Miracle-dz/UniFAR-FTUs huggingface dataset:
Categorical perception--phenomenon or epiphenomenon: evidence from experiments in the perception of melodic musical intervals.

Categorical perception was investigated in a series of experiments on the perception of melodic musical intervals (sequential frequency ratios). When procedures equivalent to those typically used in speech-perception experiments were employed, i.e., determination of identification and discrimination functions for stimuli separated by equal physical increments), musical intervals were perceived categorically by trained musicians. When a variable-step-size (adaptive) discrimination procedure was used, evidence of categorical perception (in the form of smaller interval-width DL's for ratios at identification category boundaries than for ratios within categories), although present initially, largely disappeared after subjects had reached asymptotic performance. However, equal-step-size discrimination functions obtained after observers had reached asymptotic performance in the adaptive paradigm were not substantially different from those initially obtained. The results of other experiments imply that this dependence of categorical perception on procedure may be related to differences in stimulus uncertainty between the procedures. An experiment on the perception of melodic intervals by musically untrained observers showed no evidence for the existence of "natural" categories for musical intervals.
Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis.

It is now 23 years since Lieberman first reported that serum angiotensin converting enzyme (SACE) levels were raised in patients with sarcoidosis.1 He concluded that raised SACE levels appeared to be associated with the active disease process and not a familial inherited enzyme abnormality. The paper by Takemoto and colleagues in this issue of Thorax 2 provides new evidence that the sarcoid granuloma load in patients is not the only factor to account for circulating SACE levels in sarcoidosis and that polymorphisms in both the ACE and angiotensin II receptor genes may also play a part. Angiotensin converting enzyme (ACE), a zinc metalloproteinase, catalyses the hydrolysis of carboxyterminal dipeptides, particularly the largely inactive peptide angiotensin-1 to the active angiotensin-2. This enzyme has been hypothesised to be a marker of disease activity in sarcoidosis. It is thought that ACE is produced by epithelioid …
GGF2 is neuroprotective in a rat model of cavernous nerve injury-induced erectile dysfunction.

INTRODUCTION Erectile dysfunction is a major complication of radical prostatectomy, commonly associated with penile neuropathy. In animal models of peripheral nerve injury, glial growth factor-2 (GGF2), a member of the neuregulin family of growth factors, has neuroprotective and neurorestorative properties, but this potential has not been established after cavernous nerve (CN) injury. AIMS The effectiveness of GGF2 in preserving axonal integrity and recovering erectile function in a rat model of radical prostatectomy-associated CN injury. METHODS Adult male Sprague-Dawley rats underwent bilateral CN crush injury (BCNI) or sham surgery. Rats were administered GGF2 (0.5, 5, or 15 mg/kg) or vehicle subcutaneously 24 hour pre and 24-hour post-BCNI, and once weekly for 5 weeks. Erectile function was assessed in response to electrical stimulation of the CN. CN survival was assessed by fluorogold retrograde axonal tracing in major pelvic ganglia (MPG). Unmyelinated axons in the CNs were quantitated by electron microscopy. MAIN OUTCOME MEASURES Erectile function recovery, CN survival, and unmyelinated CN axon preservation in response to GGF2 treatment following BCNI. RESULTS Erectile function was decreased (P < 0.05) after BCNI, and it was improved (P < 0.05) by all doses of GGF2. The number of fluorogold-labeled cells in the MPG was reduced (P < 0.05) by BCNI and was increased (P < 0.05) by GGF2 (0.5 and 5 mg/kg). The percentage of denervated Schwann cells in the BCNI group was higher (P < 0.05) than that in the sham-treated group and was decreased (P < 0.05) in the GGF2-treated (5 mg/kg) BCNI group. In the BCNI + GGF2 (5 mg/kg) group, the unmyelinated fiber histogram demonstrated a rightward shift, indicating an increased number of unmyelinated axons per Schwann cell compared with the BCNI group. CONCLUSIONS GGF2 promotes erectile function recovery following CN injury in conjunction with preserving unmyelinated CN fibers. Our findings suggest the clinical opportunity to develop GGF2 as a neuroprotective therapy for radical prostatectomy.
NF-E2-related Factor-2 Mediates Neuroprotection against Mitochondrial Complex I Inhibitors and Increased Concentrations of Intracellular Calcium in Primary Cortical Neurons*

NF-E2-related factor-2 (Nrf2) regulates the gene expression of phase II detoxification enzymes and antioxidant proteins through an enhancer sequence referred to as the antioxidant-responsive element (ARE). In this study, we demonstrate that Nrf2 protects neurons in mixed primary neuronal cultures containing both astrocytes (∼10%) and neurons (∼90%) through coordinate up-regulation of ARE-driven genes. Nrf2-/- neurons in this mixed culture system were more sensitive to mitochondrial toxin (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine or rotenone)-induced apoptosis compared with Nrf2+/+ neurons. To understand the underlying mechanism of this observed differential sensitivity, we compared the gene expression profiles using oligonucleotide microarrays. Microarray data showed that Nrf2+/+neuronal cultures had higher expression levels of genes encoding detoxification enzymes, antioxidant proteins, calcium homeostasis proteins, growth factors, neuron-specific proteins, and signaling molecules compared with Nrf2-/- neuronal cultures. As predicted from the microarray data, Nrf2-/- neurons were indeed more vulnerable to the cytotoxic effects of ionomycin- and 2,5-di-(t-butyl)-1,4-hydroquinone-induced increases in intracellular calcium. Finally, adenoviral vector-mediated overexpression of Nrf2 recovered ARE-driven gene expression in Nrf2-/- neuronal cultures and rescued Nrf2-/- neurons from rotenone- or ionomycin-induced cell death. Taken together, these findings suggest that Nrf2 plays an important role in protecting neurons from toxic insult.
Different Effects of Short- and Long-Chained Fructans on Large Intestinal Physiology and Carcinogen-Induced Aberrant Crypt Foci in Rats

Inulin-type fructans, which are nondigestible carbohydrates, have been shown to modulate the number of induced preneoplastic lesions in the colon as well as the colonic microflora in laboratory animals. The present study was designed to investigate the effect of a short- and long-chained inulin-type fructan on 1,2-dimethylhydrazine dihydrochloride-induced aberrant crypt foci (ACF) in the rat colon. In addition, the present study investigated the influence of chain length, dietary level (5% or 15%), and duration of feeding (5 or 10 wk) on the following intestinal parameters supposed to be involved in the development of ACF: microflora, short-chain fatty acids, pH, and cell proliferation. A 3-wk pretreatment period with both fructans was included. Feeding the long-chained fructan (5% or 15%) significantly inhibited the numbers of small and total ACF after 5 and 10 wk. The short-chained fructan (15%) inhibited the number of small and total ACF after 5 and 10 wk but significantly increased the numbers of medium and large ACF after 10 wk. In conclusion, the effect on ACF outcome was influenced by the chain length of the fructans.
The study of bacterial DNA in ancient human mummies

ecosystems with a wide variety of microorganisms (bacteria, viruses and protozoa) establishing with them a delicate equilibrium; changes in the environment, transitions in human ecology or mutations and adaptations in microorganisms often affect this delicate interaction. Most microorganisms are benevolent, and some are symbiontic, because their presence is beneficial to both host and microbe, whereas some adversely affect the host’s biology (McMichael, 2001). In the latter case we have an “infectious disease”. Before the advent of molecular techniques, the diagnosis of a disease in antiquity was fundamentally based on three sources of information: artistic representations of pathological conditions, ancient descriptive tests, and direct observations of human remains (skeletal or mummified material) by radiologic or histological examinations (Willcox, 2002). The first two methods may be criticized, but the last source is without any doubt more reliable. In the early nineties, Wood and colleagues (Wood et al., 1992) discussed “the osteological paradox” based on the evidence that in most cases the bones of the deceased do not show signs of disease, simply because in many acute conditions the illness results in death before a skeletal response occurs. The manifestations of diseases in bones are, generally, expressions of chronic conditions. For this reason, skeletons without signs of disease may belong either to healthy individuals or to individuals which have died as a result of acute illness. Hence to reconstruct the general condition of health in the past, the information available in bones should be offset with analyses of the soft tissues. Mummies (human or animal bodies that have been preserved through artificial or accidental means) are ideal for this purpose. The analysis of the microbial DNA associated with human remains provides direct evidence of the JASs Invited Reviews
Alternative medicine use in HIV-positive men and women: Demographics, utilization patterns and health status

Between 1995 and 1997, 1,675 HIV-positive men and women using complementary and alternative medicine (CAM) were enrolled into the Bastyr University AIDS Research Center's Alternative Medicine Care Outcomes in AIDS (AMCOA) study. Funded by the National Institutes of Health (NIH) Office of Alternative Medicine (OAM) and National Institute of Allergy and Infectious Diseases (NIAID), the AMCOA study collected information on participant demographics, health status and use of conventional and CAM therapies. Participants from 46 states completed a baseline questionnaire, while additional clinical information (such as CD4 count and HIV-RNA viral load) was obtained from laboratory records. AMCOA participants reported using more than 1,600 different types of CAM therapies (1,210 CAM substances, 282 CAM therapeutic activities and 119 CAM provider types) for treating HIV/AIDS. Approximately two-thirds (63% n = 1,054) of the AMCOA cohort reported using antiretroviral drug therapy (ART) during the six-months previous to completing the baseline questionnaire, while 37% (n = 621) indicated they were not using ART. Of those not using ART, 104 subjects reported never having used any conventional medications for their HIV and 12 subjects used only non-prescription diarrhoea medications. The most frequently reported CAM substances were vitamin C (63%), multiple vitamin and mineral supplements (54%), vitamin E (53%) and garlic (53%). CAM provider types most commonly consulted by the AMCOA cohort were massage therapists (49%), acupuncturists (45%), nutritionists (37%) and psychotherapists (35%). CAM activities most commonly used were aerobic exercise (63%), prayer (58%), massage (53%) and meditation (46%). The choice of CAM therapies among the AMCOA cohort does not appear to be solely based on scientific evidence of efficacy of individual therapies. The majority of AMCOA subjects could be characterized as using integrated medicine, since an overwhelming proportion of the cohort consult with both conventional and CAM providers and use both conventional and CAM medications, yet few subjects reported that their conventional and CAM providers work as a team. These data and this cohort set the stage for conducting studies of health status changes associated with specific CAM therapies.
BOUNDARYPATROLS AND INTERGROUPENCOUNTERS IN WILD CHIMPANZEES

Chimpanzees are among the few mammals that engage in lethal coalitionary aggression between groups. Most attacks on neighbors occur when parties made up mostly of adult males patrol boundaries of their community’s range. Patrols have time, energy, and opportunity costs, and entail some risks despite the tendency of males to attack only when they greatly outnumber their targets. These factors may lead to a collective action problem. Potential bene ts include protectionof community members, particularly infants; range expansion and increases in the amount and quality of food available; and incorporation of more females into the community. Males may not share these equally; for example, those able to obtain
Developmental and regional expression of sodium channel isoform NaCh6 in the rat central nervous system

The sodium channel isoform NaCh6 is abundant in the adult rat brain and is expressed in both neurons and glia (Schaller et al. [1995] J. Neurosci. 15:3231–3242; Krzemien et al. [2000] J. Comp. Neurol. 20:70–83). With reverse transcriptase‐polymerase chain reaction (RT‐PCR), in situ hybridization, and immunolabeling, NaCh6 expression was investigated in the developing rat brain and spinal cord [embryonic day 15 (E15) through postnatal day 28 (P28)]. The relative abundance of the four major central nervous system NaCh subtypes was quantitated with RT‐PCR. In all regions that were investigated (olfactory bulb, cortex, hippocampus, cerebellum, and spinal cord), each subtype had a unique pattern of expression. NaCh6 mRNA and protein were not detected in either brain or spinal cord at E15 and E18 by in situ hybridization and immunohistochemistry. Neurons in the hippocampus, cortex, and olfactory bulb began to express NaCh6 mRNA and protein shortly after birth. The mRNA signal peaked at P7–P14, and protein expression increased as development proceeded. NaCh6 mRNA was detected at P1 in the cerebellum, and a nonuniform distribution of NaCh6 immunoreactivity in both Purkinje cells and granule cells was observed by P7–P14. NaCh6 protein was expressed in granule cells as soon as they left the proliferative phase and began to migrate. Both NaCh6 mRNA and protein were detected in the spinal cord at P1 and were expressed clearly at P7 in motor neurons. The time course of appearance of NaCh6 in postnatal development is consistent with the development of neurologic symptoms in med and jolting mice, which have mutations in the mouse ortholog of NaCh6. J. Comp. Neurol. 420:84–97, 2000. © 2000 Wiley‐Liss, Inc.
Setting Requirements and Managing Risk in Complex , Networked Projects

The task of determining the optimal design requirements of a new system, which will operate along with other existing systems to provide a set of overarching capabilities, is challenging due to the tightly coupled effects that setting requirements on a system’s design can have on how the operator uses the system. In this paper, the new system is a strategic military cargo aircraft and the other systems are a fleet of different, existing cargo aircraft; a subset of actual fleet operations from the U.S. Air Force Air Mobility Command defines the example problems in this work. This research builds upon prior efforts to develop a quantitative approach that identifies optimum design requirements of new, yet-to-be-designed systems that, when serving alongside other systems, will optimize fleet-level objectives. The new efforts here address the effect of various uncertainties. The approach incorporates techniques from multidisciplinary design optimization, statistical theory, and robust/reliability-based methods to develop computationally tractable approaches for this kind of problem. The paper also demonstrates the ability to generate tradeoffs between a cost-related metric of fleet-level fuel usage and a performance related metric of fleet-wide productivity. A possible extension for application in commercial air travel also appears in the paper.
Histamine release from dispersed human intestinal mast cells

To study the human intestinal mast cell of children and adults, we combined a sensitive glassfibre‐based histamine assay with the enzymatic and mechanical dispersion of surgical specimens or mucosal biopsies. The method yields between 1.2 × 103 to 4.6 × 103 mast cells/mg tissue constituting 1.2% to 5.3% of total cell count. The mast cell yield, however, depends on the intestinal tissue specimen used for dispersion. Aliquots containing 1500 mast cells per sample are sufficient for measuring significant amounts of histamine (± 0.15 ng histamine per sample), thus making it possible, to carry out approximately 75 tests for four mucosal biopsies of 10 mg each. The intestinal mast cell releases histamine in a dose‐dependent manner on challenge with anti‐IgE (6–600 U/ml), ionophore A23187 (0.25–1.0 μM), and Concanavalin A (0.7–25.0 μg/ml). The histamine release shows interindividual variation with a net histamine release between 0 to 2.5 ng/samples dependent on the secretatogue. In general, it is not necessary to passively sensitize the mast cells to obtain a sufficient histamine release response to anti‐IgE challenge, indicating the presence of intact and functional cell‐bound IgE. However, it is shown that four of 10 non‐atopic intestinal mast cell samples could be passively sensitized with human plasma containing either mite‐ or grass‐specific IgE without stripping off the IgE first. This indicates the presence of free and preserved Fc‐receptors on the dispersed mast cells in some subjects. In addition, it is found that the phorbolester TPA increases the histamine release response to A23187 and turns anti‐IgE non‐responding mast cells into responding mast cells, but TPA alone at 2 to 16 ng/ml has no histamine releasing effect. In patients with anti‐IgE responding mast cells no additional effect of TPA is seen. Finally, no substantial differences between mast cells of children and adults are demonstrated.
Notes on the Concept of Commitment

The concept of commitment is widely used but has received little formal analysis. It contains an implicit explanation of one mechanism producing consistent human behavior. Commitments come into being when a person, by making a side bet, links extraneous interests with a consistent line of activity. Side bets are often a consequence of the person's participation in social organizations. To understand commitments fully, an analysis of the system of value within which side bets are made is necessary.
Substantive bias in phonotactic learning : Positional extension of an obstruent voicing contrast

• To what extent is the phonological typology shaped by synchronic learning biases? • Synchronic (analytic) bias: Learners biased toward acquiring certain phonological systems over others Ø Complexity bias: bias against formally complex patterns Ø Substantive/naturalness bias: bias against phonetically unnatural patterns • Research question: Does phonetic naturalness bias phonotactic learning? • Approach: Test whether learners reproduce an attested and phonetically-motivated phonotactic implicational in an artificial grammar learning (AGL) experiment
Adenovirus for Cancer Therapy With a Focus on its Surface Modification

Yu, D. 2013. Adenovirus for Cancer Therapy: With a Focus on its Surface Modification. Acta Universitatis Upsaliensis. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 914. 59 pp. Uppsala. ISBN 978-91-554-8700-3. Adenovirus serotype 5 (Ad5) is widely used as an oncolytic agent for cancer therapy. However, its infectivity is highly dependent on the expression level of coxsackievirus-adenovirus receptor (CAR) on the surface of tumor cells. We engineered Ad5 virus with the protein transduction domain (PTD) from the HIV-1 Tat protein (Tat-PTD) inserted in the hypervariable region 5 (HVR5) of the hexon protein in the virus capsid. Tat-PTD-modified Ad5 shows a dramatically increased transduction level of CAR-negative cells and bypassed fiber-mediated transduction. It also overcomes the fiber-masking problem, which is caused by release of excess fiber proteins from infected cells. To achieve specific viral replication in neuroblastoma and neuroendocrine tumor cells, we identified the secretogranin III (SCG3) promoter and constructed an adenovirus Ad5PTD(ASH1-SCG3-E1A) wherein E1A gene expression is controlled by the SCG3 promoter and the achaete-scute complex homolog 1 (ASH1) enhancer. This virus shows selective and efficient killing of neuroblastoma cell lines in vitro, and delays human neuroblastoma xenograft tumor growth on nude mice. To further enhance the viral oncolytic efficacy, we also switched the fiber 5 to fiber 35 to generate Ad5PTDf35. This vector shows dramatically increased transduction capacity of primary human cell cultures including hematopoietic cells and their derivatives, pancreatic islets and exocrine cells, mesenchymal stem cells and primary tumor cells including primary cancer initiating cells. Ad5PTDf35-based adenovirus could be a useful platform for gene delivery and oncolytic virus development. Viral oncolysis alone cannot completely eradicate tumors. Therefore, we further armed the Ad5PTDf35-D24 virus with a secreted form of Helicobacter pylori Neutrophil Activating Protein (HP-NAP). Expression of HP-NAP recruits neutrophils to the site of infection, activates an innate immune response against tumor cells and provokes a Th1-type adaptive immune response. Established tumor on nude mice could be completely eradicated in some cases after treatment with this virus and the survival of mice was significantly prolonged.
Maternal Heart Rate Variability and Fetal Behavior in Hypertensive and Normotensive Pregnancies

The relation between maternal heart rate variability (HRV) and fetal behavior was examined in hypertensive and normotensive pregnant women. A total of 40 mother—fetal pairs (n = 20 normotensive mothers; n = 20 hypertensive mothers) at 33—41 weeks' gestation were observed using a standardized procedure lasting approximately 50 min. It included the following measurements: maternal beat-by-beat arterial blood pressure and HRV; spontaneous fetal heart rate (HR), body and breathing movements; and an estimate of amniotic fluid volume. The women in the hypertensive group had higher average body mass index (BMI) (33.7 vs. 28.8 kg/m2 ) than the normotensive group. In the normotensive group, there was no association between maternal HRV and fetal gestational age, HR, body or breathing movements. In the hypertensive group, maternal HRV measures of low-frequency, high-frequency, and total power were associated with fetal gestational age; also, there was an association between maternal autonomic modulation of HR and fetal spontaneous HR. These findings suggest that the maternal autonomic system influences fetal cardiac function in pregnancies complicated by hypertension.
Autoimmune thrombocytopenia in two patients with Sneddon’s Syndrome

Thromb Haemost 2007; 98: 1368–1370 Sneddon's Syndrome reflects a progressively heterogeneous clinical picture that includes cerebrovascular events with fixed Livedo reticularis (racemosa), and frequently many other symptoms including headaches, extra cerebral thrombosis or embolic processes, cardiac valvupathy, foetal loss in women, polyarthralgia, positive tests for antinuclear factors and antiphospholipid syndrome (1–6). In addition, thrombocytopenia is common in antiphospholipid positive (APL) patients (3, 7, 8). The question as to why many patients develop thrombocytopenia has not yet been addressed. Here, we describe a study conducted on two patients, which resulted in the diagnosis of Sneddon’s Syndrome, following more than a decade of uncertainty.