Miracle-dz/UniFAR-FTUs huggingface dataset:
Increasing cisplatin sensitivity by schedule-dependent inhibition of AKT and Chk1

The effectiveness of DNA damaging chemotherapy drugs can be limited by activation of survival signaling pathways and cell cycle checkpoints that allow DNA repair. Targeting survival pathways and inhibiting cell cycle checkpoints may increase chemotherapy-induced cancer cell killing. AKT and Chk1 are survival and cell cycle checkpoint kinases, respectively, that can be activated by DNA damage. Cisplatin (CP) is a standard chemotherapy agent for osteosarcoma (OS). CP induced apoptosis to varying extents and activated AKT and Chk1 in multiple p53 wild-type and p53-null OS cell lines. A Chk1 inhibitor increased CP-induced apoptosis in all OS cell lines regardless of p53 status. In contrast, an AKT inhibitor increased CP-induced apoptosis only in p53 wild-type OS cells, but not p53 nulll cells. The increased apoptosis in p53 wild-type cells was coincident with decreased p53 protein levels, but increased expression of p53-responsive apoptotic genes Noxa and PUMA. Further studies revealed the inability of AKT inhibitor to CP-sensitize p53-null OS cells resulted from 2 things: 1) AKT inhibition stabilized/maintained p27 levels in CP-treated cells, which then mediated a protective G1-phase cell cycle arrest, 2) AKT inhibition increased the levels of activated Chk1. Finally, schedule dependent inhibition of AKT and Chk1 evaded the protective G1 arrest mediated by p27 and maximized CP-induced OS cell killing. These data demonstrate AKT and Chk1 activation promote survival in CP-treated OS cells, and that strategic, scheduled targeting of AKT and Chk1 can maximize OS cell killing by CP.
Mutations at rfc or pmi attenuate Salmonella typhimurium virulence for mice

Insertion mutations were constructed in cloned pmi and rfc genes of Salmonella typhimurium, and these mutations were recombined (singly) into the chromosome of mouse-virulent S. typhimurium C5, displacing the wild-type alleles. Phage sensitivity profiles, lipopolysaccharide analysis, and DNA blotting all confirmed that the replacement events had occurred. The mutations were complemented by plasmid-borne wild-type alleles, as judged by the restoration of wild-type phage plaquing profiles and lipopolysaccharide production (both mutants) and the restoration of pmi-encoded enzyme production (pmi mutant). The virulence, persistence, and immunizing capacities of the mutants fed to mice were compared with those of the wild-type strain and complemented mutants. Both mutants were much reduced in virulence, with the rfc mutant being avirulent even at 10(9) bacteria per mouse. This mutant was also avirulent at up to 10(6) bacteria per mouse when administered intraperitoneally. Both the rfc and pmi mutant strains persisted in the Peyer's patches of the gut after feeding and were capable of colonizing the deeper tissues of the mice from such initial infective foci. Both mutant strains were effective as live oral vaccines (10(7) bacteria or more) against oral S. typhimurium challenge (10(4) 50% lethal doses; 6 x 10(8) bacteria) in mice.
Suppressing SNAP‐25 and reversing glial glutamate transporters relieves neuropathic pain in rats by ameliorating imbalanced neurotransmission

Background Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters (inhibitory GABA transporters GAT and excitatory glutamate transporters GT). Neuronal hyper‐excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP‐25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter (GLT) is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP‐25 and GLT as well as GAT is not clearly understood. Methods We used the rat chronic constriction injury (CCI) model for research, and degraded SNAP‐25 by a single intrathecal administration of BoNT/A. The mechanical (MWT) and thermal withdrawal latency (TWL) were tested. The level of SNAP‐25, GLT, and GAT‐1 were assayed using RT‐PCR and Western blotting. Results SNAP‐25 was suppressed by a single intrathecal administration of 0.01U BoNT/A and the reduction of SNAP‐25 was correlated with the relief of nociceptive responses in CCI rats. MWT and TWL returned to normal from the 5th to 14th day (P<0.05) after the administration. On the 14th day after surgery, compared to the sham group, the upregulation of SNAP‐25 in CCI rats was reversed after BoNT/A treatment (P<0.05). The decreased GLT was reversed after BoNT/A treatment but increased GAT‐1 was not influenced by BoNT/A treatment. Conclusions SNAP‐25 and GLT play important roles in the development of neuropathic pain, and the mechanism may involve the imbalance of neurotransmission after peripheral nerve injury. Intrathecal administration of BoNT/A reversed the upregulation of SNAP‐25 and downregulation of GLT after CCI, but had no significant effect on the expression of GAT‐1.
Bipolar Disorder with Comorbid Substance Abuse: Diagnosis, Prognosis, and Treatment

Alcohol and drug abuse occur frequently in individuals with bipolar disorder, but clinicians may often feel ill-prepared to identify such multi-diagnosis syndromes, to contextualize drug abuse alongside affective symptoms, and to formulate appropriate treatment strategies. Plausible explanations for high comorbidity rates between bipolar illness and substance use disorders are complex and likely embrace numerous factors that extend beyond simple, older theories about drug use as sheer “self-medication. ” Evidence from epidemiologic, family-genetic, pharmacologic, psychosocial, and clinical psychopathology studies suggest that a majority of bipolar patients are at risk for developing lifetime drug or alcohol-related problems, which may in turn contribute to more varied and complex clinical presentations, accelerated relapses, worsening of depressive features, poorer lithium response, functional disability, and elevated suicide risk. In this article, the author reviews essential concepts about the phenomenology and treatment outcome of bipolar illness with substance use comorbidities and offers a systematic approach to the diagnosis and management of patients with such dual diagnoses.
Features of Microsatellite Instability in Colorectal Cancer: Comparison between Colon and Rectum

In one third of colorectal cancer patients, tumours occur in the rectum. Unique aetiologies may underlie the increased carcinogenesis in this region of the colorectum. Microsatellite instability (MSI) was analysed in specimens obtained from 121 colorectal carcinoma patients, using five dinucleotide markers and a new fluorescent system. The incidence of microsatellite alterations in the proximal colon, the distal colon and the rectum was 44.4% (16/36), 37.2% (16/43) and 23.8% (10/42), respectively. Patterns of microsatellite alterations could be classified into two subtypes, one showing relatively small changes within 6 bases (type A) and the other exhibiting drastic changes over 8 bases (type B). All the changes observed in tumours in the rectum were type A, and no type B mutation was noted. There was a close correlation between type B mutations and high-frequency MSI (≧2 markers), MSI-H, and between type A mutations and low-frequency MSI (1 marker), MSI-L. The type B/MSI-H phenotype significantly correlated with the proximal localisation of tumours. In the rectum, there was no tumour with the type B/MSI-H phenotype. These findings suggest that cancers occurring in the colon and the rectum have a differential molecular background for carcinogenesis.
Government Spending Multipliers in Natural Resource-Rich Developing Countries

This paper estimates government spending multiplier for natural resource-rich low-income countries (LICs). Our estimates suggest an absence of natural resource curse in government spending multiplier. In the short-run, the government spending multiplier is around 0.7 for natural resource-rich LICs and 0.43 for all LICs. The government spending has a permanent impact on the real economic activity in resource-rich countries while having a transitory long-run impact in other countries.
The Men You Will Become: Single-Sex Public Education and the Crisis of Black Boys

Author(s): Oeur, Freeden | Advisor(s): Thorne, Barrie | Abstract: Against a backdrop of massive public school reform, single-sex public schools have become an increasingly popular, but controversial, option for parents and their children. In this dissertation, I demonstrate that single-sex public education today is merely the latest twist in a long-term, historically-situated trajectory of gender- and race-separated schooling in the United States. Drawing on 11 months of intensive fieldwork, over 140 in-depth interviews, and an analysis of documents at two single-sex, nearly all-African American public high schools in the large east coast of "Morgan," I ask: What interventions do single-sex public schools make on behalf of their African American male students? And what impact do those interventions have on the boys' masculinity formation and life chances? At "Perry High," a grades 7-12 neighborhood public school, officials and community members identified mass incarceration and the lack of caregiving as acute, interrelated crises facing their young African American male students. The administrators desired for their boys to grow to become responsible husbands and fathers, and the boys themselves aspired to be these men. The school, however, lacked the resources and strategies to remove many of the boys off the school-to-prison pipeline. At "Urban Charter," a charter school serving boys in grades 9-11, staff and "consumer" buy-in and a strong formal, academic curriculum enabled the school to remove more of their boys from the school-to-prison pipeline and to place them on a college track. The school also depended on a second hidden curriculum that sought to protect the boys from the perceived degradation of regular public schools, and in particular the threatening specter of the boys who attended those schools. School officials desired for their students to become respectable, middle-class workers in a global economy.These findings extend knowledge on African American boys and schooling in several ways. I show that single-sex public schools that target this population rely little on beliefs in gender differences between boys and girls, and instead primarily on the unique vulnerabilities of African American boys. I also build on research on caregiving within schools and show how schools frame mass incarceration as a miscarriage of justice requiring certain provisions of care, and how boys desired care from adults. Last, I show how different institutional histories and capacities, particularly between regular public schools and public charters, greatly impact the ability of schools to intervene on behalf of their young Black men and to "save" them.
Prognostic significance of NPM1 mutations in the absence of FLT3-internal tandem duplication in older patients with acute myeloid leukemia: a SWOG and UK National Cancer Research Institute/Medical Research Council report.

PURPOSE Younger patients with acute myeloid leukemia (AML) harboring NPM1 mutations without FLT3-internal tandem duplications (ITDs; NPM1-positive/FLT3-ITD-negative genotype) are classified as better risk; however, it remains uncertain whether this favorable classification can be applied to older patients with AML with this genotype. Therefore, we examined the impact of age on the prognostic significance of NPM1-positive/FLT3-ITD-negative status in older patients with AML. PATIENTS AND METHODS Patients with AML age ≥ 55 years treated with intensive chemotherapy as part of Southwest Oncology Group (SWOG) and UK National Cancer Research Institute/Medical Research Council (NCRI/MRC) trials were evaluated. A comprehensive analysis first examined 156 patients treated in SWOG trials. Validation analyses then examined 1,258 patients treated in MRC/NCRI trials. Univariable and multivariable analyses were used to determine the impact of age on the prognostic significance of NPM1 mutations, FLT3-ITDs, and the NPM1-positive/FLT3-ITD-negative genotype. RESULTS Patients with AML age 55 to 65 years with NPM1-positive/FLT3-ITD-negative genotype treated in SWOG trials had a significantly improved 2-year overall survival (OS) as compared with those without this genotype (70% v 32%; P < .001). Moreover, patients age 55 to 65 years with NPM1-positive/FLT3-ITD-negative genotype had a significantly improved 2-year OS as compared with those age > 65 years with this genotype (70% v 27%; P < .001); any potential survival benefit of this genotype in patients age > 65 years was marginal (27% v 16%; P = .33). In multivariable analysis, NPM1-positive/FLT3-ITD-negative genotype remained independently associated with an improved OS in patients age 55 to 65 years (P = .002) but not in those age > 65 years (P = .82). These results were confirmed in validation analyses examining the NCRI/MRC patients. CONCLUSION NPM1-positive/FLT3-ITD-negative genotype remains a relatively favorable prognostic factor for patients with AML age 55 to 65 years but not in those age > 65 years.
Semiautomatic Road Extraction From VHR Images Based on Multiscale and Spectral Angle in Case of Earthquake

Road extraction offers great potential for research initiatives because of the complexity due to its great topological variability. The use of remote sensing imagery to accomplish this mapping is an interesting option. Indeed, satellite images can be acquired shortly after the event, and cover a large area of territory. We hope to produce a mapping of the present facilities from very high resolution images shortly after a disaster. This availability of very high spatial resolution images brings added value to the study in urban areas and their mapping. Increasing the spatial resolution generates noise, which makes extraction difficult, especially in the event of an earthquake in an urban context. This problem increases false alarm rates and generally affects the performance of road extraction algorithms in detecting linear features used to locate and extract roads on such images. During major disasters, short deadlines demand an effective response in terms of updating the mapping of affected areas. Our aim is to improve the road extraction quality after adaptation of Lowe's scale-invariant features transform descriptors jointly with spectral angle algorithms. An illustration is performed on three high-resolution images, respectively, representing a rural, suburban, and urban disaster area, captured by the Quickbird satellite. Our approach significantly reduces the false detection rate and shows an increase in overall quality of up to nearly 30% in some cases as compared to what obtain in the literature.
Clinical Experience of 1284 Free Anterolateral Thigh Flaps

The past decade has witnessed yet another rebirth in reconstructive surgery with the introduction of the so-called "perforator flaps". The demonstration of safe harvest of skin flaps based on dissection of cutaneous pedicles regardless of the course taken (through muscle or septum) has been revolutionary in allowing much greater choice in donor sites. Based on our experience in 1284 cases, the anterolateral thigh (ALT) region has proven itself to be an ideal donor site with reliable vascularity, ease of harvest and tremendous versatility. Inclusive in this flap is a large cutaneous territory, multiple components (adipofascial, muscle, fascia and skin) and possibility of chimeric applications. Although particularly useful in the head and neck (911 cases), the ALT flap was applied to reconstruct defects throughout the body. Donor site morbidity is limited as well. In short, the anterolateral thigh flap represents one of the most useful soft tissue flaps for free tissue transplantation.
Treatment of children with B‐cell non‐Hodgkin lymphoma in a low‐income country

An adapted LMB 96 derived protocol for B‐cell non‐Hodgkin lymphoma (NHL) was implemented at the pediatric oncology unit of the Children Welfare Teaching Hospital in Baghdad (Iraq) from 2000 to present. The purpose was to evaluate the feasibility and efficacy of this intensive therapeutic regimen in a limited resource country.
In Vivo Effect of Venlafaxine on Locus Coeruleus Neurons: Role of Opioid, α2-Adrenergic, and 5-Hydroxytryptamine1A Receptors

The locus coeruleus (LC) is involved in several neural pathways responsible for some somatic and emotional processes, such as pain and depression; its activity is regulated by several receptors, such as opioid, α2-adrenergic, and 5-hydroxytryptamine (5-HT)1A receptors. The present study investigates the in vivo effects of venlafaxine, an antidepressant with analgesic properties, on locus coeruleus neurons, and its modulation by opioid, α2-adrenergic, and 5-HT1A receptors. The results show that acute administration of venlafaxine produced a dose-dependent, complete inhibition of LC activity. This inhibitory effect was not reversed by the opioid receptor antagonist naloxone, but subsequent administration of idazoxan, an α2-adrenoceptor antagonist, did reverse it. The preadministration of the 5-HT1A receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT) (1 and 40 μg/kg) significantly enhanced the venlafaxine inhibitory effect, decreasing the ED50 by 56 and 44%, respectively. A 14-day treatment with venlafaxine (40 mg/kg/day) induced a suppression of the firing activity of LC neurons. In these treated animals, venlafaxine produced an inhibitory effect similar to that in nontreated animals. This inhibitory effect was not reversed by naloxone, but it was reversed by idazoxan. In addition, the preadministration of 8-OH-DPAT (40 μg/kg) significantly enhanced the venlafaxine effect, decreasing the ED50 by 60%. These results suggest that the effect of venlafaxine on LC neurons is modulated by α2-adrenergic and 5-HT1A receptors, and not by opioid receptors. These data could contribute to the further understanding of the antidepressant and analgesic mechanism of action of venlafaxine.
Effect of different post-exercise sugar diets on the rate of muscle glycogen synthesis.

The effect of repeated ingestions of fructose, sucrose, and various amounts of glucose on muscle glycogen synthesis during the first 6 h after exhaustive bicycle exercise was studied. Muscle biopsies for glycogen determination were taken before and after exercise, and every second hour during recovery. Blood samples for plasma glucose and insulin determination were taken before and after exercise, and every hour during recovery. When 0.35 (low glucose: N = 5), 0.70 (medium glucose: N = 5), or 1.40 (high glucose: N = 5) g.kg-1 body weight of glucose were given orally at 0, 2, and 4 h after exercise, the rates of glycogen synthesis were (mean +/- SE) 2.1 +/- 0.5, 5.8 +/- 1.0, and 5.7 +/- 0.9 mmol.kg-1.h-1, respectively. When 0.70 g.kg-1 body weight of sucrose (medium sucrose: N = 5), or fructose (medium fructose: N = 7) was ingested accordingly, the rates were 6.2 +/- 0.5 and 3.2 +/- 0.7 mmol.kg-1.h-1. Average plasma glucose level during recovery were similar in low glucose, medium glucose, and high glucose groups (5.76 +/- 0.24, 6.31 +/- 0.64, and 6.52 +/- 0.24 mM), while average plasma insulin levels were higher with higher glucose intake (16 +/- 1, 21 +/- 3, and 38 +/- 4 microU.ml-1). (ABSTRACT TRUNCATED AT 250 WORDS)
Importing and Firm Export Performance: New Evidence from South Africa

This article uses firm‐level data from company income tax and customs declarations from South Africa to analyse the complementary relationship between direct access to imported intermediate inputs and firm exports in the manufacturing industry. There are two main findings. The first is on firm heterogeneity, showing that firms that import and export consistently demonstrate premiums in terms of productivity, employment, wages and capital intensity in production compared to firms that do not trade, or only export or import. The second supports the hypothesis that importing raises exports, especially if inputs are sourced from advanced economies.
Nucleotide sequence analysis of small cryptic plasmid pGP2 from Acetobacter estunensis

Complete nucleotide sequence of plasmid pGP2 from Acetobacter estunensis GP2 was identified after initial cloning of EcoRI fragment followed by preparation of deletion derivatives. Its size was defined to 2,797 bp and several sites for several restriction enzymes were revealed by DNA sequencing. Sequence analysis predicts three putative open reading frames (ORFs). ORF1 shows significant identity with the bacterial excinuclease α-subunit, ORF2 is a putative replication protein with low similarity with other Acetobacter plasmid’s replication proteins, and ORF3 encodes a class B acid phosphatase/phosphotransferase. The replication module comprises a DnaA box like sequence, direct repeats, a potential prokaryotic promoter and a rep gene. The rep module is similar with several θ-replicating, iteron-containing modules from plasmids, suggesting pGP2 replication may follow the same course. Any phenotypic character determinant gene is absent in pGP2, suggesting this plasmid to be cryptic. However, a pGP2 derivative plasmid, containing the putative pGP2 rep region, can replicate and is stably maintained in Acetobacter and Escherichia coli strains; it can also carry foreign DNA fragments. Thus, pGP2-X could serve as a cloning shuttle vector between these bacteria. Prepared deletion derivatives of plasmid pGP2 suggested that Rep protein is essential for plasmid replication in host bacteria. In its natural host, A. estunensis GP2, pGP2 maintains a four-times lower copy number than in E. coli.
Experiences with a combination of group therapy and methadone maintenance in the treatment of heroin addiction.

This report describes the experience of a program for heroin abusers which combines some features of a therapeutic community with methadone maintenance therapy. The program utilized both ex-addict counselors and mental health professionals in group therapy sessions. The ex-addict counselors, while a valuable asset to a drug abuse program, demonstrated definite limitations. Our experience does indicate, however, that such a program can be set up within the confines of a general medical clinic, and that methadone maintenance and psychotherpay need not be looked upon as mutually exclusive but can be used together effectively in a treatment program.