Miracle-dz/UniFAR-FTUs huggingface dataset:
Discriminatory Effect of Cyclic Alternating Pattern in Focal Lesional and Benign Rolandic Interictal Spikes During Sleep

Summary: Twenty epileptic patients (10 male and 10 female) were polygraphically recorded during nocturnal sleep. Ten subjects, with a wide age range, were affected by focal lesional epilepsy, and 10 were children affected by benign epilepsy with rolandic spikes (BERS). In five cases a bihemispheric expression of the focal lesional bursts emerged occasionally during the night recordings. The behavior of interictal electroencephalographic (EEG) paroxysms were analyzed with respect to the two arousal states of non‐rapid‐eye‐movement (REM) sleep: (a) the cyclic alternating pattern (CAP), expressed by biphasic EEG periodic activities and related to long‐lasting fluctuations between greater (phase A) and lesser (phase B) arousal levels; and (b) the non‐CAP (NCAP), manifested by EEG stationarities that reflect a sustained relative stability of arousal. The CAP/NCAP modality affected the spiking activity and distribution of the focal lesional EEG paroxysms, which appeared enhanced during CAP and which were mostly collected in phase A. The even more powerful influence of CAP and especially phase A on the secondary bisynchronous bursts suggests a crucial integration among thalamocortical circuits, arousal modulation, and epileptic generalization mechanisms. Conversely, in the BERS recordings no significant differences emerged throughout CAP and NCAP. The intense activity of the rolandic foci induced by sleep as such could be explained on the basis of the greater dependence of these functional cortical EEG abnormalities on the degree of synchronization during sleep.
A half-type ABC transporter TAPL is highly conserved between rodent and man, and the human gene is not responsive to interferon-gamma in contrast to TAP1 and TAP2.

TAPL is a half-type ABC transporter with sequence similarity to TAP1 and TAP2 that is transcribed in various rat tissues [Yamaguchi, Y. , Kasano, M. , Terada, T. , Sato, R. , and Maeda, M. (1999) FEBS Lett. 457, 231-236]. Primary structures of the human and mouse orthologous counterparts were deduced from cDNAs cloned by means of polymerase chain reaction, and they were compared with that of the rat. The mammalian TAPLs (rat, mouse, and human) are highly conserved, since about 95% of the amino acid residues are identical between rodents and man. Phylogenetic analysis demonstrated that the evolutional rate of TAPL is much slower than those of TAP1 and TAP2, although TAPL could have diverged from an ancestor of TAP1 or that of TAP1 and TAP2. The TAPL-GFP fusion protein transiently expressed in Cos-1 cells was co-localized with PDI, suggesting that TAPL is inserted into endoplasmic reticulum membrane. The conservation of the peptide-binding motifs of TAP proteins in TAPL raises the possibility that the TAPL might be a peptide transporter. The gene for human TAPL is assigned to chromosome 12q24.31-q24.32, while those for TAP1 and TAP2 are located at the MHC locus of chromosome 6p21. 3. Furthermore, the transcription of TAPL gene is not responsive to interferon-gamma, in contrast to TAP1 and TAP2. These results indicate that the gene regulation of TAPL is different from those of TAP1 and TAP2.
Adaptation to high light intensity in Synechococcus sp. strain PCC 7942: regulation of three psbA genes and two forms of the D1 protein

The three psbA genes in the cyanobacterium Synechococcus sp. strain PCC 7942 encode two distinct forms of the D1 protein of photosystem II. The psbAI message, which encodes form I, dominates the psbA transcript pool at low to moderate light intensities; however, exposure to high light triggers a response in which the psbAI message is actively degraded while psbAII and psbAIII, which encode form II, are transcriptionally induced. We addressed whether these changes result from a generalized stress response and examined the consequence of light-responsive psbA regulation on the composition of D1 in thylakoid membranes. Heat shock and oxidative stress had some effect on levels of the three psbA transcripts but did not produce the responses generated by an increase in light intensity. Prolonged exposure to high light (24-h time course) was characterized by elevated levels of all psbA transcripts through maintenance of high levels of psbAII and psbAIII messages and a rebound of the psbAI transcript after its initial decline. Form II-encoding transcripts were enriched relative to those encoding form I at all high-light time points. Form II replaced form I in the thylakoid membrane at high light despite an abundance of psbAI transcript at later time points; this may be explained by the observed faster turnover of form I than form II in the membrane. We propose that form II is less susceptible to damage at high light and that this qualitative alteration, coupled with increased turnover of D1, protects the cells from photoinhibition.
A consistent dynamic localization model for large eddy simulation based on a variational formulation

The modeling of the unresolved or subgrid scales is a crucial aspect of large eddy simulation (LES) of turbulent flows. A very popular method of modeling relies on the subgrid (or eddy) viscosity concept, which is based on the Boussinesq turbulent (or eddy) viscosity assumption. According to this concept, the deviatoric part of the subgridscale stress tensor τ is approximated by a product of a subgrid viscosity νT and the rate-of-strain tensor of the resolved scales. The remaining unknown in this modeling approach is the subgrid viscosity νT. Several approximations for νT have been proposed. The Smagorinsky model was the earliest approach in this context and is still commonly used due to its simplicity. However, that model is based on an unknown parameter CS. Choosing a constant value for this parameter over the entire domain has been proven to be an inadequate approach in most of the cases, although recent integrations of this simple constant-coefficient-based Smagorinsky model into a multiscale environment have revitalized it and have yielded very good results for a number of test cases (see, for example, Gravemeier (2005b) and references therein). An important improvement of the Smagorinsky model was introduced in Germano et al. (1991), in which the model parameter was determined as a function of position and time by way of a dynamic algorithm. It should be remarked that this dynamic procedure is not restricted to the Smagorinsky model as the underlying model, although it has mostly been used with that model. The original formulation of the dynamic algorithm in Germano et al. (1991) contains a mathematically inconsistent assumption that disregards the fact that CS is a rapidly varying function of position, as discussed in Moin (1991). This inconsistency was later overcome in Ghosal et al. (1995) by the introduction of the dynamic localization model. Furthermore, ad hoc schemes were proposed in that publication, which were usually applied in practical simulations to prevent them from becoming unstable. By using those ad hoc schemes, the application of the dynamic model in several problem configurations was enabled, though without being justified except in a heuristic way. Overall, the study by Ghosal et al. (1995) aimed at “putting the dynamic modeling procedure on firm theoretical foundations, so that the method could be applied to arbitrary inhomogeneous flows without recourse to ad hoc procedures”. After all, however, the actual method of calculating the model parameter based on a variationally formulated condition for CS, which eventually had to make use of Fredholm’s integral equation of the second kind for its solution, appeared to be rather complicated. Moreover, an iterative procedure was necessary to solve this integral equation in practical calculations, which made it a computationally expensive part of the overall simulation.
Mathematical Modelling of Profiled Haemodialysis: A Simplified Approach

For many renal patients with severe loss of kidney function dialysis treatment is the only means of preventing excessive fluid gain and the accumulation of toxic chemicals in the blood. Typically, haemodialysis patients will dialyse three times a week, with each session lasting 4-6 hours. During each session, 2-3 litres of fluid is removed along with catabolic end-products, and osmotically active solutes. In a significant number of patients, the rapid removal of water and osmotically active sodium chloride can lead to hypotension or overhydration and swelling of brain cells. Profiled haemodialysis, in which the rate of water removal and/or the dialysis machine sodium concentration are varied according to a predetermined profile, can help to prevent wide fluctuations in plasma osmolality, which cause these complications. The profiles are determined on a trial and error basis, and differ from patient to patient. Here we describe a mathematical model for a typical profiled haemodialysis session in which the variables of interest are sodium mass and body fluid volumes. The model is of minimal complexity and so could provide simple guidelines for choosing suitable profiles for individual patients. The model is tested for a series of dialysate sodium profiles to demonstrate the potential benefits of sodium profiling. Next, using the simplicity of the model, we show how to calculate the dialysate sodium profile to model a dialysis session that achieves specified targets of sodium mass removal and weight loss, while keeping the risk of intradia-lytic complications to a minimum. Finally, we investigate which of the model profiled dialysis sessions that meet a range of sodium and fluid removal targets also predict extracellular sodium concentrations and extracellular volumes that lie within "safe" limits. Our model suggests that improvements in volume control via sodium profiling need to be set against potential problems in maintaining blood concentrations and body fluid compartment volumes within “safe” limits.
Depression as a culture-bound syndrome: implications for primary care.

This month sees the publication of the fifth edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Headline features include new diagnostic categories of anxious depression and somatic symptom disorder, and blurring of boundaries between grief and depressive disorder. However its relevance to primary care may be less than anticipated. According to its predecessor, DSM-IV, culture-bound syndromes are indigenously considered to be ‘illnesses’, limited to specific societies or culture areas, composed of localised diagnostic categories, and used to frame coherent meanings for certain repetitive, patterned, and troubling sets of experiences and observations.1 Examples commonly cited include koro in eastern Asia, latah in Malaysia, and ataque de nervios in Latin America. It can be argued that depression also fulfils the criteria for a culture-bound syndrome, in westernised societies. Our indigenous beliefs are based on the premise that depression is an illness of common and increasing prevalence, destined to become the second most disabling disease by 2020. These beliefs have societal and cultural limitations. They predominate in anglophone societies, although there is wide variation in their understanding and acceptance within these societies, depending on class, gender and culture.2 Depression can therefore be understood as a set of localised diagnostic categories, albeit currently operating on a larger scale than other culture-bound syndromes. If depression as a diagnostic category had validity and utility, it could be seen as a universal, transcultural concept. But it …
Special Invited Papers Section: Therapeutic Equivalence – Clinical Issues and Statistical Methodology in Noninferiority Trials

An essential problem in planning clinical non‐inferiority or equivalence studies is the specification of the ‘irrelevant difference’ (irrelevance margin; delta). This quantifies the amount of non‐inferiority or difference, respectively, between a new test therapy and an established standard treatment which is to be considered as tolerable. In the past, most recommendations and guidelines for clinical non‐inferiority and equivalence studies contained only general statements and formulations concerning the specification of delta. The current unsatisfactory situation was the reason for performing a systematic review of published clinical non‐inferiority and equivalence studies. It was the aim to gain an overview on the irrelevance margins used in such studies, and on reasons for choosing the particular margins. For the sake of comparability, the irrelevance margins were converted into standardized differences and odds ratios. Overall, there were 332 non‐inferiority or equivalence trials obtained by means of an extensive literature search. The results of the systematic review show that current requirements on the choice of delta and the reality of recent clinical non‐inferiority and equivalence trials differ substantially. In about one half of the trials a difference of 0.5 standard deviations or more was regarded as ‘irrelevant’ – explicitly or implicitly. Estimates of standard‐placebo differences formed the basis of the irrelevance margin in less than every tenth trial. Reasons for this very low proportion might be (1) the possibly resulting very small irrelevance margins, and (2) unsolved problems of the requirements themselves. Overall, it seems that a more global definition of ‘irrelevance’ might be warranted. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Lyme disease and the peripheral nervous system

Lyme disease, the multisystem infectious disease caused by the tick‐borne spirochete Borrelia burgdorferi, causes a broad variety of peripheral nerve disorders, including single or multiple cranial neuropathies, painful radiculopathies, and diffuse polyneuropathies. Virtually all appear to be varying manifestations of a mononeuropathy multiplex. Diagnosis requires that the patient should have had possible exposure to the only known vectors, Ixodes ticks, and also have either other pathognomonic clinical manifestations or laboratory evidence of exposure. Treatment with antimicrobial regimens is highly effective. The mechanism underlying these neuropathies remains unclear, although interactions between anti‐Borrelia antibodies and several peripheral nerve constituent molecules raise intriguing possibilities. Muscle Nerve 28: 133–143, 2003
Structure of mammalian protein geranylgeranyltransferase type‐I

Protein geranylgeranyltransferase type‐I (GGTase‐I), one of two CaaX prenyltransferases, is an essential enzyme in eukaryotes. GGTase‐I catalyzes C‐terminal lipidation of >100 proteins, including many GTP‐ binding regulatory proteins. We present the first structural information for mammalian GGTase‐I, including a series of substrate and product complexes that delineate the path of the chemical reaction. These structures reveal that all protein prenyltransferases share a common reaction mechanism and identify specific residues that play a dominant role in determining prenyl group specificity. This hypothesis was confirmed by converting farnesyltransferase (15‐C prenyl substrate) into GGTase‐I (20‐C prenyl substrate) with a single point mutation. GGTase‐I discriminates against farnesyl diphosphate (FPP) at the product turnover step through the inability of a 15‐C FPP to displace the 20‐C prenyl‐peptide product. Understanding these key features of specificity is expected to contribute to optimization of anti‐cancer and anti‐parasite drugs.
Disposition of ezetimibe is influenced by polymorphisms of the hepatic uptake carrier OATP1B1

Objectives Genetic variability in hepatic uptake was recently shown to influence the disposition and cholesterol-lowering effects of statins. Ezetimibe, an inhibitor of the intestinal cholesterol uptake protein Niemann-Pick C 1 like 1, is another drug for which genetic polymorphisms of hepatic organic anion transporting polypeptides (OATPs) are expected to be of clinical relevance because ezetimibe undergoes intensive enterohepatic circulation for which hepatic uptake transporters may be rate-limiting determinants. Methods Using OATP1B3-, OATP2B1-, and OATP1B1-transfected HEK cells, including the OATP1B1 variants OATP1B1*1b and OATP1B1*5, we measured the uptake of ezetimibe and its glucuronide and we analyzed the competition with the common OATP-substrate bromosulfophthalein. Disposition and sterol-lowering effects of 20-mg ezetimibe were measured in 35 healthy participants genotyped for OATP1B1, ABCB1, ABCC2, and UGT1A1. Results Ezetimibe glucuronide inhibited bromosulfophthalein uptake in all OATP-transfected cells (50% inhibitory concentration (IC50): 0.14–0.26 μmol/l) whereas ezetimibe was 30–100 times less potent. Only the glucuronide was accumulated significantly in cells expressing OATP1B1 and OATP2B1. Its uptake in cells expressing OATP1B1*1b and *5 was reduced. In-vivo studies showed there was a gene-dose-dependent decrease in the area under the curve of ezetimibe in participants with the OATP1B1*1b protein (*1a/*1a, N=12, 112±66 ng×h/ml vs. *1a/*1b, N=8, 88±39 ng×h/ml vs. *1b/*1b, N=5, 55±18 ng×h/ml; Jonkheere–Terpstra, P=0.041) and a tendency for increased glucuronide exposure (704±296 vs. 878±369 vs. 1059±363 ng×h/ml; P=0.092). Fecal ezetimibe excretion was significantly decreased whereas renal glucuronide excretion was increased in carriers of *1b/*1b. Fecal excretion was also diminished in carriers of OATP1B1*5 and *15. The sterol-lowering effect of ezetimibe was not influenced by OATP1B1 polymorphisms. Conclusion Pharmacokinetics of ezetimibe is influenced by OATP1B1 polymorphisms in healthy participants after single dose administration.
The PDZ domain of OutC and the N-terminal region of OutD determine the secretion specificity of the type II out pathway of Erwinia chrysanthemi.

The plant pathogens Erwinia chrysanthemi and Erwinia carotovora secrete multiple exoproteins by a type II pathway, the Out system. Secretion in Erwinia is species-specific: exoproteins of one species cannot be secreted by the other. We analysed the role of two components of the Out system, the bitopic inner membrane protein OutC and the secretin OutD, in the specific recognition of secreted proteins. We demonstrated that the PDZ domain of OutC determines its secretion specificity towards certain exoproteins. The secretin is the major determinant of specificity of the Out system: OutD of E. carotovora changes the secretion specificity of E. chrysanthemi and enables it to secrete heterologous exoproteins. Construction of chimeric OutD showed that the N-terminal region is the specificity domain of the secretin. Thus, both the PDZ domain of OutC and the N-terminal region of OutD are required for specific recognition of secreted proteins. Systematic analysis of the secretion of several exoproteins demonstrated that different exoproteins secreted by the Out machinery have different requirement for their presumed targeting signals on OutC and OutD. This strongly indicates that diverse exoproteins possess a variable number of targeting signals which are recognised by different regions of OutC and OutD.
The sequelae of Haemophilus influenzae meningitis in school-age children.

BACKGROUND Previous data on the consequences of Haemophilus influenzae type b meningitis for school-age children have been inconsistent, and much of the information on risk factors has been inconclusive. The present study was designed to evaluate the sequelae of this disease with a protocol for the comprehensive assessment of neuropsychological function. METHODS Ninety-seven school-age children (mean age, 9.6 years), each of whom had a school-age sibling, were recruited from a survey of the medical records of 519 children treated for H. influenzae type b meningitis between 1972 and 1984 (at a mean age of 17 months) at the children's hospitals of Toronto, Ottawa, and Montreal. Of the 97 children, 41 had had an acute neurologic complication. Sequelae were assessed by comparing the index children with their nearest siblings on the basis of standardized measures of cognitive, academic, and behavioral status. RESULTS Only 14 children (14 percent) had persisting neurologic sequelae: sensorineural hearing loss in 11 (unilateral in 6 and bilateral in 5), seizure disorder in 2, and hemiplegia and mental retardation in 1. Although the total sample of index children scored slightly below the siblings in reading ability, the 56 children without acute-phase neurologic complications (58 percent) were indistinguishable from their siblings on all measures. The differences between the groups were small even for the 41 pairs in which the index child had had an acute neurologic complication (mean full-scale IQ, 102 for the index children vs. 109 for the siblings). Sequelae were also associated with lower socioeconomic status and a lower ratio of glucose in cerebrospinal fluid to that in blood at the time of the meningitis. Behavioral problems were more prominent in index boys than index girls and in those who were older at the time of testing, but sex and age were not related to cognitive or academic sequelae. CONCLUSIONS We find a favorable prognosis for the majority of children who are treated for meningitis caused by H. influenzae type b.
Causative agents of acute diarrhoea in the first 3 years of life: Hospital‐based study

During the 2 years of the study, 402 patients and an equal number of age‐ and sex‐matched controls were investigated for the presence of diarrhoeal pathogens. Pathogenic organisms were recovered from 277 (68.9%) patients and 97 (24.1%) controls. In the patient group, possible bacterial pathogens were found in 210 (52.2%) cases. Enteropathogenic Escherichia coli (EPEC) was the most frequently found potential pathogen, being recovered in 132 cases (32.8%) with serotypes 026, 086, 0111 and 0124 being the most frequently identified. Other bacterial pathogens identified were enterotoxigenic E. coli (ETEC) 57 (14.2%), Shigella 13 (3.2%) and Salmonella eight (2%). Rotavirus was identified in 33 (8.2%) cases. Mixed bacterial and viral infections were also seen in 26 (6.5%) cases.
Disclosure bias for group versus individual reporting of violence amongst conflict-affected adolescent girls in DRC and Ethiopia

Methodologies to measure gender-based violence (GBV) have received inadequate attention, especially in humanitarian contexts where vulnerabilities to violence are exacerbated. This paper compares the results from individual audio computer-assisted self-administered (ACASI) survey interviews with results from participatory social mapping activities, employed with the same sample in two different post-conflict contexts. Eighty-seven internally displaced adolescent girls from the Democratic Republic of the Congo and 78 Sudanese girls living in Ethiopian refugee camps were interviewed using the two methodologies. Results revealed that the group-based qualitative method elicited narratives of violence focusing on events perpetrated by strangers or members of the community more distantly connected to girls. In contrast, ACASI interviews revealed violence predominantly perpetrated by family members and intimate partners. These findings suggest that group-based methods of information gathering frequently used in the field may be more susceptible to socially accepted narratives. Specifically, our findings suggest group-based methods may produce results showing that sexual violence perpetrated by strangers (e.g., from armed groups in the conflict) is more prevalent than violence perpetrated by family and intimate partners. To the extent this finding is true, it may lead to a skewed perception that adolescent GBV involving strangers is a more pressing issue than intimate partner and family-based sexual violence, when in fact, both are of great concern.