Miracle-dz/UniFAR-FTUs huggingface dataset:
The Asymmetric Interaction of Cas9 with Target DNA can Promote High Efficiency Homology‐Directed Genome Editing

Cas9 is an RNA‐guided endonuclease that has been adapted from its natural role in CRISPR‐mediated bacterial immunity to enable many applications demanding site‐specific DNA recognition. Wild type Cas9 has been rapidly embraced for genome engineering, either generating knockout cells and organisms via error‐prone non‐homologous end joining (NHEJ) or introducing precise edits via homology directed repair (HDR), while catalytically dead Cas9 (dCas9) fused to various effectors has been used for transcriptional regulation and genomic imaging. However, while Cas9's interaction with target DNA is central to its biological function and use as a genome targeting tool, the molecular nature of this complex is still poorly understood. We have found that the in vitro dissociation of wild type (wt) and dCas9 from double stranded DNA (dsDNA) are both remarkably slow, with a half‐life greater than six hours. However, this stable association is highly asymmetric, and wtCas9 releases only the PAM‐distal end of the non‐target DNA strand post‐cleavage while maintaining contact with the other three strands. dCas9 introduces a bubble into the target DNA that releases the non‐target strand and leaves it accessible for annealing by a complementary single stranded DNA (ssDNA). These activities are present during genome targeting in human cells and can be used to rationally design ssDNA templates that mediate highly efficient gene editing via annealing to the released strand. Optimized templates yield strand‐specific HDR rates over 50% and can furthermore mediate HDR from a single Cas9 nickase or dCas9. Our results highlight Cas9's unusually asymmetric interaction with target DNA, which could be functionally important for CRISPR spacer acquisition or viral interference. Our work also suggests that guiding the formation of specific DNA repair intermediates can dramatically increase the efficiency of genome editing. Because dCas9 is presumably incapable of introducing off‐target breaks in a genome, its use to stimulate HDR may be valuable for precision gene editing in certain therapeutic contexts.
LIZARDS OF THE GENUS TROPIDURUS (IGUANIA: TROPIDURIDAE) FROM THE SERRANIA DE HUANCHACA, BOLIVIA : NEW SPECIES, NATURAL HISTORY, AND A KEY TO THE GENUS

Four species of Tropidurus live in the vicinity of the Serrania de Huanchaca, an isolated mountain range overlapping the northeastern border of Bolivia and Brazil. We describe three of the four species as new to science. A new saxicolous species is most similar to T melano- pleurus. Like T melanopleurus, females of the new species are smaller and more brightly colored than males. A new arboreal species resembles T spinulosus and differs most strikingly by its squa- mation and brighter coloration. A second new saxicolous species resembles T etheridgei and appears to develop gravid coloration, a phenomenon widespread among iguanians but previously unreported for species of Tropidurus. Tropidurus umbra ochrocollaris from the Serranfa de Huanchaca is eco- logically and morphologically similar to T u. ochrocollaris elsewhere in Amazonia, but it has a short dorsal crest like the nominate race. Tropidurus spinulosus guarani Alvarez, Cei, and Scolaro is accorded specific status.
LipidMetabolism, Compartmentalization and Signalling in the Regulation of Pollen Tube Growth

To understand the biological context of lipid metabolism and signalling in pollen, we have to consider male gametophytes as organisms optimised for their role in sexual reproduction, but also for survival in dry conditions. While our knowledge of molecular mechanisms governing pollen development and pollen tube growth is based on the studies of a few model species (mostly Arabidopsis, tobacco, petunia and lily), important aspects of pollen development may vary substantially among species. Moreover, current understanding of pollen lipid biochemistry is rather fragmentary, since biochemically tractable amounts of pollen material are difficult to obtain, and knowledge of sporophytic lipid metabolism and signalling cannot be simply transferred to the study of male gametophytes.
Towards A Write ⊕ Execute Architecture For JIT Interpreters

JIT spraying is one of the main reasons why current web browsers still provide a large attack surface for remote exploits. It is capable of circumventing even the most sophisticated defense strategies against code injection, including address space layout randomization (ASLR), data execution prevention (DEP) or stack canaries. In this thesis, we present Lobotomy, an architecture for building injection-safe JIT engines by splitting compiler and executor into two different processes. We also present a proof-of-concept implementation of our approach by modifying the well-known JIT-Engine Tracemonkey as it is shipped with the Firefox Browser. Additionally, we provide a thorough evaluation of performance and code coverage of our version compared to the unmodified baseline.
ASSESSING THE IMPACT OF INTEREST RATE, CATERING, AND FAST-FOOD INCOME ON EMPLOYMENT IN THE SOCIAL SERVICES INDUSTRY

The employment rate is one of the economic indicators that determine a country's economic conditions. It plays a crucial role in social welfare and national development. South Africa is currently one of the countries experiencing a growing unemployment rate owing to inefficient macroeconomic performances, such as high interest rates and low income which contribute to economic instabilities. This paper intends to analyse the effect of the real interest rate, and producer income from fast-food and catering industries on social services employment in South Africa. To achieve this objective, the study applies various statistical and econometric approaches. These approaches include the unit root test, the Wald test, the error correction model, and the Toda-Yamamoto Granger non-causality test. Findings suggested a cointegration among the underpinned variables. A positive relationship was found between social services employment and income from both fast-food and catering industries. However, the interest rate was found to have a negative long-run impact on employment growth. The shortrun outcome revealed that the employment level within the social services industries may also be influenced by the lagged values of the interest rate and income from catering and fast-food industries. Grounded on these findings, the study suggests government support (subsidies and interest rate reduction) as a strategy to assist in sustaining fast-food and catering industries and creating more jobs for low-skilled workers.
A Comparison of the Effects of ABA and an Antitranspirant on Chilling Injury of Coleus, Cucumbers, and Dieffenbachia

Coleus blumei Benth ‘Buckley Supreme’, Cucumis sativus L. ‘Victory’, and Dieffenbachia picta Schott ‘Rudolph Roehrs’ plants were exposed to 5°C for 48 and 72 hr following pretreatment with abscisic acid (ABA) or an antitranspirant (ENVY). Foliar injury of untreated leaves occurred after 48 hr of exposure at 5°. Application of 200 mg.liter−1 ABA as a foliar spray provided protection against chilling symptoms in coleus and cucumber, but foliar application of ENVY had no protective effect. Dieffenbachia was not protected by either ABA or ENVY. Measurements of refreshed delayed light emission (RDLE) from excited chlorophyll molecules in intact leaves confirmed that ABA protected chilled cucumber chloroplasts; however, there was no difference between ABA-treated and untreated chilled dieffenbachia. Chemical names used: [S-(Z,E)]-5-(l-hydroxy-2,6,6-trimethyl-4-oxo-2-cyclohexen-l-yl)-3-methyl-2,4-pentadienoic acid [abscisic acid (ABA)].
Modeling germination and seedling elongation of common lambsquarters (Chenopodium album)

The ability to predict time of weed seedling emergence relative to the crop is an important component of a mechanistic model describing weed and crop competition. In this paper, we hypothesized that the process of germination could be described by the interaction of temperature and water potential and that the rate of seedling shoot and radicle elongation vary as a function of temperature. To test these hypotheses, incubator studies were conducted using seeds and seedlings of common lambsquarters. Probit analysis was used to account for variation in cardinal temperatures and base water potentials and to develop parameters for a new mathematical model that describes seed germination and shoot and radicle elongation in terms of hydrothermal time and temperature, respectively. This hydrothermal time model describes the phenology of seed germination using a single curve, generated from the relationship of temperature and water potential.
Slow Wave Dysfunction and Paroxysm Sound Detection : A case study of EEG data sonification in two patients with epilepsy

A parameter mapping sonification method can be used to convert EEG data into a sound. Sound equivalents of different EEG changes could help clinicians during EEG recording, monitoring and analysis. This method could also be used in home surveillance systems in people with epilepsy. We present an example of using a parametric based algorithm for epileptic discharge detection by non-expert listeners with short pre-training. The algorithm was applied onto data collected from two patients with epilepsy and different EEG abnormalities. Index Terms — Sonification, Epilepsy, EEG
Transversal profiles of dissolved oxygen in thin-layer open outdoor algal cultures

Differential mass balance of dissolved oxygen (DO) in algal culture layer flowing down an inclined open cultivation surface was set up. Using simplified aussumptions, a differential equation was derived for the course of DO concentration profile across algal culture layer. In the development of the equation were considered: hydraulics of culture flow on cultivation surface, rate of O 2 evolution by algae, molecular diffusivity and turbulent diffusivity of oxygen inside of layer. The equation was integrated numerically for apporopriate boundary conditions. Computations performed for 6 mm thick layer of the alga Chlorella kessleri, flowing at velocity 50 cms -1 on inclined cultivation surface (inclination 1.7 %) in 28 m long and 4 m wide outdoor culture unit revealed that main restistance against DO mass transfer from algal culture into atmosphere was found in boundary layer of culture near algal culture - atmosphere interface. Thickness 8 of the boundary layer was only several percent of thickness of the whole culture layer and was proportional to the square root of: culture temperature and mean DO concentration in the bulk of algal culture. Computations showed that turbulence in algal culture on cultivation surface was sufficient to create almost uniform DO transversal (across algal culture layer) profile outside boundary layer δ.
Description of four new species of the Cirolana ‘parva group’ (Crustacea: Isopoda: Cirolanidae) from Thailand, with supporting molecular (COI) data

ABSTRACT Four new species of the Cirolana ‘parva group’ from shallow coastal habitats in Thailand are described: Cirolana andamanensis sp. nov. and C. phangnga sp. nov., from the Andaman Sea, and C. siamensis sp. nov. and C. thailandica sp. nov. from the Gulf of Thailand. Molecular (The cytochrome oxidase subunit I gene) analysis incorporating taxa from the Cirolana ‘tuberculate group’ shows a monophyletic clade (Bayesian inference = 1 and maximum likelihood = 100%) within the Cirolana ‘parva group’ with two clades reflecting morphological characters. Cirolana andamanensis sp. nov. with antennula peduncle articles 1 and 2 entirely fused; male pereopod 1 without a setal fringe; uropod peduncle ventrolateral margin with 1 sensory seta. Cirolana phangnga sp. nov., C. siamensis sp. nov. and C. thailandica sp. nov. share the morphological characters of antennula peduncle articles 1 and 2 distinctly articulated; pereopod 1 in male with a setal fringe on the carpus and propodus; uropod peduncle ventrolateral margin with 3 sensory setae. Uncorrected p-distances strongly support the separation of these species, originally based on morphology, and show that the highest value of 32.1% is between C. thailandica sp. nov. and C. andamanensis sp. nov., while the lowest value of 22.5% is between C. phangnga sp. nov. and C. siamensis sp. nov.
Behavioral interactions among females of Halictus (Seladonia) lanei (Moure) (Hymenoptera: Halictidae)

Halictus (Seladonia) lanei (Moure) has the most extreme cephalic dimorphism, and thereby presumably also caste dimorphism, among the halictine bees. Previously known only from a few sites in Brazil, additional localities for this species are documented, including the first records for it from Bolivia, and a distribution map is provided. In order to investigate the possible social organization of this species in the absence of nest excavations, circle tube experiments were performed. In these arenas pairs of putative workers of this species generally behaved very aggressively, on average more so than any of the other halictine species studied with this apparatus. One pair, however, acted very cooperatively and perhaps they were nestmates. The circle tube behaviors are consistent with the species being eusocial, a fact also supported by the strong size dimorphism and comparisons with its sister species.
Finding common ground to treat primary and metastatic cancer: The potential of targeting tumor stroma

Primary carcinomas and metastases are complex organ-like structures composed of malignant parenchymal epithelial tissues and a desmoplastic stroma formed by accumulation of hematopoietic cells, mesenchymal stromal cells and extracellular matrix. The crosstalk between malignant epithelial cells and tumor stroma is becoming increasingly appreciated as a key determinant in tumor development, progression and metastasis, as well as inducing resistance to various cancer treatments including chemotherapy, radiotherapy and immunotherapy. Mechanistic understanding of how the tumor-stromal interaction contributes to tumor progression and therapeutic resistance will advance cancer therapies and improve clinical management, especially for patients with metastatic disease. Fibroblast activation protein (FAP) is a membrane surface protease found overexpressed in cancer-associated stromal cells. Overexpression of FAP is associated with tumor progression, metastasis and recurrence, and predicts a poorer prognosis in many types of human tumors. The central goal of my thesis project is to investigate whether FAP protease and/or FAP proteaseexpressing stromal cells play essential roles in tumor progression and metastasis. In collaboration with Drs. Steven Albelda and Carl June’s groups, we generated chimeric antigen receptor (CAR) T cells redirected against FAP+ stromal cells to study their impact on tumor progression. Conditional depletion of FAP+ stromal cells by FAP-CAR T cells restrains tumor progression without causing severe toxicity. Mechanistic investigations revealed that FAP+ stromal cells promote tumor growth via immune suppression and immuneindependent remodeling of the stromal microenvironment. Additionally, using FAP-deficient mice, I found that FAP protease promotes early malignant cell seeding and pulmonary metastatic outgrowth, possibly through regulating coagulation pathways and the inflammatory response, respectively. Finally, I observed that FAP protease promotes pancreatic cancer development, as its deletion delays the progression of preneoplastic lesions and tumor formation in a genetically engineered mouse model of pancreatic ductal carcinoma. FAP protease is also essential for inducing pancreatic cancer resistance to necrotic cell death and promoting metastasis and outgrowth in multiple target organs. Together, these findings demonstrate that molecular and cellular targeting of FAP represents a promising therapeutic approach for a variety of solid tumors. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Cell & Molecular Biology First Advisor Ellen Pure This dissertation is available at ScholarlyCommons: http://repository.upenn. edu/edissertations/1862
Dialysate magnesium, magnesium handling and clinical considerations in chronic hemodialysis patients

In a prospective study the acute impact of a 0.25 mmol/l magnesium (Mg) and of a 0.5 mmol/l Mg dialysate on the absolute amount of Mg removal, the resulting change in Mg parameters and on arrhythmias was investigated in 23 patients. Total serum Mg (tMg) was measured by atomic absorption spectrometry and ionized serum Mg (iMg) by an ion-selective electrode. In age- and sex-matched healthy controls (CO) tMg was 0.80 ± 0.06 and iMg 0.57 ± 0.02 mmol/l and Mg in red blood cells (rbc) 2.27 ± 0.16 mmol/l. The 0.5 mmol Mg/l dialysate reduced tMg from 0.99 ± 0.16 * to 0.87 ± 0.11 mmol/l and iMg from 0.69 ± 0.12 * to 0.59 ± 0.09 mmol/l and a 0.25 mmol Mg/l one tMg from 0.81 ± 0.08 * to 0.56 ± 0.06 mmol/l * and iMg from 0.57 ± 0.09 * to 0.37 ± 0.06 * mmol/l. Using the low-Mg dialysate, more arrhythmias were seen. The long-term impact of the different dialysates on intracellular Mg was studied in rbc. In the 0.25 mmol Mg/l dialysate group, rbc Mg was 2.07 ± 0.18 mmol/l which was significantly lower compared to CO indicating the development of Mg deficiency.
Dietary adaptations in the teeth of murine rodents (Muridae): a test of biomechanical predictions

Functional dental theory predicts that tooth shape responds evolutionarily to the mechanical properties of food. Most studies of mammalian teeth have focused on qualitative measures of dental anatomy and have not formally tested how the functional components of teeth adapt in response to diet. Here we generated a series of predictions for tooth morphology based on biomechanical models of food processing. We used murine rodents (Old World rats and mice) to test these predictions for the relationship between diet and morphology and to identify a suite of functional dental characteristics that best predict diets. One hundred and five dental characteristics were extracted from images of the upper and lower tooth rows and incisors for 98 species. After accounting for phylogenetic relationships, we showed that species evolving plant-dominated diets evolved deeper incisors, longer third molars, longer molar crests, blunter posteriorly angled cusps, and more expanded laterally oriented occlusal cusps than species adapting to animal-dominated diets. Measures of incisor depth, crest length, cusp angle and sharpness, occlusal cusp orientation, and the lengths of third molars proved the best predictors of dietary adaptation. Accounting for evolutionary history in a phylogenetic discriminant function analysis notably improved the classification accuracy. Molar morphology is strongly correlated with diet and we suggest that these dental traits can be used to infer diet with good accuracy for both extinct and extant murine species.
Partitioning of ecosystem respiration of CO2 released during land‐use transition from temperate agricultural grassland to Miscanthus × giganteus

Conversion of large areas of agricultural grassland is inevitable if European and UK domestic production of biomass is to play a significant role in meeting demand. Understanding the impact of these land‐use changes on soil carbon cycling and stocks depends on accurate predictions from well‐parameterized models. Key considerations are cultivation disturbance and the effect of autotrophic root input stimulation on soil carbon decomposition under novel biomass crops. This study presents partitioned parameters from the conversion of semi‐improved grassland to Miscanthus bioenergy production and compares the contribution of autotrophic and heterotrophic respiration to overall ecosystem respiration of CO2 in the first and second years of establishment. Repeated measures of respiration from within and without root exclusion collars were used to produce time‐series model integrations separating live root inputs from decomposition of grass residues ploughed in with cultivation of the new crop. These parameters were then compared to total ecosystem respiration derived from eddy covariance sensors. Average soil surface respiration was 13.4% higher in the second growing season, increasing from 2.9 to 3.29 g CO2‐C m−2 day−1. Total ecosystem respiration followed a similar trend, increasing from 4.07 to 5.4 g CO2‐C m−2 day−1. Heterotrophic respiration from the root exclusion collars was 32.2% lower in the second growing season at 1.20 g CO2‐C m−2 day−1 compared to the previous year at 1.77 g CO2‐C m−2 day−1. Of the total respiration flux over the two‐year time period, aboveground autotrophic respiration plus litter decomposition contributed 38.46% to total ecosystem respiration while belowground autotrophic respiration and stimulation by live root inputs contributed 46.44% to soil surface respiration. This figure is notably higher than mean figures for nonforest soils derived from the literature and demonstrates the importance of crop‐specific parameterization of respiration models.
Predicting Yellow Nutsedge (Cyperus esculentus) Emergence Using Degree-day Models

We examined the relationship between temperature and emergence of yellow nutsedge tubers to generate predictive models for the arid southwestern United States. Field experiments were conducted in California and Arizona to obtain phenological and temperature data needed to generate degree-day models. The effect of air temperature on emergence was tested with available programs using four methods to calculate degree-days (single sine, double sine, single triangle, and double triangle). Separate models were tested for each genotype examined (Arizona source and California source) as no one model was a good predictor of emergence when data were pooled. Results indicate that there is year to year variation in model accuracy but predictions of date of emergence can be made to within 2 d of actual emergence. This information can be used to schedule cultivations to reduce early yellow nutsedge competition in the field.
A molecular phylogeny of the “ Madascincus polleni species complex”, with description of a new species of scincid lizard from the coastal dune area of northern Madagascar

The present paper constitutes a study on a taxonomically confusing group of closely related species belonging to the Malagasy skink genus Madascincus, currently encompassing the nominal species M. polleni, M. intermedius and M. stumpffi. Based on combined analyses of mitochondrial and nuclear DNA sequences (ND1 and RAG2 genes, respectively), and morphological examination, we provide evidence for the existence of at least four distinct evolutionary lineages within this complex: Madascincus stumpffi; Madascincus arenicola sp. nov. from northern Madagascar; and two cryptic species morphologically similar to the name-bearing types of M. polleni and M. intermedius. The two latter species, although genetically distinct, appear to be morphologically indistinguishable and their taxonomic status cannot be resolved until a better sampling will be available.
Regrowth of a decimated population of Panax quinquefolium in a Missouri climax forest

A population of Panax quinquefolium was decimated by ginseng diggers in 1979, although most components of the climax forest community remained unaltered. After five years, 79% of the population size had been restored of which 25% were flowering plants; from these, 47 fruits matured. By 1985, 39% of the population consisted of flowering plants. The most logical assumption is that a majority of the new population originated from an in situ seed bank holding sufficient viable seeds to re-establish a large portion of the population until plants of the "new population" had become reproductive. Seeds of this herbaceous perennial apparently remained dormant and viable in the soil for at least five years, thus providing an adaptive mechanism for population restoration following major disruption and perhaps also adverse seasonal environmental conditions.