Miracle-dz/UniFAR-FTUs huggingface dataset:
KLRG1+ NK Cells Protect T-bet–Deficient Mice from Pulmonary Metastatic Colorectal Carcinoma

We studied the developmental and functional mechanisms behind NK cell–mediated antitumor responses against metastatic colorectal carcinoma (CRC) in mice. In particular, we focused on investigating the significance of T-box transcription factors and the immunotherapeutic relevance of IL-15 in the development and function of tumor-reactive NK cells. Pulmonary CRC metastases were experimentally seeded via an adoptive i.v. transfer of luciferase-expressing CT26 CRC cells that form viewable masses via an in vivo imaging device; genetically deficient mice were used to dissect the antitumor effects of developmentally different NK cell subsets. IL-15 precomplexed to IL-15 receptor-α was used in immunotherapy experiments. We found that mice deficient for the T-box transcription factor T-bet lack terminally differentiated antitumor CD27lowKLRG1+ NK cells, leading to a terminal course of rapid-onset pulmonary CRC metastases. The importance of this NK cell subset for effective antitumor immunity was shown by adoptively transferring purified CD27lowKLRG1+ NK cells into T-bet–deficient mice and, thereby, restoring immunity against lung metastasis formation. Importantly, immunity to metastasis formation could also be restored in T-bet–deficient recipients by treating mice with IL-15 precomplexed to IL-15 receptor-α, which induced the development of eomesodermin+KLRG1+ NK cells from existing NK cell populations. Thus, contingent upon their T-bet–dependent development and activation status, NK cells can control metastatic CRC in mice, which is highly relevant for the development of immunotherapeutic approaches in the clinic.
'Scripts' for dying at home--displayed in nurses', patients' and relatives' talk.

Perceptions and expectations reflecting what constitutes a 'good' death that seem to exist in Western societies are explored and compared with those presented by five symptom control team nurses at their home visits to 54 terminally ill cancer patients. These perceptions and expectations are termed 'scripts' for dying and are derived from the nurses', patients' and relatives' audio-recorded conversations over a 3-month period. The elements of the 'scripts' used were identified as: (a) control of physical symptoms, (b) acceptance of cancer and its prognosis, (c) preservation of hope and 'will to live', (d) mobility and 'fighting back', (e) enjoyment of life, (f) a peaceful death at home. How these components are determined from the conversations are presented and the responses of the patients to the nurses' 'scripts' are analysed. The dilemmas created by putting the 'scripts' into action for nurses, patients and relatives are discussed.
Individual versus group caging of mice with grafted tumors.

Summary Isolation of mice leads to an increase in the survival of animals with tumor grafts (leukemia, ascites tumors, and melanoma). An abrupt change in environment (isolation or grouping) provokes an increase in the weight of the grafted ascites tumors. Adrenal hyperactivity, observed after either isolation or grouping is probably the cause of the increase in ascitic fluid weight.
The effect of different speaker accents on sentence comprehension in children with speech sound disorder

ABSTRACT There is substantial evidence that a speaker’s accent, specifically an unfamiliar accent, can affect the listener’s comprehension. In general, this effect holds true for both adults and children as well as those with typical and impaired language. Previous studies have investigated the effect of different accents on individuals with language disorders, but children with speech sound disorders (SSDs) have received little attention. The current study aims to learn more about the ability of children with SSD to process different speaker accents. Fifteen children with SSD aged between 4;01 and 5;11 years, and 16 typically developing children matched on language ability, age, socioeconomic status, gender and cognitive ability participated in the current study. A sentence comprehension task was carried out with each child, requiring them to follow instructions of increasing length spoken in three different accents – (i) a local Irish (Cork) accent, (ii) a regional North American accent and (iii) a non-native Indian English accent. Results showed no significant group difference and speaker accent did not significantly impact children’s performance on the task. The results are discussed in relation to factors that influence accent comprehension, and their implications for children’s underlying phonological representations.
Characterization of junD: a new member of the jun proto‐oncogene family.

In an extensive screen of a cDNA library prepared from serum‐stimulated mouse NIH 3T3 cells, we identified three distinct jun‐related clones. Two of them were carrying c‐jun and junB sequences respectively, whereas the sequence of the third group of clones (junD) was distinct from these two and from v‐jun. The amino acid sequences derived from these jun‐related clones are very well conserved in five distinct regions including the putative DNA binding domain. Truncated c‐Jun and JunD proteins containing the C‐terminus recognize the same DNA sequences which were defined as the PEA1/AP1 binding sequence or TPA response element (TRE). Furthermore, both can trans‐activate a promoter including the TRE, and this activation is further enhanced by c‐fos. Contrary to c‐jun and junB transcription, which are strongly stimulated by serum or TPA treatment of quiescent 3T3 cells, junD transcription is not significantly stimulated in these conditions. The tissue distribution and levels of expression of junD mRNA differ from that of c‐jun and junB mRNA. These observations suggest that each of these Jun‐related gene products has a distinct role in the control of gene activity and growth in the organism.
Systematic review of the literature on postpartum care: effectiveness of postpartum support to improve maternal parenting, mental health, quality of life, and physical health.

BACKGROUND Postpartum support is recommended to prevent infant and maternal morbidity. This review examined the published evidence of the effectiveness of postpartum support programs to improve maternal knowledge, attitudes, and skills related to parenting, maternal mental health, maternal quality of life, and maternal physical health. METHODS MEDLINE, Cinahl, PsycINFO, and the Cochrane Library were searched for randomized controlled trials of interventions initiated from immediately after birth to 1 year in postnatal women. The initial literature search was done in 1999 and was enhanced in 2003 and 2005. Studies were categorized based on the the above outcomes. Data were extracted in a systematic manner, and the quality of each study was reviewed. RESULTS In the 1999 search, 9 studies met the inclusion criteria. The 2003 and 2005 searches identified 13 additional trials for a total of 22 trials. Universal postpartum support to unselected women at low risk did not result in statistically significant improvements for any outcomes examined. Educational visits to a pediatrician showed statistically significant improvements in maternal-infant parenting skills in low-income primiparous women. In women at high risk for family dysfunction and child abuse, nurse home visits combined with case conferencing produced a statistically significant improvement in home environment quality using the HOME (Home Observation for Measurement of the Environment) program. Similarly, in women at high risk for either family dysfunction or postpartum depression, home visitation or peer support, respectively, produced a statistically significant reduction in Edinburgh Postnatal Depression Scale scores (difference - 2.23, 95% CI -3.72 to -0.74, p= 0.004; and 15.0% vs 52.4%, OR 6.23, 95% CI 1.40 to 27.84, p= 0.01, respectively). Educational programs reduced repeat unplanned pregnancies (12.0% vs 28.3%, p= 0.003) and increased effective contraceptive use (RR 1.35, 95% CI 1.09 to 1.68, p= 0.007). Maternal satisfaction was higher with home visitation programs. CONCLUSIONS No randomized controlled trial evidence was found to endorse universal provision of postpartum support to improve parenting, maternal mental health, maternal quality of life, or maternal physical health. There is some evidence that high-risk populations may benefit from postpartum support.
Searching for the second oxidant in the catalytic cycle of cytochrome P450: a theoretical investigation of the iron(III)-hydroperoxo species and its epoxidation pathways.

Iron(III)-hydroperoxo, [Por(CysS)Fe(III)-OOH](-), a key species in the catalytic cycle of cytochrome P450, was recently identified by EPR/ENDOR spectroscopies (Davydov, R.; Makris, T. M.; Kofman, V.; Werst, D. E.; Sligar, S. G.; Hoffman, B. M. J. Am. Chem. Soc. 2001, 123, 1403-1415). It constitutes the last station of the preparative steps of the enzyme before oxidation of an organic compound and is implicated as the second oxidant capable of olefin epoxidation (Vaz, A. D. N.; McGinnity, D. F.; Coon, M. J. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 3555-3560), in addition to the penultimate active species, Compound I (Groves, J. T.; Han, Y.-Z. In Cytochrome P450: Structure, Mechanism and Biochemistry, 2nd ed.; Ortiz de Montellano, P. R., Ed.; Plenum Press: New York, 1995; pp 3-48). In response, we present a density functional study of a model species and its ethylene epoxidation pathways. The study characterizes a variety of properties of iron(III)-hydroperoxo, such as the O-O bonding, the Fe-S bonding, Fe-O and Fe-S stretching frequencies, its electron attachment, and ionization energies. Wherever possible these properties are compared with those of Compound I. The proton affinities for protonation on the proximal and distal oxygen atoms of iron(III)-hydroperoxo, and the effect of the thiolate ligand thereof, are determined. In accordance with previous results (Harris, D. L.; Loew, G. H. J. Am. Chem. Soc. 1998, 120, 8941-8948), iron(III)-hydroperoxo is a strong base (as compared with water), and its distal protonation leads to a barrier-free formation of Compound I. The origins of this barrier-free process are discussed using a valence bond approach. It is shown that the presence of the thiolate is essential for this process, in line with the "push effect" deduced by experimentalists (Sono, M.; Roach, M. P.; Coulter, E. D.; Dawson, J. H. Chem. Rev. 1996, 96, 2841-2887). Finally, four epoxidation pathways of iron(III)-hydroxperoxo are located, in which the species transfers oxygen to ethylene either from the proximal or from the distal sites, in both concerted and stepwise manners. The barriers for the four mechanisms are 37-53 kcal/mol, in comparison with 14 kcal/mol for epoxidation by Compound I. It is therefore concluded that iron(III)-hydroperoxo, as such, cannot be a second oxidant, in line with its significant basicity and poor electron-accepting capability. Possible versions of a second oxidant are discussed.
Involvement of the P Cluster in Intramolecular Electron Transfer within the Nitrogenase MoFe Protein (*)

Nitrogenase is the catalytic component of biological nitrogen fixation, and it is comprised of two component proteins called the Fe protein and MoFe protein. The Fe protein contains a single Fe4S4 cluster, and the MoFe protein contains two metallocluster types called the P cluster (Fe8S8) and FeMo-cofactor (Fe7S9Mo-homocitrate). During turnover, electrons are delivered one at a time from the Fe protein to the MoFe protein in a reaction coupled to component-protein association-dissociation and MgATP hydrolysis. Under conditions of optimum activity, the rate of component-protein dissociation is rate-limiting. The Fe protein's Fe4S4 cluster is the redox entity responsible for intermolecular electron delivery to the MoFe protein, and FeMo-cofactor provides the substrate reduction site. In contrast, the role of the P cluster in catalysis is not well understood although it is believed to be involved in accumulating electrons delivered from the Fe protein and brokering their intramolecular delivery to the substrate reduction site. A nitrogenase component-protein docking model, which is based on the crystallographic structures of the component proteins and which pairs the 2-fold symmetric surface of the Fe protein with the exposed surface of the MoFe protein's pseudosymmetric αβ interface, is now available. During component-protein interaction, this model places the P cluster between the Fe protein's Fe4S4 cluster and FeMo-cofactor, which implies that the P cluster is involved in mediating intramolecular electron transfer between the clusters. In the present study, evidence supporting this idea was obtained by demonstrating that it is possible to alter the rate of substrate reduction by perturbing the polypeptide environment between the P cluster and FeMo-cofactor without necessarily disrupting the metallocluster polypeptide environments or altering component-protein interaction.
Fibreoptic endoscopy and the barium meal--results and implications.

The other story is that the tumour may be a teratoma and arise from germinomatous cells which tend to occur in the midline? mediastinum, ovaries, testis, and so on. Many of these tumours have teratomatous elements such as cartilage, muscle, or thyroid? but this one did not. Table II shows a histochemical comparison between cells from a pinealoma, seminoma of the testis, and normal pineal gland. Both tumours contained alkaline phosphatase in the large cells. None was present in cells of the normal pineal gland. This is not a common enzyme and is usually associated with specific cell function. It is probably not a chance finding. So the argument remains unresolved. dr. daly : It simply remains for me to thank Dr. Nabarro for his masterly analysis and correct conclusion, and the other participants.
Saccharomyces Cerevisiae Oesophagitis in an HIV-Infected Patient

Saccharomyces species are common colonizers of human mucosal surfaces. The administration of oral Saccharomyces species in the form of Brewer’s or Baker’s yeast has purported therapeutic effect in the treatment of antibiotic-associated diarrhoea1,2. However, increasing clinical and laboratory experience suggests Saccharomyces cerevisiae may cause illness and should be considered as a potential opportunistic pathogen in the immunocompromised. We report a case of con® rmed symptomatic S. cerevisiae oesophagitis in a patient with AIDS.
Immunohistochemical Characterization of Nonhuman Primate Ovarian Sex Cord–Stromal Tumors

This study evaluates the immunoreactivity of 12 sex cord–stromal tumors of nonhuman primates (11 granulosa cell tumors and 1 luteoma). The markers selected are used in the characterization of gonadal tumors in dogs and other species, including cytokeratins AE1/AE3, GATA-4, inhibin-α, neuron-specific enolase, protein gene product 9.5, and vimentin. A normal nonhuman primate ovary was used as a control and to optimize immunolabeling. Staining was graded as follows: 0 (nonstaining), 1+ (< 10% positive cells), 2+ (10%–50% positive cells), and 3+ (> 50% positive cells). Calretinin, GATA-4, neuron-specific enolase, and vimentin were the most consistently expressed markers (12 of 12). Cytokeratins AE1/AE3 were also consistently expressed (11 of 12). Inhibin-α and protein gene product 9.5 were expressed in 8 and 10 sex cord–stromal tumors, respectively. Results indicate that immunoreactivity of nonhuman primate sex cord–stromal tumors is similar to that observed in other species and that calretinin, GATA-4, and neuron-specific enolase are the most consistently expressed markers in nonhuman primate sex cord–stromal tumors.
Not all risk is bad, playgrounds as a learning environment for children

Should all risk be eliminated from children’s playgrounds? Some experts would argue that children do not lose interest in play equipment that is not challenging (Roseveare et al. 1999), whilst school-aged children themselves indicate that an environment that is risk free is ‘no fun’ or ‘boring’ (Green and Hart 1998). How can a balance be achieved between safe play environments and play equipment, whilst enabling children to explore, face challenges, learn new skills and identify and assess risks? This brief report discusses the implications of risk-free playgrounds on the development of a young child’s social, cognitive, physical and emotional skills. It describes the trend in incidence of falls from playground equipment that required hospitalization in New South Wales (NSW), Australia and considers the effectiveness of prevention measures, such as playground safety standards, in reducing the impact of playground-related injuries to children.
Probabilistic analysis of discrete optimization problems

We investigate the performance of exact algorithms for hard optimization problems under random inputs. In particular, we prove various structural properties that lead to two general average-case analyses applicable to a large class of optimization problems. In the first part we study the size of the Pareto curve for binary optimization problems with two objective functions. Pareto optimal solutions can be seen as trade-offs between multiple objectives. While in the worst case, the cardinality of the Pareto curve is exponential in the number of variables, we prove polynomial upper bounds for the expected number of Pareto points when at least one objective function is linear and exhibits sufficient randomness. Our analysis covers general probability distributions with finite mean and, in its most general form, can even handle different probability distributions for the coefficients of the objective function. We apply this result to the constrained shortest path problem and to the knapsack problem. There are algorithms for both problems that can enumerate all Pareto optimal solutions very efficiently, so that our polynomial upper bound on the size of the Pareto curve implies that the expected running time of these algorithms is polynomial as well. For example, we obtain a bound of O(n4) for uniformly random knapsack instances, where n denotes the number of available items. In the second part we investigate the performance of knapsack core algorithms, the predominant algorithmic concept in practice. The idea is to fix most variables to the values prescribed by the optimal fractional solution. The reduced problem has only polylogarithmic size on average and is solved using the Nemhauser/Ullmann algorithm. Applying the analysis of the first part, we can prove an upper bound of O(npolylog n) on the expected running time. Furthermore, we extend our analysis to a harder class of random input distributions. Finally, we present an experimental study of knapsack instances for various random input distributions. We investigate structural properties including the size of the Pareto curve and the integrality gap and compare the running time between different implementations of core algorithms. The last part of the thesis introduces a semi-random input model for constrained binary optimization problems, which enables us to perform a smoothed analysis for a large class of optimization problems while at the same time taking care of the combinatorial structure of individual problems. Our analysis is centered around structural properties, called winner, loser, and feasibility gap. These gaps describe the sensitivity of the optimal solution to slight perturbations of the input and can be used to bound the necessary accuracy as well as the complexity for solving an instance. We exploit the gaps in form of an adaptive rounding scheme increasing the accuracy of calculation until the optimal solution is found. The strength of our techniques is illustrated by applications to various NP-hard optimization problems for which we obtain the rst algorithms with polynomial average-case/smoothed complexity.
Role of renin-angiotensin system inhibitors in patients undergoing off-pump coronary artery bypass grafting.

Patients treated with quinapril had a 77% reduction in ischemic events (death, revasculariza-tion, myocardial infarction, recurrence of angina pectoris, ischemic stroke, or transient ischemic attack stroke; 15% vs 4%; P=0.04). Quinapril was well tolerated and was not asso-ciated with any untoward perioperative hemodynamic events. In a propensity-score-based analysis of 481 patients under-going isolated on-pump CABG,
Electrical Modeling and Analysis of a Mixed Carbon Nanotube Based Differential Through Silicon via in 3-D Integration

Based on the extracted equivalent parasitic parameters, the distributed transmission line model of a mixed carbon nanotube bundle (MCB) built signal-ground-signal-type differential through silicon via (TSV) is established and validated against the multiconductor transmission line model (MTL) results and predictive experiment results over a wide frequency range. Using the proposed model, the effect of various dimensional parameters and material properties on the signal loss and characteristic impedances of the differential TSV interconnect is investigated for odd- and even-mode signal propagation, respectively. It is observed that dielectric thickness is the most important factor affecting the transmission characteristics of TSV interconnects for the proposed TSV configuration. Moreover, various electrical performances of the proposed differential TSV, such as insertion loss, eye opening area, characteristic impedances, and 50% time delay are evaluated and compared to that of a signal-ground-type single ended TSV interconnect. The results presented in this paper will be helpful to fully understand the CNT-TSV electrical characterization and provide some signal integrity-aware guidelines for circuit designers in early planning stage.
Distinct Roles for Rap1b Protein in Platelet Secretion and Integrin αIIbβ3 Outside-in Signaling*

Background: Rap1b is a small G protein that is a key regulator for platelet activation. Results: Agonist-induced Rap1b activation plays a role in platelet secretion, and integrin outside-in signaling-mediated Rap1b activation is important in platelet spreading on fibrinogen and clot retraction. Conclusion: There are dual activation mechanisms of Rap1 that play distinct roles in platelet function. Significance: Learning two novel functions of Rap1b in platelets. Rap1b is activated by platelet agonists and plays a critical role in integrin αIIbβ3 inside-out signaling and platelet aggregation. Here we show that agonist-induced Rap1b activation plays an important role in stimulating secretion of platelet granules. We also show that αIIbβ3 outside-in signaling can activate Rap1b, and integrin outside-in signaling-mediated Rap1b activation is important in facilitating platelet spreading on fibrinogen and clot retraction. Rap1b-deficient platelets had diminished ATP secretion and P-selectin expression induced by thrombin or collagen. Importantly, addition of low doses of ADP and/or fibrinogen restored aggregation of Rap1b-deficient platelets. Furthermore, we found that Rap1b was activated by platelet spreading on immobilized fibrinogen, a process that was not affected by P2Y12 or TXA2 receptor deficiency, but was inhibited by the selective Src inhibitor PP2, the PKC inhibitor Ro-31-8220, or the calcium chelator demethyl-1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis. Clot retraction was abolished, and platelet spreading on fibrinogen was diminished in Rap1b-deficient platelets compared with wild-type controls. The defects in clot retraction and spreading on fibrinogen of Rap1b-deficient platelets were not rescued by addition of MnCl2, which elicits αIIbβ3 outside-in signaling in the absence of inside-out signaling. Thus, our results reveal two different activation mechanisms of Rap1b as well as novel functions of Rap1b in platelet secretion and in integrin αIIbβ3 outside-in signaling.