Miracle-dz/UniFAR-FTUs huggingface dataset:
An Angiotensin II Type 1 Receptor Mutant Lacking Epidermal Growth Factor Receptor Transactivation Does Not Induce Angiotensin II–Mediated Cardiac Hypertrophy

We have shown previously that tyrosine 319 in a conserved YIPP motif in the C terminus of angiotensin II (Ang II) type 1 receptors (AT1Rs) is essential for transactivation of epidermal growth factor receptor (EGFR) in vitro. We hypothesized that the signaling mechanism mediated through the specific amino acid sequence in the G protein–coupled receptor plays an important role in mediating cardiac hypertrophy in vivo. Transgenic mice with cardiac-specific overexpression of wild-type AT1R (Tg-WT) and an AT1R with a mutation in the YIPP motif (Tg-Y319F) were studied. Tg-Y319F mice developed no significant cardiac hypertrophy, in contrast to the significant development of hypertrophy in Tg-WT mice. Expression of fetal-type genes, such as atrial natriuretic factor, was also significantly lower in Tg-Y319F than in Tg-WT mice. Infusion of Ang II caused an enhancement of hypertrophy in Tg-WT mice but failed to induce hypertrophy in Tg-Y319F mice. Left ventricular myocardium in Tg-Y319F mice developed significantly less apoptosis and fibrosis than that in Tg-WT mice. EGFR phosphorylation was significantly inhibited in Tg-Y319F mice, confirming that EGFR was not activated in Tg-Y319F mouse hearts. In contrast, activation/phosphorylation of protein kinase C, STAT3, extracellular signal-regulated kinase, and Akt and translocation of G&agr;q/11 to the cytosolic fraction were maintained in Tg-Y319F hearts. Furthermore, a genetic cross between Tg-WT and transgenic mice with cardiac-specific overexpression of dominant negative EGFR mimicked the phenotype of Tg-Y319F mice. In conclusion, overexpression of AT1-Y319F in cardiac myocytes diminished EGFR transactivation and inhibited a pathological form of cardiac hypertrophy. The YIPP motif in the AT1R plays an important role in mediating cardiac hypertrophy in vivo.
Targeted elimination of prostate cancer by genetically directed human T lymphocytes.

The genetic transfer of antigen receptors is a powerful approach to rapidly generate tumor-specific T lymphocytes. Unlike the physiologic T-cell receptor, chimeric antigen receptors (CARs) encompass immunoglobulin variable regions or receptor ligands as their antigen recognition moiety, thus permitting T cells to recognize tumor antigens in the absence of human leukocyte antigen expression. CARs encompassing the CD3zeta chain as their activating domain induce T-cell proliferation in vitro, but limited survival. The requirements for genetically targeted T cells to function in vivo are less well understood. We have, therefore, established animal models to assess the therapeutic efficacy of human peripheral blood T lymphocytes targeted to prostate-specific membrane antigen (PSMA), an antigen expressed in prostate cancer cells and the neovasculature of various solid tumors. In vivo specificity and antitumor activity were assessed in mice bearing established prostate adenocarcinomas, using serum prostate-secreted antigen, magnetic resonance, computed tomography, and bioluminescence imaging to investigate the response to therapy. In three tumor models, orthotopic, s.c. , and pulmonary, we show that PSMA-targeted T cells effectively eliminate prostate cancer. Tumor eradication was directly proportional to the in vivo effector-to-tumor cell ratio. Serial imaging further reveals that the T cells must survive for at least 1 week to induce durable remissions. The eradication of xenogeneic tumors in a murine environment shows that the adoptively transferred T cells do not absolutely require in vivo costimulation to function. These results thus provide a strong rationale for undertaking phase I clinical studies to assess PSMA-targeted T cells in patients with metastatic prostate cancer.
Impacts of diesel and residual fuel oil on Antarctic marine invertebrates

This thesis examines the relative toxicity of three fuels to Antarctic marine invertebrates. Fuel toxicity was related to chemical composition, and responses of biota were complex, being dependent on species, life stage, and exposure duration. Antarctic diesel was most toxic (based on lethal responses) following short term exposures, while intermediate fuel oil and marine gas oil were generally more toxic during longer exposures. Juvenile amphipods were mostly more sensitive than adults, and larval sea urchins more sensitive than embryos. Sub-lethal behavioural responses provided rapid and sensitive endpoints for inclusion in assessing ecological risks associated with fuel use in polar waters.
Expression of Semaphorin 3C in Breast Cancer and its Impact on Adhesion and Invasion of Breast Cancer Cells.

BACKGROUND The aim of the current study was to examine the role of semaphorin 3C (SEMA3C) in breast cancer. MATERIALS AND METHODS SEMA3C transcripts expressed by breast tissues were determined using real-time polymerase chain reaction (PCR). Knock-down of SEMA3C was performed in MDA-MB-231 and MCF-7 breast cancer cell lines using anti-SEMA3C hammerhead ribozyme transgenes. The effect of SEMA3C knockdown on cancer cells was determined using in vitro cellular function assays. RESULTS Higher SEMA3C transcript levels were significantly associated with poor differentiation of cancer cells, and transcript levels were significantly reduced in oestrogen receptor-positive tumours. Knock-down of SEMA3C expression resulted in a decrease in cell proliferation, adhesion and invasion of breast cancer cells. CONCLUSION Higher SEMA3C expression is correlated with tumour differentiation. Inhibition of SEMA3C reduces adhesion and invasion of breast cancer cells. This suggests that SEMA3C may play a significant role in morphological changes of cancer cells, leading to enhanced growth and dissemination.
Neuropsychological underpinnings of the dynamics of bipolar disorder

Although we have gained enormous insights into neurobiological and psychological underpinnings of bipolar disorder (BD) symptoms, our knowledge concerning pathogenic mechanisms initiating recurrent affective episodes is still fragmentary. Previous research has highlighted the role of significant life events and social rhythm in recurrent episodes of mania and depression. However, most studies share the drawback of retrospective self-report data, which are prone to recall biases and limited introspective abilities. Therefore, more objective data, such as neuropsychological and neurobiological measures are needed to further unravel the pathogenic mechanisms of the dynamics of bipolar disorder. Previous research has highlighted disturbed emotional reactivity as well as impaired emotion regulation and impulse control as major behavioural characteristics of BD and aberrancies in prefrontal–limbic–striatal networks that have been proposed to be the correlates of these behavioural alterations. However, longitudinal studies assessing these neural and behavioural alterations are rare. Future research should therefore adopt prospective study designs including behavioural and neuroimaging measures underlying cognitive, emotional and motivational deficits in bipolar disorder. Particularly, these measures should be collected continuously at multiple time points as implemented in modern ambulatory assessment tools.
Human Cytokine Genetic Variants Associated With HBsAg Reverse Seroconversion in Rituximab-Treated Non-Hodgkin Lymphoma Patients

AbstractHepatitis B virus (HBV) reactivation has been noted in HBV surface antigen (HBsAg)-seronegative patients with CD20+ B-cell non-Hodgkin lymphoma (NHL) undergoing rituximab treatment. Clinically, hepatitis flares are usually associated with the reappearance of HBsAg (reverse seroconversion of HBsAg, HBV-RS). It is unclear whether human genetic factors are related to rituximab-associated HBV reactivation.Unvaccinated HBsAg-seronegative adults (n = 104) with CD20+ NHL who had received rituximab-containing therapy without anti-HBV prophylaxis were enrolled. Eighty-nine candidate single nucleotide polymorphisms (SNPs) of 49 human cytokine genes were chosen and were analyzed using the iPLEX technique. Competing risk regression was used to identify the factors associated with HBV-RS.Participants had a median age of 66.1 years and 56.7% were male (n = 59). The anti-HBs and anti-HBc positivity rates were 82.4% and 94.1%, respectively, among patients for whom data were available (approximately 81%). A mean of 7.14 cycles of rituximab therapy were administered, and a total of 14 (13.4%) patients developed HBV-RS. Nine SNPs showed significant differences in frequency between patients with or without HBV-RS: CD40 rs1883832, IL4 rs2243248 and rs2243263, IL13 rs1295686, IL18 rs243908, IL20 rs1518108, and TNFSF13B rs12428930 and rs12583006. Multivariate analysis showed that ≥6 cycles of rituximab therapy, IL18 rs243908, and the IL4 haplotype rs2243248∼rs2243263 were independently associated with HBV-RS. The IL4 haplotype rs2243248∼rs2243263 was significantly associated with HBV-RS regardless of anti-HBs status.Polymorphisms in human cytokine genes impact the risk of rituximab-associated HBV-RS.
Fast Recovery and Low Cost Coexist: When Continuous Data Protection Meets the Cloud

SUMMARY Cloud computing has rising as a new popular service paradigm with typical advantages as ease of use, unlimited resources and pay-as-you-go pricing model. Cloud resources are more ﬂexible and cost-e ﬀ ective than private or colocation resources thus more suitable for storing the outdated backup data that are infrequently accessed by continuous data protection (CDP) systems. However, the cloud achieves low cost at the same time may slow down the recovery procedure due to its low bandwidth and high latency. In this paper, a novel block-level CDP system architecture: MYCDP is proposed to utilize cloud resources as the back-end storage. Unlike traditional delta-encoding based CDP approaches which should traverse all the dependent versions and decode the recovery point, MYCDP adopts data deduplication mechanism to eliminate data redundancy between all versions of all blocks, and constructs a version index for all versions of the protected storage, thus it can use a query-and-fetch process to recover version data. And with a speciﬁc version index data structure and a disk / memory hybrid cache module, MYCDP reduces the storage space consumption and data transfer between local and cloud. It also supports deletion of arbitrary versions without risk of invalidating some other versions. Experimental results demonstrate that MYCDP can achieve much lower cost than traditional local based CDP approaches, while remaining almost the same recovery speed with the local based deduplication approach for most recovery cases. Furthermore, MYCDP can obtain both faster recovery and lower cost than cloud based delta-encoding CDP approaches for any recovery points. And MYCDP gets more proﬁts while protecting multiple systems together.
Influence of the Southern Annular Mode on the sea ice-ocean system: the role of the thermal and mechanical forcing

Abstract. The global sea ice-ocean model ORCA2-LIM is used to investigate the impact of the thermal and mechanical forcing associated with the Southern Annular Mode (SAM) on the Antarctic sea ice-ocean system. The model is driven by idealized forcings based on regressions between the wind stress and the air temperature at one hand and the SAM index the other hand. The wind-stress component strongly affects the overall patterns of the ocean circulation with a northward surface drift, a downwelling at about 45° S and an upwelling in the vicinity of the Antarctic continent when the SAM is positive. On the other hand, the thermal forcing has a negligible effect on the ocean currents. For sea ice, both the wind-stress (mechanical) and the air temperature (thermal) components have a significant impact. The mechanical part induces a decrease of the sea ice thickness close to the continent and a sharp decrease of the mean sea ice thickness in the Weddell sector. In general, the sea ice area also diminishes, with a maximum decrease in the Weddell Sea. On the contrary, the thermal part tends to increase the ice concentration in all sectors except in the Weddell Sea, where the ice area shrinks. This thermal effect is the strongest in autumn and in winter due to the larger temperature differences associated with the SAM during these seasons. The sum of the thermal and mechaninal effects gives a dipole response of sea ice to the SAM, with a decrease of the ice area in the Weddell Sea and around the Antarctic Peninsula and an increase in the Ross and Amundsen Seas during high SAM years. This is in good agreement with the observed response of the ice cover to the SAM.
Water stress affects the germination, emergence, and growth of different sorghum cultivars

Two experiments were conducted to study the effects of water deficit stress on the germination, emergence and seedling growth of sorghum [ Sorghum bicolor (L.) Moench] using Completely Randomised Block Design in four replications. Five sorghum cultivars (Jigurti, Gambella 1107, Meko, 76 T1 #23 and P9403) were evaluated under three water deficit stress treatments (0, -0.20 and -0.85 MPa) using PEG as an osmoticum (Experiment I) and under four varying growing media water contents (100, 60, 40 and 20% of field capacity) using sand (Experiment II). In both experiments, water deficit stress significantly reduced the rate and percentage of germination and emergence and early seedlings growth. Coleoptile, mesocotyl, radicle, and seedling shoot and root lengths, as well as root area were adversely affected by water deficit stress. Cultivars differed in the rate and percentage of germination, and emergence and seedling growth. Gambella 1107, Meko and P9403 had significantly (P Keywords : emergence, germination, seedling growth, sorghum, water deficit SINET: Ethiopian Journal of Science Vol. 28(2) 2005: 119-128
Closure Property of Space-Bounded Two-Dimensional Alternating Turing Machines, Pushdown Automata, and Counter Automata

This paper investigates closure property of the classes of sets accepted by space-bounded two-dimensional alternating Turing machines (2-atm's) and space-bounded two-dimensional alternating pushdown automata (2-apda's), and space-bounded two-dimensional alternating counter automata (2-aca's). Let L(m, n): N2 → N (N denotes the set of all positive integers) be a function with two variables m (= the number of rows of input tapes) and n (= the number of columns of input tapes). We show that (i) for any function f(m) = o(log m) (resp. f(m) = o(log m/log log m)) and any monotonic nondecreasing function g(n) space-constructible by a two-dimensional Turing machine (2-Tm) (resp. two-dimensional pushdown automaton (2-pda)), the class of sets accepted by L(m,n) space-bounded 2-atm's (2-apda's) is not closed under row catenation, row + or projection, and (ii) for any function f(m) = o(m/log) (resp. for any function f(m) such that log f(m) = o(log m)) and any monotonic nondecreasing function g(n) space-constructible by a two-dimensional counter automaton (2-ca), the class of sets accepted by L(m, n) space-bounded 2-aca's is not closed under row catenation, row + or projection, where L(m, n) = f(m) + g(n) (resp. L(m, n) = f(m) × g(n)).
Semiflexible polymer conformation, distribution and migration in microcapillary flows

The flow behavior of a semiflexible polymer in microchannels is studied using multiparticle collision dynamics, a particle-based hydrodynamic simulation technique. Conformations, distributions, and radial cross-streamline migration are investigated for various bending rigidities, with persistence lengths Lp in the range 0.5 ≤ Lp/Lr ≤ 30. The flow behavior is governed by the competition between a hydrodynamic lift force and steric repulsion from the wall, which lead to migration away from the wall, and a locally varying flow induced orientation, which drives the polymer away from the channel center and towards the wall. The different dependences of these effects on the polymer bending rigidity and the flow velocity results in a complex dynamical behavior. However, a generic effect is the appearance of a maximum in the monomer and the center-of-mass distributions, which occurs at the channel center for small flow velocities, but moves off-center at higher velocities.
Developmental Patterns and Cell Lineages of Vermiform Embryos in Dicyemid Mesozoans

Patterns of cell division and cell lineages of the vermiform embryos of dicyemid mesozoans were studied in four species belonging to four genera: Conocyema polymorpha, Dicyema apalachiensis, Microcyema vespa, and Pseudicyema nakaoi. During early development, the following common features were apparent: (1) the first cell division produces prospective cells that generate the anterior peripheral region of the embryo; (2) the second cell division produces prospective cells that generate the posterior peripheral region plus the internal cells of the embryo; (3) in the lineage of prospective internal cells, several divisions ultimately result in cell death of one of the daughter cells. Early developmental processes are almost identical in the vermiform embryos of all four dicyemid genera. The cell lineages appear to be invariant among embryos and are highly conserved among species. Species-specific differences appear during later stages of embryogenesis. The number of terminal divisions determines variations in peripheral cell numbers among genera and species. Thus, the numbers of peripheral cells are fixed and hence species-specific.
EFFECT OF P-GLYCOPROTEIN ON INTESTINAL ABSORPTION AND BRAIN PENETRATION OF ANTIALLERGIC AGENT BEPOTASTINE BESILATE

The antiallergic agent bepotastine besilate is a nonsedating, second-generation H1-antagonist with high oral absorption and negligible distribution into brain. To clarify the role of P-glycoprotein (P-gp) in the pharmacokinetics of bepotastine, intestinal absorption and brain penetration studies were performed. [14C]Bepotastine transport in P-gp-overexpressed LLC-PK1 cells indicated that bepotastine was a substrate of P-gp. The affinity of bepotastine to P-gp estimated by ATPase activity assay was low, with a Km value of 1.25 mM. After i.v. administration, the brain/plasma free concentration ratio in mdr1-knockout mice was 3 times higher than that in wild-type mice. The in situ intestinal absorption studies of [14C]bepotastine in rats showed a clear regional difference, showing highest permeability at the upper part of small intestine with a decreasing permeability in the descending part of small intestine. The apparent absorption rate constant (ka) of [14C]bepotastine in the small intestine was greatly increased by cyclosporin A and verapamil, especially in the distal portion, and the site-specific absorption of [14C]bepotastine disappeared. The concentration dependence of ka of [14C]bepotastine was observed with a higher ka at higher concentration (20 mM) compared with that at lower concentration (1 μM). In conclusion, bepotastine is a substrate for P-gp, and P-gp clearly limited the brain distribution of bepotastine, whereas the effect of P-gp on intestinal absorption of bepotastine was minimal, presumably because of high membrane permeability at the upper region of small intestine where P-gp is less expressed. Such intestinal absorption property of bepotastine is distinctly different from the low membrane-permeable P-gp substrate fexofenadine.
Exposure to Corticosterone Affects Host Resistance, but Not Tolerance, to an Emerging Fungal Pathogen

Host responses to pathogens include defenses that reduce infection burden (i.e., resistance) and traits that reduce the fitness consequences of an infection (i.e., tolerance). Resistance and tolerance are affected by an organism's physiological status. Corticosterone (“CORT”) is a hormone that is associated with the regulation of many physiological processes, including metabolism and reproduction. Because of its role in the stress response, CORT is also considered the primary vertebrate stress hormone. When secreted at high levels, CORT is generally thought to be immunosuppressive. Despite the known association between stress and disease resistance in domesticated organisms, it is unclear whether these associations are ecologically and evolutionary relevant in wildlife species. We conducted a 3x3 fully crossed experiment in which we exposed American toads (Anaxyrus [Bufo] americanus) to one of three levels of exogenous CORT (no CORT, low CORT, or high CORT) and then to either low or high doses of the pathogenic chytrid fungus Batrachochytrium dendrobatidis (“Bd”) or a sham exposure treatment. We assessed Bd infection levels and tested how CORT and Bd affected toad resistance, tolerance, and mortality. Exposure to the high CORT treatment significantly elevated CORT release in toads; however, there was no difference between toads given no CORT or low CORT. Exposure to CORT and Bd each increased toad mortality, but they did not interact to affect mortality. Toads that were exposed to CORT had higher Bd resistance than toads exposed to ethanol controls/low CORT, a pattern opposite that of most studies on domesticated animals. Exposure to CORT did not affect toad tolerance to Bd. Collectively, these results show that physiological stressors can alter a host’s response to a pathogen, but that the outcome might not be straightforward. Future studies that inhibit CORT secretion are needed to better our understanding of the relationship between stress physiology and disease resistance and tolerance in wild vertebrates.
Fourth-generation spinal instrumentation: experience with adolescent idiopathic scoliosis at a tertiary care hospital in Pakistan

Objective To evaluate the radiological and functional outcome of surgical treatment of adolescent idiopathic scoliosis using fourth-generation posterior spinal instrumentation at The Aga Khan University, Karachi, Pakistan. Design Case series. Place and duration of study The Aga Khan University Hospital after a minimum of 2 years postoperatively. Patients and methods A total of 20 patients with adolescent idiopathic scoliosis were recruited into the study and evaluated for radiological and functional outcome. The study period was from 2000 to 2005. Radiological outcome was assessed using Cobb angle measurement pre and postoperatively, hence assessing percentage correction. The lower instrumented vertebra was taken as the neutral vertebra and the level was recorded. Functional outcome was determined using the Scoliosis Research Society patient administered questionnaire. All patients were called to the clinic and asked to fill in the form. Those patients who were out of the city were mailed the forms and requested via telephone to complete and return. Results Of the 20 patients operated on, twelve were female and eight were male. The average age at operation was 12.7 years. The mean Cobb angle was 69° preoperatively and 20° postoperatively, representing a percentage correction of 71%. The average duration of follow-up was 3.6 years. There was one major complication involving neurological injury post-op and two minor complications involving wound infection. The average Scoliosis Research Society score (on a scale of 1–5, with 5 being best) for pain was 4.5, self-image was 4.2, functional status was 4.1, mental status was 3.8, and satisfaction was 4.4. There was no relationship between the percentage correction of scoliosis and the functional outcome. Those patients with a high preoperative Cobb angle tended to have a better outcome for functional and mental status postoperatively. There was no relation between the lower instrumented vertebra and functional outcome. Conclusion In the correct indications, fourth-generation posterior instrumentation and fusion is a reliable and satisfactory technique to treat adolescent idiopathic scoliosis.