice for serodiagnosis of histoplasmosis, resolving 85% of the immunocompetent infected patients and 100% of the infected immunosuppressed patients. Results indicated that counterimmunoelectrophoresis in conjunction with immunodiffusion could be used as a screening protocol to determine infection in incoming patients in a cancer hospital.
Effects of verapamil on the pharmacokinetics of dihydromyricetin in rats and its potential mechanism

Abstract 1. This study investigates the effects of verapamil on the pharmacokinetics of dihydromyricetin in rats and clarifies its main mechanism. 2. The pharmacokinetic profiles of oral or intravenous administration of dihydromyricetin in Sprague-Dawley rats with or without pretreatment with verapamil were investigated. In addition, the effects of verapamil on the transport and metabolic stability of dihydromyricetin were investigated using Caco-2 cell transwell model and rat liver microsomes. 3. In the oral group, verapamil could significantly increase Cmax, and decrease oral clearance of dihydromyricetin (p < 0.05). In the intravenous group, the Cmax also increased compared with the control group, but the difference was not significant. However, the t1/2 and clearance rate decreased than that of the control (p < 0.05). The oral bioavailability increased significantly (p < 0.05) from 3.84% to 6.84% with the pretreatment of verapamil. A markedly higher transport of dihydromyricetin across the Caco-2 cells was observed in the basolateral-to-apical direction and was abrogated in the presence of the P-gp inhibitor, verapamil. Additionally, the intrinsic clearance rate of dihydromyricetin was decreased by the pretreatment with verapamil (27.0 versus 32.5 μL/min/mg protein). 4. Those results indicated that verapamil could significantly change the pharmacokinetic profiles of dihydromyricetin in rats, and it might exert these effects through increasing the absorption of dihydromyricetin by inhibiting the activity of P-gp, or through inhibiting the metabolism of dihydromyricetin in rat liver.
Role of shape and localized resonances in extraordinary transmission through periodic arrays of subwavelength holes: Experiment and theory

The effect of the aspect ratio of rectangular holes on the transmissivity of periodic arrays of subwavelength holes in optically thick metal films is investigated. The transmissivity is found to be highly dependent on the aspect ratio of the holes. Moreover, the wavelengths of maximum transmissivity show a monotonous shift as a function of the aspect ratio of the holes. We attribute the enhanced transmission of the periodic arrays to an interplay of surface plasmons at the surface of the metal and shape resonances (also known as localized modes) inside the holes. The importance of the shape resonances was confirmed by a comparison of transmission through periodic hole arrays and through randomly distributed holes. Dispersion curves of periodic and random hole arrays confirmed the existence of shape resonance as well. We suggest that the localized modes effectively act as waveguides and increase the coupling efficiency of surface plasmons between both sides of the film, which results in a higher transmissivity. The shift of the maxima of the transmissivity may in part be explained by the spectral position of the localized modes in the individual holes. Finally measurements on similar patterns in Ni and Ag revealed that the occurrence of shape resonances is independent of the material of the film.
THE OUTPUT EULER EQUATION AND REAL INTEREST RATE REGIMES

Output Euler equations (OEE) for the US deliver slope estimates that are not significantly different from zero. This finding is counterintuitive as it implies a zero elasticity of intertemporal substitution (EIS) and aggregate demand movements that are nonresponsive to the short-term real interest rate. This paper shows that failure to account for regime changes in the dynamics of the real interest rate is responsible for this result. Based on a joint specification for the OEE and the real interest rate in an unobserved components model framework with Markov-switching parameters, the means, variances, and degrees of persistence of the real interest rate are different for the periods 1966–1980, 1980–1985, and 1985–2015. Once these regime changes are taken into account, the EIS estimate is 0.1 and no longer statistically insignificant. This finding is robust to alternative measures of the output gap as well as different specifications for the natural real interest rate.
Atypical employment in crisis-hit Greek regions: Local production structures, flexibilization and labour market re/deregulation

The article addresses the shifting patterns of atypical employment across the regions of Greece, severely hit by the 2009 crisis. Changes are depicted by NUTS-II level data for the pre- and post-crisis periods of 2005–2009 and 2009–2011. A regional categorization is suggested, as different forms of atypical employment, namely part-time, temporary, solo self-employment and family work, have expanded unevenly across space. The authors argue that different patterns are related to regional specialization and industrial structures differently affected by the crisis. Established forms of atypical employment have been shaken, while new highly precarious ones have been boosted. Moreover, regulatory reforms for higher labour flexibilization have also defined the emergent atypical employment patterns in Greece. The article points out that in the Greek labour market, already marked by high flexibility and poor job security and social benefits, recent regulatory reforms increasing flexibilization have deteriorated labour and devalued atypical employment.
Evidence of Chemolithoautotrophy in the Bacterial Community Associated with Alvinella pompejana, a Hydrothermal Vent Polychaete

ABSTRACT The deep-sea polychaete Alvinella pompejana colonizes tubes on the sides of black smoker chimneys along the East Pacific Rise. A diverse, yet phylogenetically constrained episymbiotic community is obligately associated with its dorsal surface. The morphologically and phylogenetically distinct dominant episymbionts have not yet been cultured, and there are no clearly defined roles for these bacteria in this symbiosis. A large insert fosmid library was screened for the presence of the two dominant phylotypes. Two fosmids, 35.2 and 38 kb, containing phylotype-specific 16S ribosmal DNA sequences were fully sequenced. Each fosmid had a gene encoding ATP citrate lyase, a key enzyme in the reverse tricarboxylic acid (rTCA) cycle, a CO2 fixation pathway. A selection of episymbiont communities from various geographic locations and vent sites were screened for the presence, diversity, and expression (via reverse transcription-PCR) of the ATP citrate lyase gene. Our results indicate that the ATP citrate lyase gene is not only a consistent presence in these episymbiont communities but is also expressed. Phylogenetically distinct forms of ATP citrate lyase were also found associated with and expressed by bacteria extracted from the tubes of A. pompejana. Utilizing PCR with degenerate primers based on a second key enzyme in the rTCA cycle, 2-oxoglutarate:acceptor oxidoreductase, we also demonstrated the persistent presence and expression of this gene in the episymbiont community. Our results suggest that members of both the episymbiont and the surrounding free-living communities display a chemolithoautotrophic form of growth and therefore contribute fixed carbon to other organisms in the vent community.
Loss Functions for Multiset Prediction

We study the problem of multiset prediction. The goal of multiset prediction is to train a predictor that maps an input to a multiset consisting of multiple items. Unlike existing problems in supervised learning, such as classification, ranking and sequence generation, there is no known order among items in a target multiset, and each item in the multiset may appear more than once, making this problem extremely challenging. In this paper, we propose a novel multiset loss function by viewing this problem from the perspective of sequential decision making. The proposed multiset loss function is empirically evaluated on two families of datasets, one synthetic and the other real, with varying levels of difficulty, against various baseline loss functions including reinforcement learning, sequence, and aggregated distribution matching loss functions. The experiments reveal the effectiveness of the proposed loss function over the others.
Pediatric bipolar disease: current and future perspectives for study of its long-term course and treatment.

AIM AND METHODS Findings from recent long-term, prospective longitudinal studies of the course, outcome and naturalistic treatment of adults with bipolar illness are highlighted as background for long-term developmental study of pediatric bipolar illness. RESULTS Accumulating knowledge of bipolar illness in adults underscores a high risk for multiple recurrences through the lifespan, significant medical morbidity, high rates of self-harm, economic and social burden and frequent treatment resistance with residual symptoms between major episodes. At present, there is no empirical foundation to support any assumption about the long-term course or outcome of bipolar illness when it arises in childhood or adolescence, or the effects of conventional pharmacotherapies in altering its course and limiting potentially adverse outcomes. The proposed research articulates specific descriptive aims that draw on adult findings and outlines core methodological requirements for such an endeavor. CONCLUSIONS Innovations in the description and quantitative analysis of prospective longitudinal clinical data must now be extended to large, systematically ascertained pediatric cohorts recruited through multicenter studies if there is to be a meaningful scientific advance in our knowledge of the enduring effects of bipolar illness and the potential value of contemporary approaches to its management.
Numerical Investigation of High-Efficiency InGaN-Based Multijunction Solar Cell

A four-junction InGaN-based multijunction solar cell structure is proposed theoretically. The simulation results show that, with the use of appropriately designed compositional grading layers, the performance of InGaN-based multijunction solar cell can be maintained without the cost in performance degradation caused by the polarization-induced electric field and the potential barriers resulting from the heterointerfaces. After the optimization in thicknesses for current matching, a high conversion efficiency of 46.45% can be achieved under 1000-sun AM1.5D illumination, in which the short-circuit current density, open-circuit voltage, and fill factor are 12.2×103 mA/cm2, 4.18 V, and 0.77, respectively. The simulation results suggest that, in addition to the detrimental effects caused by the built-in electric polarization and potential barriers, the issue of crystalline quality is another critical factor influencing the performance of multijunction solar cells.
A2A Adenosine Receptor Signaling in Lymphocytes and the Central Nervous System Regulates Inflammation during Experimental Autoimmune Encephalomyelitis

Extracellular adenosine has an important role in regulating the severity of inflammation during an immune response. Although there are four adenosine receptor (AR) subtypes, the A2AAR is both highly expressed on lymphocytes and known as a prime mediator of adenosine’s anti-inflammatory effects. To define the importance of A2AAR signaling during neuroinflammatory disease progression, we used the experimental autoimmune encephalomyelitis (EAE) animal model for multiple sclerosis. In EAE induction experiments, A2AAR antagonist treatment protected mice from disease development and its associated CNS lymphocyte infiltration. However, A2AAR−/− mice developed a more severe acute EAE phenotype characterized by more proinflammatory lymphocytes and activated microglia/macrophages. Interestingly, very high levels of A2AAR were expressed on the choroid plexus, a well-established CNS lymphocyte entry point. To determine the contribution of A2AAR signaling in lymphocytes and the CNS during EAE, we used bone marrow chimeric mice. Remarkably, A2AAR−/− donor hematopoietic cells potentiated severe EAE, whereas lack of A2AAR expression on nonhematopoietic cells protected against disease development. Although no defect in the suppressive ability of A2AAR−/− regulatory T cells was observed, A2AAR−/− lymphocytes were shown to proliferate more and produced more IFN-γ following stimulation. Despite this more proinflammatory phenotype, A2AAR antagonist treatment still protected against EAE when A2AAR−/− lymphocytes were adoptively transferred to T cell-deficient A2AAR+/+ mice. These results indicate that A2AAR expression on nonimmune cells (likely in the CNS) is required for efficient EAE development, while A2AAR lymphocyte expression is essential for limiting the severity of the inflammatory response.
Seasonal Dynamics of Previously Unknown Fungal Lineages in Tundra Soils

The finding that microbial communities are active under snow has changed the estimated global rates of biogeochemical processes beneath seasonal snow packs. We used microbiological and molecular techniques to elucidate the phylogenetic composition of undersnow microbial communities in Colorado, the United States. Here, we show that tundra soil microbial biomass reaches its annual peak under snow, and that fungi account for most of the biomass. Phylogenetic analysis of tundra soil fungi revealed a high diversity of fungi and three novel clades that constitute major new groups of fungi (divergent at the subphylum or class level). An abundance of previously unknown fungi that are active beneath the snow substantially broadens our understanding of both the diversity and biogeochemical functioning of fungi in cold environments.
Effects of chlorhexidine, minocycline, and metronidazole on Porphyromonas gingivalis strain 381 in biofilms.

BACKGROUND Porphyromonas gingivalis is found in subgingival biofilm and is associated with periodontal disease. Bacteria in biofilms are able to resist higher antimicrobial concentrations than in suspension. Little is known about the susceptibility of P. gingivalis in biofilms to antimicrobial agents. The effects of chlorhexidine gluconate, minocycline hydrochloride, and metronidazole on P. gingivalis biofilms were examined in vitro. METHODS P. gingivalis strain 381 biofilms were prepared on 32 hydroxyapatite disks. At 0, 24, 72, and 144 hours after perfusion of the three antimicrobial agents, two disks from each device were used to assess the antimicrobial effects by adenosine triphosphate (ATP) bioluminescence, and for morphological investigation by scanning electron microscopy (SEM). RESULTS Close relationships were found between the results of the ATP analyses and the SEM observations in all groups examined. A significant decrease (P < 0.001) in ATP content was found between the chlorhexidine-treated and control groups. The extracellular matrix structure and P. gingivalis cells were altered in the presence of chlorhexidine. Minocycline hydrochloride also caused a decrease (P < 0.05) in the ATP content and morphological change on P. gingivalis biofilms. Metronidazole showed no significant efficacy against P. gingivalis biofilms. CONCLUSION Chlorhexidine gluconate was effective at reducing the viability of P. gingivalis 381 cells in biofilms, while minocycline hydrochloride and metronidazole exhibited weaker effects.
Procedurally Fair Implementation: The Cost of Insisting on Symmetry

We derive a necessary and a sufficient condition for Nash implementation with a procedurally fair mechanism. Our result has a nice analogue with the path-braking result of Maskin [Nash equilibrium and welfare optimality, Rev. Econ. Stud. 66 (1999) 23-38. ], and therefore, it allows us to give a simple characterization of those choice rules that are implementable, but not in a procedurally fair way. This reveals the constraints that insisting on procedural fairness impose on the collective.
Epidemiology of pediatric meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis in Israel: a 3-year nationwide prospective study. Israeli Pediatric Bacteremia and Meningitis Group.

In a 3-year nationwide prospective study on pediatric meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis in Israel, 1258 invasive infections with a known focus were observed. Meningitis was found in 482 (38%): 56%, 16%, and 76% of all infections by H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively. The incidence of meningitis during the first year of life was 67.1, 17.5, and 9.5/100,000 for H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively, and in children < 5 years old it was 18.5, 5.3, and 5.2. Extrapolated for a population in which 100,000 live births occur yearly, 2097 hospital days were required. The case fatality rate was 2.2%, 5.9%, and 6.3% for H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively. Boys were affected significantly more often than girls, but mortality was higher among girls. On the basis of the observed serotypes and age distribution, even with optimal vaccine development in the next 5 years, it is not likely that > 50% of all cases will be prevented.
Efficient, Accurate, and Rotation-Invariant Iris Code

The large scale of the recently demanded biometric systems has put a pressure on creating a more efficient, accurate, and private biometric solutions. Iris biometrics is one of the most distinctive and widely used biometric characteristics. High-performing iris representations suffer from the curse of rotation inconsistency. This is usually solved by assuming a range of rotational errors and performing a number of comparisons over this range, which results in a high computational effort and limits indexing and template protection. This work presents a generic and parameter-free transformation of binary iris representation into a rotation-invariant space. The goal is to perform accurate and efficient comparison and enable further indexing and template protection deployment. The proposed approach was tested on a database of 10 000 subjects of the ISYN1 iris database generated by CASIA. Besides providing a compact and rotational-invariant representation, the proposed approach reduced the equal error rate by more than 55% and the computational time by a factor of up to 44 compared to the original representation.