Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroglian stabilizes epithelial structure during Drosophila oogenesis

The vertebrate L1 family of cell adhesion molecules (CAMs) and their fly homolog, Neuroglian, are members of the immunoglobulin (Ig) superfamily of CAMs. In general, Ig CAMs have been found to play critical roles in mediating axon guidance. One Ig CAM, NCAM, has also been implicated in maintaining epithelial integrity and suppressing metastatic dissemination of tumor cells. Other Ig CAMs, such as Nrg, are also expressed in epithelia. We thus tested the hypothesis that, like NCAM, Nrg might also be required for maintaining epithelial integrity and for inhibiting tumor invasion. We used the Drosophila follicular epithelium to determine the function of Nrg in vivo in maintaining epithelial structure, and in regulating the motility of migrating border cells and invasive tumorous follicle cells. Nrg167 is expressed on the lateral membrane of follicle cells. Loss of Nrg167 causes border cells to delay delamination and causes other follicle cells to delaminate inappropriately. The delaminated cells have aberrant epithelial polarity manifested as severe mislocalization of apical and basal membrane proteins, and uniform localization of lateral membrane proteins. Furthermore, loss of Nrg167 dramatically enhances the invasive phenotype associated with loss of Discs Large, a neoplastic tumor suppressor. These results indicate that Nrg167 stabilizes epithelial polarity by regulating junctional adhesion and function in normal and tumorous epithelia. Our data also suggest that Ig superfamily members have significant functional redundancy in maintaining epithelial polarity, with individual members playing subtle, unique roles during epithelial morphogenesis. Developmental Dynamics 230:800–808, 2004. © 2004 Wiley‐Liss, Inc.
Relationship Between Mast Cell Subtypes and Cyclooxygenase-2 Expression in Uterine Leiomyomas

Objective: Mast cells (MCs) have been proved to be multifunctional cells which are known to be located at peri-and intra-tumoral sites, playing an active role physiologically or pathologically. In humans, MCs are subtyped by the difference in their neutral protease content. MCs that have granules containing tryptase alone (MCT) are predominantly found at mucosal sites. MCs whose granules possess tryptase along with chymase (MCTC) are found especially within connective tissue. MC mediators have different functions and the coexistence of both MC subtypes contributes to tissue homeostasis. Furthermore, cyclooxygenase-2 (COX-2) is an enzyme associated with inflammation, cell growth and differentiation, prevention of apoptosis and tumorigenesis. Recent studies show the clinical significance of COX-2 expression in different tumor types. However, to our knowledge, there is no data assessing the relationship between COX-2 and MC density in uterine leiomyomas. We aimed to investigate the relation between the expression of COX-2, MC density, and proportional changes of MC phenotypes in human leiomyoma uteri and control cases, and also their possible correlations between each other. Methods: We performed a retrospective study of 34 cases carried out on parafin-embedded samples obtained from 14 control (group 1) and 20 leiomyoma uteri (group 2) patients who had undergone curative hysterectomy. These specimens were investigated immunohistochemically by using anti-cyclooxygenase-2 (COX-2) antibodies to stain COX-2; anti-tryptase antibodies to stain MCT and anti-chymase antibodies to stain MCTC. Results: In leiomyoma, the median value of COX-2 staining grade was 2 (min:1-max:3) which was statistically lower than that of controls with a median value of 3 (min:2-max:4) (p=0.001). The median value of tryptase expression was 12 (min:10-max:16) in the control myometrium, slightly higher than that of the leiomyoma group which had a median value of 10.5 (min:6-max:15). On the other hand, the median value of chymase expression was 7 (min:4-max:13) in the control myometrium, which was significantly higher (p=0.001) than that of the leiomyoma group with a median value of 5 (min:2max:8). Thus, in the leiomyoma group, the mast cell subtypes, including tryptase÷chymase proportion, was found to be significantly higher than the controls (p=0.032). Moreover, COX-2, tryptase and chymase expressions showed no correlation in both groups. Conclusion: This study has demonstrated that expressions of COX-2 and mast cell subtypes are reduced in leiomyoma, and the proportion of mast cell subtypes of MCT÷MCTC increases in leiomyoma compared to the control group. However, MC subtypes neither correlated with each other nor with COX-2 expression in the leiomyoma and control series. Understanding the mechanisms for MC functions and the secretory molecules will provide a basis for a rational approach to the development of antitumoral therapy in patients with leiomyoma and other tumors. (JAREM 2011; 1: 44-8)
Potentiation of 45Ca Uptake and Acute Toxicity Mediated by the N‐Methyl‐D‐Aspartate Receptor: The Effect of Metal Binding Agents and Transition Metal Ions

Abstract: The activities mediated by the N‐methyl‐D‐aspartate (NMDA) receptor were studied in cultured rat cerebellar granule cells. Micromolar concentrations of the metal binding compounds, EDTA, cysteine, and histidine, as well as serum albumin strongly potentiated receptor activity in the presence of millimolar concentrations of Ca2+ and Mg2+. The findings indicated that these agents remove an endogenous metal, probably Zn2+, which attenuates NMDA receptor‐mediated 45Ca uptake and toxicity. Several added metal ions were therefore tested at low micromolar concentrations. Zn2+ was found to be the most potent inhibitor of NMDA‐induced 45Ca uptake, followed by Cu2+ and Fe2+. Co2+, Cd2+, Fe3+, and AI3+ had no significant effect, whereas Ni2+ potentiated the 45Ca uptake but inhibited at much higher concentrations. The potentiating agents that remove the endogenous metal had a particularly dramatic effect in the presence of Mg2+, the voltage‐dependent suppressor of the NMDA receptor. Mg2+ also played an important role in the inhibitory effect of added Zn2+. Much lower concentrations of Zn2+ were needed to achieve inhibition of NMDA‐induced 45Ca uptake in the presence of Mg2+. Under a variety of conditions, a very good correlation was found between NMDA receptor‐mediated 45Ca uptake and the magnitude of acute neurotoxicity.
Neuronal basis of auditory adaptation and temporal discrimination in the auditory cortex of the awake freely moving rat

La adaptacion que ocurre en el sistema auditivo es un fenonemo que todos experimentamos cuando dejamos de oir sonidos irrelevantes, constantes o incluso molestos. La adaptacion para sonidos conocidos aumenta tambien la sensibilidad y la percepcion para estimulos nuevos o poco conocidos. Por tanto, la similaridad entre la historia previa de estimulacion y la subsiguiente tambien puede influenciar la adaptacion. La adaptacion a la estimulacion repetida es un fenomeno que se ha visto en diferentes modalidades sensoriales o especies de animales. El curso temporal de la adaptacion en corteza auditiva primaria (A1) se ha estudiado principalmente en intervalos entre estimulos muy rapidos (<400ms) y diferentes mecanismos han sido sugeridos (inhibicion sinaptica, disbalance excitacion-inhibicion, inhibicion lateral, disminucion de la excitacion, o inhibicion aumentada), aunque los mecanismos intrinsecos neuronales casi no han sido considerados. Por otro lado, numerosos estudios han mostrado el efecto que tiene la anestesia sobre la excitabilidad cortical, pudiendo, por tanto, afectar al estudio de la adaptacion. Por ultimo, la adaptacion podria estar influenciada por estructuras subcorticales (como el coliculo inferior o el talamo) aunque la influencia intracortical tambien se ha demostrado. El primer estudio presentado en este trabajo tiene como objetivo caracterizar, en la rata despierta en movimiento, el curso temporal de la adaptacion auditiva en las neuronas unicas de A1 aisladas con tetrodos. Con este proposito, se estudio como el intervalo entre estimulos, la duracion o la intensidad de la estimulacion previa afectaba a la amplitud de respuesta y su latencia de respuesta. Tambien se estudio el curso temporal durante la estimulacion sostenida y el fenomeno de la postadaptacion. La comprension de como la actividad neuronal codifica la informacion sensorial sigue siendo una cuestion fundamental en el campo de la atencion auditiva. Asi, la codificacion de la informacion temporal es un aspecto clave en A1. El analisis de la “informacion mutua” de la respuesta neuronal nos permite cuantificar el contenido de la informacion de la actividad neuronal. Por otro lado, la variabilidad de la respuesta neuronal podria ser un parametro clave para la codificacion de los estimulos relevantes durante una tarea. Tambien, la respuesta neuronal sostenida se ha sugerido que podria aportar informacion adicional en el animal en comportamiento. Hasta el momento, se desconoce como las neuronas unicas de A1 codifican la categoria temporal de los estimulos auditivos. Con este objetivo se registro la actividad de neuronas unicas en A1, por medio de tetrodos, en el animal en comportamiento. Las ratas debian discriminar si dos sonidos identicos estaban separados por 150 o 300 ms y se ha estudiado el contenido de la informacion, la variabilidad y las respuestas post-estimulo de la actividad neuronal en el estado atentivo y el pasivo del animal.
The Enigma of Rapamycin Dosage

The mTOR pathway is a critical regulator of cell growth, proliferation, metabolism, and survival. Dysregulation of mTOR signaling has been observed in most cancers and, thus, the mTOR pathway has been extensively studied for therapeutic intervention. Rapamycin is a natural product that inhibits mTOR with high specificity. However, its efficacy varies by dose in several contexts. First, different doses of rapamycin are needed to suppress mTOR in different cell lines; second, different doses of rapamycin are needed to suppress the phosphorylation of different mTOR substrates; and third, there is a differential sensitivity of the two mTOR complexes mTORC1 and mTORC2 to rapamycin. Intriguingly, the enigmatic properties of rapamycin dosage can be explained in large part by the competition between rapamycin and phosphatidic acid (PA) for mTOR. Rapamycin and PA have opposite effects on mTOR whereby rapamycin destabilizes and PA stabilizes both mTOR complexes. In this review, we discuss the properties of rapamycin dosage in the context of anticancer therapeutics. Mol Cancer Ther; 15(3); 347–53. ©2016 AACR.
Autoradiographic study of tobramycin uptake by proximal and distal tubules of normal and pyelonephritic rats

Multiple factors may modify the pharmacokinetics of aminoglycosides and affect their nephrotoxic potential. In the present study, the influence of Escherichia coli pyelonephritis on the renal handling of [3H]tobramycin was investigated. The accumulation of [3H]tobramycin in proximal and distal tubules in both normal and infected rats was compared. Following induction of pyelonephritis, disturbed intrarenal localization of the drug was noted. Grain counts were affected in both proximal and distal tubules. Decreased labeling was observed at all time intervals in the proximal tubules. Electron microscopy showed that radioactivity was associated mostly with lysosomes in both normal and infected rats 1 and 24 h following the injection of the drug. We could detect significantly higher amounts of drug in the distal tubules of the pyelonephritic kidney than the normal levels at 10 min and 24 h postinjection. The drug did not seem to be associated with any particular organelle and was evenly distributed within the distal tubular cells. The present study shows that the transport of tobramycin within the infected nephron is disturbed. These data might shed some light on the influence of infection on the intrarenal pharmacology of aminoglycosides.
Fast Blast Wave and Ejecta in the Young Core-collapse Supernova Remnant MSH 15-52/RCW 89

One of the youngest known remnants of a core-collapse supernova (SN) in our Galaxy is G320.4−1.2/MSH 15-52, containing an energetic pulsar with a very short (1700 yr) spindown age and likely produced by a stripped-envelope SN Ibc. Bright X-ray and radio emission north of the pulsar overlaps with an Hα nebula RCW 89. The bright X-rays there have a highly unusual and quite puzzling morphology, consisting of both very compact thermally emitting knots and much more diffuse emission of nonthermal origin. We report new X-ray observations of RCW 89 in 2017 and 2018 with Chandra that allowed us to measure the motions of many knots and filaments on decade-long time baselines. We identify a fast blast wave with a velocity of km s−1 ( is the distance in units of 5.2 kpc) with a purely nonthermal spectrum, and without any radio counterpart. Many compact X-ray emission knots are moving vary fast, with velocities as high as 5000 km s−1, predominantly radially away from the pulsar. Their spectra show that they are Ne- and Mg-rich heavy-element SN ejecta. They have been significantly decelerated upon their recent impact with the dense ambient medium north of the pulsar. We see fast evolution in brightness and morphology of knots in just a few years. Ejecta knots in RCW 89 resemble those seen in Cas A at optical wavelengths in terms of their initial velocities and densities. They might have the same origin, still not understood but presumably related to stripped-envelope SN explosions themselves.
Scalable Transmission Over Heterogeneous Networks: A Stochastic Geometry Analysis

This paper focuses on the transmission of layered source information, such as scalable video coding, over heterogeneous cellular networks. Scalable transmission enables dynamic adaption of source information to the condition of user equipment (UE) devices and, thus, is suitable for cellular networks in which the transmission link quality substantially varies over space and time. Two novel transmission schemes are proposed, namely, layered digital transmission and layered hybrid digital–analog (LHDA) transmission. Leveraging tools from stochastic geometry, a comprehensive analysis is conducted focusing on three key performance metrics: outage probability, high-definition probability, and average distortion. The results show that both proposed transmission schemes can provide a scalable video experience for UE devices. For LHDA transmission, the optimal power allocation between digital and analog transmissions is also analyzed. When the proportion of frequency resource allocated to the femtotier exceeds a certain threshold, LHDA transmission is preferable by enabling continuous quality scalability, thus avoiding the cliff effect.
A Multicenter, Double‐Blind Study on Triple Therapy with Lansoprazole, Amoxicillin and Clarithromycin for Eradication of Helicobacter pylori in Japanese Peptic Ulcer Patients

Two triple therapies with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of Helicobacter pylori were studied in multicenter, double‐blind fashion to evaluate the eradication rate of H. pylori and safety of eradiation treatment in Japanese patients with H. pylori‐positive active gastric ulcers or duodenal ulcers.
Pharmacokinetics of nelfinavir in human immunodeficiency virus-infected infants.

BACKGROUND Nelfinavir dosed at approximately 20 to 30 mg/kg three times a day (TID) in older children provides exposure similar to 750 mg TID in adults. However, the pharmacokinetics (PK) of nelfinavir in infants who are < 2 years of age is not well-described. The objective of this study was to determine the pharmacokinetics of nelfinavir in infants < 2 years of age. METHODS Nelfinavir concentrations were evaluated in 22 HIV-infected infants between 15 days and 2 years of age receiving nelfinavir as part of Pediatric ACTG Study 356. Nelfinavir therapy was initiated at approximately 25 mg/kg TID (n = 18) or approximately 55 mg/kg twice a day (n = 4) and given in combination with nevirapine, stavudine and lamivudine. PK samples were obtained predose and 1.5 and 4 h postdose at approximately 6-month intervals. Eight infants (all < or = 3 months of age) also had intensive PK samples collected at Week 1. RESULTS The median apparent clearance in the infants with intensive pharmacokinetic sampling was 2.7 liters/h/kg (range, 1.8 to > or = 10) and was similar between twice a day and TID dosing cohorts. Overall nelfinavir concentrations at all collection times were lower in these infants than previously reported in older pediatric patients. CONCLUSIONS Nelfinavir concentrations in infants are highly variable and lower than those seen in adult or older pediatric populations receiving labeled dosing. Therefore it is necessary to further evaluate nelfinavir safety, effectiveness and pharmacokinetics at higher doses than used among other pediatric populations.
Kinase-deficient Pak1 mutants inhibit Ras transformation of Rat-1 fibroblasts

Among the mechanisms by which the Ras oncogene induces cellular transformation, Ras activates the mitogen-activated protein kinase (MAPK or ERK) cascade and a related cascade leading to activation of Jun kinase (JNK or SAPK). JNK is additionally regulated by the Ras-related G proteins Rac and Cdc42. Ras also regulates the actin cytoskeleton through an incompletely elucidated Rac-dependent mechanism. A candidate for the physiological effector for both JNK and actin regulation by Rac and Cdc42 is the serine/threonine kinase Pak (p65pak). We show here that expression of a catalytically inactive mutant Pak, Pak1(R299), inhibits Ras transformation of Rat-1 fibroblasts but not of NIH 3T3 cells. Typically, 90 to 95% fewer transformed colonies were observed in cotransfection assays with Rat-1 cells. Pak1(R299) did not inhibit transformation by the Raf oncogene, indicating that inhibition was specific for Ras. Furthermore, Rat-1 cell lines expressing Pak1(R299) were highly resistant to Ras transformation, while cells expressing wild-type Pak1 were efficiently transformed by Ras. Pak1(L83,L86,R299), a mutant that fails to bind either Rac or Cdc42, also inhibited Ras transformation. Rac and Ras activation of JNK was inhibited by Pak1(R299) but not by Pak1(L83,L86,R299). Ras activation of ERK was inhibited by both Pak1(R299) and Pak1(L83,L86,R299), while neither mutant inhibited Raf activation of ERK. These results suggest that Pak1 interacts with components essential for Ras transformation and that inhibition can be uncoupled from JNK but not ERK signaling.
Concurrent chemo-irradiation with weekly cisplatin and paclitaxel in the treatment of locally advanced squamous cell carcinoma of cervix: a phase II study.

BACKGROUND Cervical cancer is the most common gynecological cancer in Indian women. This study was initiated to assess whether the combination of paclitaxel and cisplatin with radiation was feasible in Indian women. AIMS AND OBJECTIVES The aim of this study was to assess the immediate tumor response and toxicity of weekly cisplatin and paclitaxel along with radiotherapy in the treatment of cervical cancer. MATERIALS AND METHODS Women with primary untreated squamous cell carcinoma of the cervix with FIGO stages IB2 to IIIB were treated with weekly injections of cisplatin 30 mg/m2 and paclitaxel 40 mg/m2 for 4 weeks along with radiotherapy. A total of 25 patients were enrolled in this study. Disease was assessed prior to treatment by pelvic examination and contrast enhanced computed tomography scan of the abdomen and pelvis. Response was assessed 6 weeks after completion of treatment using the same parameters. Clinical and radiological response was documented. The toxicity was assessed and was graded using the common toxicity criteria Version 3.0. Intention to treat analysis was used when reporting results. RESULTS A total of 23 patients completed the intended treatment. There was a complete response rate of 88%, 12% were not available for response assessment. The major toxicity was Grade 3 diarrhea (48%). The mean duration of treatment was 58 days. CONCLUSIONS Combination chemotherapy with cisplatin and paclitaxel along with radiotherapy in patients with locally advanced squamous cell carcinoma of cervix had a high incidence of acute toxicity. There was no increase in immediate tumor response and progression free survival with this treatment regimen. Hence, this regimen offers no added benefit when compared to the chemo radiation with cisplatin alone.
No cases of perioperative allergy to local anaesthetics in the Danish Anaesthesia Allergy Centre

Local anaesthetics (LA) are often suspected as possible causes of allergic reactions. The Danish Anaesthesia Allergy Centre (DAAC) is the national reference centre for investigation of perioperative allergic reactions. The purpose of this study was to investigate the incidence of IgE‐mediated immediate type perioperative allergic reactions to LA.
Change of V-Curve Behavior Depending on Ion Angle Deviation in Channeling Condition

Ion implant angle control is a critical capability as device geometry continues to shrink and device performance is pushed to the limit. The generally accepted method to verify implant angle accuracy is the V-Curve. During V-Curve studies, we found that in some cases, sheet resistances (Rs) measured using the V-Curve method is influenced not only by an average of ion angles but also by ion angle deviation (IAD). From another point of view, based on this phenomenon, IAD can be verified by measurement of Rs.
Replication of Sendai Virus

Chick embryo fibroblast cultures infected with Sendai virus were incubated with 3H-uridine in the presence of actinomycin D beginning at 18 hr after infection. The 35 and 18S virus-specific ribonucleic acid (RNA) components were found in a ribonuclease-sensitive form in the cell and appeared to be associated with polyribosomes. Newly synthesized 57S viral RNA was rapidly coated with protein to form intracellular viral nucleocapsid, and no 57S RNA was found “free” (ribonucleasesensitive) in the 2,000 × g supernatant fraction of disrupted cells. The nucleocapsid from detergent-disrupted Sendai virus and that from disrupted cells were indistinguishable in ultrastructure and buoyant density, and neither was found to be infectious or have hemagglutinating activity. Kinetic studies of nucleocapsid and virus formation indicated a relative block in conversion of viral nucleocapsid to complete enveloped virus in these cells, resulting in accumulation of large amounts of nucleocapsid in the cell cytoplasm.
Peak expiratory flow as a screening tool to detect airflow obstruction in a primary health care setting.

BACKGROUND Peak expiratory flow (PEF) measurement is less expensive and requires fewer skills than spirometry testing. It is thus expected to be a reasonable substitute for spirometry in airflow obstruction screening when spirometry is unavailable. OBJECTIVES To evaluate the validation of PEF measurement in the detection of airflow obstruction using newly established regression equations. METHODS The PEFs of 553 'normal' participants aged 40-85 years were measured using mechanical devices. Based on these data, regression equations were generated to predict normal PEF values. Data were then collected from 3379 subjects. The specificity and sensitivity of the different predicted PEF cut-off points for detecting airflow obstruction were evaluated by spirometry, based on previously generated regression equations. RESULTS Using newly established reference values for PEF, PEF had higher sensitivity and specificity than the questionnaire in detection of airflow obstruction. That PEF < 80% of predicted was more effective in the detection of airflow obstruction was confirmed by the lower limit of normal of forced expiratory volume in 1 second/forced vital capacity, Global Initiative for Chronic Obstructive Lung Disease (GOLD), and GOLD plus symptom, with a sensitivity of 78.7%, 76.8%, 85.3% and a specificity of 81.9%, 83.8%, 81.4%, respectively. CONCLUSIONS Mechanical PEF may be a reasonable method of screening for airflow obstruction in settings where spirometry is unavailable.