Miracle-dz/UniFAR-FTUs huggingface dataset:
Outsourcing strategies and distribution models in Italian Pharma Supply Chain

In the pharmaceutical supply chain, all players have to ensure the highest level of service while containing costs, because of the ethical issues concerning drugs. The outsourcing of logistics should be recognized as a competitive lever, especially in this complex and highly regulated industry. Based on these premises, the research objective of this study is to investigate the relationship between the outsourcing strategies of manufacturers and the logistics services offered by Third-Party Logistics Service providers (3PLs). To achieve this objective, a multiple case study was designed to analyse the different physical distribution models adopted by pharmaceutical companies. We collected qualitative data and the subjective perceptions of several logistics directors, conducting structured interviews with 11 pharmaceutical companies and six 3PLs. We have identified three physical distribution models, on the basis of the number and location of the warehouses used (single warehouse, dual warehouse and multi-warehouse models). We discovered that there is a strict relationship between the physical distribution model adopted by pharmaceutical companies and their features (i.e. the main distribution channel, product portfolio, target service level, transport and warehousing costs and other company related issues). Our research also offers an empirical insight into the key logistic services that 3PLs should offer within the pharma industry. In conclusion, the study draws a roadmap to guide pharmaceutical companies in their strategic logistics decisions in Italy, while also considering possible future trends deriving from changes to European regulations.
Morphology and distribution of electrophysiologically defined classes of pyramidal and nonpyramidal neurons in rat ventral subiculum in vitro

Intracellular electrophysiological recordings were made from 210 ventral subicular neurons in rat brain slices. Recordings here classified as burst‐firing or nonburst‐firing. Eighteen burst‐firing neurons were filled with Neurobiotin, and all had pyramidal morphology. Nine of these recordings were made from intrinsically burst‐firing (IB) cell bodies, and nine were made from burst‐firing dendrites (BD). Twelve nonburst‐firing neurons were also filled with Neurobiotin. Eight were regular spiking (RS) and had pyramidal morphology, four were fast spiking (FS) and nonpyramidal. Additional electrophysiological parameters distinguished IB from BD, RS from FS, and RS from IB recordings.
Receptor of Advanced Glycation End Products (RAGE) Positively Regulates CD36 Expression and Reactive Oxygen Species Production in Human Monocytes in Diabetes

Introduction: Advanced glycation end products (AGEs) engagement of a monocyte surface receptor (RAGE) induces atherosclerosis. AGEs also act as CD36 ligands. We studied reactive oxygen species (ROS) and CD36 expression after siRNA inhibition of RAGE expression in human monocytes. Methods: We isolated monocytes from: a) 10 type 2 diabetics, and b) 5 age- and sex-matched healthy individuals. CD36 expression and ROS production were evaluated before and after RAGE knockdown. Results: After incubation of monocytes with AGE + bovine serum albumin (BSA), CD36 expression and intracellular ROS increased significantly in all groups. In RAGE-knockdown monocytes, AGE-induced CD36 expression and ROS generation were also significantly inhibited. Conclusions: Blocking RAGE expression using siRNA in human monocytes led to a significant inhibition of CD36 expression and ROS production, suggesting a positive interaction between RAGE, CD36 expression and ROS generation in monocytes.
Towards a ‘Science’ of Corpus Annotation: A New Methodological Challenge for Corpus Linguistics

Corpus annotation—adding interpretive information into a collection of texts—is valuable for a number of reasons, including the validation of theories of textual phenomena and the creation of corpora upon which automated learning algorithms can be trained. This paper outlines the main challenges posed by human-coded corpus annotation for current corpus linguistic practice, describing some of the methodological steps required for this indispensable part of the research agenda of Corpus Linguistics in this decade. The first part of the paper presents an overview of the methodologies and open questions in corpus annotation as seen from the perspective of the field of Natural Language Processing. This is followed by an analysis of the theoretical and practical impact of corpus annotation in the field of Corpus Linguistics. It is suggested that collaborative efforts are necessary to advance knowledge in both fields, thereby helping to develop the kind of methodological rigour that would bring about a ‘science’ of annotation.
Is Postprandial Glucose Control Important? Is It Practical In Primary Care Settings?

In Brief Large interventional studies have shown that achieving and maintaining near-normal glycemic levels reduces the risk for microvascular and macrovascular complications in type 2 diabetes. The impact of postprandial glucose on glycemic control has become a topic of much discussion among clinicians. This article examines the literature related to the role of postprandial glucose in type 2 diabetes, both as a contributor to overall glycemia and as an independent risk factor for diabetes complications, and discusses the practicality of managing postprandial hyperglycemia in primary care settings.
Pseudomorphic InP/InGaAs Heterojunction Bipolar Transistors (PHBTs) Experimentally Demonstrating fT = 765 GHz at 25°C Increasing to fT = 845 GHz at -55°C

Pseudomorphic InP HBTs (PHBTs) with a vertically scaled design implementing a 12.5 nm base and 55 nm collector exhibit record current gain cutoff frequency performance of f<sub>T</sub>=765 GHz when measured at 25°C. When cooled to -55°C, f<sub>T</sub> improves more than 10% to f<sub>T</sub>=845 GHz due to enhanced electron transport and reduced parasitic charging delays as determined by small signal equivalent circuit parameter extraction. Peak performance current density J<sub>c</sub>=18.7 mA/μm<sup>2</sup> and BV<sub>CEO</sub> =1.65 V
A flexible protocol synthesis method for adopting requirement changes

Communicating entities in a protocol specification communicate with each other and provide services to their users. Once the behaviours of the entities (specification of the protocol) are specified they are not changed. The entities provide a fixed set of services to their users. However, different users have different requirements and their requirements change often. The requirement changes in general are small in terms of the size of the behaviour expressions of the entities. Traditional protocol synthesis techniques have given considerable attention in construction of new protocols for fixed set of services but less attention to the attractive maintenance issue of protocol to adopt new protocol requirement changes. What is desirable is a protocol synthesis method which adopts new protocol requirement changes into the behaviours of entities or protocol specifications. In this paper, we propose a protocol synthesis method which adopts the new protocol requirement changes into the protocol specification. In this way, we can use existing protocol specifications and maintain them to adopt requirement changes. We use the formal specification language LOTOS to specify requirement changes and the behaviours of entities.
Dry Climate in the Middle Bronze I and Its Impact on Settlement Patterns in the Levant and Beyond: New Pollen Evidence*

* We are grateful to Tony Wilkinson and Glenn Schwartz for reading this manuscript and commenting on the archaeology and environmental history of northern Mesopotamia. Needless to say, responsibility for the ideas expressed in this article rests only with us. This study was funded by the European Research Council under the European Community’s Seventh Framework Program (FP7/2007–2013) / ERC grant agreement no. 229418. We wish to thank F. Neumann from the University of Münster and M. Pollak, S. Salem, Y. Gottlieb, I. Ben-Ezra, and S. Ben-Dor Evian of Tel Aviv University for their help in the field and laboratory, and to M. Stein of the Israel Geological Survey and T. Litt and his team from the Bonn Palynological Laboratory as our partners in the Sea of Galilee drilling operation. 1 D. Langgut, I. Finkelstein, and T. Litt, “Climate and the Late Bronze Collapse: New Evidence from the Southern Levant,” Tel Aviv 40: 149–75; D. Langgut et al., “Dead Sea Pollen Record and History of Human Activity in the Judean Highlands (Israel) from the Intermediate Bronze into the Iron Ages (~2500–500 Bce),” Palynology 38 (2014): 1–23, respectively; for pollen identification, a reference collection of Israeli pollen flora was used (Steinhardt lution of dense 40-year time intervals between one pollen sample and another2 and deployed a robust radiocarbon dating scheme. This enabled, for the first time, a detailed reconstruction of climate conditions in historical periods, including the identification of short-term events that can be missed in low resolution pollen studies. The Sea of Galilee and Zeʾelim (Dead Sea) records corroborate each other and hence strengthen the reliability of the results. Tracing these climate fluctuations is based on the identification of shifts in vegetation frequencies: high arboreal pollen percentages of the members of the Mediterranean forest/maquis3 represent humid climate conditions,
Allosteric Activation of PTEN Phosphatase by Phosphatidylinositol 4,5-Bisphosphate*

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor that is lost in many human tumors and encodes a phosphatidylinositol phosphate phosphatase specific for the 3-position of the inositol ring. Here we report a novel mechanism of PTEN regulation. Binding of di-C8-phosphatidylinositol 4,5-P2 (PI(4,5)P2) to PTEN enhances phosphatase activity for monodispersed substrates, PI(3,4,5)P3 and PI(3,4)P2. PI(5)P also is an activator, but PI(4)P, PI(3,4)P2, and PI(3,5)P2 do not activate PTEN. Activation by exogenous PI(4,5)P2 is more apparent with PI(3,4)P2 as a substrate than with PI(3,4,5)P3, probably because hydrolysis of PI(3,4)P2 yields PI(4)P, which is not an activator. In contrast, hydrolysis of PI(3,4,5)P3 yields a potent activator, PI(4,5)P2, creating a positive feedback loop. In addition, neither di-C4-PI(4,5)P2 nor inositol trisphosphate-activated PTEN. Hence, the interaction between PI(4,5)P2 and PTEN requires specific, ionic interactions with the phosphate groups on the inositol ring as well as hydrophobic interactions with the fatty acid chains, likely mimicking the physiological interactions that PTEN has with the polar surface head groups and the hydrophobic core of phospholipid membranes. Mutations of the apparent PI(4,5)P2-binding motif in the PTEN N terminus severely reduced PTEN activity. In contrast, mutation of the C2 phospholipid-binding domain had little effect on PTEN activation. These results suggest a model in which a PI(4,5)P2 monomer binds to PTEN, initiates an allosteric conformational change and, thereby, activates PTEN independent of membrane binding.
[Inhibition of the expression of prostate specific antigen by curcumin].

AIM To study the effect of curcumin on the expression of prostate specific antigen (PSA). METHODS AXSYM system-chemical luciferase method was used to examine the content of PSA in prostate cancer cell lines, LNCap after treated with different doses of curcumin. pGL3-PSA luciferase expression vector, containing 640 bp DNA of PSA gene 5' promoter region was constructed and transfected into LNCap cell with lipofectin. Through detecting the activity of luciferase, the effect of curcumin on the promoter of PSA was studied. Western blotting was used to detect expression of androgen receptor (AR) in LNCap cell with different concentrations of curcumin. RESULTS The expression of PSA was inhibited and activity of luciferase was reduced by curcumin. There was also significant difference in AR expression as shown by Western blotting experiment after treatment of different doses of curcumin. CONCLUSION Through inhibiting AR expression, curcumin reduced the function of PSA promoter and inhibited PSA protein expression.
Uso de álcool por vítimas de homicídio no município de São Paulo

Resumo: Introdução – o consumo excessivo de álcool é considerado um grave problema de saúde pública e apontado como um importante facilitador das situações de violência, o que sugere uma forte associação entre a ingestão de bebidas alcoólicas e a vitimização por homicídio. O objetivo deste estudo foi analisar a associação entre o uso de álcool e a vitimização por homicídio em indivíduos autopsiados nos postos médico-legais do município de São Paulo. Métodos – Dados de 2042 vítimas de homicídio no ano de 2005 foram levantados a partir dos laudos necroscópicos obtidos dos arquivos do Instituto Médico Legal de São Paulo. As informações coletadas foram: sexo, idade, grupo étnico, meio de perpetração da morte, concentração de álcool no sangue das vítimas e circunstâncias dos homicídios, como o local, data e horário da morte. Resultados: O álcool estava presente em amostras de sangue de 43% das vítimas, com uma média de alcoolemia de 1,55 ± 0,86 g/l. A prevalência de alcoolemia positiva foi maior entre os homens (44,1%) do que entre as mulheres (26,6%), p<0,01. As armas de fogo causaram a maior parte das mortes (78,6%) e o consumo de álcool foi maior entre as vítimas de homicídio cujo meio utilizado foi a arma branca (p<0,01). Houve uma maior proporção de vítimas alcoolizadas aos finais de semana do que durante os dias da semana (56,4 e 38,5, respectivamente; p<0,01) e foi encontrada uma correlação positiva entre as taxas de homicídio e a média de concentração de álcool no sangue para a área Central da cidade (rs=0,90; p<0,01). Conclusões – Os resultados demonstram a magnitude da influência do álcool como fator de contribuição para a vitimização por homicídio no maior centro urbano da América do Sul, fornecendo subsídios para políticas públicas e estudos futuros com o objetivo de prevenir os homicídios e a violência relacionada ao consumo de álcool.
The plantation paradigm: colonial agronomy, African farmers, and the global cocoa boom, 1870s–1940s*

Abstract This article investigates the powerful normative role of plantation-oriented agricultural practices in what was arguably the premier indigenous crop revolution of the colonial era: the West African cocoa boom. It traces the links between the extraordinary growth of cocoa production in the region – above all in the Gold Coast – and the longer experience of cocoa estates in other parts of the world, in particular the Caribbean, which served as a key reference point for the expanding global cocoa frontier in the late nineteenth and early twentieth centuries. In spite of the manifest competitive success of African farmers’ extensive agricultural practices during this period, most outside observers retained a strong partiality towards intensive production techniques under centralized European management. This article emphasizes the role played by the transcontinental exchange of ideas in sustaining the cultural authority of such cultivation techniques long after their commercial viability came into question.
Context Sensitive Rewriting Codes for Flash Memory†

Writing data on flash memory is asymmetric in the sense that it is possible to change a 0 into a 1-bit, but erasing a 1 back to value 0 is much more expensive and can only be done in blocks. This has triggered the development of rewriting codes in which new data can overwrite the old one, subject to the constraint of never changing a 1 into a zero. The notion of context-sensitive rewriting codes is introduced and we bring here the analysis of the compression performance of a family of such codes, based on generalizations of the Fibonacci sequence. This is then compared with experimental results.
Clinical implications of serum galactomannan measurement in patients with acute invasive fungal rhinosinusitis.

BACKGROUND Acute invasive fungal rhinosinusitis (AIFR) is an aggressive opportunistic infection with a high mortality rate. Recently, non-invasive techniques have been introduced for diagnosis of invasive fungal disease. The purpose of this study is to evaluate the diagnostic significance of serum galactomannan measurement in patients with AIFR. METHODOLOGY We conducted a retrospective case-control study of 28 patients with AIFR and 36 fungus ball (FB) patients. We evaluated clinical, laboratory, and pathologic findings along with disease course. RESULTS In 28 patients with AIFR, there were 21 cases of invasive aspergillosis (IA) and 7 cases of invasive mucormycosis (IM). The control group was comprised of 36 patients with FB. The three-group analysis showed a statistically significant difference among the groups. At the cut-off value of 0.48, the sensitivity and specificity were 71.4% and 93.0%, respectively. Comparison of mean serum galactomannan levels in 5 non-survivors and 9 survivors at initial measurement showed no significant difference, but that became significantly different 1 week later. Statistical analysis showed that the levels of serum galactomannan decreased significantly according to the measurement-point in within survivor-group analysis. The difference in between survivor-groups analysis was also significant. CONCLUSION Serum galactomannan measurement seems useful for early diagnosis and discrimination of fungal species in patients with AIFR. In addition, clinical outcomes may be related to the levels and patterns of serum galactomannan, especially in IA. The appropriate measurement of galactomannan might be helpful in treating the patients at high risk for AIFR.
The paradox of human population genetics at the end of the twentieth century

Cavalli‐Sforza, L. Luca, Paolo Menozzi, and Alberto Piazza. The History and Geography of Human Genes. Princeton, NJ: Princeton University Press, 1994. xi + 1032 pp. including appendices, literature cited, index, 8 color illustrations, 233 line drawings, and 522 maps. $150.00 cloth. Gamble, Clive. Timewalkers: The Prehistory of Global Colonization. Cambridge, MA: Harvard University Press, 1993. X + 309 pp. including notes, bibliography, and index. $24.95 cloth.
S‐allyl cysteine attenuated CCl4‐induced oxidative stress and pulmonary fibrosis in rats

This study examined effects of S‐allyl cysteine (SAC) on carbon tetrachloride (CCl4)‐induced interstitial pulmonary fibrosis in Wistar rats. CCl4 (0.5 ml/kg) was intraperitoneally injected into rats twice a week for 8 weeks, and SAC (50, 100, or 200 mg/kg), N‐acetyl cysteine (NAC, 200 or 600 mg/kg), or L‐cysteine (CYS, 600 mg/kg) were orally administrated to rats everyday for 8 weeks. SAC significantly reduced the increases of transforming growth factor beta, lipid peroxides, AST, and ALT in plasma, induced by CCl4. Although CCl4 is mainly metabolized by hepatic cytochrome P450, CCl4 induced systemic inflammation and some organ fibrosis. SAC dose‐dependently and significantly attenuated CCl4‐induced systemic inflammation and fibrosis of lung. SAC also inhibited the decrease of thiol levels, the increase of inducible nitric oxide synthase expression, the infiltration of leukocytes, and the generation of reactive oxygen species in lungs. Although NAC and CYS attenuated CCl4‐induced pulmonary inflammation and fibrosis, the order of preventive potency was SAC > NAC > CYS according to their applied doses. These results indicate that SAC is more effective than other cysteine compounds in reducing CCl4‐induced lung injury, and might be useful in prevention of interstitial pulmonary fibrosis.
Using trusted computing in trusted mail transfer protocol

In this era, hacking techniques have become more dangerous and more widely used across the Internet. If we want to send and receive a trusted email, our current techniques would not be efficient. In this paper, we propose a new protocol for trusting our emails based on Trusted Computing. We combine the hardware-based cryptography of the Trusted Platform Module and the Remote Attestation with the email protocols. The details of the proposed protocol and its security analysis are discussed in this paper. Copyright ©2013 John Wiley & Sons, Ltd.
Herpes Virus Replication

Herpesviruses are large double stranded DNA animal viruses with the distinguishing ability to establish latent, life‐long infections. To date, eight human herpesviruses that exhibit distinct biological and corresponding pathological/clinical properties have been identified. During their life cycles, herpesviruses execute an intricate chain of events geared towards optimizing their replication. This sets an interesting paradigm to study fundamental biological processes. This review summarizes recent developments in herpesvirus research with emphasis on genome transactions, particularly with respect to the prototypic herpes simplex virus type‐1. IUBMB Life, 55: 13‐22, 2003
Requirements for Visual Interaction Analysis Systems

Designers who deploy visualization applications usually want to assess how those applications are being used in the field. A promising and scalable method for understanding such use is to collect event logs of people’s interactions with the applications. The challenge is how to then analyze the interactions in the logs in order to discover insights. Researchers have used visual analytics to support this analyst-driven process with some success. However, we found that existing visual interaction analysis systems are limited in their flexibility, scalability, and generalizability to fully support this challenging task. In this article we identify the primary tasks of interaction log analysis, discuss the main units of analysis, and derive a set of system requirements to inform the design of future visual interaction analysis systems.
Characterization of the Pseudomonas aeruginosa alginate lyase gene (algL): cloning, sequencing, and expression in Escherichia coli

Mucoid strains of Pseudomonas aeruginosa produce a viscous exopolysaccharide called alginate and also express alginate lyase activity which can degrade this polymer. By transposon mutagenesis and gene replacement techniques, the algL gene encoding a P. aeruginosa alginate lyase enzyme was found to reside between algG and algA within the alginate biosynthetic gene cluster at 35 min on the P. aeruginosa chromosome. DNA sequencing data for algL predicted a protein product of ca. 41 kDa, including a 27-amino-acid signal sequence, which would be consistent with its possible localization in the periplasmic space. Expression of the algL gene in Escherichia coli cells resulted in the expression of alginate lyase activity and the appearance of a new protein of ca. 39 kDa detected on sodium dodecyl sulfate-polyacrylamide gels. In mucoid P. aeruginosa strains, expression of algL was regulated by AlgB, which also controls expression of other genes within the alginate gene cluster. Since alginate lyase activity is associated with the ability to produce and secrete alginate polymers, alginate lyase may play a role in alginate production.
Optimize Observational Time Points to Maximize the Inferability of Gene Networks

In the post-genomic era methods that are capable to estimate gene networks, e.g., signalling, metabolic or transcriptional regulatory networks, from high-throughput data are of utmost interest. In this paper we study the inferability of gene networks from time series data of a simulated gene network mimicking microarray data. The stochastic model we apply is capable of reproducing characteristic features of experimental data and, hence, can serve as a biologically plausible model of gene expression. The major purpose of this paper is to investigate the influence of the selected observational time points on the inference of a gene network. More precisely, we aim to find the optimal observational time points P of a long time series T >> P that lead to a maximization of a scoring function evaluating the quality of the estimated gene network structure.