Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Mesh Learning for pattern analysis of cognitive processes

We propose a statistical learning model for classifying cognitive processes based on distributed patterns of neural activation in the brain, acquired via functional magnetic resonance imaging (fMRI). In the proposed learning machine, local meshes are formed around each voxel. The distance between voxels in the mesh is determined by using functional neighborhood concept. In order to define functional neighborhood, the similarities between the time series recorded for voxels are measured and functional connectivity matrices are constructed. Then, the local mesh for each voxel is formed by including the functionally closest neighboring voxels in the mesh. The relationship between the voxels within a mesh is estimated by using a linear regression model. These relationship vectors, called Functional Connectivity aware Local Relational Features (FC-LRF) are then used to train a statistical learning machine. The proposed method was tested on a recognition memory experiment, including data pertaining to encoding and retrieval of words belonging to ten different semantic categories. Two popular classifiers, namely k-Nearest Neighbor and Support Vector Machine, are trained in order to predict the semantic category of the item being retrieved, based on activation patterns during encoding. The classification performance of the Functional Mesh Learning model, which range in 62-68% is superior to the classical multi-voxel pattern analysis (MVPA) methods, which range in 40-48%, for ten semantic categories.
Colorectal cancer and diet in an asian population—A case‐control study among Singapore Chinese

A hospital‐based case‐control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low‐, medium‐ and high‐intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p < 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p < 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p < 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta‐carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p < 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non‐dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p < 0.05) and colon cancer alone (OR = 4.39, p < 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.
Effect of Agaricus blazei Murill on the Pulmonary Tissue of Animals with Streptozotocin-Induced Diabetes

The present study was designed to evaluate the oxidative stress as well as the therapeutic effect of Agaricus blazei Muril (A. Blazei) in rats with streptozotocin-induced diabetes. We used 25 Wistar rats, and DM was induced by injecting streptozotocin (70 mg/Kg i.p.). Agaricus blazei Muril was administered daily starting 40 days after disease onset. A. Blazei was tested as an aqueous extract for its phytochemical composition, and its antioxidant activity in vitro was also evaluated. Lipoperoxidation (LPO), and superoxide dismutase (SOD), catalase, and glutathione peroxidase activities were measured in the pulmonary tissue, as well as the presence of inducible nitric oxide synthase (iNOS), through immunohistochemistry. An anatomopathologic study was also performed. Phytochemical screening of A. Blazei detected the presence of alkaloids and saponins. The extract exhibited a significant antioxidant activity in the DPPH-scavenging and the hipoxanthine/xanthine oxidase assays. Pulmonary LPO increased in diabetic animals (0.43 ± 0.09; P < .001) as compared to the control group (0.18 ± 0.02), followed by a reduction in the A. Blazei-treated group (0.33 ± 0.04; P < .05). iNOS was found increased in the lung in diabetic rats and reduced in the A. Blazei-treated group. The pulmonary tissue in diabetic rats showed oxidative alterations related to the streptozotocin treatment. The A. Blazei treatment effectively reduced the oxidative stress and contributed to tissue recovery.
Leukotriene B4 Creates a Favorable Microenvironment for Murine Melanoma Growth

Chronic inflammation has long been associated with neoplastic progression. Our group had recently shown that the addition of a large number of apoptotic tumor cells to the tumor microenvironment induces a potent acute inflammatory reaction capable of promoting melanoma growth; however, primarily necrotizing cells do not cause such a reaction. Here, we show that potent inflammatory agents, such as lipopolysaccharide (LPS) and carrageenan, also promote growth of subtumorigenic doses of melanoma cells, having no effect on melanoma proliferation in vitro. Inhibition of 5-lipoxygenase (5-LOX) seems to have a pivotal role in this model because caffeic acid and MK886, a FLAP (5-LOX–activating protein) inhibitor, partially hindered tumor growth induced by apoptotic cells or LPS. Other enzymes of the arachidonic acid pathway, cyclooxygenase-1 and cyclooxygenase-2, seem to have no participation in this tumor promoter effect, as the inhibitor of both enzymes (indomethacin) did not alter melanoma growth. Leukotriene B4 (LTB4), the main product of the 5-LOX pathway, was able to induce growth of subtumorigenic inocula of melanoma cells, and a LTB4 receptor antagonist inhibited acute inflammation-associated tumor growth. Addition to the tumor inflammatory microenvironment of eicosapentaenoic acid, an ω3-polyunsaturated fatty acid with anti-inflammatory properties, or leukotriene B5, an eicosapentaenoic acid–derived leukotriene, significantly inhibited tumor development. These results give new insights to the mechanisms through which inflammation may contribute to tumor progression and suggest that LOX has an important role in tumor progression associated with an inflammatory state in the presence of apoptosis, which may be a consideration for apoptosis-inducing treatments, such as chemotherapy and radiotherapy. (Mol Cancer Res 2009;7(9):1417–24)
[Evaluation of Cystic Echinococcosis Suspected Patients Applied to National Parasitology Reference Laboratory of Public Health Institution of Turkey Between 2009-2013].

OBJECTIVE Cystic echinococcosis (CE) caused by the metacestode form of Echinococcus granulosus is an important public health problem common in our country. In this study, anti-E. granulosus antibodies were aimed to investigate in the serum samples of CE suspected patients who applied to the National Parasitology Reference Laboratory of Public Health Institution of Turkey. METHODS In the study, serum samples of 2921 patients which were sent to our laboratories from different hospitals between 1 January 2009 and 31 December 2013 were evaluated with at least one of the following tests: Enzyme-Linked Immunosorbent Assay (ELISA), Indirect Hemaglutination Assay (IHA) and Western Blot (WB) techniques. RESULTS Four hundred thirty nine (15.03%) of inspected 2921 samples were determined seropositive with at least one of the methods. When the results analyzed by gender, 13% of males and 16.40% of females were found positive. Examined the distribution of the results by years, with a maximum of 25% positivity was observed in 2009. Compatibility was determined at the rate of 91.4% among ELISA and IHA results; also 89.7% among WB and the other tests results. CONCLUSION Despite the gradual decreases the CE in Ankara and its surroundings, it is still continues to be a major public health problem. Essential prevention and control measures should be taken to reduce the prevalence of the disease. Also in the diagnosis of the disease, more reliable results can obtained with applying two tests (ELISA/IHA) together and confirm the positivity with WB.
Angiotensin-(1-9) Attenuates Cardiac Fibrosis in the Stroke-Prone Spontaneously Hypertensive Rat via the Angiotensin Type 2 Receptor

The renin-angiotensin system regulates cardiovascular physiology via angiotensin II engaging the angiotensin type 1 or type 2 receptors. Classic actions are type 1 receptor mediated, whereas the type 2 receptor may counteract type 1 receptor activity. Angiotensin-converting enzyme 2 metabolizes angiotensin II to angiotensin-(1-7) and angiotensin I to angiotensin-(1-9). Angiotensin-(1-7) antagonizes angiotensin II actions via the receptor Mas. Angiotensin-(1-9) was shown recently to block cardiomyocyte hypertrophy via the angiotensin type 2 receptor. Here, we investigated in vivo effects of angiotensin-(1-9) via the angiotensin type 2 receptor. Angiotensin-(1-9) (100 ng/kg per minute) with or without the angiotensin type 2 receptor antagonist PD123 319 (100 ng/kg per minute) or PD123 319 alone was infused via osmotic minipump for 4 weeks into stroke-prone spontaneously hypertensive rats. We measured blood pressure by radiotelemetry and cardiac structure and function by echocardiography. Angiotensin-(1-9) did not affect blood pressure or left ventricular mass index but reduced cardiac fibrosis by 50% (P<0.01) through modulating collagen I expression, reversed by PD123 319 coinfusion. In addition, angiotensin-(1-9) inhibited fibroblast proliferation in vitro in a PD123 319-sensitive manner. Aortic myography revealed that angiotensin-(1-9) significantly increased contraction to phenylephrine compared with controls after N-nitro-L-arginine methyl ester treatment, an effect abolished by PD123 319 coinfusion (area under the curve: angiotensin-(1-9) N-nitro-L-arginine methyl ester=98.9±11.8%; control+N-nitro-L-arginine methyl ester=74.0±10.4%; P<0.01), suggesting that angiotensin-(1-9) improved basal NO bioavailability in an angiotensin type 2 receptor–sensitive manner. In summary, angiotensin-(1-9) reduced cardiac fibrosis and altered aortic contraction via the angiotensin type 2 receptor supporting a direct role for angiotensin-(1-9) in the renin-angiotensin system.
The Perturbed Variation

We introduce a new discrepancy measure between two distributions that gives an indication on their similarity. The new measure, termed the Perturbed Variation (PV), gives an intuitive interpretation of similarity; it optimally perturbs the distributions so that they best fit each other. The PV is defined between continuous and discrete distributions, and can be efficiently estimated from samples. We provide bounds on the convergence of the estimated score to its distributional value, as well as robustness analysis of the PV to outliers. A number of possible applications of the score are presented, and its ability to detect similarity is compared with that of other known measures on real data. We also present a new visual tracking algorithm based on the PV, and compare its performance with known tracking algorithms.
Practical low-overhead enforcement of memory safety for c programs

The serious bugs and security vulnerabilities that result from C's lack of bounds checking and unsafe manual memory management are well known, yet C remains in widespread use. Unfortunately, C's arbitrary pointer arithmetic, conflation of pointers and arrays, and programmer-visible memory layout make retrofitting C with memory safety guarantees challenging. Existing approaches suffer from incompleteness, have high runtime overhead, or require non-trivial changes to the C source code. Thus far, these deficiencies have prevented widespread adoption of such techniques. This dissertation proposes mechanisms to provide comprehensive memory safety that works with mostly unmodified C code with a low performance overhead. We use a pointer-based approach where we maintain metadata with pointers and check every pointer dereference. To enable compatibility with existing code, we maintain the metadata for the pointers in memory in a disjoint metadata space leaving the memory layout of the program intact. For detecting spatial violations, we maintain bounds metadata with every pointer. For detecting temporal violations, we also maintain a unique identifier metadata with each pointer. This pointer metadata is propagated with pointer operations and checked on pointer dereferences. Coupling disjoint metadata with a pointer-based approach enables comprehensive detection of all memory safety violations in unmodified C programs. This dissertation demonstrates the compatibility of this approach by hardening legacy C/C++ code with minimal source code changes. Further, this dissertation shows the effectiveness of the approach by detecting new memory safety errors and previously known memory safety errors in large code bases. To attain low performance overheads, this dissertation proposes efficient instantiations of this approach (1) within a compiler, (2) within hardware, and (3) with a hybrid hardware accelerated compiler instrumentation that reduces the overhead of enforcing memory safety, and thereby enabling their use in deployed systems.
ROLE OF CELL MEMBRANE FATTY ACIDS IN INSULIN SENSITIVITY IN DIABETIC RATS TREATED WITH FLAXSEED OIL

Introduction: The cell functions involved in the action of insulin receptor binding enzyme and transporter activities are controlled by membrane properties, and the amount of dietary fat as well as the nature of fatty acids regulates various steps in the biosynthesis of membrane phospholipids. Objective: To investigate the effect of flaxseed oil on improving erythrocyte membrane components and insulin sensitivity in diabetic rats. Methods: Thirty two adult male albino rats were used in this study and classified into four groups control, flaxseed oil, diabetic and treated groups. Fasting blood glucose and plasma insulin were estimated. Total lipids in the red blood cells membrane were extracted with chloroform/methanol method. Erythrocyte membrane total lipids, total cholesterol and triglycerides were determined. Fatty acids and phospholipids fractions were measured by HPLC.
On the mechanism of action of the alkylating agents. II. Effects of nitrogen mustard, Myleran, and x-radiation on nucleic acid biosynthesis.

The effects of nitrogen mustard, Myleran, and x-radiation on the incorporation of isotopic orotic acid, aspartic acid, formaldehyde, adenine, and phosphate into the nucleic acids of the L1210 ascites leukemia are reported. The lack of uniformity in the incorporation pattern following pretreatment with each of the three drugs was considered significant. The treatments could result in stimulation as well as inhibition of precursor utilization. It was concluded that the alkylating agents attack numerous sites with varying degrees of specificity.
In vivo protection against NMDA-induced neurodegeneration by MK-801 and nimodipine: combined therapy and temporal course of protection.

Neuroprotection against excitotoxicity by a combined therapy with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the L-type Ca2+ channel blocker nimodipine was examined using an in vivo rat model of NMDA-induced neurodegeneration. Attention was focused on the neuroprotective potential of this combined drug treatment before and after NMDA-exposure. NMDA was unilaterally injected in the magnocellular nucleus basalis (MBN). Neuronal damage was assessed 12 days after the NMDA-injection by measuring the reduction of cholinergic cortical fibres that originate from the MBN neurons. In controls that received no drug treatment, NMDA-exposure damaged MBN neurons such that 66% of the cholinergic terminals were lost in the ipsilateral parietal cortex. Pretreatment with a nimodipine diet (860 ppm) combined with application of MK-801 (5 mg/kg i.p.) before NMDA-exposure reduced fibre loss by 89% thereby providing a near complete neuroprotection. Combined therapy of MK-801 (5 mg/kg i.p.) and nimodipine (15 mg/kg i.p.) 8 min after NMDA-infusion reduced neuronal injury by 82%, while the same combination given 2 h after the excitotoxic treatment still yielded a 66% protection against neurotoxic damage invoked by NMDA. In conclusion, the present data show that a dual blockade of NMDA-channels and voltage-dependent calcium channels (VDCC's) up to 2 h after NMDA-exposure is able to provide a significant protection against NMDA-neurotoxicity.
Variation of the Specificity of the Human Antibody Responses after Tick-Borne Encephalitis Virus Infection and Vaccination

ABSTRACT Tick-borne encephalitis (TBE) virus is an important human-pathogenic flavivirus endemic in large parts of Europe and Central and Eastern Asia. Neutralizing antibodies specific for the viral envelope protein E are believed to mediate long-lasting protection after natural infection and vaccination. To study the specificity and individual variation of human antibody responses, we developed immunoassays with recombinant antigens representing viral surface protein domains and domain combinations. These allowed us to dissect and quantify antibody populations of different fine specificities in sera of TBE patients and vaccinees. Postinfection and postvaccination sera both displayed strong individual variation of antibody titers as well as the relative proportions of antibodies to different domains of E, indicating that the immunodominance patterns observed were strongly influenced by individual-specific factors. The contributions of these antibody populations to virus neutralization were quantified by serum depletion analyses and revealed a significantly biased pattern. Antibodies to domain III, in contrast to what was found in mouse immunization studies with TBE and other flaviviruses, did not play any role in the human neutralizing antibody response, which was dominated by antibodies to domains I and II. Importantly, most of the neutralizing activity could be depleted from sera by a dimeric soluble form of the E protein, which is the building block of the icosahedral herringbone-like shell of flaviviruses, suggesting that antibodies to more complex quaternary epitopes involving residues from adjacent dimers play only a minor role in the total response to natural infection and vaccination in humans. IMPORTANCE Tick-borne encephalitis (TBE) virus is a close relative of yellow fever, dengue, Japanese encephalitis, and West Nile viruses and distributed in large parts of Europe and Central and Eastern Asia. Antibodies to the viral envelope protein E prevent viral attachment and entry into cells and thus mediate virus neutralization and protection from disease. However, the fine specificity and individual variation of neutralizing antibody responses are currently not known. We have therefore developed new in vitro assays for dissecting the antibody populations present in blood serum and determining their contribution to virus neutralization. In our analysis of human postinfection and postvaccination sera, we found an extensive variation of the antibody populations present in sera, indicating substantial influences of individual-specific factors that control the specificity of the antibody response. Our study provides new insights into the immune response to an important human pathogen that is of relevance for the design of novel vaccines.
Laminin α5 Is Required for Dental Epithelium Growth and Polarity and the Development of Tooth Bud and Shape*

In tooth development, the oral ectoderm and mesenchyme coordinately and reciprocally interact through the basement membrane for their growth and differentiation to form the proper shape and size of the tooth. Laminin α5 subunit-containing laminin-10/11 (LM-511/521) is the major laminin in the tooth germ basement membrane. Here, we have examined the role of laminin α5 (Lama5) in tooth development using laminin α5-null mouse primary dental epithelium and tooth germ organ cultures. Lama5-null mice develop a small tooth germ with defective cusp formation and have reduced proliferation of dental epithelium. Also, cell polarity and formation of the monolayer of the inner dental epithelium are disturbed. The enamel knot, a signaling center for tooth germ development, is defective, and there is a significant reduction of Shh and Fgf4 expression in the dental epithelium. In the absence of laminin α5, the basement membrane in the inner dental epithelium becomes discontinuous. In normal mice, integrin α6β4, a receptor for laminin α5, is strongly localized at the basal layer of the epithelium, whereas in mutant mice, integrin α6β4 is expressed around the cell surface. In primary dental epithelium culture, laminin-10/11 promotes cell growth, spreading, and filopodia-like microspike formation. This promotion is inhibited by anti-integrin α6 and β4 antibodies and by phosphatidylinositol 3-kinase inhibitors and dominant negative Rho-GTPase family proteins Cdc42 and Rac. In organ culture, anti-integrin α6 antibody and wortmannin reduce tooth germ size and shape. Our studies demonstrate that laminin α5 is required for the proliferation and polarity of basal epithelial cells and suggest that the interaction between laminin-10/11-integrin α6β4 and the phosphatidylinositol 3-kinase-Cdc42/Rac pathways play an important role in determining the size and shape of tooth germ.
CRL3IBTK Regulates the Tumor Suppressor Pdcd4 through Ubiquitylation Coupled to Proteasomal Degradation

Background: IBtkα is an uncharacterized protein belonging to the family of BTB proteins. Results: IBtkα is the substrate receptor for a Cullin3-dependent ubiquitin ligase promoting ubiquitylation and proteasomal degradation of Pdcd4. Conclusion: By regulating Pdcd4 stability, IBtkα can modulate the translation of specific mRNAs under different cellular conditions. Significance: The identification of new players in the ubiquitin/proteasome pathways contributes to a better understanding of protein homeostasis. The human inhibitor of Bruton's tyrosine kinase isoform α (IBtkα) is a BTB protein encoded by the IBTK gene, which maps to chromosomal locus 6q14.1, a mutational hot spot in lymphoproliferative disorders. Here, we demonstrate that IBtkα forms a CRL3IBTK complex promoting its self-ubiquitylation. We identified the tumor suppressor Pdcd4 as IBtkα interactor and ubiquitylation substrate of CRL3IBTK for proteasomal degradation. Serum-induced degradation of Pdcd4 required both IBtkα and Cul3, indicating that CRL3IBTK regulated the Pdcd4 stability in serum signaling. By promoting Pdcd4 degradation, IBtkα counteracted the suppressive effect of Pdcd4 on translation of reporter luciferase mRNAs with stem-loop structured or unstructured 5′-UTR. IBtkα depletion by RNAi caused Pdcd4 accumulation and decreased the translation of Bcl-xL mRNA, a well known target of Pdcd4 repression. By characterizing CRL3IBTK as a novel ubiquitin ligase, this study provides new insights into regulatory mechanisms of cellular pathways, such as the Pdcd4-dependent translation of mRNAs.