gebhart/patrepeval huggingface dataset:
Study of the early steps of the Hepatitis B Virus life cycle (2004)

Hepatitis B virus (HBV) is a human pathogen, causing the serious liver disease. Despite considerable advances in the understanding of the natural history of HBV disease, most of the early steps in the virus life cycle remain unclear. Virus attachment to permissive cells, fusion and penetration through cell membranes and subsequent genome release, are largely a mystery. Current knowledge on the early steps of HBV life cycle has mostly come from molecular cloning, expression of individual genes and studies of the infection of duck hepatitis B virus (DHBV) with duck primary duck hepatocytes. However, considering of the difference of the surface protein of HBV and DHBV both in the composition and sequence, the degree to which information from DHBV applies to human HBV attachment and entry may be limited. A major obstacle to the study HBV infection is the lack of a reliable and sensitive in vitro infection system. We have found that the digestion of HBV and woodchuck hepatitis virus (WHBV) by protease V8 led to the infection of HepG2 cell, a cell line generally is refractory for their infection [Lu et al. J Virol. 1996. 70. 2277-2285 . Lu et al. Virus Research. 2001. 73(1): 27-4].. Further studies showed that a serine protease inhibitor Kazal (SPIK) was over expressed in the HepG2 cells. Therefore, it is possible that to silence the over expressed SPIK and thus to reinstate the activity of indispensable cellular proteases can result in the restoration of the susceptibility of HepG2 cells for HBV infection. The establishing a stable cell line for study of the early steps of HBV life cycle by silencing of SPIK is discussed.
Hepatic hypolipidemia in phospholipase A2 VIA-null mice mediates apoptosis, chronic persistent hepatitis, and sensitivity for autoimmune hepatitis (2013)

Introduction: Calcium-independent phospholipaseA2 VIA (iPLA2β), which is one of the patatin-like phospholipase domain-containing genes, catalyzes the hydrolysis of phospholipids providing lysophospholipids which have been identified as 'find me' signals for the removal of apoptotic cells by phagocytes. The deletion of iPLA2β may cause accumulation of apoptotic hepatocytes. iPLA2β transcription is known to be regulated by SREBP1c which is a transcription factor for de novo lipogenesis. It is thus postulated that alterations of hepatic lipids by iPLA2β deficiency may lead to apoptosis in vivo. Methods: Whole body iPLA2β-null and wild-type male mice were used. Serum and hepatic lipids were measured by using kits. Gene expression was performed by quantitative TaqMan RT-PCR. Histology (H&E), Sirius red and α-smooth muscle actin (α-SMA) staining was performed. Concanavalin A (10mg/kg) was i.p. injected for 16h. Results: iPLA2β-null mice exhibited reduced body and liver weight concomitant with reduced hepatic triglyceride and cholesterol levels. Mild increases of serum alkaline phosphatase and decreases of albumin and total protein were observed in mutant mice. mRNA expression of SREBP1c, FAS and Elovl6 was decreased in mutant mice, this was accompanied with mild infiltration of immune cells and increases of inflammatory and fibrosis mRNAs including TNF-α, MCP-1, VCAM-1, CCL3, CCL4, CCL5, CCR2, α -SMA, TGF- β1, PAI-1, and CTGF. iPLA2β-null mice were more susceptible towards ConA-induced autoimmune hepatitis with increased liver enzymes, hepatocellular necrosis and fibrosis. Conclusions: Whole body deficiency of iPLA2β was well-tolerated causing reduced liver weight and hepatic hypolipidemia. This was associated with increased hepatic apoptosis and secondarily inflammation/fibrosis. These findings are consistent with altered lipid metabolism seen in patients undergoing liver failure, chronic aggressive hepatitis and liver cirrhosis. Thus, deficiency of iPLA2β may mediate chronic persistent hepatitis by its inability to synthesize lipids.
High-Titer Production of the Fungal Anhydrotetracycline, TAN-1612, in Engineered Yeasts (2022)

Antibiotic resistance is a growing global health threat, demanding urgent responses. Tetracyclines, a widely used antibiotic class, are increasingly succumbing to antibiotic resistance; generating novel analogues is therefore a top priority for public health. Fungal tetracyclines provide structural and enzymatic diversity for novel tetracycline analogue production in tractable heterologous hosts, like yeasts, to combat antibiotic-resistant pathogens. Here, we successfully engineered <i>Saccharomyces cerevisiae</i> (baker's yeast) and <i>Saccharomyces boulardii</i> (probiotic yeast) to produce the nonantibiotic fungal anhydrotetracycline, TAN-1612, in synthetic defined media─necessary for clean purifications─through heterologously expressing TAN-1612 genes mined from the fungus, <i>Aspergillus niger</i> ATCC 1015. This was accomplished via (i) a promoter library-based combinatorial pathway optimization of the biosynthetic TAN-1612 genes coexpressed with a putative TAN-1612 efflux pump, reducing TAN-1612 toxicity in yeasts while simultaneously increasing supernatant titers and (ii) the development of a medium-throughput UV-visible spectrophotometric assay that facilitates TAN-1612 combinatorial library screening. Through this multipronged approach, we optimized TAN-1612 production, yielding an over 450-fold increase compared to previously reported <i>S. cerevisiae</i> yields. TAN-1612 is an important tetracycline analogue precursor, and we thus present the first step toward generating novel tetracycline analogue therapeutics to combat current and emerging antibiotic resistance. We also report the first heterologous production of a fungal polyketide, like TAN-1612, in the probiotic <i>S. boulardii</i>. This highlights that engineered <i>S. boulardii</i> can biosynthesize complex natural products like tetracyclines, setting the stage to equip probiotic yeasts with synthetic therapeutic functionalities to generate living therapeutics or biocontrol agents for clinical and agricultural applications.
Obesity-related phenotypes and the beta3-adrenoceptor gene variant in postmenopausal women. (1999)

We examined the hypothesis that postmenopausal women with the beta3-adrenoceptor gene variant (Trp64Arg) have reduced total daily energy expenditure (TEE), altered free fatty acid kinetics, and increased intra-abdominal fat. A secondary objective was to examine whether the obese state masks the effect of the variant on resting metabolic rate (RMR). There were 23 obese heterozygous women with the genetic variant (age 58 +/- 6 years; BMI 36 +/- 7 kg/m2) who were compared with 19 homozygous obese women with the normal allele (age 56 +/- 4 years; BMI 36 +/- 3 kg/m2). Daily energy expenditure was determined from doubly labeled water and indirect calorimetry, lipolysis from infusion of [1-13C]palmitate, and body fat distribution from computed tomography. No significant differences were found in TEE, RMR, energy expenditure of physical activity, the thermic effect of a meal, fat oxidation as estimated by fasting and postprandial respiratory quotients (RQs), or rate of lipolysis. Similarly, no difference was found in visceral adipose tissue and abdominal subcutaneous fat areas. When RMR was compared between obese (n = 23) and never-obese women with the Trp64Arg variant (n = 16), we found a 317 kcal/day lower RMR in never-obese women after controlling for fat mass, fat-free mass, and age (P < 0.0017). These results do not support the hypothesis that already obese women with the Trp64Arg polymorphism of the beta3-adrenergic receptor gene have lower daily energy expenditure, altered lipolysis, and increased abdominal obesity. On the other hand, the lower RMR in never-obese women suggests that the obese state may mask a moderate effect of the Trp64Arg variant on energy expenditure. Although these results need to be confirmed in other populations, the obese state may have been a confounding factor in previous studies of the beta3-adrenoceptor Trp64Arg variant and energy expenditure.
Interleukin-2 family cytokines stimulate phosphorylation of the Pro-Ser-Pro motif of Stat5 transcription factors in human T cells: resistance to suppression of multiple serine kinase pathways (2002)

Signal transducer and activator of transcription (Stat)5a and Stat5b are critical for normal immune function. Progression of T cells through G(1)-S phase of cell cycle requires T cell receptor (TCR)- and/or cytokine-inducible tyrosine phosphorylation of Stat5a/b. Stat5a/b may also, in a cell-dependent manner, be constitutively or cytokine-inducibly phosphorylated on a Pro-Ser-Pro (PSP) motif located within the transcriptional activation domain. Phosphorylation of the PSP motif is needed for maximal transcriptional activation by Stat5, at least in certain promoter contexts. The basal and cytokine-inducible serine phosphorylation state of Stat5a/b has not been determined in T cells. Using primary human T cells and T lymphocytic cell lines coupled with novel phospho-specific antibodies to this conserved phosphoserine motif in Stat5a or Stat5b, we report that: Stat5a and Stat5b were unphosphorylated on the PSP motif under basal conditions and became markedly phosphorylated in response to several T cell growth factor stimuli, including interleukin (IL)-2, -7, -9, and -15 and phorbol ester 12-myristate 13-acetate but not TCR engagement; inducible Stat5a/b serine phosphorylation differed quantitatively and temporally; and Stat5a/b serine phosphorylation was, in contrast to inducible Stat3 serine phosphorylation, insensitive to inhibitors of mitogen-activated protein kinase, phosphatidylinositol-3 kinase, and mammalian target of rapamycin or deletion of Raf-A, -B, or -C by antisense oligonucleotides. We conclude that IL-2 family cytokines tightly control Stat5 serine phosphorylation through a kinase distinct from the Stat3 serine kinase.
Microbial Approach to Low-Cost Production of Photovoltaic Nanomaterials (2019)

Photovoltaic (PV)-generated electricity can participate in renewable grid parity after meeting conditions of low-cost PV materials and economic manufacturing of solar cells. Here, we report low-cost, scalable microbial synthesis of Cu(In,Ga)Se2 (CIGSe) and Cu(In,Ga)S2 (CIGS), which are among the promising candidates to serve as light absorbing layers in solar panels. Microbial synthesis uses reducible chalcophiles and empirically stoichiometric metal components to produce CIGSe and CIGS with band gaps and intra- and intercrystallite compositional homogeneity similar to that produced with traditional techniques. Importantly, microbially produced photovoltaic materials described herein use inexpensive precursor materials at moderate temperatures (65 °C). The microbially facilitated processes do not utilize high temperature, vacuum, or toxic organic solvents. The potential to upscale microbial synthesis without loss of material quality is demonstrated here, indicating a high potential for industrial applications of this technology for production of nanomaterials for PV applications. We estimate that a 50 000 gallon fermentor could generate about 100 kg/month of CIGSe nanoparticles, which could be processed into 0.2 MW of PV cells.
Along the path towards extremely precise radial velocity measurements (2010)

In the last six years, thanks to the very high radial velocity precision of the HARPS spectrograph, it was possible to detect 21 out of the 30 super-Earth (extrasolar planets masses below 20 times the mass of the Earth) discovered up to date. The radial velocity precision of the instrument is estimated around 80 cm/s on a single measurement. The main instrumental limitations are the wavelength calibration and the stability of the light injection. We address both factors and present the results of recent tests on the HARPS spectrograph. We have identified the laser frequency comb as the ideal wavelength calibrator, due to the width, density and flux of the lines, and to its intrinsic stability. The results from the recent tests that we performed on HARPS are encouraging. The accurate guiding of the telescope is critical to maintain a stable light distribution at the injection stage, where the light is sent into the spectrograph entrance fiber. To pursue this goal we are testing a secondary guiding system which is able to apply the guiding corrections twenty times faster than the primary guiding system.
SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation (2015)

We have studied the in vivo role of SLIRP in regulation of mitochondrial DNA (mtDNA) gene expression and show here that it stabilizes its interacting partner protein LRPPRC by protecting it from degradation. Although SLIRP is completely dependent on LRPPRC for its stability, reduced levels of LRPPRC persist in the absence of SLIRP in vivo. Surprisingly, Slirp knockout mice are apparently healthy and only display a minor weight loss, despite a 50-70% reduction in the steady-state levels of mtDNA-encoded mRNAs. In contrast to LRPPRC, SLIRP is dispensable for polyadenylation of mtDNA-encoded mRNAs. Instead, deep RNA sequencing (RNAseq) of mitochondrial ribosomal fractions and additional molecular analyses show that SLIRP is required for proper association of mRNAs to the mitochondrial ribosome and efficient translation. Our findings thus establish distinct functions for SLIRP and LRPPRC within the LRPPRC-SLIRP complex, with a novel role for SLIRP in mitochondrial translation. Very surprisingly, our results also demonstrate that mammalian mitochondria have a great excess of transcripts under basal physiological conditions in vivo.
Continuous Flow Chlorination of Alkenyl Iodides Promoted by Copper Tubing (2018)

A simple continuous flow synthesis of alkenyl chlorides from the corresponding readily available alkenyl iodides in copper reactor tubing is described. A variety of alkenyl chlorides were obtained in good to excellent yields with full retention of the double bond geometry. The reaction time was reduced by a factor of 24–48 compared to the batch process.
Experiment and analysis of two-photon absorption spectroscopy using a white-light continuum probe (2002)

We present an experimental technique along with the method of data analysis to give nondegenerate two-photon absorption (2PA) spectra. We use a femtosecond pump pulse and a white-light continuum (WLC) probe to rapidly generate the 2PA spectra of a variety of materials. In order to analyze data taken with this method, the spectral and temporal characteristics of the WLC must be known, along with the linear dispersion of the sample. This allows determination of the temporal walk-off of the pump and probe pulses as a function of frequency caused by group-velocity mismatch. Data correction can then be performed to obtain the nonlinear losses. We derive an analytical formula for the normalized nonlinear transmittance that is valid under quite general experimental parameters. We verify this on ZnS and use it for the determination of 2PA spectra of some organic compounds in solution. We also compare some of the data on organics with two-photon fluorescence data and find good agreement.
On Determining Optimal Reverberation Parameters for Late Residual Echo Suppression (2016)

When deploying acoustic echo cancellation systems in large rooms, using short filters may result in significant amount of residual echo caused by room reverberation. In this paper, we model the late residual echo as exponentially decaying and use a parametric IIR filter to estimate its power in the subband domain for application in residual echo suppression. Working in an offline system identification setup, the problem of finding the optimal parameters of the IIR filter is addressed, with an analysis conducted on the performance of two parameter estimation methods: output error and equation error. The late residual echo power estimates obtained using the two methods are furthermore judged using the mean squared error and the mean squared log error cost functions. Results indicate that minimizing the mean squared log error for the output error method provides accurate estimates for the late residual echo power and the reverberation decay parameter.
Presenilins Interact with Armadillo Proteins Including Neural‐Specific Plakophilin‐Related Protein and β‐Catenin (1999)

Missense substitutions in the presenilin 1 (PS1) and presenilin 2 (PS2) proteins are associated with early-onset familial Alzheimer's disease. We have used yeast-two-hybrid and coimmunoprecipitation methods to show that the large cytoplasmic loop domains of PS1 and PS2 interact specifically with three members of the armadillo protein family, including beta-catenin, p0071, and a novel neuronal-specific armadillo protein--neural plakophilin-related armadillo protein (NPRAP). The PS1:NPRAP interaction occurs between the arm repeats of NPRAP and residues 372-399 at the C-terminal end of the large cytoplasmic loop of PS1. The latter residues contain a single arm-like domain and are highly conserved in the presenilins, suggesting that they form a functional armadillo protein binding site for the presenilins.
A white paper: the product of a pancreas cancer think tank. (2001)

Contrasting with improved survival for most other gastrointestinal cancers, the 5-year survival of patients with ductal adenocarcinoma of the pancreas remains low at a dismal 4%. In 2000, an estimated 28,300 patients were diagnosed with pancreatic cancer in the United States These patients can
Treatment of Amyotrophic Lateral Sclerosis: Lessons Learned from Many Failures (2014)

Amyotrophic lateral sclerosis (ALS) is one of the most complex neurodegenerative diseases, involving both cortical and spinal components of motor neuron circuitry and non-neuronal cells that support the motor neurons. There is no effective therapeutic for ALS, and compounds that have extended the lifespan of ALS mouse models have failed in clinical trials. This viewpoint discusses current information regarding the changing views about ALS and what the failures in clinical trials can teach us in the search for an effective treatment. Previous challenges and roadblocks in drug discovery for ALS are noted, and solutions to current limitations are discussed. Learning from the past and moving forward with a new mindset can translate into successful and effective treatment strategies in ALS and other related diseases.
MOCVD of BaSrTiO3 for ulsi drams (1995)

Abstract The CVD of high permittivity materials such as BaSrTiO3 presents new challenges to the semiconductor equipment and materials industries. The electrical properties of the material are a strong function of composition, microstructure and dopant concentration (electronic and ionic). However, the source reagents are typically low vapor pressure liquids, solids or solids dissolved in liquids which are challenging to manufacture with ultra-high purity and difficult to deliver with high accuracy and precision. Reactor walls must be heated to avoid condensation of the source materials and deposition temperatures are high where radiative heat transfer becomes significant. Reaction products are difficult to remove by standard dry chemical etching techniques because the halides of many of the metals are involatile inorganic salts. Design strategies to overcome these challenges and the resulting properties of BaSrTiO3 films will be discussed.
Oral minoxidil for the treatment of late alopecia in cancer survivors. (2022)

12022 Background: Late alopecia is defined as incomplete hair regrowth &gt; 6 months following cytotoxic chemotherapy or from initiation of endocrine therapy. It has been reported in up to 25-30% of cancer survivors and is associated with decreased quality of life and reduced dose intensity of cancer therapies. Minoxidil is an aminopyridine potassium channel opener, resulting in vasodilation and premature entry of resting hair follicles into the anagen (growth) phase and increase in hair follicle size. This study aims to assess clinical outcomes and adverse events of oral minoxidil for the treatment of cancer therapy-related late alopecia. Methods: We retrospectively assessed all women with late alopecia treated with oral minoxidil (1.25 mg daily) evaluated at an oncodermatology referral program between 1/2018-5/2021. Outcomes were assessed by standardized photography (4 views) and trichoscopy (HairMetrix, Canfield Scientific, Inc.). Trichoscopy recorded hair density (hair count/cm 2 ) and hair thickness (shaft diameter) at uniform frontal and occipital target areas (12 and 36 cm midline from the glabella, respectively). Adverse events were recorded and graded using CTCAE v5.0. Descriptive statistics were used to summarize the patient demographics and clinical characteristics. Changes in trichoscopy measurements from baseline to follow-up were estimated using paired t-tests. Results: Two hundred and sixteen patients (mean age 57.8±13.7) were included for analysis. Thirty-one (14%) received chemotherapy alone, 65 (30%) endocrine monotherapy, and 120 (56%) chemotherapy followed by endocrine therapy. The majority of patients (n = 170, 79.1%) had a history of breast cancer. Standardized photography assessments (n = 119) after a median of 105 days (IQR = 70) on oral minoxidil revealed clinical improvement in 88 (74%). Trichoscopy assessments (n = 42) after a median of 91 days (IQR = 126) demonstrated increased frontal hair density (124.2 vs 153.2 hairs/cm 2 , p = 0.008) and occipital hair density (100.3 vs 123.5 hairs/cm 2 , p = 0.004). There was no statistically significant difference in average frontal or occipital hair thickness (69.3 vs 67.3 μm, p = 0.22, and 70.3 vs 69.9 μm, p = 0.84, respectively). No patients reported discontinuation of oral minoxidil due to adverse effects. Conclusions: Oral minoxidil may benefit both frontal and occipital late alopecia in cancer survivors treated with cytotoxic and/or endocrine therapy. This regimen was well tolerated by patients. Prospective, controlled studies are needed to confirm these observations.
Monitoring VLSIC fabrication processes: a Bayesian approach (2002)

We have developed a process monitoring system, in a Bayesian framework, which is designed to be used for monitoring VLSIC and other multi-stage manufacturing processes. For a single step process, the Bayesian monitor is at least as good as the Shewhart-CUSUM combination charts for detecting changes in the distribution of the in-lines collected from the step. For a multi-stage process, however, the Bayesian monitor can significantly reduce the detection time by using in-line correlation information from earlier stages.
The Modular Segmental Kinematic Rotating Hinge for Nonneoplastic Limb Salvage (2004)

From January 1980 to July 1998, 25 patients (26 knees) were treated with an arthroplasty using a Modular Segmental Kinematic Rotating Hinge total knee prosthesis for nonneoplastic limb salvage. The indications included: nonunion of a periprosthetic femur fracture (11 knees), severe bone loss and ligamentous instability (eight knees), nonunion of a supracondylar femur fracture (four knees), acute periprosthetic fracture (one knee), fracture of a previous hinge (one knee), and prior resection arthroplasty (one knee). The average age of the patients was 72.3 years. Twenty-two arthroplasties were revisions. The average followup was 58.5 months. At the latest followup, knee extension averaged 2.4 degrees and flexion averaged 93.6 degrees. The Knee Society knee score improved from an average of 45.4 preoperatively to 75.5. Preoperatively, functional scores averaged 8.6 and improved to 25. Complications occurred in eight patients. The most common was deep infection (five patients). The use of the Modular Kinematic Rotating Hinge for nonneoplastic limb salvage represents a small proportion (0.14%) of all primary and revision knee arthroplasties done at our institution. The indications for the surgery are for a highly complex and small subset of patients. The patients in the current study gained significant improvement in overall range of motion, Knee Society knee scores, and functional scores when this prosthesis was used.