gebhart/patrepeval huggingface dataset:
The Nature of the Attenuation ofSalmonella typhimuriumStrains Expressing Human Papillomavirus Type 16 Virus-Like Particles Determines the Systemic and Mucosal Antibody Responses in Nasally Immunized Mice (1999)

We have recently shown by using a recombinant Salmonella typhimurium PhoPc strain in mice the feasibility of using a Salmonella-based vaccine to prevent infection by the genital human papillomavirus type 16 (HPV16). Here, we compare the HPV16-specific antibody responses elicited by nasal immunization with recombinant S. typhimurium strains harboring attenuations that, in contrast to PhoPc, are suitable for human use. For this purpose, chi4989 (Deltacya Deltacrp) and chi4990 [Deltacya Delta(crp-cdt)] were constructed in the ATCC 14028 genetic background, and comparison was made with the isogenic PhoPc and PhoP- strains. Although the levels of expression of HPV16 virus-like particle (VLP) were similar in all strains, only PhoPc HPV16 induced sustained specific antibody responses after nasal immunization, while all strains induced high antibody responses with a single nasal immunization when an unrelated viral hepatitis B core antigen was expressed. The level of the specific antibody responses induced did not correlate with the number of recombinant bacteria surviving in various organs 2 weeks after immunization. Our data suggest that the immunogenicity of attenuated Salmonella vaccine strains does not correlate with either the number of persisting bacteria after immunization or the levels of in vitro expression of the antigen carried. Rather, the PhoPc phenotype appears to provide the unique ability in Salmonella to induce immune responses against HPV16 VLPs.
Immuno-oncology Combinations: A Review of Clinical Experience and Future Prospects (2014)

Immuno-oncology is an evolving treatment modality that includes immunotherapies designed to harness the patient's own immune system. This approach is being studied for its potential to improve long-term survival across multiple tumor types. It is now important to determine how immunotherapies may be most effectively used to achieve the best possible patient outcomes. Combining or sequencing immunotherapies that target distinct immune pathways is a logical approach, with the potential to further enhance the magnitude of the antitumor immune response over single agents. Early clinical data in patients with melanoma treated with two immune checkpoint inhibitors, ipilimumab and nivolumab, suggest support for this combination approach. Numerous other combination approaches are being evaluated in early-phase clinical trials; however, their clinical activity remains unknown. Clinical experience to date has shown that when combining an immuno-oncology agent with an existing therapeutic modality, it is important to determine the optimal dose, schedule, and sequence.
Enhancing the catalytic repertoire of nucleic acids. II. Simultaneous incorporation of amino and imidazolyl functionalities by two modified triphosphates during PCR (2001)

The incorporation of potentially catalytic groups into DNA is of interest for the in vitro selection of novel deoxyribozymes. We have devised synthetic routes to a series of three C7 modified 7-deaza-dATP derivatives with pendant aminopropyl, Z-aminopropenyl and aminopropynyl side chains. These modified triphosphates have been tested as substrates for Taq polymerase during PCR. All the modifications are tolerated by this enzyme, with the aminopropynyl side chain giving the best result. Most protein enzymes have more than one type of catalytic group located in their active site. By using C5-imidazolyl-modified dUTPs together with 3-(aminopropynyl)-7-deaza-dATP in place of the natural nucleotides dTTP and dATP, we have demonstrated the simultaneous incorporation of both amino and imidazolyl moieties into a DNA molecule during PCR. The PCR product containing the four natural bases was fully digested by XbaI, while PCR products containing the modified 7-deaza-dATP analogues were not cleaved. Direct evidence for the simultaneous incorporation during PCR of an imidazole-modified dUTP and an amino-modified 7-deaza-dATP has been obtained using mass spectrometry.
Efficacy of Intravenous Furosemide Versus a Novel, pH-Neutral Furosemide Formulation Administered Subcutaneously in Outpatients With Worsening Heart Failure (2017)

This study sought to determine the efficacy and safety of a novel, pH-neutral formulation of furosemide administered subcutaneously (SC) for treatment of acute decompensated heart failure (HF). Congestion requiring intravenous (IV) administration of a diuretic agent is the main reason patients with HF present for acute medical care. Outpatients presenting with decompensated HF were randomized to receive a single SC or IV dose of furosemide. Primary outcome was 6-h urine output, and secondary outcomes were weight change, natriuresis, and adverse events. Forty-one patients were randomized: 19 were treated with IV (mean dose: 123 ± 47 mg) and 21 with SC furosemide (fixed dose of 80 mg over 5 h). The 6-h urine output in the IV group was not significantly different from that in the SC furosemide group (median IV: 1,425 ml; interquartile range [IQR]: 1,075 to 1,950 ml; vs. median SC: 1,350 ml; IQR: 900 to 1,900 ml; p = 0.84). Additionally, mean weight loss was not significantly different (−1.5 ± 1.1 kg in the IV group vs. −1.5 ± 1.2 kg in the SC group; p = 0.95). Hourly urine output was significantly higher in the IV group at hour 2 (425 ml in the IV group vs. 250 ml in the SC group; p = 0.02) and higher in the SC group at hour 6 (125 ml, IV group vs. 325 ml, SC group; p = 0.005). Natriuresis was higher in the SC group (IV: 7.3 ± 35.3 mEq/l vs. SC: 32.8 ± 43.6 mEq/l; p = 0.05). There was no worsening renal function, ototoxicity, or skin irritation with either formulation. Thirty-day hospitalization rates were similar. In this phase II trial, we did not identify significant differences between urine output obtained with pH-neutral furosemide administered SC and that obtained by IV. This method of decongestion may allow treatment at home and reduced HF resources and warrants further investigation. (Sub-Q Versus IV Furosemide in Acute Heart Failure; NCT02579057)
Novel uses of the Rashkind ductal umbrella in adults and children with congenital heart disease. (1993)

The Rashkind ductal umbrella may be used successfully to treat some patients with aortopulmonary collateral vessels, ventricular septal defects, and interatrial communications after the fenestrated Fontan procedure.
An Intrinsically Disordered Peptide-Peptide Stapler for Highly Efficient Protein Ligation Both in Vivo and in Vitro (2018)

Herein, we report an intrinsically disordered protein SpyStapler that can catalyze the isopeptide bond formation between two peptide tags, that is, SpyTag and BDTag, both in vitro and in vivo. SpyStapler and BDTag are developed by splitting SpyCatcher—the cognate protein partner of SpyTag—at the more solvent exposed second loop region. Regardless of their locations in protein constructs, SpyStapler enables efficient covalent coupling of SpyTag and BDTag under a variety of mild conditions in vitro (yield ∼80%). Co-expression of SpyStapler with telechelic dihydrofolate reductase (DHFR) bearing a SpyTag at N-terminus and a BDTag at C-terminus leads to direct cellular synthesis of a circular DHFR. Mechanistic studies involving circular dichroism and nuclear magnetic resonance spectrometry reveal that SpyStapler alone is disordered in solution and forms a stable folded structure (Tm ∼ 55 °C) in the presence of both SpyTag and BDTag upon isopeptide bonding. No ordered structure can be formed in the absence of either tag. The catalytically inactive SpyStapler-EQ mutant cannot form a stable physical complex with SpyTag and BDTag, but it can fold into ordered structure in the presence of the ligated product (SpyTag-BDTag). It suggests that the isopeptide bond is important in stabilizing the complex. Given its efficiency, resilience, and robustness, SpyStapler provides new opportunities for bioconjugation and creation of complex protein architectures.
B7–CTLA4 interaction enhances both production of antitumor cytotoxic T lymphocytes and resistance to tumor challenge (1998)

Expression of B7-family costimulatory molecules CD80 (B7-1) and CD86 (B7-2) on tumor cells enhances host immunity. However, the role of the two B7 receptors, CD28 and CTLA4 (CD152), on T cells in antitumor immune response has not been clearly elucidated. Based on the effects of anti-CD28 and anti-CTLA4 mAbs on T cell response, it was proposed that CD28-B7 interaction promotes antitumor immunity, whereas B7-CTLA4 interaction down-regulates it. A critical test for the hypothesis is whether selective engagement of CTLA4 receptors by their natural ligands CD80 and CD86 enhances or reduces antitumor immunity. Here we used tumors expressing wild-type and mutant CD80, as well as mice with targeted mutation of CD28, to address this issue. We report that in syngeneic wild-type mice, B7W (W88>A), a CD80 mutant that has lost binding to CD28 but retained binding to CTLA4, can enhance the induction of antitumor cytotoxic T lymphocytes (CTL); B7Y (Y201>A), which binds neither CD28 nor CTLA4, fails to do so. Consistent with these observations, B7W-transfected J558 plasmocytoma and EL4 thymoma grow significantly more slowly than those transfected with either vector alone or with B7Y. Optimal tumor rejection requires wild-type CD80. Moreover, expression of a high level of CD80 on thymoma EL4 cells conveys immunity in mice with a targeted mutation of CD28 gene. Taken together, our results demonstrate that B7-CTLA4 interaction enhances production of antitumor CTL and resistance to tumor challenge and that optimal enhancement of antitumor immunity by CD80 requires its engagement of both CD28 and CTLA4.
Recessively inherited coagulation disorders (2004)

Deficiencies of coagulation factors other than factor VIII and factor IX that cause bleeding disorders are inherited as autosomal recessive traits and are rare, with prevalences in the general population varying between 1 in 500 000 and 1 in 2 million for the homozygous forms. As a consequence of the rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects, and the actual management of bleeding episodes are not as well established as for hemophilia A and B. We investigated more than 1000 patients with recessively inherited coagulation disorders from Italy and Iran, a country with a high rate of recessive diseases due to the custom of consanguineous marriages. Based upon this experience, this article reviews the genetic basis, prevalent clinical manifestations, and management of these disorders. The steps and actions necessary to improve the condition of these often neglected patients are outlined.
Enabling FPGAs in Hyperscale Data Centers (2015)

FPGAs (Field Programmable Gate Arrays) are making their way into data centers (DCs) and are used to offload and accelerate specific services, but they are not yet available to cloud users. This puts the cloud deployment of compute-intensive workloads at a disadvantage compared with on-site infrastructure installations, where the performance and energy efficiency of FPGAs are increasingly being exploited for application-specific accelerators and heterogeneous computing. The cloud is housed in DCs, and DCs are based on ever shrinking servers. Today, we observe the emergence of hyper scale data centers, which are based on densely packaged servers. The shrinking form factor brings the potential to deploy FPGAs on a large scale in such DCs. These FPGAs must be deployed as independent DC resources, and they must be accessible to the cloud users. Therefore, we propose to change the traditional paradigm of the CPU-FPGA interface by decoupling the FPGA from the CPU and connecting the FPGA as a standalone resource to the DC network. This allows cloud vendors to offer an FPGA to users in a similar way as a standard server. As existing infrastructure-as-a-service (IaaS) mechanisms are not suitable, we propose a new Open Stack (open source cloud computing software) service to integrate FPGAs in the cloud. This proposal is complemented by a framework that enables cloud users to combine multiple FPGAs into a programmable fabric. The proposed architecture and framework address the scalability problem that makes it difficult to provision large numbers of FPGAs. Together, they offer a novel solution for processing large and heterogeneous data sets in the cloud.
Practical Classroom English (2009)

Practical Classroom English (PCE) is a course for non-native teachers of English at secondary and tertiary level who wish to improve the amount and quality of English they use in their classes. It is similar in aims to English for Primary Teachers (Slattery and Willis 2001) and Willis’ (1981) classic Teaching English through English. According to the Introduction, it is based on Hughes’ (1981) earlier A Handbook of Classroom English, but as I myself had not reached secondary school at that point I cannot comment on any similarities and changes! The book is also based on ‘more than thirty years’ experience of running classroom English courses’, ‘the observation reports of some 1,500 practice lessons’, and ‘thirty hours of classroom recordings from eight different countries’ (all p. vi). Although ‘PCE is primarily meant as a coursebook for use in pre-service and in-service teacher training’, the authors also intend it to be suitable for use as a ‘handbook or work of reference’ and for teachers working ‘alone or in a study group’ (all p. vi). It is also meant to be suitable for teachers with a wide range of levels of language and confidence with using it in class. As that potentially covers every non-native speaking teacher of English, such a book is potentially of interest to a huge range of such teachers and the people who train them.
Chemical gene synthesis: strategies, softwares, error corrections, and applications (2008)

Chemical synthesis of DNA sequences provides a powerful tool for modifying genes and for studying gene structure, expression and function. Modified genes and consequently protein/enzymes can bridge genomics and proteomics research or facilitate commercial applications of gene and protein technologies. In this review, we will summarize various strategies, designing softwares and error correction methods for chemical gene synthesis, particularly for the synthesis and assembly of long DNA molecules based on polymerase cycling assembly. Also, we will briefly discuss some of the major applications of chemical synthesis of DNA sequences in basic research and applied areas.
Combining dual-supply, dual-threshold and transistor sizing for power reduction (2003)

Multiple supply voltages, multiple transistor thresholds and transistor sizing could be used to reduce the power dissipation of digital blocks. This paper presents a framework for evaluating the effectiveness of each of these approaches independently and in conjunction with each other. Results show the advantages of multiple supply, transistor sizing, and multiple threshold can be compounded to maximize power reduction. The order of application of these techniques determines the final savings in active and leakage power.
Preparation, Characterization and Applications of Liposomes: State of the Art (2012)

Liposomes, spherical-shaped nanovesicles, were discovered in the 60ies by Bangham. Since that, they were extensively studied as potential drug carrier. Due to their composition variability and structural properties, liposomes are extremely versatile leading to a large number of applications including pharmaceutical, cosmetics and food industrial fields. This bibliographic paper offers a general review on the background and development of liposomes with a focus on preparation methods including classic (thin film hydration, reverse-phase evaporation, ethanol injection…) and novel scalable techniques. Furthermore, liposome characterization techniques including mean size, zetapotential, lamellarity, encapsulation efficiency, in vitro drug release, vesicles stability and lipid analysis synthesized from different published works are reported. The current deepening and widening of liposome interest in many scientific disciplines and their application in pharmaceutics, cosmetics and food industries as promising novel breakthroughs and products were also handled. Finally, an opinion on the usefulness of liposomes in various applications ranging from unsubstantiated optimism to undeserved pessimism is given. The obtained information allows establishing criteria for selecting liposomes as a drug carrier according to its advantages and limitations.
PDM-Nyquist-32QAM for 450-Gb/s Per-Channel WDM Transmission on the 50 GHz ITU-T Grid (2011)

We discuss the generation and transmission of 450 Gb/s wavelength-division multiplexed (WDM) channels over the standard 50 GHz ITU-T grid optical network at a net spectral efficiency of 8.4 b/s/Hz. This result is accomplished by the use of Nyquist-shaped, polarization-division-multiplexed (PDM) 32-quadrature amplitude modulation (QAM) and both pre- and post-transmission digital equalization. To overcome the limitation of available digital-to-analog converter bandwidth, a novel method is introduced for the generation of the five-subcarriers of the 450 Gb/s signal. Nearly ideal Nyquist pulse-shaping (roll-off factor = 0.01) enables guard bands of only 200 MHz between subcarriers. To mitigate the narrow optical filtering effects from the 50 GHz-grid reconfigurable optical add-drop multiplexer (ROADM), a broadband optical pulse-shaping method has been proposed and demonstrated. By combined use of electrical and optical shaping techniques, transmission of 5 × 450 Gb/s PDM-Nyquist 32 QAM on the 50 GHz grid over 800 km and one 50 GHz-grid ROADM has been successfully demonstrated.
Influence of noninvasive ventilation by BiPAP® on exercise tolerance and respiratory muscle strength in chronic obstructive pulmonary disease patients (COPD) (2006)

This study aimed to assess the effect of BiPAP, by nasal mask, on exercise tolerance and respiratory muscle strength in patients with a clinical and spirometric diagnosis of moderate/severe COPD (FEV1 < 60% of predicted). Ten patients of 59.4+/-8.9 years old, with FEV1/FVC <70% of predicted level, were treated with 30 minutes of BiPAP (IPAP:10 and 15 cmH2O; EPAP:4 cmH2O), three days per week, during two months. Before and after the treatment, spirometry, inspiratory (MIP) and expiratory (MEP) muscle strength and the distance walked in six minutes (6MWT) were measured. We observed a significant increase (Wilcoxon, p<0.05) in the mean values of MIP (from -55+/-17 to -77+/-19, respectively), MEP (from 75+/-20 to 109+/-36, respectively) and walking distance (from 349+/-67 to 448+/-75). Based on these results, we concluded that BiPAP improves respiratory muscle strength and exercise tolerance in these COPD patients.
Overall survival and PD‐L1 expression in metastasized malignant melanoma (2010)

Abstract BACKGROUND: Cancers are known to elude the immune system, for example, by MHC loss, FAS up‐regulation, or increased secretion of TGF‐beta. Recently, ligands of coinhibitory receptors like programmed cell death ligand–1 (PD‐L1, B7‐H1) have come to attention for their role in tumor immune escape. Various tumors have been tested for PD‐L1 expression, and conflicting results were obtained regarding its correlative impact on patient survival. This study aimed to determine the prognostic relevance of PD‐L1 expression for the survival of melanoma patients. METHODS: Paraffin‐embedded nevi, primary melanoma, and in‐transit, lymph node, and distant organ metastases from a set of 63 stages III‐IV melanoma patients referred to the Netherlands Cancer Institute between 2000 and 2004 for a sentinel‐node procedure or systemic therapy were studied. A large effort was invested in validating specific PD‐L1 staining. In addition to immunological factors such as T‐cell infiltration (CD8, CD4, and regulatory T cells), TGF‐beta and MHC‐I expression were assessed. RESULTS: Longitudinal analysis revealed no relevant PD‐L1 expression on primary melanoma compared with metastatic disease. No significant correlations with prognosis were found regarding immunological factors, whereas known prognostic markers such as Breslow thickness and sex could be confirmed. Analyses of the overall survival of our patient cohort did not reveal a negative association with PD‐L1 expression. CONCLUSIONS: Correlation of overall survival with PD‐L1 expression by melanoma cells remains controversial, and future clinical studies should focus on antibody validation and time of analysis in respect to disease progression. Cancer 2011. © 2010 American Cancer Society.
Nebula: Distributed edge cloud for data-intensive computing (2014)

Today, centralized data-centers or clouds have become the de-facto platform for data-intensive computing in the commercial, and increasingly, scientific domains. This is because clouds such as Amazon AWS and Microsoft Azure offer large amounts of monetized co-located computation and storage well suited to typical processing tasks such as batch analytics. However, many Big Data applications rely on data that is geographically distributed, and is not collocated with the centralized computational resources provided by clouds. Examples of such applications include analysis of user data such as blogs, video feeds taken from geographically separated cameras, monitoring and log analysis of server and content distribution network (CDN) logs, and scientific data collected from distributed instruments and sensors. Such applications lead to a number of challenges for efficient data analytics in today's cloud platforms. First, in many applications, data is both large and widely distributed and data upload may constitute a non-trivial portion of the execution time. Second, centralized cloud resources present a single point of failure and network partitions between the data sources and the cloud can also lead to service disruptions. Third, the cost to transport, store, and process data may be outside of the budget of the small-scale application designer or end-user. The paper present Nebula: a dispersed edge cloud infrastructure that provides both computation and data storage to address the above challenges. The use of edge resources is attractive for several reasons. First, there is an increasing amount of computing and storage resources available on the edge, as evidenced by their use in several volunteer computing, filesharing as well as content delivery (CDN) environments. This capacity is likely to increase further with the provision of powerful multi-core, multi-node desktop and home machines coupled with increasing amount of high bandwidth Internet connectivity. Second, edge resources provide locality to data and users naturally, and hence, can be exploited easily for insitu processing. Finally, if cost is an issue, then volunteer edge resources can be utilized at a relatively low cost.