Miracle-dz/UniFAR-FTUs huggingface dataset:
Does neuroinflammation sustain neurodegeneration in ALS?

Amyotrophic lateral sclerosis (ALS), the most prevalent type of motor neuron disease in adults, affecting 4–6 per 100,000, is a fatal neurodegenerative disease. ALS is characterized by the degeneration of both upper motor neurons comprising the corticospinal tract and lower motor neurons arising from the brainstem nuclei and ventral roots of the spinal cord. The only drug approved for ALS—riluzole—provides a modest survival benefit. An improved understanding of the pathophysiology of ALS has potential for the development of more effective therapeutic interventions.
Diabetes mellitus, CYP2C19 genotype, and response to escalating doses of clopidogrel

Summary Both diabetes mellitus (DM) and carriage of the CYP2C19*2 allele are associated with a reduced response to clopidogrel. The relative contributions of these factors and whether higher clopidogrel doses can overcome both factors remain unknown. The objective of this study was to test the ability of clopidogrel doses up to 300 mg daily to decrease platelet reactivity in patients with DM and/or CYP2C19*2. ELEVATE-TIMI 56 randomised 333 patients with coronary artery disease to different maintenance doses of clopidogrel in four treatment periods, each lasting approximately 14 days. On-treatment platelet reactivity was compared between patients stratified by DM, CYP2C19*2 status and clopidogrel dose. Both DM and CYP2C19*2 were independently associated with elevated on-treatment platelet reactivity with clopidogrel 75 mg daily (p<0.0001 for each). With 75 mg, mean on-treatment PRU was progressively higher (p trend <0.001) when evaluating patients: with neither DM nor CYP2C19*2 (150.7; 95 % CI 140.5–162.6), with only DM (187.2; 95 % CI, 171.3–206.9), with only CYP2C19*2 (227.9; 95 % CI, 205.1–250.8), and with both DM and CYP2C19*2 (239.9; 95 % CI, 209.7–270.1). Notably, with 75 mg, patients with only CYP2C19*2 had higher ontreatment platelet reactivity than those with only DM (p=0.0068). To achieve on-treatment platelet reactivity similar to that seen with clopidogrel 75 mg in patients with neither DM nor CYP2C19*2, the following doses were required: 150 mg with only DM, 225 mg with only CYP2C19*2, and 300 mg with both DM and CYP2C19*2. Patients with both DM and CYP2C19*2 required a four-fold increase in clopidogrel maintenance dose as compared to patients without these factors to achieve a similar antiplatelet response.
EMF dose in patients and medical staff during hyperthermia treatment of cancer

At the Erasmus Medical Center, we apply hyperthermia treatments (HT) of cancer in the pelvic area using an electromagnetic applicator installed in a Faraday shielded treatment room. Consequently, medical staff and accompanying persons are exposed to electromagnetic fields (EMF) during treatment. In the past, procedures were defined based on measurements defining compliant areas where the fields are expected to be below the exposure guidelines. Today, advanced electromagnetic models enable more precise dose assessment in the human anatomy and better evaluation of the procedures. The objective of this study was to investigate theoretically if the exposure of medical staff and accompanying persons is compliant to the guidelines when adhering to the procedures. Therefore, the whole-body averaged (SARwb) and spatial-averaged (SAR10g) specific absorption rate was assessed numerically in whole-body models of the patient, medical staff and an accompanying person. We found that predicted fields can exceed the exposure guidelines ten fold. However, the basic restrictions on SARwb and SAR10g are not exceeded for workers, but SARwb can exceed the guideline by a factor of two for accompanying persons that are in close vicinity of the applicator. In conclusion, adhering to the procedures defined in the early nineties is effective in keeping the exposure in medical staff and accompanying persons compliant to the exposure guidelines.
Retraction. Cyclic di-GMP: a second messenger required for long-term survival, but not for biofilm formation, in Mycobacterium smegmatis.

Cyclic di-GMP (c-di-GMP) plays an important role in bacterial adaptation to enable survival in changing environments. It orchestrates various pathways involved in biofilm formation, changes in the cell surface, host colonization and virulence. In this article, we report the presence of c-di-GMP in Mycobacterium smegmatis, and its role in the long-term survival of the organism. M. smegmatis has a single bifunctional protein with both GGDEF and EAL domains, which show diguanylate cyclase (DGC) and phosphodiesterase (PDE)-A activity, respectively, in vitro. We named this protein MSDGC-1. Deletion of the gene encoding MSDGC-1 did not affect growth and biofilm formation in M. smegmatis, but long-term survival under conditions of nutritional starvation was affected. Most of the proteins that contain GGDEF and EAL domains have been demonstrated to have either DGC or PDE-A activity. To gain further insight into the regulation of the protein, we cloned the individual domains, and tested their respective activities. MSDGC-1, the full-length protein, is required for activity, as its GGDEF and EAL domains are inactive when separated.
Conservation of function and regulation within the Cdc28/cdc2 protein kinase family: characterization of the human Cdc2Hs protein kinase in Saccharomyces cerevisiae

Whereas the Cdc28 protein kinase of the budding yeast Saccharomyces cerevisiae plays an essential role in cell cycle progression during the G1 interval, a function in the progression from the G2 interval into M phase has been inferred for its homologs, including the Cdc2Hs protein kinase of humans. To better understand these apparently disparate roles, we constructed a yeast strain in which the resident CDC28 gene was replaced by its human homolog, CDC2Hs. This transgenic yeast strain was able to perform the G1 functions attributed to the Cdc28 protein kinase, including the ability to grow and divide normally, to respond to environmental signals that induce G1 arrest, and to regulate the Cdc2Hs protein kinase appropriately in response to these signals.
Identification of dna components required for induction of cotton leaf curl disease.

Cotton leaf curl disease (CLCuD) is a major constraint to cotton production in Pakistan. Infectious clones of the monopartite begomovirus cotton leaf curl virus (CLCuV), associated with diseased cotton, are unable to induce typical symptoms in host plants. We have identified and isolated a single-stranded DNA molecule approximately 1350 nucleotides in length which, when coinoculated with the begomovirus to cotton, induces symptoms typical of CLCuD, including vein swelling, vein darkening, leaf curling, and enations. This molecule (termed DNA beta) requires the begomovirus for replication and encapsidation. The CLCuV/DNA 1/DNA beta complex, together with a similar complex previously identified in Ageratum conyzoides, represent members of an entirely new type of infectious, disease-causing agents. The implications of this finding to our understanding of the evolution of new disease-causing agents are discussed.
Underlying Graphs of 3-Quasi-Transitive Digraphs and 3-Transitive Digraphs

Abstract A digraph is 3-quasi-transitive (resp. 3-transitive), if for any path x0x1 x2x3 of length 3, x0 and x3 are adjacent (resp. x0 dominates x3). C´esar Hern´andez-Cruz conjectured that if D is a 3-quasi-transitive digraph, then the underlying graph of D, UG(D), admits a 3-transitive orientation. In this paper, we shall prove that the conjecture is true.
Relative impact of childhood and adulthood socioeconomic conditions on cause specific mortality in men

Increasing evidence suggests that social inequality in mortality risk in developed countries is mediated by social and biological chains of risk accumulating over the life course.1 Both childhood and adulthood socioeconomic conditions have been found to be independently associated with mortality risk.2,3 The relative importance of childhood and adulthood social conditions is likely to vary depending on cause of death.4,5 Lack of full life course cohorts with large enough study power prevents many researchers from studying this issue across causes of death. A cohort of all inhabitants in Oslo aged 30–54 years in 1990 was linked to the Census, Tax, and the Death Registers, for 58 751 people. Housing conditions from the 1960 census provided information on childhood social conditions. Six aspects of housing conditions were included in a housing index. This included information on rooms per household capita (0,1,2), type of dwelling (0,1,2), ownership (0,1), toilet (0,1), bath (0,1), and telephone in dwelling (0,1). This was summed for each individual and categorised to five approximately similar size groups. Income information for 1990, derived from taxation authorities, was used as the indicator of social conditions in adult age. Yearly wages, social security benefits, and other earnings were …
An algorithm for multisource beamforming and multitarget tracking

A new algorithm for simultaneous robust multisource beamforming and adaptive multitarget tracking is proposed. Self-robustness to locations errors or variations is introduced by a source-subspace-based tracking procedure of steering vectors in the array manifold. This LMS-type procedure is generalized from a former work we developed in the single source case. Two beamforming structures are actually proposed. The first is adaptive and optimal for uncorrelated sources and correlated noise. The second is conventional and optimal for correlated sources and uncorrelated white noise. The proposed algorithm and MUSIC show an identical asymptotic variance in localization for immobile sources, whereas for the mobile case, the proposed algorithm is highly advantageous. Then, it is shown that the additional use of some kinematic parameters (i.e., speed, acceleration, etc.) inferred from the reconstructed trajectories improves the tracking performance and overcomes some of the problems of crossing targets. The efficiency of multitarget tracking and the robustness of multisource beamforming are proved and then confirmed by simulation. The number of sources can be initialized and tracked by a marginal proposed procedure. The beamforming performance is shown to be optimal as the single source case. Finally, the algorithm has a very low order of arithmetic complexity.
The Partially Diabetic Pancreas: A Histological Study of a New Animal Model

An animal model in which part of the pancreas was made diabetic due to almost total loss of insulin-secreting B cells, while the remainder of the gland remained normal, is described. In rabbits, a vascular clamp was placed across the junction of the body and tail of the pancreas, thus occluding the circulation to the tail. Alloxan (200 mg/kg) was injected i.v. , and 4 min later dextrose (0.5 g/kg) was given by the same route. After a further 2 min the clamp was removed. Thirty-four animals were studied, 17 of which died in the first postoperative week of surgical complications or of alloxan-induced toxicity to the liver and kidneys. The survivors were killed between 4 and 12 weeks after surgery and were not metabolically diabetic. They had a virtually complete absence of B cells but a normal population of A, D, and PP cells in the head and body of the pancreas. The islets in the tail of the pancreas appeared entirely normal. This model appears suitable for studying the effects of locally produced insulin on pancreatic exocrine function in metabolically normal animals.
Fenestrated Capillaries in Mice Submesothelial Mesenteric Microvasculature

This study demonstrates the existence of fenestrated capillaries in the microvascular bed of mice mesentery. The 26.6% incidence of fenestrated capillaries observed in this study is similar to that found in rabbit diaphragmatic peritoneum. Fenestral diameters are too large to be identified as the large pore of Pappenheimer's theory. They appear to be too frequent to become the predicted large pore. Peritoneal permeability should be analyzed on the basis that molecular transfer occurs through multiple ways.
Blocking the Receptor for Interleukin 10 Protects Mice from Lethal Listeriosis

ABSTRACT High doses of Listeria monocytogenes overcome the ability of a normal mouse to control the infection, due to massive bacterial replication. Treatment with an anti-interleukin 10 (IL-10) receptor monoclonal antibody prevented the fatal course of infection with high doses of bacteria. This work shows that blocking the receptor for IL-10 may have useful therapeutic applications.
Pathophysiology of L-Dopa Induced Dyskinesia — Changes in D1/D3 Receptors and Their Signaling Pathway

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic mesencephalic neurons. The most used and successful therapy for this condition is L-3, 4 dihydroxyphenylalanine (L-DOPA), a precursor in the synthesis of dopa‐ mine. However long-term treatment leads to disabling abnormal involuntary movements known as L-DOPA-induced Dyskinesia (LID), which are uncontrolled and repetitive move‐ ment in the axis, arms, legs and oro-facial zone [1-2]. The LID is a serious limitation in the usage of L-DOPA and it can be thought that solving the diskinesia by new therapeutic tar‐ gets could extend the time of treatment with L-DOPA in the parkinsonian patients with an acceptable quality of life. To propose new alternatives is necessary to know the pathogenesis and pathophysiology of this phenomenon.
Up regulation of the Epstein-Barr virus (EBV)-encoded membrane protein LMP in the Burkitt's lymphoma line Daudi after exposure to n-butyrate and after EBV superinfection

The Burkitt's lymphoma line Daudi carries a nontransforming Epstein-Barr virus (EBV) strain that has a deletion in the BamHI WYH region of the genome coding for the EBV nuclear antigen 2 (EBNA-2). Daudi cells fail to express the EBV-encoded latent membrane protein (LMP) (D. Ghosh and E. Kieff, J. Virol. 64:1855-1858, 1990). We show that LMP expression can be up regulated by exposure to n-butyrate and by superinfection with the B95-8 (B virus)- and P3HR1 (P virus)-derived EBV strains. Two LMP polypeptides of 60 and 48 kilodaltons (kDa) were detected in immunoblots of Daudi cells that had been exposed to 3 mM n-butyrate for 24 h. The intensity of the 48-kDa LMP increased during 72 h, in parallel with the appearance of early antigen-positive cells. The 60-kDa LMP was expressed at a low level and remained constant. Superinfection of Daudi cells with B and P virus induced the 60-kDa LMP within 3 h. In addition, P virus induced the 48-kDa LMP at a low level. The B virus-encoded EBNA-2 and EBNA-5 were detected 12 h after superinfection. The B virus-encoded 63-kDa LMP was coexpressed with the endogenous LMP after 48 h. Inactivation of the virus by UV illumination abolished the expression of the B virus-encoded antigens but did not affect the induction of the endogenous LMP. The B-cell activation marker CD23 was up regulated by B virus superinfection but not by n-butyrate exposure. CD23 was also expressed at a higher level in a stable B virus-converted subline, E95A-Daudi, that was EBNA-2 positive and coexpressed the Daudi virus- and B virus-encoded LMP. The results suggest that LMP expression is regulated by the interaction of cellular and viral factors. Binding of the virus to its membrane receptor might be involved in the triggering of cellular control mechanisms. Viral gene products are not directly involved in this function but may contribute to create a permissive cellular environment for LMP expression.
A method of program refactoring based on code clone detection and impact analysis

This paper proposes a method that aggregates similar portions in a program into one common portion and redesigns current program structure to appropriate program structure. When a new function is added to an existing program, the function tends to be developed by copying & pasting a portion in the program and modifying its portion. As a result, it becomes to exist many similar portions in the program. In the case that error modifications or changes occurs in the similar portion, appropriate modifications are required to the all similar portions. It would be considered that the quality and efficiency of those tasks are decreased. So that, this paper proposes a method that detect similar portions with minor modifications and a method that aggregates those similar portions to one appropriate common portion with well-defined program structure. As a result, current program becomes to be refined to the program that can accommodate future modification or changes properly.
Activation of CD40 favors the growth and vascularization of Kaposi's sarcoma.

Although CD40 is expressed by several tumor lines and is up-regulated in tumor vascular endothelium, its role in tumor biology is still unclear. In the present study, we investigated the role of CD40 in the growth and vascularization of Kaposi's sarcoma (KS). In vitro, stimulation of CD40 induced migration of KS cells and inhibited vincristine-induced apoptosis. Similarly, the CD40 engagement on endothelial cells resulted in cell contraction, migration, and prevention of serum withdrawal-apoptosis. To understand the biological relevance of CD40 in vivo, KS cells were engineered to express and release a soluble form of CD40 (KS-sCD40) able to disrupt CD40-CD154 interaction. SCID mice s.c. injected with KS-sCD40 cells developed tumors that were significantly smaller than those induced by control cells (KS-neo). In addition, KS-sCD40 tumors showed several areas of necrosis, diffuse presence of apoptotic cells, and poor vascularization. In contrast, KS-neo tumors showed few or absent areas of necrosis and apoptosis and intense vascularization. Moreover, anti-CD40 Abs stimulated neo-angiogenesis in a murine model in which s.c. implantation of Matrigel was used as a vehicle for the delivery of mediators. These observations provide demonstration that CD40 supports tumor cell survival, growth, and neo-vascularization of KS.
Epstein-Barr virus-associated gastric carcinoma and Epstein-Barr virus infection of the stomach.

BACKGROUND Epstein-Barr virus (EBV) has been found to be associated with a type of gastric carcinoma (EBVaGC). However, many questions remain unanswered, such as epidemiology, and pathologic features of EBVaGC and the significance of EBV in the genesis of EBVaGC. EXPERIMENTAL DESIGN Gastric carcinoma and non-neoplastic mucosa were evaluated to reveal the following issues: the incidence of EBVaGC in Japanese population, pathologic features and EBV genotype, clonality, and gene-expression in EBVaGC, localization of EBV in non-neoplastic stomach, and serum titer of anti-EBV antibodies in EBVaGC-carrying patients. RESULTS Using PCR and EBER1 in situ hybridization, EBVaGC (definitely amplifiable EBV-DNA and positive EBER1-signal in the nuclei of carcinoma cells) was found in 8 of 72 gastric carcinomas (11%). The dominant genotype of EBV was type A (7/8), with type C (6/8), and F (8/8) restriction enzyme polymorphism, which are the predominant type of EBV found in throat washing of the general population in Japan. EBVaGC was found in the cardia (4/8) or body (4/8) of the stomach, and consisted of 7 advanced and 1 intramucosal carcinoma. By Southern blot analysis of EBVaGC hybridized with right- and left-side probe adjacent to the terminal repeats, EBV was present in a monoclonal episomal form in all of the EBVaGC. EBVaGC lacked expression of EBNA2 (0/8) and LMP1 (0/8) by immunocytochemistry. In non-neoplastic mucosa, EBER1 signal was identified in the infiltrating lymphocytes and shedding epithelial cells predominantly in fundic gland mucosa of patients with EBVaGC (8/8). Patients with EBVaGC showed high titers of anti-VCA IgG (8/8), anti-VCA IgA (2/8) and anti-EA IgG (7/8) antibodies just before surgery. CONCLUSIONS EBV may infect the surface epithelium of the stomach through the reactivated EBV-carrying lymphocytes. EBV may be a factor initiating EBVaGC. Anti-EBV antibodies or EBER1 in situ hybridization may help to identify patients at high risk for EBVaGC.
Recent improvements in neural network acoustic modeling for LVCSR in low resource languages

In this paper we focus on several techniques that improve deep neural network (DNN) acoustic modeling for low-resource languages. We explore the use of different features such as, fundamental-frequency variation (FFV), tonal features, and normalization of these features for deep neural network training. Speciﬁcally we study the impact of these features in conjunction with a tonal lexicon and several neural network architectures including hybrid and bottleneck feature-based conﬁgurations. We also explore the use of un-transcribed data and ways to balance it with transcribed data, to enhance the performance of the best performing LVCSR system. Results are presented in the context of the IARPA Babel program on development languages from Babel option period as well as on the surprise language from the base period of the program. We show that these improved methods can provide up to 15% relative reduction in WER and improvements in keyword search, in the languages explored under the BABEL program.
Noise-Like Sequences to Resonant Excite the Writing of a Universal Memory Based on Spin-Transfer-Torque MRAM

The effects of a noise-like weak signal in the resonant switching of the magnetization driven by spin transfer torque have been systematically studied by means of micromagnetic simulations in both in-plane spin valves and out-of-plane magnetic tunnel junctions. The use of a noise-like resonant excitation allows the overpassing of some critical points compared to the traditional microwave assisted switching. In particular, the application of binary spreading sequences (BSS) does not require the precise knowledge of the resonant frequency and of the optimum relative phase, allowing the use of the same resonant excitation for all the devices in a matrix of memory cells, even if small variations of the physical and geometrical parameters are present. In addition, we also found that in spin valves the switching probabilities close to 100% can be achieved with a smaller current pulse, and in magnetic tunnel junctions a significant energy saving can be obtained.