gebhart/patrepeval huggingface dataset:
Engineered Biosynthesis of a Novel Amidated Polyketide, Using the Malonamyl-Specific Initiation Module from the Oxytetracycline Polyketide Synthase (2006)

Tetracyclines are aromatic polyketides biosynthesized by bacterial type II polyketide synthases (PKSs). Understanding the biochemistry of tetracycline PKSs is an important step toward the rational and combinatorial manipulation of tetracycline biosynthesis. To this end, we have sequenced the gene cluster of oxytetracycline (oxy and otc genes) PKS genes from Streptomyces rimosus. Sequence analysis revealed a total of 21 genes between the otrA and otrB resistance genes. We hypothesized that an amidotransferase, OxyD, synthesizes the malonamate starter unit that is a universal building block for tetracycline compounds. In vivo reconstitution using strain CH999 revealed that the minimal PKS and OxyD are necessary and sufficient for the biosynthesis of amidated polyketides. A novel alkaloid (WJ35, or compound 2) was synthesized as the major product when the oxy-encoded minimal PKS, the C-9 ketoreductase (OxyJ), and OxyD were coexpressed in CH999. WJ35 is an isoquinolone compound derived from an amidated decaketide backbone and cyclized with novel regioselectivity. The expression of OxyD with a heterologous minimal PKS did not afford similarly amidated polyketides, suggesting that the oxy-encoded minimal PKS possesses novel starter unit specificity.
Stereotaxic computerized tomography with a GE 8800 scanner (1980)

A stereotaxic system is described that uses computerized tomography scanning for target localization. This system is unique in that the sterotaxic localization may be carried out using the scanner computer without the addition of any extra software. The hardware of the system is built up around a base plate which is fastened to the scanner's patient table. The head is positioned and fixed to the base plate with aluminum bars, which are fixed to the calvaria with screws. Various stereotaxic devices may be fastened to the base plate. The system has been in clinical use for 4 months at the time of writing. Its main application has been in tumor biopsies, but it has also been used for functional operations.
5′- and 3′-terminal sequences of the chloroplast 16S and 23S ribosomal RNAs ofEuglena gracilis (1992)

Prior to analysis of Euglena gracilis chloroplast 16S and 23S rRNAs, the sequence of an entire rRNA operon (rrnC) was completed, annotated in full, and deposited in the EMBL database (accession no. X12890, updated). To determine precisely the termini of the mature rRNAs, we directly sequenced the individual end-labeled species. 5'-Terminal and 3'-terminal sequences were determined by the enzymatic (1, 2) and chemical (3) methods, respectively. There were some minor bands in the sequencing ladders, most of which could be accounted for by cross-contamination with the other chloroplast rRNA species and/or cytoplasmic small subunit rRNA. Comparison of these RNA sequences with published DNA sequences allowed precise assignment of termini. Photographs of the relevant sequencing gels have been supplied to referees.
The Germ Cell Determinant Blimp1 Is Not Required for Derivation of Pluripotent Stem Cells (2012)

Blimp1 (Prdm1), the key determinant of primordial germ cells (PGCs), plays a combinatorial role with Prdm14 during PGC specification from postimplantation epiblast cells. They together initiate epigenetic reprogramming in early germ cells toward an underlying pluripotent state, which is equivalent to embryonic stem cells (ESCs). Whereas Prdm14 alone can promote reprogramming and is important for the propagation of the pluripotent state, it is not known whether Blimp1 is similarly involved. By using a genetic approach, we demonstrate that Blimp1 is dispensable for the derivation and maintenance of ESCs and postimplantation epiblast stem cells (epiSCs). Notably, Blimp1 is also dispensable for reprogramming epiSCs to ESCs. Thus, although Blimp1 is obligatory for PGC specification, it is not required for the reversion of epiSCs to ESCs and for their maintenance thereafter. This study suggests that reprogramming, including that of somatic cells to ESCs, may not entail an obligatory route through a Blimp1-positive PGC-like state.
Subsecond Electrophoretic Separations from Droplet Samples for Screening of Enzyme Modulators (2014)

High-throughput screening (HTS) using multiwell plates and fluorescence plate readers is a powerful tool for drug discovery and evaluation by allowing tens of thousands of assays to be completed in 1 day. Although this method has been successful, electrophoresis-based methods for screening are also of interest to avoid difficulties associated fluorescence assays such as requirements to engineer fluorogenic reactions and false positives. We have developed a method using droplet microfluidics to couple multiwell plate-based assays to microchip electrophoresis (MCE) to screen enzyme modulators. Samples contained in multiwell plates are reformatted in to plugs with a sample volume of 8 nL segmented by an immiscible oil. The segmented flow sample streams are coupled to a hybrid polydimethylsiloxane-glass microfluidic device capable of selectively extracting the aqueous samples from the droplet stream and rapidly analyzing by MCE with laser-induced fluorescence detection. This system was demonstrated by screening a test library of 140 compounds against using protein kinase A. For each sample in the screen, two droplets are generated, allowing approximately 6 MCE injections per sample. Using a 1 s separation at 2000 V/cm, we are able to analyze 96 samples in 12 min. Separation resolution between the internal standard, substrate, and product is 1.2 and average separation efficiency is 16,000 plates/s using real samples. Twenty-five compounds were identified as modulators during primary screening and verified using dose-response curves.
Severe myoclonic epilepsy in infancy: A systematic review and a meta‐analysis of individual patient data (2007)

Severe myoclonic epilepsy in infancy (SMEI) is a rare, but severe disorder with seizures typically resistant to conventional antiepileptic drugs. The objective of the present study was to systematically review the literature on the available treatments for SMEI. Databases searched included Medline, Embase, and Cochrane. We used a fixed effect model to summarize the odds ratio of seizures rates and a logistic model to evaluate the influence of patient characteristics on treatment effect. We found 23 uncontrolled studies and 2 randomized controlled trials (RCTs) that compared stiripentol with placebo. Overall, 64 children aged between 3 and 20 years were included in the two RCTs. The odds ratio of responding to stiripentol relative to placebo was 32 (CI: 6.2, 161) and stiripentol reduced seizure rate by 70% (93%; 47%). The multivariate analysis does not suggest any differences within subgroups of participants and cotherapy. Results of uncontrolled studies in children with SMEI are potentially biased and do not provide valid information on the benefits and harms of treatments. The two RCTs identified, however, were performed with the same objectives and design and showed that seizure frequency is greatly reduced by stiripentol in children with SMEI after 2 months of treatment.
Implementing a faster string search algorithm in Ada (1988)

article Free Access Share on Implementing a faster string search algorithm in Ada Authors: P. Wood Softech,Inc., 2000 N .Beauregard St., Alexandria, Va. Softech,Inc., 2000 N .Beauregard St., Alexandria, Va.View Profile , D. Turcaso Softech,Inc., 2000 N .Beauregard St., Alexandria, Va. Softech,Inc., 2000 N .Beauregard St., Alexandria, Va.View Profile Authors Info & Claims ACM SIGAda Ada LettersVolume VIIIIssue 3May/June, 1988 pp 87–97https://doi.org/10.1145/44772.44777Online:01 April 1988Publication History 0citation161DownloadsMetricsTotal Citations0Total Downloads161Last 12 Months0Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Bispecific antibodies reactive with the multidrug‐resistance‐related glycoprotein and CD3 induce lysis of multidrug‐resistant tumor cells (1989)

We describe the lysis of multidrug-resistant (MDR) tumor cells by various lymphocytic effector cells, retargeted with bispecific antibodies (heteroconjugates). The Ab-heteroconjugate used was prepared by chemically cross-linking the OKT3 monoclonal antibody (MAb) reactive with CD3 antigen on T lymphocytes, with the MRK16 MAb, which recognizes the MDR-associated P-glycoprotein. Cloned TCR alpha beta/CD3+ T lymphocytes, OKT3-activated peripheral-blood mononuclear cells and peripheral-blood mononuclear blood lymphocytes, stimulated with allogeneic irradiated cells in a mixed lymphocyte culture, could be induced to lyse MDR ovarian tumor cells in the presence of Ab-heteroconjugate CD3/MRK16, whereas the drug-sensitive parental tumor cells lacking the P-glycoprotein were not lysed by these retargeted effector cells. Cloned TCR gamma delta/CD3+ T lymphocytes showed a high MHC-unrestricted lysis of MDR tumor cells. Addition of Ab-heteroconjugate CD3/MRK16 could therefore not enhance target-cell lysis. Melanoma tumor cells transfected with the mdr-I gene which codes for the P-glycoprotein were also efficiently lysed by Ab-heteroconjugate retargeted cloned TCR alpha beta/CD3+ T cells. Tumor cell lines derived from organs known to express the P-glycoprotein also were lysable by the retargeted effector cells.
Long‐term impact of balloon postdilatation on neointimal formation: An experimental comparative study between second‐generation self‐expanding versus balloon‐expandable stent technologies (2012)

Background: Self-expanding stents (SES) are reemerging as therapeutic alternatives to treat coronary artery disease. It has been proposed that SES can improve clinical outcomes by inducing less injury at implantation and achieving better vessel wall apposition.To date, little data exists comparing the vascular response to both methods of deployment in a controlled experimental setting. Objective: To quantify differences in vascular injury and healing between second-generation SES and balloon-expandable stents (BES) and the effects of balloon post-dilatation in a porcine coronary model. Methods: Seventy-five bare SES (AXXESS or vProtect) and 42 BES (Vision) were implanted in porcine coronaries. A subset of these received balloon post-dilatation(SES 1 D 5 22, BES 1 D 5 20). Follow-up was scheduled at 30 (BES 5 10, BES 1 D 56, SES 5 19, SES 1 D 5 8), 90 (BES 5 6, BES 1 D 5 8, SES 5 19, SES 1 D 5 8), and 180 days (BES 5 6, BES 1 D 5 6, SES 5 15, SES 1 D 5 6). Results: In vivo imaging and histological analysis showed that neointimal formation peaks early (30 days) in BES. Conversely, for SES, the peak occurred later (90 days). However, the neointimal formation achieved in either group equalized at 180 days. For SES, post-dilatation shortened the peak of neointimal formation to 30 days. Conversely, for BES, post-dilatation delayed the peak of neointimal formation to 90 days. At 30 days, histology showed that SES had significantly less injury. However, at 90 days, injury scores tended to be higher for SES. By 180 days, injury scores were comparable between both groups. Conclusions: The mechanism of stent expansion influences the degree of vascular injury and healing. The synergistic use of balloon post dilatation changes the dynamics of healing and may impact the potential beneficial effects inherent to SES technologies.
Intravaginal administration of herpes simplex virus type 2 to mice leads to infection of several neural and extraneural sites. (2003)

Female mice have been used extensively to study mucosal immunity against herpes simplex virus type 2 (HSV-2) infection of the vagina, but comparatively little is known about the spread of this virus to other tissues. Here the authors have used immunolabeling to demonstrate that HSV-2 infected the vaginal epithelium; the epithelium covering the vulva, perineum, and anal canal; and perineal hair follicles and sebaceous glands. The kinetics and basal localization of the immunolabeling indicated that the virus spread horizontally within the epithelial layer, starting in the vagina and then proceeding to the distal epithelial sites. HSV-2 also spread from the vagina to multiple neuronal sites including the paracervical ganglia (PCG), which are the major autonomic ganglia of the pelvis. The authors demonstrated both sympathetic and parasympathetic neurons in the PCG by labeling of acetylcholinesterase and tryosine hydroxlyase, and noted that infection was limited mainly or entirely to parasympathetic neurons. Infection of the PCG was correlated with the presence of virus in the autonomic ganglia in the walls of the rectum and urinary bladder, which in turn correlated with distention of these organs and retention of urine and feces. HSV-2 infection was also detected in cell bodies and axons in the lumbosacral sympathetic chain, in lumbosacral dorsal root ganglia, and in the dorsal portions of the lumbar spinal cord. Collectively, the data show that vaginal HSV-2 infection in mice leads to subsequent infection of multiple neural and epithelial sites. This information should be useful for development of a mouse model that can be used to study HSV-2 latency and for development of therapeutic vaccines to prevent recurrent infections.
Human thermal sensation and comfort in transient and non-uniform thermal environments (2003)

Most existing thermal comfort models are only applicable only in uniform, steady-state thermal environments. This thesis presents results from 109 human subject tests that were performed under non-uniform and transient conditions in the UC Berkeley Controlled Environmental Chamber. In these tests, local body surfaces of the subjects were independently heated or cooled while the rest of the body was exposed to a warm, neutral or cool environment. Skin temperatures, core temperature, thermal sensation and comfort responses were collected at one- to three-minute intervals. Based on these tests, we have developed predictive models of local and overall thermal sensation and comfort:Local thermal sensation for 19 body partsLocal thermal comfort model for 19 body partsOverall sensation modelOverall comfort modelA separate set of tests was carried out in an automobile in a climate-controlled wind tunnel at the Delphi Harrison facility in Lockport, NY. These tests simulated conditions found in vehicles during both hot and cold weather. The subjects’ body temperatures, thermal sensation and thermal comfort were measured similarly to those in the UCB chamber tests. The results of the Delphi tests were primarily used for model validation. The validation results show that the models predicted the actual sensation and comfort votes well.The models will be useful for designing and evaluating non-uniform and transient environments in buildings, vehicles, and outdoors.
O4‐04‐02: Investigation of dose‐responses and longitudinal effects of combination therapy with a plaque‐specific amyloid beta antibody and bace inhibitor in aged transgenic mice (2015)

The utilization of combination therapies in the clinic is an exciting new avenue for the Alzheimer's disease field. Although there are non-clinical data in transgenic mice that support the rationale for combination therapy, the design of these studies were largely limited to the demonstration of proof of concept and they did not include detailed experimental designs that are important for clinical translation. In order to extend the understanding of the timing and dose-relationships of the combination therapies, we performed two large combination studies. Aged PDAPP transgenic mice (17-19 months) were used in two large combination studies. Combination Dose-Response: 285 aged mice were randomized into a multi-arm study that consisted of a BACE inhibitor (LY2811376) monotherapy dose response, plaque specific Aβ antibody (anti-Aβp3-x) + BACE inhibitor dose response and control/time zero cohorts. Longitudinal pharmacodynamic study: 359 aged mice were randomized into four large cohorts: compound controls, plaque-specific Aβ antibody, BACE inhibitor, and Aβ antibody + BACE inhibitor and analyzed longitudinally at the following time points: 0, 4, 8, 12, and 16-weeks. We observed a significant dose-response relationship on deposited Aβ1-42 (ELISA) for the BACE inhibitor monotherapy (-7%, -23%, and -60%). For the combination drug treatment arms, we observed a significant broad dose response in the presence of high dose antibody and varying dose levels of BACE inhibitor (from -33% through -84%). The combination drug treatments of a high dose BACE inhibitor in the presence of varying dose levels of Aβ antibody revealed a significant, yet steeper dose response (from -60% through -84%). Several of the of drug combination treatments resulted in significant synergistic lowering of deposited Aβ. The longitudinal study demonstrated significant time dependent effects on plaque removal that was detected as early as 4-weeks and the combination therapy showed a continual significant reduction over time that resulted in a dramatic reduction of deposited Aβ as compared to the time zero cohort. The combination therapy studies demonstrated significant dose-response and longitudinal relationships for the plaque specific antibody and BACE inhibitor that further support/enable the rationale for utilizing combinational anti-amyloid therapies in the clinic.
Polarization dependence of optoelectronic properties in quantum dots and quantum wires-consequences of valence-band mixing (1994)

The electronic bandstructure in quantum dots and quantum wires is studied, including the valence-band mixing effects. Based on the bandstructure, results for the polarization dependence of absorption and gain (at room temperature) are examined. The related differential gain and the /spl alpha/-parameter is also studied. Our results show that it is extremely important to include valence-band mixing effects in predicting the laser performance of such structures.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Substrate-Induced Stability of Glyceraldehyde 3-Phosphate Dehydrogenase from Mung Beans (Vigna radiata L.) (1992)

Time-dependent thermal inactivation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) present in the extract of mung beans at different periods of germination showed biphasic kinetics in the 12-h germinated seeds but single exponential decay at 24 h of germination. The glyceraldehyde 3-phosphate (G-3-P) concentration in the deproteinated extracts was found to increase with period of germination up to 36 h, parallel to that of GAPDH activity. G-3-P was found to offer protection of the enzyme against thermal inactivation and trypsin digestion. It is suggested that accumulation of G-3-P in germinating mung beans may be of physiological significance and it might offer protection to the enzyme in vivo against thermal inactivation and proteolysis.
Synthesis and biological activity of resolved carbon-10 diastereomers of 10-methyl- and 10-ethyl-10-deazaminopterin (1986)

Synthesis and evaluation of the antitumor drugs 10-methyl- and 10-ethyl-10-deazaminopterin (15a,b) were previously reported for the diastereomeric mixtures, lacking resolution at the C-10 position. In order to assess biological properties of the individual diastereomers, the C-10 isomers of 4-amino-4-deoxy-10-methyl- and 10-ethyl-10-deazapteroic acids (13a,b) were prepared by total synthesis. Coupling with L-glutamate afforded the appropriate diastereomers of the title compounds. Biochemical, transport, and cell growth inhibitory properties in L1210 cells and folate-dependent bacteria were measured. Differences were generally less than 2-fold between diastereomeric pairs, but a factor of 3 was noted for d,L-15b vs. l,L-15b in inhibition of DHFR from L1210 cells and in cytotoxicity toward L1210 cells. An in vivo comparison of the isomers of 15b with racemic compound against L1210 in mice did not show a significant efficacy difference (ILS) among the compounds. However, d,L-15b showed an acute toxicity about 2.5 times that of l,L-15b.
Pump-dump control and the related transient absorption spectroscopies (1999)

We combine theories of optimal pump-dump control and the related transient probe absorption spectroscopy in order to elucidate the relation between these two optical processes and the possibility of experimental realization. In the weak response regime, we identify the globally optimal pair of pump-dump control fields, and further propose a second-order difference detection scheme to monitor the wave packets dynamics that is jointly controlled by both the pump and dump fields. The globally optimal solution serves also as the initial input for the iterative search for the optimal control fields in the strong response regime. We use a model I2 molecule to demonstrate numerically the pump-dump control and the detection of a highly vibrationally excited wave packet focusing dynamics on the ground X surface in both the weak and strong response regimes. The I2B surface serves as the intermediate to assist the pump-dump control and the optical detection processes. Demonstrated in the strong response regime are the optimal pair of pump-dump molecular-π pulses that invert nearly total population onto the predefined target region within a half period of vibration motion.
CD70 as a therapeutic target in human malignancies (2008)

Humanized anti-CD70 antibodies have shown significant antitumor activity in preclinical xenograft models of cancer. Additionally, anti-CD70 antibody-drug conjugates exhibit potent antitumor activity in solid tumor xenograft models, confirming increased therapeutic efficacy through cytotoxic drug delivery. Thus, preclinical animal models have provided strong evidence that targeting CD70 either with unconjugated antibodies or with antibody-drug conjugates represents a promising approach to treat human malignancies.
Transition dipole moment orientation in films of solution processed fluorescent oligomers: investigating the influence of molecular anisotropy (2016)

The transition dipole moments of long fluorescent oligomers in a solution processed host align with the plane of the film when aggregated.
Application of dibutyltin oxide method to regioselective acylation and alkylation of tylosin at C-4". (1989)

4''-O-Acyl-, 4''-O-alkyl- and 4''-deoxy-tylosin derivatives were synthesized using 2'-O-acetyl-3'',4''-O-(dibutyl-stannio)tylosin as a synthetic intermediate. The in vitro biological evaluation showed that the new derivatives were active against macrolide-resistant clinical isolates of bacteria and mycoplasmas, and that they were resistant to hepatic esterase.