gebhart/patrepeval huggingface dataset:
315. Identification and Control of Bacterial Contamination in an Academic Good Manufacturing Practice Facility (2006)

An ongoing monitoring program is an essential component of operating a Good Manufacturing Practice (GMP) facility. To support manufacture of clinical grade viral gene transfer vectors, the Belfer Gene Therapy Core Facility has a Class 100,000 GMP facility with three production laboratories, in which all open operations of production are conducted in Class 100 biological safety cabinets. The routine monitoring program measures viable and non-viable particles weekly and temporal trending is assessed to identify emerging problems. In July 2005, a series of vector batches were found to be contaminated by slow growing bacteria, necessitating an extensive investigation. Among the questions posed were: Are our environmental monitoring protocols adequate for detecting contamination? What are the sources of contamination? Do our cleaning protocols/products remove it? Can our production methods be improved to reduce the risk of contamination? The routine viable particle testing uses tryptic soy agar plates and contact slides, which we suspected may not support growth of certain bacteria that could grow in the DMEM medium (with 10% serum) used to culture HEK 293 cells for vector production. We created a semi-solid medium by addition of agar to cell culture medium and found that multiple samples that tested negative by the routine method now showed bacterial growth, including an occasional production contaminant later identified as Methylobacterium organophilum. Monitoring was repeated using this improved medium and several locations yielded bacteria upon swabbing, particularly the insides of cell culture incubators and water from incubator humidifiers. To identify the species and possible sources, 16S rRNA genes were PCR-amplified from bacterial isolates and, based on the sequence of the PCR product, the bacterium was identified. The most common contaminants were Bacillis licheniformis, Paenibacillus favisporus and Pseudomonas marginalis. Only one typical human flora, Staphylococcus epidermidis, was identified, in the access corridor where approved personnel enter without gowning. The data suggest that environmental bacteria, brought in inadvertently on materials, were the major contamination source. A complete cleaning of incubators was initiated, including flushing the water reservoirs and humidity chambers with a sporicidal cleaner, followed by normal rotation detergents. A complete facility cleaning followed the incubator cleaning and then another environmental monitoring round. Cycles of cleaning and expanded environmental monitoring continued until no contamination was detectable, at which point production resumed. The production process since has been contamination-free. Expanded cleaning and monitoring has been added to the routine facility maintenance, and procedures have been added to increase wipe down of materials entering the facility and during production. Modifications in monitoring and production resulting from the investigation represent improvements in our overall GMP quality assurance program.
Delivery ofChlamydiavaccines (2005)

The plethora of ocular, genital and respiratory diseases of Chlamydia, including nongonococcal urethritis, cervicitis pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, conjunctivitis, blinding trachoma and interstitial pneumonia, and chronic diseases that may include atherosclerosis, multiple sclerosis, adult onset asthma and Alzheimer's disease, still pose a considerable public health challenge to many nations. Although antibiotics are effective against Chlamydia when effectively diagnosed, asymptomatic infections are rampart, making clinical presentation of complications often the first evidence of an infection. Consequently, the current medical opinion is that an effective prophylactic vaccine would constitute the best approach to protect the human population from the most severe consequences of these infections. Clinical and experimental studies have demonstration that Chlamydia immunity in animals and humans is mediated by T cells and a complementary antibody response, and the completion of the genome sequencing of several isolates of Chlamydia is broadening our knowledge of the immunogenic antigens with potential vaccine value. Thus, major advances have been made in defining the essential elements of a potentially effective subunit vaccine design and parameters for evaluation. However, the challenge to develop effective delivery systems and human compatible adjuvants that would boost the immune response to achieve long-lasting protective immunity remains an elusive objective in chlamydial vaccine research. In response to evolving molecular and cellular technologies and novel vaccinology approaches, considerable progress is being made in the construction of novel delivery systems, such as DNA and plasmid expression systems, viral vectors, living and nonliving bacterial delivery systems, the use of chemical adjuvants, lipoprotein constructs and the codelivery of vaccines and specific immuno-modulatory biological agonists targeting receptors for chemokines, Toll-like receptors, and costimulatory molecules. The application of these novel delivery strategies to Chlamydia vaccine design could culminate in timely achievement of an efficacious vaccine.
Physical Interaction Between Retinoic Acid Receptor and Sp1: Mechanism for Induction of Urokinase by Retinoic Acid (1999)

Induction of urokinase plasminogen activator (uPA) by retinoic acid (RA) is the initial event preceding certain subsequent biological changes in vascular endothelial cells. We investigated the molecular mechanism by which RA stimulates the expression of uPA, which lacks a canonical RA receptor (RAR)-responsive element, in bovine and human aortic endothelial cells. Upon stimulation with RA, mRNA levels of RAR and β transiently increased in parallel with the induction of uPA, and this increase was inhibited by cycloheximide. Results of transient transfection of RAR/RXR cDNAs and experiments using specific agonists and antagonists suggested that uPA induction is dependent upon RAR (initially, RAR) with the help of RXR. Deletion analysis of the uPA promoter suggested that RAR/RXR acts on GC box region within the uPA promoter. This was further supported by inhibition of Sp1 binding to this region. Coimmunoprecipitation studies, glutathioneS-transferase pull-down experiment, and mammalian two-hybrid assays suggested a physical interaction between RAR/RXR and Sp1. Furthermore, gel shift studies showed that the binding of Sp1 to the uPA GC box is significantly potentiated in the presence of RARs/RXRs. Finally, Sp1 and RAR/RXR synergistically enhanced the transactivation activity of the uPA promoter. These results suggest that (1) RA induces RARs mainly via RAR and that (2) RAR/RXR physically and functionally interact with Sp1, resulting in a potentiation of uPA transcription.
Modular Binding Domains in Signal Transduction Proteins Review (1995)

The transduction of a signal is a change in form of the signal as it is passed from one carrier to another. The root duce meansto lead in Latin; thus, a signal is led through a cell by steps of transduction (the same root is in the words seduce and duct as well as II Duce). The earliest transduction steps that were elucidated involved massive release of small molecule second messengers, originally cAMP, that flooded a cell with information. With the understanding that such proteins as tyrosine kinases and Ras relatives are signal transducers, came the realization that many signaling pathways are more precise, sending controlled and probably weakly amplified signals to specific targets. These intracellular signals are often maintained in macromolecular form rather than being passed to small molecules. The proteins that carry these signals are not acting in the classic fashion of enzymes that are designed to modify large numbers of substrate molecules. These signal transducers, even if they catalyze an event such as phosphorylation, generally affect small numbers of target molecules and have often separated their catalytic function from their binding regions, which can bring substrates to the catalytic centers, link the signal transducers to upstream proteins, and localize protein complexes to particular cellular subregions. The binding domains are often modular ones constructed with a common core recognition ability coupled to a fine specificity control. They modulate the interaction of proteins with other proteins and therefore determine the paths of signal transduction systems. They are generally controlled, also, so that the aggregates they form are transient, pathways forming only when the signal is being transmitted and then disaggregating when the signal has passed. The signal transduction protein must be highly integrated, with all of the elements working together to send just the appropriate quanta of signal for the specific need. The preceding paragraphs are generalizations based on scanty and fragmentary evidence. With many transduction pathways known only in outline and more sure to be found, there is a deeply exciting richness yet to be elucidated. But many investigators are now working within the framework presented above, trying to find the relevant units and understand their integration. Protein-protein interaction has long been studied, but the realization of the importance of defined binding rood-
Experimental evidence that symbiotic bacteria produce chemical cues in a songbird (2019)

Symbiotic microbes that inhabit animal scent glands can produce volatile compounds used as chemical signals by the host animal. Though several studies have demonstrated correlations between scent gland bacterial community structure and host animal odour profiles, none have systematically demonstrated a causal relationship. In birds, volatile compounds in preen oil secreted by the uropygial gland serve as chemical cues and signals. Here, we tested whether manipulating the uropygial gland microbial community affects chemical profiles in the dark-eyed junco (<i>Junco hyemalis</i>). We found an effect of antibiotic treatment targeting the uropygial gland on both bacterial and volatile profiles. In a second experiment, we cultured bacteria from junco preen oil, and found that all of the cultivars produced at least one volatile compound common in junco preen oil, and that most cultivars produced multiple preen oil volatiles. In both experiments, we identified experimentally generated patterns in specific volatile compounds previously shown to predict junco reproductive success. Together, our data provide experimental support for the hypothesis that symbiotic bacteria produce behaviourally relevant volatile compounds within avian chemical cues and signals.
Coherence domain restriction on large scale systems (2015)

Designing massive scale cache coherence systems has been an elusive goal. Whether it be on large-scale GPUs, future thousand-core chips, or across million-core warehouse scale computers, having shared memory, even to a limited extent, improves programmability. This work sidesteps the traditional challenges of creating massively scalable cache coherence by restricting coherence to flexible subsets (domains) of a system's total cores and home nodes. This paper proposes Coherence Domain Restriction (CDR), a novel coherence framework that enables the creation of thousand to million core systems that use shared memory while maintaining low storage and energy overhead. Inspired by the observation that the majority of cache lines are only shared by a subset of cores either due to limited application parallelism or limited page sharing, CDR restricts the coherence domain from global cache coherence to VM-level, application-level, or page-level. We explore two types of restriction, one which limits the total number of sharers that can access a coherence domain and one which limits the number and location of home nodes that partake in a coherence domain. Each independent coherence domain only tracks the cores in its domain instead of the whole system, thereby removing the need for a coherence scheme built on top of CDR to scale. Sharer Restriction achieves constant storage overhead as core count increases while Home Restriction provides localized communication enabling higher performance. Unlike previous systems, CDR is flexible and does not restrict the location of the home nodes or sharers within a domain. We evaluate CDR in the context of a 1024-core chip and in the novel application of shared memory to a 1,000,000-core warehouse scale computer. Sharer Restriction results in significant area savings, while Home Restriction in the 1024-core chip and 1,000,000-core system increases performance by 29% and 23.04x respectively when comparing with global home placement. We implemented the entire CDR framework in a 25-core processor taped out in IBM's 32nm SOI process and present a detailed area characterization.
Are Solvent and Dispersion Effects Crucial in Olefin Polymerization DFT Calculations? Some Insights from Propylene Coordination and Insertion Reactions with Group 3 and 4 Metallocenes (2014)

The primary insertion (or 1,2-insertion) of propylene into (C5Me5)2YCH2CH2CH(Me)2, as well as the primary and secondary (or 2,1) insertions of propylene into the activated ansa-zirconocene complex [{Ph(H)C-(3,6-tBu2Flu)(3-tBu-5-Me-C5H2)}ZrMe]+ were calculated with several DFT methods to find the most adequate methodology for the computation of metallocene-catalyzed olefin polymerization reactions. For the yttrium system, both solvent corrections and dispersion corrections are needed to determine energies of coordination and activation barriers in agreement with experimental data. Dispersion corrections were included directly via the use of specific functionals like B97D and M06 or were added as empirical corrections (GD3BJ) to the B3PW91 calculations. For the zirconocene system, the best method is a combination of B3PW91 with solvent corrections incorporated with the SMD continuum model. The dispersion corrections, included via both GD3BJ and M06, tend to overestimate the stabilization of the adducts because of the high steric bulk of the zirconocene system. The addition of dispersion corrections shifts the energy profiles toward lower values but does not affect the relative activation barriers. Implementation of entropy corrections counterbalances almost perfectly the dispersion corrections. The same observations arise from the study of the C–H activations of propylene induced by the zirconocene complex.
Supplementary Figures S1-S10 from Endothelial Thermotolerance Impairs Nanoparticle Transport in Tumors (2023)

&lt;p&gt;Tumor accumulation of AS750 after PEG-NR heat exposure with varying delta T (S1); Diminished window of tumor transport after re-exposure to PEG-NR heating (S2); Animal weights during PEG-NR and doxorubicin liposome therapeutic trial (S3); Transvascular transport in tumors after single exposure and re-exposure to PEGNR heating (S4); Vascular endothelial growth factor (VEGF) expression in PEG-NR heated tumors (S5); Endothelial cell F-Actin dynamics during heat exposure and recovery (S6); Visualizing PEG-NRs in the tumor microenvironment using multiphoton microscopy (S7); Cargo accumulation in tumors with Hsf1+/+ and Hsf1-/- vasculature after single exposure to PEG-NR heating (S8); HSF1 expression in tumor-associated vasculature following PEG-NR heating (S9); Size-dependent macromolecular extravasation from the unheated vasculature (S10).&lt;/p&gt;
Least in-sequence probability heuristic for mixed-volume production lines (2006)

The paper focuses on the sequencing aspects of a stochastic hybrid flexible assembly system (FAS) operating in a build-to-order environment. In such a system, although the flow of parts is unidirectional, parallel paths can exist for accommodating different types of parts produced and potential rework of the parts that fail inspection at a given production stage. As a result, the original sequential order of parts can become distorted, resulting in an exit demand sequence which is at variance with the input sequence. To compensate for such sequence disturbances, an adequately sized buffer is installed at the exit end of the FAS. From a practical viewpoint, the study is relevant to the sequencing of upstream operations in an automotive assembly plant functioning in an in-line vehicle sequencing mode. An important feature of the FAS considered in this study is that the demand sequence of part types is known and fixed for a given period of time. Further, the different part types that constitute the demand sequence can have different frequencies of occurrence in a range specified from low to high. We exploit this property of the demand sequence in the development of the least in-sequence probability (LISP) algorithm. The development of LISP is based on the trade-off of pulling low-volume parts ahead in the input sequence while delaying the high-volume parts. We propose the use of the heuristic as a means to achieve both of the following: (a) to improve customer service levels in terms of the number of in-sequence parts output from the system, given a fixed size for the re-sequencing buffers; and (b) to reduce re-sequencing buffer sizes given target levels of customer service.
The bioavailability of iron picolinate is comparable to iron sulfate when fortified into a complementary fruit yogurt: a stable iron isotope study in young women (2019)

Therefore, Fe picolinate is a promising compound for the fortification of difficult-to-fortify foods, to help meet Fe requirements of infants, young children and women of childbearing age.
Data from Cumulative Effect of Multiple Loci on Genetic Susceptibility to Familial Lung Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Genetic factors play important roles in lung cancer susceptibility. In this study, we replicated the association of 5p15.33 and 6p21.33 with familial lung cancer. Taking into account the previously identified genetic susceptibility variants on 6q23-25/&lt;i&gt;RGS17&lt;/i&gt; and 15q24-25.1, we further determined the cumulative association of these four genetic regions and the population attributable risk percent of familial lung cancer they account for.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; One hundred ninety-four case patients and 219 cancer-free control subjects from the Genetic Epidemiology of Lung Cancer Consortium were used for the association analysis. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members. Single nucleotide polymorphisms (SNP) on chromosomal regions 5p15.33, 6p21.33, 6q23-25/&lt;i&gt;RGS17&lt;/i&gt;, and 15q24-25.1 were assessed for their associations with familial lung cancer. The cumulative association of the four chromosomal regions with familial lung cancer was evaluated with the use of a linear logistic model. Population attributable risk percent was calculated for each SNP using risk ratio.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; SNP rs31489 showed the strongest evidence of familial lung cancer association on 5p15.33 (&lt;i&gt;P&lt;/i&gt; = 2 × 10&lt;sup&gt;−4&lt;/sup&gt;; odds ratio, 0.57; 95% confidence interval, 0.42-0.77), whereas rs3117582 showed a weak association on 6p21.33 (&lt;i&gt;P&lt;/i&gt; = 0.09; odds ratio, 1.47; 95% confidence interval, 0.94-2.31). Analysis of a combination of SNPs from the four regions provided a stronger cumulative association with familial lung cancer (&lt;i&gt;P&lt;/i&gt; = 6.70 × 10&lt;sup&gt;−6&lt;/sup&gt;) than any individual SNPs. The risk of lung cancer was increased to 3- to 11-fold among those subjects who had at least one copy of risk allele at each region compared with subjects without any of the risk factors. These four genetic regions contribute to a total of 34.6% of familial lung cancer in smokers.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The SNPs in four chromosomal regions have a cumulative and significant association with familial lung cancer and account for about one-third of the population attributable risk for familial lung cancer. Cancer Epidemiol Biomarkers Prev; 19(2); 517–24&lt;/p&gt;&lt;/div&gt;
Injection-locked passively mode-locked semiconductor laser for optical heterodyne detection using a single axial mode (2004)

The optical heterodyne detection for an extremely densely channelized coherent communication systems using phase coherent optical combs is demonstrated by using a passively modelocked semiconductor laser injection locked to a master laser oscillator. The single sideband noise of the heterodyne beat tone at 13.160 GHz was reduced to -123 dBc/Hz at 100 kHz offset from the carrier by exploiting the excellent noise rejection performance of a commercially available microwave bandpass filter. A signal-to-noise ratio of over 65 dB/Hz has been achieved in a single channel filtered from two analog RF signals detuned by only 200 MHz. These results show improved signal-to-noise ratio and superior crosstalk reduction between densely packed neighboring channels via electrical manipulation of the optical heterodyne detection signal.
Flow Analysis in Screw Extruders-Effect of Kinematic Conditions (1998)

Abstract Recently, several investigators have challenged the simplifying assumption of using a stationary screw with a rotating barrel when analyzing the flow in single screw extruders. The investigators claim that there are significant differences between the realistic and simplified cases, such as a 12 percent difference in throughput [1]. This paper presents an analytical derivation for the flow in a laid out system and one which includes the curvature of the screw. An experimental set-up was built which allows the rotation of the barrel with a stationary screw and the rotation of the screw with a stationary barrel, and a three dimensional flow simulation program was used to model the flow in the extruder using the two conditions. The analytical, experimental and numerical analyses show that it is justified to use the stationary screw assumption when modeling the flow in single screw extruders.
Multicore fiber with one-ring structure (2013)

The characteristics of a multicore fiber with one-ring structure are reviewed. The one-ring structure, which has no center core, can overcome issues on the hexagonal close-pack structure that is the most popular multicore structure. The onering structure has flexibility in the number of cores and is unrelated to the core pitch limitation due to cutoff wavelength lengthening thank to no center core structure. The one-ring structure is effective to suppress the worst case crosstalk that is crosstalk assuming all cores carry equal signal power. In the case of hexagonal close-pack structure, the worst case crosstalk of an inner core is 7.8 dB larger than that between two cores. The different worst crosstalk is observed depending on the number of nearest neighbor cores. The one-ring structure can limit the degradation to 3.0 dB for all cores. Fabricated 12-core fiber with the one-ring structure based on the simulation realized effective core area of 80 m2 and very low crosstalk less than -40 dB after 100-km propagation.