Miracle-dz/UniFAR-FTUs huggingface dataset:
Functions of the unique N-terminal region of glycoprotein E in the pathogenesis of varicella-zoster virus infection

Varicella-zoster virus (VZV) is an alphaherpesvirus that infects skin, lymphocytes, and sensory ganglia. VZV glycoprotein E (gE) has a unique N-terminal region (aa1-188), which is required for replication and includes domains involved in secondary envelopment, efficient cell-cell spread, and skin infection in vivo. The nonconserved N-terminal region also mediates binding to the insulin-degrading enzyme (IDE), which is proposed to be a VZV receptor. Using viral mutagenesis to make the recombinant rOka-ΔP27-G90, we showed that amino acids in this region are required for gE/IDE binding in infected cells; this deletion reduced cell-cell spread in vitro and skin infection in vivo. However, a gE point mutation, linker insertions, and partial deletions in the aa27-90 region, and deletion of a large portion of the unique N-terminal region, aa52-187, had similar or more severe effects on VZV replication in vitro and in vivo without disrupting the gE/IDE interaction. VZV replication in T cells in vivo was not impaired by deletion of gE aa27-90, suggesting that these gE residues are not essential for VZV T cell tropism. However, the rOka-ΔY51-P187 mutant failed to replicate in T cell xenografts as well as skin in vivo. VZV tropism for T cells and skin, which is necessary for its life cycle in the human host, requires this nonconserved region of the N-terminal region of VZV gE.
Essays in corporate finance

This thesis contributes to the empirical literature on how firms meet exceptional financing needs in relation to “investment spikes” or years with unusually large investment activities. In the earlier part of the thesis, I show that the financing of investment during an investment spike is very different from that at other times. I have done this using data for publicly traded US firms over the period 1988 to 2007 and a filtering procedure suggested by Bond et al. (2006). Specifically, external finance, in particular debt finance, is very important in financing investment in years categorized as investment spikes, confirming the findings of Mayer and Sussman (2005). In addition, it has been found that firms with smaller size, lower profitability, more future growth opportunities, fewer tangible assets and more RD spending tend to use more equity finance in relation to large investment requirements. I also propose the use of the Markov-switching filter to identify investment spikes. In implementing the Markov-switching filter, I apply a first-order two-state Markov-switching mean model to the investment rates de-trended using Hodrick and Prescott's (1997) filter. A Gibbs-sampling procedure is used to produce the marginal posterior distributions of unobserved state variables and model parameters. Among other advantages, this filter allows us to identify multi-year investment spikes. I show that two-year investment spikes identified by the Markov-switching filter are financed quite similarly to single-year investment spikes and that main findings are robust to calendar-time-dependent clustering of investment spikes generated by macroeconomic shocks. In the later part of the thesis, I find there is a positive effect of share liquidity on the propensity to raise debt finance. Using a sample of firm-year observations identified as investment spikes, I find that firms with more liquid shares tend to rely more heavily on debt to finance investment spikes. This result is robust to a control for the effects of firm size and other firm characteristics, the use of various leverage measures, and the use of a whole sample with investment spike characteristics. Another important finding is that firms with more liquid shares tend to have higher target leverage ratios. One interpretation of these results is that information spillovers from the presence of more informative share prices allow firms with more liquid shares to borrow on more favourable terms in normal times, as well as to obtain additional debt finance at lower costs when taking advantage of unusually large investment opportunities.
History matters more when explaining genetic diversity within the context of the core–periphery hypothesis

The core–periphery hypothesis (CPH) predicts that populations located at the periphery of a species' range should have lower levels of genetic variation than those at the centre of the range. However, most of the research on the CPH focuses on geographic distance and not on ecological distance, or uses categorical definitions of core and periphery to explain the distribution of genetic diversity. We use current climate data and historical climate data from the last glacial maxima to develop quantitative estimates of contemporary and historical ecological suitability using ecological niche models. We analysed genetic diversity using 12 polymorphic microsatellites to estimate changes in heterozygosity, allelic richness and population differentiation in 31 populations of the wood frog (Lithobates sylvaticus) spanning the species’ entire eastern clade (33o to 45o latitude) from Alabama, USA, to Nova Scotia, Canada. Our data support predictions based on the CPH. Populations showed significant differences in genetic diversity across the range, with lower levels of genetic variation at the geographic range edge and in areas with lower levels of historical and contemporary ecological suitability. However, history and geography (not current ecological suitability) best explain the patterns. This study highlights the importance of examining more than just geography when assessing the CPH, and the importance of historical ecological suitability in the maintenance of genetic diversity and population differentiation.
Identification of Murine H2-Dd- and H2-Ab-Restricted T-Cell Epitopes on a Novel Protective Antigen, MPT51, of Mycobacterium tuberculosis

ABSTRACT Both CD4+ type 1 helper T (Th1) cells and CD8+ cytotoxic T lymphocytes (CTL) play pivotal roles in protection against Mycobacterium tuberculosis infection. Here, we identified Th1 and CTL epitopes on a novel protective antigen, MPT51, in BALB/c and C57BL/6 mice. Mice were immunized with plasmid DNA encoding MPT51 by using a gene gun, and gamma interferon (IFN-γ) production from the immune spleen cells was analyzed in response to a synthetic overlapping peptide library covering the mature MPT51 sequence. In BALB/c mice, only one peptide, p21-40, appeared to stimulate the immune splenocytes to produce IFN-γ. Flow cytometric analysis with intracellular IFN-γ and the T-cell phenotype revealed that the p21-40 peptide contains an immunodominant CD8+ T-cell epitope. Further analysis with a computer-assisted algorithm permitted identification of a T-cell epitope, p24-32. In addition, a major histocompatibility complex class I stabilization assay with TAP2-deficient RMA-S cells transfected with Kd, Dd, or Ld indicated that the epitope is presented by Dd. Finally, we proved that the p24-32/Dd complex is recognized by IFN-γ-producing CTL. In C57BL/6 mice, we observed H2-Ab-restricted dominant and subdominant Th1 epitopes by using T-cell subset depletion analysis and three-color flow cytometry. The data obtained are useful for analyzing the role of MPT51-specific T cells in protective immunity and for designing a vaccine against M. tuberculosis infection.
Optimal detection, classification, and superposition resolution in neural waveform recordings

The effects of noise autocorrelation on neural waveform recognition (detection, classification, and superposition resolution) are investigated, using microelectrode recordings from the cortex of a monkey. Optimal waveform recognition is accomplished by passing the data through a whitening filter before matched filtering for detection or template matching for classification and superposition resolution. Template matching without whitening requires about 40% higher signal-to-noise ratio (SNR) than template matching with whitening for comparable classification and superposition resolution. The comparable difference for detection is 15%. <<ETX>>
Understanding Green IS Initiatives: A Multi-theoretical Framework

Sustainability is one of the key issues that organizations confront today, and ecologically responsible ("green") information systems (IS) initiatives are manifestations of sustainable business practices. Engaging in green IS initiatives can be challenging due to poor understanding of their holistic process. In this research, we develop a multi-theoretical framework to provide a holistic understanding of the process of implementing and adopting green IS initiatives. The framework examines how these initiatives’ structures, organizational attributes, and environment may influence this process. The framework also provides an agenda for how future studies of green IS can use the constructs proposed and develop them, undertake case studies to expand our propositions, and conduct surveys to verify propositions. In addition, practitioners can use our framework to better understand the differences between various types of green IS initiatives, identify which organizational and environmental factors to adopt, and gain a holistic view of the entire process.
Performance enhancement of 3D posts based antenna using high impedance surface

3D integrated antenna is a suitable choice for 24 GHz system on chip RF applications. The proposed 3D posts based antenna requires considerably smaller foot print (0.22 λ × 0.22 λ) and still provides better bandwidth (4.7%) as compared to a patch antenna. The paper proposes that by optimally placing the HIS cells surrounding the antenna feed structure or backing the antenna structure in the available space on the chip, a considerable improvement can be achieved in the impedance and gain bandwidth of the 3D antenna. Via-less HIS cells have been used and the performance is observed to be comparable to HIS with via, and a bandwidth of up to 28.6% has been obtained without any additional complexity in the design. The antenna has been designed at 2.5 GHz for ease of fabrication and has been demonstrated to be scalable to 25 GHz band working over a wide range from approximately 23 GHz to 30 GHz.
Natural variation in toxicity of wheat: potential for selection of nontoxic varieties for celiac disease patients.

BACKGROUND & AIMS Celiac disease (CD) is an intestinal disorder caused by T-cell responses to peptides derived from the gluten proteins present in wheat. Such peptides have been found both in the gliadin and glutenin proteins in gluten. The only cure for CD is a lifelong gluten-free diet. It is unknown, however, if all wheat varieties are equally harmful for patients. We investigated whether wheat varieties exist with a natural low number of T-cell-stimulatory epitopes. METHODS Gluten proteins present in public databases were analyzed for the presence of T-cell-stimulatory sequences. In addition, wheat accessions from diploid (AA, SS/BB, and DD genomes), tetraploid (AABB), and hexaploid (AABBDD) Triticum species were tested for the presence of T-cell-stimulatory epitopes in gliadins and glutenins by both T-cell and monoclonal antibody-based assays. RESULTS The database analysis readily identified gluten proteins that lack 1 or more of the known T-cell-stimulatory sequences. Moreover, both the T-cell- and antibody-based assays showed that a large variation exists in the amount of T-cell-stimulatory peptides present in the wheat accessions. CONCLUSIONS Sufficient genetic variation is present to endeavor the selection of wheat accessions that contain low amounts of T-cell-stimulatory sequences. Such materials may be used to select and breed wheat varieties suitable for consumption by CD patients, contributing to a well-balanced diet and an increase in their quality of life. Such varieties also may be useful for disease prevention in individuals at risk.
The Various Sources of Mitochondrial Oxygen Radicals: A Minireview

The mitochondrial respiratory chain is the main source of reactive oxygen species in the cell. The main sites of superoxide radical production are within Complexes I and III; however, Complex II, glycerol phosphate dehydrogenase and dihydroorotate dehydrogenase, are also sources of oxygen radicals. By using specific inhibitors within the complexes it is possible to obtain indications at the sites where redox components react with oxygen and in the compartments where they are released. The production of oxygen radicals is enhanced when the electron flow is lowered, and partial uncoupling is believed to be a means of preventing excess radical production.
Image-based reconstruction of three-dimensional myocardial infarct geometry for patient-specific modeling of cardiac electrophysiology.

PURPOSE Accurate three-dimensional (3D) reconstruction of myocardial infarct geometry is crucial to patient-specific modeling of the heart aimed at providing therapeutic guidance in ischemic cardiomyopathy. However, myocardial infarct imaging is clinically performed using two-dimensional (2D) late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) techniques, and a method to build accurate 3D infarct reconstructions from the 2D LGE-CMR images has been lacking. The purpose of this study was to address this need. METHODS The authors developed a novel methodology to reconstruct 3D infarct geometry from segmented low-resolution (Lo-res) clinical LGE-CMR images. Their methodology employed the so-called logarithm of odds (LogOdds) function to implicitly represent the shape of the infarct in segmented image slices as LogOdds maps. These 2D maps were then interpolated into a 3D image, and the result transformed via the inverse of LogOdds to a binary image representing the 3D infarct geometry. To assess the efficacy of this method, the authors utilized 39 high-resolution (Hi-res) LGE-CMR images, including 36 in vivo acquisitions of human subjects with prior myocardial infarction and 3 ex vivo scans of canine hearts following coronary ligation to induce infarction. The infarct was manually segmented by trained experts in each slice of the Hi-res images, and the segmented data were downsampled to typical clinical resolution. The proposed method was then used to reconstruct 3D infarct geometry from the downsampled images, and the resulting reconstructions were compared with the manually segmented data. The method was extensively evaluated using metrics based on geometry as well as results of electrophysiological simulations of cardiac sinus rhythm and ventricular tachycardia in individual hearts. Several alternative reconstruction techniques were also implemented and compared with the proposed method. RESULTS The accuracy of the LogOdds method in reconstructing 3D infarct geometry, as measured by the Dice similarity coefficient, was 82.10% ± 6.58%, a significantly higher value than those of the alternative reconstruction methods. Among outcomes of electrophysiological simulations with infarct reconstructions generated by various methods, the simulation results corresponding to the LogOdds method showed the smallest deviation from those corresponding to the manual reconstructions, as measured by metrics based on both activation maps and pseudo-ECGs. CONCLUSIONS The authors have developed a novel method for reconstructing 3D infarct geometry from segmented slices of Lo-res clinical 2D LGE-CMR images. This method outperformed alternative approaches in reproducing expert manual 3D reconstructions and in electrophysiological simulations.
Productivity growth at the sectoral level: measurement and projections

Global simulation models are increasingly used to assess future scenarios and the impact of policies related to food security, land use and climate change. A crucial element in these studies are assumptions on productivity change and technical progress, the key drivers of long-run economic growth and structural change. However, despite their importance, these assumptions are often simplistic or rather ad hoc. This paper addresses this issue by presenting sector and country specific projections for labour productivity till the year 2050 for seven economic regions in the world.
Training - Overtraining. A Prospective, Experimental Study with Experienced Middle- and Long-Distance Runners*

Overtraining may be one frequent cause of stagnation or decrease in performance capacity of athletes. Israel (19) differentiates between addisonoid (parasympathetic) and basedowoid (sympathetic) overtraining, characterized by inhibition or excitation. We tried to induce an overtraining syndrome in 8 experienced middle- and long-distance runners, based on an increase in training volume from an average 85.9 km (week 1) to 115.1 km (week 2) and 143.1 km (week 3) to 174.6 km per week (week 4). The influence of this training on cardiovascular, metabolic and hormonal parameters was examined with special respect to plasma and urinary catecholamines. Laboratory testing including graded treadmill running was performed on the days 0, 14 and 28. Training was held six days each week, with nearly 30 km per day in the fourth week. A stagnation in endurance performance capacity (running velocity at the aerobic-anaerobic transition range) and a decrease in maximum working capacity were observed in 6 and a stagnation in 2 of the 8 sportsmen, indicated by a decrease in total running distance from 4719 + 912 m to 4361 + 788 m during incremental treadmill ergometry. The sportsmen could neither improve nor could they even approximately reach their personal records during the subsequent competitive season. Subjective complaints, classified on a four-point scale, increased from 1.2 (week 1) to 3.2 in week 4. Glucose, lactate, ammonia, glycerol, free fatty acids, albumin, LDL, VLDL cholesterol, hemoglobin level (transient), leukocytes, and heart rate (before and during exercise) decreased significantly. Urea, creatinine, uric acid, GOT, GPT, gamma-GT, serum electrolytes (except phosphate and calcium) remained constant at the measuring times, CPK was elevated. (ABSTRACT TRUNCATED AT 250 WORDS)
Two separation-of-function isoforms of human TPP1 and a novel intragenic noncoding RNA dictate telomerase regulation in somatic and germ cells

Telomerase replicates chromosome ends in germ and somatic stem cells to facilitate continued proliferation. Telomerase action depends on the telomeric protein TPP1, which recruits telomerase to telomeres and facilitates processive DNA synthesis. Here we identify separation-of-function long (TPP1-L) and short (TPP1-S) isoforms of TPP1 differing only in 86 amino acids at their N-terminus. While both isoforms retain the ability to recruit telomerase, only TPP1-S facilitates telomere synthesis. We identify a novel intragenic noncoding RNA in the 3’-UTR of the TPP1-encoding gene that specifically shuts down telomerase activation-incompatible TPP1-L to establish TPP1-S as the predominant isoform in somatic cells. Strikingly, TPP1-L is the major isoform in testes, where it can function to restrain telomerase in mature germ cells. Our studies uncover how differential expression of two isoforms allows TPP1 to perform separate functions in different cells, and demonstrate how isoform choice can be determined by an intragenic noncoding RNA.
The study on the two characters in a kind of Markov chain's CRM model

Based on a previous study, the paper focuses on finding the two characters in a type of Markov chain transition matrix, which is using in describing a customer relationship management (CRM) model for a sales targeted application. The study demonstrates the inner characters of this type of model-variable structure characters and its LU decomposed result.
Design of camp–CRP‐activated promoters in Escherichia coli

We have studied the doeP2 promoter of Escherichia coli to define features that are required for optimal activation by the complex of adenosine 3′, 5′ monophosphate (cAMP) and the cAMP receptor protein (CRP). Systematic mutagenesis of deoP2 shows that the distance between the CRP site and the ‐10 hexamer is the crucial factor in determining whether the promoter is activated by camp–CRP. Based on these observations, we propose that camp–CRP‐activated promoters can be created by correctly aligning a CRP target and a ‐ 10 hexamer. This idea has been successfully tested by converting both a CRP‐in‐dependent promoter and a sequence resembling the consensus ‐10 hexamer to strongly camp–CRP‐activated promoters.
Retrospective Analysis of Beta-Blocker Instituted for Treatment of Hemangiomas (RABBIT Study)

Objective. To evaluate the safety and efficacy of our institutional beta-blocker protocol for treatment of complicated infantile hemangiomas (IH). Study Design. A retrospective descriptive study of 76 infants/children with IH treated with oral propranolol at the Children’s Hospital of Philadelphia between June 2008 and August 2010 was performed, assessing both the safety and efficacy of propranolol. Based on preliminary data showing hemangioma recrudescence off-treatment, we reviewed 9 additional patients with recrudescence between August 2010 and December 2011. Results. Mild adverse events included asymptomatic bradycardia, gastrointestinal symptoms, asymptomatic hypotension, cool hands/feet, asymptomatic hypoglycemia, and sleep disturbance. Sixteen patients had recrudescence of IH off-treatment, with propranolol discontinued at a median age of 14 months (interquartile range 10-15 months). Conclusions. Propranolol appears to be associated with minor, not severe symptomatic adverse events. Propranolol appears to be effective in treating complicated IH. Recrudescence can occur off-treatment, even with discontinuing propranolol as late as 15 months of age.
Long‐time overdamped Langevin dynamics of molecular chains

We present a novel algorithm of constrained, overdamped dynamics to study the long‐time properties of peptides, proteins, and related molecules. The constraints are applied to an all‐atom model of the molecule by projecting out all components of the nonbonding interactions which tend to alter fixed bond lengths and angles. Because the overdamped dynamical equations are first order in time, the constraints are satisfied by inversion of a banded matrix at each timestep, which is computationally efficient. Thermal effects are included through a Langevin noise term in the equation of motion. Because high‐frequency components of the motion have been eliminated, the timestep of the algorithm is determined by the nonbonding forces, which are two to three orders of magnitude weaker than the bonding forces. Using polyalanine as a test example, we demonstrate that trajectories simulating a microsecond of motion can be run about 103 times faster than an equivalent molecular dynamics simulation. © 1994 by John Wiley & Sons, Inc.
Phylogeography of the Cape velvet worm (Onychophora: Peripatopsis capensis) reveals the impact of Pliocene/Pleistocene climatic oscillations on Afromontane forest in the Western Cape, South Africa

Habitat specialists such as soft‐bodied invertebrates characterized by low dispersal capability and sensitivity to dehydration can be employed to examine biome histories. In this study, the Cape velvet worm (Peripatopsis capensis) was used to examine the impacts of climatic oscillations on historical Afromontane forest in the Western Cape, South Africa. Divergence time estimates suggest that the P. capensis species complex diverged during the Pliocene epoch. This period was characterized by dramatic climatic and topographical change. Subsequently, forest expansion and contraction cycles led to diversification within P. capensis. Increased levels of genetic differentiation were observed along a west‐to‐south‐easterly trajectory because the south‐eastern parts of the Cape Fold Mountain chain harbour larger, more stable fragments of forest patches, have more pronounced habitat heterogeneity and have historically received higher levels of rainfall. These results suggest the presence of three putative species within P. capensis, which are geographically discreet and genetically distinct.