Miracle-dz/UniFAR-FTUs huggingface dataset:
Optic neuropathies: characteristic features and mechanisms of retinal ganglion cell loss

Abstract Optic neuropathy refers to dysfunction and/or degeneration of axons of the optic nerve with subsequent optic nerve atrophy. A common feature of different optic neuropathies is retinal ganglion cell (RGC) apoptosis and axonal damage. Glaucoma and optic neuritis are the two major degenerative causes of optic nerve damage. Here, we review the anatomy and pathology of the optic nerve, and etiological categories of optic neuropathies, and discuss rodent models that can mimic these conditions. Electrophysiology can reveal signature features of RGC damage using the pattern electroretinogram (PERG), scotopic threshold response (STR) and photopic negative response (PhNR). The amplitude of the visual evoked potential (VEP) also reflects RGC axonal damage. The neurotrophin-mediated survival pathways, as well as the extrinsic and intrinsic cell apoptotic pathways, play a critical role in the pathogenesis of RGC loss. Finally, promising neuroprotective approaches based on the molecular signaling are analyzed for the treatment of optic neuropathies.
Clinical and genetic abnormalities in patients with Friedreich's ataxia.

BACKGROUND Friedreich's ataxia, the most common inherited ataxia, is associated with a mutation that consists of an unstable expansion of GAA repeats in the first intron of the frataxin gene on chromosome 9, which encodes a protein of unknown function. METHODS We studied 187 patients with autosomal recessive ataxia, determined the size of the GAA expansions, and analyzed the clinical manifestations in relation to the number of GAA repeats and the duration of disease. RESULTS One hundred forty of the 187 patients, with ages at onset ranging from 2 to 51 years, were homozygous for a GAA expansion that had 120 to 1700 repeats of the trinucleotides. About one quarter of the patients, despite being homozygous, had atypical Friedreich's ataxia; they were older at presentation and had intact tendon reflexes. Larger GAA expansions correlated with earlier age at onset and shorter times to loss of ambulation. The size of the GAA expansions (and particularly that of the smaller of each pair) was associated with the frequency of cardiomyopathy and loss of reflexes in the upper limbs. The GAA repeats were unstable during transmission. CONCLUSIONS The clinical spectrum of Friedreich's ataxia is broader than previously recognized, and the direct molecular test for the GAA expansion on chromosome 9 is useful for diagnosis, determination of prognosis, and genetic counseling.
Letter: Sand pneumoconiosis in an egyptian mummy.

membrane-active non-beta-blocking D-isomer of propranotol has no hypotensive effect. The same is true of angina pectoris,I and even of arrhythmias.7 It was emphasized in discussion at the sotaiol symposisum that the cardiac inhibitory effects of beta Nblodtng drugs at the dosage used in man was a function of beta-blodkde and nothing -to do with the membranestabilizing action of these drugs. 2 This has been amply suppor.ted by an;imal work.8 It is quite untrue 'to sy that there is any evidence to suggest thamt the membrane-stabilizing action of betareceptor-bJocking drugs is concerned in the production of lef-t ventricular failure in susceptible subjects. All effective betareceptor-inhibiting drugs are likely to precipitate heart failure in paients in whom cardiac function is cri-tically dependent on increased sympathetic activity,2 a predictable effect, as such a pharmacokogical action is interfering with the compensatory tachycardia of cardiac insufficiency. Again experimental work suggests that it is betablockade per se-not membrane activity or intrinsic sympathetic activitythat is relevant in producing this action.9 Tis conclusion was not effectively dhalenged aft the sotalol symposium. Secondly, it is premature and almost cerainly untrue to suggest that in hypertension sotalol is independent of plasma renin levels unlike propranolol. While Verniory et al.10 found no correlation between plasma renin and the response of hy,pertensive patients 'to sotalol, so others have failed to find such a correlation with other betabWocking drugs," 12 though this remains very much a matter for debate. While the mode of beta-receptor-blocking drugs in hypertension is stilil disputed, it is unlikely tat there is a difference between one beta-bloking agent and anotber. -I am, etc.,
Thin‐skinned deformation of sedimentary rocks in Valles Marineris, Mars

Deformation of sedimentary rocks is widespread within Valles Marineris, characterized by both plastic and brittle deformation identified in Candor, Melas, and Ius Chasmata. We identified four deformation styles using HiRISE and CTX images: kilometer-scale convolute folds, detached slabs, folded strata, and pull-apart structures. Convolute folds are detached rounded slabs of material with alternating dark- and light-toned strata and a fold wavelength of about 1 km. The detached slabs are isolated rounded blocks of material, but they exhibit only highly localized evidence of stratification. Folded strata are composed of continuously folded layers that are not detached. Pull-apart structures are composed of stratified rock that has broken off into small irregularly shaped pieces showing evidence of brittle deformation. Some areas exhibit multiple styles of deformation and grade from one type of deformation into another. The deformed rocks are observed over thousands of kilometers, are limited to discrete stratigraphic intervals, and occur over a wide range in elevations. All deformation styles appear to be of likely thin-skinned origin. CRISM reflectance spectra show that some of the deformed sediments contain a component of monohydrated and polyhydrated sulfates. Several mechanisms could be responsible for the deformation of sedimentary rocks in Valles Marineris, such as subaerial or subaqueous gravitational slumping or sliding and soft sediment deformation, where the latter could include impact-induced or seismically induced liquefaction. These mechanisms are evaluated based on their expected pattern, scale, and areal extent of deformation. Deformation produced from slow subaerial or subaqueous landsliding and liquefaction is consistent with the deformation observed in Valles Marineris.
FROM COMPRESSIVE SPECTRAL-POLARIMETRIC IMAGE DATA

We present simulation-based studies of the use of compressively sensed spectral-polarimetric spatial image data from a solar-illuminated reflecting surface to recover its material signature, three-dimensional (3D) shape, pose, and degree of surface roughness. The spatial variations of the polarimetric BRDF around glint points contain unique information about the shape and roughness of the reflecting surface that is revealed most dramatically in polarization-difference maps from which the spatially generalized diffuse-scattering contibutions to brightness are largely absent. Here we employ a specific compressed-sensing protocol, the so-called Coded-Aperture Snapshot Spectral Polarimetric Imager advanced recently by Tsai and Brady, to simulate noisy measurements from which these surface attributes are recovered in a sequential manner. Even in the presence of additive sensor noise, the recovery of these surface attributes for roughened, highly reflecting surfaces seems to be quite robust.
Neutrophil-derived S100A12 in acute lung injury and respiratory distress syndrome

Objective:Both persistent accumulation and activation of neutrophils may contribute to the most severe form of acute lung injury, acute respiratory distress syndrome. We analyzed the expression of neutrophil-derived S100A12 and the proinflammatory receptor for advanced glycation end products (RAGE) in patients with acute respiratory distress syndrome. Additional in vivo and in vitro experiments were performed to further analyze the contribution of S100A12 to pulmonary inflammation. Subjects:We included 14 patients with acute respiratory distress syndrome and eight controls. In addition, 16 healthy subjects were included in an experimental lipopolysaccharide challenge model. Interventions:Concentrations of S100A12 and soluble RAGE were analyzed in bronchoalveolar lavage fluid. The expression of S100A12 and RAGE in lung biopsies from patients was analyzed by immunohistochemistry. S100A12 was also analyzed in bronchoalveolar lavage fluid from eight healthy subjects after challenge with lipopolysaccharide and compared with eight controls who received placebo inhalation. Effects of S100A12 on endothelial cells were analyzed in vitro. Main Results:Patients with acute respiratory distress syndrome had significantly enhanced pulmonary S100A12 expression and higher S100A12 protein concentrations in bronchoalveolar lavage fluid than controls. Levels of soluble RAGE were not significantly elevated in acute respiratory distress syndrome. S100A12 concentrations decreased with time from disease onset. In healthy volunteers, S100A12 was elevated in bronchoalveolar lavage fluid after lipopolysaccharide inhalation. In vitro experiments confirmed strong proinflammatory effects of human S100A12. Conclusions:S100A12 and its receptor RAGE are found at high concentrations in pulmonary tissue and bronchoalveolar lavage fluid in acute lung injury. S100A12 expression may reflect neutrophil activation during lung inflammation and contribute to pulmonary inflammation and endothelial activation via binding to RAGE.
Neutropenia associated with the comedication of quetiapine and valproate in 2 elderly patients.

To the Editors: Quetiapine is an atypical antipsychotic that is widely used in the treatment of schizophrenia and mood disorders. Compared with clozapine, other atypical antipsychotics including quetiapine are considered to have less hematologic toxicity. However, numerous cases of quetiapine-induced neutropenia have been recently reported. The hematologic toxicity of quetiapine occurs more frequently when comedication is involved. One study showed that the incidence and severity of neutropenia are greater with the combined treatment of quetiapine and valproate than with quetiapine used as monotherapy in children and adolescents. However, such adverse effect may not be limited to younger patients. We report 2 elderly patients with neutropenia when receiving combined treatment with quetiapine and valproate.
Visualization of Helicobacter Species Within the Murine Cecal Mucosa Using Specific Fluorescence In Situ Hybridization

Background. Members of the genus Helicobacter have been associated with colitis development in a number of immunodeficient animal models. While it is known that these organisms can initiate colitis development, the location and spatial distribution of these bacteria within the intestinal tract is currently unknown. In this study, we developed and optimized fluorescence in situ hybridization (FISH) probes specifically for Helicobacter species.
Measles virus synthesizes both leaderless and leader-containing polyadenylated RNAs in vivo

The minus-sense RNA genome of measles virus serves as a template for synthesizing plus-sense RNAs of genomic length (antigenomes) and subgenomic length [poly(A)+ RNAs]. To elucidate how these different species are produced in vivo, RNA synthesized from the 3'-proximal N gene was characterized by Northern RNA blot and RNase protection analyses. The results showed that measles virus produced three size classes of plus-sense N-containing RNA species corresponding to monocistronic N RNA, bicistronic NP RNA, and antigenomes. Unlike vesicular stomatitis virus, measles virus does not produce a detectable free plus-sense leader RNA. Instead, although antigenomes invariably contain a leader sequence, monocistronic and bicistronic poly(A)+ N-containing RNAs are synthesized either without or with a leader sequence. We cloned and characterized a full-length cDNA representing a product of the latter type of synthesis. mRNAs and antigenomes appeared sequentially and in parallel with leaderless and leader-containing RNAs. These various RNA species accumulated concurrently throughout infection. However, cycloheximide preferentially inhibited accumulation of antigenomes and leader-containing RNA but not leaderless and subgenomic RNAs late in infection, suggesting that synthesis of the former RNA species requires a late protein function or a continuous supply of structural proteins or both. These results reveal a previously undescribed mechanism for RNA synthesis in measles virus.
RAB2A controls MT1‐MMP endocytic and E‐cadherin polarized Golgi trafficking to promote invasive breast cancer programs

The mechanisms of tumor cell dissemination and the contribution of membrane trafficking in this process are poorly understood. Through a functional siRNA screening of human RAB GTPases, we found that RAB2A, a protein essential for ER‐to‐Golgi transport, is critical in promoting proteolytic activity and 3D invasiveness of breast cancer (BC) cell lines. Remarkably, RAB2A is amplified and elevated in human BC and is a powerful and independent predictor of disease recurrence in BC patients. Mechanistically, RAB2A acts at two independent trafficking steps. Firstly, by interacting with VPS39, a key component of the late endosomal HOPS complex, it controls post‐endocytic trafficking of membrane‐bound MT1‐MMP, an essential metalloprotease for matrix remodeling and invasion. Secondly, it further regulates Golgi transport of E‐cadherin, ultimately controlling junctional stability, cell compaction, and tumor invasiveness. Thus, RAB2A is a novel trafficking determinant essential for regulation of a mesenchymal invasive program of BC dissemination.
A 56-to-66 GHz quadrature phase-locked loop with a wide locking range divider chain in 65nm CMOS

A low power and low phase noise phase-locked loop (PLL) is proposed in this paper to provide a quadrature millimeter-wave source for the 60GHz direct-conversion transceiver. An in-phase injection-coupled quadrature voltage controlled oscillator (IPIC-QVCO) [1] whose symmetric coupling structure is composed of four diode-connected transistors is implemented to optimize both phase noise and phase error. Besides, a novel feedback is proposed in the QVCO to reduce phase noise while remaining the oscillation frequency range unchanged. This PLL employs divider chain with a wide locking range consisting of a digitally controlled injection-locked frequency divider (ILFD) with a 2-bit binary-weighted switch-capacitor bank, 3 current mode logic (CML) dividers, and a multiple modulator divider (MMD). The proposed PLL is designed with a 65nm CMOS technology, and the QCVO achieves a tuning range of 16.39% from 55.95GHz to 65.94GHz with a phase noise of -97.5dBc/Hz at 1MHz offset while consuming 12mW of power. Extensive simulation show that the PLL achieves an excellent phase noise performance of -92dBc/Hz at 1MHz offset and covers all the four required frequency in IEEE802.11ad (58.32GHz, 60.48GHz, 62.64GHz, and 64.80GHz, respectively.) while consuming only 30mW of power from a 1.2 V supply.
New phases in an extended Hubbard model explicitly including atomic polarizabilities.

We consider the influence of a nearest-neighbor Coulomb interaction in an extended Hubbard model and introduce a new interaction term which simulates atomic polarizabilities. This has the effect of screening the on-site Coulomb interaction for charged excitations, unlike a neighbor Coulomb interaction which reduces energies of locally neutral excitations. We find that the spin density to charge density wave phase transition, however, is determined by the unscreened on-site Coulomb repulsion. The order of this phase transition is affected by polarization. We show that new phases appear, one of which is ferroelectric, when atomic polarizabilities are explicitly included.
Autocrine and paracrine mechanisms regulating primordial germ cell proliferation

Although several mitogens and survival factors have been previously shown to act on primordial germ cells (PGCs) in culture, it is not clear whether they are responsible for controlling proliferation of PGCs in the embryo. We show here that during their migratory phase, PGCs do not express FGF‐4, FGF‐8, or FGF‐17, but these FGFs are expressed by neighboring cells. Thus, any FGF action on migrating PGCs would appear to be through a paracrine mechanism. We found that after entering into the gonads, PGCs start to express FGF‐4 and FGF‐8. On this basis, we hypothesize that FGF signaling is involved in both a paracrine manner in initiating PGC proliferation during their migration and an autocrine manner in sustaining PGC proliferation after their arrival in the gonads. We then studied the role of soluble stem cell factor (SCF), which acts as a survival factor or a mitogen in culture, to determine whether it interacts with FGFs. We found that SCF has a complex effect on PGC proliferation. On one hand, soluble SCF promoted PGC proliferation synergistically with FGF in the absence of membrane‐bound SCF. Conversely, soluble SCF inhibited FGF‐stimulated proliferation of PGCs in the presence of membrane‐bound SCF. We account for these findings in a model involving regulation of PGC proliferation, in which SCF modulates the response to FGFs. Mol. Reprod. Dev. 68: 5–16, 2004. © 2004 Wiley‐Liss, Inc.
Future therapeutic options in food allergy

Up to 5% of young children and 2% of adults suffer from food allergy. Among them many have immunoglobulin E (IgE)‐mediated food allergy, a condition with potentially fatal allergic reactions. Several studies have addressed possible definite treatment options for food allergy. Immunotherapy, by the oral route or by systemic injections shows promising preliminary results, but current interpretation of these therapeutic options are mostly handicapped by studies with insufficient scientific support, or by severe side‐effects. Currently, no studies can support pharmacotherapy. Finally, most promising results were recently published with anti‐IgE antibodies in a human trial, or various approaches in a mouse model of food allergy (chinese herbal medicine, specific modulation of the T cell response). Rapidly evolving findings might provide hope for a cure of food allergy in the near future.
Small GTP-Binding Proteins and Membrane Biogenesis in Plants

One of the amazing features of the cellular machinery is that all organeller and membrane proteins, as well as those destined for secretion, have an attached address label for targeting to a specific site. Following synthesis, these proteins are folded, shipped, delivered, and received at the right compartment. Their assigned functions are performed only when they are properly placed at a designated site in the cell. Membrane vesicles play an essential role in protein transport as carriers of specific proteins to intracellular compartments. This process begins immediately after perception of specific signals and involves membrane ruffling, budding and transport of ER vesicles, fusion and passage through the Golgi, and release of vesicles from trans-Golgi cisternae to target to the vacuoles and plasma membrane. The components of the vesicle-mediated protein trafficking system are not, however, well defined. It is not known what kind of biochemical principles are operative for unidirectional transport of vesicles. How are vesicles fused to the target compartment? Although much remains to be understood, many studies from yeast and mammalian systems have identified some key players in this pathway. Isolation of plant homologs of some of these proteins has confirmed that these steps are conserved in evolution and must involve well-defined reactions. We focus here on the relevance of small GTP-binding proteins in vesicle-mediated protein transport (for earlier reviews, see Balch, 1990; Bednarek and Raikhel, 1992; Pryer et al., 1992; Terryn et al., 1993; Zerial and Stenmark, 1993).
Giant Intracranial Aneurysms at 7T MRI

Seven giant intracranial aneurysms were evaluated, and 2 aneurysms were available for histopathologic examination. Aneurysm walls were depicted as hypointense in TOF-MRA and SWI sequences with excellent contrast ratios to adjacent brain parenchyma. A triple-layered microstructure of the aneurysm walls was visualized in all aneurysms in TOF-MRA and SWI. This could be related to iron deposition in the wall, and similar findings were seen in 2 available histopathologic specimens. In vivo 7T TOF-MRA and SWI can delineate the aneurysm wall and the triple-layered wall microstructure in giant intracranial aneurysms. SUMMARY: Giant intracranial aneurysms are rare vascular pathologies associated with high morbidity and mortality. The purpose of this in vivo study was to assess giant intracranial aneurysms and their wall microstructure by 7T MR imaging, previously only visualized in histopathologic examinations. Seven giant intracranial aneurysms were evaluated, and 2 aneurysms were available for histopathologic examination. Six of 7 (85.7%) showed intraluminal thrombus of various sizes. Aneurysm walls were depicted as hypointense in TOF-MRA and SWI sequences with excellent contrast ratios to adjacent brain parenchyma (range, 0.01–0.60 and 0.58–0.96, respectively). The triple-layered microstructure of the aneurysm walls was visualized in all aneurysms in TOF-MRA and SWI. This could be related to iron deposition in the wall, similar to the findings in 2 available histopathologic specimens. In vivo 7T TOF-MRA and SWI can delineate the aneurysm wall and the triple-layered wall microstructure in giant intracranial aneurysms.
Crushed Septal Cartilage Graft in Rhinoplasty and Nasal Septal Surgery : Clinical Outcomes and Complications

Objectives: To assess clinical outcomes and complications with the use of crushed septal cartilage graft in rhinoplasty and nasal septal surgery. Method: A prospective clinical study has done at a tertiary referral centre included 32 patients who underwent crushed cartilage grafting during rhinoplasty and nasal septal surgery with autogenous septal cartilage as the graft material. Slight or moderately crushed septal cartilage grafts were used to augment nasal dorsum, nasal tip and for septal correction. Photographic and endoscopic assessment was done preoperatively and postoperatively at 10th day, 1, 3 and 6 months to assess clinical outcomes and complications including graft resorption, warping, extrusion and any postoperative deformity. Result: Among 32 patients, 19 underwent rhinoplasty and rest 13 nasal septal correction. Complications encountered were postoperative deformity in 3 patients of rhinoplasty and persistent septal deviation in 2 patients of septoplasty. There was no graft resorption, rejection, or extrusion. Conclusion: Crushed cartilage appears to be a good graft material to conceal nasal irregularities and fill nasal dorsal defects in rhinoplasty and to obtain good functional outcomes in septoplasty.