Assessment of academic departments efficiency using data envelopment analysis

Purpose: In this age of knowledge economy, universities play an important role in the development of a country. As government subsidies to universities have been decreasing, more efficient use of resources becomes important for university administrators. This study evaluates the relative technical efficiencies of academic departments at the Islamic University in Gaza (IUG) during the years 2004-2006. Design/methodology/approach: This study applies Data Envelopment Analysis (DEA) to assess the relative technical efficiency of the academic departments. The inputs are operating expenses, credit hours and training resources, while the outputs are number of graduates, promotions and public service activities. The potential improvements and super efficiency are computed for inefficient and efficient departments respectively. Further, multiple linear -regression is used to develop a relationship between super efficiency and input and output variables. Findings: Results show that the average efficiency score is 68.5% and that there are 10 efficient departments out of the 30 studied. It is noted that departments in the faculty of science, engineering and information technology have to greatly reduce their laboratory expenses. The department of economics and finance was found to have the highest super efficiency score among the efficient departments. Finally, it was found that promotions have the greatest contribution to the super efficiency scores while public services activities come next. Research limitations/implications: The paper focuses only on academic departments at a single university. Further, DEA is deterministic in nature. Practical implications: The findings offer insights on the inputs and outputs that significantly contribute to efficiencies so that inefficient departments can focus on these factors. Originality/value: Prior studies have used only one type of DEA (BCC) and they did not explicitly answer the question posed by the inefficient departments "Which of the resources should be given priority so that these inefficient DMUs become efficient?". This study uses both (BCC) and (CCR) in addition to relating efficiencies to input and output variables.Peer Reviewe

The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model

BACKGROUND: Favipiravir and Molnupiravir, orally available antivirals, have been reported to exert antiviral activity against SARS-CoV-2. First efficacy data have been recently reported in COVID-19 patients. METHODS: We here report on the combined antiviral effect of both drugs in a SARS-CoV-2 Syrian hamster infection model. The infected hamsters were treated twice daily with the vehicle (the control group) or a suboptimal dose of each compound or a combination of both compounds. FINDINGS: When animals were treated with a combination of suboptimal doses of Molnupiravir and Favipiravir at the time of infection, a marked combined potency at endpoint is observed. Infectious virus titers in the lungs of animals treated with the combination are reduced by ∼5 log10 and infectious virus are no longer detected in the lungs of >60% of treated animals. When start of treatment was delayed with one day a reduction of titers in the lungs of 2.4 log10 was achieved. Moreover, treatment of infected animals nearly completely prevented transmission to co-housed untreated sentinels. Both drugs result in an increased mutation frequency of the remaining viral RNA recovered from the lungs of treated animals. In the combo-treated hamsters, an increased frequency of C-to-T mutations in the viral RNA is observed as compared to the single treatment groups which may explain the pronounced antiviral potency of the combination. INTERPRETATION: Our findings may lay the basis for the design of clinical studies to test the efficacy of the combination of Molnupiravir/Favipiravir in the treatment of COVID-19. FUNDING: stated in the acknowledgment

Pan-viral protection against arboviruses by activating skin macrophages at the inoculation site

Arthropod-borne viruses (arboviruses) are important human pathogens for which there are no specific antiviral medicines. The abundance of genetically distinct arbovirus species, coupled with the unpredictable nature of their outbreaks, has made the development of virus-specific treatments challenging. Instead, we have defined and targeted a key aspect of the host innate immune response to virus at the arthropod bite that is common to all arbovirus infections, potentially circumventing the need for virus-specific therapies. Using mouse models and human skin explants, we identify innate immune responses by dermal macrophages in the skin as a key determinant of disease severity. Post-exposure treatment of the inoculation site by a topical TLR7 agonist suppressed both the local and subsequent systemic course of infection with a variety of arboviruses from the Alphavirus, Flavivirus, and Orthobunyavirus genera. Clinical outcome was improved in mice after infection with a model alphavirus. In the absence of treatment, antiviral interferon expression to virus in the skin was restricted to dermal dendritic cells. In contrast, stimulating the more populous skin-resident macrophages with a TLR7 agonist elicited protective responses in key cellular targets of virus that otherwise proficiently replicated virus. By defining and targeting a key aspect of the innate immune response to virus at the mosquito bite site, we have identified a putative new strategy for limiting disease after infection with a variety of genetically distinct arboviruses

Multivalent Tryptophan- and Tyrosine-Containing [60]Fullerene Hexa-Adducts as Dual HIV and Enterovirus A71 Entry Inhibitors

Unprecedented 3D hexa-adducts of [60]fullerene peripherally decorated with twelve tryptophan (Trp) or tyrosine (Tyr) residues have been synthesized. Studies on the antiviral activity of these novel compounds against HIV and EV71 reveal that they are much more potent against HIV and equally active against EV71 than the previously described dendrimer prototypes AL-385 and AL-463, which possess the same number of Trp/Tyr residues on the periphery but attached to a smaller and more flexible pentaerythritol core. These results demonstrate the relevance of the globular 3D presentation of the peripheral groups (Trp/Tyr) as well as the length of the spacer connecting them to the central core to interact with the viral envelopes, particularly in the case of HIV, and support the hypothesis that [60]fullerene can be an alternative and attractive biocompatible carbon-based scaffold for this type of highly symmetrical dendrimers. In addition, the functionalized fullerenes here described, which display twelve peripheral negatively charged indole moieties on their globular surface, define a new and versatile class of compounds with a promising potential in biomedical applications.status: publishe

SNAP-tagged Chikungunya Virus Replicons Improve Visualisation of Non-Structural Protein 3 by Fluorescence Microscopy

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes febrile disease, muscle and joint pain, which can become chronic in some individuals. The non-structural protein 3 (nsP3) plays essential roles during infection, but a complete understanding of its function is lacking. Here we used a microscopy-based approach to image CHIKV nsP3 inside human cells. The SNAP system consists of a self-labelling enzyme tag, which catalyses the covalent linking of exogenously supplemented synthetic ligands. Genetic insertion of this tag resulted in viable replicons and specific labelling while preserving the effect of nsP3 on stress granule responses and co-localisation with GTPase Activating Protein (SH3 domain) Binding Proteins (G3BPs). With sub-diffraction, three-dimensional, optical imaging, we visualised nsP3-positive structures with variable density and morphology, including high-density rod-like structures, large spherical granules, and small, low-density structures. Next, we confirmed the utility of the SNAP tag for studying protein turnover by pulse-chase labelling. We also revealed an association of nsP3 with cellular lipid droplets and examined the spatial relationships between nsP3 and the non-structural protein 1 (nsP1). Together, our study provides a sensitive, specific, and versatile system for fundamental research into the individual functions of a viral non-structural protein during infection with a medically important arthropod-borne virus (arbovirus)

The Impact of Immigrant Faculty Members on U.S. Universities and Research Institutes

To further understand the impact of immigrants on institutions of higher education, the IIR conducted an analysis of the publicly available Survey of Doctorate Recipients, which is a longitudinal biennial survey conducted by the National Science Foundation to provide demographic and career information about individuals with a research doctoral degree in a science, engineering, or health field (STEM) from a U.S. academic institution

Exploring molecular targets for inhibition of alpha- and enterovirus replication

Chikungunya virus (CHIKV) is a mosquito-transmitted virus belonging to the genus alphavirus of the Togaviridae family. The symptoms of an acute infection with CHIKV include fever and arthralgia which may evolve in some patients into persistent disabling polyarthritis that can last for weeks and even up to several years after the acute phase. Despite the worldwide re-emergence of CHIKV and the high morbidity rate associated with it, there is no approved vaccine or antiviral treatment available at the moment. Therefore, the development of potent antiviral drugs against CHIKV is urgently needed. We showed that prostratin, a potent activator of protein kinases C (PKC), reduced CHIKV RNA and infectious particles in a dose-dependent manner at a post-entry step during virus replication. The antiviral effect of the compound was cell-dependent, with potent antiviral activity observed in human skin fibroblasts cells, the primary target cells of CHIKV infection. The antiviral activity of prostratin was markedly reduced in the presence of PKC inhibitors, therefore confirming that the antiviral effect results from an activation of PKCs and that PKCs are potential targets for inhibition of CHIKV replication. In the same context, we identified that salicylate-based analogs of bryostatin, another PKC activator, protected cells from CHIKV-induced cell death. Interestingly, 'capping' a hydroxyl group of a lead bryostatin analog, which is crucial for binding to PKCs, did not abrogate the anti-CHIKV activity of the scaffold, putatively indicating the involvement of a PKC-independent pathway. A detailed comparative analysis of the effect of the non-capped versus the two capped bryostatin analogs revealed that the non-capped analog acts both at early and late stages in CHIKV replication cycle, while the capped analogs only interfere with a later stage process. Co-dosing with PKC inhibitors counteracted the antiviral activity of non-capped analog without affecting that of capped analogs. Thus, the capped bryostatin analogs can inhibit CHIKV replication through a novel, yet still elusive, non-PKC dependent pathway. Interestingly, treatment of CHIKV-infected cells with a combination of a non-capped and a capped analog resulted in a pronounced synergistic antiviral effect. Favipiravir (T-705) is a broad-spectrum antiviral agent with a potent inhibitory effect on CHIKV replication in cell culture. We evaluated the potential protective effect of favipiravir , during both the acute and chronic phase of the infection in a CHIKV arthritis mouse model. Interestingly, favipiravir treatment during the acute phase of CHIKV infection completely inhibited systemic viral spread and reduced the viral RNA levels in the ankles of inoculated feet. On the other hand, favipiravir treatment during the late stage of infection did not result in significant differences in viral RNA levels among the treated and untreated mice in the ankles. cDNA amplification of the major parts of the CHIKV coding region of the viral RNA extracted from both the acute and chronic phase ankle samples revealed that the band for the viral RNA-dependent RNA polymerase (RdRp) amplicon is missing and the bands representing some viral proteins have a smaller size than expected. These results gave an initial indication that the viral RNA detected during the chronic phase may be a defective viral genome or degraded RNA and not the genome of actively replicating virus. A previous study in our lab showed that the K291R substitution in the CHIKV RdRp is implicated in low-level resistance against favipiravir in vitro. Interestingly, this lysine is a highly conserved amino acid in the RdRp of positive-sense, single-stranded RNA [+ssRNA] viruses. To obtain insights into the unique broad-spectrum antiviral activity of favipiravir, we explored the role of this lysine using the coxsackievirus B3 (CVB3). Introduction of the corresponding K-to-R substitution in the CVB3 RdRp (K159R) resulted in a non-viable virus. Replication competence was restored after spontaneous acquisition of an A239G substitution in the RdRp. A mutagenesis analysis at position K159 resulted in only one additional viable variant (K159M) that also acquired the A239G mutation. The K159 mutations markedly decreased the RdRp efficiency in polymerase assays, which was restored by the introduction of the A239G mutation. The K159R-A239G and K159M-A239G viruses were more susceptible to favipiravir than wild-type virus (WT) and exhibited lower fidelity in polymerase assays. Furthermore, the K159R-A239G virus showed a highly attenuated phenotype in mice. These results thus corroborated that this conserved lysine of the viral RdRp is a key residue for both the functionality of this enzyme as well as for the broad-spectrum mechanism of action of favipiravir. Besides CHIKV, many other viruses lack an available antiviral treatment, including enteroviruses (Picornaviridae family). Although infections with enteroviruses are usually mild, they can occasionally result in severe diseases such as paralytic poliomyelitis by polioviruses (PVs) and myocarditis by CVBs. We identified a novel and selective benzene sulfonamide derivative inhibitor (i.e. compound 17) of CVB3 replication which was in silico designed to inhibit the viral 3C protease. We showed that compound 17 inhibited the replication of a panel of group B enteroviruses, but had no antiviral activity against representative viruses from other enterovirus groups. In contrast to what was expected for a protease inhibitor, a time-of-drug-addition study revealed that compound 17 interfered with an early step in the virus replication cycle. This observation was corroborated by the results of a thermostability study, which provided additional evidence for an interaction between the compound and the viral capsid. Subsequently, this latter target was confirmed by the genotyping of independently-selected compound 17-resistant CVB3 variants, which were all found to carry a mutation in the VP1 gene. Interestingly, the mutated VP1 residues are not located inside the classical drug-binding pocket for capsid binders such as pleconaril. On the other hand, both the VP1 glutathione binding pocket as well as the ion channel at the 5-fold axis of the VP1 pentamer appear to be implicated in the mechanism of action of compound 17. Finally, we showed that glutathione (GSH), an essential host factor for stabilization of the enterovirus capsid during morphogenesis, has a pronounced heat-stabilizing effect for the three types of PV Sabin vaccine strains. CVB3 was also used as a surrogate for PV to assess whether the GSH-stabilized virus would still be infectious in mice (a requirement for the live-attenuated vaccine). Indeed, whereas heat-inactivated CVB3 was no longer infectious in highly susceptible SCID mice, GSH-stabilized virus remained as infectious as non-heated virus. Several studies are ongoing to generate genetically stable Sabin polioviruses to be used as a safe, oral live attenuated vaccine during the post-polio eradication era. The fact that GSH is naturally present at high concentration in the human body makes it a safe and efficient candidate stabilizer for these new oral poliomyelitis vaccine (OPV) formulations.status: publishe

PHYSIOLOGY AND REPRODUCTION: Plasma 17\u3ci\u3eβ\u3c/i\u3e-Estradiol Levels and Ovarian Interstitial Cell Structure in Embryonic Japanese Quail

Plasma concentrations of 17β-estradiol (E2) and left ovarian histology were investigated by light and electron microscopy in female Japanese quail from Day 10 of embryonic development through Day 7, posthatch. Plasma E2 levels remained relatively constant (102 to 140 pg/mL) in the embryo followed by a sharp decrease posthatch (47 to 70 pg/mL). Beginning on Day 10 of incubation, cells in the medullary portion (medullary cell; MC) of the left ovaries exhibited ultrastructural evidence of steroidogenic capability. The MC had numerous lipid droplets in close proximity to the smooth endoplasmic reticulum (SER). Mitochondria were also observed in the vicinity of the lipid droplets and SER. On Days 10 and 12, the cristae of the inner mitochondrial membranes were of a lamellar configuration; the cristae of some mitochondria in MC had a tubular appearance by Day 14. These data document relative ontogenic changes in ovarian morphology and plasma E2 levels during the early developmental period in female Japanese quail. These data further support the role of this steroid in sexual differentiation

Assessment of academic departments efficiency using data envelopment analysis

Purpose: In this age of knowledge economy, universities play an important role in the development of a country. As government subsidies to universities have been decreasing, more efficient use of resources becomes important for university administrators. This study evaluates the relative technical efficiencies of academic departments at the Islamic University in Gaza (IUG) during the years 2004-2006. Design/methodology/approach: This study applies Data Envelopment Analysis (DEA) to assess the relative technical efficiency of the academic departments. The inputs are operating expenses, credit hours and training resources, while the outputs are number of graduates, promotions and public service activities. The potential improvements and super efficiency are computed for inefficient and efficient departments respectively. Further, multiple linear -regression is used to develop a relationship between super efficiency and input and output variables. Findings: Results show that the average efficiency score is 68.5% and that there are 10 efficient departments out of the 30 studied. It is noted that departments in the faculty of science, engineering and information technology have to greatly reduce their laboratory expenses. The department of economics and finance was found to have the highest super efficiency score among the efficient departments. Finally, it was found that promotions have the greatest contribution to the super efficiency scores while public services activities come next. Research limitations/implications: The paper focuses only on academic departments at a single university. Further, DEA is deterministic in nature. Practical implications: The findings offer insights on the inputs and outputs that significantly contribute to efficiencies so that inefficient departments can focus on these factors. Originality/value: Prior studies have used only one type of DEA (BCC) and they did not explicitly answer the question posed by the inefficient departments "Which of the resources should be given priority so that these inefficient DMUs become efficient?". This study uses both (BCC) and (CCR) in addition to relating efficiencies to input and output variables.Peer Reviewe