Miracle-dz/UniFAR-FTUs huggingface dataset:
Differences in Neural Activation for Object-Directed Grasping in Chimpanzees and Humans

The human faculty for object-mediated action, including tool use and imitation, exceeds that of even our closest primate relatives and is a key foundation of human cognitive and cultural uniqueness. In humans and macaques, observing object-directed grasping actions activates a network of frontal, parietal, and occipitotemporal brain regions, but differences in human and macaque activation suggest that this system has been a focus of selection in the primate lineage. To study the evolution of this system, we performed functional neuroimaging in humans' closest living relatives, chimpanzees. We compare activations during performance of an object-directed manual grasping action, observation of the same action, and observation of a mimed version of the action that consisted of only movements without results. Performance and observation of the same action activated a distributed frontoparietal network similar to that reported in macaques and humans. Like humans and unlike macaques, these regions were also activated by observing movements without results. However, in a direct chimpanzee/human comparison, we also identified unique aspects of human neural responses to observed grasping. Chimpanzee activation showed a prefrontal bias, including significantly more activity in ventrolateral prefrontal cortex, whereas human activation was more evenly distributed across more posterior regions, including significantly more activation in ventral premotor cortex, inferior parietal cortex, and inferotemporal cortex. This indicates a more “bottom-up” representation of observed action in the human brain and suggests that the evolution of tool use, social learning, and cumulative culture may have involved modifications of frontoparietal interactions.
Lack of Association of Transforming Growth Factor-β1 Polymorphisms and Haplotypes with Prostate Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Trial

Transforming growth factor β (TGF-β) plays a key role in cell cycle control and carcinogenic processes. TGF-β regulates growth and proliferation of cells and may play a dual role in carcinogenesis, inhibiting early-stage growth and promoting later-stage growth ([1][1]). TGF-β1, the predominant
Temporal and spatial sampling influence on the estimates of superimposed narrowband signals: when less can mean more

This paper addresses the influence that the sampling locations have on the estimated frequencies of superimposed sinusoids. This problem has application in harmonic time-series analysis or direction-finding phased-array systems. Generalized mathematical bounds are developed in terms that are independent of the array locations and have an intuitively appealing physical interpretation. They establish the influence of the sampling locations on the variance of the frequency estimate and the limit at which two sources can be resolved using signal subspace estimators. For the resolution criteria, an expression dominated by the fourth central moment of the sensor locations expresses the resolving ability of the sensing array, irrespective of the array aperture or number of sensors. Increasing the fourth central moment increases an array's resolution ability. The commonly accepted notion that resolution necessarily depends on the array aperture is misleading and, indeed, that fewer snapshots from a reduced aperture array can outperform a larger array of more elements. For the estimator variance criteria, it is found that the product of the number of sensors and the second central moment (array variance) characterizes the estimator variance lower bound. The metrics developed demonstrate that the sampling topology is itself an important factor in determining the performance of the sampling system (and not the covariance lags sampled or the aperture spanned). Simulations are used to describe the results.
Generalized pustular psoriasis responsive to PUVA and oral cyclosporin therapy

A patient with acute generalized pustular psoriasis was successfully treated with a combination of oral cyclosporin (6 mg/kg per day) and photochemotherapy (PUVA). Although early inpatient treatment with weak topical steroids and PUVA produced initial improvement, the patient's clinical condition fluctuated, with the subsequent development of erythroderma. The addition of oral cyclosporin produced dramatic improvement within 1 week of its commencement. The patient remained in remission 12 months following cessation of therapy.
Substrate availability limits human skeletal muscle oxidative ATP regeneration at the onset of ischemic exercise.

We have demonstrated previously that dichloroacetate can attenuate skeletal muscle fatigue by up to 35% in a canine model of peripheral ischemia (Timmons, J.A., S.M. Poucher, D. Constantin-Teodosiu, V. Worrall, I.A. Macdonald, and P.L. Greenhaff. 1996. J. Clin. Invest. 97:879-883). This was thought to be a consequence of dichloroacetate increasing acetyl group availability early during contraction. In this study we characterized the metabolic effects of dichloroacetate in a human model of peripheral muscle ischemia. On two separate occasions (control-saline or dichloroacetate infusion), nine subjects performed 8 min of single-leg knee extension exercise at an intensity aimed at achieving volitional exhaustion in approximately 8 min. During exercise each subject's lower limbs were exposed to 50 mmHg of positive pressure, which reduces blood flow by approximately 20%. Dichloroacetate increased resting muscle pyruvate dehydrogenase complex activation status by threefold and elevated acetylcarnitine concentration by fivefold. After 3 min of exercise, phosphocreatine degradation and lactate accumulation were both reduced by approximately 50% after dichloroacetate pretreatment, when compared with control conditions. However, after 8 min of exercise no differences existed between treatments. Therefore, it would appear that dichloroacetate can delay the accumulation of metabolites which lead to the development of skeletal muscle fatigue during ischemia but does not alter the metabolic profile when a maximal effort is approached.
Salmonella Pathogenicity Island 2 Influences Both Systemic Salmonellosis andSalmonella-Induced Enteritis in Calves

ABSTRACT We have used signature-tagged mutagenesis to identify mutants of the host-specific Salmonella enterica serotype Dublin which were avirulent in calves and/or BALB/c mice. A mutant with a transposon insertion in the sseD gene ofSalmonella pathogenicity island 2 (SPI-2), which encodes a putative secreted effector protein, was identified. This mutant was recovered from the bovine host but not from the murine host following infection with a pool of serotype Dublin mutants. However, a pure inoculum of the sseD mutant was subsequently shown to be attenuated in calves following infection either by the intravenous route or by the oral route. The sseD mutant was fully invasive for bovine intestinal mucosa but was subsequently unable to proliferate to the same numbers as the parental strain in vivo. Both the sseD mutant and a second SPI-2 mutant, with a transposon insertion in the ssaT gene, induced significantly weaker secretory and inflammatory responses in bovine ligated ileal loops than did the parental strain. These results demonstrate that SPI-2 is required by serotype Dublin for the induction of both systemic and enteric salmonellosis in calves.
No Workflow Can Ever Be Enough

The dominant crowdsourcing infrastructure today is the workflow, which decomposes goals into small independent tasks. However, complex goals such as design and engineering have remained stubbornly difficult to achieve with crowdsourcing workflows. Is this due to a lack of imagination, or a more fundamental limit? This paper explores this question through in-depth case studies of 22 workers across six workflow-based crowd teams, each pursuing a complex and interdependent web development goal. We used an inductive mixed method approach to analyze behavior trace data, chat logs, survey responses and work artifacts to understand how workers enacted and adapted the crowdsourcing workflows. Our results indicate that workflows served as useful coordination artifacts, but in many cases critically inhibited crowd workers from pursuing real-time adaptations to their work plans. However, the CSCW and organizational behavior literature argues that all sufficiently complex goals require open-ended adaptation. If complex work requires adaptation but traditional static crowdsourcing workflows can't support it, our results suggest that complex work may remain a fundamental limitation of workflow-based crowdsourcing infrastructures.
Unraveling the Interplay of Community Assembly Processes Acting on Multiple Niche Axes across Spatial Scales

How the relative importance of community assembly processes varies with spatial scale is the focus of intensive debate, in part because inferring the scales at which specific niche-based processes act is difficult. One obstacle is that standard phylogenetic and functional diversity metrics may integrate the signals of multiple processes when combining separate niche axes into one variable (multiple-niche-axis metrics), potentially obscuring overlapping niche-based processes. We use simulations to evaluate the power of these metrics to detect competition and habitat filtering when these processes operate across multiple niche axes and vary in their relative importance. We then test for both processes at a range of spatial scales in a Neotropical bird assemblage. Simulations revealed that multiple-niche-axis metrics had low power to detect competition and habitat filtering when a mix of both processes acts across niche axes, whereas metrics focused on single-niche axes were better able to deal with this complexity. We found the same contrast in bird communities, where both competition and habitat filtering were detected at the scale of individual territories, but only by single-niche-axis metrics focused on specific niche axes (e.g., foraging traits). Our results suggest that multiple-niche-axis metrics may produce misleading evidence that niche-based processes are partitioned, particularly across scales, and highlight the importance of analyzing functional diversity patterns on individual niche axes when testing assembly models.
Association of GB virus C (GBV‐C)/hepatitis G virus (HGV) with haematological diseases of different malignant potential

Among risk groups for GB virus C (GBV‐C)/HGV infection, patients with haematological diseases are particularly exposed due to the combination of transfusional support and immunodeficiency status. To examine any association between GBV‐C/HGV positivity and different malignancy potential of hematological diseases, we investigated two groups of patients, one with clonal stem cell disease with long latency period (myelodysplasia, myeloproliferative disease) and one with malignant haematological diseases (Hodgkin's lymphoma, non‐Hodgkin's lymphoma, acute leukemia, multiple myeloma). Virus positivity was compared with the data from cytogenetic analysis at first diagnosis. The frequency of GBV‐C/HGV infection in these patients was studied using reverse transcription‐polymerase chain reaction (RT‐PCR) and E2 antibody assay. Serum GBV‐C RNA was found in 29/47 (62%) patients. The prevalence of GBV‐C RNA in the group of oncological cases (72%) was significantly higher (P = .02) than in the patients with clonal stem cell diseases (28%). Among the GBV‐C negative cases, only 25% had malignant haematological diseases. The data from GBV‐C/HGV tested cases for which cytogenetic analysis was carried out indicated an association of GBV‐C/HGV positivity with genomic destabilization in general. Of the cases with numerical and structural aberrations, 64% were GBV‐C positive. A correlation could not be confirmed between GBV‐C/HGV and liver enzyme levels, blood transfusions, chemotherapy treatment, or viral coinfection. These findings suggest a high risk of GBV‐C/HGV infection in patients with haematological disorders especially in the group of malignant diseases. These observations may indicate that the persistence of GBV‐C/HGV in these patients could be associated with susceptibility to genomic destabilisation. J. Med. Virol. 57:361–366, 1999. © 1999 Wiley‐Liss, Inc.
Cancer Therapy : Preclinical Preclinical Pharmacokinetics and Safety of Sym 004 : A Synergistic Antibody Mixture Directed against Epidermal Growth Factor Receptor

Purpose: Sym004 is a novel therapeutic antibody mixture product comprising two unmarketed monoclonal antibodies (mAb) targeting the epidermal growth factor receptor (EGFR). In previous preclinical proof-of-concept studies, Sym004 was shown to elicit superior cancer cell growth inhibition activities compared with marketed anti-EGFR mAbs. This article describes the design and results of the preclinical safety program conducted to support early clinical development of Sym004. Experimental Design: Tissue cryosections from various species were stained with Sym004 to evaluate tissue cross reactivity. The pharmacokinetics of Sym004 were evaluated in a mouse xenograft model and in Cynomolgus monkeys. Monkeys received once weekly intravenous infusions of Sym004 in the range 2 to 24 mg/kg for 6 to 8 weeks. Cetuximab (a marketed anti-EGFR mAb) and the individual antibodies comprising Sym004 were included in the repeat-dose toxicity studies at single-dose level. Results: Sym004 had a staining pattern similar to cetuximab in tissue panels from both human and nonhuman primates. Once weekly dosing of Sym004 to Cynomolgus monkeys did not cause accumulation, whereas administration of the individual antibodies resulted in prolonged half-life and accumulation. In direct comparisons with cetuximab, Sym004 did not induce any distinct or novel adverse findings in the animals. However, an early onset of pronounced, reversible, and anticipated anti-EGFR–mediated pharmacologic effects, such as skin rash, dehydration, and liquid feces, was observed. Only minor adverse effects were recorded in animals treated with the individual antibodies comprising Sym004. Conclusion: Sym004 was well tolerated and did not induce any unexpected toxicities. The preclinical safety data enabled initiation of the ongoing clinical development. Clin Cancer Res; 17(18); 5962–72.
Community detection in feature-rich networks to meet K-means

We derive two extensions of the celebrated K-means algorithm as a tool for community detection in feature-rich networks. We define a data-recovery criterion additively combining conventional least-squares criteria for approximation of the network link data and the feature data at network nodes by a partition along with its within-cluster "centers". The dimension of the space at which the method operates is the sum of the number of nodes and the number of features, which may be high indeed. To tackle the so-called curse of dimensionality, we may replace the innate Euclidean distance with cosine distance sometimes. We experimentally validate our proposed methods and demonstrate their efficiency by comparing them to most popular approaches.
A RECONSIDERATION OF IMMUNOLOGICAL PRIVILEGE WITHIN THE ANTERIOR CHAMBER OF THE EYE

The immunologically privileged status of the anterior chamber of the eye has been confirmed on the basis of skin and thyroid allografts with use of inbred strains of rats. Skin grafts, transplanted across both major and minor histocompatibility barriers, enjoy prolonged survival within the anterior chamber. However, several factors have been found to restrict the privilege exhibited by this site: the magnitude of the immunogenetic disparity between donor and recipient, graft size, type of tissue grafted, and, at least in the case of thyroid grafts, the endocrine status of the host. Although a defect in the afferent limb of the immune response has been the popular explanation offered for immunological privilege in an alymphatic site, this was not the basis of the privilege encountered in the anterior chamber. Furthermore, because the efferent limb of the immunological reflex arc within the anterior chamber has been demonstrated to be intact, it was suggested that the unique properties of the anterior chamber may depend upon the forced intravascular presentation of antigen and consequent aberrant central processing.
Extracellular proteins produced by different species of the fungus Trichoderma on a secondary paper mill sludge substrate

Kraft pulping is the most commonly used pulping process in the pulp and paper industry. In this process wood chips are chemically delignified using sodium sulfide and sodium hydroxide. Delignification is usually followed by mechanical fiberization and a bleaching process of the resulting wood pulp. In addition to lignin-free wood pulp, this process also produces waste that contains residues of used chemicals, lignin, cellulose, hemicelluloses, and small amounts of other wood components. Because of the worldwide large-scale production of paper, the sludge from paper mills contributes significantly to environmental pollution. Although there have been great efforts being made to utilize this lignin-rich material, sludge is mostly disposed in landfills or incinerated in a boiler. This research project used secondary sludge as a substrate for 7 wood-decay fungi taxonomically belonging to the genus Trichoderma. The examined fungi expressed the capability of consuming sludge components as a carbon source to produce extracellular proteins. The proteins were separated by gel electrophoresis. Before and after fungi cultivation, the sludge was analyzed by Fourier transform infrared spectroscopy (FTIR).
The fine structure of wound repair in an insect (Rhodnius prolixus)

The cells surrounding a wound in the integument of Rhodnius adults show an increase in RNA content, cytochrome oxidase and esterase activity. An excision in the integument is filled by blood which coagulates and is tanned into an insoluble membrane. The basement membrane of the adjoining epidermis acts as a self‐sealing membrane and contracts to cover the excision. The epidermis is attached to the cuticle by the subcuticular layer which it resorbs and by pore canal filaments which are left behind as it migrates. The epidermis migrates as a sheet in contact with the cuticle then with the coagulated blood and basement membrane which cover the excision. Blood cells migrate individually into an excision and do not adhere to a surface in the process. Microtubules cannot be identified with movement. Both epidermal and blood cells remove the cells killed by wounding as evidenced by the appearance of coated vesicles and phagocytic bodies in both cell types. The reconstituted integument consists of a surface membrane in which the layers of the epicuticle are not distinguishable, a nonlamellate cuticle secreted by an epidermis which also appears to secrete the new basement membrane.
Expanding the prion concept to cancer biology: dominant-negative effect of aggregates of mutant p53 tumour suppressor

p53 is a key protein that participates in cell-cycle control, and its malfunction can lead to cancer. This tumour suppressor protein has three main domains; the N-terminal transactivation domain, the CTD (C-terminal domain) and the core domain (p53C) that constitutes the sequence-specific DBD (DNA-binding region). Most p53 mutations related to cancer development are found in the DBD. Aggregation of p53 into amyloid oligomers and fibrils has been shown. Moreover, amyloid aggregates of both the mutant and WT (wild-type) forms of p53 were detected in tumour tissues. We propose that if p53 aggregation occurred, it would be a crucial aspect of cancer development, as p53 would lose its WT functions in an aggregated state. Mutant p53 can also exert a dominant-negative regulatory effect on WT p53. Herein, we discuss the dominant-negative effect in light of p53 aggregation and the fact that amyloid-like mutant p53 can convert WT p53 into more aggregated species, leading into gain of function in addition to the loss of tumour suppressor function. In summary, the results obtained in the last decade indicate that cancer may have characteristics in common with amyloidogenic and prion diseases.
Creation and preliminary characterization of a Tp53 knockout rat

SUMMARY The tumor suppressor TP53 plays a crucial role in cancer biology, and the TP53 gene is the most mutated gene in human cancer. Trp53 knockout mouse models have been widely used in cancer etiology studies and in search for a cure of cancer with some limitations that other model organisms might help overcome. Via pronuclear microinjection of zinc finger nucleases (ZFNs), we created a Tp53 knockout rat that contains an 11-bp deletion in exon 3, resulting in a frameshift and premature terminations in the open reading frame. In cohorts of 25 homozygous (Tp53Δ11/Δ11), 37 heterozygous (Tp53Δ11/+) and 30 wild-type rats, the Tp53Δ11/Δ11 rats lived an average of 126 days before death or removal from study because of clinical signs of abnormality or formation of tumors. Half of Tp53Δ11/+ were removed from study by 1 year of age because of tumor formation. Both Tp53Δ11/+ and Tp53Δ11/Δ11 rats developed a wide spectrum of tumors, most commonly sarcomas. Interestingly, there was a strikingly high incidence of brain lesions, especially in Tp53Δ11/Δ11 animals. We believe that this mutant rat line will be useful in studying cancer types rarely observed in mice and in carcinogenicity assays for drug development.
NHS heart failure survey: a survey of acute heart failure admissions in England, Wales and Northern Ireland

Objectives: To obtain national data on demographics, investigation, treatment and short-term outcome for patients admitted with acute heart failure. Design: Retrospective survey of emergency admissions with acute heart failure from October 2005 to March 2006. Setting: Acute NHS trusts in England, Wales and Northern Ireland. Main outcome measures: Patient demographics, referral source, admission characteristics, admission pathway, patient heart failure treatment on admission, length of stay, short-term mortality, discharge heart failure treatment, specialist follow-up and delayed discharge. Results: 176/177 (99%) acute trusts responded and 9387 records were surveyed. Patients mean age was 77 (SD 11) years, 50% were women and 56% had prior history of heart failure. On average, women were 5 years older than men (80 vs 75 years, p<0.001), were less likely to have had echocardiography (52% vs 60%, p<0.001), and if previously diagnosed with heart failure less likely to be treated with ACE inhibitors (58.3% vs 66.8%, p<0.001), β-blockers (30.1% vs 35.5%, p = 0.033) or aldosterone antagonists (18.9% vs 22.5%, p<0.001) at admission. In-hospital mortality was 15%. Age-adjusted mortality was higher in men (16% vs 14%, p = 0.042). 75% of patients were admitted with moderate to severe symptoms (NYHA class III or IV). Women were less likely to be prescribed anti-failure medication, except diuretics, on discharge (ACE-I/AIIRA 66.5% vs 73.4%, β-blocker 31.3% vs 37.5%, aldosterone antagonists 23.4% vs 30.1%, all p<0.001). Only 20% of patients had planned specialist heart failure follow-up, with <1% referred for rehabilitation or specialist palliative care. Conclusion: Many patients admitted to acute hospitals in England, Wales and Northern Ireland are not being managed fully in accordance with international evidence-based guidelines. In comparison with earlier UK studies, the use of echocardiography and ACE-I and β-blockers has increased, and length of stay reduced. Only a minority of patients are seen, or followed up, by a specialist service. Women seem to be less well managed against recommended guidelines. Significant and sustained effort is required to address gender inequalities in the provision of heart failure care.