Black Laundry is a queer anti-occupation group which grew out of the feminist peace movement in Israel and adopted imaginative and humorous ways to re-imagine citizenship and solidarity in a ...nationalist militaristic context. The following essay describes the evolution of the group from the perspective of one of its co-founders, and focuses on the group's improvisational, non-exclusionary strategies, and on different reactions to the high visibility of the group's interventions during the Al-Aqsa Intifada years 2002-2003.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Isotope effects for the encapsulation of deuterated versus nondeuterated guests are determined. This system involves the use of social isomers, and the origin of the isotope effect is localized to ...methyl groups interacting with aromatic rings.
The challenge in controlling stochastic systems in which low-probability events can set the system on catastrophic trajectories is to develop a robust ability to respond to such events without ...significantly compromising the optimality of the baseline control policy. This paper presents CelluDose, a stochastic simulation-trained deep reinforcement learning adaptive feedback control prototype for automated precision drug dosing targeting stochastic and heterogeneous cell proliferation. Drug resistance can emerge from random and variable mutations in targeted cell populations; in the absence of an appropriate dosing policy, emergent resistant subpopulations can proliferate and lead to treatment failure. Dynamic feedback dosage control holds promise in combatting this phenomenon, but the application of traditional control approaches to such systems is fraught with challenges due to the complexity of cell dynamics, uncertainty in model parameters, and the need in medical applications for a robust controller that can be trusted to properly handle unexpected outcomes. Here, training on a sample biological scenario identified single-drug and combination therapy policies that exhibit a 100% success rate at suppressing cell proliferation and responding to diverse system perturbations while establishing low-dose no-event baselines. These policies were found to be highly robust to variations in a key model parameter subject to significant uncertainty and unpredictable dynamical changes.
Background Most cases of colorectal cancer (CRC) are initiated by inactivation mutations in the APC gene, which is a negative regulator of the Wnt-beta-catenin pathway. Patients with familial ...adenomatous polyposis (FAP) inherit a germline mutation in one APC allele, and loss of the second allele leads to the development of polyps that will turn malignant if not removed. It is not fully understood which molecular mechanisms are activated by APC loss and when the loss of the second APC allele occurs. Methods Two FAP human embryonic stem cell (hESCs) lines were derived from APC mutated embryos following pre-implantation genetic diagnosis (PGD) for FAP. These FAP-hESCs were cultured in vitro and following extended culture: 1) beta-catenin expression was analyzed by Western blot analysis; 2) Wnt-beta-catenin/TCF-mediated transcription luciferase assay was performed; 3) cellular localization of beta-catenin was evaluated by immunoflorecence confocal microscopy; and 4) DNA sequencing of the APC gene was performed. Results We have established a novel human in-vitro model for studying malignant transformation, using hESCs that carry a germline mutation in the APC gene following PGD for FAP. Extended culturing of FAP1 hESCs led to activation of the Wnt signaling pathway, as demonstrated by enhanced beta-catenin/TCF-mediated activity. Additionally, beta-catenin showed a distinct perinuclear distribution in most (91 %) of the FAP1 hESCs high passage colonies. DNA sequencing of the whole gene detected several polymorphisms in FAP1 hESCs, however, no somatic mutations were discovered in the APC gene. On the other hand, no changes in beta-catenin were detected in the FAP2 hESCs, demonstrating the natural diversity of the human FAP population. Conclusions Our results describe the establishment of novel hESC lines from FAP patients with a predisposition for cancer mutation. These cells can be maintained in culture for long periods of time and may serve as a platform for studying the initial molecular and cellular changes that occur during early stages of malignant transformation. Keywords: Human embryonic stem cells (hESCs), Familial adenomatous polyposis (FAP), Adenomatous polyposis coli (APC), Cancer
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
► We develop a model of welfare stigma where stigma affects employment prospects. ► We find two contrasting effects: a deterrence effect (D) and an entrapment effect (E). ► Rational individuals ...foreseeing the reduction in employability defer welfare entry (D). ► Once assisted, individuals experience less welfare-to-employment transitions (E). ► Differently from other models, more stigma might yield to less employment.
Stigma has been modeled in the literature as a cost of welfare participation, providing a disincentive to welfare entry; hence, traditional models predict that stigma leads to higher search effort and higher employment. We develop a more comprehensive model that accounts for the fact that welfare stigma may elicit psychological effects and foster negative attitudes towards welfare recipients, affecting their employment prospects. We find two contrasting effects. The first reinforces the standard prediction: rational individuals foreseeing the reduction in employability defer welfare entry (deterrence effect); the second goes in the opposite direction: once assisted, individuals experience less welfare-to-employment transitions, both because of reduced search effectiveness and of reduced search effort (entrapment effect). When stigma is not too high, the latter effect prevails: more stigma yields to less employment and more welfare participation. The result is stronger if individuals are not able to foresee their loss of employability.
Misfit-layered compounds (MLCs) are formed by the combination of different lattices and exhibit intriguing structural and morphological characteristics. MLC Sr
La
S-TaS
nanotubes with varying Sr ...composition (10, 20, 40, and 60 Sr atom %, corresponding to
= 0.1, 0.2, 0.4 and 0.6, respectively) were prepared in the present study and systematically investigated using a combination of high-resolution electron microscopy and spectroscopy. These studies enable detailed insight into the structural aspects of these phases to be gained at the atomic scale. The addition of Sr had a significant impact on the formation of the nanotubes with higher Sr content, leading to a decrease in the yield of the nanotubes. This trend can be attributed to the reduced charge transfer between the rare earth/S unit (La
Sr
S) and the TaS
layer in the MLC which destabilizes the MLC lattice. The influence of varying the Sr content in the nanotubes was systematically studied using Raman spectroscopy. Density functional theory calculations were carried out to support the experimental observations.
In diametric opposition to the marital love of Jer 2:2, vv. 20–25 accuse the people את צעה זנה, “you recline as a whore” (v. 20b), and the following verses elaborate on this adulterous behavior. The ...goal of this study is to present the intrinsic role of the literary allusions to pentateuchal Priestly and Deuteronomic traditions in this prophecy, to acknowledge the variety of sources evoked, and to suggest a specific allusion to a Priestly legal tradition (or even text) that seems to give Jeremiah's prophecy special force. Three markers point to the sôṭâtrial of Num 5:11–31 as the evoked legal tradition (or text). Focusing on one specific poetic passage, commonly taken as “Jeremianic,” a portion of the prophet's words in his early career, the article calls attention to Priestly allusions in Jeremiah and raises some of the intriguing questions about Jeremiah's acquaintance with Priestly materials, questions that should be addressed in the study of both the prophetic literature of Jeremiah and in pentateuchal studies.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, ZRSKP
We present a computational model of the interaction between hydrophobic cations, such as the antimicrobial peptide, Magainin2, and membranes that include anionic lipids. The peptide’s amino acids ...were represented as two interaction sites: one corresponds to the backbone
α-carbon and the other to the side chain. The membrane was represented as a hydrophobic profile, and its anionic nature was represented by a surface of smeared charges. Thus, the Coulombic interactions between the peptide and the membrane were calculated using the Gouy-Chapman theory that describes the electrostatic potential in the aqueous phase near the membrane. Peptide conformations and locations near the membrane, and changes in the membrane width, were sampled at random, using the Metropolis criterion, taking into account the underlying energetics. Simulations of the interactions of heptalysine and the hydrophobic-cationic peptide, Magainin2, with acidic membranes were used to calibrate the model. The calibrated model reproduced structural data and the membrane-association free energies that were measured also for other basic and hydrophobic-cationic peptides. Interestingly, amphipathic peptides, such as Magainin2, were found to adopt two main membrane-associated states. In the first, the peptide resided mostly outside the polar headgroups region. In the second, which was energetically more favorable, the peptide assumed an amphipathic-helix conformation, where its hydrophobic face was immersed in the hydrocarbon region of the membrane and the charged residues were in contact with the surface of smeared charges. This dual behavior provides a molecular interpretation of the available experimental data.
Context: Several studies assessed adiponectin levels in anorexia nervosa (AN) patients, however, data regarding the dynamics of changes in adiponectin levels during refeeding of these patients is ...limited and contradicting.
Objective: Our objective was to assess adiponectin levels and the distribution of its different isoforms in AN patients before and after long-term refeeding, and to relate them to alterations in body mass index, leptin, insulin sensitivity, and additional endocrine parameters.
Design, Setting, and Participants: We conducted a longitudinal controlled study of 38 female adolescent malnourished AN inpatients, with 13 young, lean, healthy women serving as controls. Blood samples were obtained upon admission and thereafter at 1, 3, and 5 months (at target weight).
Main Outcome Measures: Changes in body mass index, leptin, adiponectin, insulin sensitivity, and adiponectin multimeric forms were measured.
Results: At admission, leptin levels of AN patients were significantly lower, whereas insulin sensitivity (assessed by homeostasis model assessment-insulin resistance), adiponectin levels, and the ratio of high molecular weight (HMW) adiponectin to total adiponectin were significantly higher compared with controls. During weight recovery, leptin levels and homeostasis model assessment-insulin resistance increased significantly, whereas adiponectin and HMW adiponectin/total adiponectin ratio decreased significantly, to levels similar to controls. An initial increase in adiponectin levels was observed after 1 month of refeeding. There was no correlation between adiponectin and either T4 or cortisol levels.
Conclusions: Our study demonstrates hyperadiponectinemia, increased adiponectin HMW isoform, and increased insulin sensitivity in adolescent AN female patients and reversal of these findings with weight rehabilitation. We hypothesize that increased adiponectin levels may have a protective role in maintaining energy homeostasis during extreme malnourishment.
In obese children, bone age (BA) tends to significantly exceed chronological age (CA). In vitro studies in mice suggest that insulin may directly modulate skeletal growth. We investigated whether ...there is an association between fasting insulin and BA maturation in obese children.
The study cohort comprised 74 overweight and obese children ages 4 to 13 years. BA divided by CA was used as an index for bone advancement. Participants were classified into tertiles based on their BA:CA ratio. Advanced BA maturation was defined as the third tertile, with BA:CA > 1.21. Components of the metabolic syndrome, including fasting insulin, fasting glucose, triglycerides, and high-density lipoprotein (HDL) levels, were measured.
Children with advanced BA were significantly younger, had a higher body mass index (BMI)-Z score (BMI-Z), and were taller than children with bone advancement in the lower tertiles. Females had a 4.7-fold increased risk for advanced BA compared with males (95% confidence interval CI, 1.29-17.1; P = .02). Children with a BMI-Z ≥ 1.96 and fasting insulin ≤ 30 μU/L had a 3.6-fold increased risk of advanced BA (95% CI, 1.00-12.8; P = 0.05). Moreover, hyperinsulinemia (fasting insulin > 30 μU/L) was associated with a 6.8-fold increased risk for advanced BA, independent of the degree of obesity (95% CI, 1.45-32.1; P = .01).
Marked hyperinsulinemia is associated with advanced BA in obese children. Insulin appears to modulate skeletal growth in humans.
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