Miracle-dz/UniFAR-FTUs huggingface dataset:
Routing and spectrum assignment algorithm with most fragmented path first in elastic optical networks

Elastic Optical Networks have drawn a lot of attention in recent years because of its ability to transmit different data rates by increasing or decreasing the optical spectrum according to the necessary demand, ensuring a high spectral efficiency. However, establishing and tearing down different connections end up segmenting the spectrum in several small fragments, making it difficult to attend incoming requests. Another recurrent problem in elastic optical networks, called Routing and Spectrum Assignment (RSA), aims to find a path and assign to it a contiguous number of spectrum slots using the smallest possible amount of spectral resources. This paper proposes a novel RSA algorithm to minimize the spectrum fragmentation problem in Elastic Optical Networks by choosing the most fragmented path first. Results obtained through simulations indicate that the proposed algorithm outperforms other conventional algorithms in terms of blocking probability and spectrum fragmentation ratio.
Early Defect of Phagocytic Cell Function in Subjects at Risk for Acquired Immunodeficiency Syndrome

We studied the functions of peripheral blood monocytes and polymorphonuclear cells in 15 apparently healthy homosexual men, eight homosexual or bisexual subjects with unexplained generalized lymphadenopathies (pre‐AIDS), four homosexual men with acquired immunodeficiency syndrome (AIDS), and 15 heterosexual men. In comparison with normal controls, the homosexual groups studied presented a decreased monocyte candidacidal activity for Candida pseudotropicalis that gradually deteriorates as the clinical symptoms progress towards AIDS. The monocyte phagocytic function was retained. Although the phagocytic and candidacidal activities of the polymorphonuclear cells did not differ from those of the normal controls, the candidacidal activity in some of the cases studied was unusually enhanced, indicating that the cells were in an activated state. In addition, only two of nine sera tested from asymptomatic homosexual males were positive for antibodies to HTLV‐III/LAV, while six out of eight pre‐AIDS and both of the two AIDS patients tested had antibodies to AIDS‐associated retrovirus. We suggest that in AIDS the phagocytic system is already involved, together with B and T lymphocyte abnormalities, during the early events of the syndrome, even without the detection of AIDS‐associated retrovirus antibodies.
Learning to Mix n-Step Returns: Generalizing lambda-Returns for Deep Reinforcement Learning

Reinforcement Learning (RL) can model complex behavior policies for goal-directed sequential decision making tasks. A hallmark of RL algorithms is Temporal Difference (TD) learning: value function for the current state is moved towards a bootstrapped target that is estimated using next state's value function. $\lambda$-returns generalize beyond 1-step returns and strike a balance between Monte Carlo and TD learning methods. While lambda-returns have been extensively studied in RL, they haven't been explored a lot in Deep RL. This paper's first contribution is an exhaustive benchmarking of lambda-returns. Although mathematically tractable, the use of exponentially decaying weighting of n-step returns based targets in lambda-returns is a rather ad-hoc design choice. Our second major contribution is that we propose a generalization of lambda-returns called Confidence-based Autodidactic Returns (CAR), wherein the RL agent learns the weighting of the n-step returns in an end-to-end manner. This allows the agent to learn to decide how much it wants to weigh the n-step returns based targets. In contrast, lambda-returns restrict RL agents to use an exponentially decaying weighting scheme. Autodidactic returns can be used for improving any RL algorithm which uses TD learning. We empirically demonstrate that using sophisticated weighted mixtures of multi-step returns (like CAR and lambda-returns) considerably outperforms the use of n-step returns. We perform our experiments on the Asynchronous Advantage Actor Critic (A3C) algorithm in the Atari 2600 domain.
Proliferation of smooth muscle cells in the inner and outer layers of the tunica media of arteries: An in vitro study

During the development of atherosclerotic and fibromuscular proliferates/lesions, smooth muscle cells (SMC in the media, particularly near the lumen, are activated to migrate into the intima, where they continue to proliferate to form an intimal thickening. It is to date unclear whether SMCs situated adjacent to the adventitia possess a lower capacity to proliferate because they are a special subpopulation of medial SMCs or because the adventitia excerts an inhibitory effect. We have, therefore, developed an in vitro system whereby we have attempted to clear up this uncertainty. The following observations were made from the in vitro experiments:
Endoscopic Biopsy for Tumors of the Third Ventricle

Twelve patients underwent endoscopic biopsy of a tumor involving the third ventricle. Nine patients had no significant medical history while 3 had a history of cancer. Unique characteristics of each case dictated the optimal surgical technique. Endoscopic tumor biopsy was combined with additional procedures in 9 cases; shunt insertion (3), shunt insertion with endoscopic septostomy (5), and transcallosal craniotomy (1). Diagnosis was established in 11 patients (92%); 6 primary brain tumors, 3 metastatic central nervous system tumors, 1 metastatic systemic cancer, and 1 region of post-treatment gliosis. One case was aborted due to poor visualization. Therapy was directly influenced by endoscopic biopsy in 11/12 cases (92%) and craniotomy for tumor resection was avoided in 10/12 patients (83%). Of the 5 patients who underwent endoscopic septostomy, 4 required no subsequent procedures for hydrocephalus. There were no complications, and hospital stay averaged 1.78 days for patients who underwent successful endoscopic biopsy. Tumors of the third ventricle are amenable to endoscopic biopsy with excellent diagnostic yield and low morbidity. The procedure must be tailored depending upon the tumor location within the third ventricle, the degree of ventriculomegaly, and the need to perform a septostomy. Singularly or combined with other endoscopic procedures, patients can be spared multiple and more invasive surgical procedures.
Visualization of Negative Signaling in B Cells by Quantitative Confocal Microscopy

ABSTRACT Numerous biochemical experiments have invoked a model in which B-cell antigen receptor (BCR)-Fc receptor for immunoglobulin (Ig) G (FcγRII) coclustering provides a dominant negative signal that blocks B-cell activation. Here, we tested this model using quantitative confocal microscopic techniques applied to ex vivo splenic B cells. We found that FcγRII and BCR colocalized with intact anti-Ig and that the SH2 domain-containing inositol 5′-phosphatase (SHIP) was recruited to the same site. Colocalization of BCR and SHIP was inefficient in FcγRII−/− but not gamma chain−/− splenic B cells. We also examined the subcellular location of a variety of enzymes and adapter proteins involved in signal transduction. Several proteins (CD19, CD22, SHP-1, and Dok) and a lipid raft marker were corecruited to the BCR, regardless of the presence or absence of FcγRII and SHIP. Other proteins (Btk, Vav, Rac, and F-actin) displayed reduced colocalization with BCR in the presence of FcγRII and SHIP. Colocalization of BCR and F-actin required phosphatidylinositol (PtdIns) 3-kinase and was inhibited by SHIP, because the block in BCR/F-actin colocalization was not seen in B cells of SHIP−/− animals. Furthermore, BCR internalization was inhibited with intact anti-Ig stimulation or by expression of a dominant-negative mutant form of Rac. From these results, we propose that SHIP recruitment to BCR/FcγRII and the resulting hydrolysis of PtdIns-3,4,5-trisphosphate prevents the appropriate spatial redistribution and activation of enzymes distal to PtdIns 3-kinase, including those that promote Rac activation, actin polymerization, and receptor internalization.
Quantitative and correlation analysis of the DNA methylation and expression of DAPK in breast cancer

Background Death-associated protein kinase 1 (DAPK) is an important tumor suppressor kinase involved in the regulation of multiple cellular activities such as apoptosis and autophagy. DNA methylation of DAPK gene was found in various types of cancers and often correlated with the clinicopathological characteristics. However, the mRNA and protein expression of DAPK in the same sample was rarely measured. Thus, it was unclear if the correlation between DAPK gene methylation and clinicopathological parameters was due to the loss of DAPK expression. Methods In this study, the DNA methylation rate, mRNA and protein expression of DAPK was quantitatively detected in 15 pairs of breast cancer patient samples including tumor (T) and adjacent non-tumor (N) tissues. Results The correlation between DNA methylation rate and mRNA expression, together with the correlation between mRNA and protein expression, was calculated. No correlation was observed between any levels using either the measurement value of each sample or the T/N ratio of each pair. Discussion These data suggested that the DNA methylation status of DAPK did not correlate well with its mRNA or protein expression. Extra caution is needed when interpreting the DNA methylation data of DAPK gene in clinical studies.
Blockade of Electron Transport during Ischemia Protects Cardiac Mitochondria*

Subsarcolemmal mitochondria sustain progressive damage during myocardial ischemia. Ischemia decreases the content of the mitochondrial phospholipid cardiolipin accompanied by a decrease in cytochrome c content and a diminished rate of oxidation through cytochrome oxidase. We propose that during ischemia mitochondria produce reactive oxygen species at sites in the electron transport chain proximal to cytochrome oxidase that contribute to the ischemic damage. Isolated, perfused rabbit hearts were treated with rotenone, an irreversible inhibitor of complex I in the proximal electron transport chain, immediately before ischemia. Rotenone pretreatment preserved the contents of cardiolipin and cytochrome c measured after 45 min of ischemia. The rate of oxidation through cytochrome oxidase also was improved in rotenone-treated hearts. Inhibition of the electron transport chain during ischemia lessens damage to mitochondria. Rotenone treatment of isolated subsarcolemmal mitochondria decreased the production of reactive oxygen species during the oxidation of complex I substrates. Thus, the limitation of electron flow during ischemia preserves cardiolipin content, cytochrome c content, and the rate of oxidation through cytochrome oxidase. The mitochondrial electron transport chain contributes to ischemic mitochondrial damage that in turn augments myocyte injury during subsequent reperfusion.
Shared Early Autoantibody Recognition Events in the Development of Anti‐Sm B/B' in Human Lupus

Many aspects of the immune maturation are uncharted. For ordinary human autoimmune systems there are no complete descriptions of the progression from an initial antigenic epitope to a maximally complex immune response. In this study we have exploited a large serial collection of human sera to investigate the development of the anti‐Sm autoimmune response in systemic lupus ertythematosus (SLE). The results suggest a similar, if not virtually identical, stepwise progression in the early humoral immune maturation of anti‐Sm. The amino acid sequence PPPGMRPP comprises the first epitope in the anti‐Sm B/B'response and its close relative, PPPGMRGP, the second. Epitopes are subsequently enlarged by the incorporation of neighbouring amino acids. The third and fourth epitopes are also recognised by an antibody in a nearly identical sequence in different lupus patients. A column absorption with PPPGMRPP demonstrates that the epitope spreading among the first four early epitopes appears to occur by the sequential generation of cross‐reactive antibodies. Unexpectedly, epitope spreading in this system occurs in a predictable fashion by involving essentially the same sequence of antigenic structures from person to person. In addition, these data support the lupus anti‐Sm antibodies originating against a single antigenic structure and, hence, strongly support a unifying mechanism in the generation of these autoantibodies.
Interaction of TorsinA with Its Major Binding Partners Is Impaired by the Dystonia-associated ΔGAG Deletion*

Early onset (DYT1) torsion dystonia is a dominantly inherited movement disorder associated with a three-base pair (ΔGAG) deletion that removes a glutamic acid residue from the protein torsinA. TorsinA is an essential AAA+ (ATPases associated with a variety of cellular activities) ATPase found in the endoplasmic reticulum and nuclear envelope of higher eukaryotes, but what it does and how changes caused by the ΔGAG deletion lead to dystonia are not known. Here, we asked how the DYT1 mutation affects association of torsinA with interacting proteins. Using immunoprecipitation and mass spectrometry, we first established that the related transmembrane proteins LULL1 and LAP1 are prominent binding partners for torsinA in U2OS cells. Comparative analysis demonstrates that these two proteins are targeted to the endoplasmic reticulum or nuclear envelope by their divergent N-terminal domains. Binding of torsinA to their C-terminal lumenal domains is stabilized when residues in any one of three motifs implicated in ATP hydrolysis (Walker B, sensor 1, and sensor 2) are mutated. Importantly, the ΔGAG deletion does not stabilize this binding. Indeed, deleting the ΔGAG encoded glutamic acid residue from any of the three ATP hydrolysis mutants destabilizes their association with LULL1 and LAP1C, suggesting a possible basis for loss of torsinA function. Impaired interaction of torsinA with LULL1 and/or LAP1 may thus contribute to the development of dystonia.
Medication Use in Residential Care Facilities for the Elderly

OBJECTIVE: To describe medication use by residents of residential care facilities for the elderly (RCFEs). DESIGN: A cross-sectional survey of medication use. SETTING: Licensed, private RCFEs recruited from a roster of all licensed RCFEs in the Los Angeles area. SUBJECTS: Residents who were ≥60 years of age and whose medications were centrally stored in the facility. MEASURES: Age, gender, race, health insurance coverage, dietary restrictions, ambulation status, medical diagnoses, and medication profile. RESULTS: A total of 818 residents were surveyed. Residents were primarily white women who were >80 years. The average number of medications per resident was five; 94% of the sample took at least one medication. Cardiovascular drugs, central nervous system drugs, analgesics, diuretics, and potassium supplements were most commonly used. Use of multiple drugs within a therapeutic class was also common, with means ranging from 1.46 to 1.81 per resident for the most commonly prescribed classes. Diagnoses supporting the use of many medications were not documented in the residents' health records. CONCLUSIONS: This RCFE sample was medically frail and took many medications. The frequent use of cardiovascular medication reflected the prevalence of cardiac disease in the elderly. The frequency of psychotropic drug use without a corresponding indication suggested prescribing for symptoms rather than documented medical conditions. Lack of recorded diagnoses limited the ability to evaluate drug therapy. Improved record keeping; periodic medication review; and resident, staff, and prescriber education are necessary to ensure appropriate medication use in this setting.
Neurologic symptoms due to possible chromium deficiency in long-term parenteral nutrition that closely mimic metronidazole-induced syndromes.

BACKGROUND We previously described a patient on home parenteral nutrition (HPN) who developed glucose intolerance and neuropathy that only responded to an infusion of chromium. A patient on HPN who had neuropathy and glucose intolerance was studied. He was also on metronidazole, which could have caused the neuropathy, but the symptoms and signs persisted. METHODS Baseline clinical examination, nerve conduction studies, serum vitamin and trace element levels, and glucose tolerance were measured. Then, 250 micrograms of trivalent chromium as the chloride salt was infused daily for 2 weeks. The above studies were repeated. RESULTS The patient at baseline had peripheral neuropathy of the axonal type and was glucose intolerant. Serum chromium was raised in this patient above the reference range. Despite raised serum levels, the infusion of chromium resulted in clinical remission that was marked 4 days after starting the infusion. Normalization of nerve conduction also occurred within 3 weeks of the initial study. CONCLUSIONS Neuropathy and glucose intolerance may occur despite increased serum chromium levels and respond to chromium infusion. The previous use of drugs such as metronidazole should not exclude chromium as a potential treatment for neuropathy in HPN patients.
Amphotericin B colloidal dispersion

Amphotericin B colloidal dispersion (ABCD) is a colloidal dispersion of a stable complex of amphotericin B with cholesteryl sulphate in a 1:1 proportion, forming uniform disk-shaped particles. ABCD is associated with less nephrotoxicity than conventional amphotericin B deoxycholate. Infusion-related adverse events are more frequent in patients receiving ABCD than in patients receiving liposomal amphotericin B or amphotericin B deoxycholate. ABCD has been shown in a randomised, double-blind study, to be an effective alternative to amphotericin B deoxycholate for empirical treatment of patients with fever and neutropenia. ABCD is active in the treatment of invasive Candida spp. and Aspergillus spp. infections in immunocompromised hosts, however most of the data supporting its use for these types of infections is derived from non-comparative open-label clinical trials of patient refractory to or intolerant of conventional antifungal therapy. ABCD is approved by the US FDA for the treatment of invasive aspergillosis in patients where renal impairment or unacceptable toxicity precludes the use of amphotericin B deoxycholate in effective doses, and in patients with invasive aspergillosis where prior amphotericin B deoxycholate therapy has failed. Two other lipid formulations of amphotericin B, amphotericin B lipid complex and liposomal amphotericin B, are available and, like ABCD, are associated with reduced nephrotoxicity as compared to amphotericin B deoxycholate. The role of ABCD in comparison with these other lipid formulations of amphotericin B is discussed herein. High cost remains an issue with all lipid formulations of amphotericin B.
Improving cord blood unit quantity and quality at King Abdullah International Medical Research Center Cord Blood Bank

Public cord blood banks (CBBs) store cord blood unit (CBU) donations for anyone in need. However, strict regulations need to be followed to build up high‐quality bank products that can be used worldwide. We established a public CBB at a tertiary hospital in Saudi Arabia. Here, we investigated the reasons behind rejecting or not collecting CBUs over 2 years (2011‐2012) and which steps were implemented to improve the number and quality of storable units.
Synapsin I in PC12 cells. I. Characterization of the phosphoprotein and effect of chronic NGF treatment

PC12 cells contain a synapsin I-like molecule. Several serum and monoclonal antibodies raised against bovine brain synapsin I bind to and precipitate this molecule, demonstrating immunochemical similarity between the brain and PC12 species. PC12 synapsin I, like brain synapsin I, is a phosphoprotein: It is phosphorylated in intact cells and, when partially purified, serves as a substrate for several synapsin I kinases. PC12 cell synapsin I is structurally similar to brain synapsin I as shown by peptide mapping of 35S-methionine-and 32P- phosphate-labeled molecules from the 2 sources. Chronic NGF treatment of the cells induces a significant increase in the amount of synapsin I relative to total cell protein, measured either by immunolabeling or incorporation of 35S-methionine. The synapsin I present in untreated PC12 cells migrates predominantly as a singlet and that present in cells treated chronically with NGF as a doublet in SDS-PAGE.
Genetic analysis of the 9.5-kilobase virulence plasmid of Yersinia pestis

The 9.5-kilobase plasmid of Yersinia pestis determines plasminogen activator, coagulase, pesticin, and pesticin immunity activities. We have mapped and cloned the loci encoding these activities and demonstrated that both plasminogen activator and coagulase were determined by the same gene, designated pla. The primary translation product of this gene (38 kilodaltons [kDa]) was processed in two sequential steps to produce peptides of 37 and 35 kDa. The first step in this processing occurred rapidly and probably cotranslationally and was blocked when protein export was inhibited. The second step was much slower and resulted in the presence of both the 37- and 35-kDa species in significant quantities. We also showed that the plasmid had a polA-dependent replicon and identified the region that contained its origin of replication and incompatibility functions.
Inhibition of adhesive activity of K88 fibrillae by peptides derived from the K88 adhesin

A cyanogen bromide fragment derived from the K88ab adhesin inhibited the hemagglutinating activity of K88 fibrillae. Smaller fragments which inhibited the adherence of K88 fibrillae to erythrocytes or to intestinal epithelial cells were obtained by digestion of K88ab fibrillae with alpha-chymotrypsin. Active peptides were isolated from the digestion mixture and identified as Ser-Leu-Phe and Ala-Ile-Phe. Both tripeptides correspond to the peptide stretches Ser-148-Leu-Phe-150 and Ala-156-Ile-Phe-158, respectively, which are part of conserved regions in the primary structure of the K88 variants ab, ac, and ad. The isolated tripeptides inhibited the hemagglutinating activity of purified K88 fibrillae in the 1 to 5 microM range, while adherence of the fibrillae to intestinal epithelial cell brush borders was inhibited in the 10 to 50 microM range. Furthermore, the tripeptides were capable of eluting attached bacteria from agglutinated erythrocytes. The inhibitory activity of the isolated peptides was confirmed by testing various synthetic peptides for their ability to inhibit the interaction of the different K88 variants with various species of erythrocytes. The significance of these findings for the localization of the receptor-binding domain is discussed.