Miracle-dz/UniFAR-FTUs huggingface dataset:
Apo 2 Ligand / TNF-related Apoptosis-inducing Ligand and Death Receptor 5 Mediate the Apoptotic Signaling Induced by Ionizing Radiation in Leukemic Cells 1

Ionizing radiation is a major tool for cancer treatment. The response of eukaryotic cells to ionizing radiation includes apoptosis, a process which requires activation of multiple genes. We sought to determine whether radiation-induced gene expression plays a role in radiation-induced apoptosis. We found Apo2 ligand (Apo2L, also called TRAIL) mRNA induction following g-irradiation of Jurkat, MOLT-4, CEM, and PBMC, all human T lineage-derived cells. Increased Apo2L protein levels were found in MOLT-4 and Jurkat cells. Radiation also activated the Apo2L death receptor (DR)5 (also called Apo2, TRAIL-R2, or KILLER) in MOLT-4 cells, which harbor a wild-type p53. We isolated 1152 bp of 5* flanking region of the Apo2L gene and a shorter fragment of 716 bp, both of which showed promoter activity driving the expression of a luciferase reporter gene; however, the response to radiation in MOLT-4 cells was lost when only 430 bp of 5*proximal flanking sequence was maintained. Exogenous Apo2L induced phosphatidylserine exposure on cell membranes, caspase 8 and caspase 3 activation, key markers of apoptosis, confirming that the Apo2L/DR5 pathway is functional in these cells. Bid, a Bcl-2 family protein also known to contribute to receptor-mediated apoptosis, was also activated. To determine whether Apo2L and DR5 were critical for radiation signaling to apoptosis, we stably expressed a dominant negative DR5D-receptor in Jurkat cells. Cell survival was significantly augmented, indicating that increased Apo2L expression contributed to radiation-induced apoptosis. Clonogenic assays demonstrated that purified, recombinant soluble Apo2L enhanced the lethality of low, therapeutic doses (1–2 Gy) of g-irradiation. These data suggest that production of Apo2L may cooperate synergistically with the cytotoxic effect of radiation, and that combinations of Apo2L and radiation may become a powerful tool in clinical therapy.
Patterning droplets with durotaxis

Numerous cell types have shown a remarkable ability to detect and move along gradients in stiffness of an underlying substrate—a process known as durotaxis. The mechanisms underlying durotaxis are still unresolved, but generally believed to involve active sensing and locomotion. Here, we show that simple liquid droplets also undergo durotaxis. By modulating substrate stiffness, we obtain fine control of droplet position on soft, flat substrates. Unlike other control mechanisms, droplet durotaxis works without imposing chemical, thermal, electrical, or topographical gradients. We show that droplet durotaxis can be used to create large-scale droplet patterns and is potentially useful for many applications, such as microfluidics, thermal control, and microfabrication.
Disaccharides as a New Class of Nonaccumulated Osmoprotectants for Sinorhizobium meliloti

ABSTRACT Sucrose and ectoine (1,4,5,6-tetrahydro-2-methyl-4-pyrimidine carboxylic acid) are very unusual osmoprotectants forSinorhizobium meliloti because these compounds, unlike other bacterial osmoprotectants, do not accumulate as cytosolic osmolytes in salt-stressed S. meliloti cells. Here, we show that, in fact, sucrose and ectoine belong to a new family of nonaccumulated sinorhizobial osmoprotectants which also comprises the following six disaccharides: trehalose, maltose, cellobiose, gentiobiose, turanose, and palatinose. Also, several of these disaccharides were very effective exogenous osmoprotectants for strains of Rhizobium leguminosarumbiovars phaseoli and trifolii. Sucrose and trehalose are synthesized as endogenous osmolytes in various bacteria, but the other five disaccharides had never been implicated before in osmoregulation in any organism. All of the disaccharides that acted as powerful osmoprotectants in S. meliloti and R. leguminosarum also acted as very effective competitors of [14C]sucrose uptake in salt-stressed cultures of these bacteria. Conversely, disaccharides that were not osmoprotective for S. meliloti and R. leguminosarum did not inhibit sucrose uptake in these bacteria. Hence, disaccharide osmoprotectants apparently shared the same uptake routes in these bacteria. Natural-abundance 13C nuclear magnetic resonance spectroscopy and quantification of cytosolic solutes demonstrated that the novel disaccharide osmoprotectants were not accumulated to osmotically significant levels in salt-stressed S. meliloti cells; rather, these compounds, like sucrose and ectoine, were catabolized during early exponential growth, and contributed indirectly to enhance the cytosolic levels of two endogenously synthesized osmolytes, glutamate and the dipeptideN-acetylglutaminylglutamine amide. The ecological implication of the use of these disaccharides as osmoprotectants is discussed.
Histochemical responses at a biomaterial's interface.

A series of nonporous glasses and glass materials designed with controlled surface ion activities to allow chemical bonding to bone are described. Surface reactivities of these materials in vitro are correlated with biological activities in vivo and in tissue culture. Direct chemical bonding of the materials to bone is demonstrated. The mechanism for development of this bond is through the production of an amorphous ion surface gel on the bioglass. This gel induces osteogenesis by a chemotactic response of osteoblasts.
Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers

Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI or weight in our study. These findings contribute to further understand the pharmacokinetic characteristics of ivermectin, highlighting its safety across different dosing regimens. They also correlate with known pharmacokinetic parameters showing stable levels of AUC and Cmax across a wide range of body weights, which justifies the strategy of fix dosing from a pharmacokinetic perspective. Trial registration ClinicalTrials.gov NCT03173742.
The role of extracorporeal membrane oxygenation circulatory support in the ‘crash and burn’ patient: from implantation to weaning

Purpose of review In advanced cardiogenic shock, early mechanical circulatory support may prevent multiorgan failure and death. In this article, we are describing our experience with extracorporeal membrane oxygenation (ECMO) application. Recent findings Venoarterial ECMO has been used successfully as a therapeutic option for patients with advanced cardiogenic shock and cardiac arrest. Summary In this review, based on the daily routine of the Hershey group using ECMO for therapy of advanced cardiogenic shock, the application of ECMO is described. The aim is to share our hands-on experience during emergent implantation and to contribute to the knowledge within the field of mechanical circulatory support.
Growth of Francisella tularensis LVS in macrophages: the acidic intracellular compartment provides essential iron required for growth

Murine macrophages supported exponential intracellular growth of Francisella tularensis LVS in vitro with a doubling time of 4 to 6 h. LVS was internalized and remained in a vacuolar compartment throughout its growth cycle. The importance of endosome acidification to intracellular growth of this bacterium was assessed by treatment of LVS-infected macrophages with several different lysosomotropic agents (chloroquine, NH4Cl, and ouabain). Regardless of the agent used or its mechanism of action, macrophages treated with agents that blocked endosome acidification no longer supported replication of LVS. Over several experiments for each lysosomotropic agent, the number of CFU of LVS recovered from treated macrophage cultures was equivalent to the input inoculum (approximately 10(4) CFU) at 72 h. In contrast, over 10(8) CFU was consistently recovered from untreated cultures. Pretreatment of macrophages with these endosome acidification inhibitors did not alter their ingestion of bacteria. Further, the effects of the inhibitors were completely reversible: inhibitor-pretreated LVS-infected macrophages washed free of the agent and cultured in medium fully supported LVS growth over 72 h. Endosome acidification is an important cellular event essential for release of iron from transferrin. The growth-inhibitory effects of both chloroquine and NH4Cl were completely reversed by addition of ferric PPi, a transferrin-independent iron source, at a neutral pH but not by addition of excess holotransferrin. Thus, intracellular localization in an acidic vesicle which facilitates the availability of iron essential for Francisella growth is a survival tactic of this bacterium, and iron depletion is one mechanism that macrophages use to inhibit its growth.
Application of the bilateral dual-grid FDTD method to the calculation of specific absorption rate in fetal brain

This paper presents an application of the bilateral dual-grid finite-difference time-domain (DG-FDTD) method. We propose to determine in a short computation time the specific absorption rate in the fetal brain of a pregnant woman at 900 MHz. The principle of the new technique consists in splitting the overall simulation into three FDTD simulations sequentially executed with an appropriate mesh. Results obtained with this approach are compared to the original FDTD and DG-FDTD methods.
Temperature‐dependent variation in Anopheles merus larval head capsule width and adult wing length: implications for anopheline taxonomy

Abstract. Seasonal variations in mosquito larval head capsule width and adult female wing length were investigated in a field population of Anopheles merus Donitz at Nceswana Lake, Ophansi, within the endemic malaria area of Natal, South Africa. An inverse relationship was detected between each of these morphological characters and seasonal fluctuations in air/water temperatures. Mean head capsule width in all larval instars decreased by 4.8‐7.9% in summer, while mean wing length decreased by 19.6%. These changes are discussed in relation to the annual range in mean air temperature in southern Africa and the distribution of An. merus. Implications for the use of such morphological characteristics in existing taxonomic keys are discussed.
Absence of the TP53 poly-A signal sequence variant rs78378222 in oral, cervical and breast cancers in South India.

With recent advancements in genomics, rare genetic variants attract the attention of cancer researchers as they represent one among the many diverse mechanisms that determine cancer risk and outcome. One such rare variant is the Single Nucleotide Polymorphism rs78378222 that alters the polyadenylation signal (AATAAA to AATACA) of TP53. Initially identified in Caucasian population, the variant ‘C’ allele was associated with an increased risk for prostate cancer, brain cancer and colorectal adenoma but not with colorectal cancer, breast cancer and melanoma (Stacey et al., 2011). Further, the risk allele impaired the proper termination of TP53 resulting in ‘cancer promoting’ longer mRNA transcripts that hindered p53 expression and its downstream functions in apoptosis (Stacey et al., 2011; Li et al., 2013). Simultaneously it was reported that rs78378222 increased the risk of esophageal cancer in Han Chinese population (Zhou et al., 2012). A similar study based on Caucasian population, showed that the rare variant was associated with risk for glioma and also significantly improved survival in patients (Egan et al., 2012). However, the association to survival was not observed in glioma patients of Northern European ancestry although it increased glioma risk (Enciso-Mora et al., 2013). A recent study showed that the heterozygous ‘AC’ genotype was not associated with melanoma and lung cancer, but had a protective role against squamous cell carcinoma of head and neck in non-Hispanic whites (Guan et al., 2013). Given the multitude of effects of rs78378222 in cancer patients of different ethnicity and on account of paucity of information on ‘C’ allele frequency in Indian population, we genotyped 439 genomic DNA samples from oral (108), cervical (96) and breast (235) cancer patients of Indian ethnicity. Blood samples were collected from Government Royapettah Hospital & Government Kasturba Gandhi Hospital for Women and Children, Chennai and clinical information from subjects was undertaken with informed consent and relevant ethical review board approval was accorded. We adopted the PCR-RFLP methodology described by Zhou et al (2012), with a single base mismatch in reverse primer creating a Hind III recognition site when the wild type A allele is present (Figure 1). The RFLP results were confirmed by direct sequencing of 10% of case/control samples chosen at random (Figure 2). We found that the ‘C’ allele was totally absent in cancer samples. We also genotyped 504 healthy controls LETTER to the EDITOR
Strengthening Distance Nursing Laboratory Courses Through Application of Theoretical Foundations: A Literature Review

Abstract A literature review was conducted to assess study results and theoretical foundations regarding distance nursing lab courses. A variety of education and nursing-specific theories were utilized during curriculum development. No two studies applied the same theoretical foundations. Further research and integration of theoretical foundations, including the synthesis of multiple theories regarding the distance teaching of psychomotor skills, will strengthen distance nursing lab courses and allow for more effective and evidence-based learning of psychomotor skills.
Segmental composite porous scaffolds with either osteogenesis or anti‐bone resorption properties tested in a rabbit ulna defect model

A functional biomaterial with a therapeutic effect is desirable as an adjuvant therapy to enhance bone formation and prevent local recurrence of bone tumours, especially when the resection margins are not identifiable. In this study, novel composite materials were developed with dual properties of osteopromotion and bone resorption to mimic the tumour inhibition effect, including water‐soluble phosphorylated chitosan (P‐chitosan) for increasing osteoblasts activity and disodium (1 → 4)‐2‐deoxy‐2‐sulphoamino‐β‐d‐glucopyranuronan (S‐chitosan) for inhibiting bone resorption activity. First, P‐chitosan and S‐chitosan were respectively incorporated into two kinds of PLGA/TCP‐based scaffold, i.e. PLGA–TCP–P‐chitosan (P/T/P‐chitosan) and PLGA–TCP–S‐chitosan (P/T/S‐chitosan) scaffolds. We subsequently tested combined scaffolds of PLGA–TCP–P–S–P‐chitosan (P/T/PSP‐chitosan) made of P/T/P‐chitosan and P/T/S‐chitosan to assess their integral effect, on enhancement of bone formation with P/T/P‐chitosan and inhibition of tissue regeneration with P/T/S‐chitosan, in an established rabbit ulnar bone defect model to imitate bone resection post‐bone tumour. To compare bone healing in the defects, the P/T/P‐chitosan group was regarded as a bone formation enhancement group, while the P/T group served as a control. Bone mineral density (BMD) in the P/T/P‐chitosan and P/T/PSP‐chitosan groups were found to be significantly higher than those in the P/T group, while that in the P/T/P‐chitosan group was greater than that in the P/T/PSP‐chitosan group (p < 0.05). These findings demonstrated that P/T/PSP‐chitosan scaffolds possessed more osteogenic potential than the P/T scaffold but less osteogenic effect than the P/T/P‐chitosan scaffold, as the S‐chitosan component inhibited the activities of osteoblasts for bone formation. These findings implied a dual function of the designed P/T/PSP‐chitosan for further preclinical validation and potential applications in the prevention of local recurrence and for enhancing bone repair after bone tumour resection. Copyright © 2013 John Wiley & Sons, Ltd.
The effect of spatiality on multiplex networks

Many multiplex networks are embedded in space, with links more likely to exist between nearby nodes than distant nodes. For example, interdependent infrastructure networks can be represented as multiplex networks, where each layer has links among nearby nodes. Here, we model the effect of spatiality on the robustness of a multiplex network embedded in 2-dimensional space, where links in each layer are of variable but constrained length. Based on empirical measurements of real-world networks, we adopt exponentially distributed link lengths with characteristic length ζ. By changing ζ, we modulate the strength of the spatial embedding. When ζ → ∞, all link lengths are equally likely, and the spatiality does not affect the topology. However, when only short links are allowed, and the topology is overwhelmingly determined by the spatial embedding. We find that, though longer links strengthen a single-layer network, they make a multi-layer network more vulnerable. We further find that when ζ is longer than a certain critical value, , abrupt, discontinuous transitions take place, while for the transition is continuous, indicating that the risk of abrupt collapse can be eliminated if the typical link length is shorter than .
Interaction of the New Ketolide ABT-773 (Cethromycin) with Human Polymorphonuclear Neutrophils and the Phagocytic Cell Line PLB-985 In Vitro

ABSTRACT A classical velocity centrifugation technique was used to study the in vitro uptake of the new ketolide ABT-773 by human polymorphonuclear neutrophils (PMNs) and a myelomonoblastic cell line, PLB-985, which can be differentiated into PMNs under certain culture conditions, compared to that of HMR 3004. ABT-773 was rapidly taken up by PMNs (cellular concentration to extracellular concentration ratio [C/E], about 34 at 30 s and up to 207 at 5 min), and uptake plateaued from 30 to 180 min (C/E, about 300). ABT-773 was accumulated significantly better than HMR 3004 from 5 to 180 min. Nondifferentiated PLB-985 cells (ND-PLB) accumulated significantly less ABT-773 and HMR 3004 than PMNs and PLB-985 cells differentiated into PMNs (D-PLB). Whatever the cell type and in contrast to the results obtained with HMR 3004, ABT-773 was mainly located in the cytosol (about 75%) and was rapidly released from loaded cells (about 40% at 5 min), followed by a plateau, likely owing to avid reuptake. Verapamil and H89, an inhibitor of protein kinase A, increased drug efflux. Uptake was sensitive to external pH, and the activation energy was moderate (about 50 kJ/mol). The existence of an active transport system on the PMN membrane was suggested by the following findings: concentration-dependent and saturable uptake (Vmax, about 10 000 ng/2.5 × 106 PMNs/5 min; Km, about 60 μg/ml) the inhibitory effects of PMN activators or inhibitors (phorbol myristate acetate, verapamil, Ni2+) and the significantly decreased levels of accumulation by killed cells and cells treated at low temperatures. In addition, various macrolides impaired ABT-773 uptake, contrary to the findings for the quinolone levofloxacin. ND- and D-PLB also presented saturation kinetics that defined an active transport system (Vmax and Km values were similar to those obtained with PMNs), but the activation pathway of the carrier system did not seem to be fully functional in ND-PLB. As has been observed with other erythromycin A derivatives, ABT-773 impaired oxidant production by phagocytes in a time- and concentration-dependent manner. These data extend our previous results on the existence of an active transport system common to all macrolides and ketolides, at least in PMNs.
Nearwork-Induced Changes in Topography, Aberrations, and Thickness of the Human Cornea After Interrupted Reading

Purpose: Recent experiments have suggested transient changes in corneal optics after short durations of reading. This study investigated an interrupted 1-hour period of reading on corneal topography in a sample of young myopic and emmetropic adults. Methods: Ten myopic and 9 emmetropic young adult subjects were recruited for the study. They read adult-level text binocularly at 40 cm with ∼30 degree downward gaze for 1 hour, with distance correction in place. Orbscan II corneal topography was performed at baseline and 5, 15, 30, and 60 minutes after reading during 1 test session to assess for changes in corneal power, aberrations, and thickness. Results: Myopes exhibited greater corneal power and spherical aberration than emmetropes both before and after reading. Increased corneal higher-order aberrations (at baseline only) and thickness (superior position only) were observed in myopes versus emmetropes. Conclusions: Several corneal parameters differed in the myopes after reading as compared with emmetropes. Differences in corneal parameters were smaller in this study than found in earlier studies, perhaps because of the interrupted nature of the task in the former versus the continuous nature in the latter.
Wireless capsule endoscopy in the investigation of patients with chronic renal failure and obscure gastrointestinal bleeding (preliminary data).

AIM To investigate the role of wireless capsule endoscopy (WCE) in detection of small bowel (SB) pathology in patients with chronic renal failure (CRF) and obscure bleeding. METHODS Consecutive CRF patients with obscure bleeding were prospectively studied. Patients with normal renal function and obscure bleeding, investigated during the same period with WCE, were used for the interpretation of results. RESULTS Seventeen CRF patients (11 overt, 6 occult bleeding) and 51 patients (33 overt, 18 occult bleeding) with normal renal function were enrolled in this study. Positive SB findings were detected in 70.6% of CRF patients and in 41.2% of non-CRF patients (P < 0.05). SB angiodysplasia was identified in 47% of CRF patients and in 17.6% of non-CRF patients. Univariate logistic regression revealed CRF as a significant predictive factor for angiodysplasia (P < 0.05). Therapeutic measures were undertaken in 66% of the patients with the positive findings. CONCLUSION According to our preliminary results, SB angiodysplasia was found in an increased prevalence among CRF patients with obscure bleeding. WCE is useful in diagnosis of gastrointestinal pathologies and in planning appropriate therapeutic intervention and, therefore, should be included in the work-up of this group of patients.