gebhart/patrepeval huggingface dataset:
Formulations of Support Vector Machines: A Note from an Optimization Point of View (2001)

In this article, we discuss issues about formulations of support vector machines (SVM) from an optimization point of view. First, SVMs map training data into a higher- (maybe infinite-) dimensional space. Currently primal and dual formulations of SVM are derived in the finite dimensional space and readily extend to the infinite-dimensional space. We rigorously discuss the primal-dual relation in the infinite-dimensional spaces. Second, SVM formulations contain penalty terms, which are different from unconstrained penalty functions in optimization. Traditionally unconstrained penalty functions approximate a constrained problem as the penalty parameter increases. We are interested in similar properties for SVM formulations. For two of the most popular SVM formulations, we show that one enjoys properties of exact penalty functions, but the other is only like traditional penalty functions, which converge when the penalty parameter goes to infinity.
Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer (2003)

Gefitinib showed clinically meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients. At 250 mg/d, gefitinib had a favorable AE profile. Gefitinib 250 mg/d is an important, novel treatment option for patients with pretreated advanced NSCLC [corrected]
Whither Triazolam? (1997)

An open and advisory-type formulary can affect providers' drug selection behavior.
ChemInform Abstract: A NEW PROCESS FOR OBTAINING HYDROGEN CHLORIDE FROM DILUTE HYDROCHLORIC ACID (1983)

Abstract Die Isolierung von HCl‐Gas aus verdünnter Salzsäure erfolgt in 2 Arbeitsgängen durch eine Gegenstromextraktion in einem (tert.)‐Amin/Lösungsmittelgemisch und anschließende destillative Abspaltung von HCl‐Gas aus dem Extrakt.
Modulation of aqueous humor outflow facility by the Rho kinase-specific inhibitor Y-27632. (2001)

Based on the Rho kinase inhibitor-induced changes in myosin light-chain phosphorylation and actomyosin organization, it is reasonable to conclude that cellular relaxation and loss of cell-substratum adhesions in HTM and SC cells could result in either increased paracellular fluid flow across Schlemm's canal or altered flow pathway through the JCT, thereby lowering resistance to outflow. This study also suggests Rho kinase as a potential therapeutic target for the development of drugs to modulate intraocular pressure in glaucoma patients.
High-Performance Liquid Chromatographic Separation of 3-[(Cyclopentylhydroxyphenylacetyl)oxy]-1,1-dimethyl-pyrrolidinium Bromide Diastereomers (1990)

Abstract Retention of glycopyrrolate and its diastereomeric impurity was studied on a β-cyclodextrin-bonded phase column as function of pH and salt additives. The retention can be modeled by a linear model with pH and ionic strength as independent variables. On the basis of these data, simple and precise method for diastereomeric purity determination of glycopyrrolate was developed.
Cyclin A-Associated Kinase Activity Is Rate Limiting for Entrance into S Phase and Is Negatively Regulated in G1 by p27Kip1 (1995)

We have created fibroblast cell lines that express cyclin A under the control of a tetracycline-repressible promoter. When stimulated to reenter the cell cycle after serum withdrawal, these cells were advanced prematurely into S phase by induction of cyclin A. In an asynchronous population, induction of cyclin A caused a decrease in the percentage of cells in G1. These results demonstrate that expression of cyclin A is rate limiting for the G1-to-S transition and suggest that cyclin A can function as a G1 cyclin. Although the level of exogenous cyclin A was constant throughout the cell cycle, its associated kinase activity increased as cells approached S phase. Low kinase activity in early G1 was found to correlate with the presence of p27Kip1 in cyclin A-associated complexes, while high kinase activity in late G1 was correlated with its absence. These results suggest that a function of p27Kip1 in G1 is to prevent premature activation of cyclin A-associated kinase. Cyclin A expression in early G1 led to phosphorylation of the product of the retinoblastoma susceptibility gene (pRb). Thus, cyclin A expression can be rate limiting for pRb phosphorylation, implicating pRb as a physiological substrate of the cyclin A-dependent kinase. Taken together, these results demonstrate that deregulated expression of cyclin A can perturb the normal regulation of the G1-to-S transition.
Atomic Layer Deposition of Nickel Nitride Thin Films using NiCl2(TMPDA) and Tert‐Butylhydrazine as Precursors (2019)

This article describes the atomic layer deposition (ALD) of nickel nitride and nickel thin films using a diamine adduct of Ni(II) chloride, NiCl 2 (TMPDA) (TMPDA = N,N,N′,N′, ‐tetramethyl‐1,3‐propanediamine), as the metal precursor. Owing to the high reducing power of tert‐butylhydrazine (TBH), the films are grown at low temperatures of 190–250 °C. This is one of the few low‐temperature ALD processes that can be used to grow Ni 3 N and Ni metal on both insulating and conductive substrates. The films are characterized in terms of crystallinity, morphology, composition, resistivity, and coercivity. X‐ray diffraction shows reflections compatible with either hexagonal Ni or Ni 3 N. Composition analyses suggest that the films are close to stoichiometric Ni 3 N. Despite the nitride component, the films exhibit low resistivity values and at the lowest, a resistivity of 37 μΩ cm is achieved. The result is lower than what is typically observed for Ni x N films and not much higher than the best results concerning ALD Ni metal. The nitrogen content of the films is lowered down to 1.2 at% by postdeposition reduction at 150 °C in 10% forming gas. After the reduction, the nonmagnetic nitride films are converted to ferromagnetic Ni metal.
Review: T helper 17 cells: Their role in glomerulonephritis (2010)

T helper (Th) cells are an integral part of the host's immune response to eliminate invading pathogens. However, autoimmune or 'autoinflammatory' diseases can develop if Th cell responses are not effectively regulated. Several subsets of Th cells exist, including the Th17 subset that produces interleukin-17A, important in experimental models of organ-specific autoimmune inflammation. Its discovery has explained paradoxical observations in model systems thought to be Th1 mediated but were exacerbated in the absence of interferon-gamma, the prototypic Th1 effector cytokine. Th17 cells express unique transcription factors and secrete a unique pattern of cytokines. Interleukin-17A induces pro-inflammatory cytokines and chemokines and mediates neutrophil recruitment. Th17 cells have a reciprocal relationship with T regulatory cells and can also mediate suppression of Th1 responses. Recent studies also suggest that Th17 cells are not terminally differentiated but can switch into Th1 cells. Th17 cells have themselves been recently shown to induce antigen-specific cell-mediated proliferative glomerulonephritis. There is increasing evidence implicating Th17 cells in anti-glomerular basement membrane disease, lupus nephritis and pauci-immune glomerulonephritis. This review will review the discovery of the Th17 subset, its properties, its relationship with other Th subsets and assess the current evidence implicating Th17 cells in glomerulonephritis.
Evidence for an Upper Affinity Threshold for Anti-IgM–Induced Apoptosis in a Human B-Cell Lymphoma (1998)

The influence of ligand:receptor affinity on B-cell antigen receptor (BCR)-induced apoptosis in the IgM+ Burkitt lymphoma line, Ramos, was evaluated with a group of affinity-diverse murine monoclonal antibodies (MoAbs) specific for human B-cell IgM. The studies showed not only a minimal affinity threshold for the induction of apoptosis, but, interestingly, also a maximal affinity threshold above which increases in affinity were associated with diminished apoptosis. The lesser capacity of high-affinity MoAb to induce apoptosis was paralleled by a lesser capacity to induce receptor cross-linking. At high ligand concentration, high MoAb affinity was also associated with a diminished capacity to induce early protein tyrosine phosphorylation. The compromised capacity of two high-affinity MoAbs to trigger apoptosis may be, at least in part, explained by two separate phenomena that can impair the formation of mIgM cross-links: (1) more stable univalent binding and (2) a tendency for monogamous binding of both MoAb Fab to two Fab epitopes on mIgM. These in vitro studies suggest that the use of the highest affinity MoAbs for antireceptor immunotherapies that depend on receptor cross-linking might, on occasion, be contraindicated.
Necrotizing Fasciitis of the Abdominal Wall with Lethal Outcome: A Case Report (2006)

Necrotizing fasciitis is an acute surgical condition that demands prompt and multi-faceted treatment. Early recognition, aggressive surgical debridement, and targeted antibiotic therapy significantly affect the overall course of treatment and survival. The author reports here the case of a woman with necrotizing fasciitis of the abdominal wall and the course and methods of treatment. Two comorbidity factors (extreme obesity, diabetes) and the late diagnosis of necrotizing fasciitis, the latter masked by celullitis and phlegmona of the abdominal wall, resulted in overdue adequate surgical treatment. The combination of these factors contributed to medical treatment failure and, consequently, a lethal outcome.
Genes of the sbo-alb Locus of Bacillus subtilis Are Required for Production of the Antilisterial Bacteriocin Subtilosin (1999)

Bacillus subtilis JH642 and a wild strain of B. subtilis called 22a both produce an antilisterial peptide that can be purified by anion-exchange and gel filtration chromatography. Amino acid analysis confirmed that the substance was the cyclic bacteriocin subtilosin. A mutant defective in production of the substance was isolated from a plasmid gene disruption library. The plasmid insertion conferring the antilisterial-peptide-negative phenotype was located in a seven-gene operon (alb, for antilisterial bacteriocin) residing immediately downstream from the sbo gene, which encodes the precursor of subtilosin. An insertion mutation in the sbo gene also conferred loss of antilisterial activity. Comparison of the presubtilosin and mature subtilosin sequences suggested that certain residues undergo unusual posttranslational modifications unlike those occurring during the synthesis of class I (lantibiotic) or some class II bacteriocins. The putative products of the genes of the operon identified show similarities to peptidases and transport proteins that may function in processing and export. Two alb gene products resemble proteins that function in pyrroloquinoline quinone biosynthesis. The use of lacZ-alb and lacZ-sbo gene fusions, along with primer extension analysis, revealed that the sbo-alb genes are transcribed from a major promoter, residing upstream of sbo, that is very likely utilized by the sigma(A) form of RNA polymerase. The sbo and alb genes are negatively regulated by the global transition state regulator AbrB and are also under positive autoregulation that is not mediated by the subtilosin peptide but instead requires one or more of the alb gene products.
Effects of Growth Hormone-Releasing Hormone on Bone Turnover in Human Immunodeficiency Virus-Infected Men with Fat Accumulation (2005)

GHRH is a potentially appealing strategy to simultaneously improve fat distribution and increase bone turnover in HIV-infected patients. We investigated the effects of GHRH (1 mg sc twice a day over 12 wk) in 31 HIV-infected men with abdominal fat accumulation (age 46 +/- 1 yr, body mass index 26.2 +/- 0.6 kg/m2) in a randomized, double-blind, placebo-controlled study. We previously reported significant effects of GHRH on IGF-I and truncal fat. In this study, we assessed whether GHRH increased markers of bone turnover. At baseline, 32% of our subjects (n = 10) demonstrated a bone density Z score less than -1.0 sd and greater than or equal to -2.5 sd, and 3% (n = 1) demonstrated a Z score of less than -2.5 sd. IGF-I correlated with N-terminal telopeptide (NTx) (r = 0.49, P = 0.005) and tended to correlate with C-terminal telopeptide (CTx) (r = 0.35, P = 0.06) at baseline. Of the bone resorption markers, CTx increased significantly (0.16 +/- 0.07 vs. -0.03 +/- 0.03 ng/ml, GHRH vs. placebo, P = 0.02), and NTx tended to increase in response to GHRH (2.8 +/- 1.4 vs. -0.5 +/- 1.0 nm bone collagen equivalent, GHRH vs. placebo, P = 0.07). Of the bone formation markers, N-terminal propeptide of type 1 procollagen increased (14.6 +/- 9 vs. -6.8 +/- 3.1 microg/liter, GHRH vs. placebo, P = 0.03) and osteocalcin tended to increase (8.4 +/- 3.0 vs. 2.0 +/- 1.6 ng/ml, GHRH vs. placebo, P = 0.06) in response to GHRH. The calciotropic hormones, calcium and phosphorus, did not change significantly. The change in IGF-I correlated with the change in NTx (r = 0.45, P = 0.02), CTx (r = 0.38, P = 0.05), and osteocalcin (r = 0.55, P = 0.002). GHRH improves fat distribution and bone metabolism in men with HIV-related fat accumulation. Long-term studies are needed to determine whether the stimulatory effects of GHRH on bone turnover will translate into increased bone density in this population.
Peptide Phage Display: Opportunities for Development of Personalized Anti-Cancer Strategies (2002)

Personalized medicine is critical for cancer patients, because (1) cancer is a highly heterogeneous disease with major molecular differences in the expression and distribution of tumor cell surface markers among patients with the same type and grade of cancer, (2) cellular mutations tend to accumulate as cancer progresses, further increasing tumor heterogeneity, and (3) currently used cancer therapies often are toxic to normal cells, causing severe side effects rarely seen in other diseases. To prevent side effects and to improve effectiveness, cytotoxic therapies should be targeted and each patient should be profiled for the presence of cancer targets before the therapy is administered. Phage display technology utilizes combinatorial libraries of proteins expressed on phage particles that can be selected for specific binding to cancer cells. Such cancer-specific molecules can be used in a variety of applications, including identification of cell-specific targeting molecules; identification of cell surface biomarkers; profiling of specimens obtained from individual cancer patients, and the design of peptide-based anti-cancer therapeutics for personalized treatments. This review is focused on peptide phage display strategies that target cell surfaces because many biomarkers important in cancer are differentially expressed molecules located on the outside of the cell membranes.
The density and distribution of endothelin 1 and endothelin receptor subtypes in normal and diabetic rat corpus cavernosum (1995)

ET-1 and ETA receptor binding is increased in diabetic rat cavernosal tissue. A reduction in receptor linked nitric oxide (NO) release has previously been reported in diabetic rats. This finding may provide an explanation for the upregulation of ET-1 and ETA receptor binding in the diabetic rat.
Novel Multiplex Real-Time PCR Diagnostic Assay for Identification and Differentiation of Mycobacterium tuberculosis, Mycobacterium canettii, and Mycobacterium tuberculosis Complex Strains (2010)

Tuberculosis (TB) in humans is caused by members of the Mycobacterium tuberculosis complex (MTC). Rapid detection of the MTC is necessary for the timely initiation of antibiotic treatment, while differentiation between members of the complex may be important to guide the appropriate antibiotic treatment and provide epidemiological information. In this study, a multiplex real-time PCR diagnostics assay using novel molecular targets was designed to identify the MTC while simultaneously differentiating between M. tuberculosis and M. canettii. The lepA gene was targeted for the detection of members of the MTC, the wbbl1 gene was used for the differentiation of M. tuberculosis and M. canettii from the remainder of the complex, and a unique region of the M. canettii genome, a possible novel region of difference (RD), was targeted for the specific identification of M. canettii. The multiplex real-time PCR assay was tested using 125 bacterial strains (64 MTC isolates, 44 nontuberculosis mycobacteria [NTM], and 17 other bacteria). The assay was determined to be 100% specific for the mycobacteria tested. Limits of detection of 2.2, 2.17, and 0.73 cell equivalents were determined for M. tuberculosis/M. canettii, the MTC, and M. canettii, respectively, using probit regression analysis. Further validation of this diagnostics assay, using clinical samples, should demonstrate its potential for the rapid, accurate, and sensitive diagnosis of TB caused by M. tuberculosis, M. canettii, and the other members of the MTC.
Enhanced Activity of Monomethylauristatin F through Monoclonal Antibody Delivery:  Effects of Linker Technology on Efficacy and Toxicity (2005)

We have previously shown that antibody-drug conjugates (ADCs) consisting of cAC10 (anti-CD30) linked to the antimitotic agent monomethylauristatin E (MMAE) lead to potent in vitro and in vivo activities against antigen positive tumor models. MMAF is a new antimitotic auristatin derivative with a charged C-terminal phenylalanine residue that attenuates its cytotoxic activity compared to its uncharged counterpart, MMAE, most likely due to impaired intracellular access. In vitro cytotoxicity studies indicated that mAb-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-MMAF (mAb-L1-MMAF) conjugates were >2200-fold more potent than free MMAF on a large panel of CD30 positive hematologic cell lines. As with cAC10-L1-MMAE, the corresponding MMAF ADC induced cures and regressions of established xenograft tumors at well tolerated doses. To further optimize the ADC, several new linkers were generated in which various components within the L1 linker were either altered or deleted. One of the most promising linkers contained a noncleavable maleimidocaproyl (L4) spacer between the drug and the mAb. cAC10-L4-MMAF was approximately as potent in vitro as cAC10-L1-MMAF against a large panel of cell lines and was equally potent in vivo. Importantly, cAC10-L4-MMAF was tolerated at >3 times the MTD of cAC10-L1-MMAF. LCMS studies indicated that drug released from cAC10-L4-MMAF was the cysteine-L4-MMAF adduct, which likely arises from mAb degradation within the lysosomes of target cells. This new linker technology appears to be ideally suited for drugs that are both relatively cell-impermeable and tolerant of substitution with amino acids. Thus, alterations of the linker have pronounced impacts on toxicity and lead to new ADCs with greatly improved therapeutic indices.
Protein Interaction Screening for the Ankyrin Repeats and Suppressor of Cytokine Signaling (SOCS) Box (ASB) Family Identify Asb11 as a Novel Endoplasmic Reticulum Resident Ubiquitin Ligase (2013)

The ankyrin and SOCS (suppressor of cytokine signaling) box (ASB) family of proteins function as the substrate recognition subunit in a subset of Elongin-Cullin-SOCS (ECS) E3 ubiquitin ligases. Despite counting 18 members in humans, the identity of the physiological targets of the Asb proteins remains largely unexplored. To increase our understanding of the function of ASB proteins, we conducted a family-wide SILAC (stable isotope labeling by amino acids in cell culture)-based protein/protein interaction analysis. This investigation led to the identification of novel as well as known ASB-associated proteins like Cullin 5 and Elongins B/C. We observed that several proteins can be bound by more than one Asb protein. The additional exploration of this phenomenon demonstrated that ASB-Cullin 5 complexes can oligomerize and provides evidence that Cullin 5 forms heterodimeric complexes with the Cullin 4a-DDB1 complex. We also demonstrated that ASB11 is a novel endoplasmic reticulum-associated ubiquitin ligase with the ability to interact and promote the ubiquitination of Ribophorin 1, an integral protein of the oligosaccharyltransferase (OST) glycosylation complex. Moreover, expression of ASB11 can increase Ribophorin 1 protein turnover in vivo. In summary, we provide a comprehensive protein/protein interaction data resource that can aid the biological and functional characterization of ASB ubiquitin ligases.
Positively charged amino acid residues can act as topogenic determinants in membrane proteins. (1989)

When alkaline phosphatase is fused to the periplasmic domain of a cytoplasmic membrane protein, it is efficiently exported to the periplasm. Such a hybrid protein exhibits high alkaline phosphatase enzymatic activity. When alkaline phosphatase is fused to the cytoplasmic domain of a membrane protein, it remains, for the most part, in the cytoplasm. Such fusions exhibit low enzymatic activity. However, stable retention of alkaline phosphatase in the cytoplasm requires the presence in the fusion protein of the cytoplasmic loop ordinarily present in that position in the native, unfused protein. Using oligonucleotide-directed mutagenesis, we have shown that positively charged amino acids are required for the stable cytoplasmic localization of the fused alkaline phosphatase. We propose that, in addition to hydrophobic transmembrane segments, positively charged amino acids in the hydrophilic cytoplasmic domains of a membrane protein are determinants of the protein's topology.
2-18F-Fluoropropionic Acid as a PET Imaging Agent for Prostate Cancer (2009)

The data presented here indicate that (18)F-FPA accumulates in prostate cancers with high tumor-to-background ratios. (18)F-FPA has potential for use in the clinical diagnosis of prostate cancer in humans.
To Lube or Not to Lube: Experiences and Perceptions of Lubricant Use in Women with and Without Dyspareunia (2011)

ABSTRACT Introduction There are few studies examining the relationship between lubricant use and sexual functioning, and no studies have examined this relationship in women with dyspareunia. Vaginal dryness is a prevalent complaint among women of all ages. There is an association between vaginal dryness and painful intercourse; therefore, women with dyspareunia represent a particularly relevant sample of women in which to investigate lubricant use. Aim The aim of this study was to examine differences between women with and without dyspareunia in self-reported natural lubrication and attitudes toward and use of personal lubricants. Methods Respondents completed an online survey including questions on demographics, gynecological/medical history, sexual functioning, and lubricant use and attitudes. Main Outcome Measures The main outcome measures used were the Female Sexual Function Index (FSFI) and questions regarding attitudes toward and use of lubricants. Results Controls scored higher on the lubrication subscale of the FSFI than women with dyspareunia (P &amp;lt; 0.001). Women with dyspareunia reported greater frequency of lubricant use during sexual activity over the last year (P &amp;lt; 0.01). They were also more likely to use lubricant prior to penetration (P &amp;lt; 0.05). The most common use for controls was to enhance sexual experiences. This was also a common answer for women with dyspareunia; however, in this group, the most common reason was to reduce/alleviate pain. Lubricants were rated as less effective among women with dyspareunia vs. controls across all reported reasons for use. Nevertheless, lubricant use was still rated as being moderately effective in alleviating pain for women with dyspareunia. Conclusions Women with dyspareunia have more difficulty with natural lubrication; it is consequently not surprising that they reported using lubricant more frequently than control women. Women with dyspareunia reported using lubricants more often than controls to try to prevent or alleviate pain and reported this as being a moderately effective strategy, suggesting that it may be a useful tool for some women with dyspareunia.