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The role of iron metabolism in Alzheimer's disease (AD) is well documented. Regulation of the proteins that maintain cellular iron metabolism is mediated by two cytoplasmic RNA-binding proteins, the Iron Regulatory Proteins (IRP1 and IRP2), that function through post-transcriptional interactions with RNA stem loop structures called iron-responsive elements. As the primary mediator of iron homeostasis in neuronal cells, IRP2 is a strong candidate for polymorphisms that could impact AD pathogenesis. Thus, we performed a pilot study to assess polymorphisms in the gene encoding IRP2 (IREB2) on clinically well-characterized, post-mortem samples (50 AD and 50 controls). DNA sequence analysis of the IREB2 gene region revealed 14 polymorphisms. Two (rs2656070 and rs13180) showed statistically significant skewing of allelic and genotypic distributions between AD patients and controls. In silico analyses revealed that rs2656070 lies within a probable promoter and disrupts the binding sites of at least two known transcription factors. Though silent and likely not functionally relevant, rs13180 is in complete LD with rs2656070 (D' > 0.999), creating an IREB2-haplotype that is significantly associated with AD. Confirmation of this association in a larger cohort of cases and controls would further support the role of iron regulation in the pathogenesis of this catastrophic and increasingly common neurodegenerative disorder.

This article is a preliminary edition — introduction, text, translation, commentary — of a previously unknown commentary on Aristotle’s Categories, recently discovered in the Archimedes Palimpsest. The two lemmas covered (both incompletely) in the fourteen surviving pages are 1a20-b15, concerning the distinction between ‘said of a subject’ and ‘in a subject’, and 1b16-24, where Aristotle maintains that different genera are divided by different differentiae. By extrapolating from this sample, the commentary can be inferred to have been considerably longer than the longest Categories commentary to survive intact, that of Simplicius. On this and other grounds, we argue that it is probably a fragment of Porphyry’s monumental lost commentary, the Ad Gedalium. A prominent feature of the new commentary is its extensive concentration on resolving puzzles raised against the Categories. Some of the material is completely absent from the remainder of the surviving Categories tradition. The earlier commentators and critics cited by name in it are Andronicus, Boethus, Nicostratus and Herminus.

Demyelination and axonal loss have been described as the histological hallmarks of inflammatory lesions of multiple sclerosis (MS) and are the pathological correlates of persistent disability. However, the immune mechanisms underlying axonal damage in MS remain unknown. Here, we report the use of single chain-variable domain fragments (scFv) from clonally expanded cerebrospinal fluid (CSF) B cells to show the role of an anti-axon immune response in the central nervous system (CNS) in MS. The cellular and subcellular distribution of the antigen(s) recognized by these CSF-derived clonal scFv antibodies (CSFC-scFv Abs) was studied by immunochemical staining of brain tissues obtained at autopsy from patients with MS. Immunochemistry showed specific binding of CSFC-scFv Abs to axons in acute MS lesions. The stained axons showed three major types of axonal pathological changes: 1) linear axons, axonal ovoid formation, and axonal transection were seen in the myelinated white matter adjacent to the lesion; 2) accumulation of axonal ovoid formations and Wallerian degeneration were seen at the border between demyelinated lesions and the adjacent white matter; and 3) Wallerian degeneration occurred at the center and edge of acute demyelinated lesions. These findings suggest a B cell axonal specific immune response in the CNS in MS.

A 1200 m long shallow seismic reflection profile is acquired across Uemachi fault system to explore the subsurface geology in and around the fault zone area. Our aim is to investigate the subsurface geometry of Uemachi fault plane as well as the shallow structures in the vicinity of the fault zone....

L'articolo considera il significato storico e filosofico dei commentatori neoplatonici di Aristotele. Gli autori situano il recente Sourcebook sui commentatori edito da Richard Sorbji in un contesto più ampio, che include il contributo dei commentatori nella formazione della filosofia tardo-antica e la loro posterità nella tradizione filosofica islamica. Dopo una sezione introduttiva (1) sullo stato attuale della ricerca in questo ambito, gli autori affrontano i temi seguenti: (2) Plotino, i commentatori e lo sviluppo del pensiero tardo antico; (3) il Sourcebook e la filosofia islamica. Riccardo Chiaradonna è co-autore della sezione (1) e autore della sezione (2), dove la ricezione dei trattati di scuola aristotelici è presentata come una caratteristica fondamentale nella transizione dalla filosofia post-ellenistica a quella tardo-antica. Plotino ha un ruolo cruciale in questo processo e l'assimilazione neoplatonica dei trattati di Aristotele non avrebbe avuto luoro senza il suo contributo. This article considers the historical and philosophical significance of the Neoplatonic commentators on Aristotle. The authors set Richard Sorabji's recent Sourcebook on the commentators within a wider backgroung, which covers the commentators' contribution in the shaping of late antique philosophy and their posterity in the Islamic philosophical tradition. After an introductory section (1) regarding the current status of research in this area, the authors tackle the following issues: (2) Plotinus, the commentators and the development of late antique thought; (3) the Sourcebook and Islamic Philosophy. Riccardo Chiaradonna is co-author of section (1) and author of section (2), where the reception of Aristotle's school treatises is set out as a key feature in the transition from Post Hellenistic to Late Antique philosophy. Plotinus has a pivotal position in this process and the Neoplatonic incorporation of Aristotle's treatises would have not taken place without Plotinus' contribution.

Since the onshore discovery of oil in the Eastern Desert in 1886, the petroleum industry in Egypt has accumulated reserves of more than 15.5 billion barrels of oil equivalent. An understanding of the tectono-stratigraphic history of each major basin, combined with drilling history and field-size distributions, justifies the realization of the complete replacement of these reserves in the coming decades. Most of the increase in reserves will be the result of offshore exploration. In addition to the 25 trillion cubic feet already discovered, the offshore Mediterranean may hold 64 to 84 trillion cubic feet and the onshore Western Desert may contribute 15 to 30 trillion cubic feet in new gas resources. Many of the new fields are expected to be in the giant-field class that contains greater than 100 million barrels of oil equivalent. Challenges include sub-salt imaging, market constraints for predominantly gas resources and economic constraints imposed by the high cost of development of the current deep-water gas discoveries that are probably unique worldwide. The offshore Gulf of Suez may yield an additional 1.5 to 3.3 billion barrels of oil equivalent, but it continues to be technologically constrained by poor-quality seismic data. Advances in multiple suppression and development of new ‘off-structure’ play concepts with higher quality seismic data should result in continual new pool discoveries. Offshore frontier exploration includes the Red Sea rift (currently under reassessment with area-wide 3-D surveys) and the Gulf of Aqaba. Deep-water and sub-salt imaging remain significant challenges to be overcome. Despite a relatively complex history, the Phanerozoic geological framework of Egypt is extremely prospective for oil and gas. Eight major tectono-stratigraphic events are: (1) Paleozoic craton; (2) Jurassic rifting; (3) Cretaceous passive margin; (4) Cretaceous Syrian Arc deformation and foreland transgressions; (5) Oligocene-Miocene Gulf of Suez rifting; (6) Miocene Red Sea opening; (7) the Messinian salinity crisis; and (8) Pliocene-Pleistocene delta progradation. Each of these events has created multiple reservoir and seal combinations. Source rocks occur from the Paleozoic through to the Pliocene and petroleum is produced from reservoirs that range in age from Precambrian to Pleistocene. The offshore Mediterranean, Gulf of Suez and Red Sea/Gulf of Aqaba contain significant exploration potential and will provide substantial reserve replacements in the coming decades.

Chlorpropham, also known as isopropyl-N-(3-chlorophenyl) carbamate or CIPC is a sprout suppressant and plant growth regulator of the chemical class derived from carbamic acid (NH2COOH). The substance was first developed as a pre-emergence herbicide, and it was quickly identified as a useful potato sprout suppressant for long-term tuber storage (Marth & Schultz 1952). Today CIPC is the major sprout inhibitor used in the potato industry (UK Potato Council 2013c). As a consequence there is environmental concern about CIPC reaching the aquatic environment from potato washing plants. An RP-HPLC method for the analysis of CIPC and IPC in methanol solvent with an automatic integration method was developed and validated. The correlation coefficients for CIPC and IPC regression lines at all calibration levels (0.001–100 mg/L) were (R2>0.999) while IPC exhibited a slightly less linear calibration curve (R2>0.98) at the lowest concentration range of (0.001–0.1 mg/L). An acceptable precision of 10% based on 10 injections was obtained at the limit of quantification of 0.001 mg/L for both analytes. The 3CA was excluded at this stage as it overlapped with an extra peak which required extensive investigations. The identification led to the conclusion that the artefact peak was a methanol-oxygen peak and elimination of the methanol-oxygen peak was not possible. The evaluation of five different columns and conditions in separating the methanol-oxygen peak from 3CA in a mixture containing 3CA, IPC and CIPC was studied. For the four peaks, the best separation at low eluant concentration was obtained at 55% methanol, but the run time was considerable. In contrast, the best separation at high eluant concentration was obtained at 75% methanol; however, the methanol-oxygen peak was still incompletely separated from the IPC peak due to the high size of the methanol-oxygen peak. Further investigations were conducted to reduce the size of the methanol-oxygen peak by changing the mobile phase pH which had no effect. Changing detection wavelength from 210 – 260 nm reduced the peak size, but considerable loss in sensitivity was observed. Five different instruments were tried and at the end the Thermo HPLC system was chosen because it provided a smaller methanol-oxygen peak along with temperature control to enhance the methanol-oxygen and 3CA peak separation at 60% methanol eluant, but the run time was still very long. Therefore, to enable a compromise between baseline peak resolutions as well as high-throughput separations; two separate methods for 3CA and CIPC, including IPC were developed and validated. The precision for both analytes at two levels of 0.01 and 1.0 mg/L based on 10 injections was ≤ 1%, the calibration curves at all levels were (R2>0.999) and the limit of quantification was 0.001 mg/L. Preparation of CIPC, IPC and 3CA standards in water from stock solutions in methanol and directly by dissolution in water was investigated. The peak areas were not affected even at 0% methanol concentration and the peak shapes were sharper than that in methanol without affecting the peak area. This validated the use of water as sample solvent to carry out the analysis by HPLC. To successfully prepare CIPC, IPC and 3CA in 100% water, it was necessary to develop methods for preparation and handling aqueous solution of CIPC, IPC and 3CA. The solubility of CIPC and IPC were studied. Both CIPC and IPC have low solubility in water while 3CA has higher solubility and dissolved quite rapidly. The solubility time curve for CIPC showed a gradual concentration increase from initial time until day 3 stirring but after that the solubility was consistent and values of 106, 89 and 61 mg/L CIPC were obtained at 25°C, 22°C and 4°C respectively. IPC exhibited similar solubility behaviour and the corresponding values were found to be 222, 200 and 140 mg/L at same temperatures respectively.The solubility results agreed with the literature values. Stock solutions and standards in aqueous solution were found to be stable on storage at 4°C (refrigerator) and ~20°C (lab temperature) for up to 90 days.For this work it was necessary to investigate possible CIPC, IPC and 3CA adsorption from aqueous solutions by glassware and filters. All plastic glassware were avoided as they have measurable adsorption (20-40%) for the analytes, except high clarity polypropylene. In contrast, glass materials particularly borosilicate and soda glass provided nearly zero adsorption for all three analytes. Although it was possible to identify suitable glassware that did not adsorb CIPC, IPC and 3CA it was necessary to discard the first 25 mL of filtrate to overcome adsorption onto filters (Cellulose, Glass microfiber, PTFE and Nylon). The Glass microfiber, type GF/B filter, has a pore size of 1.0 µm and is often used as a prefilter. However, the 25 mL discarding from filtrate was suitable only for filtering sample larger than 25 mL. For small scale filtration, a much smaller 0.2 µm PTFE filter in a 17 mm chemically resistant polypropylene housing disk attached to 3 mL BD syringe was used and only 1.5 mL of the sample was required to saturate the filter. A liquid-liquid extraction method with vortex mixer (LLE-Vortex) was successfully developed and validated for the extraction of CIPC and 3CA from dilute soil–water suspensions (0.001 g/mL) with a high recovery 98%–100% and RSD% less than 1.34%. In addition, the method was reliable for extraction from high soil suspensions formed with 0.02 g/mL of soil and for 0.1 g/mL of soils with low adsorption capacity. The average precision of extracting CIPC at 0.02 g/mL and 0.1 g/mL soil content was 1.6% and 3.2% while more precise extraction observed for 3CA of about 0.91% and 1.86%, respectively. However, the extraction method did not work for soil suspension with the highest organic matter content and concentration equal or more than 0.1 g/mL. Investigations were carried out to examine the adsorption- desorption behaviour of CIPC and 3CA from aqueous solutions onto different clay and sandy air dried soils. The suitable contact time of two days using 1 g material size was determined. At all temperatures, CIPC and 3CA were strongly adsorbed in clay soils while only slightly adsorbed in sandy soils. A paired t-test was used to compare between the adsorption at 5°C and 30°C for CIPC and 3CA and concluded that there was a statistically significant difference between the two temperatures for both analytes (p-value < 0.05). The effect of pH was also studied and it was found that the soil pH had a negligible impact on the adsorption of CIPC, while for 3CA the adsorption at low and high pH was significant (p-value

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by autoimmune-mediated demyelination and neurodegeneration. The CNS of patients with MS harbors expanded clones of antigen-experienced B cells that reside in distinct compartments including the meninges, cerebrospinal fluid (CSF), and parenchyma. It is not understood whether this immune infiltrate initiates its development in the CNS or in peripheral tissues. B cells in the CSF can exchange with those in peripheral blood, implying that CNS B cells may have access to lymphoid tissue that may be the specific compartment(s) in which CNS-resident B cells encounter antigen and experience affinity maturation. Paired tissues were used to determine whether the B cells that populate the CNS mature in the draining cervical lymph nodes (CLNs). High-throughput sequencing of the antibody repertoire demonstrated that clonally expanded B cells were present in both compartments. Founding members of clones were more often found in the draining CLNs. More mature clonal members derived from these founders were observed in the draining CLNs and also in the CNS, including lesions. These data provide new evidence that B cells traffic freely across the tissue barrier, with the majority of B cell maturation occurring outside of the CNS in the secondary lymphoid tissue. Our study may aid in further defining the mechanisms of immunomodulatory therapies that either deplete circulating B cells or affect the intrathecal B cell compartment by inhibiting lymphocyte transmigration into the CNS.

Human herpesvirus 6 (HHV-6), the etiologic agent of roseola in young children, has been reported to be detectable in the brain of many neurologically normal adults, although regional localization to plaques of multiple sclerosis has also been demonstrated. Large amounts of this virus were present in multifocal demyelinating white matter lesions of fulminant encephalomyelitis with seizures in a 21-year-old woman with normal immune parameters. Brain biopsy after 3 weeks of neurologic deterioration revealed a viral etiology by light and electron microscopy; the virus was identified as HHV-6 by immunohistochemistry and by polymerase chain reaction (PCR) amplification in biopsy and autopsy specimens.

A new two layer hierarchical routing protocol called Cluster Based Hierarchical Routing Protocol (CBHRP) is proposed in this paper. It is an extension of LEACH routing protocol. We introduce cluster head-set idea for cluster-based routing where several clusters are formed with the deployed sensors to collect information from target field. On rotation basis, a head-set member receives data from the neighbor nodes and transmits the aggregated results to the distance base station. This protocol reduces energy consumption quite significantly and prolongs the life time of sensor network. It is found that CBHRP performs better than other well accepted hierarchical routing protocols like LEACH in term of energy consumption and time requirement., 11 pages

Elective percutaneous coronary intervention (PCI) is associated with myocardial necrosis, as evidenced by troponin release, in approximately one-third of cases. This is known to be linked with subsequent cardiovascular events. This study assessed the ability of remote ischemic preconditioning (RIPC) to attenuate cardiac troponin T (cTnT) release after elective PCI.Evaluation of effect of RIPC on myocardial markers following elective PCI.One hundred and forty nine consecutive patients undergoing elective PCI with undetectable preprocedural cTnT were recruited. Subjects were randomized to receive RIPC (induced by three 5-min inflations of a blood pressure cuff to 200 mm Hg around the upper arm, followed by 5-min intervals of reperfusion) or control (cuff deflated) immediately before arrival in the cardiac catheterization room. The primary outcome was cTnT level at approximately 16 hr after PCI. Secondary outcomes included occurrence of postprocedural myocardial infarction (MI), CKMB levels at 16 hr after PCI and assessment of the inflammatory response as measured by C-reactive protein (CRP) levels.The mean cTnT at 16 hr after PCI was lower in the RIPC group compared with the control group. (0.020 vs. 0.047 ng/ml; P = 0.047) Occurrence of postprocedural MI, CKMB and CRP levels did not differ in both groups (P = 0.097, 0.537, and 0.481 respectively).The use of RIPC immediately prior to PCI attenuates procedure-related cTnT release and does not affect occurrence of post procedural MI, CKMB, or CRP levels.

Multiple sclerosis (MS) is a demyelinating disease of unknown origin that affects the central nervous system of an estimated 400,000 Americans. GBV-C or hepatitis G is a flavivirus that is found in the serum of 1–2% of blood donors. It was originally associated with hepatitis, but is now believed to be a relatively non-pathogenic lymphotropic virus. Fifty frozen specimens from the brains of deceased persons affected by MS were obtained along with 15 normal control brain specimens. RNA was extracted and ribosomal RNAs were depleted before sequencing on the Illumina GAII. These 36 bp reads were compared with a non-redundant database derived from the 600,000+ viral sequences in GenBank organized into 4080 taxa. An individual read successfully aligned to the viral database was considered to be a “hit”. Normalized MS specimen hit rates for each viral taxon were compared to the distribution of hits in the normal controls. Seventeen MS and 11 control brain extracts were sequenced, yielding 4–10 million sequences (“reads”) each. Over-representation of sequence from at least one of 12 viral taxa was observed in 7 of the 17 MS samples. Sequences resembling other viruses previously implicated in the pathogenesis of MS were not significantly enriched in any of the diseased brain specimens. Sequences from GB virus C (GBV-C), a flavivirus not previously isolated from brain, were enriched in one of the MS samples. GBV-C in this brain specimen was confirmed by specific amplification in this single MS brain specimen, but not in the 30 other MS brain samples available. The entire 9.4 kb sequence of this GBV-C isolate is reported here. This study shows the feasibility of deep sequencing for the detection of occult viral infections in the brains of deceased persons with MS. The first isolation of GBV-C from human brain is reported here.

Extraocular muscles (EOMs) are unique as they show greater variation in anatomical and physiological properties than any other skeletal muscles. To investigate the muscle fiber types and to understand better the structure-function correlation of the extraocular muscles, the present study examined the ultrastructural characteristics of the superior rectus muscle of rat. The superior rectus muscle is organized into two layers: a central global layer of mainly large-diameter fibers and an outer C-shaped orbital layer of principally small-diameter fibers. Six morphologically distinct fiber types were identified within the superior rectus muscle. Four muscle fiber types, three single innervated fibers (SIFs) and one multiple innervated fiber (MIF), were recognized in the global layer. The single innervated fibers included red, white and intermediate fibers. They differed from one another with respect to diameter, mitochondrial size and distribution, sarcoplasmic reticulum and myofibrillar size. The orbital layer contained two distinct MIFs in addition to the red and intermediate SIFs. The orbital MIFs were categorized into low oxidative and high oxidative types according to their mitochondrial content and distribution. The highly specialized function of the superior rectus extraocular muscle is reflected in the multiplicity of its fiber types, which exhibit unique structural features. The unique ultrastructural features of the extraocular muscles and their possible relation to muscle function are discussed.