Miracle-dz/UniFAR-FTUs huggingface dataset:
Support vector machines in data mining

Our smooth support vector machine (SSVM) algorithm generates an SVM classifier by solving a strongly convex unconstrained minimization problem without using any optimization package. We use a Newton-Armijo algorithm that can be shown to converge globally and quadratically to the unique solution of the SSVM. Numerical results are given to demonstrate the effectiveness and speed of SSVM. We present a novel rectangular kernel idea for nonlinear SSVM that can be applied to all nonlinear kernel algorithms to avoid the difficulty of dealing with a huge dense kernel matrix. This leads to our reduced support vector machine (RSVM) algorithm. The RSVM algorithm uses a random subset of the dataset to generate a nonlinear classifier. Instead of solving an unconstrained minimization problem in m + 1 variables, m is the number of data points, RSVM solves an unconstrained minimization problem in m + 1 variables where m is the size of the reduced set and in m << m. This reduces computational complexity from O((m + 1)3) to O(( m + 1)3). In addition, we only need to keep the reduced set to characterize the nonlinear classifier for classifying new unseen data. Numerical results show that RSVM is much faster than other methods and has similar or better test set correctness. An application of data mining is the identification of breast cancer patients for whom chemotherapy could prolong longevity. We cluster 253 breast cancer patients into three prognostic groups: Good, Poor and Intermediate. Each of the three groups has a significantly distinct survival curve. Of particular significance is the Intermediate group, because patients with chemotherapy in this group do better than those without chemotherapy in the same group. This is the reverse case to that of the overall population of 253 patients for which patients undergoing chemotherapy have worse survival than those who do not. We also prescribe a procedure for classifying breast cancer patients into the three above prognostic groups. These results suggest that patients in the Good group should not receive chemotherapy while Intermediate group patients should receive chemotherapy based on our survival curve analysis.
Characterization of a monoclonal antibody capable of reliably quantifying expression of Human Copper Transporter 1 (hCTR1): Characterization of hCTR1

Human copper transporter 1 (hCTR1) is the high-affinity copper influx transporter in mammalian cells that also mediates the influx of cisplatin. Loss of hCTR1 expression has been implicated in the development of resistance to this cancer chemotherapeutic agent. It has turned out to be very difficult to develop antibodies to hCTR1 and polyclonal antibodies produced by different laboratories have yielded conflicting results. We have characterized a newly-available rabbit monoclonal antibody that reacts with an epitope on the N-terminal end of hCTR1 that now permits rigorous identification and quantification of hCTR1 using Western blot analysis. Postnuclear membrane (PNM) preparations made from cells engineered to express high levels of myc-tagged hCTR1, and cells in which the expression of hCTR1 was knocked down, were used to characterize the antibody. The identity of the bands detected was confirmed by immunoprecipitation, surface biotinylation and deglycosylation of myc-tagged hCTR1. Despite the specificity expected of a monoclonal antibody, the anti-hCTR1 detected a variety of bands in whole cell lysates (WCL), which made it difficult to quantify hCTR1. This problem was overcome by isolating post-nuclear membranes and using these for further analysis. Three bands were identified using this antibody in PNM preparations that migrated at 28, 33–35 and 62–64 kDa. Multiple lines of evidence presented here suggest that the 33–35 and 62–64 kDa bands are hCTR1 whereas the 28 kDa band is a cross-reacting protein of unknown identify. The 33–35 kDa band is consistent with the expected MW of the glycosylated hCTR1 monomer. This analysis now permits rigorous identification and quantification of hCTR1.
High-resolution mapping of a standardized transcriptional reporter reveals positions of high and low transcription in the Escherichia coli chromosome

Summary Recent studies on targeted gene integrations in bacteria have demonstrated that chromosomal location can substantially affect a gene’s expression level. However, these studies have only provided information on small numbers of sites. To measure position effects on transcriptional propensity at high resolution across the genome, we built and analyzed a library of over 144,000 genome-integrated, standardized reporters in a single mixed population of Escherichia coli. We observed more than 20-fold variation in transcriptional propensity across the genome when the length of the chromosome was binned into broad 4 kbp regions; greater variability was observed over smaller regions. Our data reveal peaks of high transcriptional propensity centered on ribosomal RNA operons and core metabolic genes, while prophages and mobile genetic elements were enriched in less transcribable regions. In total, our work supports the hypothesis that E. coli has evolved gene-independent mechanisms for regulating expression from specific regions of its genome. Abstract eTOC Scholz et al. use barcodes to track thousands of reporters integrated into various sites across the E. coli genome in order to create a high-resolution map of the propensity for transcription. They find that ribosomal RNA operons and core metabolic genes are enriched in highly transcribable regions, while mobile genetic elements such as prophages are enriched in silenced regions.
Facial Nerve Neuroma: Surgical Concept and Functional Results

This study reviewed the management and outcomes of 11 facial nerve neuromas treated in our institution during the past two decades with particular emphasis on surgical concepts and functional outcomes. All patients underwent complete surgical resection of their tumor. Eight patients (73%) were followed on an outpatient basis. A retrospective chart review for pre- and postoperative clinical and radiological data was performed. All facial neuromas were multisegment tumors. All segments of the facial nerve were represented, but 54% involved the geniculate ganglion and 45% involved the labyrinthine or tympanic portions of the nerve, or both. Depending on the extent of sensorineural hearing loss, surgical removal was performed through the middle cranial fossa or translabyrinthine approach. To obtain adequate nerve reconstruction, we combined intra- and extracranial approaches (e.g., the transmastoidal and transtemporal routes). Regardless of the type of nerve reconstruction, the best recovery achieved was moderate facial weakness (House-Brackmann Grade III) in 75% of the patients, even in a patient who was Grade IV preoperatively. The choice of treatment for facial neuromas and surgical approach depends on the extent of tumor, grade of facial palsy, and hearing function. When facial palsy is present, complete resection is clearly indicated. In patients without facial dysfunction, a conservative strategy consisting of clinical and radiological observation should be considered as a treatment option.
Animal Model Transfer of the Active Form of Transforming Growth Factor- (cid:1) 1 Gene to Newborn Rat Lung Induces Changes Consistent with Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia is a chronic lung disease of premature human infancy that shows pathological features comprising varying sized areas of interstitial fibrosis in association with distorted large alveolar spaces. We have previously shown that transfer of active transforming growth factor (TGF)- (cid:1) 1 (AdTGF (cid:1) 1 223/225 ) genes by adenovirus vector to embryonic lungs results in inhibition of branching morphogenesis and primitive peripheral lung development, whereas transfer to adult lungs results in progressive interstitial fibrosis. Herein we show that transfer of TGF- (cid:1) 1 to newborn rat pups results in patchy areas of interstitial fibrosis developing throughout a period of 28 days after transfer. These areas of fibrosis appear alongside areas of enlarged alveolar spaces similar to the prealveoli seen at birth, suggesting that postnatal lung development and alveolarization has been inhibited. In rats treated with AdTGF (cid:1) 1 223/225 , enlarged alveolar spaces were evident by day 21, and by 28 days, the mean alveolar cord length was nearly twice that in control vector or untreated rats. Hydroxyproline measurements con-firmed the presence of fibrosis. These data suggest that overexpression of TGF- (cid:1)
Leptin Enhances NR2B-mediated NMDA Responses Via a MAPK-dependent Process in Cerebellar Granule Cells.

It is well documented that the hormone leptin regulates energy balance via its actions in the hypothalamus. However, evidence is accumulating that leptin plays a key role in numerous CNS functions. Indeed, leptin receptors are expressed in many extrahypothalamic brain regions, with high levels found in the hippocampus and cerebellum. In the hippocampus, leptin has been shown to facilitate NMDA receptor function and modulate synaptic plasticity. A role for leptin in cerebellar function is also indicated as leptin-deficient rodents display reduced mobility that is unrelated to obesity. Here we show that leptin receptor immunolabeling can be detected in cultured cerebellar granule cells, being expressed at the somatic plasma membrane and also concentrated at synapses. Furthermore, leptin facilitated NR2B NMDA receptor-mediated Ca 2+ influx in cerebellar granule cells via a mitogen-activated protein kinase-dependent pathway. These findings provide the first direct evidence for a cellular action of leptin in cerebellar neurons. In addition, given that NMDA receptor activity in the cerebellum is crucial for normal locomotor function, these data also have important implications for the potential role of leptin in the control of movement.
Impact of obsessive-compulsive personality disorder (OCPD) symptoms in Internet users

, Abstract Background— Internet use is pervasive in many cultures. Little is known about the impact of Obsessive-Compulsive Personality Disorder (OCPD) symptoms on impulsive and compulsive psychopathologies in people who use the Internet. Method— 1323 adult Internet users completed an online questionnaire quantifying OCPD symptoms, likely occurrence of select mental disorders (OCD, ADHD, problematic Internet use, anxiety), and personality questionnaires of impulsivity (Barratt) and compulsivity (Padua). Predictors of presence of OCPD symptoms (endorsement of at least 4 of 8 DSM criteria) were identified using binary logistic regression. Results— In regression (p<0.001, AUC 0.77), OCPD symptoms were significantly associated with (in order of decreasing effect size): lower non-planning impulsivity, higher ADHD symptoms, problematic Internet use, avoidant personality disorder, female gender, generalized anxiety disorder, and some types of compulsions (checking, dressing/washing). Conclusions— These data suggest that OCPD symptoms, defined in terms of at least 4 of 8 DSM tick-list criteria being met, are common in Internet users. OCPD symptoms were associated with considerably higher levels of psychopathology relating to both impulsive (ADHD) and compulsive (OC-related and problematic Internet use) disorders. These data merit replication and extension using gold-standard in-person clinical assessments, as the current study relied on self-report over the Internet. disorders
Globoside (Gb4) promotes activation of ERK by interaction with the epidermal growth factor receptor

Background— Globoside (Gb4), a globo-series glycosphingolipid (GSL), has been characterized as a stage-specific embryonic antigen (SSEA), and is highly expressed during embryogenesis as well as in cancer tissues. However, the functional role and molecular mechanism of Gb4 is so far unknown. Methods— GSLs were preferentially inhibited by treatment with D-threo-1-ethylenedioxyphenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (EtDO-P4), a nanomolar inhibitor of GSL synthesis, in two carcinoma cell lines, HCT116 and MCF7. The effect of EtDO-P4 was examined by MTT assay, FACS analysis, wound assay, western blotting, and RTK array analysis. The functional role of Gb4 was determined by the exogenous addition of various GSLs, and an assay utilizing GSL-coated latex beads. Results— Both cell lines contained higher levels of neutral GSLs than of sialic acid-containing GSLs. Gb4 was one of the major neutral GSLs. The depletion of total GSLs caused significant reduction of cell proliferation, but had less effect on cell apoptosis or motility. EtDO-P4 treatment also suppressed activation of the epidermal growth factor receptor (EGFR)-induced ERK pathway and various receptor tyrosine kinases (RTKs). The reduced activation of ERK was restored by the exogenous addition of Gb4, but not by the addition of gangliosides (GM1, GM2, GM3, GD1a). The GSL-coated bead assay indicated that Gb4 forms a complex with EGFR, but not with other RTKs. Conclusions— Gb4 promotes activation of EGFR-induced ERK signaling through direct interaction with EGFR. General significance— A globo-series GSL, Gb4, promotes EGFR-induced MAPK signaling, resulting in cancer cell proliferation. These findings suggest a possible application of Gb4 in cancer diagnostics and drug targeting.
Does the preclinical evidence for functional remyelination following engraftment into the injured spinal cord support progression to clinical trials?

This article reviews all historical literature in which rodent-derived myelinating cells have been engrafted into the contused adult rodent spinal cord. From 2,500 initial PubMed citations identified, human cells grafts, bone mesenchymal stem cells, olfactory ensheathing cells, non-myelinating cell grafts, and rodent grafts into hemisection or transection models were excluded, resulting in the 67 studies encompassed in this review. Forty five of those involved central nervous system (CNS)-derived cells, including neural stem progenitor cells (NSPCs), neural restricted precursor cells (NRPs) or oligodendrocyte precursor cells (OPCs), and 22 studies involved Schwann cells (SC). Of the NSPC/NPC/OPC grafts, there was no consistency with respect to the types of cells grafted and/or the additional growth factors or cells co-grafted. Enhanced functional recovery was reported in 31/45 studies, but only 20 of those had appropriate controls making conclusive interpretation of the remaining studies impossible. Of those 20, 19 were properly powered and utilized appropriate statistical analyses. Ten of those 19 studies reported the presence of graft-derived myelin, 3 reported evidence of endogenous remyelination or myelin sparing, and 2 reported both. For the SC grafts, 16/21 reported functional improvement, with 11 having appropriate cellular controls and 9/11 using proper statistical analyses. Of those 9, increased myelin was reported in 6 studies. The lack of consistency and replication among these preclinical studies are discussed with respect to the progression of myelinating cell transplantation therapies into the clinic. and NCT02354625, both involving The Miami Project to Cure Paralysis. The first Phase 1 study, which is no longer enrolling patients, will evaluate the safety of autologous SC transplant into subacute SCI patients. Safety and efficacy assessments including International Standards of Neurological Classification for SCI (ISNCSCI), MRI, and neuropathic pain will be performed 1 week, 2 weeks, and 2, 6, and 12 months post-transplantation. Although no results have been reported, the study is estimated to be completed in the next 6 months. In the second Phase 1 study, safety of autologous SC transplant into chronic SCI patients will be assessed by measuring ISNCSCI, MRI, neuropathic pain, ISCI Basic Pain dataset v2, Pain Diagram, and Quantitative Sensory Testing at 1 week, 2 weeks, and 2, and 6 months post-transplantation. The estimated completion date of the study, which is currently enrolling patients, is January 2018.
Protein Kinase C– z Mediates Lung Injury Induced by Diesel Exhaust Particles

Recently, we reported that diesel exhaust particles (DEPs) disrupt tight junctions (TJs) in alveolar epithelial cells (AECs) via an increase in reactive oxygen species (ROS). In this study, we investigated the role of protein kinase C (PKC)– z activation in DEP-induced lung injury. C57/bl6 mice were instilled intratracheally with 50 m l of saline containing 100 m g of DEPs or titanium dioxide (TiO 2 ). Twenty-four hourslater,bronchoalveolarlavagewasperformedtoassessneutro-phil counts and protein concentrations. In addition, in vitro experi- ments were performed in primary rat and human AECs exposed to DEPs(50 m g/cm 2 )for3hours.Transepithelialelectricalconductance was measured, and TJ protein association was analyzed by immuno- precipitation. To determine whether the overexpression of antiox-idants prevented DEP-induced lung injury, AECs and mice were infected with adenoviruses containing catalase and manganese superoxide dismutase (MnSOD) plasmids. In vivo , the overexpression of catalase and MnSOD prevented DEP-induced neutrophil recruit-ment.TheinhibitionofPKC- z activationalsopreventedDEP-induced neutrophil recruitment invivo . In vitro ,DEPsactivatedPKC- z in AECs, butnotinalveolarmacrophages. UsingaspeciﬁcmyristolatedPKC- z pseudosubstrate pepetide (PKC- z ps), we showed that PKC- z medi-atedtheDEP-induceddissociationofoccludinandzonulaoccludin–1 (ZO1) in rat and human AECs. In addition, the overexpression of constitutively active PKC- z induced the dissociation of occludin and ZO1 in AECs. DEP-induced TJ disruption occurs via PKC- z . TJ disruption seems to be in part responsible for DEP-induced lung injury.
REVIEW: PART OF A SPECIAL ISSUE ON PLANT CELL WALLS Back to the future with the AGP – Ca 2 1 ﬂux capacitor

† Background Arabinogalactan proteins (AGPs) are ubiquitous in green plants. AGPs comprise a widely varied group of hydroxyproline (Hyp)-rich cell surface glycoproteins (HRGPs). However, the more narrowly deﬁned classical AGPs massively predominate and cover the plasma membrane. Extensive glycosylation by pendant polysac- charides O-linked to numerous Hyp residues like beads of a necklace creates a unique ionic compartment essential to a wide range of physiological processes including germination, cell extension and fertilization. The vital clue to a precise molecular function remained elusive until the recent isolation of small Hyp–arabinogalactan polysaccharide subunits; their structural elucidation by nuclear magentic resonance imaging, molecular simulations and direct experiment identiﬁed a 15-residue consensus subunit as a b -1,3-linked galactose trisaccharide with two short branched sidechains each with a single glucuronic acid residue that binds Ca 2 + when paired with its adjacent sidechain. † Scope AGPsbindCa 2 + ( K d (cid:2) 6 m M )attheplasmamembrane(PM)atpH (cid:2) 5.5butreleaseitwhenauxin-dependent PM H + -ATPase generates a low periplasmic pH that dissociates AGP–Ca 2 + carboxylates (p k a (cid:2) 3); the consequen-tial large increase in free Ca 2 + drives entry into the cytosol via Ca 2 + channels that may be voltage gated. AGPs are thus arguably the primary source of cytosolic oscillatory Ca 2 + waves. This differs markedly from animals, in which cytosolicCa 2 + originatesmostlyfrominternalstoressuchasthesarcoplasmicreticulum.Incontrast,weproposethat external dynamic Ca 2 + storage by a periplasmic AGP capacitor co-ordinates plant growth, typically involving exocytosis of AGPs and recycled Ca 2 + , hence an AGP–Ca 2 + oscillator. † Conclusions The novel concept of dynamic Ca 2 + recycling by an AGP–Ca 2 + oscillator solves the long-standing problem of a molecular-level function forclassical AGPs andthus integratesthree ﬁelds: AGPs, Ca 2 + signalling and auxin. This accounts for the involvement of AGPs in plant morphogenesis, including tropic and nastic movements.
Unique and redundant roles of α 4 and β 2 integrins in kinetics of recruitment of lymphoid versus myeloid cell subsets to the inflamed peritoneum revealed by studies of genetically deficient mice

OBJECTIVE— Leukocyte recruitment to inflammatory sites is a prominent feature of acute and chronic inflammation. Instrumental in this process is the coordinated upregulation of leukocyte integrins (among which α 4 β 1 and β 2 integrins are major players) and their cognate receptors in inflamed tissues. To avoid the ambiguity of previous short-term antibody-based studies and to allow for long-term observation, we used genetically deficient mice to compare roles of α 4 and β 2 integrins in leukocyte trafficking. METHODS— Aseptic peritonitis was induced in α 4 or β 2 integrin-deficient (conditional and conventional knockouts, respectively) and control mice, and recruitment of major leukocyte subsets to the inflamed peritoneum was followed for up to 4 days. RESULTS— Despite normal chemokine levels in the peritoneum and adequate numbers, optimal recruitment of myeloid cells was impaired in both α 4- and β 2-deficient mice. Furthermore, clearance of recruited neutrophils and macrophages was delayed in these mice. Lymphocyte migration to the peritoneum in the absence of α 4 integrins was drastically decreased, both at steady state and during inflammation, a finding consistent with impaired lymphocyte in vitro adhesion and signaling. By contrast, in the absence of β 2 integrins, defects in lymphocyte recruitment were only evident when peritonitis was established. CONCLUSIONS— Our data with concurrent use of genetic models of integrin deficiency reveal non-redundant functions of α 4 integrins in lymphocyte migration to the peritoneum and further refine specific roles of α 4 and β 2 integrins concerning trafficking and clearance of other leukocyte subsets at homeostasis and during inflammation. subsets to the peritoneum before and after inflammation in α 4 or β 2 integrin-deficient mice, using a well-studied model of aseptic thioglycolate-induced peritonitis. Our results revealed intrinsic differences of migratory responses in the absence of α 4 integrins in lymphoid versus myeloid subsets. Parallel studies using mice with single α 4- or β 2-, as well as mice with double ( α 4 and β 2) integrin deficiency allowed fine-tuning of the roles of α 4 and β 2 integrins in leukocyte trafficking.
Chloroplast targeting factor AKR2 evolved from an ankyrin repeat domain coincidentally binds two chloroplast lipids

SUMMARY In organellogenesis of the chloroplast from endosymbiotic cyanobacterium, the establishment of protein targeting mechanisms to the chloroplast should have been pivotal. However, it is still mysterious how these mechanisms were established and how they work in plant cells. Here, we show that AKR2A, the cytosolic targeting factor for chloroplast outer membrane (COM) proteins, evolved from the ankyrin repeat domain (ARD) of the host cell by stepwise extensions of its N-terminal domain, and two lipids monogalactosyldiacylglycerol (MGDG) and phosphatidylglycerol (PG) of the endosymbiont were selected to function as the AKR2A receptor. Structural analysis, molecular modeling and mutational analysis of the ARD identified two adjacent sites for coincidental and synergistic binding of MGDG and PG. Based on these findings, we propose that the targeting mechanism of COM proteins was established using components from both the endosymbiont and host cell through a modification of the protein-protein interacting ARD into a lipid binding domain.