Miracle-dz/UniFAR-FTUs huggingface dataset:
Weaponizing human EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) for 21st century cancer therapeutics

De-regulated EFEMP1 gene expression in solid tumors has been widely reported with conflicting roles. We dissected EFEMP1 to identify domains responsible for its cell context-dependent dual functions, with the goal being to construct an EFEMP1-derived tumor-suppressor protein (ETSP) that lacked tumor-promoting function. Exon/intron boundaries of EFEMP1 were used as boundaries of functional modules in constructing EFEMP1 variants, with removal of various module(s), and/or mutating an amino acid residue to convert a weak integrin binding-site into a strong one. A series of in vitro assays on cancerous features, and subcutaneous and intracranial xenograft-formation assays, were carried out for effects from overexpression of wild-type and variant forms of EFEMP1 in two glioma subpopulations characterized as tumor mass-forming cells (TMCs) or stem-like tumor initiating cells (STICs), where EFEMP1 showed cellcontext- dependent dual functions. One of the EFEMP1 variants was identified as the sought-after ETSP, which had a stronger tumor-suppression function in TMCs by targeting EGFR and angiogenesis, and a new tumor-suppression function in STICs by targeting NOTCH signaling and MMP2-mediated cell invasion. Therefore, ETSP may form the basis for further important research to develop a novel cancer therapy to treat many types of cancer by its tumor suppressor effect in the extracellular matrix compartment.
Low Dose Isoflurane Exerts Opposing Effects on Neuronal Network Excitability in Neocortex and Hippocampus

The anesthetic excitement phase occurring during induction of anesthesia with volatile anesthetics is a well-known phenomenon in clinical practice. However, the physiological mechanisms underlying anesthetic-induced excitation are still unclear. Here we provide evidence from in vitro experiments performed on rat brain slices that the general anesthetic isoflurane at a concentration of about 0.1 mM can enhance neuronal network excitability in the hippocampus, while simultaneously reducing it in the neocortex. In contrast, isoflurane tissue concentrations above 0.3 mM expectedly caused a pronounced reduction in both brain regions. Neuronal network excitability was assessed by combining simultaneous multisite stimulation via a multielectrode array with recording intrinsic optical signals as a measure of neuronal population activity.
Fatigue Damage and Degradation in Random Short-Fiber SMC Composite

Damage accumulation and cyclic degradation in a random short-fiber SMC com posite subjected to tensile fatigue loading are studied. Fatigue damage in various forms of microcracking is examined. The transient nature of the nonlinear, monotonic stress- strain curve is investigated first, and subsequent property degradation and hysteresis loop changes are examined. Contrary to the behavior of certain metals and polymers, a cyclic stable state is never reached in general; cyclic softening is always observed in this class of materials. Owing to the random microstructure of the SMC material, the fatigue damage is viewed as being macroscopically homogeneous and uniform, and the damage growth is treated in a continuous sense. A parameter is then introduced to define the degree of the homogeneous damage. A power-law relationship among the rate of damage evolution, loading variables, and cyclic history is established. The homogeneous fatigue damage decreases rapidly with the loading cycle due to combined effects of rapid depletion of microcrack initiation sites and presence of various crack arrest mechanisms.
Mechanisms of retarded apical filling in acute ischemic left ventricular failure.

BACKGROUND We examined the hypothesis that retardation of apical filling as measured by color M-mode Doppler echocardiography in the diseased left ventricle (LV) reflects a decrease in the intraventricular mitral-to-apical pressure gradient. METHODS AND RESULTS In 9 open-chest anesthetized dogs, micromanometers were placed near the mitral tip and in the apical region. From the color M-mode Doppler images, the time delay (TD) between peak velocity at the mitral tip and the apical region was determined as an index of LV flow propagation. Acute ischemic LV failure was induced by coronary microembolization. Induction of ischemia caused a marked increase in LV end-diastolic pressure and a decrease in LV ejection fraction. The time constant of LV isovolumic apical pressure decay (tau) increased from 31+/-8 to 49+/-16 ms (P<0.001). The peak early diastolic mitral-to-apical pressure gradient (DeltaPLVmitral-apex) decreased from 1.9+/-0.9 to 0.7+/-0.5 mm Hg (P<0.01), and TD increased from 5+/-3 to 57+/-26 ms (P<0.001). The slowing of flow propagation was limited to the apical portion of the LV cavity. The TD correlated with DeltaPLVmitral-apex (r=-0.94, P<0.01) and with tau (r=0.92, P<0.01). Before ischemia, the mitral-to-apical flow propagation velocity far exceeded the velocity of the individual blood cells, whereas during ischemia, flow propagation velocity approximated the blood velocity. CONCLUSIONS Retardation of apical filling in acute ischemic failure was attributed to a decrease in the mitral-to-apical driving pressure, reflecting slowing of LV relaxation. The slowing of flow propagation appeared to represent a shift in apical filling from a pattern of column motion to a pattern dominated by convection.
Evaluation of alternative arbitration policies fo myrinet switches

Interconnection networks consist of a set of switches interconnected by point-to-point links, and hosts linked to those switches through a network interface card. These networks are becoming increasingly popular as a cost-effective alternative to parallel computers. One of the most well-known example is the Myrinet network. These networks use techniques and incorporate components that have been successfully applied to interconnection networks for parallel computers. One of these techniques is the use of crossbar chips as the main component of switches, allowing to connect the input channel of any of their ports to the output channel of any of their ports for forwarding incoming packets. Of course, when several packets request the same output channel, certain criterion must be used for selecting one of them. This criterion may affect performance in terms of latency and throughput, specially in wormhole networks (Myrinet) where a packet occupies several resources while it is waiting for the output channel. In Myrinet, an arbitration policy based on round-robin criterion is used. However, there exist other arbitration policies that, when applied to Myrinet networks, could increase their performance. In this paper, several arbitration policies for selecting the packet for a free output channel have been considered and evaluated. We have found that strategies based on injection time and remaining distance to travel reduce the average and maximum packet latency of the current policy used in Myrinet.
Growth Patterns in Early Childhood and Final Attained Stature: Data from Five Birth Cohorts from Low- and Middle-Income Countries

Growth failure is cumulative, and short stature is associated with multiple indices of reduced human capital. Few studies have been able to address in a single analysis both consideration of the timing of growth failure and comparison across populations. We analyzed data from birth cohorts in Brazil, Guatemala, India, the Philippines, and South Africa (n = 4,659). We used data on length at birth (available for three of the five cohorts), 12 mo, 24 mo, and mid‐childhood to construct cohort‐ and sex‐ specific conditional length measures. We modeled adult height as a function of conditional length in childhood. The five cohorts experienced varying degrees of growth failure. As adults, the Brazil sample was 0.35 ± 0.89 standard deviations (SD) below the World Health Organization reference, while adult Guatemalans were 1.91 ± 0.87 SD below the reference. All five cohorts experienced a nadir in height for age Z‐score at 24 mo. Birth length (in the three cohorts with this variable), and conditional length at 12 mo (in all five cohorts) were the most strongly associated with adult height. Growth in the periods 12–24 mo and 24 mo to mid‐childhood showed inconsistent patterns across tertiles of adult height. Despite variation in the magnitude of cumulative growth failure across cohorts, the five cohorts show highly consistent age‐specific associations with adult stature. Growth failure prior to age 12 mo was most strongly associated with adult stature. These consistencies speak to the importance of interventions to address intrauterine growth failure and growth failure in the first 12 mo of life. Am. J. Hum. Biol. 2010. © 2009 Wiley‐Liss, Inc.
Hydroxytyrosol protects retinal pigment epithelial cells from acrolein‐induced oxidative stress and mitochondrial dysfunction

Hydroxytyrosol (HTS) is a natural polyphenol abundant in olive oil. Increasing evidence indicates HTS has beneficial effect on human health for preventing various diseases. In the present study, we investigated the protective effects of HTS on acrolein‐induced toxicity in human retinal pigment epithelial cell line, ARPE‐19, a cellular model of smoking‐ and age‐related macular degeneration. Acrolein, a major component of the gas phase cigarette smoke and also a product of lipid peroxidation in vivo, at 75 μmol/L for 24 h caused significant loss of cell viability, oxidative damage (increase in oxidant generation and oxidative damage to proteins and DNA, decrease in antioxidants and antioxidant enzymes, and also inactivation of the Keap1/Nrf2 pathway), and mitochondrial dysfunction (decrease in membrane potential, activities of mitochondrial complexes, viable mitochondria, oxygen consumption, and factors for mitochondrial biogenesis, and increase in calcium). Pre‐treatment with HTS dose dependently and also time dependently protected the ARPE‐19 cells from acrolein‐induced oxidative damage and mitochondrial dysfunction. A short‐term pre‐treatment with HTS (48 h) required > 75 μmol/L for showing protection while a long‐term pre‐treatment (7 days) showed protective effect from 5 μmol/L on. The protective effect of HTS in this model was as potent as that of established mitochondria‐targeting antioxidant nutrients. These results suggest that HTS is also a mitochondrial‐targeting antioxidant nutrient and that dietary administration of HTS may be an effective measure in reducing and or preventing cigarette smoke‐induced or age‐related retinal pigment epithelial degeneration, such as age‐associated macular degeneration.
In Vivo Regulatory Phosphorylation of Novel Phosphoenolpyruvate Carboxylase Isoforms in Endosperm of Developing Castor Oil Seeds1

Our previous research characterized two phosphoenolpyruvate (PEP) carboxylase (PEPC) isoforms (PEPC1 and PEPC2) from developing castor oil seeds (COS). The association of a shared 107-kD subunit (p107) with an immunologically unrelated bacterial PEPC-type 64-kD polypeptide (p64) leads to marked physical and kinetic differences between the PEPC1 p107 homotetramer and PEPC2 p107/p64 heterooctamer. Here, we describe the production of antiphosphorylation site-specific antibodies to the conserved p107 N-terminal serine-6 phosphorylation site. Immunoblotting established that the serine-6 of p107 is phosphorylated in COS PEPC1 and PEPC2. This phosphorylation was reversed in vitro following incubation of clarified COS extracts or purified PEPC1 or PEPC2 with mammalian protein phosphatase type 2A and is not involved in a potential PEPC1 and PEPC2 interconversion. Similar to other plant PEPCs examined to date, p107 phosphorylation increased PEPC1 activity at pH 7.3 by decreasing its Km(PEP) and sensitivity to l-malate inhibition, while enhancing glucose-6-P activation. By contrast, p107 phosphorylation increased PEPC2's Km(PEP) and sensitivity to malate, glutamic acid, and aspartic acid inhibition. Phosphorylation of p107 was promoted during COS development (coincident with a >5-fold increase in the I50 [malate] value for total PEPC activity in desalted extracts) but disappeared during COS desiccation. The p107 of stage VII COS became fully dephosphorylated in planta 48 h following excision of COS pods or following 72 h of dark treatment of intact plants. The in vivo phosphorylation status of p107 appears to be modulated by photosynthate recently translocated from source leaves into developing COS.
Nucleotide analogs related to acyclovir and ganciclovir are effective against murine cytomegalovirus infections in BALB/c and severe combined immunodeficient mice

Acyclovir phosphonate [9-(3-phosphono-propyloxymethyl)guanine; SR3722] and the S enantiomer (SR3772), R enantiomer (SR3773), and R,S enantiomeric mixture (SR3745A) of ganciclovir phosphonate (9-[((+/-)-1-hydroxymethyl-3-phosphono)propyloxymethyl]guanine) were evaluated for their antiviral activities against murine cytomegalovirus. In severe combined immunodeficient mice infected with murine cytomegalovirus, SR3773 and SR3745A (12.5, 25, and 50 mg/kg of body weight per day) were superior to ganciclovir in extending the mean time to death, whereas SR3722 and SR3772 was less potent than ganciclovir. In normal BALB/c mice, SR3773 and ganciclovir were approximately equally active in preventing death. SR3773 caused renal tubular damage when administered at 50 mg/kg/day for 15 days. These results suggest that SR3773 may have potential for use in the treatment of human cytomegalovirus infections, but it may also exhibit renal toxicity.
Bank Supervision and Corporate Finance

The authors examine the impact of bank supervision on the financing obstacles faced by almost 5,000 corporations across 49 countries. They find that firms in countries with strong official supervisory agencies that directly monitor banks tend to face greater financing obstacles. Moreover, powerful official supervision tends to increase firm reliance on special connections and corruption in raising external finance, which is consistent with political and regulatory capture theories. Creating a supervisory agency that is independent of the government and banks mitigates the adverse consequences of powerful supervision. Finally, the authors find that bank supervisory agencies that force accurate information disclosure by banks and enhance private monitoring tend to ease the financing obstacles faced by firms.
Palifermin for management of treatment-induced oral mucositis in cancer patients

Oral mucositis (OM) remains a major side effect of various cancer therapies, which exacts a significant price in terms of morbidity and cost of care. Efforts aimed at prevention and/or therapy of OM have been largely unsuccessful. Few agents have shown efficacy, and even those were applicable to limited types of patients. The advent of small-molecule targeted agents opened new possibilities for intervention in the mucopathogenic processes induced by cancer therapies. One of these agents, recombinant human keratinocyte growth factor (KGF), has been studied extensively and has shown promising results in reducing chemotherapy induced OM. This drug’s effects on stem cell engraftment, graft-versus-host disease and other treatment-induced morbidities remain undefined. In this article we evaluate the pre-clinical and clinical evidence and discuss the clinical applications of KGF as an adjunct therapeutic agent in oncology.
Surgical Remedies for Postpartum Hemorrhage

When medical therapy is unsuccessful, surgical approaches to postpartum hemorrhage are often considered. These may include uterine curettage, laceration repair, balloon tamponade, compressive suture techniques, uterine or hypogastric artery ligation, and ultimately hysterectomy. A systems approach to the care of these patients includes identification of rapid response teams, assessment of risk factors, and the timely and knowledgeable use of blood and blood products. Comprehensive care of patients with massive obstetric hemorrhage will improve the outcome of this largely preventable cause of maternal mortality.
Urban emergency department overcrowding: defining the problem and eliminating misconceptions.

STUDY OBJECTIVE To develop an operational definition and a parsimonious list of postulated determinants for urban emergency department (ED) overcrowding. METHODS A panel was formed from clinical and administrative experts in pre-hospital, ED and hospital domains. Key studies and reports were reviewed in advance by panel members, an experienced health services researcher facilitated the panel's discussions, and a formal content analysis of audiotaped recordings was conducted. RESULTS The panel considered community, patient, ED and hospital determinants of overcrowding. Of 46 factors postulated in the literature, 21 were not retained by the experts as potentially important determinants of overcrowding. Factors not retained included access to primary care services and seasonal influenza outbreaks. Key determinants retained included admitted patients awaiting beds and patient characteristics. Ambulance diversion was considered to be an appropriate operational definition and proxy measure of ED overcrowding. CONCLUSION These results help to clarify the conceptual framework around ED overcrowding, and may provide a guide for future research. The relative importance of the determinants must be assessed by prospective studies.
Quantum and classical message identification via quantum channels

We discuss concepts of message identification in the sense of Ahlswede and Dueck via general quantum channels, extending investigations for classical channels, initial work for classical-quantum (cq) channels and "quantum fingerprinting". We show that the identification capacity of a discrete memoryless quantum channel for classical information can be larger than that for transmission; this is in contrast to all previously considered models, where it turns out to equal the common randomness capacity (equals transmission capacity in our case): in particular, for a noiseless qubit, we show the identification capacity to be 2, while transmission and common randomness capacity are 1. Then we turn to a natural concept of identification of quantum messages (i.e. a notion of "fingerprint" for quantum states). This is much closer to quantum information transmission than its classical counterpart (for one thing, the code length grows only exponentially, compared to double exponentially for classical identification). Indeed, we show how the problem exhibits a nice connection to visible quantum coding. Astonishingly, for the noiseless qubit channel this capacity turns out to be 2: in other words, one can compress two qubits into one and this is optimal. In general however, we conjecture quantum identification capacity to be different from classical identification capacity.
Resolving the phylogenetic and taxonomic status of dark-spored teleomorph genera in the Botryosphaeriaceae

Species in the Botryosphaeriaceae are common plant pathogens and saprobes found on a variety of mainly woody hosts. Teleomorphs typically have hyaline, aseptate ascospores. However, some have been reported with brown ascospores and their taxonomic status is uncertain. A multi-gene approach (SSU, ITS, LSU, EF1-α and β-tubulin) was used to resolve the correct phylogenetic position of the dark-spored ‘Botryosphaeria’ teleomorphs and related asexual species. Neodeightonia and Phaeobotryon are reinstated for species with brown ascospores that are either 1-septate (Neodeightonia) or 2-septate (Phaeobotryon). Phaeobotryosphaeria is reinstated for species with brown, aseptate ascospores that bear an apiculus at either end. The status of Sphaeropsis is clarified and shown to be the anamorph of Phaeobotryosphaeria. Two new genera, namely Barriopsis for species having brown, aseptate ascospores without apiculi and Spencermartinsia for species having brown, 1-septate ascospores with an apiculus at either end are introduced. Species of Dothiorella have brown, 1-septate ascospores and differ from Spencermartinsia in the absence of apiculi. These six genera can also be distinguished from one another based on morphological characters of their anamorphs. Although previously placed in the Botryosphaeriaceae, Dothidotthia, was shown to belong in the Pleosporales, and the new family Dothidotthiaceae is introduced to accommodate it.
Mitotic regulation of fungal cell-to-cell connectivity through septal pores involves the NIMA kinase

Septal pores—the intercellular bridges of fungi—are open during interphase but closed at mitosis. The NIMA kinase mitotically regulates septal pore closing and opening potentially via mechanisms analogous to how it regulates mitotic nuclear pores. The findings explain how and why physically connected Aspergillus cells can maintain mitotic autonomy.
Intracellular uptake and intracavitary targeting of folate-conjugated liposomes in a mouse lymphoma model with up-regulated folate receptors

The folate receptor is overexpressed in a broad spectrum of malignant tumors and represents an attractive target for selective delivery of anticancer agents to folate receptor–expressing tumors. This study examines folate-lipid conjugates as a means of enhancing the tumor selectivity of liposome-encapsulated drugs in a mouse lymphoma model. Folate-derivatized polyethylene glycol (PEG3350)-distearoyl-phosphatidylethanolamine was post-loaded at various concentrations into the following preparations: radiolabeled PEGylated liposomes, PEGylated liposomes labeled in the aqueous compartment with dextran fluorescein, and PEGylated liposomal doxorubicin (PLD, Doxil). We incubated folate-targeted radiolabeled or fluorescent liposomes with mouse J6456 lymphoma cells up-regulated for their folate receptors (J6456-FR) to determine the optimal ligand concentration required in the lipid bilayer for liposomal cell association, and to examine whether folate-targeted liposomes are internalized by J6456-FR cells in suspension. Liposomal association with cells was quantified based on radioactivity and fluorescence-activated cell sorting analysis, and internalization was assessed by confocal fluorescence microscopy. We found an optimal ligand molar concentration of ∼0.5% using our ligand. A substantial lipid dose-dependent increase in cell-associated fluorescence was found in folate-targeted liposomes compared with nontargeted liposomes. Confocal depth scanning showed that a substantial amount of the folate-targeted liposomes are internalized by J6456-FR cells. Binding and uptake of folate-targeted PLD by J6456-FR cells were also observed in vivo after i.p. injection of folate-targeted PLD in mice bearing ascitic J6456-FR tumors. The drug levels in ascitic tumor cells were increased by 17-fold, whereas those in plasma were decreased by 14-fold when folate-targeted PLD were compared with nontargeted PLD in the i.p. model. Folate-targeted liposomes represent an attractive approach for the intracellular delivery of drugs to folate receptor–expressing lymphoma cells and seem to be a promising tool for in vivo intracavitary drug targeting. [Mol Cancer Ther 2006;5(4):818–24]