Miracle-dz/UniFAR-FTUs huggingface dataset:
Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets

ABSTRACT Human APOBEC3 enzymes are cellular DNA cytidine deaminases that inhibit and/or mutate a variety of retroviruses, retrotransposons, and DNA viruses. Here, we report a detailed examination of human APOBEC3 gene expression, focusing on APOBEC3G (A3G) and APOBEC3F (A3F), which are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection but are suppressed by HIV-1 Vif. A3G and A3F are expressed widely in hematopoietic cell populations, including T cells, B cells, and myeloid cells, as well as in tissues where mRNA levels broadly correlate with the lymphoid cell content (gonadal tissues are exceptions). By measuring mRNA copy numbers, we find that A3G mRNA is ∼10-fold more abundant than A3F mRNA, implying that A3G is the more significant anti-HIV-1 factor in vivo. A3G and A3F levels also vary between donors, and these differences are sustained over 12 months. Responses to T-cell activation or cytokines reveal that A3G and A3F mRNA levels are induced ∼10-fold in macrophages and dendritic cells (DCs) by alpha interferon (IFN-α) and ∼4-fold in naïve CD4+ T cells. However, immunoblotting revealed that A3G protein levels are induced by IFN-α in macrophages and DCs but not in T cells. In contrast, T-cell activation and IFN-γ had a minimal impact on A3G or A3F expression. Finally, we noted that A3A mRNA expression and protein expression are exquisitely sensitive to IFN-α induction in CD4+ T cells, macrophages, and DCs but not to T-cell activation or other cytokines. Given that A3A does not affect HIV-1 infection, these observations imply that this protein may participate in early antiviral innate immune responses.
Ric-8A and Giα Recruit LGN, NuMA, and Dynein to the Cell Cortex To Help Orient the Mitotic Spindle

ABSTRACT In model organisms, resistance to inhibitors of cholinesterase 8 (Ric-8), a G protein α (Gα) subunit guanine nucleotide exchange factor (GEF), functions to orient mitotic spindles during asymmetric cell divisions; however, whether Ric-8A has any role in mammalian cell division is unknown. We show here that Ric-8A and Gαi function to orient the metaphase mitotic spindle of mammalian adherent cells. During mitosis, Ric-8A localized at the cell cortex, spindle poles, centromeres, central spindle, and midbody. Pertussis toxin proved to be a useful tool in these studies since it blocked the binding of Ric-8A to Gαi, thus preventing its GEF activity for Gαi. Linking Ric-8A signaling to mammalian cell division, treatment of cells with pertussis toxin, reduction of Ric-8A expression, or decreased Gαi expression similarly affected metaphase cells. Each treatment impaired the localization of LGN (GSPM2), NuMA (microtubule binding nuclear mitotic apparatus protein), and dynein at the metaphase cell cortex and disturbed integrin-dependent mitotic spindle orientation. Live cell imaging of HeLa cells expressing green fluorescent protein-tubulin also revealed that reduced Ric-8A expression prolonged mitosis, caused occasional mitotic arrest, and decreased mitotic spindle movements. These data indicate that Ric-8A signaling leads to assembly of a cortical signaling complex that functions to orient the mitotic spindle.
Candida albicans-epithelial interactions and pathogenicity mechanisms: scratching the surface

Until recently, epithelial cells have been a largely ignored component of host responses to microbes. However, this has been largely overturned over the last decade as an ever increasing number of studies have highlighted the key role that these cells play in many of our interactions with our microbiota and pathogens. Interactions of these cells with Candida albicans have been shown to be critical not just in host responses, but also in fungal cell responses, regulating fungal morphology and gene expression profile. In this review, we will explore the interactions between C. albicans and epithelial cells, and discuss how these interactions affect our relationship with this fungus.
Influence of diverse chemical modifications on the ADME characteristics and toxicology of antisense oligonucleotides

Introduction: Therapeutic gene silencing is a huge promise for the treatment of a variety of diseases. The translation of this widely used scientific technique toward clinical application has been hindered by insufficient ADME properties of antisense and siRNA oligonucleotides. Despite reasonable therapeutic response after local administration, reaching adequate concentrations at the site of action after systemic application is still a major hurdle and this has resulted in poor efficiency in preclinical and clinical situations. Areas covered: This review focuses on the influence on the ADME parameters of chemical modifications already tested in clinical trials, such as phosphorothioates (PSs), 2′-modified agents, including locked nucleic acids (LNA) and phosphorodiamidate morpholino oligomers (PMO). The dominating PS backbone modification, while conferring adequate nuclease resistance and improving biodistribution, has been shown to be involved in unspecific protein binding and off-target effects on apoptosis pathways. PS-free antisense agents such as PMO generally show poorer pharmacokinetic characteristics. Expert opinion: In terms of pharmacokinetics and cell membrane permeation, there is currently no efficient alternative to PS, although doubts about long-term toxicity of this class still remain. Consequently, improved structural modifications or galenic formulations are deemed necessary to create entities with higher efficiency and lower toxicity.
Enhancing tool availability in the forging industry by adjusting PPC and tool maintenance

The day-to-day business of the forging industry is characterized by fluctuating order quantities and production of numerous variants. Within the framework of the Collaborative Research Centre (CRC) 489 “Process chain for the manufacturing of precision forged high performance components” a simulation based approach was developed for the implementation of operative tool management to reduce delays caused by the allocation of tools.
Acute kidney injury: global health alert

Acute kidney injury (AKI) is increasingly prevalent in developing and developed countries and is associated with severe morbidity and mortality. Most etiologies of AKI can be prevented by interventions at the individual, community, regional, and in-hospital levels. Effective measures must include community-wide efforts to increase an awareness of the devastating effects of AKI and provide guidance on preventive strategies, and early recognition and management. Efforts should be focused on minimizing the causes of AKI, increasing awareness of the importance of serial measurements of serum creatinine in high-risk patients, and documenting urine volume in acutely ill people to achieve early diagnosis; there is as yet no definitive role for alternative biomarkers. Protocols need to be developed to systematically manage prerenal conditions and specific infections. More accurate data about the true incidence and clinical impact of AKI will help raise the importance of the disease in the community and increase awareness of AKI by governments, the public, and general and family physicians and other health care professionals to help prevent the disease. Prevention is the key to avoid the heavy burden of mortality and morbidity associated with AKI.
Study of the hot-wire TIG process with AISI-316L filler material, analysing the effect of magnetic arc blow on the dilution of the weld bead

Abstract The TIG process with hot-wire addition is described as a highly productive process in comparison with conventional TIG process with cold-wire and achieves large deposition rates and low dilution percentages, characteristics that permit to the process to be an optimum alternative for cladding applications. There are many options of electrical circuit configurations to heat the addition wire in the TIG Hot-Wire process, highlighting the utilization of the continuous pulsed current and the alternating current. In the present paper were studied two configurations of the electrical circuit for heating the addition materials, which in theory provoke different behaviours in the welding arc, and therefore, in the geometrical properties of the welding bead too. A first analysis done on the welding arc, which demonstrates that to heat the wire with continuous constant current generates a permanent magnetic blow over the arc. According to trials made, the direction and intensity of the magnetic blow will depend on the polarity and on the current value to heat the wire. A macrographic analysis of the weld beads demonstrated that the best results were for the tests made with hot-wire, achieving dilutions up to 2% for a wire velocity of 7.5 m/min, 1 kW of power for to heat the wire and using a welding velocity of 30 cm/min.
Plasma 25-Hydroxyvitamin D Is Related to Protein Signaling Involved in Glucose Homeostasis in a Tissue-Specific Manner

Vitamin D has been suggested to play a role in glucose metabolism. However, previous findings are contradictory and mechanistic pathways remain unclear. We examined the relationship between plasma 25-hydroxyvitamin D (25(OH)D), insulin sensitivity, and insulin signaling in skeletal muscle and adipose tissue. Seventeen healthy adults (Body mass index: 26 ± 4; Age: 30 ± 12 years) underwent a hyperinsulinemic-euglycemic clamp, and resting skeletal muscle and adipose tissue biopsies. In this cohort, the plasma 25(OH)D concentration was not associated with insulin sensitivity (r = 0.19, p = 0.56). However, higher plasma 25(OH)D concentrations correlated with lower phosphorylation of glycogen synthase kinase-3 (GSK-3) αSer21 and βSer9 in skeletal muscle (r = −0.66, p = 0.015 and r = −0.53, p = 0.06, respectively) and higher GSK-3 αSer21 and βSer9 phosphorylation in adipose tissue (r = 0.82, p < 0.01 and r = 0.62, p = 0.042, respectively). Furthermore, higher plasma 25(OH)D concentrations were associated with greater phosphorylation of both protein kinase-B (AktSer473) (r = 0.78, p < 0.001) and insulin receptor substrate-1 (IRS-1Ser312) (r = 0.71, p = 0.01) in adipose tissue. No associations were found between plasma 25(OH)D concentration and IRS-1Tyr612 phosphorylation in skeletal muscle and adipose tissue. The divergent findings between muscle and adipose tissue with regard to the association between 25(OH)D and insulin signaling proteins may suggest a tissue-specific interaction with varying effects on glucose homeostasis. Further research is required to elucidate the physiological relevance of 25(OH)D in each tissue.
Feasibility study of delamination in rotary ultrasonic-assisted drilling of glass fiber reinforced plastics

Glass fiber reinforced plastics are used in variety of industrial and constructional applications for their superb mechanical and physical properties. Delamination is one of the most important and prevalent damages in machining of glass fiber reinforced plastics. Diamond core drills have the capability of simultaneously drilling and grinding of fiber reinforced plastics, which results in hole quality improvement. Rotary ultrasonic-assisted drilling is the new machining process to drill holes on fiber reinforced plastics and has attracted increasing attention in recent years. In this paper, thrust force and delamination in rotary ultrasonic-assisted drilling of glass fiber reinforced plastics using diamond core drill have been investigated. A proper ultrasonic system for a core drill in ABAQUS was designed and fabricated. Influence of ultrasonic vibration and then tool grain size, fiber-volume fraction and machining parameters including spindle speed and feed rate on thrust force and delamination was investigated. Higher thrust force induces more delamination. As a result of the study, less delamination was achieved in ultrasonic-assisted mode by using a tool with larger grain size onto lower fiber-volume fraction composites. Additionally, experiments showed that lower spindle speed and higher feed rate induce more delamination.
Combination of glycolysis inhibition with chemotherapy results in an antitumor immune response

Most DNA-damaging agents are weak inducers of an anticancer immune response. Increased glycolysis is one of the best-described hallmarks of tumor cells; therefore, we investigated the impact of glycolysis inhibition, using 2-deoxyglucose (2DG), in combination with cytotoxic agents on the induction of immunogenic cell death. We demonstrated that 2DG synergized with etoposide-induced cytotoxicity and significantly increased the life span of immunocompetent mice but not immunodeficient mice. We then established that only cotreated cells induced an efficient tumor-specific T-cell activation ex vivo and that tumor antigen-specific T cells could only be isolated from cotreated animals. In addition, only when mice were immunized with cotreated dead tumor cells could they be protected (vaccinated) from a subsequent challenge using the same tumor in viable form. Finally, we demonstrated that this effect was at least partially mediated through ERp57/calreticulin exposure on the plasma membrane. These data identify that the targeting of glycolysis can convert conventional tolerogenic cancer cell death stimuli into immunogenic ones, thus creating new strategies for immunogenic chemotherapy.
Reduced high-density lipoprotein 2b in non-obese type 2 diabetic patients analysed by a microfluidic chip method in a case–control study

Background: Alterations in high-density lipoprotein (HDL) subfractions, especially in the HDL2b subfraction, have been reported in type 2 diabetes mellitus (T2DM). However, new methods for convenient and reliable quantitation of HDL2b are yet to be developed. Methods: Thirty-eight patients with T2DM were enrolled and age-, sex- and body mass index (BMI)-matched controls were selected from the same population. A microfluidic chip method was employed to analyse serum HDL subfractions. Results: The microfluidic chip method revealed a significant reduction in HDL2b and its ratio to total HDL in T2DM patients. There was a reverse correlation for total HDL and HDL2b, and its ratio with triglycerides, homeostasis model assessment-insulin sensitivity index (HOMA-IS) and insulin resistance index (HOMA-IR). Conclusions: We have shown a reduction of HDL2b and its ratio to total HDL by a novel chip method in T2DM patients. The significant correlation between HDL2b and HOMA-IS and HOMA-IR may have further predictive value in clinical utility.
Glycerol-3-phosphate Acyltransferase Isoform-4 (GPAT4) Limits Oxidation of Exogenous Fatty Acids in Brown Adipocytes*

Background: GPAT4 is a major glycerol-3-phosphate acyltransferase (GPAT) isoform in brown adipose tissue (BAT). Results: Compared with control cells, brown adipocytes lacking GPAT4 oxidize 40% more exogenous fatty acids. Conclusion: GPAT4 in BAT is required to limit oxidation of exogenous fatty acid. Significance: The function of each GPAT isoform is tissue-specific and evolved to perform a unique function within a physiological context. Glycerol-3-phosphate acyltransferase-4 (GPAT4) null pups grew poorly during the suckling period and, as adults, were protected from high fat diet-induced obesity. To determine why Gpat4−/− mice failed to gain weight during these two periods of high fat feeding, we examined energy metabolism. Compared with controls, the metabolic rate of Gpat4−/− mice fed a 45% fat diet was 12% higher. Core body temperature was 1 ºC higher after high fat feeding. Food intake, fat absorption, and activity were similar in both genotypes. Impaired weight gain in Gpat4−/− mice did not result from increased heat loss, because both cold tolerance and response to a β3-adrenergic agonist were similar in both genotypes. Because GPAT4 comprises 65% of the total GPAT activity in brown adipose tissue (BAT), we characterized BAT function. A 45% fat diet increased the Gpat4−/− BAT expression of peroxisome proliferator-activated receptor α (PPAR) target genes, Cpt1α, Pgc1α, and Ucp1, and BAT mitochondria oxidized oleate and pyruvate at higher rates than controls, suggesting that fatty acid signaling and flux through the TCA cycle were enhanced. To assess the role of GPAT4 directly, neonatal BAT preadipocytes were differentiated to adipocytes. Compared with controls, Gpat4−/− brown adipocytes incorporated 33% less fatty acid into triacylglycerol and 46% more into the pathway of β-oxidation. The increased oxidation rate was due solely to an increase in the oxidation of exogenous fatty acids. These data suggest that in the absence of cold exposure, GPAT4 limits excessive fatty acid oxidation and the detrimental induction of a hypermetabolic state.
Animal Rights as a Mainstream Phenomenon

Simple Summary The twentieth century has witnessed a bewildering array of ethical revolutions, from civil rights to environmentalism to feminism. Often ignored is the rise of massive societal concern across the world regarding animal treatment. Regulation of animal research exists in virtually all western countries, and reform of “factory farming” is regnant in Europe and rapidly emerging in the United States. Opponents of concern for animals often dismiss the phenomenon as rooted in emotion and extremist lack of appreciation of how unrestricted animal use has improved human life. Such a view totally ignores the rational ethical basis for elevating legal protection for animals, as explained in this essay. Abstract Businesses and professions must stay in accord with social ethics, or risk losing their autonomy. A major social ethical issue that has emerged in the past four decades is the treatment of animals in various areas of human use. Society's moral concern has outgrown the traditional ethic of animal cruelty that began in biblical times and is encoded in the laws of all civilized societies. There are five major reasons for this new social concern, most importantly, the replacement of husbandry-based agriculture with industrial agriculture. This loss of husbandry to industry has threatened the traditional fair contract between humans and animals, and resulted in significant amounts of animal suffering arising on four different fronts. Because such suffering is not occasioned by cruelty, a new ethic for animals was required to express social concerns. Since ethics proceed from preexisting ethics rather than ex nihilo, society has looked to its ethic for humans, appropriately modified, to find moral categories applicable to animals. This concept of legally encoded rights for animals has emerged as a plausible vehicle for reform.
An exact algorithm for coupling-free routing

In this wrok, we develop methods to reduce interconnect delay and noise caused by coupling. First, we explain the Coupling-Free Routing (CFR) problem. CFR takes a set of nets and tries to find a one-bend couple-free routing for a subset of nets. A routed net must not couple with any other routed net. We define coupling as a boolean variable which is true when the coupling of two nets is greater than some threshold. Any pair-wise coupling definition can be used. We argue that this problem is useful in both global and detailed routing We develop an exact algorithm for the CFR decision problem via a transformation to 2-satisfiability. This algorithm runs in linear time. The decision problem determines whether the given set of nets is coupling-free routable. Next, we present the implication graph which models the dependencies associated with CFR. Also, we look at some of the properties associated with the graph. Finally, we develop a new algorithm for the Maximum Coupling-Free Layout (MAX-CFL) problem. Given a set of nets, the MAX-CFL is defined as finding a subset of nets that are coupling-free routable. The subset should have maximum size and/or critically. The new algorithm, called implication algorithm, uses properties assoicated with the implication graph and experiments show that it consistently finds the best solution in terms of number of nets routed as compared to previous algorithms
Validation of long‐term primary neuronal cultures and network activity through the integration of reversibly bonded microbioreactors and MEA substrates

In vitro recording of neuronal electrical activity is a widely used technique to understand brain functions and to study the effect of drugs on the central nervous system. The integration of microfluidic devices with microelectrode arrays (MEAs) enables the recording of networks activity in a controlled microenvironment. In this work, an integrated microfluidic system for neuronal cultures was developed, reversibly coupling a PDMS microfluidic device with a commercial flat MEA through magnetic forces. Neurons from mouse embryos were cultured in a 100 µm channel and their activity was followed up to 18 days in vitro. The maturation of the networks and their morphological and functional characteristics were comparable with those of networks cultured in macro‐environments and described in literature. In this work, we successfully demonstrated the ability of long‐term culturing of primary neuronal cells in a reversible bonded microfluidic device (based on magnetism) that will be fundamental for neuropharmacological studies. Biotechnol. Bioeng. 2012;109: 166–175. © 2011 Wiley Periodicals, Inc.
Revisiting the firewall abolition act

Mobility and the new global economy are accompanied by requirements for dynamism and flexibility, with respect to e-commerce, inter-organizational activity, and security. The classical approach to computer security, typified by firewalls, is no longer suitable to encourage and facilitate the growth and nomadic collaboration foreseen for current and future corporate environs. This paper investigates the nature of firewalls, their concepts, goals, history and implementations, in order to determine the validity of the claims of inadequacy made. We present arguments surrounding these claims from both business and technical perspectives. This includes consideration of real-world scenarios and identification of the fundamental concerns for corporate network administration. We further present possibilities for application level security to address the shortfalls of firewalls and providing end-to-end security over heterogeneous networks. This includes a formal definition, proposed architecture, comparison to firewalls, and references to existing technologies and research in this direction.
Macular Thickness Measured by Stratus Optical Coherence Tomography in Patients with Diabetes Type 2 and Mild Nonproliferative Retinopathy without Clinical Evidence of Macular Edema

To evaluate macular thickness in eyes with mild nonproliferative diabetic retinopathy (NPDR), patients with diabetes type 2, NPDR level 20 or 35, and without evidence of clinical macular edema underwent best-corrected visual acuity assessment, color fundus photography and Stratus optical coherence tomography. Mean center point thickness (CPT) and mean central subfield (CSF) thickness were compared with those of a healthy control population. 410 eyes/patients aged 61.2 ± 8.3 years, and with glycosylated hemoglobin of 7.9 ± 1.5% were included. Mean CPT and CSF were 186.6 ± 28.4 and 215.2 ± 25 µm, respectively, significantly increased compared to healthy subjects (p < 0.001). CSF thickness was abnormally increased in 17.6% of the patients, with values within the normal range in 79.5%, and abnormally decreased in 2.9%. CPT and CSF thickness were significantly thicker in men. No systemic factors showed a significant association. A significant increase in the macular thickness was found in eyes/patients with mild NPDR without clinical macular edema; however, only 17.6% of the eyes/patients had abnormally increased values and less than 3% abnormally decreased values.