cssi/SciSciGPT-SciSciNet huggingface dataset:
Post-translational Introduction of D-Alanine into Ribosomally Synthesized Peptides by the Dehydroalanine Reductase NpnJ.

Ribosomally synthesized peptides are generally limited to l-amino acid building blocks. Given the advantageous properties of peptides containing d-amino acids such as stabilization of certain turns and against proteolytic degradation, methods to introduce d-stereocenters are valuable. Here we report the first in vitro reconstitution and characterization of a dehydrogenase that carries out the asymmetric reduction of dehydroalanine. NpnJA reduces dehydroalanine to d-Ala using NAPDH as cosubstrate. The enzyme displays high substrate tolerance allowing introduction of d-Ala into a range of non-native substrates. In addition to the in vitro reactions, we describe five examples of using Escherichia coli as biosynthetic host for d-alanine introduction into ribosomal peptides. A deuterium-label-based coupled-enzyme assay was used to rapidly determine the stereochemistry of the newly installed alanine.
Neuroanatomy of the pelvis: implications for colonic and rectal resection.

PURPOSE: Urinary dysfunction remains a common complication of radical pelvic surgery, particularly after abdominoperineal resection. In treating rectal carcinoma, the extent of primary resection and lymphadenectomy are major determinants in the degree of postoperative urologic morbidity. METHODS. Twelve male and eight female hemipelves from fresh cadavers were dissected with reference to the neuroanatomy of the lower genitourinary tract. These cadavers were dissected within twelve hours of thaw from frozen state. The cadavers were hemisected at the level of the sacral promontory for better exposure of neural trunks and vascular structures leading into the pelvis. These structures were followed down sequentially into the true pelvis, using magnified dissection under operating microscope or loupe dissection or both. RESULTS: Coordinated lower urinary tract function relies on both autonomic and somatic nerve activity. Emanating from the inferior hypogastric plexus, the pelvic nerve supplies sympathetic and parasympathetic innervation to the pelvic viscera. The course of the pelvic nerve is as follows: 1) from the inferior hypogastric plexus, it has multiple branches forming a web-like complex within the endopelvic fascial sleeve, some of which innervate the bladder detrusor; 2) a main branch traveling inferolateral to the rectum remains deep to the fascia of the levator ani muscle and courses to the external urinary sphincter; 3) at the level of the prostatic apex (or bladder neck in females), this pelvic nerve branch sends direct branches to the urinary sphincter. The pudendal nerve traverses the pelvis in the pudendal canal, and before leaving the pelvis to enter the perineum, it gives an intrapelvic branch that courses alongside the ischium to enter the external urinary sphincter. In the ischiorectal fossa, terminal branches of the pudendal nerve (i.e., perineal nerve) can be seen inserting into the urinary sphincter. CONCLUSIONS. Urinary retention and urinary incontinence represent two distinct urologic complications after abdominoperineal resection. Injury to detrusor branches of the pelvic nerve can cause detrusor denervation and urinary retention. In addition, injury to intrapelvic branches of the pelvic and pudendal nerves to the urinary sphincter can result in intrinsic sphincter deficiency and urinary incontinence. A better understanding of the neuroanatomy of the lower genitourinary tract can give a physiologic basis for clinical findings of postoperative voiding dysfunction and may help the surgeon refine surgical technique by more precisely determining resection limits to minimize urologic complications.
Improving clinical instruction: comparison of literature.

Context Clinical education in radiologic technology and athletic training is similar in that both programs use clinical sites and clinical instructors to instruct and evaluate student competency. Objective The purpose of this paper is to review and compare the literature from radiologic technology and athletic training clinical education. Methods The literature for this review was obtained using ProQuest and PubMed databases, from the years 1998 to 2006. Research is available for both radiologic technology and athletic training and provides a good comparison. Results Radiologic technology students experience various clinical stressors that can be remedied by properly trained clinical instructors and instructors who spend quality time with students. The opinions regarding the necessary behaviors of clinical instructors vary between program directors, clinical instructors and students. Conclusion Cooperation and communication between programs and clinical instructors is important for students to achieve clinical success. A comparison of the literature demonstrates that radiologic technology and athletic training programs are similar; thus, ideas from athletic training can be applied to radiologic technology clinical education.
Intraperitoneal catheter leads to prolongation of the time to normalization of serum CA125 levels.

Objective: The intraperitoneal (IP) catheter has the potential to cause peritoneal irritation, which may contribute to an elevated CA125 level. We hypothesize that patients undergoing IP chemotherapy may have elevated CA125 values when compared with patients receiving intravenous (IV) chemotherapy. Methods: From February 2006 to July 2007, optimally debulked patients with stage III and stage IV ovarian carcinoma from a single institution were offered an outpatient IV/IP chemotherapy regimen modified from Gynecologic Oncology Group 172. They were matched to a cohort of similar patients who received IV paclitaxel and carboplatin. Demographic data and CA125 levels were collected before each cycle of chemotherapy and after the removal of the IP catheter. Statistical analysis was completed using a χ2 test with a significance level of P Results: Fifty patients received the standard IV regimen, and 38 patients completed the modified IV/IP regimen. There was no statistical difference in the median CA125 values between the 2 groups during the treatment. After 6 cycles of therapy, 68.4% (26/38) of the IP cohort had a normal CA125 level before IP catheter removal compared with 78% (39/50) in the IV chemotherapy cohort (P = 0.44). After removal of the IP catheter, 86.8% (33/38) of the patients had a normal CA125 value (68.4% vs 86.8%, P = 0.049). Conclusions: After removal of the IP catheter, an additional 18.2% (7/38) of patients in the IP group had normalized their CA125 level. Because CA125 levels at the end of the treatment have prognostic significance, the role of the IP catheter in an elevated CA125 level must be considered.
ELECTROLYTE AND WATER EXCHANGES IN THE ESTROGEN TREATED OVARIECTOMIZED-ADRENALECTOMIZED RAT.

SummaryDaily administration of 10, 25, 50 or 100 μg of diethylstilbestrol (DES) to overiectomized-adrenalectomized rats for 7 days significantly reduced the Na+, Cl- and K+ excretions and the urinary Na:K ratio. Pair-feeding (to the 100 μg DES group) also reduced the electrolyte excretions, though significantly less than that of the 100 μg DES treated animals, but did not alter the urinary Na:K ratio which remained normal. Thus, at these dosages, DES can effect a diminished electrolyte excretion in the absence of adrenal cortical tissue and independently of electrolyte intake.The authors express their gratitude to Mrs, S. Muda, Mr. J. Hegmann and Miss J. Moroney for technical assistance.
Effects of an Alternative to Suspension Intervention in a Therapeutic High School

The purpose of the current study was to assess the effects of an alternative to suspension intervention on students' subsequent major referrals. The intervention included activities designed to teach social coping strategies as well as mediation to resolve interpersonal conflicts. The intervention was implemented in a therapeutic high school, and the sample consisted of 31 students who accrued at least one major referral for physical violence or drug-related offenses. Archival office discipline referral data were collected and analyzed using a posttest-only nonequivalent control group design. The results suggest that, among students with two referrals, the intervention may lengthen the amount of time between referrals, and participation in at least one intervention session may reduce the likelihood of a subsequent referral.
PLUGGING EFFECTS OF DRILLING FLUID AND COMPLETION FLUID ON FRACTURED FORMATION BY MUD FILTER PRESS

Current borehole evaluation methods such as mud shale specific area measuring method, mud shale hydration swelling measuring method, drilling fluid cake compressibility evaluation method and so on are suitable for shale formation collapse. Whereas there is no a feasible evaluation method on how to stabilize fracture formation and crack strata. Plugging effects of drilling fluid and completion fluid on fractured formation have been evaluated by mud filter press 387-42 and results have show that it is a effective method for evaluating drilling fluid and completion fluid in the oilfield.
Viruses and Breast Cancer

With the viral causation of murine mammary cancer firmly established, it appears most unlikely that the striking parallels found in the human disease can be coincidental. Thus in both species electron microscopy demonstrates typical virus-like particles in tumor tissue and milk, and immunologic studies indicate the presence of antibodies in the serum. It may be time to act on the clinical implications of these findings.
Millennials’ Attitudes on the US Armed Forces

The military for what? Millennials respond to what they think the US armed forces should be doing both in the US (such as domestic disaster relief) and around the world (such as peacekeeping, war, and nation building). Current military-affiliated and civilian Millennials are compared to those of the past. Both civilians and military affiliates today hold that the number one goal of the armed forces is to fight America’s wars. Civilians are more supportive than their military-affiliated peers of using the military for nonwar related duties such as peacekeeping missions but these differences are not substantial.
Steady State Urinary Excretion of Theophylline and its Metabolities in the Presence of Erythromycin

The effect of erythromycin on the quantitative pattern of urinary excretion of theophylline and its known metabolites at steady state in eight human subjects was examined. The percent of dose excreted of the various compounds in the absence and presence of the antibiotic were as follows: theophylline, 9.3% vs. 16.3%; 1, 3-dimethyluric acid, 51.9% vs. 59.6%; 3-methylxanthine, 11.9% vs. 13.0%; and 1-methyluric acid, 27.3% vs. 31.6%. These results show that erythromycin did not influence the metabolism of theophylline under the experimental protocol employed.
Patients with Pain Need Less Stigma, Not More.

“Protection from and relief of pain and suffering are a fundamental feature of the human contract we make as parents, partners, children, family, friends, and community members, as well as a cardinal underpinning of the art and science of healing.” With these words a blue-ribbon panel of clinicians, researchers and policymakers convened by the prestigious Institute of Medicine opened its landmark 2011 report, Relieving Pain in America . To prepare this report, the panel distilled a vast literature and developed new, detailed estimates of the economic cost of pain in the United States. The panel also reached out to the public, soliciting written or oral testimonies from more than 2,000 persons with pain, their family members and care providers. These testimonies eloquently convey the stigma experienced by nearly every patient with chronic pain: Stigma—shaming and shunning—continues to befall patients with chronic pain, as do inequities in access to care. Tragically, people with the fewest resources to resist pain’s debilitating effects—minorities, the very young or very old, those with HIV, cancer, or substance abuse, the poor or homeless—are also marginalized by society. These “outsiders” have the least access to appropriate pain assessment and treatment. Even prosperous individuals often find their need for pain prevention or control is not addressed. Why is appropriate pain treatment so hard to deliver? The reasons are complex but must be addressed now. First, humans are social animals who look to their peers to …
Estrogen receptor α (ER), BRCA1 and FANCF promoter methylation occur in distinct subsets of sporadic breast cancers

PR-12 Women of African ancestry are more likely to develop ER-negative, PR-negative and HER2-negative basal-like breast cancers, with worse prognoses and lack of therapeutic targets (Polite and Olopade, 2005). The underlying biological mechanisms are still largely unknown. ER and its ligand estrogen play vital roles in the development, progression and treatment of breast cancer. A potential mechanism for hormone resistance is the acquired loss of ER gene expression at the transcriptional level during disease progression. Methylation of the CpG islands in the 59 regulatory region of the ER gene has been associated with loss of ER gene expression in ER-negative breast cancers (Lapidus RG et al., 1998). An increasing number of studies have also provided evidence linking disruption of the Fanconi anemia/BRCA cascade to breast cancer. BRCA1-mutated and promoter-methylated cancers are often of high grade and are ER-negative, suggesting that alterations of the BRCA1 or related pathways might contribute to some sporadic breast cancers (Wei M et al., 2005). Our objectives were to examine the methylation status and expression profiles of ER, correlate the findings with BRCA1 and FANCF methylation and map the critical CpGs for ER expression. In analyzing a subset of domestic samples, we found that the CpG islands in the 59 region of the ER gene are methylated in 59 of 120 (49.2%) primary breast cancers, including 45 of 59 ER-negative tumors (76.3%, P
S11-3 Laser ablation ICP-MS of hair strands for time-resolved exposure measurements to support health studies of welders exposed to manganese

Hair has been proposed as a tool to assess individual’s exposures to manganese (Mn). Previous health effect studies have shown increasing concentrations of Mn in hair with increased levels of Mn exposure (Bader et al. 1999; Reiss et al. 2016), and years of exposure (Xie et al. 1995; Lin 2002) However, individual exposures were not quantified. Use of Laser ablation-ICP-MS is explored as a tool for time-resolved Mn exposure among welders. We present calibration methods for hair and gelatin as a proxy-matrix, and the challenges and opportunities for analysing time-specific exposures in individual hair strands. Triplicate hair strands were selected from 23 one-cm hair bundle samples that were collected from welding school students in the US. The bundles were acid digested and analysed with ICP-MS for Mn content. The individual hair strands and ten flakes of each dried Mn gelatin mixture (0.05–250 ppm) were analysed with LA-ICPMS. Ablated Mn concentrations were normalised to sulfur. Preliminary results suggest very good associations between ablated and digest hair (log-log: 0.90) and between ablated gelatin and gelatin mixtures (log-log: 0.89). A LOD of approximately 1 ppm was estimated. This suggests that gelatin could be a suitable proxy calibration standard for hair. From a cohort of welding trainees with variable exposure, twelve individual hair strands of at least 2 cm length were ablated. MnS profiles in the hair strands will be compared with time specific exposure profiles of the apprentice. Results of this work could provide the basis for using hair strands as a means of measuring individual manganese exposure in welders with much higher time resolution than has previously been done.
Effectiveness of a Time-limited Incentive on Participation by Hard-to-reach Respondents in a Panel Study:

We describe an experiment to provide a time-limited incentive among a random sample of 594 hard-to-reach respondents, 200 of whom were offered the incentive to complete all survey components of a study during a three-week winter holiday period. Sample members were primary caregivers of children included in the 2014 Child Development Supplement to the U.S. Panel Study of Income Dynamics. The incentive provided US$50 to caregivers who completed a 75-minute telephone interview and whose eligible children each completed a 30-minute interview. Results indicate that the incentive was an effective and cost-efficient strategy to increase short-term response rates with hard-to-reach respondents and had no negative impact on final response rates.
Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis

Objective To assess the comparative efficacy and safety of candidate agents (low and high dose aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), calcium, vitamin D, folic acid, alone or in combination) for prevention of advanced metachronous neoplasia (that is, occurring at different times after resection of initial neoplasia) in individuals with previous colorectal neoplasia, through a systematic review and network meta-analysis. Data sources Medline, Embase, Web of Science, from inception to 15 October 2015; clinical trial registries. Study selection Randomized controlled trials in adults with previous colorectal neoplasia, treated with candidate chemoprevention agents, and compared with placebo or another candidate agent. Primary efficacy outcome was risk of advanced metachronous neoplasia; safety outcome was serious adverse events. Data extraction Two investigators identified studies and abstracted data. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities (ranging from 1, indicating that the treatment has a high likelihood to be best, to 0, indicating the treatment has a high likelihood to be worst). Quality of evidence was appraised with GRADE criteria. Results 15 randomized controlled trials (12 234 patients) comparing 10 different strategies were included. Compared with placebo, non-aspirin NSAIDs were ranked best for preventing advanced metachronous neoplasia (odds ratio 0.37, 95% credible interval 0.24 to 0.53; SUCRA=0.98; high quality evidence), followed by low-dose aspirin (0.71, 0.41 to 1.23; SUCRA=0.67; low quality evidence). Low dose aspirin, however, was ranked the safest among chemoprevention agents (0.78, 0.43 to 1.38; SUCRA=0.84), whereas non-aspirin NSAIDs (1.23, 0.95 to 1.64; SUCRA=0.26) were ranked low for safety. High dose aspirin was comparable with low dose aspirin in efficacy (1.12, 0.59 to 2.10; SUCRA=0.58) but had an inferior safety profile (SUCRA=0.51). Efficacy of agents for reducing metachronous colorectal cancer could not be estimated. Conclusions Among individuals with previous colorectal neoplasia, non-aspirin NSAIDs are the most effective agents for the prevention of advanced metachronous neoplasia, whereas low dose aspirin has the most favorable risk:benefit profile. Registration PROSPERO (CRD42015029598).
The effects of base-salt relief on salt flow and suprasalt deformation patterns — Part 2: Application to the eastern Gulf of Mexico

AbstractIn the eastern Gulf of Mexico, the pattern of early stage salt flow is complicated by basement topography consisting of a series of plunging arches that trend obliquely to the early flow direction. Seismic lines downdip of the Florida Middle Ground Arch reveal a puzzling array of structures. Sections trending roughly north–south (parallel to the regional dip) document predominantly extensional structures; however, east–west sections reveal shortening structures. Both sets of structures occur well updip of the downdip salt pinchout. We designed a physical-modeling study to investigate these puzzling relationships. Models presented in Part 1 of this paper indicate that localized shortening and extension can occur as salt passes over simple base-salt steps. Physical models were run with complex salt isopachs featuring plunging arches oblique to dip and salt flow. Models reveal the formation of shortening belts as the salt and its thin prekinematic overburden are translated across the arches. The comp...
Replication Protein A Prohibits Diffusion of the PCNA Sliding Clamp along Single-Stranded DNA.

The replicative polymerases cannot accommodate distortions to the native DNA sequence such as modifications (lesions) to the native template bases from exposure to reactive metabolites and environmental mutagens. Consequently, DNA synthesis on an afflicted template abruptly stops upon encountering these lesions, but the replication fork progresses onward, exposing long stretches of the damaged template before eventually stalling. Such arrests may be overcome by translesion DNA synthesis (TLS) in which specialized TLS polymerases bind to the resident proliferating cell nuclear antigen (PCNA) and replicate the damaged DNA. Hence, a critical aspect of TLS is maintaining PCNA at or near a blocked primer/template (P/T) junction upon uncoupling of fork progression from DNA synthesis by the replicative polymerases. The single-stranded DNA (ssDNA) binding protein, replication protein A (RPA), coats the exposed template and might prohibit diffusion of PCNA along the single-stranded DNA adjacent to a blocked P/T ju...
Renal water conservation determines the increase in body weight after surgery: A randomized, controlled trial.

Background: The present study was undertaken to identify factors that correlate with the gain in body weight after surgery. Methods: Twenty-one patients (median age of 49 years) were randomized to receive either Ringer × s acetate or 6% dextran 70 as their first infusion fluid during cholecystectomy or hysterectomy. Each patient's body weight was measured before the surgery and on the first postoperative morning. Blood and urine samples were analyzed for signs of stress, inflammation, and kidney injury. The fluid retention index (FRI), which reflects how strongly the kidneys excrete or retain fluid, was also calculated. Results: The body weight increased by a median of 0.4 kg in the crystalloid fluid group and by 1.0 kg in the colloid fluid group (maximum 2.5 kg, P P r = 0.64; P r = 0.72; P Conclusion: How strongly the kidneys excrete or retain fluid, which can be assessed by urine sampling, was the strongest indicator of the increase in body weight during the day of surgery. The amount of fluid alone did not correlate with the gain in body weight.
sRAGE Is Elevated in the Lungs of Premature Infants Receiving Mechanical Ventilation.

Background Soluble receptor for advanced glycation end-products (sRAGE), a soluble isoform of the RAGE receptor, is elevated in lungs from patients with acute conditions such as acute respiratory distress syndrome and bronchiolitis. This study investigated whether sRAGE is present in ventilated infants. Methods Tracheal aspirates from the first week or the fifth week of life were obtained from intubated very low birth weight subjects and analyzed by Western blot. Immunohistochemistry analysis for sRAGE was performed on paraffin-embedded lung autopsy slides from 19 other infants. Results The sRAGE band densities were similar among the seven infants who fully recovered, eight who developed bronchopulmonary dysplasia (BPD), and 5 who died (analysis of variance p = 0.797) but was higher at 4 weeks, p = 0.0324. There was minimal sRAGE staining in the autopsied lungs from previable infants (20–21 weeks) or from those who were not ventilated or had mild lung disease. In contrast, substantial staining was present in two of three with BPD, and those who received high ventilatory support. Conclusion sRAGE is present in ventilated infants. Levels are generally higher in those who receive prolonged or vigorous mechanical ventilation. Since sRAGE may have roles in inflammation and cell adherence, its role in the development of BPD may warrant study.
Properties of the immunogenic and sensitizing activities of Bordetella pertussis in mice. I. Enhancement of peptone shock.

Abstract The capacity of pertussis vaccine to enhance peptone shock in mice paralleled the immunogenic and histamine-sensitizing activities in fractionation and was similarly labile to heat and to tryptic degradation. It is, therefore, suggested that the immunogen itself may be responsible for these sensitizing activities. Elicitation of heightened susceptibility to peptone shock by the administration of a beta-adrenergic blocking agent, propranolol, would suggest that pertussis vaccine may induce this effect, as had earlier been reported and is presently confirmed, with histamine, via autonomic nervous pathways. Several significant differences were found, however, between pertussis-mediated hypersensitivity to histamine and to peptone, including degree of sensitivity engendered, mouse strain specificity, and duration of symptoms.
Secure and Efficient Query Processing over Hybrid Clouds

This paper explores secure data processing in hybrid clouds wherein local computing capability is exploited alongside public cloud services to deliver an efficient and secure data management solution. Hybrid clouds offer numerous advantages including the ability to selectively outsource data and computations based on sensitivity/confidentiality. Data processing in hybrid clouds must address two interrelated challenges: (i) data distribution: how is data distributed across public and private machines, and (ii) distributed query processing: how are queries executed efficiently without leaking sensitive data to untrusted public machines. This paper addresses these challenges and incorporates the respective solutions into an add-on tool for a Hadoop, Spark, and Hive based cloud computing infrastructure. Our results show performance advantages in using our strategy as compared to other secure alternatives, even when the percentage of sensitive data is as high as 50%.
Ocular disposition of ciprofloxacin from topical, PEGylated nanostructured lipid carriers: Effect of molecular weight and density of poly (ethylene) glycol.

Abstract Ciprofloxacin (CIP) is an antibacterial agent prescribed for the treatment of ocular infections. The objective of the present project is to investigate the effect of surface PEG functionalization of the Nano structured lipid carriers (NLCs) on formulation stability, ocular penetration and distribution. CIP NLCs were tested with different molecular weight (poly ethylene glycol) PEGs ranging from (2 K to 20 K) grafted onto the phospholipid and with different chain lengths (14–18 carbons) of phospholipids derivatized with PEG–2K. Drug load in the formulations was maintained at 0.3%w/v. Formulations prepared were evaluated with respect to in vitro release, transcorneal permeation, autoclavability, morphological characteristics and in vivo ocular tissue distribution. Scanning Transmission electron microscopy (STEM) studies revealed that the PEG-CIP-NLCs were spherical in shape. Transcorneal penetration of CIP was optimum with PEG molecular weight in between 2 K–10 K. Carbon chain length of the phospholipid, however, did not affect transcorneal penetration of CIP. In vivo ocular tissue CIP concentrations attained from the various formulations was consistent with the in vitro data obtained. The results suggest that surface functionalization of PEGs, within a specified range of molecular weight and surface packing density, significantly enhance trans-ocular penetration and impart sterilization-stabilization characteristics into the formulations.
Inhibition of Carbonic Anhydrase Activity in Cultured Bovine Corneal Endothelial Cells by Dorzolamide

PURPOSE Fluid transport by the corneal endothelium is dependent on the presence of HCO(3)(-) and the activity of carbonic anhydrase (CA)-II and -IV, the cytoplasmic and membrane-bound CAs, respectively. This study was conducted to examine the inhibition of CA activity in cultured bovine corneal endothelial cells (BCECs) by dorzolamide, a topical CA inhibitor used in glaucoma therapy. METHODS BCECs were grown on glass coverslips and then perfused with HCO(3)(-)-free Ringer's. The inward flux of CO(2) was induced by exposure to CO(2)-HCO(3)(-) Ringer's and the opposing outward flux by returning to HCO(3)(-)-free Ringer's. Consequent transients in intracellular pH (pH(i)) were measured using the pH-sensitive fluorescent dye 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF). During the inward flux of CO(2,) the maximum rate of change of pH(i) was taken as a quantitative measure of the overall CA activity in BCECs. RESULTS Exposure to CO(2)-HCO(3)(-) Ringer's led to a transient decrease in pH(i) (component A), followed by a rapid increase to a new steady state (component B). However, when the CO(2)-HCO(3)(-) Ringer's was removed, the pH(i) increased transiently (component C) and then rapidly returned to the original pH(i) (component D). Component A, caused by an inward flux of CO(2) and its subsequent hydration by CA-II, was blocked by dorzolamide in a dose-dependent manner with an 50% inhibitory concentration (IC)(50) of 2.4 micro M (95% confidence interval: 0.5 -10.85 microM). However, the inhibition of the outward flux of CO(2), inward flux of HCO(3)(-), and outward flux of HCO(3)(-) (associated with components C, B, and D, respectively) was not dose dependent. Cells that were exposed to 500 nM of the drug for longer than 30 minutes did not show a significantly greater inhibition of any of the components. Dorzolamide and acetazolamide (500 microM) did not show additive inhibition of any of the components (P = 0.13; n = 6). CONCLUSIONS Dorzolamide significantly inhibits CA activity in BCECs at micromolar levels. Because these levels are encountered in the cornea and aqueous humor after topical administration, dorzolamide may compromise corneal hydration control, especially when the functional reserve of corneal endothelium is low. Dorzolamide does not appear to accumulate in the cells, because the inhibition of CA-II did not increase after prolonged exposure to the drug.
A Multidisciplinary Approach to Puberty and Fertility in Girls with Turner Syndrome.

Abstract Women with Turner Syndrome (TS) have a variety of medical needs throughout their lives; however, the peripubertal years are particularly challenging. From a medical perspective, the burden of care increases during this time due to growth optimization strategies, frequent health screenings, and puberty induction. Psychologically, girls begin to comprehend the long-term implications of the condition, including their diminished fertility potential. Unfortunately, clear guidelines for how to best approach this stage have not been established. It remains to be determined what is the best age to begin treatment; the best compound, dose, or protocol to induce puberty; how, when or what to discuss regarding fertility and potential fertility preservation options; and how to support them to accept their differences and empower them to take an active role in their care. Given the complexity of this life stage, a multidisciplinary treatment team that includes experts in endocrinology, gynecology, and psychology is optimal.
Impact Response of Density Graded Cellular Polymers

Full-field deformation response of density-graded cellular polymers subjected to high velocity impact is investigated experimentally. Recently developed experimental setup consisting of ultra-high speed imaging in conjunction with digital image correlation is used to measure in-situ full-field deformation on density-graded polymeric foam specimens. Loading of the specimens is performed using a direct impact configuration in a modified Hopkinson bar apparatus. Discretely-layered foam specimens made from three distinct layers each with a different bulk density are subjected to direct impact, while their deformation response is studied via ultra-high speed digital image correlation. Formation and propagation of compaction waves from the impact side to the support end of the specimen are observed and analyzed. Spatial distribution of inertia stress is determined from acceleration fields and density of the layers. Full-field stress distribution in the specimen is later used to estimate the stress gradients within compaction waves. Mechanisms associated with the energy dissipation in graded foam specimens are discussed.
Donor skin allograft survival after bone marrow transplantation: Case report and systematic review of the literature☆.

Abstract Background We present a case of skin allograft survival in a patient who previously received a bone marrow transplant from the same HLA-matched donor. DNA fingerprinting of skin biopsies showed mixed cellularity originating from the donor and recipient (68% and 32% donor DNA in the allograft skin and the native recipient's skin, respectively). Histologic sections demonstrated both grade 3/4 rejection and graft-versus-host-disease. We have conducted a systematic review in search for other cases of donor skin allograft survival after a bone marrow or hematopoietic stem cell transplantation. Methods All reported cases in English, Spanish, French, and German were captured using the electronic databases. Bibliographies of relevant articles were manually searched. Results Nineteen patients (12 females) who received skin allografts from their bone marrow or hematopoietic stem cell donors were identified. Average age was 27.2 years (range: 5 months to 64 years). Skin allografts were used to treat graft-versus-host-disease, Herlitz junctional epidermolysis bullosa, and to test tolerance before a kidney transplantation from the same donor. Eight cases were not receiving immunosuppressive therapy. Allografts survived in all patients. In three patients, skin punch biopsies were taken, and these biopsies demonstrated mixed donor and recipient cellularity. The pathology result is specified in two more cases, with no signs of rejection. Conclusions The same donor skin allografts may be a safe option to treat severe cutaneous conditions in recipients of a bone marrow/hematopoietic stem cell transplantation. However, future studies are needed to confirm these results.
Glutamate Signaling in Alcohol Abuse and Dependence

Glutamate is the major excitatory neurotransmitter in the brain and activates two major classes of integral membrane receptors. Ionotropic glutamate receptors are cation-permeable ion channels localized primarily on dendritic spines. They provide most of the direct depolarizing current that initiates action potential firing in central neurons. Metabotropic glutamate receptors are G protein-coupled receptors that modulate neuronal activity via production of intracellular messengers that act on presynaptic neurotransmitter-release processes and postsynaptic signaling complexes. Alcohol has important actions on both ionotropic and metabotropic glutamate receptors, both during acute intoxication and in response to chronic drinking. Adaptations in the glutamate neurotransmitter system are critical in the development of alcohol dependence and likely contribute to the CNS excitability that accompanies withdrawal as well as changes in neurocircuits that underlie motivational and cognitive behaviors affected by alcohol.
Stochastic Learning Models

How subjects learn has long been of interest to psychologists. Large amounts of data are available from experiments in which various outputs (responses) of subjects have been studied as functions of a range of experimenter-controlled input factors (stimuli). To account for these inputoutput relationships is a task for the theorist. In this unit we first consider a mathematical model for learning (the so-called all-or-none or one-element model) as applied by Bower [7] to a paired-associate experiment. After characterizing the formal structure of this model, we introduce a slight generalization, the two-stage all-or-none model. The analysis of a learning experiment using stimulus sampling theory and leading to a three-state Markov chain is outlined in some detail in the Exercises. These models are samples from a wide variety of stochastic learning models, mainly developed since 1950, and applicable to many different experimental situa­tions. A guide for further reading in mathematical learning theory concludes the unit.
Assisted and Unassisted Falls: Different Events, Different Outcomes, Different Implications for Quality of Hospital Care

Article-at-a-Glance Background Many hospitals classify inpatient falls as assisted (if a staff member is present to ease the patient's descent or break the fall) or unassisted for quality measurement purposes. Unassisted falls are more likely to result in injury, but there is limited research quantifying this effect or linking the assisted/unassisted classification to processes of care. A study was conducted to link the assisted/unassisted fall classification to both processes and outcomes of care, thereby demonstrating its suitability for use in quality measurement. This was only the second known published study to quantify the increased risk of injury associated with falling unassisted (versus assisted), and the first to estimate the effects of falling unassisted (versus assisted) on the likelihood of specific levels of injury. Methods A cross-sectional analysis of falls from all available 2011 data for 6,539 adult medical, surgical, and medical-surgical units in 1,464 general hospitals participating in the National Database of Nursing Quality Indicators® (NDNQI®) was performed. Results Participating units reported 166,883 falls (3.44 falls per 1,000 patient-days). Excluding repeat falls, 85.5% of falls were unassisted. Assisted and unassisted falls were associated with different processes and outcomes: Fallers for whom a fall prevention protocol was not in place were more likely to fall unassisted than those for whom one was in place (adjusted odds ratio [aOR], 1.39 [95% confidence interval (CI), 1.32, 1.46]), and unassisted falls were more likely to result in injury (aOR, 1.59 [95% CI, 1.52, 1.67]). Conclusions The assisted/unassisted fall classification is associated with care processes and patient outcomes, making it suitable for quality measurement. Unassisted falls are more likely than assisted falls to result in injury and should be considered a target for future prevention efforts.
Nutritional & Metabolic Control of Brain Amino Acid Concentrations

Stability of brain total free pools of indispensable amino acids (IAA) of rats with widely differing intakes of good quality protein is impressive. For example, protein intakes of young rats that were fed for 4 hr diets containing from 5 to 55% of casein, ranged from 0.4 to 3.9 g/100 g body weight, a 7.5-fold difference. Plasma total IAA concentrations reflected these differences in protein intake and ranged from 1.3 to 5.5 µmol/ml, a 4.5-fold difference. At the same time, brain IAA concentrations differed by only 32%, ranging from 1.5 to 2.1 µmol/g brain (1). Coefficients of variation of fasting brain IAA concentrations are about ± 20%. This degree of stability in concentrations of blood constituents, e. g. glucose or sodium, is usually maintained only through actions of specific and highly responsive regulatory systems.
Shock physics at the nanoscale [Invited]

Shock waves can achieve extreme states of pressure and temperature, of particular interest because those conditions can result in non-equilibrium material dynamics that evolve on ultrafast timescales. Examples of such phenomena include shock-induced chemistry and phase transitions. Traditional plate impact methods lack the necessary time and space resolution needed to observe the onset of ultrafast nanoscale phenomena. Sub-picosecond time scale and nanometer spatial scale shock compression and diagnostics methods have been developed to surmount such difficulties. This paper reviews a number of nanoscale shock wave generation methods, as well as the diagnostics that are applicable at these restrictive time and spatial scales.
Dynamic Analysis of a Seven-span Power Transmission Line Section following Ice Shedding and Its Suppression Method

Ice shedding is one of the major threats for overhead electric transmission lines and the suppression method of the resulting large amplitude vibration is essential to ensure the mechanical and electrical safety of lines in cold regions. The dynamic response of single and multiple span line under ice shedding have been well studies, while only few of previous studies focus on the suppression method. In this paper, a section of real 500 kV seven-span line section was modeled as case study with nonlinear finite element method. The static analysis of the case is conducted to obtain the initial static configuration after icing. Then, dynamic analysis is performed to obtain the influence of span length, ice thickness, ice shedding ratio on the dynamic response of the line section, in terms of midpoint displacement and suspension point tension. Finally, a kind of conductor vibration (due to ice shedding) suppression method with insulating guys is investigated, the results of which show that the proposed method can significantly reduce the dynamic effect of the line section following ice shedding. This study provides important information for the design of multi-span transmission lines and for the suppression of conductor vibration.
Kant’s Morality of Law and Morality of Freedom

Kant’s comments on moral philosophy prior to the Groundwork oftheMetaphysics ofMorals of 1785 include two striking claims. The first is the substantive claim that freedom is the source of all value—that it is intrinsically valuable, and that other valuable things must not merely be compatible with freedom but actually derive their value from the value of freedom. Kant made this claim in the lectures on ethics that he gave in the early 1780s: Freedom is, on the one hand, that faculty which gives unlimited usefulness to all the other faculties. It is the highest order of life, which serves as the foundation of all perfections and is their necessary condition. All animals have the faculty of using their powers according to will. But this will is not free. It is necessitated through the incitement of stimuli, and the actions of animals involve a bruta necessitas. If the will of all beings were so bound to sensuous impulse, the world would possess no value. The inherent value of the world, the summum bonum , is freedom in accordance with a will which is not necessitated to action. Freedom is thus the inner value of the world.1
Suspected or Known Neonatal Sepsis and Neurodevelopmental Outcomes by Five Years

Background: Neonatal sepsis has been linked to adverse neurodevelopmental outcomes. Previous studies examined this association, but did not include term infants, extend beyond two years, delve into specific types of developmental delay, or explore the role of suspected sepsis on developmental delay. Objective: We sought to evaluate the impact of both known and suspected neonatal …
Distance travelled to tertiary pediatric care impacts care-seeking behavior and hospital outcome in Vietnam

# Background The absence of appropriate and timely critical care in resource-limited countries like Vietnam contributes to poor outcomes and excessive mortality in the acutely ill, pediatric population. Often, tertiary care is limited to major urban centers and patients from remote locations face lengthy travel. How these distances impact care-seeking behavior of the patients’ caregiver, patient acuity on admission, and hospitalization outcome in critically ill children remains unknown. # Methods We assessed 471 pediatric patients admitted to intensive care units (ICUs) from the emergency department in a pediatric referral center in Hanoi that serves northern Vietnam. Demographic information from caregivers and medical information was collected by trained staff on site and from the medical record. Patient outcome was followed for sixty days in the ICUs. We analyzed associations between patient admission acuity and outcome to socio-geographic and-demographic data using bivariate logistic regression and log-rank analyses. # Results The median child’s age in our study was 1.8 months, with the majority under 1 year (83.3%). On admission to the ICU, 40.5% of patients required life-saving treatment. Within sixty days of admission, 73.3% of patients were discharged, 21.8% experienced extended admission and 3.08% expired in the ICU. Patient and caretaker’s distance from home residence to Vietnam National Children’s Hospital (VNCH) greater than 60 kilometers was significantly associated with a more severe patient acuity on ICU admission (Odds Ratio, OR=2.01, 95% Confidence Limit, CL=1.33, 3.06), an extended admission or expiration in the ICU (OR=1.94, 95% CL=1.15, 3.20), a lower family income (OR=3.74, 95% CL=2.46, 5.64), lack of caregiver college education (OR=3.73, 95% CL=2.34, 6.05), and greater referrals and days delayed seeking care. # Conclusions These findings highlight numerous barriers facing acutely ill children and their caretakers, who must travel long distances to reach appropriate critical care at a tertiary referral hospital. Research into current protocols, skills, and staffing at lower facilities and public health education in these regions is needed to determine the best avenues for improvement of critical care services beyond tertiary centers.
#SendHelpNow: Mental wellness and virtual connection in the age of coronavirus.

Coronavirus, coronavirus disease (COVID‐19) and social/physical distancing are among the words that have become household names amidst this pandemic. Not only has our vocabulary changed, but also the ways we connect with others. We have become even more reliant on technological advances for business, education, pleasure and other activities. In fact, 93% of Americans report that an outage in internet or cellular service during the outbreak would cause problems in their daily lives (Pew Research Center, 2020).
Women and the American Civil War: North-South Counterpoints

Review of: "Women and the American Civil War: North-South Counterpoints," edited by Judith Giesberg and Randall M. Miller.
The Best Donut in Class: A Lean Approach to Visual Design in Technical Communication Pedagogy

In this experience report I describe a specific day of instruction, deemed by colleagues and former students as “donut day,” developed for teaching smartphone design strategies in service courses in TPC. The report begins with a brief definition of “lean” practices for programmatic innovation in technical communication and bring-your-own-device (BYOD) pedagogy as one such practice. I then provide an outline of the lesson itself, including the preparatory work, the activity itself, and resulting discussion questions. Finally, I assess how donut day succeeds and fails as a “lean” practice and consider how the next decade of smartphone use will affect the relationship between design and technology in TPC service courses.
Chassis Design and Analysis of an Autonomous Ground Vehicle (AGV) using Genetic Algorithm

This paper analyzes the design of a prototype chassis for an autonomous ground vehicle (AGV). This prototype is a four-wheel powered vehicle which would be used for identifying and removal of potatoes affected by virus Y (PVY) in the field. Potato fields are fraught with rough terrain and deep irrigation ruts. Navigation of such a terrain is very challenging and demanding on the robot chassis. An optimization routine was used for finding the ideal size and material for the chassis. Seven different stress analysis were conducted to help narrow down the chassis design and material for the prototype. In addition to a general overview of the various vehicle sub-systems, a detailed description of the force and stress analysis for the chassis of this vehicle is provided. All stress analysis for this chassis passed the design requirements in CAD model (SolidWorks) and has been built and tested in the field.