Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA ORGANIZATION IN THE MATURE SPERM OF SEVERAL ORTHOPTERA BY THE METHOD OF POLARIZED FLUORESCENCE MICROSCOPY

Mature sperm of Acheta domesticus, Acheta assimilis, Nemobius fasciatus, Nemobius confusus, Melanoplus femur-rubrum, Romalea microptera, Scudderia curvicauda, and Ceuthophilus nigricans were examined for DNA configuration by means of polarized fluorescence microscopy. In all cases, the results suggest that the DNA lies in unsupercoiled array, predominantly parallel to the elongate sperm head axes. Detailed calculations of the factors influencing the degree of polarization of the fluorescent emission from supercoiled DNA are contained in an appendix.
Critical Loss of the Balance between Th17 and T Regulatory Cell Populations in Pathogenic SIV Infection

Chronic immune activation and progression to AIDS are observed after SIV infection in macaques but not in natural host primate species. To better understand this dichotomy, we compared acute pathogenic SIV infection in pigtailed macaques (PTs) to non-pathogenic infection in African green monkeys (AGMs). SIVagm-infected PTs, but not SIVagm-infected AGMs, rapidly developed systemic immune activation, marked and selective depletion of IL-17-secreting (Th17) cells, and loss of the balance between Th17 and T regulatory (Treg) cells in blood, lymphoid organs, and mucosal tissue. The loss of Th17 cells was found to be predictive of systemic and sustained T cell activation. Collectively, these data indicate that loss of the Th17 to Treg balance is related to SIV disease progression.
Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer

KRAS mutation is often present in many hard-to-treat tumors such as colon and pancreatic cancer and it is tightly linked to serious alterations in the normal cell metabolism and clinical resistance to chemotherapy. In 1931, the winner of the Nobel Prize in Medicine, Otto Warburg, stated that cancer was primarily caused by altered metabolism interfering with energy processing in the normal cell. Increased cell glycolytic rates even in the presence of oxygen is fully recognized as a hallmark in cancer and known as the Warburg effect. In the late 1970′s, Linus Pauling and Ewan Cameron reported that vitamin C may have positive effects in cancer treatment, although deep mechanistic knowledge about this activity is still scarce. We describe a novel antitumoral mechanism of vitamin C in KRAS mutant colorectal cancer that involves the Warburg metabolic disruption through downregulation of key metabolic checkpoints in KRAS mutant cancer cells and tumors without killing human immortalized colonocytes. Vitamin C induces RAS detachment from the cell membrane inhibiting ERK 1/2 and PKM2 phosphorylation. As a consequence of this activity, strong downregulation of the glucose transporter (GLUT-1) and pyruvate kinase M2 (PKM2)-PTB dependent protein expression are observed causing a major blockage of the Warburg effect and therefore energetic stress. We propose a combination of conventional chemotherapy with metabolic strategies, including vitamin C and/or other molecules targeting pivotal key players involved in the Warburg effect which may constitute a new horizon in anti-cancer therapies.
Allopurinol Improves Myocardial Efficiency in Patients With Idiopathic Dilated Cardiomyopathy

Background—Dilated cardiomyopathy is characterized by an imbalance between left ventricular performance and myocardial energy consumption. Experimental models suggest that oxidative stress resulting from increased xanthine oxidase (XO) activity contributes to this imbalance. Accordingly, we hypothesized that XO inhibition with intracoronary allopurinol improves left ventricular efficiency in patients with idiopathic dilated cardiomyopathy. Methods and Results—Patients (n=9; ejection fraction, 29±3%) were instrumented to assess myocardial oxygen consumption (M&OV0312;o2), peak rate of rise of left ventricular pressure (dP/dtmax), stroke work (SW), and efficiency (dP/dtmax/M&OV0312; o2 and SW/M&OV0312;o2) at baseline and after sequential infusions of intracoronary allopurinol (0.5, 1.0, and 1.5 mg/min, each for 15 minutes). Allopurinol caused a significant decrease in M&OV0312;o2 (peak effect, −16±5%;P <0.01; n=9) with no parallel decrease in dP/dtmax or SW and no change in ventricular load. The net result was a substantial improvement in myocardial efficiency (peak effects: dP/dtmax/M&OV0312; o2, 22±9%, n=9; SW/M&OV0312; o2, 40±17%, n=6; both P <0.05). These effects were apparent despite concomitant treatment with standard heart failure therapy, including ACE inhibitors and &bgr;-blockers. XO and its parent enzyme xanthine dehydrogenase were more abundant in failing explanted human myocardium on immunoblot. Conclusions—These findings indicate that XO activity may contribute to abnormal energy metabolism in human cardiomyopathy. By reversing the energetic inefficiency of the failing heart, pharmacological XO inhibition represents a potential novel therapeutic strategy for the treatment of human heart failure.
Working Paper Information Disclosure and Consumer Awareness

Whether consumers are aware of potentially adverse product effects is key to private and social incentives to disclose information about undesirable product characteristics. In a monopoly model with a mix of aware and unaware consumers, a larger share of unaware consumers makes information disclosure less likely to occur. Since the firm is not interested in releasing information to unaware consumers, a more precise targeting technology that allows the firm to better keep unaware consumers in the dark leads to more disclosure. A regulator may want to intervene in this market and impose mandatory disclosure rules.
Reducing Overtreatment in Gynecologic Oncology: The Case for Less in Endometrial and Ovarian Cancer

A growing awareness of the harms of overtreatment in cancer care has reached physicians, patients, health policy makers, and medical researchers. Overtreatment exposes patients to the risk of adverse events from procedures or medications that were not necessary. This review examines common practices in gynecologic malignancies that are unlikely to produce direct benefit to patients with these malignancies, but are likely to produce harms. Specifically, we will explore the utility of lymphadenectomy and adjuvant radiation for women with early-stage endometrial cancer; and screening for recurrence and continuous chemotherapy for advanced-stage ovarian cancer patients.
Boundary load flow solutions

The load flow is one of the most fundamental tools used in power system analysis. The need for a load flow approach, which would incorporate uncertainty into the solution process, has been long recognized. The boundary load flow finds solutions given uncertain nodal powers. Here, a new concept for finding accurate boundary load flow solutions given fuzzy/interval numbers is presented. Extending an idea from probabilistic load flow, an optimization procedure for implicitly defined functions is introduced. Test systems are used for performance evaluation and comparison between the new method and extant methods that give approximate solutions.
Two Dot1 isoforms in Saccharomyces cerevisiae as a result of leaky scanning by the ribosome

Dot1 is a conserved histone methyltransferase that methylates histone H3 on lysine 79. We previously observed that in Saccharomyces cerevisiae, a single DOT1 gene encodes two Dot1 protein species. Here, we show that the relative abundance of the two isoforms changed under nutrient-limiting conditions. A mutagenesis approach showed that the two Dot1 isoforms are produced from two alternative translation start sites as a result of leaky scanning by the ribosome. The leaky scanning was not affected by the 5′- or 3′-untranslated regions of DOT1, indicating that translation initiation is determined by the DOT1 coding sequence. Construction of yeast strains expressing either one of the isoforms showed that both were sufficient for Dot1’s role in global H3K79 methylation and telomeric gene silencing. However, the absence of the long isoform of Dot1 altered the resistance of yeast cells to the chitin-binding drug Calcofluor White, suggesting that the two Dot1 isoforms have a differential function in cell wall biogenesis.
Advice Sharing Between Paired Users in Online Travel Planning

There have been few studies investigating the effects of collaboration on online shopping. In this paper, we consider an online shopping scenario where the user and a partner, who are not collocated, plan the travel collaboratively. We develop a research model based on Website Trust to explain the user's Website Intentions. To test the model, we conducted a field experiment with 605 individuals and a partner using LiveLook, an online co-browsing platform. A PLS analysis of the influence of advice sharing showed the following variance explained: Website Trust 20.6 percent, Website Enjoyment 55.2 percent, Perceived Control 59.4 percent, and Website Intentions 55.3 percent. We also show separate models for two different user interfaces: one for packaged travel and one for customizable travel. The resulting models show the packaged travel interface to have greater website intentions while the customizable travel interface has greater variance explained. Overall, the results shed light on the network of influences that advice sharing has in online travel planning.
Effects of Climate Change on Habitat Availability and Configuration for an Endemic Coastal Alpine Bird

North America’s coastal mountains are particularly vulnerable to climate change, yet harbour a number of endemic species. With little room “at the top” to track shifting climate envelopes, alpine species may be especially negatively affected by climate-induced habitat fragmentation. We ask how climate change will affect the total amount, mean patch size, and number of patches of suitable habitat for Vancouver Island White-tailed Ptarmigan (Lagopus leucura saxatilis; VIWTP), a threatened, endemic alpine bird. Using a Random Forest model and a unique dataset consisting of citizen science observations combined with field surveys, we predict the distribution and configuration of potential suitable summer habitat for VIWTP under baseline and future (2020s, 2050s, and 2080s) climates using three general circulation models and two greenhouse gas scenarios. VIWTP summer habitat is predicted to decline by an average of 25%, 44%, and 56% by the 2020s, 2050s, and 2080s, respectively, under the low greenhouse gas scenario and 27%, 59%, and 74% under the high scenario. Habitat patches are predicted to become fragmented, with a 52–79% reduction in mean patch size. The average elevation of suitable habitat patches is expected to increase, reflecting a loss of patches at lower elevations. Thus ptarmigan are in danger of being “squeezed off the mountain”, as their remaining suitable habitat will be increasingly confined to mountaintops in the center of the island. The extent to which ptarmigan will be able to persist in increasingly fragmented habitat is unclear. Much will depend on their ability to move throughout a more heterogeneous landscape, utilize smaller breeding areas, and survive increasingly variable climate extremes. Our results emphasize the importance of continued monitoring and protection for high elevation specialist species, and suggest that White-tailed Ptarmigan should be considered an indicator species for alpine ecosystems in the face of climate change.
Neural progenitors derived from human embryonic stem cells are targeted by allogeneic T and natural killer cells

Neural progenitor cells (NPC) of foetal origin or derived from human embryonic stem cells (HESC) have the potential to differentiate into mature neurons after transplantation into the central nervous system, opening the possibility of cell therapy for neurodegenerative disorders. In most cases, the transplanted NPC are genetically unrelated to the recipient, leading to potential rejection of the transplanted cells. Very few data provide reliable information as to the potential immune response of allogeneic neural progenitors derived from HESC. In this study, we analyzed in vitro the allogeneic immune response of T lymphocytes and natural killer (NK) cells to NPC derived from HESC or of foetal origin. We demonstrate that NPC induce T‐cell stimulation and a strong NK cytotoxic response. NK‐cell activity is unrelated to MHC‐I expression but driven by the activating NKG2D receptor. Cyclosporine and dexamethasone previously used in clinical studies with foetal NPC did not only fail to prevent NK alloreactivity but strongly inhibited the terminal maturation from NPC into mature neurons. We conclude that allogenic transplantation of NPC in the central nervous system will most likely require an immunosuppressive regimen targeting allogenic T and NK cells, whereas possible interference with the differentiation of NPC needs to be carefully evaluated.
Metabolic efficiency and turnover of soil microbial communities in biodegradation tests

Biodegradability screening tests of soil commonly measure 14CO2 evolution from radiolabeled test compounds, and glucose has often served as a positive control. When constant amounts of radiolabel were added to soil in combination with increasing amounts of unlabeled substrates, glucose and some related hexoses behaved in an anomalous manner. In contrast to that of formate, benzoate, n-hexadecane, or bis(2-ethylhexyl) phthalate, dilution of glucose radiocarbon with unlabeled glucose increased rather than decreased the rate and extent of 14CO2 evolution. [14C]glucose incorporation into biomass and Vmax values were consistent with the interpretation that application of relatively high concentrations of glucose to soil shifts the balance of the soil microbial community from the autochthonous (humus-degrading) to the zymogeneous (opportunistic) segment. The higher growth and turnover rates that define zymogeneous microorganisms, combined with a lower level of carbon incorporation into their biomass, result in the evolution of disproportionate percentages of 14CO2. When used as positive controls, glucose and related hexoses may raise the expectations for percent 14CO2 evolution to levels that are not realistic for other biodegradable compounds.
Review Eradication: What Can Go Wrong Viewing Invasive Species Removal in a Whole-ecosystem Context

Invasive alien species interact with other elements of global change to cause considerable damage to managed and natural systems and to incur huge costs to society 1. In response, several measures have been developed and deployed to control, contain or eradicate a wide range of invasive species in affected areas. Where possible, ERADICATION (see Glossary) is the favored approach. Control, which reduces the presence of the invader, and containment, which limits further spread, both require indefinite investments of time, tools and money to keep an invader at bay. Although eradication can require large short-term investments, successful removal can be achieved within months or years and gives the best chance for native biodiversity to recover. The results of eradication efforts so far are encouraging and have been detailed recently 2. Many case studies demonstrate success for a range of taxa, particularly on small islands and at local scales. Additional examples include the removal of the exotic little red fire ant Wasmannia auropunctata from Santa Fe Island in the Galapagos 3 (which resulted in the increase in density of several native ant species), and the nearly complete removal from Laysan Island, Hawaii of the exotic annual grass Cenchrus echinatus, which once covered 30% of the vegetated area of the island (E.N. Flint, unpublished). Successful eradications often lead to dramatic recovery of native species and ecosystems. Removal of introduced rabbits from Pacific islands off Mexico (C.J. Donlan, unpublished) and the USA have allowed recovery of two rapidly declining endemic species of native succulents Dudleya linearis and D. traskiae 4. Lowland vegetation on Santa Fe Island has recovered steadily following the removal of exotic goats Capra hircus nearly 30 years ago. However, other cases suggest that more refined and integrated approaches to invasive removal could improve results. Successes are still largely confined to small islands. The ecological context of eradication is increasingly complex. Major damage caused by long-established invaders, systems that are affected by multiple invaders, and systems that are affected by both invaders and other global changes are now common. In these settings, straightforward deployment of standard eradication tools, such as poisons, trapping and mechanical harvesting, might not accomplish the desired level of recovery of native ecosystems 5. We suggest that, although there is a crucial need for the continued development and application of effective eradication methodologies, a parallel need exists to place these methodologies in the context of the overall ecosystem that …
Genetic Diversity of the tet(M) Gene in Tetracycline-Resistant Clonal Lineages of Streptococcus pneumoniae

ABSTRACT The aim of the present study was to examine the stability and evolution of tet(M)-mediated resistance to tetracyclines among members of different clonal lineages of Streptococcus pneumoniae. Thirty-two tetracycline-resistant isolates representing three national (Spanish serotype 14, Spanish serotype 15, and Polish serotype 23F) and one international (Spanish serotype 23F) multidrug-resistant epidemic clones were all found to betet(M) positive and tet(O), tet(K), and tet(L) negative. These isolates all carried the integrase gene, int, which is associated with the Tn1545-Tn916 family of conjugative transposons. High-resolution restriction analysis of tet(M) products identified six alleles, tet(M)1 to tet(M)6:tet(M)1 to tet(M)3 and tet(M)5 in isolates of the Spanish serotype 14 clone, tet(M)4 in both the Spanish serotype 15 and 23F clones, and tet(M)6, the most divergent allele, in the Polish 23F clone. This indicates thattet(M) variation can occur at the inter- and intraclone levels in pneumococci. Two alleles of int were identified, with int1 being found in all isolates apart from members of the international Spanish 23F clone, which carried int2. Susceptibility to tetracycline, doxycycline, and minocycline was evaluated for all isolates with or without preincubation in the presence of subinhibitory concentrations of tetracyclines. Resistance to tetracyclines was found to be inducible in isolates of all clones; however, the strongest induction was observed in the Spanish serotype 15 and 23F clones carrying tet(M)4. Tetracycline was found to be the strongest inducer of resistance, and minocycline was found to be the weakest inducer of resistance.
Biphasic Dose Response in Low Level Light Therapy

The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing cell death and tissue damage has been known for over forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in LLLT, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response.
Using Knowledge Ontologies and Neural Networks to Control Service-Oriented Robots

In recent years, researchers have been building home robots able to interact and work with people. However, due to the complexity and diversity of the environments for developing robots, it is difficult to share and reuse robot code created by different providers. In this work we present a servicebased approach that exploits the standard web interface to develop reusable robotic services. Our approach includes knowledge ontology and neural network learning strategies for robot control. In addition, several service functions, including service discovery, selection, and composition have been developed for operating the services. The proposed approach has been implemented and evaluated, and the results show that it can be used to build robotic services successfully.
Multilevel Splitting for Estimating Rare Event Probabilities

We analyze the performance of a splitting technique for the estimation of rare event probabilities by simulation. A straightforward estimator of the probability of an event evaluates the proportion of simulated paths on which the event occurs. If the event is rare, even a large number of paths may produce little information about its probability using this approach. The method we study reinforces promising paths at intermediate thresholds by splitting them into subpaths which then evolve independently. If implemented appropriately, this has the effect of dedicating a greater fraction of the computational effort to informative runs. We analyze the method for a class of models in which, roughly speaking, the number of states through which each threshold can be crossed is bounded. Under additional assumptions, we identify the optimal degree of splitting at each threshold as the rarity of the event increases: It should be set so that the expected number of subpaths reaching each threshold remains roughly constant. Thus implemented, the method is provably effective in a sense appropriate to rare event simulations. These results follow from a branching-process analysis of the method. We illustrate our theoretical results with some numerical examples for queueing models.
Ssh4, Rcr2 and Rcr1 Affect Plasma Membrane Transporter Activity in Saccharomyces cerevisiae

Nutrient uptake in the yeast Saccharomyces cerevisiae is a highly regulated process. Cells adjust levels of nutrient transporters within the plasma membrane at multiple stages of the secretory and endosomal pathways. In the absence of the ER-membrane-localized chaperone Shr3, amino acid permeases (AAP) inefficiently fold and are largely retained in the ER. Consequently, shr3 null mutants exhibit greatly reduced rates of amino acid uptake due to lower levels of AAPs in their plasma membranes. To further our understanding of mechanisms affecting AAP localization, we identified SSH4 and RCR2 as high-copy suppressors of shr3 null mutations. The overexpression of SSH4, RCR2, or the RCR2 homolog RCR1 increases steady-state AAP levels, whereas the genetic inactivation of these genes reduces steady-state AAP levels. Additionally, the overexpression of any of these suppressor genes exerts a positive effect on phosphate and uracil uptake systems. Ssh4 and Rcr2 primarily localize to structures associated with the vacuole; however, Rcr2 also localizes to endosome-like vesicles. Our findings are consistent with a model in which Ssh4, Rcr2, and presumably Rcr1, function within the endosome–vacuole trafficking pathway, where they affect events that determine whether plasma membrane proteins are degraded or routed to the plasma membrane.