gebhart/patrepeval huggingface dataset:
Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues. (1991)

The role of human papillomavirus (HPV) proteins in the pathogenesis of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer is poorly understood. To characterize E4 protein expression in 49 paraffin-embedded cervical biopsies representing different histopathologic grades of disease, antibodies were elicited to a synthetic peptide corresponding to amino acids 20-34 of a protein predicted to be encoded by the HPV 16 E4 open reading frame. The E4 protein was detected throughout the spectrum of CIN, from CIN1 to CIN3. Expression was localized to the cell nucleus, primarily in the superficial layers of the squamous cervical epithelium. Ultrastructural studies showed that the E4 protein was organized into compact, intranuclear arrays 25-35 nm in diameter. E4 protein expression was also demonstrated in some histologically normal tissues containing HPV 16 DNA, but not in any of five cervical cancers containing HPV 16 DNA. These results suggest that E4 protein expression may precede development of light microscopic tissue abnormalities, that it may continue through the spectrum of CIN, and that expression of this protein may be reduced or terminated in invasive cancer. The function of this protein remains unknown, but its nuclear localization may be consistent with a role in viral maturation.
Diffractive Beam Combining of a 2.5-kW Fiber Laser Array* (2012)

Five 500-W fiber amplifiers were coherently combined with 79% efficiency using a diffractive optical element (DOE) combiner, generating a single beam whose M2 = 1.1 beam quality exceeded that of the inputs.
De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer (2012)

Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.
Incidence of Post-Surgical Complications among Ulcerative Colitis (UC) Patients (Pts): A Population-Based Study (2007)

Purpose: We sought to describe the incidence of and factors associated with post-colectomy complications among UC pts in Olmsted County, Minnesota. Methods: We identified all pts who had undergone ≥1 surgery for UC in a cohort diagnosed with UC between 1970–2001. Colectomies were classified as: total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA), subtotal colectomy (SC) with ileostomy, TPC with ileostomy, and partial colectomy (PC). We examined post-colectomy complications by colectomy type. The association between colectomy type and time to first complication was assessed with proportional hazards regression analysis. Results: A total of 47/316 UC pts (14.8%) underwent colectomy during the follow-up (f/u) period. The colectomy distribution was: TPC-IPAA 60%, SC-ileostomy 5%, TPC-ileostomy 33%, and PC 2%. Within the first 2 yrs of f/u, a variety of complications were observed, including (rate/1,000 pt-yrs): wound infection (204.9), anastomotic leak (56.9), fistula (22.8), abscess (68.3), small bowel obstruction (148.0), anastomotic stricture (56.9), ileus (11.4), pouchitis (148.0), and stomal problems (45.5). During the same period, the crude rate of infective and non-infective complications was 296 and 512 per 1000 pt-yrs, respectively. The total crude rate was 808/1000 pt-yrs. See table for cumulative risk of any complication following colectomy. Regression analysis indicated that, relative to TPC-ileostomy, IPAA patients had a 1.7 times greater risk of experiencing an infective complication (95% CI, 0.5–6.3) and a 2.4 times greater risk of experiencing a non-infective complication (95% CI, 0.98–6.1), but only the latter was of borderline significance. Conclusion: In this population-based study of UC pts undergoing colectomy, a number of post-surgical complications were observed, for a crude rate of over 800 per 1,000 pt-yrs of f/u in the first 2 yrs, and a cumulative risk of 68.0% at 5 yrs. There was a borderline significant association between IPAA and time to first non-infective complication.
Nuclear hormone receptor-dependent regulation of hepatic transporters and their role in the adaptive response in cholestasis (2008)

1. Hepatobiliary transport systems are essential for the uptake and excretion of a variety of organic anions including bile acids and bilirubin. Perturbation of this vital liver function can result in pathological conditions such as cholestasis, where the formation of bile at the canaliculus is impaired resulting in the intrahepatic accumulation of toxic bile constituents. 2. Members of the nuclear hormone receptor superfamily are important mediators of the adaptive response during cholestasis controlling the expression of transporters and other proteins with the aim to limit tissue damage. Bile acids are the endogenous ligands for these nuclear hormone receptors and therefore directly participate in the control of their own transport and metabolism. 3. Adaptive events include repression of bile acid uptake and de novo bile acid synthesis as well as a concomitant induction of alternative efflux routes and bile acid detoxification. Importantly, the adaptation also extends to other organs such as intestine and kidney to facilitate elimination of bile acids from the body. 4. This review provides an overview of the transcriptional regulation of bile acid transporting proteins and metabolizing enzymes mediated by nuclear hormone receptors. Furthermore, the complex networks between nuclear hormone receptors and regulated genes are illustrated and implications of targeting these receptors for the treatment of cholestasis are discussed.
High-k / metal gate innovations enabling continued CMOS scaling (2011)

High-k dielectrics and metal gate electrodes have entered complementary metal-oxide-semiconductor (CMOS) logic technology, integrated in both gate-first and gate-last schemes. We review gate-first high-k / metal gate (HKMG) innovations enabling continued device scaling to the 22 and 14 nm nodes and beyond. First, we summarize some of the insight that allowed early HKMG challenges such as equivalent oxide thickness (EOT) and threshold voltage control to be overcome. Then, we discuss HKMG approaches that enable ultimate EOT scaling, pitch scaling via borderless source/drain contact formation, and the fabrication of multi-gate field-effect transistors. Finally, we summarize recent progress in gate stack development for high-mobility channel materials such as germanium and III-V compound semiconductors.
Comment on "Linear and passive silicon optical isolator" in Scientific Reports 2, 674 (2013)

Wang et al. [1] demonstrated different power transmission coefficients for forward and backward propagation in simulation and experiment. From such a demonstration, the central claim of their paper is that "the spatial inversion symmetry breaking diode can construct an optical isolator in no conflict with any reciprocal principle". Their claim contradicts the Lorentz reciprocity theorem, from which it is well known that one cannot construct an isolator this way.
Quantum Multiple Kernel Learning (2020)

Kernel methods play an important role in machine learning applications due to their conceptual simplicity and superior performance on numerous machine learning tasks. Expressivity of a machine learning model, referring to the ability of the model to approximate complex functions, has a significant influence on its performance in these tasks. One approach to enhancing the expressivity of kernel machines is to combine multiple individual kernels to arrive at a more expressive combined kernel. This approach is referred to as multiple kernel learning (MKL). In this work, we propose an MKL method we refer to as quantum MKL, which combines multiple quantum kernels. Our method leverages the power of deterministic quantum computing with one qubit (DQC1) to estimate the combined kernel for a set of classically intractable individual quantum kernels. The combined kernel estimation is achieved without explicitly computing each individual kernel, while still allowing for the tuning of individual kernels in order to achieve better expressivity. Our simulations on two binary classification problems---one performed on a synthetic dataset and the other on a German credit dataset---demonstrate the superiority of the quantum MKL method over single quantum kernel machines.
Composition dependence of field induced anisotropy in ferromagnetic (Co,Fe)89Zr7B4 and (Co,Fe)88Zr7B4Cu1 amorphous and nanocrystalline ribbons (2008)

The composition dependence of field induced anisotropy KU of field annealed soft ferromagnetic (Co1−xFex)89Zr7B4 and (Co1−xFex)88Zr7B4Cu1 amorphous and amorphous/nanocrystalline “nanocomposite” melt spun ribbons is investigated. With the exception of the highest Co-containing alloys (x&amp;lt;∼0.10), the observations are discussed in terms of a superposition of directional pair ordering of Fe,Co atoms and an additional contribution presumably due to the presence of Zr and B in both the field crystallized and field annealed amorphous ribbons. The highest Co-containing alloys (x&amp;lt;∼0.10) contain multiple nanocrystalline phases (bcc, fcc, and hcp) for which a peak in KU is observed (KU∼2000–2500 J/m3). In this framework, asymmetry in the compositional dependence of KU resulting in larger values for Co-rich alloys relative to Fe-rich alloys for both the field crystallized and field annealed amorphous alloys is explained in terms of a strong dependence of the Curie temperature of the amorphous phase on the Co content.
Interventional procedures and future drug therapy for hypertension (2016)

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care.
Methylglyoxal: Its Presence in Beverages and Potential Scavengers (2008)

Nonenzymic glycation, also known as the Maillard reaction, is a complex series of reactions between reducing sugars and amino compounds. Previous studies have demonstrated that reactive dicarbonyl compounds (e.g., methylglyoxal [MG] and glyoxal [GO]), formed as intermediate products of the Maillard reaction, irreversibly and progressively modify proteins over time and yield advanced glycation end products (AGEs), which are thought to contribute to the development of diabetes mellitus and its complications. Several studies have shown that higher levels of MG are present in diabetic patients' plasma than in healthy people's plasma. Thus, decreasing the levels of MG and GO will be an effective approach to reduce the formation of AGEs and the development of diabetic complications. Here, we briefly describe our effort in searching for non- or less-toxic trapping agents of reactive dicarbonyl species from dietary sources. In addition, we have discovered that commercial beverages contain extremely high levels of MG. The potential hazardous effects of dietary MG on humans remain to be explored.
Rearrangement of Simian Virus 40 Regulatory Region Is Not Required for Induction of Progressive Multifocal Leukoencephalopathy in Immunosuppressed Rhesus Monkeys (2005)

Rearrangements of the JC virus (JCV) regulatory region (RR) are consistently found in the brains of patients with progressive multifocal leukoencephalopathy (PML), whereas the archetype RR is present in their kidneys. In addition, the C terminus of the large T antigen (T-Ag) shows greater variability in PML than does the rest of the coding region. To determine whether similar changes in simian virus 40 (SV40) are necessary for disease induction in monkeys, we sequenced the SV40 RR and the C terminus of the T-Ag from the brain of simian/human immunodeficiency virus (SHIV)-infected monkey 18429, which presented spontaneously with an SV40-associated PML-like disease, as well as from the peripheral blood mononuclear cells (PBMC), kidneys, and brains of SV40-seronegative, SHIV-infected monkeys 21289 and 21306, which were inoculated with the 18429 brain SV40 isolate. These animals developed both SV40-associated PML and meningoencephalitis. Thirteen types of SV40 RR were characterized. Compared to the SV40 archetype, we identified RRs with variable deletions in either the origin of replication, the 21-bp repeat elements, or the late promoter, as well as deletions or duplications of the 72-bp enhancer. The archetype was the most prominent RR in the brain of monkey 18429. Shortly after inoculation, a wide range of RRs could be found in the PBMC of monkeys 21289 and 21306. However, the archetype RR became the predominant type in their blood, kidneys, and brains at the time of sacrifice. On the contrary, the T-Ag C termini remained identical in all compartments of the three animals. These results indicate that unlike JCV in humans, rearrangements of SV40 RR are not required for brain disease induction in immunosuppressed monkeys.
Interplay between yield, nitrogen application, and logistics on the potential energetic and greenhouse gas emissions from biomass crops (2013)

Abstract The interplay between nitrogen fertilization (N), yield, nitrous oxide emissions (N 2 O), and diesel fuel utilization associated with harvest and transport logistics of biomass crops remains poorly understood. In this research, we show that intensification (in terms of N) of bioenergy cropping to maximize yield supports not only minimized land use but also maximized logistics efficiency in terms of diesel use. This paradigm was examined within the scope of the billion‐ton biofuels vision and the Energy Independence and Security Act of 2007 using potential yields on marginal and prime agricultural land. Sixteen scenarios were investigated that considered the primary factors with agriculture bioenergy; biomass yield (11.2 and 22.4 Mg ha −1 yr −1 ), two nitrogen fertilizer application rates (50 and 100 kg N ha −1 yr −1 ), two Greenhouse Gas Emissions ( GHGE ) factors for synthetic nitrogen to nitrous oxide (1.5 and 5%), and three harvest/transportation efficiencies (50, 65, and 80%). These scenarios resulted in energy consumption between 747 and 1351 MJ Mg −1 and GHGE between 72 and 311 kg CO 2 eq Mg −1 . GHGE emissions are strongly related to the emission of nitrous oxide from soils due to nitrogen fertilization and could represent over 80% of the GHGE relative to biomass harvest logistics. These data imply that synthetic N supplementation to maximize yield could reduce the burden due to diesel fuel for harvest, but would rapidly become the most significant contributor to GHGE . Minimizing the impact of N fertilization will be critical for reducing the GHGE associated with biomass production.
Production of Human CRISPR-Engineered CAR-T Cells (2021)

Adoptive cell therapies using chimeric antigen receptor T cells (CAR-T cells) have demonstrated remarkable clinical efficacy in patients with hematological malignancies and are currently being investigated for various solid tumors. CAR-T cells are generated by removing T cells from a patient's blood and engineering them to express a synthetic immune receptor that redirects the T-cells to recognize and eliminate target tumor cells. Gene editing of CAR-T cells has the potential to improve safety of current CAR-T cell therapies and further increase the efficacy of CAR-T cells. Here, we describe methods for the activation, expansion, and characterization of human CRISPR-engineered CD19 directed CAR-T cells. This comprises transduction of the CAR lentiviral vector and use of single guide RNA (sgRNA) and Cas9 endonuclease to target genes of interest in T cells. The methods described in this protocol can be universally applied to other CAR constructs and target genes beyond the ones used for this study. Furthermore, this protocol discusses strategies for gRNA design, lead gRNA selection and target gene knockout validation to reproducibly achieve high-efficiency, multiplex CRISPR-Cas9 engineering of clinical grade human T cells.
A stochastic approach to analog physical unclonable function (2016)

As cybersecurity becomes increasingly relevant with advancing technology, Physically Unclonable Functions (PUFs) have become a promising technique that utilize process variation and device mismatch to create unique device identifiers, secure keys, and other security features that are virtually impossible to duplicate. Many PUF circuits with diverse characteristics have been proposed, all of which exhibit a clear tradeoff between reliability, robustness, and size. This paper proposes a novel PUF which utilizes the nature of stochastic flash analog-to-digital (ADCs) to minimize hardware without sacrificing reliability or robustness against cloning. The proposed PUF creates a unique device identifier by employing the comparators used in a stochastic ADC, which are designed for maximum offset voltage due to device mismatch. The proposed PUF was modeled and simulated using a 130nm CMOS process. Simulation results show that the PUF has a normalized inter-hamming distance (uniqueness) of 48.5% and is reliable with a normalized average bit flip of 2-3% over ±10% variance in supply voltage and temperatures up to 100°C.
CTR plasma engineering studies. Annual progress report, 1 November 1981-30 October 1982 (1982)

During FY 82, much effort was devoted to work in support of alternate confinement concepts, especially those involving field reversal. This work includes: (1) development of particle and energy confinement scaling for the Reversed Field Pinch (RFP) and the Field Reversed Theta Pinch (FRTP), and (2) analysis of start-up (heating and plasma build) for the spheromak and Field Reversed Mirror (FRM). In addition, a block of projects were concerned with fusion product effects, including heating and ash build-up. These include, (1) a study of possible use of radial electric fields to control ash build-up in tokamaks, (2) effects of alpha-driven microinstabilities on heating in tokamaks, and (3) fusion product transport, including effects of large angle scattering on orbits, in EBT and FRM devices. In a related study, the possibility of hot-ion mode operation (assuming strong transfer of fusion product energy to ions, e.g. via microinstabilities) was done with emphasis on calculation of ion-electron equilibration rates.
Promotion of Optimized Protein Therapy by Bioconjugation as a Polymeric DDS (2006)

In recent years, clinical applications of recombinantly produced bioactive proteins such as cytokines have attracted attention. However, since these recombinant proteins are rather unstable in vivo, their clinical use as therapeutic agents requires frequent administration at a high dosage. This regimen disrupts homeostasis and results in severe side effects. To overcome these problems, bioactive proteins have been conjugated with water-soluble synthetic (WSS) polymeric carriers. Chemical modification of a protein with a WSS polymeric carrier (bioconjugation) regulates tissue distribution, resulting in a selective increase in its desirable therapeutic effects and a decrease in undesirable side effects. Among several drug delivery system (DDS) technologies, bioconjugation has been recognized as one of the most efficient methods for improving therapeutic potency of proteins. However, for further enhancement of the therapeutic potency and safety of conjugated bioactive proteins, more precise regulation of the in vivo behavior of each protein is necessary for selective expression of its therapeutic effect. Therefore, alternative WSS polymeric modifiers in which new functions such as targeting and controlled release of drugs can be added are required for further development of bioconjugated drugs. Recently, we have synthesized a novel polymeric drug carrier, poly(vinylpyrrolidone-co-dimethyl maleic anhydride) [PVD], which was a powerful candidate drug carrier for cancer therapy. In this review, we introduce useful information that enabled us to design polymeric drug carriers and their application for protein therapy.
In-network evaluation of body-carried mobile terminal performance (2002)

This paper investigates the body loss when a mobile handset is carried on the user's body, e.g., when a hands-free kit is used and the handset is carried in a pocket. A number of measurements were carried out in a live GSM network, using logging of data from the Abis interface of the network. Four commercially available handsets were tested and 18 test users were involved. In addition a full body phantom mimicking the user's body was tested.
Transduction of Macaque Hematopoietic Repopulating Cells with Lenti and Foamy Retroviral Vectors with MGMT Selection Cassettes To Evaluate AIDS Gene Therapy Strategies. (2006)

Abstract AIDS remains a significant health problem worldwide despite the advent of highly active antiretroviral therapy (HAART). Although substantial efforts have been made to develop a vaccine there is still no cure and alternative strategies are needed to treat HIV infection and to control its spread. Our goal is to evaluate lenti and foamy retroviral vectors that inhibit HIV replication by RNAi in a non-human primate SHIV model to develop a hematopoietic stem cell (HSC) gene therapy for AIDS. SHIV is a chimeric virus comprised of an SIV genome that contains the tat, rev and env genes of HIV and infects both T lymphocytes and macrophages. Infection of non-human primates with SHIV results in significant decreases in CD4+ T cells as early as 4 weeks post infection, and is currently the best large animal model available to test gene therapy strategies for AIDS. However inefficient gene delivery to hematopoietic stem cells has limited progress for AIDS gene therapy. We have developed both lenti and foamy retroviral vectors that contain methylguanine-DNA-methyltransferase (MGMT) expression cassettes to allow for in vivo selection, and have transduced macaque (M. nemestrina) long term repopulating cells with both vector systems. Following transplantation we observed rapid engraftment and levels of gene marking in the peripheral blood that should allow us to in vivo select both lenti and foamy-marked hematopoietic repopulating cells. In one animal transplanted with a lentiviral vector we obtained marking at 265 days post-transplant of over 30% in peripheral blood granulocytes and 20% in peripheral blood lymphocytes prior to in vivo selection. Anti-SHIV/HIV transgene cassettes targeting tat and rev that allow for potent inhibition of SHIV and HIV replication in vitro have been incorporated into both lenti and foamy vectors and we have transduced macaque long term repopulating cells with lenti vectors containing an anti-HIV cassette. We are currently developing protocols for efficient in vivo selection and future studies will investigate the ability of macaque hematopoietic repopulating cells transduced with lenti and foamy MGMT anti-HIV vectors to inhibit SHIV infection ex vivo and in vivo.