Miracle-dz/UniFAR-FTUs huggingface dataset:
3848 THE FIRST STEP OF KNOCKOUT GRIEF : DENIAL

In the early 1980s several labs independently discovered and characterized the glycoprotein that eventually became known as tenascin. Immunohistochemistry revealed tenascin in everyone’s favorite extracellular matrix: around motile cells, at hot spots of proliferation and at sites of branching morphogenesis, near inductive events, in cartilage, tendons and quite prominently in the developing nervous system. Tenascin was also shown to be upregulated at the margins of healing wounds and in the stroma of many tumours (for reviews see Erickson, 1993a; Tucker, 1994; ChiquetEhrismann, 1995; Mackie, 1997). The results of in vitro studies were just as titillating. In contrast to most substrateadhesion molecules, purified tenascin has anti-adhesive properties. Most cells can attach weakly to tenascin-coated substrata, but they remain rounded and particularly motile (e.g. Lotz et al., 1989; Halfter et al., 1989). Tenascin was touted as a ‘magic bullet’, potentially responsible for key events in systems as diverse as neural-crest morphogenesis and tumour metastasis. The cloning and sequencing of tenascin eventually revealed a family of molecules in which tenascin’s distinctive EGF-like repeats and fibrinogen-like C terminus are separated by a series of fibronectin type III repeats (Fig. 1; reviewed by ChiquetEhrismann et al., 1994a). The tenascin discovered first was named tenascin-C to distinguish it from tenascin-R, which is found almost exclusively in the central nervous system (CNS), and tenascin-X, a mammalian tenascin found in some connective tissue and around blood vessels. Tenascin-C was cloned from zebrafish, amphibians, birds and mammals, and its highly conserved sequences provided further evidence for its fundamental function (Fig. 1; Chiquet-Ehrismann et al., 1994a; Erickson, 1994). The precise function(s), however, remained elusive. Cell culture studies showed that tenascin-C promotes both adhesion and detachment, and can stimulate and inhibit cell division, and that its ability to bind to classic integrins depends on the species from which the tenascin-C was isolated (for reviews see Erickson, 1993a; Faissner et al., 1994). Some of the differences are probably related to the type of cell under investigation or the bioassay used. It also seemed likely that at least some of the contradictory observations would be explained by studies of the many tenascin-C splice variants (e.g. Mackie and Tucker, 1992). Many of us were shocked to learn that tenascin-C-knockout mice, among the first to be made by homologous recombination, were indistinguishable from their wild-type littermates (Saga et al., 1992): the tenascin-C-knockout mice were the same size as the controls; they were fertile; and cursory histological examinations revealed no gross deficits in neuroarchitecture or principal organ systems (Fig. 2). Not only had gene-knockout technology failed to clarify a function for tenascin-C, it pointed to a minor or even completely redundant role for this protein (Erickson, 1993b). 3847 Journal of Cell Science 112, 3847-3853 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 JCS0725
Tumor response and negative distal resection margins of rectal cancer after hyperthermochemoradiation therapy.

BACKGROUND The safety of regional hyperthermia has been tested in locally advanced rectal cancer. The aim of this study was to assess the effects of shorter distal margins on local control and survival in rectal cancer patients who were treated with preoperative hyperthermochemoradiation therapy (HCRT) and underwent rectal resection by using the total mesorectal excision (TME) method. PATIENTS AND METHODS Ninety-three patients with rectal adenocarcinoma who received neoadjuvant HCRT (total radiation: 50 Gy) were included in this study. Surgery was performed 8 weeks after HCRT, and each resected specimen was evaluated histologically. Length of distal surgical margins, status of circumferential margins, pathological response, and tumor node metastasis stage were examined for their effects on recurrence and survival. RESULTS Fifty-eight (62.4%) patients had tumor regression, and 20 (21.5%) had a pathological complete response. Distal margin length ranged from 1 to 55 mm (median, 21 mm) and did not correlate with local recurrence (p=0.57) or survival (p=0.75) by univariate analysis. Kaplan-Meier estimates of recurrence-free survival and local recurrence for the <10 mm versus ≥10 mm groups were not significantly different. Positive circumferential margins and failure of tumors to respond were unfavorable factors in survival. CONCLUSION Distal resection margins that are shorter than 10 mm but are not positive appear to be equivalent to longer margins in patients who undergo HCRT followed by rectal resection with TME. To improve the down-staging rate, additional studies are needed.
Drug-resistant tuberculosis in Budapest.

SETTING Sixteen districts of Budapest, Hungary. OBJECTIVE To determine the frequency of primary and secondary drug resistance, and to recommend treatment regimens. DESIGN A retrospective survey. METHODS Mycobacterium tuberculosis isolates were collected from 264 newly diagnosed and 147 previously treated patients. All strains were tested against isoniazid (INH), rifampicin (RIF), streptomycin (SM) and ethambutol (EMB) using the proportion method. Bacteriologic examinations were performed in the Diagnostic Laboratory of the Koranyi National Institute for Tuberculosis and Pulmonology in Budapest. RESULTS Primary resistance to INH alone was 4%, to SM alone 2%, to RIF alone 0.4%, to INH and SM 1%, and to INH, RIF, SM and EMB 0.4%. Of the isolates of 78 relapse cases, six (8%) were resistant to INH alone, one (1%) to INH and RIF, two (3%) to INH, RIF, SM and EMB. Of the isolates of 69 patients notified with active tuberculosis for over a year, 51 (74%) were susceptible to the drugs tested. CONCLUSION Based on the level of primary drug resistance as well as on the resistance pattern of relapse cases, it is recommended to start the treatment of newly detected and relapse cases with four drugs. The high rate of chronic cases with susceptible strains can be explained by poor compliance. To prevent development of resistant cases and to achieve good compliance, it is necessary to apply direct observation of treatment in all types of patients.
Spinal nerve segmentation in the chick embryo: analysis of distinct axon-repulsive systems.

In higher vertebrates, the segmental organization of peripheral spinal nerves is established by a repulsive mechanism whereby sensory and motor axons are excluded from the posterior half-somite. A number of candidate axon repellents have been suggested to mediate this barrier to axon growth, including Sema3A, Ephrin-B, and peanut agglutinin (PNA)-binding proteins. We have tested the candidacy of these factors in vitro by examining their contribution to the growth cone collapse-inducing activity of somite-derived protein extracts on sensory, motor, and retinal axons. We find that Sema3A is unlikely to play a role in the segmentation of sensory or motor axons and that Ephrin-B may contribute to motor but not sensory axon segmentation. We also provide evidence that the only candidate molecule(s) that induces the growth cone collapse of both sensory and motor axons binds to PNA and is not Sema3A or Ephrin-B. By grafting primary sensory, motor, and quail retinal neurons into the chick trunk in vivo, we provide further evidence that the posterior half-somite represents a universal barrier to growing axons. Taken together, these results suggest that the mechanisms of peripheral nerve segmentation should be considered in terms of repellent molecules in addition to the identified molecules.
Characterization of calcium carbonate obtained from oyster and mussel shells and incorporation in polypropylene

There is a high content of calcium carbonate in mussel and oyster shells, which can be used in the formulation of medicine, in construction or as filler in polymer materials. This work has as its main objective to obtain calcium carbonate from mussel and oyster shells and used as filler in polypropylene compared their properties with polypropylene and commercial calcium carbonate composites. The shellfish was milling and heated at 500 °C for 2 hours. The powder obtained from shellfish were characterized by scanning electron microscopy (SEM), X-ray fluorescence, particle size distribution and abrasiveness and compared with commercial CaCO
ALK Folic Acid Transport and Integrin Signal Induced-Angiogenesis Network in Human Hepatocellular Carcinoma (HCC) by Systems-Theoretical Analysis

We constructed the high-expression ALK activated transport and signal network in human hepatocellular carcinoma (HCC) compared with low-expression (fold change ≥2) no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) in GEO data set, by using integration of gene regulatory activated and inhibited network inference method with gene ontology (GO) analysis. Our result showed that ALK transport and signal upstream network ECT2, FOLR1, GNAZ, GRM1, ITGA2, LEF1, NR5A1, PTHLH, RIMS3, SORT1, SOX2 activated ALK, and downstream ALK-activated BAP1, CAD, CDH13, CNTNAP2, GRM1, ITGA2, LAPTM4B, MAP2K6, NR5A1, STMN1 in HCC. We obtained that the different biological processes of ALK activated network consisted of folic acid transport, cell surface receptor linked signal transduction, cell-cell signaling, G-protein coupled receptor protein signaling pathway, integrin-mediated signaling pathway, intracellular signaling cascade, low density lipoprotein mediated signaling, Rac protein signal transduction, Rho protein signal transduction in HCC compared with the activated network of no-tumor hepatitis/cirrhotic tissues, as a result of inducing folic acid transport and integrin signal induced-angiogenesis in HCC. Our hypothesis was verified by the different and the same biological processes of ALK activated transport and signal network of HCC compared with the corresponding inhibited network of no-tumor hepatitis/cirrhotic tissues and HCC, respectively.
ARTEFACT REMOVAL APPROACH FOR EPILEPTIC EEG DATA

In clinical neuroscience the EEG is used for diagnosis and monitoring of treatment efficacy in several diseases and dysfunctions of the brain. Data from long-term recordings of EEG become available in monitoring scenarios such as pre-surgical epilepsy and intensive care monitoring. In neuroscience and cognitive sciences, the EEG provides the data for many advanced analysis strategies, like source localization and connectivity analysis. EEG recordings have a low amplitude and are very sensitive to movement artefacts that can be caused by head movements (e.g. electrode displacement), eye and eyelid movements and by muscle activity (face and neck muscles). An analysis of contaminated EEG data can lead to misinterpretations of the results. Consequently, artefact removal is an important pre-processing step. Many studies have focused on methods that aim at the reduction of artefacts' influence on EEG data. A high number of approaches that focus on artefact removal exist and most of them are specialized on a type of artefact (ocular, heartbeat, movement). Methods that use a co-registered reference signal are applicable when recordings
Hemin-induced Activation of the Thioredoxin Gene by Nrf2

Thioredoxin plays an important role in various cellular processes through redox regulation. Here, we have demonstrated that thioredoxin expression is transcriptionally induced in K562 cells by hemin (ferriprotoporphyrin IX) through activation of a regulatory region positioned from −452 to −420 bp of the thioredoxin gene. Insertion of a mutation in the antioxidant responsive element (ARE)/AP-1 consensus binding sequence in this region abolished the response to hemin. With electrophoretic mobility shift and DNA affinity assays, we have shown that the NF-E2p45/small Maf complex constitutively binds to the ARE. The binding of the Nrf2/small Maf complex to ARE was induced by hemin, whereas the binding of Jun/Fos proteins to ARE was induced by phorbol 12-myristate 13-acetate, but not hemin. Hemin induced nuclear translocation of Nrf2 but did not affect nuclear expression of Jun/Fos proteins. Overexpression of Nrf2 augmented the response to hemin in a dose-dependent manner. In contrast, overexpression of the dominant negative mutant of Nrf2 suppressed hemin-induced activation through the ARE. We show here hemin-induced activation of the thioredoxin gene by Nrf2 through the ARE and propose a novel mechanism of the regulation of the ARE through a switch of its binding factors.
A RelA‐dependent two‐tiered regulated proteolysis cascade controls synthesis of a contact‐dependent intercellular signal in Myxococcus xanthus

Proteolytic cleavage of precursor proteins to generate intercellular signals is a common mechanism in all cells. In Myxococcus xanthus the contact‐dependent intercellular C‐signal is a 17 kDa protein (p17) generated by proteolytic cleavage of the 25 kDa csgA protein (p25), and is essential for starvation‐induced fruiting body formation. p25 accumulates in the outer membrane and PopC, the protease that cleaves p25, in the cytoplasm of vegetative cells. PopC is secreted in response to starvation, therefore, restricting p25 cleavage to starving cells. We focused on identifying proteins critical for PopC secretion in response to starvation. PopC secretion depends on the (p)ppGpp synthase RelA and the stringent response, and is regulated post‐translationally. PopD, which is encoded in an operon with PopC, forms a soluble complex with PopC and inhibits PopC secretion whereas the integral membrane AAA+ protease FtsHD is required for PopC secretion. Biochemical and genetic evidence suggest that in response to starvation, RelA is activated and induces the degradation of PopD thereby releasing pre‐formed PopC for secretion and that FtsHD is important for PopD degradation. Hence, regulated PopC secretion depends on regulated proteolysis. Accordingly, p17 synthesis depends on a proteolytic cascade including FtsHD‐dependent degradation of PopD and PopC‐dependent cleavage of p25.
A monolithic optical frequency comb generator

A monolithic optical frequency comb (OFC) generator was realized by coating high reflection films on the facets of a LiNbO/sub 3/ crystal used for an electro-optic (EO) phase modulator. The optical round-trip loss in the monolithic OFC generator was reduced to extend the span of an OFC. It is confirmed that the envelope of the OFC extended to a span as wide as 48 nm (or 6.1 THz) around 1.5 /spl mu/m. The maximum measurable frequency difference, which was defined as the sideband frequency with the signal-to-noise ratio of 0 dB, was estimated to be also 6.1 THz. <<ETX>>
Pre-steady-state kinetics of the microtubule-kinesin ATPase.

The pre-steady-state kinetics of the microtubule-kinesin ATPase were investigated by chemical-quench flow methods using the Drosophila kinesin motor domain (K401) expressed in Escherichia coli [Gilbert, S. P., & Johnson, K. A. (1993) Biochemistry 32, 4677-4684]. The results define a minimal mechanism: M.K + ATP in equilibrium with (M). K.ATP in equilibrium with (M). K.ADP. Pi in equilibrium with M.K.ADP + Pi in equilibrium with M.K + ADP, where M, K, and Pi represent microtubules, kinesin, and inorganic phosphate, respectively, with k+1 = 0.8-3 microM-1 s-1, k-1 = 100-300 s-1, k+2 = 70-120 s-1, k+4 = 10-20 s-1, and k+3 >> k-2 and k+3 >> k+4. Conditions were as follows: 25 degrees C, 20 mM HEPES, pH 7.2 with KOH, 5 mM magnesium acetate, 0.1 mM EDTA, 0.1 mM EGTA, 50 mM potassium acetate, 1 mM DTT. The experiments presented do not determine the step in the cycle where kinesin dissociates from the microtubule or the step at which kinesin reassociates with the microtubule; therefore, the steps that may represent kinesin as the free enzyme are indicated by (M). A burst of ADP product formation was observed during the first turnover of the enzyme in the acid-quench experiments that define the ATP hydrolysis transient. The observation of the burst demonstrates that product release is rate limiting even in the presence of saturating microtubule concentrations. The pulse-chase experiments define the time course of ATP binding to the microtubule-K401 complex. At low ATP concentrations, ATP binding limits the rate of the burst. However, at high concentrations of ATP, ATP binding is faster than the rate of ATP hydrolysis with k+2 = 70-120 s-1. The amplitude of the burst of the ATP binding transient reached a maximum of 0.7 per site at saturating concentrations of ATP and microtubules. The amplitude of less than 1 is attributed to the fast k(off) for ATP (k-1 = 100-300 s-1) that leads to a partitioning of the M.K.ATP complex between ATP hydrolysis (k+2) and ATP release (k-1). These results indicate that ATP binds weakly to the M.K complex (Kd,ATP app approximately 100 microM). ADP release (k+4 = 10-20 s-1) is rate limiting during steady-state turnover, indicating that microtubules activate the kinesin ATPase by increasing k(off),ADP from 0.01 s-1 in the absence of microtubules to 10-20 s-1 at saturating microtubule concentrations.
Validity and Diagnostic Efficiency of the Kaufman Brief Intelligence Test in Reevaluating Students with Learning Disability

The present study examined the concurrent validity and diagnostic efficiency of the Kaufman Brief Intelligence Test (K-BIT). Seventy-five students with learning disability were administered the K-BIT, Wechsler Intelligence Scale for Children-Third Edition (WISC-III), and Woodcock-Johnson-Revised Tests of Achievement (WJ-R ACH) as part of their triennial reevaluation. Correlations between the K-BIT and the WISC-III ranged from . 18 (r2 = .03) to . 82 (r2 = .67), M, = . 62 (Mr2 = .38). High levels of agreement were obtained between the K-BIT and WISC-III in identifying severe achievement-ability discrepancies on the WJ-R ACH. The K-BIT appears to be a promising general intellectual screening instrument when more comprehensive assessment is not possible or needed.
Recent advances in the surgical management of necrotizing pancreatitis

Purpose of reviewTo summarize advances and new concepts in the surgical management of necrotizing pancreatitis published within the past year with emphasis on the evolving importance of the recognition of abdominal compartment syndrome as a significant contributor to early development of organ failure. Recent findingsUnderdiagnosed and untreated, abdominal compartment syndrome is a potential contributing factor to the development of early organ failure in patients with severe acute pancreatitis and warrants routine measurement of intra-abdominal pressure in patients treated for severe pancreatitis. The current estimate of the prevalence of intra-abdominal hypertension in severe acute pancreatitis is about 40%, with about 10% overall developing abdominal compartment syndrome, associated with increased hospital mortality rates. Early surgical decompression without exploring the pancreas further seems to be the most effective treatment. Primary fascial closure of the abdominal wall following abdominal decompression can be attempted, but in most cases the prolonged inflammatory process in the abdomen and the risk of recurrent abdominal compartment syndrome favors use of gradual closure or delayed reconstruction of the abdominal wall. SummaryRecent studies confirm the overall validity of the established surgical principles for necrotizing pancreatitis: delayed necrosectomy in patients with infected peripancreatic necrosis, mostly nonoperative management of sterile necrosis, and delayed cholecystectomy in severe gallstone-associated pancreatitis. The role of abdominal compartment syndrome as an important contributing factor to early development of multiple organ failure and the potential benefit of surgical decompression are gaining support from recent reports and should be carefully assessed in future studies.
Involvement of a Disulfide Bond in the Binding of Flunitrazepam to the Benzodiazepine Receptor from Bovine Cerebral Cortex

Abstract: The effects of chemical modification of a disulfide bond(s) (‐SS‐) or sulfhydryl group(s) (‐SH) on the [3H]‐flunitrazepam ([3H]FNZ) binding to membrane‐bound or immunoprecipitated benzodiazepine (BZD) receptors (BZD‐R) from bovine cerebral cortex were examined. Reduction of ‐SS‐ with dithiothreitol (DTT) brought about a reversible, time‐ and dose‐dependent inhibition of [3H]FNZ binding to the membrane‐bound BZD‐R. Alkylation of the membranes with the ‐SH‐modifying reagent iodoacetamide (IAA) or 5,5′‐dithiobis‐(2‐nitrobenzoic acid) (DTNB) produced a slight inhibition of [3H]FNZ binding in a dose‐dependent manner. Scatchard analysis of saturation curves of [3H]FNZ binding in the presence and absence of 5 mM DTT revealed changes in affinity without modification in the maximal binding capacity, thus indicating a competitive mode of interaction. DTT pretreatment of both the membrane‐bound and the immunoprecipitated BZD‐R led to [3H]FNZ binding inhibition. Consistent with the modification of a binding site is the observation that reduction of ‐SS‐ does not bear on the binding affinity, but rather reduces the number of sites. Complete protection from DTT inhibition of [3H]FNZ binding by FNZ (an agonist) or by Ro 15–1788 (an antagonist) suggests the presence of ‐SS‐ at, or very close to, the BZD recognition binding site. No protection against IAA or DTNB inhibition was provided by FNZ. Photoaffinity labeling experiments with [3H]FNZ revealed a clear‐cut band of 50 kDa in native and alkylated membranes but an extremely weak label in 5 mM DTT/IAA‐treated membranes. The present results provide evidence for the participation of a disulfide bond in the recognition binding site of the bovine cerebral cortex BZD‐R.
From Beginning to End: Video‐based Introductory, Instructional, and Evaluation Applications

To assess the feasibility of incorporating video applications into distance education courses, faculty and student produced videos to aid in transferring knowledge from nursing courses to clinical practice. Student videos validated prerequisite physical assessment knowledge and skills, allowing identification of students who needed remedial work, therefore, facilitating progression into the advanced content. Faculty-generated video vignettes simulated family dynamics, thus making abstract content concrete. Vignettes were also used to evaluate students' attainment of counseling techniques through testing applications.