Miracle-dz/UniFAR-FTUs huggingface dataset:
Mammalian social odours: attraction and individual recognition

Mammalian social systems rely on signals passed between individuals conveying information including sex, reproductive status, individual identity, ownership, competitive ability and health status. Many of these signals take the form of complex mixtures of molecules sensed by chemosensory systems and have important influences on a variety of behaviours that are vital for reproductive success, such as parent–offspring attachment, mate choice and territorial marking. This article aims to review the nature of these chemosensory cues and the neural pathways mediating their physiological and behavioural effects. Despite the complexities of mammalian societies, there are instances where single molecules can act as classical pheromones attracting interest and approach behaviour. Chemosignals with relatively high volatility can be used to signal at a distance and are sensed by the main olfactory system. Most mammals also possess a vomeronasal system, which is specialized to detect relatively non-volatile chemosensory cues following direct contact. Single attractant molecules are sensed by highly specific receptors using a labelled line pathway. These act alongside more complex mixtures of signals that are required to signal individual identity. There are multiple sources of such individuality chemosignals, based on the highly polymorphic genes of the major histocompatibility complex (MHC) or lipocalins such as the mouse major urinary proteins. The individual profile of volatile components that make up an individual odour signature can be sensed by the main olfactory system, as the pattern of activity across an array of broadly tuned receptor types. In addition, the vomeronasal system can respond highly selectively to non-volatile peptide ligands associated with the MHC, acting at the V2r class of vomeronasal receptor. The ability to recognize individuals or their genetic relatedness plays an important role in mammalian social behaviour. Thus robust systems for olfactory learning and recognition of chemosensory individuality have evolved, often associated with major life events, such as mating, parturition or neonatal development. These forms of learning share common features, such as increased noradrenaline evoked by somatosensory stimulation, which results in neural changes at the level of the olfactory bulb. In the main olfactory bulb, these changes are likely to refine the pattern of activity in response to the learned odour, enhancing its discrimination from those of similar odours. In the accessory olfactory bulb, memory formation is hypothesized to involve a selective inhibition, which disrupts the transmission of the learned chemosignal from the mating male. Information from the main olfactory and vomeronasal systems is integrated at the level of the corticomedial amygdala, which forms the most important pathway by which social odours mediate their behavioural and physiological effects. Recent evidence suggests that this region may also play an important role in the learning and recognition of social chemosignals.
Pathogenesis, Diagnosis and Monitoring of Residual Disease in Acute Promyelocytic Leukaemia

The clinical course of acute promyelocytic leukaemia (APL) has changed over the last 25 years from one that was fatal for the majority of patients to representing one of the most curable subtypes of acute myeloid leukaemia. Besides improved supportive care this has mainly been achieved through the introduction of novel targeted therapies in the form of all-trans retinoic acid (ATRA) and arsenic trioxide that specifically address the underlying molecular lesion. APL is characterized by chromosomal rearrangements of 17q21 leading to the formation of fusion proteins involving retinoic acid receptor alpha (RARA). To date five different fusion partners of RARA have been identified, but the vast majority of cases are characterized by the presence of the t(15;17)(q22;q12–21), which involves the promyelocytic leukaemia (PML) gene. The identification of different breakpoint microclusters within RARA intron 2 suggests that sequence-associated or structural factors play a role in the formation of the t(15;17). In addition, the comparison of forward and reverse genomic junctions has revealed microhomologies, deletions and/or duplications of either gene consistent with the hypothesis that the t(15;17) occurs by non-homologous recombination of DNA after processing of the double strand breaks by a dysfunctional DNA damage repair mechanism. The detection of the PML-RARA fusion gene by reverse-transcription polymerase chain reaction (RT-PCR) is routinely used for diagnosis and monitoring of minimal residual disease (MRD). In PML-RARA-positive APL about 70% of patients are expected to be cured with a combination of ATRA and anthracycline-based chemotherapy. However, relapse remains a major problem. The identification of patients at high risk of relapse and the development of risk-adapted treatment schedules are therefore clearly the most challenging tasks in the treatment of APL. Recent studies have shown that pre-emptive chemotherapy at the time of molecular relapse improves survival compared to treatment at the point of haematological relapse. Quantitative RT-PCR technology is expected to further improve the predictive value of MRD monitoring and therefore to guide therapy in order to reduce the rate of relapses and to increase rates of cure in high-risk patients.
Hippuric acid as a major excretion product associated with black tea consumption

1. Nine habitual tea-drinking volunteers were recruited and asked to follow a low-polyphenol and low-caffeine diet for 6 days and to provide daily 24-h urine samples. On day 4 of the experiment strong black tea brewed under standardized conditions was reintroduced to the volunteers' diet. 2. 1H-NMR and HPLC profiling of the urine samples indicated that consumption of black tea (6-10 mugs per day) was associated with a significant (p=0.00017) increase in hippuric acid excretion relative to control, increasing from 153-512 to 742-1374 mg day-1. The excretion of substantial amounts of hippuric acid has not previously been associated with black tea consumption. 3. For some volunteers, the quantity of benzoic acid processed exceeded the acceptable daily intake (ADI), but this is not considered to constitute any hazard. 4. A mass-balance analysis indicated that the necessary quantity of benzoic acid could not be obtained from the contents of gallic acid, flavanols, flavonol glycosides and theaflavins in black tea even if 100% transformation was obtained, suggesting that the thearubigins (the major and chemically ill-defined polyphenols of black tea) may be an important source.
Design and Synthesis of RGD Mimetics as Potent Inhibitors of Platelet Aggregation

Vascular diseases, such as heart attacks and strokes, are known to be caused by the aggregation of platelets which form clots within blood vessels. These diseases can be prevented through the use of drugs that inhibit platelet aggregation by blocking a key platelet receptor, GPIIb/IIIa. The recognition of the arginine-glycine-aspartic acid (RGD) amino acid sequence by this receptor has been exploited in formulating a drug strategy to prevent vascular diseases. Thus, the RGD sequence or its mimetics have been incorporated into drug candidates that inhibit platelet aggregation. Through a process of rational design, mimetics of the RGD sequence were synthesized, providing deeper insight into the structural requirements for high inhibitory activity. These mimetics were found to be extremely potent inhibitors of platelet aggregation.
Proportionality of the long bones and their relation to stature among Mesoamericans.

A total of 235 (176 ♂ and 59 ♀) cadavers were measured. Of these blood samples of 132 (103 ♂ and 29 ♀) are drawn. Only those cadavers of which the long bones could be measured afterwards were used in the investigation, and of these only those whose blood was of group O and Rh +. A sample of 98 (69 ♂ and 29 ♀) was thus arrived at and divided morphoscopically into seven categories going from “pure” Indian to “pure” white. With electronic computers, means and standard deviations were calculated for all six unpaired long bones and for stature, as well as the coefficient of multiple correlation among the seven variables, for both males and females. As categories leading from “pure” white towards the other extreme were withdrawn, the sample size was reduced but the coefficient of multiple correlation increased from 0.71 to 0.90 in males, and from 0.74 to 0.94 in females, indicating that a more homogeneous population was being dealt with. Mean stature for this population was 161.50 cm and 149.80 cm for males and females, after 2.5 cm are deducted from cadaveral measurements. As the sample is morphoscopically and serologically as close as one could get to pre-hispanic conditions and as the statures arrived at are representative of what is known, tables were drawn giving the corresponding values of statures of males and females going from 180 cm to 130 cm at steps of 0.5 cm. It is submitted that until a larger sample is obtained, the newly drawn tables and formulae are more appropriate to calculate stature from long bones of American pre-hispanic populations than any other hitherto used.
Estimating a tail exponent by modelling departure from a Pareto distribution

We suggest two semiparametric methods for accommodating departures from a Pareto model when estimating a tail exponent by fitting the model to extreme-value data. The methods are based on approximate likelihood and on least squares, respectively. The latter is somewhat simpler to use and more robust against departures from classical extreme-value approximations, but produces estimators with approximately 64% greater variance when conventional extreme-value approximations are appropriate. Relative to the conventional assumption that the sampling population has exactly a Pareto distribution beyond a threshold, our methods reduce bias by an order of magnitude without inflating the order of variance. They are motivated by data on extrema of community sizes and are illustrated by an application in that context.
Annotation Agreement of Emotions in Text: The Influence of Counsellors' Emotional State on their Emotion Perception

We investigate the influence of counsellors' state of emotions on their emotion perception through annotation agreement of emotions in text. Selected counsellors were tasked to annotate sample corpora from International Survey on Emotion Antecedents and Reactions (ISEAR), and students' life stories. We explore the intra and inter-counsellors' annotation agreements of emotions in the corpora during several annotation sections. The results show strong intra-counsellors' annotation agreement of emotions in both corpora, whereas the inter-counsellors' annotation agreement yielded weakly in both corpora. Results also show that counsellors' emotions vary and influence their decisions when analysing emotions in text.
Patients with superficial transitional cell carcinoma of the bladder and their smoking status

Over 95% of bladder cancers are urothelial in origin (i.e., transitional cell carcinomas). Nonetheless, transitional cell bladder carcinoma includes a heterogeneous group of tumors that occupy a spectrum extending from papillary Grade 1 lesions, which have been considered virtually benign, to poorly differentiated cancers, which often lead to a fatal outcome. The term “superficial” bladder carcinoma, as used by Fleshner et al. in this issue of Cancer, should probably be abandoned. Even within the category of tumors with depth of infiltration superficial to the detrusor muscle of the bladder, there is marked variation in tumor behavior. Thus, the term “superficial” can be misleading. Some 70% of transitional cell bladder carcinomas are non-muscleinvasive at the time of presentation. Tumor infiltration of the muscular wall of the bladder has been considered a poor prognostic feature that usually triggers aggressive therapeutic intervention, such as radical cystectomy. Most often, high grade tumors tend to be invasive, whereas it is unusual to find low grade tumors that infiltrate into muscle. Furthermore, regional lymph node metastasis or distant metastasis is unusual in the absence of demonstrable muscle invasion. The primary clinical problem with non-muscle-invasive bladder carcinoma is not the management of existing, visible lesions, but the implications for future tumor behavior. Transurethral resection or laser ablation effectively eradicates non-muscle-invasive bladder carcinomas and the risk of local recurrence from persistent, inadequately treated tumor is low. However, recurrent tumor, or, more accurately, new tumor occurrence, is a frequently observed phenomenon. Overall, over half of patients who present with a non-muscle-invasive bladder carcinoma are destined to have a new tumor develop within the bladder, often at a site remote from the initial lesion. Some of these recurrences may be a consequence of tumor cell implantation. Transitional cell carcinoma is known to be a tumor that readily implants in extravesical tissue if spillage occurs during open surgical procedures. Likewise, intravesical implantation can occur either as a consequence of surgical manipulation during tumor resection or from malignant cells shed from the tumor surface during the course of normal bladder filling and emptying. The clinical observation that tumor recurrence is often seen on the bladder dome is 2192
The Endgame of Telecommunications Policy? A Survey

Abstract Telecommunications policy has come a long way from regulation of vertically integrated monopolies to the current state of competition. As competition becomes self-sustainable, will telecommunications policy in the form of industry-specific regulation go away or, if not, what form will it take? The economics literature suggests that the regulatory efficiency frontier is shifted by new technological and market developments, such as convergence of networks, fixed-mobile substitution (and integration) and next generation access networks. The frontier is also affected by the existing capital stock and other physical and institutional characteristics of a country. The insights from a review of the theoretical and empirical literature are applied to five policy areas. They are: (1) termination monopoly; (2) local bottleneck access; (3) net neutrality; (4) spectrum management; and (5) universal service. While in some of them, deregulation and a move to competition policy will soon be the efficient state of the art, regulation will remain efficient in others for some time. Deregulation will likely become efficient for one-way access and universal service, with the exception of some universal service policies in remote areas and for the poor. Termination will move to bill and keep with a duty to interconnect. In addition, some (more symmetric) regulation should persist for net neutrality in the form of transparency requirements, (quasi-) common carrier obligations and minimum quality standards. Also, spectrum management, while moving towards full-blown ownership rights, will continue to see regulators providing zoning and other services, particularly for unlicensed spectrum. All these assessments are premised on the success of making additional spectrum as the key resource available. They are also premised on the absence of a killer technology like P2P FTTH that potentially dominates all other technologies. What determines the endgame in telecommunications regulation? Although technical and market developments will dominantly shape the regulatory efficiency frontier, institutional and political economy factors have an additional and mostly slowing effect on policy changes.
Need for Susceptibility Testing Guidelines for Fastidious or Less-Frequently Isolated Bacteria

In the United States, clinical microbiology laboratories rely upon the National Committee for Clinical Laboratory Standards (NCCLS) for written standards that guide the important elements of antimicrobial susceptibility testing. Whether a laboratory performs a direct version of an NCCLS standard method (e.g., disk diffusion) or uses a commercial device that has been “cleared” by the Food and Drug Administration because it provides results that are essentially equivalent to the NCCLS reference dilution susceptibility method, the NCCLS standards provide important, up-to-date guidance on the most relevant drugs to report on specific organisms, quality control ranges to assure reproducible results, and “breakpoints” to interpret disk diffusion zones or MICs.
Interaction of chemokine receptor CXCR4 in monomeric and dimeric state with its endogenous ligand CXCL12: coarse-grained simulations identify differences

Despite the recent resolutions of the crystal structure of the chemokine receptor CXCR4 in complex with small antagonists or viral chemokine, a description at the molecular level of the interactions between the full-length CXCR4 and its endogenous ligand, the chemokine CXCL12, in relationship with the receptor recognition and activation, is not yet completely elucidated. Moreover, since CXCR4 is able to form dimers, the question of whether the CXCR4–CXCL12 complex has a 1:1 or 2:1 preferential stoichiometry is still an open question. We present here results of coarse-grained protein–protein docking and molecular dynamics simulations of CXCL12 in association with CXCR4 in monomeric and dimeric states. Our proposed models for the 1:1 and 2:1 CXCR4–CXCL12 quaternary structures are consistent with recognition and activation motifs of both partners provided by the available site-directed mutagenesis data. Notably, we observed that in the 2:1 complex, the chemokine N-terminus makes more steady contacts with the receptor residues critical for binding and activation than in the 1:1 structure, suggesting that the 2:1 stoichiometry would favor the receptor signaling activity with respect to the 1:1 association.
Multimodality ( MM ) imaging : Enhancement through interlacing

In the changing world of medicine, fused and hybrid imaging with SPECT/CT, PET/CT and other modalities is undergoing very rapid growth, with important professional implications. In 2005, the leaderships of the European Association of Nuclear Medicine and the European Society of Radiology, as well as the UEMS Sections of both specialties, started discussing areas of common interest in order to define avenues for potential cooperation and to advance multimodality imaging in medicine. The first result of this process was the “White paper of the European Association of Nuclear Medicine and the European Society of Radiology on multimodality imaging”. Acknowledging the fact that nuclear medicine and clinical radiology are separate medical specialties recognised by the European Union, this paper set the tone for working together on an equal and constructive basis for the future benefit of both disciplines. The white paper was designed to serve both as a template for further discussions in countries where the two specialties already engage in cooperation and as a stimulus to commence discussions in those countries where this is not the case. It is noteworthy that in 2006 the Netherlands societies of Nuclear Medicine and Radiology established a task group to discuss areas of common interest, to define options for potential cooperation and to advance multimodality imaging in medicine. The major goal of this initiative was to ensure that new technologies are used to the best possible effect in patient care. The two boards were convinced that this goal could only be achieved through close cooperation between nuclear medicine physicians and radiologists. The task group set up by the Netherlands societies was charged with identifying the concrete steps that need to be taken at this early stage, such as: What adaptations should be made to the curricula for trainee specialists? How should the further education of registered medical specialists and fellowships be arranged? What will be the consequences for clinical tasks? The following article presents the shared vision of the boards of the Netherlands societies of Nuclear Medicine and Radiology and clearly indicates the steps that need to be considered if we are to reach our goals. This initiative is entirely consistent with developments on the European level and further demonstrates that clinical reality has made close collaboration a self-evident objective. Eur J Nucl Med Mol Imaging (2008) 35:1221–1229 DOI 10.1007/s00259-008-0768-3
Design of a linearly assisted switcher for a supply modulated RF transmitter

A broadband modulated power supply for envelope tracking or polar RF transmitters has been built. To study the design constraints, an efficient state-based simulation tool was developed. Based on the simulations, a prototype supply was built. It can deliver up to 1 W (6 V, 150 mA) to a resistive load of 30 ohms with spectral purity of ca. −45 dBc. The power efficiency using a QAM-signal is 49%.
The serotonin inhibition of high‐voltage‐activated calcium currents is relieved by action potential‐like depolarizations in dissociated cholinergic nucleus basalis neurons of the guinea‐pig

The aim of the present study was to investigate whether the voltage‐dependent inhibition of calcium currents by serotonin 5‐HT1A agonists can be alleviated (facilitated) by action potential‐like depolarizations. In dissociated cholinergic basal forebrain neurons using whole‐cell recordings, it is shown that a selective serotonin 5‐HT1A agonist (8‐OH‐DPAT) predominantly blocks N‐type HVA calcium current, although a minor reduction of P‐type current was also observed. The inhibition may principally occur through Gi‐Go subtypes of G‐proteins because it was prevented by N‐ethylmaleimide, a substance known to block specifically pertussis‐sensitive G‐proteins. The inhibitory effect of 8‐OH‐DPAT on calcium currents is voltage‐dependent because it was alleviated by long‐lasting depolarizing prepulses. Interestingly, the inhibition could also be reversed by prepulses made‐up of action potential‐like depolarizations that were given at a frequency of 200 Hz. This observation may have important implications during periods of high‐frequency rhythmic bursts, a firing pattern that is prevalent in cholinergic basal forebrain neurons.
Aztreonam, cefoperazone, and gentamicin in the treatment of experimental Enterobacter aerogenes endocarditis in rabbits

The effectiveness of aztreonam, cefoperazone, and gentamicin alone and in combination was evaluated in Enterobacter aerogenes endocarditis in rabbits. The minimal inhibitory concentration/minimal bactericidal concentration ratios for E. aerogenes were as follows: aztreonam, 0.4/0.4 microgram/ml; cefoperazone, 0.8/0.8 microgram/ml; and gentamicin, 3.1/3.1 micrograms/ml. With an inoculum of 10(9) organisms per ml, aztreonam and cefoperazone were equivalent in reducing titers of E. aerogenes in broth, and both drugs demonstrated an increased rate of reduction when gentamicin was added; gentamicin alone was least effective. E. aerogenes endocarditis in rabbits was treated intramuscularly with aztreonam (60 mg/kg) every 6 h, with cefoperazone (60 mg/kg) every 6 h, with gentamicin (1.7 mg/kg) every 8 h, and with aztreonam plus gentamicin or cefoperazone plus gentamicin for 5 and 10 days, respectively. All of the therapeutic regimens were effective in reducing vegetation titers as compared with untreated controls. Aztreonam plus gentamicin was more effective than either aztreonam or gentamicin alone. Cefoperazone plus gentamicin was more effective than cefoperazone alone but was not more effective than gentamicin alone. Neither aztreonam and cefoperazone nor aztreonam and gentamicin differed significantly, but gentamicin was significantly more effective than cefoperazone. Aztreonam plus gentamicin did not differ significantly in effectiveness from cefoperazone plus gentamicin. Aztreonam gave a peak level of about 135 micrograms/ml and a half-life of 0.7 h. Cefoperazone gave a peak level of about 155 micrograms/ml and a half-life of 1.1 h. Gentamicin gave a peak level of 7.4 micrograms/ml and a half-life of 1.3 h.