Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting integrin-linked kinase inhibits Akt signaling pathways and decreases tumor progression of human glioblastoma

The phosphatidylinositol 3-kinase pathway is an important regulator of a wide spectrum of tumor-related biological processes, including cell proliferation, survival, and motility, as well as neovascularization. Protein kinase B/Akt is activated in a complex manner through the phosphorylation of protein kinase B/Akt on Thr308 and Ser473. Although protein-dependent kinase-1 has been shown to phosphorylate Akt at Thr308, it is not clear whether there is a distinct kinase that exclusively phosphorylates Akt at Ser473. A possible candidate is integrin-linked kinase (ILK), which has been shown to phosphorylate Akt at Ser473 in vitro. ILK is a multidomain focal adhesion protein that is believed to be involved in signal transmission from integrin and growth factor receptors. Further, ILK is implicated in the regulation of anchorage-dependent cell growth/survival, cell cycle progression, invasion and migration, and tumor angiogenesis. In this study, we tested the hypothesis that ILK inhibition would inhibit these processes in gliomas in which it is constitutively expressed. We found that a newly developed small-molecule compound (QLT0267) effectively inhibited signaling through the ILK/Akt cascade in glioma cells by blocking the phosphorylation of Akt and downstream targets, including mammalian target of rapamycin and glycogen synthase kinase-3β. Treatment of glioma cells with 12.5 μmol/L QLT0267 inhibited cell growth by 50% at 48 hours. An anchorage-dependent cell growth assay confirmed the cell growth-inhibitory effect of QLT0267. Further, the decrease in cell growth was associated with a dramatic accumulation of cells in the G2-M phase of the cell cycle. Although the cell growth-inhibitory effects of the ILK inhibitor were achieved only at a high concentration, the QLT0267 was able to reduce cellular invasion and angiogenesis at much lower concentrations as shown by in vitro invasion assays and vascular endothelial growth factor secretion. Thus, blocking the ILK/Akt pathway is a potential strategy for molecular targeted therapy for gliomas.
“The Reality of Today Has Required Us to Change”: Negotiating Gender Through Informal Work in Contemporary Argentina

Within Argentina and beyond, the characteristics of work are changing as work becomes increasingly informal and precarious. Drawing on interviews conducted with informal workers in Buenos Aires in 2002, this article analyzes the ways that the informalization of work during the economic crisis in Argentina shaped the interplay between normative and practiced manifestations of gender, including masculinity and femininity. I argue that although normative understandings of gender in Argentina remain largely uncomplicated by economic restructuring and crisis, the activity of informal work interacts very differently with the performances of these norms, depending on the class and sex of the worker. In particular, I demonstrate that among workers in the popular classes, the characteristics of informal work serve to mediate tensions resulting from women's engagement in paid work, while constituting an obstacle to men's performance of the hegemonic masculinity of the provider. Among middle-class workers, however, engaging in informal work does not result in the same types of tensions between gender norms and performances. I conclude by questioning the long-term nature of changes in gender relations resulting from this crisis and stressing the importance of intersectionality on understanding impacts of economic change. In addressing the question of how an increased dependence on informal work has affected gender relations in Argentina, this article seeks to contribute to wider discussions regarding the malleability of gender systems and the need to understand the effects of global restructuring on local gender relations, including performances of masculinity.
A novel action of quinine and quinidine on the membrane conductance of neurons from the vertebrate retina

The cinchona alkaloids quinine and quinidine have been shown to block a broad range of voltage-gated membrane conductances in a variety of excitable tissues. Using the whole-cell version of the patch clamp technique, we examined the effects of these compounds on voltage- dependent currents from horizontal cells dissociated enzymatically from the all-rod retina of the skate. We report here a novel and unexpected action of quinine and quinidine on isolated horizontal cells. In addition to blocking several of the voltage-activated currents of these cells, the introduction of the alkaloids evoked a large outward current when the cells were held at depolarized potentials. Using tail current analysis, the reversal potential of the outward current was close to O mV, and the current was markedly suppressed by extracellularly applied cobalt, acetate, and halothane. Depolarization in the presence of quinine also permitted entry into the cells of extracellularly applied Lucifer yellow (MW = 443 D), whereas a 3-kD fluorescein-dextran complex was excluded. These findings suggest that the large, apparently nonselective conductance induced by quinine and quinidine results from the opening of hemi-gap junctional channels.
Task-based control of articulated human pose detection for OpenVL

Human pose detection is the foundation for many applications, particularly those using gestures as part of a natural user interface. We introduce a novel task-based control method for human pose detection, encoding specialist knowledge in a descriptive abstraction for application by non-experts, such as developers, artists and students. The abstraction hides the details of a set of algorithms which specialise either in different estimations of pose (e.g. articulated, body part) or under different conditions (e.g. occlusion, clutter). Users describe the conditions of their problem, which is used to select the most suitable algorithm (and automatically set up the parameters). The task-based control is evaluated with images described using the abstraction. Expected outcomes are compared to results and demonstrate that describing the conditions is sufficient to allow the abstraction to produce the required result.
The Kidney Donor Profile Index (KDPI) of Marginal Donors Allocated by Standardized Pretransplant Donor Biopsy Assessment: Distribution and Association With Graft Outcomes

Pretransplant donor biopsy (PTDB)‐based marginal donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the highest range (e.g. >80 or >90), whose discard rate approximates 50% in the United States. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score <4 [median KDPI: 87; interquartile range (IQR): 78–94] and 62 with a score = 4 [median KDPI: 87; IQR: 76–93]; 102 dual transplants [median KDPI: 93; IQR: 86–96]) and 248 single standard transplant controls (median KDPI: 36; IQR: 18–51). PTDB‐based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80–90 and of 37% for kidneys with a KDPI of 91–100. Although 1‐year estimated GFRs were significantly lower in recipients of marginal kidneys (−9.3, −17.9 and −18.8 mL/min, for dual transplants, single kidneys with PTDB score <4 and =4, respectively; p < 0.001), graft survival (median follow‐up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 [95% confidence interval: 0.80–1.79; p = 0.38]). In conclusion, PTDB‐based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.
Technique for Studying Adaptation to Disarranged Hand-Eye Coordination

Errors in localization are produced by any optical device that intercepts the line of sight and displaces the retinal image. The viewer's error in reaching for or pointing to an object tends to equal the angular displacement of the retinal image. However, according to many reports this error in localizacion is reduced during prolonged viewing. Helmholtz (2, Sect. 29) was one of rhe first to report that an S shifted his localization after viewing his hand through a prism. In general, Ss have adapted to the disarranged condition provided by mirrors or prisms and more recently by a dosed circuit television system ( 3 ) . Many of these disarrangement experiments, e.g., with mirror drawing, are designed to study the learning of altered skills. Consequently, some variant of that classical paradigm of learning-trial, error, and correction-is often used to explain the observed reduction of error. However, in at least one related experiment ( 1 ) adaptation to the disarrangement of a spatial coordination has been observed although S had no information concerning his actual or potencial errors in localization. This result casts doubt on the adequacy of the trial-and-error explanation; a doubt that is neither raised nor eliminated by the resulrs of most experiments on disarranged coordination simply because their designs incorporate the assumption thac recognition of error is essential to adaptation. In these experiments S, watching his clumsy attempts to mark targets in repeated trials, sees the errors he makes, the same errors measured by E. Clearly the applicability of a trial-and-error theory must be checked under condirions wherein S's recognition of error is eliminated. Measurable errors of hand-eye coordination are obtained by instructing S to make either his hand or his markings coincide with a visible object (target). E can then measure the deviation from coincidence of hand and objecc. S recognizes his errors only when he can see these deviations from coincidence. If he sees neither his hand nor his markings he cannot recognize his errors. To this end he can be instructed to make the felt position of his hand coincide with the seen position of an object. This method of localization, described in detail below, allows E to measure errors in localization which S cannoc view. The adaptation, discussed originally by Helmholtz, occurs only when S does view his hand under the disarranged condicion. This viewing, called here the exposure condition, need include no visible objecc (set of contours) other than the hand. S may see only his hand in an otherwise dark field.
NLR family member NLRC5 is a transcriptional regulator of MHC class I genes

MHC class I plays a critical role in the immune defense against viruses and tumors by presenting antigens to CD8 T cells. An NLR protein, class II transactivator (CIITA), is a key regulator of MHC class II gene expression that associates and cooperates with transcription factors in the MHC class II promoter. Although CIITA also transactivates MHC class I gene promoters, loss of CIITA in humans and mice results in the severe reduction of only MHC class II expression, suggesting that additional mechanisms regulate the expression of MHC class I. Here, we identify another member of the NLR protein family, NLRC5, as a transcriptional regulator of MHC class I genes. Similar to CIITA, NLRC5 is an IFN-γ–inducible nuclear protein, and the expression of NLRC5 resulted in enhanced MHC class I expression in lymphoid as well as epithelial cell lines. Using chromatin immunoprecipitation and reporter gene assays, we show that NLRC5 associates with and activates the promoters of MHC class I genes. Furthermore, we show that the IFN-γ–induced up-regulation of MHC class I requires NLRC5, because knockdown of NLRC5 specifically impaired the expression of MHC class I. In addition to MHC class I genes, NLRC5 also induced the expression of β2-microglobulin, transporter associated with antigen processing, and large multifunctional protease, which are essential for MHC class I antigen presentation. Our results suggest that NLRC5 is a transcriptional regulator, orchestrating the concerted expression of critical components in the MHC class I pathway.
Alternating d(GA)n DNA sequences form antiparallel stranded homoduplexes stabilized by the formation of G.A base pairs.

Alternating d(GA)n DNA sequences form antiparallel stranded homoduplexes which are stabilized by the formation of G.A pairs. Three base pairings are known to occur between adenine and guanine: AH+ (anti). G(syn), A(anti). G(anti) and A(syn). G(anti). Protonation of the adenine residues is not involved in the stabilization of this structure, since it is observed at any pH value from 8.3 to 4.5; at pH < or = 4.0 antiparallel stranded d(GA.GA) DNA is destabilized. The results reported in this paper strongly suggest that antiparallel stranded d(GA.GA) homoduplexes are stabilized by the formation of alternating A(anti). G(anti) and G(anti). A(syn) pairs. In this structure, all guanine residues are in the anti conformation with their N7 position freely accessible to DMS methylation. On the other hand, adenines in one strand adopt the anti conformation, with their N7 position also free for reaction, while those of the opposite strand are in the syn conformation, with their N7 position hydrogen bonded to the guanine N1 group of the opposite strand. A regular right‐handed helix can be generated using alternating G(anti). A(syn) and A(anti). G(anti) pairs.
Racism in a Time of Terror

t is still mourning time here in New York City. It has been several months since the terrorist attack destroyed the World Trade Center towers, but the tragedy remains brutally fresh and terribly vivid to millions of residents in this overcrowded metropolis. The horrific spectra of 3,000 human beings incinerated in less than 100 minutes, of screaming people free-falling more than a thousand feet to their deaths cannot be comprehended or even explained. As I first witnessed the smoke billowing across the city’s skyline, I knew that the criminals who had obliterated the World Trade Center and part of the Pentagon were attempting to make a symbolic political statement about the links between transnational capitalism and U.S. militarism. But by initiating acts of mass murder, any shred of political credibility sought by those who plotted and carried out these crimes was totally destroyed. There can be no justification, excuse, or rationale for the deliberate use of deadly force and unprovoked violence against any civilian population. This was not essentially an act of war, but a criminal act, a crime against not only the American people, but all of humanity. All of those who planned, financed, and assisted in carrying out these crimes must be apprehended and brought to justice—but, I would add, under the aegis of international law and the United Nations. In the immediate days following the terrorist attacks, some elements of the sectarian U.S. left, including a few black activists, took the bizarre position that those who carried out these crimes were somehow “freedom fighters. ” These “left” critics implied that these vicious, indiscriminate actions must be interpreted within the political context of the oppression that gave rise to those actions. In short, the brutal reality of U.S. imperialism, including America’s frequent military occupation of Third World countries, somehow justifies the use of political terrorism as a legitimate avenue for expressing their political resistance. It is certainly true that the American left must vigorously and I Racism in a Time of Terror
Synthesis of Robust , Semi-Intelligble Isar Proofs from ATP Proofs

Sledgehammer is a tool that integrates external automatic theorem provers (ATPs) into the Isabelle/HOL proof assistant, allowing users to delegate proof search to the computer. To guard against bugs, ATP proofs must be reconstructed in Isabelle. Reconstructing complex proofs involves translating them to detailed Isabelle proof texts, using suitable proof methods to justify the inference steps. This thesis addresses the main issues that have prevented previous implementations of this approach from working in practice: Sledgehammer now reconstructs skolemization inferences correctly, and it equips proof texts with the right amount of type annotations to ensure formulas are parsed correctly without overwhelming them with types. In addition, Sledgehammer now employs algorithms to test and optimize its output, resulting in simpler, faster, and more robust proofs.
Critical Incident Stress in Victoria State Emergency Service Volunteers: Characteristics of Critical Incidents, Common Stress Responses, and Coping Methods

Abstract This study was an exploratory investigation of key elements in Critical Incident Stress in 25 volunteer members of the Victoria State Emergency Service, a service which responds to road accident rescues in Victoria, amongst other emergency activities. The principal findings were as follows: (a) six factors were found to be most characteristic of Critical Incidents (CIs), and those factors reflected three themes, namely knowing or identifying with the victim or their family; large scale incidents; and suprise or novelty of the event; (b) stress responses often did not occur during the CI, those symptoms which did emerge were predominantly cognitive; (c) after a CI, cognitive and physiological responses were most common; (d) avoidance styles of coping (e.g., “keep active” and “switch off”) were more common during a CI, whereas approach styles of coping (e.g., “discussion” and “debriefing”) were more common afterwards; (e) participants reported having learnt how to cope more effectively following a .
Avian Melatonin Synthesis: Photic and Circadian Regulation of Serotonin N‐Acetyltransferase mRNA in the Chicken Pineal Gland and Retina

Abstract: The circadian rhythms in melatonin production in the chicken pineal gland and retina reflect changes in the activity of serotonin N‐acetyltransferase (arylalkylamine N‐acetyltransferase; AA‐NAT; EC 2.3.1.87). Here we determined that the chicken AA‐NAT mRNA is detectable in follicular pineal cells and retinal photoreceptors and that it exhibits a circadian rhythm, with peak levels at night. AA‐NAT mRNA was not detected in other tissues. The AA‐NAT mRNA rhythm in the pineal gland and retina persists in constant darkness (DD) and constant lighting (LL). The amplitude of the pineal mRNA rhythm is not decreased in LL. Light appears to influence the phase of the clock driving the rhythm in pineal AA‐NAT mRNA in two ways: The peak is delayed by ∼6 h in LL, and it is advanced by >4 h by a 6‐h light pulse late in subjective night in DD. Nocturnal AA‐NAT mRNA levels do not change during a 20‐min exposure to light, whereas this treatment dramatically decreases AA‐NAT activity. These observations suggest that the rhythmic changes in chicken pineal AA‐NAT activity reflect, at least in part, clock‐generated changes in mRNA levels. In contrast, changes in mRNA content are not involved in the rapid light‐induced decrease in AA‐NAT activity.
L-DOPA treatment modulates nicotinic receptors in monkey striatum.

Nicotinic acetylcholine receptor (nAChR) activation is well known to stimulate dopamine release in the striatum. This phenomenon may be physiologically significant in the control of motor function, as well as in pathological conditions such as Parkinson's disease. An understanding of the mechanisms that influence nAChR expression and function is therefore important. Because the dopamine precursor l-DOPA is the most commonly used therapeutic agent for Parkinson's disease, we investigated the effects of l-DOPA treatment on striatal nAChR expression in unlesioned and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. In unlesioned animals, l-DOPA (15 mg/kg) administered twice daily for 2 weeks decreased both 125I-epibatidine and [125I]iodo-3-[2(S)-azetidinylmethoxy]pyridine (A-85380) binding sites in the caudate and putamen, but did not affect 125I-alpha-CtxMII sites. alpha-CtxMII inhibition of striatal 125I-epibatidine and [125I]A-85380 binding with alpha-CtxMII suggest that there are both high- (Ki < 0.2 nM) and low-affinity (Ki > 100 nM) alpha-CtxMII-sensitive sites, as well as alpha-CtxMII-resistant sites, and that l-DOPA treatment influences only the low-affinity alpha-CtxMII-sensitive subtype. The l-DOPA effect was selective for striatal nAChRs with no change in cortical sites. Monkeys with severe nigrostriatal damage did not exhibit l-DOPA-induced declines in striatal nAChRs, suggesting that l-DOPA primarily affects nAChRs associated with dopaminergic terminals. In summary, these data show that l-DOPA treatment decreases nAChR expression, in contrast with the well established up-regulation of these sites by chronic nicotine exposure. Furthermore, they demonstrate preferential l-DOPA regulation of a novel low-affinity alpha-CtxMII-sensitive site. These declines in nAChRs with l-DOPA may be relevant to both the therapeutic and side effect profiles of l-DOPA therapy in Parkinson's disease.
Angels and Devils: Moral Landscapes of Childhood

What it means to be a child varies over space and time. Historically, the dominant Western construction of childhood has oscillated between representing children as the bearers of original sin—devils—or as innocent—angels, in the United Kingdom in the 19th and for much of the 20th century it was this latter imagining of childhood that took hold. But the murder of toddler Jamie Bulger by two 10-year-old boys in 1993 has been pivotal in reengaging a demonised conceptualisation of what it means to be a child. The author begins by considering some of the contested meanings of childhood and then goes on to explore the contemporary ‘othering’ of children and some of the spatial restrictions being imposed on young people by adults in an attempt to (re)draw boundaries between ‘us’ and ‘them’.
Effects of a Target Object Orientation Task on Recall in Older Adults with Probable Alzheimer's Disease

ABSTRACT In this study, six older adults with probable Alzheimer's Disease were trained to recall everyday objects using the spaced-retrieval method (Camp, 1989). We administered three training sessions on alternate days over a week. On each trial, participants selected a target object from an array of items at increasingly longer retention intervals. Half of the participants were given a target object orientation task prior to training to improve spaced-retrieval performance. Results yielded a positive effect of the orientation task on recall of the target object across trials. These data provide support for the view that task-relevant orienting activities enhance the effectiveness of spaced-retrieval training.