Miracle-dz/UniFAR-FTUs huggingface dataset:
Progressive biparietal atrophy: an atypical presentation of Alzheimer's disease.

OBJECTIVES: To define the clinical, neuropsychological, and radiological features of bilateral parietal lobe atrophy. METHODS: Four patients underwent a comprehensive longitudinal neuropsychological assessment, as well as MRI and HMPAO-SPECT. RESULTS: The consistent findings in the patients were early visuospatial problems, agraphia of a predominantly peripheral (or apraxic) type, and difficulty with bimanual tasks, all of which outweighted deficits in memory and language until later in the course of the illness. As the disease progressed, impairments in the phonological aspects of language and in auditory-verbal short term memory were often striking, perhaps reflecting spread from the parietal lobe to perisylvian language areas. Three patients went on to develop a global dementia and fulfilled the criteria for a clinical diagnosis of probable Alzheimer's disease; the fourth patient has only recently been identified. Neuroimaging disclosed bilateral parietal lobe atrophy (MRI) and hypoperfusion (SPECT), which was out of proportion to that seen elsewhere in the brain. One patient has died and had pathologically confirmed Alzheimer's disease with particular concentration in both superior parietal lobes. CONCLUSIONS: Bilateral biparietal atrophy is a recognisable clinical syndrome which can be the presenting feature of Alzheimer's disease. Although the label "posterior cortical atrophy" has been applied to such cases, review of the medical literature suggests that this broad rubric actually consists of two main clinical syndromes with features reflecting involvement of the occipitotemporal (ventral) and biparietal (dorsal) cortical areas respectively.
Differential Targeting of Hsp70 Heat Shock Proteins HSPA6 and HSPA1A with Components of a Protein Disaggregation/Refolding Machine in Differentiated Human Neuronal Cells following Thermal Stress

Heat shock proteins (Hsps) co-operate in multi-protein machines that counter protein misfolding and aggregation and involve DNAJ (Hsp40), HSPA (Hsp70), and HSPH (Hsp105α). The HSPA family is a multigene family composed of inducible and constitutively expressed members. Inducible HSPA6 (Hsp70B') is found in the human genome but not in the genomes of mouse and rat. To advance knowledge of this little studied HSPA member, the targeting of HSPA6 to stress-sensitive neuronal sites with components of a disaggregation/refolding machine was investigated following thermal stress. HSPA6 targeted the periphery of nuclear speckles (perispeckles) that have been characterized as sites of transcription. However, HSPA6 did not co-localize at perispeckles with DNAJB1 (Hsp40-1) or HSPH1 (Hsp105α). At 3 h after heat shock, HSPA6 co-localized with these members of the disaggregation/refolding machine at the granular component (GC) of the nucleolus. Inducible HSPA1A (Hsp70-1) and constitutively expressed HSPA8 (Hsc70) co-localized at nuclear speckles with components of the machine immediately after heat shock, and at the GC layer of the nucleolus at 1 h with DNAJA1 and BAG-1. These results suggest that HSPA6 exhibits targeting features that are not apparent for HSPA1A and HSPA8.
Epidemiology of Imported Leishmaniasis in Italy: Implications for a European Endemic Country

In the past decade, the number of imported leishmaniasis cases has increased in countries of Western Europe. The trend is associated with increasing travels, ecotourism activity, military operations and immigration. While in endemic countries leishmaniasis is usually well diagnosed, accurate patient history and parasite identification are necessary to distinguish between autochthonous and imported cases. This is particularly important, as new Leishmania species/genotypes may be introduced and transmitted by local phlebotomine vectors without appropriate surveillance, with unpredictable consequences. We report on the surveillance of imported leishmaniasis performed by the Leishmania Identification Reference Centre of Rome from 1986 through 2012, involving health care centres from 16/20 Italian regions. Suspected imported cases were analyzed and conclusions were based on clinical, epidemiological and diagnostic findings. Over the years, different parasite identification methods were employed, including MultiLocus Enzyme Electrophoresis and molecular techniques combining disease diagnosis (SSU rDNA nested-PCR) and Leishmania typing (nuclear repetitive sequence and ITS-1 PCR-RFLPs). A total of 105 imported cases were recorded (annual range: 0-20) of which 36 were visceral (VL) (16 HIV-coinfections) and 69 cutaneous (CL) cases; 85 cases (52 CL) were from the Old World and 20 (17 CL) from the New World. Eight Leishmania species were identified, of which 7 were exotic to Italy. VL importation until 1995 was associated with the spread of Mediterranean Leishmania-HIV co-infections in early 1990s. Following the introduction of HAART treatment, such cases became occasional in Italians but relatively frequent among immigrants. In contrast, a steady increase of CL cases was observed from different areas of the Old and New Worlds, that in recent years included mainly immigrants ‘visiting friends and relatives’ and Italian tourists. This positive trend likely depends on better diagnosis and reporting; however, we suspect that many CL cases remained unrecognized. Given the relatively low incidence of leishmaniasis importation, the risk of introduction of exotic parasites appears limited, although the detection of anthroponotic species requires attention.
Heritable influences on behavioural problems from early childhood to mid-adolescence: evidence for genetic stability and innovation

Background Although behavioural problems (e.g. anxiety, conduct, hyperactivity, peer problems) are known to be heritable both in early childhood and in adolescence, limited work has examined prediction across these ages, and none using a genetically informative sample. Method We examined, first, whether parental ratings of behavioural problems (indexed by the Strengths and Difficulties questionnaire) at ages 4, 7, 9, 12, and 16 years were stable across these ages. Second, we examined the extent to which stability reflected genetic or environmental effects through multivariate quantitative genetic analysis on data from a large (n > 3000) population (UK) sample of monozygotic and dizygotic twins. Results Behavioural problems in early childhood (age 4 years) showed significant associations with the corresponding behavioural problem at all subsequent ages. Moreover, stable genetic influences were observed across ages, indicating that biological bases underlying behavioural problems in adolescence are underpinned by genetic influences expressed as early as age 4 years. However, genetic and environmental innovations were also observed at each age. Conclusion These observations indicate that genetic factors are important for understanding stable individual differences in behavioural problems across childhood and adolescence, although novel genetic influences also facilitate change in such behaviours.
The Optical Phenomena of Interplay between Nanobio Complexes: A Theoretical Insight into Their Biomedical Applications

The subnanometer‐sized coinage metal nanoparticles (NPs) have attracted more attention due to their unique electronic structures and subsequent physical, chemical and excellent photoluminescent properties. The DNA‐stabilized metal clusters had become a remark‐ ably good choice for the selection of fluorescent color by the sequence of the stabilizing DNA oligomer. Similarly, the single‐wall carbon nanotubes (SWCNTs) also have unique optical properties which make them useful in many applications. The interaction of DNA and SWCNT is also useful in molecular sensors and it is assumed that amplification of the DNA sensing element may be necessary in the presence of SWCNTs. As the application of NP‐CNT system represents a great interest in nanobiotechnology, it can be used for the design of the electronic mobile diagnostic facilities for blood analysis and the chemical or drug delivery inside the living cell. The SWCNTs are used as a drug delivery vehicles used to target the specific cancer cells. Separately, along with DNA‐NP, the DNA‐CNT system also represents a great interest, nowadays, in biomedical applications due to diagnostics and treatment of oncology diseases. So combining the DNA‐NP‐SWCNT system can rep‐ resent a potential target of modern research. The interplay of DNA, NP and SWCNTs has now become a current topic of research for further nanobiomedical applications.
Environmental Health: a Global Access Science Source Selected Science: an Industry Campaign to Undermine an Osha Hexavalent Chromium Standard

While exposure to hexavalent chromium (Cr(VI)) has been associated with increased lung cancer risk for more than 50 years, the chemical is not currently regulated by the U.S. Occupational Safety and Health Administration (OSHA) on the basis of its carcinogenicity. The agency was petitioned in 1993 and sued in 1997 and 2002 to lower the workplace Cr(VI) exposure limit, resulting in a court order to issue a final standard by February 2006. Faced with the threat of stronger regulation, the chromium industry initiated an effort to challenge the scientific evidence supporting a more protective standard. This effort included the use of "product defense" consultants to conduct post hoc analyses of a publicly-funded study to challenge results viewed unfavorably by the industry. The industry also commissioned a study of the mortality experience of workers at four low-exposure chromium plants, but did not make the results available to OSHA in a timely manner, despite multiple agency requests for precisely these sorts of data. The commissioned study found a statistically significant elevation in lung cancer risk among Cr(VI)-exposed workers at levels far below the current standard. This finding changed when the multi-plant cohort was divided into two statistically underpowered components and then published separately. The findings of the first paper published have been used by the chromium industry to attempt to slow OSHA's standard setting process. The second paper was withheld from OSHA until it was accepted for publication in a scientific journal, after the rulemaking record had closed. Studies funded by private sponsors that seek to influence public regulatory proceedings should be subject to the same access and reporting provisions as those applied to publicly funded science. Parties in regulatory proceedings should be required to disclose whether the studies were performed by researchers who had the right to present their findings without the sponsor's consent or influence, and to certify that all relevant data have been submitted to the public record, whether published or not.
Traffic engineering with traditional IP routing protocols

Traffic engineering involves adapting the routing of traffic to network conditions, with the joint goals of good user performance and efficient use of network resources. We describe an approach to intradomain traffic engineering that works within the existing deployed base of interior gateway protocols, such as Open Shortest Path First and Intermediate System-Intermediate System. We explain how to adapt the configuration of link weights, based on a networkwide view of the traffic and topology within a domain. In addition, we summarize the results of several studies of techniques for optimizing OSPF/IS-IS weights to the prevailing traffic. The article argues that traditional shortest path routing protocols are surprisingly effective for engineering the flow of traffic in large IP networks.
Acute effect of alcohol on estradiol, estrone, progesterone, prolactin, cortisol, and luteinizing hormone in premenopausal women.

BACKGROUND Heavy alcohol consumption is associated with menstrual irregularities, including anovulation, luteal-phase dysfunction, recurrent amenorrhea, and early menopause. In addition, moderate to heavy alcohol intake has been found to increase the risk of spontaneous abortions and breast cancer. These adverse effects could at least in part originate from alcohol-mediated changes in hormone levels. METHODS The acute effect of alcohol on the hormone balance in women using oral contraceptives (OC+) and also in nonusers (OC-), was evaluated in 30 OC- and 31 OC+ subjects, representing the whole period of the menstrual cycle. It was also evaluated in 40 OC- and 47 OC+ subjects during the midcycle phase and in 10 OC+ subjects with unknown cycle phase. RESULTS We found that among subjects who used oral contraceptives, estradiol levels increased and progesterone levels decreased after intake of alcohol (0.5 g/kg). No dose effect (0.34-1.02 g/kg) on progesterone was observed in a substudy on 10 OC+ subjects. With regard to estrone levels, no effect was observed, although a significant increase was found in the estradiol-to-estrone ratio. Among subjects not using oral contraceptives, progesterone levels decreased after intake of alcohol (0.5 g/kg). No effect was found in estradiol, estrone, or the estradiol-to-estrone ratio during midcycle in this study group. A transient elevating effect of alcohol (0.5 g/kg) on prolactin levels was observed in both study groups. We found that alcohol (0.5 g/kg) had no significant effect on luteinizing hormone (LH) levels among subjects not using oral contraceptives, and observed a decline among subjects using oral contraceptives at midcycle. CONCLUSIONS We suggest that the estradiol and progesterone effects are related to decreased steroid catabolism, resulting from the alcohol-mediated increase in the hepatic NADH-to-NAD ratio. The transient effect on prolactin levels may reflect acute changes in opioid and dopamine levels in the hypothalamus. The present findings regarding female sex steroids may be of relevance in the association between moderate to heavy alcohol consumption and the development of breast cancer.
Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease

The scurfy mutant mouse strain suffers from a fatal lymphoproliferative disease leading to early death within 3–4 wk of age. A frame-shift mutation of the forkhead box transcription factor Foxp3 has been identified as the molecular cause of this multiorgan autoimmune disease. Foxp3 is a central control element in the development and function of regulatory T cells (T reg cells), which are necessary for the maintenance of self-tolerance. However, it is unclear whether dysfunction or a lack of T reg cells is etiologically involved in scurfy pathogenesis and its human correlate, the IPEX syndrome. We describe the generation of bacterial artificial chromosome–transgenic mice termed “depletion of regulatory T cell” (DEREG) mice expressing a diphtheria toxin (DT) receptor–enhanced green fluorescent protein fusion protein under the control of the foxp3 gene locus, allowing selective and efficient depletion of Foxp3+ T reg cells by DT injection. Ablation of Foxp3+ T reg cells in newborn DEREG mice led to the development of scurfy-like symptoms with splenomegaly, lymphadenopathy, insulitis, and severe skin inflammation. Thus, these data provide experimental evidence that the absence of Foxp3+ T reg cells is indeed sufficient to induce a scurfy-like phenotype. Furthermore, DEREG mice will allow a more precise definition of the function of Foxp3+ T reg cells in immune reactions in vivo.
Changes in process performance and microbial characteristics of retained sludge during low-temperature operation of an EGSB reactor

A lab-scale expanded granular sludge bed (EGSB) reactor was seeded with granular sludge and operated to investigate the influence of temperature decrease on both process performance and the microbial community structure of the granular sludge. Synthetic wastewater containing sucrose and volatile fatty acids was used as feed. The EGSB reactor was brought online at a starting temperature of 15°C and was reduced stepwise to a final temperature of 5°C. The reactor exhibited sufficient COD removal efficiency between 10°C and 15°C. However at 5°C serious deterioration of process performance was observed. The methane-producing activity of the retained sludge increased when it was compared to the activity of the seed sludge (day 0) during 10°C to 15°C operation. When hydrogen fed, sludge showed much higher methanogenic activity as compared with seed sludge activity at test temperatures of 15°C and 20°C on day 196 of reactor operation. At this time, proliferation of the genus Methanospirillum in the retained sludge was observed and a decrease in Methanobacterium species was also measured. Throughout the experiment, the genus Methanosaeta was detected in abundance and the community structure of the Domain Bacteria was stably maintained. The sugar-degrading acid-forming bacteria, Lactococcus and Anaerovibrio were detected in the retained sludge throughout the experiment as well and the propionate-degrading acetogen Syntrophobacter fumaroxidans was also detected, although its population size decreased at 5°C.
Noise, nonlinearity and seasonality: the epidemics of whooping cough revisited

Understanding the mechanisms that generate oscillations in the incidence of childhood infectious diseases has preoccupied epidemiologists and population ecologists for nearly two centuries. This body of work has generated simple yet powerful explanations for the epidemics of measles and chickenpox, while the dynamics of other infectious diseases, such as whooping cough, have proved more challenging to decipher. A number of authors have, in recent years, proposed that the noisy and somewhat irregular epidemics of whooping cough may arise due to stochasticity and its interaction with nonlinearity in transmission and seasonal variation in contact rates. The reason underlying the susceptibility of whooping cough dynamics to noise and the precise nature of its transient dynamics remain poorly understood. Here we use household data on the incubation period in order to parametrize more realistic distributions of the latent and infectious periods. We demonstrate that previously reported phenomena result from transients following the interaction between the stable annual attractor and unstable multiennial solutions.
Distinct RNA degradation pathways and 3' extensions of yeast non-coding RNA species

Non-coding transcripts originating from bidirectional promoters have been reported in a wide range of organisms. In yeast, these divergent transcripts can be subdivided into two classes. Some are designated Cryptic Unstable Transcripts (CUTs) because they are terminated by the Nrd1-Nab3-Sen1 pathway and then rapidly degraded by the nuclear exosome. This is the same processing pathway used by yeast snoRNAs. Whereas CUTs are only easily observed in cells lacking the Rrp6 or Rrp47 subunits of the nuclear exosome, Stable Uncharacterized Transcripts (SUTs) are present even in wild-type cells. Here we show that SUTs are partially susceptible to the nuclear exosome, but are primarily degraded by cytoplasmic 5’ to 3’ degradation and nonsense-mediated decay (NMD). Therefore, SUTs may be processed more similar to mRNAs. Surprisingly, both CUTs and SUTs were found to produce 3' extended species that were also subject to cytoplasmic degradation. The functions, if any, of these extended CUTs and SUTs are unknown, but their discovery suggests that yeasts generate transcripts reminiscent of long noncoding RNAs found in higher eukaryotes.
Estimating the near-surface permafrost-carbon feedback on global warming

Abstract. Thawing of permafrost and the associated release of carbon constitutes a positive feedback in the climate system, elevating the effect of anthropogenic GHG emissions on global-mean temperatures. Multiple factors have hindered the quantification of this feedback, which was not included in climate carbon-cycle models which participated in recent model intercomparisons (such as the Coupled Carbon Cycle Climate Model Intercomparison Project – C4MIP) . There are considerable uncertainties in the rate and extent of permafrost thaw, the hydrological and vegetation response to permafrost thaw, the decomposition timescales of freshly thawed organic material, the proportion of soil carbon that might be emitted as carbon dioxide via aerobic decomposition or as methane via anaerobic decomposition, and in the magnitude of the high latitude amplification of global warming that will drive permafrost degradation. Additionally, there are extensive and poorly characterized regional heterogeneities in soil properties, carbon content, and hydrology. Here, we couple a new permafrost module to a reduced complexity carbon-cycle climate model, which allows us to perform a large ensemble of simulations. The ensemble is designed to span the uncertainties listed above and thereby the results provide an estimate of the potential strength of the feedback from newly thawed permafrost carbon. For the high CO2 concentration scenario (RCP8.5), 33–114 GtC (giga tons of Carbon) are released by 2100 (68 % uncertainty range). This leads to an additional warming of 0.04–0.23 °C. Though projected 21st century permafrost carbon emissions are relatively modest, ongoing permafrost thaw and slow but steady soil carbon decomposition means that, by 2300, about half of the potentially vulnerable permafrost carbon stock in the upper 3 m of soil layer (600–1000 GtC) could be released as CO2, with an extra 1–4 % being released as methane. Our results also suggest that mitigation action in line with the lower scenario RCP3-PD could contain Arctic temperature increase sufficiently that thawing of the permafrost area is limited to 9–23 % and the permafrost-carbon induced temperature increase does not exceed 0.04–0.16 °C by 2300.
Patients with impaired verb-tense processing: do they know that yesterday is past?

This paper begins with a focus on the task of stem inflection, where participants are given a verb stem and asked to produce the verb's past-tense form, which can produce a neuropsychological double dissociation with respect to regular versus irregular verbs. Two differing theoretical interpretations are outlined: one is based on specifically morphological and separate brain mechanisms for processing regular versus irregular verbs; the other argues that the two sides of the dissociation can arise from one procedure, which is not specifically morphological, and which relies to differing extents on phonological versus semantic information for regular versus irregular verbs. We then present data from a different version of the task, in which patients were given past-tense forms and asked to produce the present-tense or stem forms (talked → talk and ate → eat). This change yielded a very different pattern of performance in four non-fluent aphasic patients as a function of the regular–irregular manipulation, an outcome which is argued to be more compatible with the single- than the dual-mechanism account. Finally, we present a small amount of data from a task in which the patient was asked to judge whether spoken regular and irregular verb stems and past-tense forms indicated actions occurring today or yesterday. This task produced an even more different and intriguing pattern of performance suggesting a deficit in morpho-syntactic knowledge: not how to produce past-tense forms but what such forms mean and how that understanding interacts with verb regularity. The paper concludes with a discussion of how the research field of acquired disorders of tense processing might advance as a result of new approaches, in particular those informed by studies of developmental disorders.