gebhart/patrepeval huggingface dataset:
Clinical Outcome of Hematopoietic Stem Cell Transplantation (HSCT) Using Plasma Depleted Umbilical Cord Blood Units (UCB) That Were Not Depleted of Red Blood Cells Prior to Cryopreservation. (2005)

Abstract Background: UCB is an attractive source for HSCT because of less stringent HLA matching requirements, lower incidence and severity of GvHD, and ready availability of a physical inventory. However, unlike BMT or PSCT, the limiting cell dose associated with UCB units has hampered its widespread use. The red cell depletion (RCD) techniques that are widely used by UCB banks incur significant nucleated cell loss after processing. One method of minimizing cell loss during processing is to deplete plasma (PD) but not red blood cells. A large racially diverse inventory of 18,000 PD UCB is now available on stem cell registries; however, clinical outcome for HSCT using PD UCB products is unavailable. Hypothesis: Usage of PD UCB in unrelated HSCT will result in acceptable clinical outcome for myeloid (ANC 500) and platelet engraftment, overall survival (OS), event-free-survival (EFS), and transplant related mortality (TRM). Methods: A retrospective analysis limited to patients without prior transplants and transplanted during remission (“eligible”) was performed on 98 HSCT using PD UCB. An additional 20 “high risk” patients with prior transplants or transplanted during relapse were included in the engraftment and survival analysis. Results: Average loss of less than 0.1% nucleated cells was found in the discarded plasma fraction after PD UCB processing (n=27), though cell clumping limited the cellular fraction recovery to 90%. Outcome on engraftment and/or survival was available for 98 patients (median age 6.7 yo, range 0.3–54 yo, 24 &gt;16 yo; median weight 23.5 kg, range 4.5–88 kg, 27 &gt;50kg; male 60%; median # HLA ABDR matches 4.0; median pre-freeze TNC dose 5.7 x 107/kg; transplant center reported median post-thaw TNC dose 5.5 x 107/kg; median pre-freeze CD34 dose 2.0 x 105/kg; malignant indications 71%; transplants outside U.S. 37%; double unit transplant 14%; and non-myeloablative 7%). The median time to engraftment for ANC 500 (n=87), platelet 20K (n=72) and 50K (n=68) were 22.0 days (range 7–49 days), 49.5 days (range 13–94 days), and 58.0 days (range 21–132 days) respectively. The unadjusted cumulative incidence of ANC500 and platelet 20K and 50K engraftment were 94±3%, 81±5% and 80±5% respectively for 98 eligible patients, and 90±3%, 77±5% and 75±5% respectively for the eligible plus high risk patients. The incidence of grade III–IV acute GVHD and extensive chronic GVHD were 15% and 14% respectively. Relapse rate for malignancies (n=67) and TRM (n=98) were 20±6% and 20±4% respectively at 1 year. With a median follow-up of 297 days (range 50–1,263 days), the Kaplan-Meier estimates of 1-year survival (n=98) and disease-free survival (n=67) are 73±5% and 59±7% respectively for the eligible patients, and 65±5% (n=118) and 50±6% (n=85) respectively for the eligible plus high risk patients. Conclusion: These results demonstrate that HSCT using PD UCB can be performed safely and effectively.
Evaluation of a Novel Hexavalent Humanized Anti-IGF-1R Antibody and Its Bivalent Parental IgG in Diverse Cancer Cell Lines (2012)

A major mechanism of monoclonal antibodies that selectively target the insulin-like growth factor type 1 receptor (IGF-1R) to inhibit tumor growth is by downregulating the receptor, regardless whether they are capable (antagonistic) or incapable (agonistic) of blocking the binding of cognate ligands. We have developed and characterized a novel agonistic anti-IGF-1R humanized antibody, hR1, and used the Dock-and-Lock (DNL) method to construct Hex-hR1, the first multivalent antibody comprising 6 functional Fabs of hR1, with the aim of enhancing potency of hR1. Based on cross-blocking experiments, hR1 recognizes a region of cysteine-rich domain on the α-subunit, different from the epitopes mapped for existing anti-IGF-1R antibodies, yet hR1 is similar to other anti-IGF-1R antibodies in downregulating IGF-1R and inhibiting proliferation, colony formation, or invasion of selected cancer cell lines in vitro, as well as suppressing growth of the RH-30 rhabdomyosarcoma xenograft in nude mice when combined with the mTOR inhibitor, rapamycin. Hex-hR1 and hR1 are generally comparable in their bioactivities under the in-intro and in-vivo conditions investigated. Nevertheless, in selective experiments involving a direct comparison of potency, Hex-hR1 demonstrated a stronger effect on inhibiting cell proliferation stimulated by IGF-1 and could effectively downregulate IGF-1R at a concentration as low as 20 pM.
The resolvase/invertase domain of the site-specific recombinase TnpX is functional and recognizes a target sequence that resembles the junction of the circular form of the Clostridium perfringens transposon Tn4451 (1997)

Tn4451 is a 6.3-kb chloramphenicol resistance transposon from Clostridium perfringens and is found on the conjugative plasmid pIP401. The element undergoes spontaneous excision from multicopy plasmids in Escherichia coli and C. perfringens and conjugative excision from pIP401 in C. perfringens. Tn4451 is excised as a circular molecule which is probably the transposition intermediate. Excision of Tn4451 is dependent upon the site-specific recombinase TnpX, which contains potential motifs associated with both the resolvase/invertase and integrase families of recombinases. Site-directed mutagenesis of conserved amino acid residues within these domains was used to show that the resolvase/invertase domain was essential for TnpX-mediated excision of Tn4451 from multicopy plasmids in E. coli. An analysis of Tn4451 target sites revealed that the transposition process showed target site specificity. The Tn4451 target sequence resembled the junction of the circular form, and insertion occurred at a GA dinucleotide. Tn4451 insertions were flanked by directly repeated GA dinucleotides, and there was also a GA at the junction of the circular form, where the left and right termini of Tn4451 were fused. We propose a model for Tn4451 excision and insertion in which the resolvase/invertase domain of TnpX introduces 2-bp staggered cuts at these GA dinucleotides. Analysis of Tn4451 derivatives with altered GA dinucleotides provided experimental evidence to support the model.
The benefits and risks of testosterone replacement therapy: a review (2009)

Increased longevity and population aging will increase the number of men with late onset hypogonadism. It is a common condition, but often underdiagnosed and undertreated. The indication of testosterone-replacement therapy (TRT) treatment requires the presence of low testosterone level, and symptoms and signs of hypogonadism. Although controversy remains regarding indications for testosterone supplementation in aging men due to lack of large-scale, long-term studies assessing the benefits and risks of testosterone-replacement therapy in men, reports indicate that TRT may produce a wide range of benefits for men with hypogonadism that include improvement in libido and sexual function, bone density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life and cardiovascular disease. Perhaps the most controversial area is the issue of risk, especially possible stimulation of prostate cancer by testosterone, even though no evidence to support this risk exists. Other possible risks include worsening symptoms of benign prostatic hypertrophy, liver toxicity, hyperviscosity, erythrocytosis, worsening untreated sleep apnea or severe heart failure. Despite this controversy, testosterone supplementation in the United States has increased substantially over the past several years. The physician should discuss with the patient the potential benefits and risks of TRT. The purpose of this review is to discuss what is known and not known regarding the benefits and risks of TRT.
Investigation of chitosan used in the clarifying of the apple juice. (2009)

Objective To investigate the influence of chitosan on the clarity of apple juice and determine the optimal clarity conditions.Methods The percent transmittance of apple juice obtained by spectrophotometer at 720 nm was used to determine the better clarity conditions.Results The optimum conditions for the clarity of apple juice were as follows: 0.15 g/L chitosan at 40℃ for 1 h,pH 3.Under the above conditions,the nutritional ingredients and the taste of apple juice were not changed.Conclusion The chitosan can be used for the clarity of apple juice.
A Computer Aided Engineering Workstation For Registration Control (1989)

A computer aided engineering workstation is described which provides for the comprehensive characterization and control of registration performance over an entire process, from stepper set-up through layer-to-layer inspection. The workstation accepts data entered manually and from a number of automated metrology tools. The measurement layout is user defmed and supports the diverse sampling needs of set-up and production. Layouts can be defmed to obtain grid and intrafield placement data simultaneously. Data obtained from all sources can be displayed, manipulated, and analyzed in a user-friendly workstation environment that has been optimized for direct visual and numeric comparison of lithography data. Registration modeling, grid and intrafield, is performed to relate the measured quantities to assignable causes, predict worst case overlay, and to allow for the trending of error components. The workstation can be connected to many steppers and metrology tools at once to provide a registration control center. The application of the workstation to stepper set-up and production line monitoring is demonstrated. Use of the workstation as the registration control center for a production line is discussed.
Quantitation of targets for PCR by use of limiting dilution. (1992)

We describe a general method to quantitate the total number of initial targets present in a sample using limiting dilution, PCR and Poisson statistics. The DNA target for the PCR was the rearranged immunoglobulin heavy chain (IgH) gene derived from a leukemic clone that was quantitated against a background of excess rearranged IgH genes from normal lymphocytes. The PCR was optimized to provide an all-or-none end point at very low DNA target numbers. PCR amplification of the N-ras gene was used as an internal control to quantitate the number of potentially amplifiable genomes present in a sample and hence to measure the extent of DNA degradation. A two-stage PCR was necessary owing to competition between leukemic and non-leukemic templates. Study of eight leukemic samples showed that approximately two potentially amplifiable leukemic IgH targets could be detected in the presence of 160,000 competing non-leukemic genomes. The method presented quantitates the total number of initial DNA targets present in a sample, unlike most other quantitation methods that quantitate PCR products. It has wide application, because it is technically simple, does not require radioactivity, addresses the problem of excess competing targets and estimates the extent of DNA degradation in a sample.
Isolation and characterization of two Saccharomyces cerevisiae genes encoding homologs of the bacterial HexA and MutS mismatch repair proteins. (1992)

Homologs of the Escherichia coli (mutL, S and uvrD) and Streptococcus pneumoniae (hexA, B) genes involved in mismatch repair are known in several distantly related organisms. Degenerate oligonucleotide primers based on conserved regions of E. coli MutS protein and its homologs from Salmonella typhimurium, S. pneumoniae and human were used in the polymerase chain reaction (PCR) to amplify and clone mutS/hexA homologs from Saccharomyces cerevisiae. Two DNA sequences were amplified whose deduced amino acid sequences both shared a high degree of homology with MutS. These sequences were then used to clone the full-length genes from a yeast genomic library. Sequence analysis of the two MSH genes (MSH = mutS homolog), MSH1 and MSH2, revealed open reading frames of 2877 bp and 2898 bp. The deduced amino acid sequences predict polypeptides of 109.3 kD and 109.1 kD, respectively. The overall amino acid sequence identity with the E. coli MutS protein is 28.6% for MSH1 and 25.2% for MSH2. Features previously found to be shared by MutS homologs, such as the nucleotide binding site and the helix-turn-helix DNA binding motif as well as other highly conserved regions whose function remain unknown, were also found in the two yeast homologs. Evidence presented in this and a companion study suggest that MSH1 is involved in repair of mitochondrial DNA and that MSH2 is involved in nuclear DNA repair.
ATR Is Not Required for p53 Activation but Synergizes with p53 in the Replication Checkpoint (2002)

ATR (ataxia telangiectasia and Rad-3-related) is a protein kinase required for survival after DNA damage. A critical role for ATR has been hypothesized to be the regulation of p53 and other cell cycle checkpoints. ATR has been shown to phosphorylate p53 at Ser(15), and this damage-induced phosphorylation is diminished by expression of a catalytically inactive (ATR-kd) mutant. p53 function could not be examined directly in prior studies of ATR, however, because p53 was mutant or because cells expressed the SV40 large T antigen that blocks p53 function. To test the interactions of ATR and p53 directly we generated human U2OS cell lines inducible for either wild-type or kinase-dead ATR that also have an intact p53 pathway. Indeed, ATR-kd expression sensitized these cells to DNA damage and caused a transient decrease in damage-induced serine 15 phosphorylation of p53. However, we found that the effects of ATR-kd expression do not result in blocking the response of p53 to DNA damage. Specifically, prior ATR-kd expression had no effect on DNA damage-induced p53 protein up-regulation, p53-DNA binding, p21 mRNA up-regulation, or G(1) arrest. Instead of promoting survival via p53 regulation, we found that ATR protects cells by delaying the generation of mitotic phosphoproteins and inhibiting premature chromatin condensation after DNA damage or hydroxyurea. Although p53 inhibition (by E6 or MDM2 expression) had little effect on premature chromatin condensation, when combined with ATR-kd expression there was a marked loss of the replication checkpoint. We conclude that ATR and p53 can function independently but that loss of both leads to synergistic disruption of the replication checkpoint.
A Simple Method for Site-Specific Mutagenesis that Leaves the Rest of the Template Unaltered (2003)

Site-directed mutagenesis is an important component of modern molecular biology. The use of this technique became necessary both in our studies of promoter function and in the analysis of protein structure-function relationships. Although several polymerase chain reaction (PCR)-based methods of site-specific mutagenesis have been described (1–4), we have developed a simple procedure that can introduce either a single or a small cluster of mutations into any DNA segment in the range 0.3–3 kb. Importantly, using this technique, only the designed changes are incorporated into the target sequence, all other positions remain unaltered.
Targeted drug delivery to C6 glioma by transferrin-coupled liposomes (2000)

Recent advances in liposome technology have shown promise relative to the introduction of chemotherapeutic agents with reduced toxicity, extended longevity, and potential for cell-specific targeting. In this study we report the engineering of a liposomal delivery system for the chemotherapeutic drug doxorubicin. The system was targeted specifically to C6 glioma in vitro by coupling transferrin to the distal ends of liposomal polyethylene glycol (PEG) chains. The transferrin receptor is overexpressed on glioma, with the extent of overexpression correlated to the severity of the tumor. Significantly increased gliomal doxorubicin uptake was achieved by drug encapsulation within transferrin-coupled liposomes compared to other liposome populations. Doxorubicin encapsulated within transferrin-coupled liposomes exhibited 70% of free doxorubicin uptake as compared to 54, 14, and 34% for non-PEG, PEG, and albumin-coupled PEG liposomes, respectively. Competitive binding assays support the receptor-mediated mechanism of targeting. The addition of one microM free transferrin reduced the uptake of doxorubicin encapsulated within transferrin-coupled liposomes by 30%.
A Novel Peptide Antagonist of CXCR4 Derived from the N-Terminus of Viral Chemokine vMIP-II (2000)

The viral macrophage inflammatory protein-II (vMIP-II) encoded by Kaposi's sarcoma-associated herpesvirus is unique among all known chemokines in that vMIP-II shows a broad-spectrum interaction with both CC and CXC chemokine receptors including CCR5 and CXCR4, two principal coreceptors for the cell entry of human immunodeficiency virus type 1 (HIV-1). To elucidate the mechanism of the promiscuous receptor interaction of vMIP-II, synthetic peptides derived from the N-terminus of vMIP-II were studied. In contrast to the full-length protein that recognizes both CXCR4 and CCR5, a peptide corresponding to residues 1-21 of vMIP-II (LGASWHRPDKCCLGYQKRPLP) was shown to strongly bind CXCR4, but not CCR5. The IC(50) of this peptide in competing with CXCR4 binding of (125)I-SDF-1alpha is 190 nM as compared to the IC(50) of 14.8 nM of native vMIP-II in the same assay. The peptide selectively prevented CXCR4 signal transduction and coreceptor function in mediating the entry of T- and dual-tropic HIV-1 isolates, but not those of CCR5. Further analysis of truncated peptide analogues revealed the importance of the first five residues for the activity with CXCR4. These results suggest that the N-terminus of vMIP-II is essential for its function via CXCR4. In addition, they reveal a possible mechanism for the distinctive interactions of vMIP-II with different chemokine receptors, a notion that may be further exploited to dissect the structural basis of its promiscuous biological function. Finally, the potent CXCR4 peptide antagonist shown here could serve as a lead for the development of new therapeutic agents for HIV infection and other immune system diseases.
Biomarkers for Lupus Nephritis (2009)

Current treatment of severe lupus nephritis is unsatisfactory in terms of both outcome and toxicity. To improve the efficacy and decrease the adverse effects of immunosuppression, it would be ideal to be able to predict the course and pathology of lupus nephritis and adjust therapy appropriately. This will require biomarkers that reflect disease activity. Recently, significant effort has been put into identifying biomarkers that can anticipate impending lupus renal flare, forecast development of chronic kidney disease, or reflect kidney histology at the time of flare. Although these biomarkers are potentially useful, to date none has been clinically validated in a large, prospective cohort of patients with SLE. This article reviews the current status of lupus nephritis biomarker investigation and articulates a perspective of how future efforts should be focused.
The protease inhibitory properties of the Alzheimer's beta-amyloid precursor protein. (1990)

We have expressed the 57-amino acid Kunitz domain of the Alzheimer's beta-amyloid precursor protein (APP751) as a bacterial fusion protein. The protease inhibitory properties of the purified fusion protein, BX9, were virtually identical in all respects tested to those of purified secreted APP751. Both proteins strongly inhibited pancreatic trypsin (Kis = 0.2 and 0.3 nM) and less well epidermal growth factor-binding protein (Kis = 1 and 3.5 nM), alpha-chymotrypsin (Kis = 3 and 6 nM), and the gamma-subunit of nerve growth factor (Kis = 8 and 9 M). Neither protein appreciably inhibited plasma and pancreatic kallikreins, thrombin, lung tryptase, neutrophil elastase, or cathepsin G. The remarkable similarity of the protease inhibitory profile of BX9 to that of secreted APP751 suggests that proper intramolecular disulfide bond formation has occurred in the bacterial fusion protein and leads to the conclusion that the amyloid precursor protein Kunitz domain is a relatively specific inhibitor of only a few trypsin-like arginine esterases.
Targeting IL‐13Rα2 in human pancreatic ductal adenocarcinoma with combination therapy of IL‐13‐PE and gemcitabine (2010)

Pancreatic cancer is an aggressive disease with only limited therapeutic options available. We have identified that 71% pancreatic ductal adenocarcinoma (PDA) express high levels of IL-13Rα2, a high-affinity receptor for IL-13. To target IL-13Rα2, we have developed a recombinant immunotoxin, which is a fusion of IL-13 and Pseudomonas exotoxin (IL-13-PE). Since IL-13-PE and a commonly used cytotoxic drug gemcitabine act by a different mechanism, we hypothesized that they synergize in mediating antitumor response. Both IL-13-PE and gemcitabine-mediated cytotoxicity to two pancreatic cancer cell lines and when combined synergistic cytotoxicity was observed. This synergism was also demonstrated in vivo in an orthotopic mouse model of human PDA. IL-13-PE and gemcitabine showed complete eradiation of tumors as assessed by whole body imaging of GFP-transfected tumors in 57% of mice in an early cancer model resulting into prolongation of survival. In contrast, monotherapy with either agent did not produce complete eradiation, but tumor volumes were significantly decreased. In advanced PDA model, combination therapy also produced dramatic reduction in tumor growth and enhanced survival compared to animals treated with either agent alone. When IL-13Rα2 was knocked-down by RNAi prior to tumor implantation, IL-13-PE and gemcitabine did not synergize indicating that IL-13Rα2 is essential. Mechanistically, gemcitabine increased IL-13Rα2 expression in vitro and in vivo, which resulted in a synergism of combination therapy. Interestingly, PDA cancer stem cells were resistant to gemcitabine, but not to IL-13-PE. These results suggest that combination therapy with IL-13-PE and gemcitabine may be a useful strategy for PDA therapy.
Conformation-sensitive Antibodies against Alzheimer Amyloid-β by Immunization with a Thioredoxin-constrained B-cell Epitope Peptide (2007)

Immunotherapy against the amyloid-beta (Abeta) peptide is a valuable potential treatment for Alzheimer disease (AD). An ideal antigen should be soluble and nontoxic, avoid the C-terminally located T-cell epitope of Abeta, and yet be capable of eliciting antibodies that recognize Abeta fibrils and neurotoxic Abeta oligomers but not the physiological monomeric species of Abeta. We have described here the construction and immunological characterization of a recombinant antigen with these features obtained by tandem multimerization of the immunodominant B-cell epitope peptide Abeta1-15 (Abeta15) within the active site loop of bacterial thioredoxin (Trx). Chimeric Trx(Abeta15)n polypeptides bearing one, four, or eight copies of Abeta15 were constructed and injected into mice in combination with alum, an adjuvant approved for human use. All three polypeptides were found to be immunogenic, yet eliciting antibodies with distinct recognition specificities. The anti-Trx(Abeta15)4 antibody, in particular, recognized Abeta42 fibrils and oligomers but not monomers and exhibited the same kind of conformational selectivity against transthyretin, an amyloidogenic protein unrelated in sequence to Abeta. We have also demonstrated that anti-Trx(Abeta15)4, which binds to human AD plaques, markedly reduces Abeta pathology in transgenic AD mice. The data indicate that a conformational epitope shared by oligomers and fibrils can be mimicked by a thioredoxin-constrained Abeta fragment repeat and identify Trx(Abeta15)4 as a promising new tool for AD immunotherapy.
2021 Reviewer Acknowledgment (2021)

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Clinical Surgery Research Communications maintains its standards for the high quality of its published papers. We would like to express our sincere gratitude to the following reviewers for their precious time and dedication in the year of 2021.