Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug Repurposing Using the Anthrax Toxin Internalization Pathway

of the Dissertation Drug Repurposing Using the Anthrax Toxin Internalization Pathway By Leeor Zilbermintz Keck Graduate Institute of Applied Life Sciences: 2017 Pathogens and pathogenic agents such as lethal toxin, exploit host proteins for their success. Antibiotic discovery efforts have been focused on developing drugs that selectively target pathogens, despite the potential for drug resistance and providing no guarantee of fewer side effects for the patient. This dissertation describes the systematic efforts to identify drugs that alter those host proteins that are involved in the anthrax toxin internalization pathway. Anthrax is a rare and lethal disease caused by the toxin producing, gram-positive bacterium, Bacillus anthracis. The lethality of anthrax is largely attributed to the toxins that circulate within the host, destroying host tissues as well as the immune system, thus hampering host efforts to destroy the bacteria. Drug candidates were identified through cellular and protein-based screens using a drug library comprised of previously approved and off-patent drugs. Such a library creates the potential for identifying therapies for new indications, while potentially reducing the time and capital necessary for regulatory approval. We have successfully identified an anthrax antitoxin drug that interferes with host Cathepsin B, a lysosomal protein necessary for authophagic flux. On the observation that Cathepsin B is necessary for the success of other pathogenic agents, we demonstrated that our drug hit could prevent other infections, such as Ebola. Subsequent screens were designed to optimize the search for broad-spectrum therapies that interfere with those host proteins involved in the anthrax toxin internalization pathway but which play a role in internalizing other pathogenic agents such as Pseudomonas exotoxin A, Cholera, and Diphtheria toxin. We were able to identify a drug that inhibits host caspases, proteases involved in programmed cell death, and showed that this drug was a successful broad-spectrum therapy for Zika virus. Finally we aimed to indentify drugs that could simultaneously interfere with host proteins and anthrax lethal toxin, and identified two drugs. Drug optimization and drug combinations based on our host-oriented and broad-spectrum identification methods could provide for more effective and better-tolerated therapies for patients suffering from infectious diseases. Dedication To my Ima and Aba who’ve supported my learning and education for nearly three decades
What does positive psychology tell us about early intervention and prevention with children and adolescents? A review of positive psychological interventions with young people

ABSTRACT This paper reviews school-based (n = 212) and clinically-based (n = 68) positive psychological interventions (PPIs) for children and adolescents. A new 3 × 3 classification of PPIs was developed based on the processes and content of the PPI and the outcomes measured. This classification involves 9 different types of interventions depending on whether the intervention focuses on positive, remedial, or both positive and remedial processes and content, and whether the intervention aims to evade or address challenges, deficits, or disorders or improve or elicit positive outcomes. Positive content-balanced outcomes interventions were the most common type used in schools (38%) and clinical settings (63%). Mindfulness was the most common approach used (49% in schools and 71% in clinical settings). Surprisingly, relatively few studies focused on well-established positive psychological constructs, such as strengths, hope, and gratitude. Overall, the results suggest strong support for the use of PPIs in school and clinical contexts.
Comparative Assessment of Different Methods in Generating Design Storm Hyetographs for the Philippines

Design storm hyetographs are synthetic temporal rainfall patterns used as input for flood modeling studies, drainage design and hydrodynamic modeling. In practice, the Philippines adopts the alternating block (AB) method to derive hyetographs using PAGASA-synthesized rainfall intensity-duration-frequency (RIDF) curves. In this study, six other methods- AB from actual RIDF curve, actual normalized 24-hour storms and four different patterns derived by Huff (1967)- were tested using the tipping-bucket raingauge records of a local weather station. Nonparametric statistical tests were employed to determine the significant difference between and among distributions. Moreover, Chi-squared goodness-of-fit test was used to compare the hyetographs with data from actual storms. The PAGASA AB hyetographs, while accurate in some instances, do not always represent actual storms well. Furthermore, other methods may have better fits for other storms. This study recommends further research in establishing design hyetographs in the Philippines.
International Journal of Engineering

Annually, web search engine providers spend a lot of money on re-ranking documents in search engine result pages (SERP). Click models provide advantageous information for re-ranking documents in SERPs through modeling interactions among users and search engines. Here, three modules are employed to predict users' clicks on SERPs simultaneously, the first module tries to predict users' click behaviors using Probabilistic Graphical Models , the second module is a Time-series Deep Neural Click Model which predicts users' clicks on documents and finally, the third module is a similarity-based measure which creates a graph of document-query relations and uses SimRank Algorithm to predict the similarity. After running these three simultaneous processes, three click probability values are fed to an MLP classifier as inputs. The MLP classifier learns to decide on top of the three preceding modules, then it predicts a probability value which shows how probable a document is to be clicked by a user. The proposed system is evaluated on the Yandex dataset as a standard click log dataset. The results demonstrate the superiority of our model over the well-known click models in terms of perplexity
Plasma Membrane H+-ATPase during Embryo Dormancy and Dormancy Release in Horse Chestnut Seeds

Horse chestnut seeds harvested in October were exposed to wet cold stratification for 14 weeks, thus providing a way for seeds to overcome the state of deep physiological dormancy and acquire the ability to germinate. During first 5-6 weeks, a small portion of seeds germinated hardly and slowly while later on seeds germinated more uniformly and rapidly. The experiments with facilitated water supply have shown that 5-6 weeks is the state of embryo dormancy, which did not depend on water inflow, whereas during 6-14 weeks these embryos became capable to germinate, but this capacity was limited by water penetration through seed coat. Two distinct periods were identified in deep dormancy, namely embryo dormancy and coat-imposed dormancy (dormancy release). They differ in plasma membrane H + -ATPase behavior. During embryo dormancy, the the transformation occurred from autoinhibited form preformed during seed maturation to an active form, whereas during dormancy release the activity of enzyme increased up to the levels typical for germinating seeds.
Psychological status of Wuhan medical staff in fighting against COVID-19/ 新型冠状病毒肺炎疫情对武汉市一线医护人员心理状况的影响

Objective: To investigate the mental health conditions of Chinese medical staff in response to coronavirus disease 2019 (COVID-19) outbreak in Wuhan, Hubei. Methods: We did a survey with SCL-90 in 112 frontline medical staff who were working in the period of COVID-19 outbreak. Results: There were significant differences in somatization, anxiety, and terror (P<0.01), and had significant differences (P<0.05) in obsession and psychosis between the frontline medical staff and the general population. There was significant difference only in somatization factor of medical staff between different genders (P<0.05). The factors of somatization, anxiety, and psychotic had significant differences between the medical staff with a monthly household income <10 000 Yuan(RMB) and those with income ≥10 000 Yuan (P<0.05), and interpersonal sensitivity, hostility, and paranoid factors also had significant differences between two different monthly household income groups (P<0.01). Conclusion: The frontline medical staff had a lower level of psychological status, which is manifested by stronger somatization, anxiety, and horror of medical staff. The medical staff with different gender and different family income had different psychological status. We need to pay attention to the mental health of frontline medical staff in the epidemic, and provide guarantees to the medical staff to maintain a healthy working status.
Founder relationships and conservation management: empirical kinships reveal the effect on breeding programmes when founders are assumed to be unrelated

Conservation breeding programmes have become widespread as natural habitats shrink, and have been historically managed using pedigree data and an assumption that population founders are unrelated. Molecular genotyping is able to determine founder relatedness, but is rarely used. To empirically test the impact of assuming founders to be unrelated, we utilized data from 203 founding individuals and 11 subsequent years of breeding records for the Tasmanian devil (Sarcophilus harrisii) insurance population. We integrated molecular data (N = 119 founders) and detailed trapping information (N = 203 founders) to test how founder relationship assumptions impacted the genetic characteristics of the population over time (N = 942 unique individuals). We developed a method to combine molecular kinship (using the TrioML estimator), year of birth and trapping location, and integrated the resulting empirical kinship estimates into population management software. We tested the effect of using pedigree data only, versus our integrated approach, on population outcomes. Inbreeding coefficients evaluated using the integrated approach were significantly higher than pedigree‐only inbreeding coefficients in the first few years following population establishment. A geographic distance‐only approach showed an association between kinship and probability of successful breeding. Our results show the value in using field and/or molecular data combined with pedigree data in conservation breeding programmes to provide new information for managing crucial populations and improving their success. We caution population managers against commencing expensive conservation breeding programmes in the absence of understanding founder relatedness, especially when wild augmentation is a goal. Long‐term costs of assuming founders are unrelated include financial costs, reduced productivity and release of potentially highly inbred individuals.
Cambium Disconnection, Rootstock, and Canopy Training Impacts on Growth and Leaf Mineral Nutrients in ‘Aztec Fuji’ Apple

ABSTRACT The impacts of cambium disconnection in ‘Aztec Fuji’ apple (Malus x domestica Borkh) trees on two rootstocks, each with either tall spindle (TS) or central leader with four lower main scaffolds (CL) architectures, on growth and leaf minerals were studied over 2015 and 2016 seasons. Trees on Bud 9 had shorter terminal shoots, smaller trunk cross sectional area (TCSA), and lower concentrations of leaf nitrogen (N), potassium (K), magnesium (Mg), and zinc (Zn) but higher leaf calcium (Ca) and leaf percentage dry weight than those on Nic 29. Trees trained into a CL had longer terminal shoots and higher leaf N (based on a percentage dry wt), but lower leaf fresh and dry weights and percentage dry weight than did those with a TS system in 2015. Trees with a CL system had higher concentration and content of leaf K as compared to trees on TS system in 2016. Application of bark girdling in 2015 (BG15) or bark girdling in both 2015 and 2016 (BG1516) reduced concentrations of leaf N, Ca, and Mg within the same year. Trees receiving a BG15 treatment had higher concentration of leaf K in 2015.
STRUCTURAL STUDIES OF TRANSCRIPTIONAL REGULATION BY LysR-TYPE TRANSCRIPTIONAL REGULATORS IN BACTERIA

LysR-type transcriptional regulators (LTTRs) comprise one of the largest families of transcriptional regulators in bacteria and control gene expression of various types of metabolic, virulence and physiological functions. LTTRs typically form homotetramers and require an inducer molecule(s) to activate the transcription of target genes. The N-terminal region of LTTRs contains a DNAbinding domain (DBD) with the winged helix-turn-helix motif that specifically binds the promoter region of target genes. The C-terminal region of LTTRs is connected to the DBD by a linker helix and forms the regulatory domain (RD) that contains a binding pocket for inducer molecules. Crystal structures of several LTTR family members together with their biochemical analyses have provided a potential mechanism for the initial process of transcriptional activation by LTTRs. First, helix α3 of the winged helix-turn-helix motif in DBD is supposed to distinguish the recognition binding site (RBS) in the promoter region, resulting in complex formation through interactions between two DBDs in the tetrameric LTTR and RBS. Formation of this complex seems to enable interactions between the other two DBDs in the LTTR tetramer and the activation binding site (ABS) in the promoter region. The binding of the tetrameric LTTR to both the RBS and ABS causes the promoter DNA to adopt a bent structure because the four DBDs in the tetrameric LTTR are arranged in a V-shaped manner at the bottom of the LTTR. Interaction of an inducer molecule(s) with the RD seems to cause a quaternary structural change of the LTTR that relaxes the bending angle of the promoter DNA with a concomitant shift of the bound DBDs at the ABS. These events facilitate recruitment of RNA polymerase to its binding site in the promoter region, which overlaps with the ABS for LTTR.
The Effect of Setting a Warning Vaccination Level on a Stochastic SIVS Model with Imperfect Vaccine

This paper deals with a stochastic Susceptible-Infective-Vaccinated-Susceptible (SIVS) model with infection reintroduction. Health policies depend on vaccine coverage, v 0 , that guarantees herd immunity levels in the population. Vaccine failures occur when an organism develops a disease despite of being vaccinated against it. After vaccination, a proportion of healthy individuals unsuccessfully tries to increase antibody levels and, consequently these individuals are not immune to the vaccine preventable disease. When an infectious process is in progress, the initial vaccine coverage drops down and herd immunity will be lost. Our objective was to introduce a warning vaccination level and define random measures quantifying the time until the number of vaccinated descends to a warning vaccination level (i.e., the so-called sleeping period), and the epidemic size. A sensitivity analysis was performed to assess the influence of the model parameters on the variation and robustness of the sleeping period and the number of infections observed within it.
Bycatch composition of cutlassfish trawlers during fishing season in Bushehr and Hormozgan, Persian Gulf, Iran

Fouladi Sabet A, Paighambari SY, Pouladi M, Raeisi H, Abbaspour Naderi R. 2018. Bycatch composition of cutlassfish trawlers during fishing season in Bushehr and Hormozgan, Persian Gulf, Iran. Biodiversitas 19: 2275-2282. This investigation was conducted to determine the bycatch composition of cutlassfish (Trichiurus lepturus) trawlers in Bushehr and Hormozgan waters during fishing season 2013. Data collection was carried out in the summer for Bushehr and in the autumn for Hormozgan province for one month. All trawler vessels were equipped with a 36 m head rope and 75 mm stretched mesh size in the codend and 90 to 200 mm stretched mesh size in the panel. 47 species included 35 species of teleosts, 9 species of elasmobranches and 3 species of invertebrates were identified in Bushehr. Also, 48 species included 38 species of teleosts, 7 species of elasmobranches and 3 species of invertebrates were identified in Hormozgan. The weight and numerical averages of bycatch species were 25.41 (kg h-1) and 205.9 (n h-1) in Bushehr, and 92.58 (kg h-1) and 440.4 (n h-1) in Hormozagan. I. megaloptera, S. tumbil, N. japonicus, D. acuta, C. sexfasciatus, L. equulus in Bushehr and P. sextarius, I. megalopteran, M. cinereus, P. macrophthalmus, N. japonicus and S. tumbil in Hormozgan had highest catch weight. Based on the weight and number, PCA and nMDS methods were indicative of two different assemblages in hunting places. Furthermore, ANOSIM similarity analysis confirmed the results of PCA and nMDS and showed a significant difference in the catch composition of two fishing zones.
Twelve years of low nutrient input stimulates growth of trees and dwarf shrubs in the treeline ecotone

Almost all natural terrestrial ecosystems are nutrient limited in terms of growth, and we expect treeline vegetation to be no exception. However, direct constraints of low temperature on tissue formation may superimpose effects of low nutrient availability. We examined growth responses of two tree (Larix decidua and Pinus uncinata) and two dwarf shrub species (Vaccinium myrtillus and Vaccinium gaultherioides) to 12 years of moderate fertilizer addition (NPK applied at a rate of 15 and 30 kg nitrogen ha−1 a−1) along an elevation gradient within the treeline ecotone in the Swiss Alps (2,083 to 2,225 m a.s.l.). We measured annual top‐ and side‐shoot increments as well as stem ring width in trees and shoot increments in dwarf shrubs. Fertilizer addition increased soil nutrient availability, indicated by enhanced soil extractable N, higher concentrations of N, P and K in leaves and higher foliar δ15N. Fertilizer addition stimulated annual growth of all four species: by 11%–20% for L. decidua and 15%–36% for P. uncinata (depending on trait) and by 8%–16% for the two dwarf shrub species. Growth stimulation by the higher fertilizer dose was not significantly stronger than by the lower dose (except for V. gaultherioides), suggesting an overall low nutrient demand for growth and saturation at a rather low nutrient input. Synthesis. Even slightly enhanced nutrient availability can stimulate growth of trees and dwarf shrubs in an alpine treeline ecosystem. Ongoing atmospheric nutrient deposition, in conjunction with global warming, may accelerate plant growth at the treeline.
Effect of Raw Extract of Hybanthus enneaspermus (L.) F. Muell. on the Fertility Test in Female Mice (Mus musculus L)

Hybanthus ennespermus (L.) (Violaceae) has no toxicity asper the earlier reports of fertility traditional medicine used by the tribal people of Grizzled Giant Squirrel Wildlife Sanctuary, Srivilliputur, Southern India. In the present study, fertility effect of Hybanthus enneaspermus (Violaceae) whole part of plant evaluated in adult female mice (Mus musculus). Raw extract of Hybanthus enneaspermus (REHE) was administered orally at the doses of 100 mg/kg body weight for a duration of 30 days and normal salinw (0.9%) to control groups. There were no significance changes in the body weight (P<0.05). The Possibility of marked increase in serum estradiol level (P<0.05) significantly. Administered of REHE in mice did not show any variation in the hematological and biochemical parameters. It is raw extract of Hybanthus enneaspermus (REHE) showed on above result indicated that this alcoholic free extract of Hybanthus ennaespermus confirm the fertility effect of above study.
Design of Drug Recovery Scheme Based on Path Optimization

Countries with the upsurge of garbage sorting, all over the Word attach importance to the recycling of expired medical products. The design of reverse logistics network of expired drugs has become a key problem in the field of pharmaceutical safety. Considering that expired drugs can not be recovered effectively, this paper studies the problem of drug recovery logistics by using TSP model and mileage saving model. It is beneficial to arouse the enthusiasm of enterprises and residents to participate in the recovery of expired drugs, thus reducing the production and manufacturing costs of pharmaceutical enterprises in China and reducing the pollution of waste drugs to the environment.
Nano-enhanced optical gene delivery to retinal degenerated mice

The efficient and targeted delivery of genes and other impermeable therapeutic molecules into retinal cells is of immense importance for therapy of various visual disorders. Traditional methods for gene delivery require viral transfection, or chemical methods that suffer from one or many drawbacks such as invasiveness, low efficiency, lack of spatially targeted delivery, and can generally have deleterious effects such as unexpected inflammatory responses and immunological reactions. Here, we introduce a continuous wave near-infrared laser-based Nano-enhanced Optical Delivery (NOD) method for spatially controlled delivery of opsin-encoding genes into retina in-vivo. In this method, the optical field enhancement by gold nanorods is utilized to transiently permeabilize cell membrane enabling delivery of exogenous impermeable molecules to nanorod-binding cells in laser-irradiated regions. The successful delivery and expression of opsin in targeted retina after in-vivo NOD in the mice models of retinal degeneration opens new vista for re-photosensitizing retina with geographic atrophies as in dry age-related macular degeneration (AMD).
Retinoic acid and androgens interact to regulate spermatogenesis in a non-mammalian vertebrate lacking stra8

In mammals, retinoic acid (RA) signaling is critical for spermatogonial differentiation and for entering meiosis, the latter depending on RA-induced Stra8 gene expression. Many fish species, including zebrafish, do not contain a stra8 gene, but RA signaling nevertheless is important for sperm production. However, it is not known which stages of spermatogenesis respond to RA. Here, we show in zebrafish that RA promotes spermatogonial differentiation and reduces the apoptotic loss of spermatids, but is not required for meiosis. Some of the RA effects are mediated by other genes, in particular rec8a. Surprisingly, androgens can partially compensate for the loss of RA signaling, and we identify a link between the endocrine system and RA signaling: follicle-stimulating hormone (Fsh) stimulates testicular RA production. While RA signaling is relevant at the basis of the vertebrates, it also targets processes and mechanisms that are different from those known in mammals so far.